Bio


I am a neuroradiologist with a specific interest and expertise in stroke, traumatic brain injury, epilepsy, movement disorders and psychiatric disorders. I received my training in Diagnostic Radiology at the University of Lausanne in Switzerland followed by a fellowship in Diagnostic Neuroradiology at the University of California, San Francisco. I have a degree in biomedical engineering from the Swiss federal Institute of technology and a master in clinical research from the University of San Francisco. I worked as a faculty at the University of California, San Francisco, at the University of Virginia, and I am currently a Professor of Radiology and the Chief of Neuroradiology at the Stanford University.

I am the chair of the research committee of the American Society of Neuroradiology (ASNR). In this role, I developed the ASNR research study groups, including one focusing on cervical and intracranial wall imaging, one focusing on brain tumor imaging and genomics, and one addressing clinical translation of functional MRI (fMRI) and diffusion tensor imaging (DTI) to conditions such as traumatic brain injury and chronic stroke.

I am the chair of the imaging working group of the NINDS-funded stroke clinical trial network (StrokeNET). I was a member of the neuroimaging core lab in the DIAS 2 trial, and reviewed centrally the imaging data collected as part of this trial. I helped with the implementation of perfusion-CT as a penumbral imaging method for the MR-RESCUE trial. I am currently leading the imaging core lab for the NIH-funded Vasculopathy in Pediatric Stroke (VIPS) study, which aims at identifying the role and etiology of arteriopathy in pediatric stroke patients.

Clinical Focus


  • Neuroradiology

Academic Appointments


Administrative Appointments


  • Meeting Program Committee, American Society of Neuroradiology (2011 - Present)
  • Fellowship Directors Committee, American Society of Neuroradiology (2011 - Present)
  • Evidence-Based Medicine Committee, American Society of Neuroradiology (2012 - Present)
  • Co-Chair, Website Committee, American Society of Neuroradiology (2014 - Present)
  • Co-Chair, Research Committee, American Society of Neuroradiology (2013 - Present)
  • Executive Committee, American Society of Neuroradiology (2013 - Present)
  • Vice-Chair, RSNA Public Information Committee, Radiological Society of North America (2011 - Present)
  • RSNA Public Information Advisors Network, Radiological Society of North America (2011 - Present)
  • Neuroradiology/Head&Neck Subcommittee of the Scientific Program Committee, Radiological Society of North America (2013 - Present)
  • Co-Chair, HI-RADS Committee of the ACR Head Injury Institute, American College of Neuroradiology (2013 - Present)
  • Chair, Clinical Research Impact Committee for ACR 2015 Meeting, American College of Radiology (2013 - Present)
  • Commission on Clinical Research and Information Technology, American College of Radiology (2012 - Present)
  • Commission on Neuroradiology, ACR Neuroradiology Commission Writing Group, American College of Radiology (2012 - Present)
  • Commission on Neuroradiology, Guidelines and Standards Committee, American College of Radiology (2012 - Present)
  • Committee of Practice Parameters - NeuroAppropriateness Criteria® (AC) Expert Panel on Neuroimaging, American College of Radiology (2014 - Present)
  • Steering Committee, Stroke Imaging Repository (2007 - Present)

Professional Education


  • Fellowship: UCSF Neuroradiology Fellowship (2005) CA
  • Residency: CHUV - University Hospital of Lausanne - Department of Radiology (2004) Switzerland
  • Board Certification: American Board of Radiology, Neuroradiology (2011)
  • Board Certification: American Board of Radiology, Diagnostic Radiology (2009)
  • Internship: GHOL - Hospital of Nyon (2000) Switzerland
  • Medical Education: University of Lausanne School of Medicine (1998) Switzerland
  • MD, University of Lausanne (Switzerland), Medical School, Doctor of Medicine (1998)
  • Bioengineering Degree, Swiss Federal Institute of Technology, Bioengineering and Biomedical Engineering (1999)
  • Board of Radiology, Centre Hospitalier Universitaire Vaudois, Radiology Residency (2003)
  • CAQ Neuroradiology, University of California, San Francisco, Neuroradiology Fellowship (2004)
  • MAS, University of California, San Francisco, Clinical Research (2009)
  • MBA, University of Massachusetts, Isenberg School of Management, Business Administration (2014)

Current Research and Scholarly Interests


Stroke, cerebrovascular diseases, cardiovascular diseases, carotid arteries, coronary arteries
Stroke diagnosis, stroke triage, stroke treatment
Traumatic brain injury
Traumatic brain injury diagnosis and prognosis
Psychiatric disorders, including depression and post-traumatic stress disorders
Epilepsy
Movement disorders, including essential tremor and Parkinson’s tremor
Brain tumors
Image-guided clinical trials
CT, multidetector-row CT, perfusion-CT, CT angiography
MRI, diffusion-weighted MRI, perfusion-weighted MRI, diffusion tensor imaging, functional MRI
Brain perfusion imaging techniques
Functional imaging
Post-processing techniques of medical images, signal and image processing
3D visualization
MR-guided focused ultrasound

2021-22 Courses


Graduate and Fellowship Programs


  • Neuroradiology (Fellowship Program)

All Publications


  • Cerebrovascular Collateral Integrity in Pediatric Large Vessel Occlusion: Analysis of the Save ChildS Study. Neurology Lee, S., Jiang, B., Wintermark, M., Mlynash, M., Christensen, S., Strater, R., Broocks, G., Grams Austria, A., Dorn, F., Nikoubashman, O., Kaiser, D., Morotti, A., Jensen-Kondering, U., Trenkler, J., Mohlenbruch, M., Fiehler, J., Wildgruber, M., Kemmling, A., Psychogios, M., Sporns, P. B., Save ChildS Investigators 2021

    Abstract

    BACKGROUND AND OBJECTIVES: Robust cerebrovascular collaterals in adult stroke patients have been associated with longer treatment windows, better recanalization rates, and improved outcomes. No studies have investigated the role of collaterals in pediatric stroke. The primary aim was to determine whether favorable collaterals correlated with better radiographic and clinical outcomes in children with ischemic stroke who underwent thrombectomy.METHODS: This study analyzed a subset of children enrolled in SaveChildS, a retrospective, multi-center, observational cohort study of 73 pediatric stroke patients who underwent thrombectomy between 2000-2018 at 27 US and European centers. Included patients had baseline angiographic imaging and follow-up modified Rankin Scale scores available for review. Posterior circulation occlusions were excluded. Cerebrovascular collaterals were graded on acute neuroimaging by 2 blinded neuroradiologists according to the Tan collateral score, where favorable collaterals are defined as >50% filling and unfavorable collaterals as <50% filling distal to the occluded vessel. Collateral status was correlated with clinical and neuroimaging characteristics and outcomes. Between-group comparisons were performed using the Wilcoxon rank-sum test for continuous variables or Fisher's exact test for binary variables.RESULTS: Thirty-three children (mean age 10.9 [SD±4.9]) years were included; 14 (42.4%) had favorable collaterals. Median final stroke volume as a percent of total brain volume (TBV) was significantly lower in patients with favorable collaterals (1.35% [IQR 1.14-3.76] versus 7.86% [1.54-11.07], p=0.049). Collateral status did not correlate with clinical outcome, infarct growth or final ASPECTS in our cohort. Patients with favorable collaterals had higher baseline ASPECTS (7 [IQR 6-8] versus 5.5 [4-6], p=0.006), smaller baseline ischemic volume (1.57% TBV [IQR 1.09-2.29] versus 3.42% TBV [IQR 1.26-5.33], p=0.035) and slower early infarct growth rate (2.4 mL/hr [IQR 1.5-5.1] versus 10.4 mL/hr [IQR 3.0-30.7], p=0.028).DISCUSSION: Favorable collaterals were associated with smaller final stroke burden and slower early infarct growth rate, but not with better clinical outcome in our study. Prospective studies are needed to determine the impact of collaterals in childhood stroke.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in children with ischemic stroke undergoing thrombectomy, favorable collaterals were associated with improved radiographic outcomes but not with better clinical outcomes.

    View details for DOI 10.1212/WNL.0000000000013081

    View details for PubMedID 34795051

  • Cerebral venous outflow profiles are associated with the first pass effect in endovascular thrombectomy. Journal of neurointerventional surgery van Horn, N., Heit, J. J., Kabiri, R., Mader, M. M., Christensen, S., Mlynash, M., Broocks, G., Meyer, L., Nawabi, J., Lansberg, M. G., Albers, G. W., Wintermark, M., Fiehler, J., Faizy, T. D. 2021

    Abstract

    BACKGROUND: Recent studies found that favorable venous outflow (VO) profiles are associated with higher reperfusion rates after mechanical thrombectomy (MT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Fewer retrieval attempts and first-pass revascularization during MT lead to better functional outcomes.OBJECTIVE: To examine the hypothesis that favorable VO profiles assessed on baseline CT angiography (CTA) images correlate with successful vessel reperfusion after the first retrieval attempt and fewer retrieval attempts.METHODS: A multicenter retrospective cohort study of patients with AIS-LVO treated by MT. Baseline CTA was used to determine the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcomes were successful with excellent vessel reperfusion status, defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 and 2c/3 after first retrieval attempt.RESULTS: 617 patients were included in this study, of whom 205 (33.2%) had first pass reperfusion. In univariate analysis, ordinal COVES (p=0.011) values were significantly higher in patients with first pass than in those with non-first pass reperfusion, while the number of patients exhibiting favorable pial arterial collaterals using the Maas scale on CTA did not differ (p=0.243). In multivariable logistic regression analysis, higher COVES were independently associated with TICI 2b/3 (OR=1.25, 95%CI 1.1 to 1.42; p=0.001) and TICI 2c/3 (OR=1.2, 95%CI 1.04 to 1.36; p=0.011) reperfusion after one retrieval attempt, controlling for penumbra volume and time from symptom onset to vessel reperfusion.CONCLUSIONS: Favorable VO, classified as higher COVES, is independently associated with successful and excellent first pass reperfusion in patients with AIS-LVO treated by endovascular thrombectomy.

    View details for DOI 10.1136/neurintsurg-2021-018078

    View details for PubMedID 34750110

  • Convergence, preliminary findings and future directions across the four human connectome projects investigating mood and anxiety disorders. NeuroImage Tozzi, L., Anene, E. T., Gotlib, I. H., Wintermark, M., Kerr, A. B., Wu, H., Seok, D., Narr, K. L., Sheline, Y. I., Whitfield-Gabrieli, S., Williams, L. M. 2021: 118694

    Abstract

    In this paper we provide an overview of the rationale, methods, and preliminary results of the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders. The first study, "Dimensional connectomics of anxious misery" (HCP-DAM), characterizes brain-symptom relations of a transdiagnostic sample of anxious misery disorders. The second study, "Human connectome Project for disordered emotional states" (HCP-DES), tests a hypothesis-driven model of brain circuit dysfunction in a sample of untreated young adults with symptoms of depression and anxiety. The third study, "Perturbation of the treatment resistant depression connectome by fast-acting therapies" (HCP-MDD), quantifies alterations of the structural and functional connectome as a result of three fast-acting interventions: electroconvulsive therapy, serial ketamine therapy, and total sleep deprivation. Finally, the fourth study, "Connectomes related to anxiety and depression in adolescents" (HCP-ADA), investigates developmental trajectories of subtypes of anxiety and depression in adolescence. The four projects use comparable and standardized Human Connectome Project magnetic resonance imaging (MRI) protocols, including structural MRI, diffusion-weighted MRI, and both task and resting state functional MRI. All four projects also conducted comprehensive and convergent clinical and neuropsychological assessments, including (but not limited to) demographic information, clinical diagnoses, symptoms of mood and anxiety disorders, negative and positive affect, cognitive function, and exposure to early life stress. The first round of analyses conducted in the four projects offered novel methods to investigate relations between functional connectomes and self-reports in large datasets, identified new functional correlates of symptoms of mood and anxiety disorders, characterized the trajectory of connectome-symptom profiles over time, and quantified the impact of novel treatments on aberrant connectivity. Taken together, the data obtained and reported by the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders describe a rich constellation of convergent biological, clinical, and behavioral phenotypes that span the peak ages for the onset of emotional disorders. These data are being prepared for open sharing with the scientific community following screens for quality by the Connectome Coordinating Facility (CCF). The CCF also plans to release data from all projects that have been pre-processed using identical state-of-the-art pipelines. The resultant dataset will give researchers the opportunity to pool complementary data across the four projects to study circuit dysfunctions that may underlie mood and anxiety disorders, to map cohesive relations among circuits and symptoms, and to probe how these relations change as a function of age and acute interventions. This large and combined dataset may also be ideal for using data-driven analytic approaches to inform neurobiological targets for future clinical trials and interventions focused on clinical or behavioral outcomes.

    View details for DOI 10.1016/j.neuroimage.2021.118694

    View details for PubMedID 34732328

  • Cerebral Perfusion in Pediatric Stroke: Children Are Not Little Adults. Topics in magnetic resonance imaging : TMRI Lee, S., Jiang, B., Heit, J. J., Dodd, R. L., Wintermark, M. 2021; 30 (5): 245-252

    Abstract

    ABSTRACT: Cerebral perfusion imaging provides useful information about the hemodynamic state of the brain that is relevant to a number of neurologic conditions, including stroke, epilepsy, and brain tumors. Multiple imaging modalities have been developed to evaluate brain perfusion, primarily by the use of different tracers to measure cerebral blood volume and cerebral blood flow. Here, we provide an overview of magnetic resonance imaging perfusion techniques; summarize the role of perfusion imaging in adult stroke; describe changes in cerebral blood flow over childhood; and discuss the relevance and future directions of perfusion imaging in pediatric cerebrovascular disorders and stroke.

    View details for DOI 10.1097/RMR.0000000000000275

    View details for PubMedID 34613947

  • A Web-based System to Assist With Etiology Differential Diagnosis in Children With Arterial Ischemic Stroke. Topics in magnetic resonance imaging : TMRI Karthik, A., Jiang, B., Li, Y., Hills, N. K., Kuchherzki, M., deVeber, G. A., Barkovich, A. J., Fullerton, H. J., Wintermark, M., VIPS Investigators (Appendix 1) 2021; 30 (5): 253-257

    Abstract

    BACKGROUND AND PURPOSE: The diagnosis of childhood arteriopathy is complex. We present a Web-based, evidence-backed classification system to return the most likely cause(s) of a pediatric arterial ischemic stroke. This tool incorporates a decision-making algorithm that considers a patient's clinical and imaging features before returning a differential diagnosis, including the likelihood of various arteriopathy subtypes.METHODS: The Vascular Effects of Infection in Pediatric Stroke study prospectively enrolled 355 children with arterial ischemic stroke (2010-2014). Previously, a central panel of experts classified the stroke etiology. To create this tool, we used the 174 patients with definite arteriopathy and spontaneous cardioembolic stroke as the "derivation cohort" and the 34 with "possible" arteriopathy as the "test cohort." Using logistic regression models of clinical and imaging characteristics associated with each arteriopathy subtype in the derivation cohort, we built a decision framework that we integrated into a Web interface specifically designed to create a probabilistic differential diagnosis. We applied the Web-based tool to the "test cohort."RESULTS: The differential diagnosis returned by our tool was in complete agreement with the experts' opinions in 20.6% of patients. We observed a partial agreement in 41.2% of patients and an overlap in 29.4% of patients. The tool disagreed with the experts on the diagnoses of 3 patients (8.8%).CONCLUSIONS: Our tool yielded an overlapping differential diagnosis in most patients that defied definitive classification by experts. Although it needs to be validated in an independent cohort, it helps facilitate high-quality, and timely diagnoses of arteriopathy in pediatric patients.

    View details for DOI 10.1097/RMR.0000000000000285

    View details for PubMedID 34613948

  • Automated Brain Perfusion Imaging in Acute Ischemic Stroke: Interpretation Pearls and Pitfalls. Stroke Nicolas-Jilwan, M., Wintermark, M. 2021: STROKEAHA121035049

    Abstract

    Recent advancements in computed tomography technology, including improved brain coverage and automated processing of the perfusion data, have reinforced the use of perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. The DAWN (Diffusion Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trials have established the benefit of endovascular thrombectomy in patients with acute ischemic stroke with anterior circulation large vessel occlusion up to 24 hours of last seen normal, using perfusion imaging-based patient selection. The compelling data has prompted stroke centers to increasingly introduce automated perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. We present a comprehensive overview of the acquisition and interpretation of automated perfusion imaging in patients with acute ischemic stroke with a special emphasis on the interpretation pearls, pitfalls, and stroke mimicking conditions.

    View details for DOI 10.1161/STROKEAHA.121.035049

    View details for PubMedID 34565174

  • The mid-term effects of carotid endarterectomy on cognition and regional neural activity analyzed with the amplitude of low frequency fluctuations technique. Neuroradiology Porcu, M., Cocco, L., Cau, R., Suri, J. S., Mannelli, L., Yang, Q., Defazio, G., Wintermark, M., Saba, L. 2021

    Abstract

    PURPOSE: The study aims to evaluate the mid-term effects of carotid endarterectomy (CEA) on cognition and resting-state functional magnetic resonance imaging (rs-fMRI) using the Amplitude of Low Frequency Fluctuations (ALFF) technique.METHODS: In this observational study, patients eligible for CEA were prospectively included. On the same day, within 1week of the CEA procedure performed and 12months after the CEA procedure, all patients underwent (i) an MRI examination for rs-fMRI analysis and (ii) a cognitive evaluation using the Italian version of the Mini-Mental State Examination (MMSE) corrected for age and schooling. Pre-CEA and post-CEA MMSE scores were evaluated using paired sample t-tests, adopting a p-value<0.05 as statistical threshold. The ALFF technique was used for analyzing the differences between pre-CEA and post-CEA rs-fMRI scans in terms of regional neural activation. This was accomplished by applying non-parametric statistics based on randomization/permutation for cluster-level inferences, adopting a cluster-mass p-value corrected for false discovery<0.05 for cluster threshold, and a p-uncorrected<0.01 for the voxel threshold.RESULTS: Twenty asymptomatic patients were enrolled. The mean MMSE score resulted improved following CEA procedure (p-value=0.001). The ALFF analysis identified a single cluster of 6260 voxels of increased regional neural activity following CEA, and no cluster of reduced activity. The majority of voxels covered the right precentral gyrus, the right middle frontal gyrus, and the anterior division of the cingulate gyrus.CONCLUSION: Mid-term cognitive improvements observed after CEA are associated to increased regional neural activity of several cerebral regions.

    View details for DOI 10.1007/s00234-021-02815-7

    View details for PubMedID 34562140

  • Diffuse Axonal Injury Grade on Early MRI is Associated with Worse Outcome in Children with Moderate-Severe Traumatic Brain Injury. Neurocritical care Janas, A. M., Qin, F., Hamilton, S., Jiang, B., Baier, N., Wintermark, M., Threlkeld, Z., Lee, S. 2021

    Abstract

    BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in children, but effective tools for predicting outcome remain elusive. Although many pediatric patients receive early magnetic resonance imaging (MRI), data on its utility in prognostication are lacking. Diffuse axonal injury (DAI) is a hallmark of TBI detected on early MRI and was shown previously to improve prognostication in adult patients with TBI. In this exploratory study, we investigated whether DAI grade correlates with functional outcome and improves prognostic accuracy when combined with core clinical variables and computed tomography (CT) biomarkers in pediatric patients with moderate-severe TBI (msTBI).METHODS: Pediatric patients (≤19years) who were admitted to two regional level one trauma centers with a diagnosis of msTBI (Glasgow Coma Scale [GCS] score<13) between 2011 and 2019 were identified through retrospective chart review. Patients who underwent brain MRI within 30days of injury and had documented clinical follow-up after discharge were included. Age, pupil reactivity, and initial motor GCS score were collected as part of the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. Imaging was reviewed to calculate the Rotterdam score (CT) and DAI grade (MRI) and to evaluate for presence of hypoxic-ischemic injury (MRI). The primary outcome measure was the Pediatric Cerebral Performance Category Scale (PCPCS) score at 6months after TBI, with favorable outcome defined as PCPCS scores 1-3 and unfavorable outcome defined as PCPCS scores 4-6. The secondary outcome measure was discharge disposition to home versus to an inpatient rehabilitation facility.RESULT: Of 55 patients included in the study, 45 (82%) had severe TBI. The most common mechanism of injury was motor vehicle collision (71%). Initial head CT scans showed acute hemorrhage in 84% of patients. MRI was acquired a median of 5days after injury, and hemorrhagic DAI lesions were detected in 87% of patients. Each 1-point increase in DAI grade increased the odds of unfavorable functional outcome by 2.4-fold. When controlling for core IMPACT clinical variables, neither the DAI grade nor the Rotterdam score was independently correlated with outcome and neither significantly improved outcome prediction over the IMPACT model alone.CONCLUSIONS: A higher DAI grade on early MRI is associated with worse 6-monthfunctional outcome and with discharge to inpatient rehabilitation in children with acute msTBI in a univariate analysis but does not independently correlate with outcome when controlling for the GCS score. Addition of the DAI grade to the core IMPACT model does not significantly improve prediction of poor neurological outcome. Further study is needed to elucidate the utility of early MRI in children with msTBI.

    View details for DOI 10.1007/s12028-021-01336-8

    View details for PubMedID 34462880

  • Distinct intraarterial Clot Localizations affect Tissue-Level Collaterals and Venous Outflow Profiles. European journal of neurology Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Broocks, G., Flottmann, F., Meyer, L., Leischner, H., Lansberg, M. G., Albers, G. W., Marks, M. P., Fiehler, J., Wintermark, M., Heit, J. J. 2021

    Abstract

    BACKGROUND AND AIM: Arterial clot localization affects collateral flow to ischemic brain in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We determined the association between vessel occlusion locations, tissue-level collaterals (TLC) and venous outflow (VO) profiles and their impact on good functional outcomes.MATERIALS AND METHODS: Multicenter retrospective cohort study of consecutive AIS-LVO patients who underwent thrombectomy triage. Baseline CT angiography (CTA) was used to localize vessel occlusion, which was dichotomized into proximal vessel occlusion (PVO; internal carotid artery and proximal M1) and distal vessel occlusion (DVO; distal M1 and M2) and to assess collateral score. TLC were assessed on CT perfusion data using the Hypoperfusion Intensity Ratio (HIR). VO was determined on baseline CTA by the cortical vein opacification score. Primary outcomes were favorable VO and TLC, secondary outcome the Modified Ranking Scale (mRS) after 90 days.RESULTS: 649 patients met inclusion criteria. 376 patients (58%) had a PVO and 273 patients (42%) had a DVO. Multivariable ordinal logistic regression showed that DVO predicted favorable TLC (OR=1.77 [95% CI: 1.24-2.52]; p=0.002) and favorable VO (OR=7.2 [95% CI: 5.2-11.9]; p<0.001). DVO (OR=3.4 [95% CI: 2.1-5.6]; p<0.001), favorable VO (OR=6.4 [95% CI: 3.8-10.6]; p<0.001) and favorable TLC (OR=3.2 [95% CI: 2-5.3]; p<0.001), but not CTA collaterals (OR=1.07 [95% CI: 0.60-1.91]; p=0.813), were predictors of good functional outcome.CONCLUSION: DVO in AIS-LVO patients correlate with favorable TLC and VO profiles, which are associated with good functional outcome.

    View details for DOI 10.1111/ene.15079

    View details for PubMedID 34424584

  • Neuroradiologic Evaluation of MRI in High-Contact Sports FRONTIERS IN NEUROLOGY McAllister, D., Akers, C., Boldt, B., Mitchell, L. A., Tranvinh, E., Douglas, D., Goubran, M., Rosenberg, J., Georgiadis, M., Karimpoor, M., DiGiacomo, P., Mouchawar, N., Grant, G., Camarillo, D., Wintermark, M., Zeineh, M. M. 2021; 12
  • Distant histories of mild traumatic brain injury exacerbate age-related differences in white matter properties. Neurobiology of aging Vakhtin, A. A., Zhang, Y., Wintermark, M., Ashford, J. W., Furst, A. J. 2021; 107: 30-41

    Abstract

    We examined associations of distant histories of mild traumatic brain injury (mTBI) with non-linear and linear trajectories of white matter (WM) properties across a wide age range (23-77). Diffusion tensor imaging (DTI) data obtained from 171 Veterans with histories of clinically diagnosed mTBIs and 115 controls were subjected to tractography, isolating 20 major WM tracts. Non-linear and linear effects of age on each tract's diffusion properties were examined in terms of their interactions with group (mTBI and control). The non-linear model revealed 7 tracts in which the mTBI group's DTI metrics rapidly deviated from control trajectories in middle and late adulthoods, despite the injuries having occurred in the late 20s, on average. In contrast, no interactions between prior injuries and age were detected when examining linear trajectories. Distant mTBIs may thus accelerate normal age-related trajectories of WM degeneration much later in life. As such, life-long histories of head trauma should be assessed in all patients in their mid-to-late adulthoods, whether neurologically healthy or presenting with seemingly unrelated neuropathology.

    View details for DOI 10.1016/j.neurobiolaging.2021.07.002

    View details for PubMedID 34371285

  • Volume of White Matter Hyperintensities, and Cerebral Micro-Bleeds. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Balestrieri, A., Lucatelli, P., Suri, H. S., Montisci, R., Suri, J. S., Wintermark, M., Serra, A., Cheng, X., Jinliang, C., Sanfilippo, R., Saba, L. 2021; 30 (8): 105905

    Abstract

    PURPOSE: In the past years the significance of white matter hyperintensities (WMH) has gained raising attention because it is considered a marker of severity of different pathologies. Another condition that in the last years has been assessed in the neuroradiology field is cerebral microbleeds (CMB). The purpose of this work was to evaluate the association between the volume of WMH and the presence and characteristics of CMB.MATERIAL AND METHODS: Sixty-five consecutive (males 45; median age 70) subjects were retrospectively analyzed with a 1.5 Tesla scanner. WMH volume was quantified with a semi-automated procedure considering the FLAIR MR sequences whereas the CMB were studied with the SWI technique and CMBs were classified as absent (grade 1), mild (grade 2; total number of CMBs: 1-2), moderate (grade 3; total number of CMBs: 3-10), and severe (grade 4; total number of CMBs: >10). Moreover, overall number of CMBs and the maximum diameter were registered.RESULTS: Prevalence of CMBs was 30.76% whereas WMH 81.5%. Mann-Whitney test showed a statistically significant difference in WMH volume between subjects with and without CMBs (p<0.001). Pearson analysis showed significant correlation between CMB grade, number and maximum diameter and WMH. The better ROC area under the curve (Az) was obtained by the hemisphere volume with a 0.828 (95% CI from 0.752 to 0,888; SD=0.0427; p value=0.001). The only parameters that showed a statistically significant association in the logistic regression analysis were Hemisphere volume of WMH (p=0.001) and Cholesterol LDL (p=0.0292).CONCLUSION: In conclusion, the results of this study suggest the presence of a significant correlation between CMBs and volume of WMH. No differences were found between the different vascular territories.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2021.105905

    View details for PubMedID 34107418

  • Nusinersen Treatment in Adults With Spinal Muscular Atrophy. Neurology. Clinical practice Duong, T., Wolford, C., McDermott, M. P., Macpherson, C. E., Pasternak, A., Glanzman, A. M., Martens, W. B., Kichula, E., Darras, B. T., De Vivo, D. C., Zolkipli-Cunningham, Z., Finkel, R. S., Zeineh, M., Wintermark, M., Sampson, J., Hagerman, K. A., Young, S. D., Day, J. W. 2021; 11 (3): e317-e327

    Abstract

    Objective: To determine changes in motor and respiratory function after treatment with nusinersen in adults with spinal muscular atrophy (SMA) during the first two years of commercial availability in the USA.Methods: Data were collected prospectively on adult (age >17 years at treatment initiation) SMA participants in the Pediatric Neuromuscular Clinical Research (PNCR) Network. Baseline assessments of SMA outcomes including the Expanded Hammersmith Functional Rating Scale (HFMSE), Revised Upper Limb Module (RULM), and 6-Minute Walk Test (6MWT) occurred <5 months before treatment, and post-treatment assessments were made up to 24 months after nusinersen initation. Patient-reported experiences, safety laboratory tests and adverse events were monitored. The mean annual rate of change over time was determined for outcome measures using linear mixed effects models.Results: Forty-two adult SMA participants (mean age: 34 years, range 17-66) receiving nusinersen for a mean of 12.5 months (range 3-24 months) were assessed. Several motor and respiratory measures showed improvement distinct from the progressive decline typically seen in untreated adults. Participants also reported qualitative improvements including muscle strength, stamina, breathing and bulbar related outcomes. All participants tolerated nusinersen with normal surveillance labs and no significant adverse events.Conclusions: Trends of improvement emerged in functional motor, patient-reported, and respiratory measures, suggesting nusinersen may be efficacious in adults with SMA. Larger well-controlled studies and additional outcome measures are needed to firmly establish the efficacy of nusinersen in adults with SMA.Classification of Evidence: This study provides Class IV evidence regarding nusinersen tolerability and efficacy based on reported side effects and pulmonary and physical therapy assessments in an adult SMA cohort.

    View details for DOI 10.1212/CPJ.0000000000001033

    View details for PubMedID 34476123

  • Development of a realistic, dynamic digital brain phantom for CT Perfusion validation SPIE Medical Imaging 2016: Physics of Medical Imaging Divel, S. E., Segars, W. P., Christensen, S., Wintermark, M., Lansberg, M. G., Pelc, N. J. 2016

    View details for DOI 10.1117/12.2214997

  • MR perfusion imaging: Half-dose gadolinium is half the quality. Journal of neuroimaging : official journal of the American Society of Neuroimaging Heit, J. J., Christensen, S., Mlynash, M., Marks, M. P., Faizy, T. D., Lansberg, M. G., Wintermark, M., Bammer, R., Albers, G. W. 2021

    Abstract

    BACKGROUND AND PURPOSE: Patients with acute ischemic stroke due to a large vessel occlusion (AIS-LVO) undergo emergent neuroimaging triage for thrombectomy treatment. MRI is often utilized for this evaluation, and cerebral magnetic resonance perfusion (MRP) imaging is used to identify the presence of the salvageable penumbra. To determine if dose reduction is feasible, we assessed whether a half-dose reduction in gadobenate provided sufficient MRP quality in AIS-LVO patients.METHODS: A prospective observational study of all patients presenting to our neurovascular referral center with AIS-LVO was performed. MRP was done with a half-dose of gadolinium (0.1 ml/kg body weight) over a period of 10 months. MRP images were compared to a consecutive historical cohort of full-dose gadolinium (0.2 ml/kg body weight) MRP studies and rated for image quality (poor, borderline, or good) that determined thrombectomy eligibility.RESULTS: Fifty-four half-dose and 127 full-dose patients were included. No differences in patient demographics or stroke presentation details were identified. MRP quality differed between half- and full-dose scans (p < 0.001), which were rated as poor (40.7% vs. 6.3%), borderline (18.5% vs. 26.8%), and good quality (40.7% vs. 66.9%), respectively. MRP image quality was then dichotomized into poor and sufficient (borderline and good) quality groups; half-dose studies were more likely to have poor quality compared to full-dose studies (40.7% vs. 6.3%; p < 0.001).CONCLUSIONS: Half-dose gadolinium administration for MRP in AIS-LVO patients results in poor image quality in a substantial number of studies. MR cerebral perfusion performed with half-dose gadolinium may adversely affect stroke patient triage for thrombectomy.

    View details for DOI 10.1111/jon.12879

    View details for PubMedID 34002424

  • Semiautomated Characterization of Carotid Artery Plaque Features From Computed Tomography Angiography to Predict Atherosclerotic Cardiovascular Disease Risk Score. Journal of computer assisted tomography Zhu, G. n., Li, Y. n., Ding, V. n., Jiang, B. n., Ball, R. L., Rodriguez, F. n., Fleischmann, D. n., Desai, M. n., Saloner, D. n., Gupta, A. n., Saba, L. n., Hom, J. n., Wintermark, M. n. ; 43 (3): 452–59

    Abstract

    To investigate whether selected carotid computed tomography angiography (CTA) quantitative features can predict 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores.One hundred seventeen patients with calculated ASCVD risk scores were considered. A semiautomated imaging analysis software was used to segment and quantify plaque features. Eighty patients were randomly selected to build models using 14 imaging variables and the calculated ASCVD risk score as the end point (continuous and binarized). The remaining 37 patients were used as the test set to generate predicted ASCVD scores. The predicted and observed ASCVD risk scores were compared to assess properties of the predictive model.Nine of 14 CTA imaging variables were included in a model that considered the plaque features in a continuous fashion (model 1) and 6 in a model that considered the plaque features dichotomized (model 2). The predicted ASCVD risk scores were 18.87% ± 13.26% and 18.39% ± 11.6%, respectively. There were strong correlations between the observed ASCVD and the predicted ASCVDs, with r = 0.736 for model 1 and r = 0.657 for model 2. The mean biases between observed ASCVD and predicted ASCVDs were -1.954% ± 10.88% and -1.466% ± 12.04%, respectively.Selected quantitative imaging carotid features extracted from the semiautomated carotid artery analysis can predict the ASCVD risk scores.

    View details for PubMedID 31082951

  • Non-invasive, neurotoxic surgery reduces seizures in a rat model of temporal lobe epilepsy. Experimental neurology Zhang, Y., Buckmaster, P. S., Qiu, L., Wang, J., Keunen, O., Ghobadi, S. N., Huang, A., Hou, Q., Li, N., Narang, S., Habte, F. G., Bertram, E. H., Lee, K. S., Wintermark, M. 2021: 113761

    Abstract

    Surgery can be highly effective for treating certain cases of drug resistant epilepsy. The current study tested a novel, non-invasive, surgical strategy for treating seizures in a rat model of temporal lobe epilepsy. The surgical approach uses magnetic resonance-guided, low-intensity focused ultrasound (MRgFUS) in combination with intravenous microbubbles to open the blood-brain barrier (BBB) in a transient and focal manner. During the period of BBB opening, a systemically administered neurotoxin (Quinolinic Acid: QA) that is normally impermeable to the BBB gains access to a targeted area in the brain, destroying neurons where the BBB has been opened. This strategy is termed Precise Intracerebral Non-invasive Guided Surgery (PING). Spontaneous recurrent seizures induced by pilocarpine were monitored behaviorally prior to and after PING or under control conditions. Seizure frequency in untreated animals or animals treated with MRgFUS without QA exhibited expected seizure rate fluctuations frequencies between the monitoring periods. In contrast, animals treated with PING targeting the intermediate-temporal aspect of the hippocampus exhibited substantial reductions in seizure frequency, with convulsive seizures being eliminated entirely in two animals. These findings suggest that PING could provide a useful alternative to invasive surgical interventions for treating drug resistant epilepsy, and perhaps for treating other neurological disorders in which aberrant neural circuitries play a role.

    View details for DOI 10.1016/j.expneurol.2021.113761

    View details for PubMedID 33991523

  • Association of Venous Outflow Profiles and Successful Vessel Reperfusion After Thrombectomy. Neurology Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Marc-Daniel Mader, M., Albers, G. W., Lansberg, M. G., Fiehler, P. J., Wintermark, M., Marks, M. P., Heit, J. J. 2021

    Abstract

    OBJECTIVE: Robust arterial collaterals are associated with successful reperfusion after thrombectomy treatment of acute ischemic stroke due to large vessel occlusion (AIS-LVO). Excellent venous outflow (VO) reflects excellent tissue perfusion and collateral status in AIS-LVO patients. To determine whether favorable VO profiles assessed on pre-treatment CT angiography (CTA) images correlate with successful vessel reperfusion after thrombectomy in AIS-LVO patients.METHODS: Multicenter retrospective cohort study of consecutive AIS-LVO patients treated by thrombectomy. Baseline CTA was used to assess collateral status (Tan scale) and VO using the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcome was excellent vessel reperfusion status (modified Thrombolysis In Cerebral Infarction [TICI] 2c-3). Secondary outcome was good functional outcome defined as 0-2 on the Modified Ranking Scale (mRS) after 90 days.RESULTS: 565 patients met inclusion criteria. Multivariable logistic regression analysis showed that favorable VO (OR= 2.10 [95% CI 1.39-3.16]; p<0.001) was associated with excellent vessel reperfusion during thrombectomy, regardless of good CTA collateral status (OR= 0.87 [95%CI 0.58-1.34]; p=0.48). A favorable VO profile (OR= 8.9 [95%CI 5.3-14.9]; p<0.001) and excellent vessel reperfusion status (OR = 2.7 [95%CI 1.7-4.4]; p<0.001) were independently associated with good functional outcome adjusted for age, sex, glucose, tPA administration, good CTA collateral status and presentation NIHSS.CONCLUSION: A favorable VO profile is associated with reperfusion success and good functional outcomes in patients with AIS-LVO treated by endovascular thrombectomy.

    View details for DOI 10.1212/WNL.0000000000012106

    View details for PubMedID 33952649

  • Clinical Review of Computed Tomography and MR Perfusion Imaging in Neuro-Oncology. Radiologic clinics of North America Trinh, A., Wintermark, M., Iv, M. 2021; 59 (3): 323–34

    Abstract

    Neuroimaging plays an essential role in the initial diagnosis and continued surveillance of intracranial neoplasms. The advent of perfusion techniques with computed tomography and MR imaging have proven useful in neuro-oncology, offering enhanced approaches for tumor grading, guiding stereotactic biopsies, and monitoring treatment efficacy. Perfusion imaging can help to identify treatment-related processes, such as radiation necrosis, pseudoprogression, and pseudoregression, and can help to inform treatment-related decision making. Perfusion imaging is useful to differentiate between tumor types and between tumor and nonneoplastic conditions. This article reviews the clinical relevance and implications of perfusion imaging in neuro-oncology and highlights promising perfusion biomarkers.

    View details for DOI 10.1016/j.rcl.2021.01.002

    View details for PubMedID 33926680

  • Computed Tomography-Based Imaging Algorithms for Patient Selection in Acute Ischemic Stroke. Neuroimaging clinics of North America Pulli, B., Heit, J. J., Wintermark, M. 2021; 31 (2): 235–50

    Abstract

    Computed tomography remains the most widely used imaging modality for evaluating patients with acute ischemic stroke. Landmark trials have used computed tomography imaging to select patients for intravenous thrombolysis and endovascular treatment. This review summarizes the most important acute ischemic stroke trials, provides an outlook of ongoing studies, and proposes possible image algorithms for patient selection. Although evaluation with anatomic computed tomography imaging techniques is sufficient in early window patients, more advanced imaging techniques should be used beyond 6hours from symptoms onset to quantify the ischemic core and evaluate for the salvageable penumbra.

    View details for DOI 10.1016/j.nic.2020.12.002

    View details for PubMedID 33902877

  • Venous Outflow Profiles Are Linked to Cerebral Edema Formation at Noncontrast Head CT after Treatment in Acute Ischemic Stroke Regardless of Collateral Vessel Status at CT Angiography. Radiology Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Meyer, L., Marks, M. P., Broocks, G., Flottmann, F., Lansberg, M. G., Albers, G. W., Fiehler, J., Wintermark, M., Heit, J. J. 2021: 203651

    Abstract

    Background Ischemic lesion net water uptake (NWU) at noncontrast head CT enables quantification of cerebral edema in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Purpose To assess whether favorable venous outflow (VO) profiles at CT angiography are associated with reduced NWU and good functional outcomes in patients with AIS due to LVO. Materials and Methods This multicenter retrospective cohort study evaluated consecutive patients with AIS due to LVO who underwent thrombectomy triage between January 2013 and December 2019. Arterial collateral vessel status (Tan scale) and venous output were measured at CT angiography. Venous outflow was graded with use of the cortical vein opacification score, which quantifies opacification of the vein of Labbe, sphenoparietal sinus, and superficial middle cerebral vein. Favorable VO was regarded as a score of 3-6 and unfavorable VO as a score of 0-2. NWU was determined at follow-up noncontrast CT. Multivariable regression analyses were performed to determine the association between favorable VO profiles and NWU after treatment and good functional outcome (modified Rankin Scale, ≤2). Results A total of 580 patients were included. Of the 580 patients, 231 had favorable VO (104 women; median age, 73 years [interquartile range {IQR}, 62-81 years]) and 349 had unfavorable VO (190 women; median age, 77 years [IQR, 66-84 years]). Compared with patients with unfavorable VO, those with favorable VO exhibited lower baseline National Institutes of Health Stroke Scale score (median, 12.5 [IQR, 7-17] vs 17 [IQR, 13-21]), higher Alberta Stroke Program Early CT Score (median, 9 [IQR, 7-10] vs 7 [IQR, 6-8]), and less NWU after treatment (median, 7% [IQR, 4.6%-11.5%] vs 17.9% [IQR, 12.3%-22.2%]). In a multivariable regression analysis, NWU mean difference between patients with unfavorable VO and those with favorable VO was 6.1% (95% CI: 4.9, 7.3; P < .001) regardless of arterial CT angiography collateral vessel status (b coefficient, 0.72 [95% CI: -0.59, 2.03; P = .28]). Favorable VO (odds ratio [OR]: 4.1 [95% CI: 2.2, 7.7]; P < .001) and reduced NWU after treatment (OR: 0.77 [95% CI: 0.73, 0.83]; P < .001) were independently associated with good functional outcomes. Conclusion Favorable venous outflow (VO) correlated with reduced ischemic net water uptake (NWU) after treatment. Reduced NWU and favorable VO were associated with good functional outcomes regardless of CT angiography arterial collateral vessel status. ©RSNA, 2021 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2021203651

    View details for PubMedID 33825511

  • ADC, D, f dataset calculated through the simplified IVIM model, with MGMT promoter methylation, age, and ECOG, in 38 patients with wildtype IDH glioblastoma. Data in brief Maralani, P. J., Myrehaug, S., Mehrabian, H., Chan, A. K., Wintermark, M., Heyn, C., Conklin, J., Ellingson, B. M., Rahimi, S., Lau, A. Z., Tseng, C., Soliman, H., Detsky, J., Daghighi, S., Keith, J., Munoz, D. G., Das, S., Atenafu, E. G., Lipsman, N., Perry, J., Stanisz, G., Sahgal, A. 2021; 35: 106950

    Abstract

    Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm2) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient (D) and perfusion fraction (f) maps; ADC was calculated using the natural logarithm of b=1000 over b=0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMTPMS), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, "Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma", published in Radiotherapy and Oncology [1].

    View details for DOI 10.1016/j.dib.2021.106950

    View details for PubMedID 33850982

  • Does Carotid Artery Tortuosity Play a Role in Stroke? Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes Saba, L., Sanfilippo, R., Suri, J. S., Cademartiri, F., Corrias, G., Mannelli, L., Zucca, S., Senis, I., Montisci, R., Wintermark, M. 2021: 846537121991057

    Abstract

    PURPOSE: To explore the association between carotid artery length and tortuosity, and the occurrence of stroke.MATERIAL AND METHODS: In this retrospective study, IRB approved, 411 consecutive patients (males: 245; median age: 56 ± 12 years, age range: 21-93 years) with anterior circulation ischemic stroke were included. Only patients that underwent CTA within 7 days were considered and stroke caused by cardiac embolism and thoracic aorta embolism were excluded. For each patient, both carotid arteries were considered, and the ICA, CCA-ICA length and tortuosity were calculated. Inter-observer analysis was quantified with the Bland-Altman test. Mann-Whitney test and logistic regression analysis were also calculated to test the association between length and tortuosity with the occurrence of stroke.RESULTS: In the final analysis, 166 patients (males: 72; median age: 54 ± 12 years, age range: 24-89 years) with anterior circulation ischemic stroke that were admitted to our hospital between February 2008 and December 2013 were included. The results showed a good concordance for the length of the vessels with a mean variation of 0.7% and 0.5% for CCA-ICA and ICA length respectively an for the tortuosity with a mean variation of 0.2% and -0.4% for CCA-ICA and ICA respectively. The analysis shows a statistically significant association between the tortuosity index of the ICA and CCA-ICA sides with stroke (P value = 0.0001 in both cases) and these findings were confirmed also with the logistic regression analysis.CONCLUSION: Results of this study suggest that tortuosity index is associated with the presence of stroke whereas the length of the carotid arteries does not play a significant role.

    View details for DOI 10.1177/0846537121991057

    View details for PubMedID 33656944

  • The Cerebral Collateral Cascade: Rethinking the Assessment of Vascular Pathways in Acute Ischemic Stroke Patients. Faizy, T. D., Mlynash, M., Kabiri, R., Christensen, S., Kuraitis, G., Mader, M., Flottmann, F., Broocks, G., Lansberg, M. G., Albers, G., Marks, M., Fiehler, J., Wintermark, M., Heit, J. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • Altered cerebral perfusion in response to chronic mild hypercapnia and head-down tilt Bed rest as an analog for Spaceflight. Neuroradiology Roberts, D. R., Collins, H. R., Lee, J. K., Taylor, J. A., Turner, M., Zaharchuk, G., Wintermark, M., Antonucci, M. U., Mulder, E. R., Gerlach, D. A., Asemani, D., McGregor, H. R., Seidler, R. D. 2021

    Abstract

    PURPOSE: Following prolonged stays on the International Space Station (ISS), some astronauts exhibit visual acuity changes, ophthalmological findings, and mildly elevated intracranial pressures as part of a novel process called spaceflight-associated neuro-ocular syndrome (SANS). To determine the pathophysiology of SANS, NASA conducted a multi-investigator study in which 11 healthy participants underwent head-down tilt bed rest, mimicking microgravity-induced cephalad fluid shifts, combined with elevated ambient CO2 levels similar to those on the ISS (HDT+CO2). As part of that study, we examined the effects of HDT+CO2 on cerebral perfusion.METHODS: Using arterial spin labeling, we compared cerebral perfusion before, during, and after HDT+CO2 in participants who developed SANS (n = 5) with those who did not (n = 6).RESULTS: All participants demonstrated a decrease in perfusion during HDT+CO2 (mean decrease of 25.1% at HDT7 and 16.2% at HDT29); however, the timing and degree of change varied between the groups. At day 7 of HDT+CO2, the SANS group experienced a greater reduction in perfusion than the non-SANS group (p =.05, 95% CI:-0.19 to 16.11, d=.94, large effect). Conversely, by day 29 of HDT+CO2, the SANS group had significantly higher perfusion (approaching their baseline) than the non-SANS group (p=.04, 95% CI:0.33 to 13.07, d=1.01, large effect).CONCLUSION: Compared with baseline and recovery, HDT+CO2 resulted in reduced cerebral perfusion which varied based on SANS status. Further studies are needed to unravel the relative role of HDT vs hypercapnia, to determine if these perfusion changes are clinically relevant, and whether perfusion changes contribute to the development of SANS during spaceflight.

    View details for DOI 10.1007/s00234-021-02660-8

    View details for PubMedID 33587162

  • The Utility of Domain-Specific End Points in Acute Stroke Trials. Stroke Cramer, S. C., Wolf, S. L., Saver, J. L., Johnston, K. C., Mocco, J., Lansberg, M. G., Savitz, S. I., Liebeskind, D. S., Smith, W., Wintermark, M., Elm, J. J., Khatri, P., Broderick, J. P., Janis, S., NIH StrokeNet Recovery and Rehabilitation Group and the Acute Stroke Group, Chen, D., Dromerick, A., Dunning, K., Grande, A. W., Marshall, R. S., Meinzer, C., Page, S., Reiss, A., Richards, L., Wechsler, L., Winstein, C., Bushnell, C., Edwards, D., Lo, W., Lee, J., Amlie-Lefond, C. M., Albers, G. W., Dempsey, R., Gropen, T. I., Jauch, E. C., Leira, E. C., Martin, R., Meyer, B. C., Schindler, K., Scott, P., Singhal, A. B., Moy, C. S. 2021: STROKEAHA120031939

    View details for DOI 10.1161/STROKEAHA.120.031939

    View details for PubMedID 33563009

  • Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Broocks, G., Hanning, U., Nawabi, J., Lansberg, M. G., Marks, M. P., Albers, G. W., Fiehler, J., Wintermark, M., Heit, J. J. 2021: 271678X21992200

    Abstract

    Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (HIR; volume ratio of brain tissue with [Tmax>10sec/Tmax>6sec]); favorable TLC were regarded as HIR ≤ 0.4. NWU was determined using a quantitative densitometry approach on follow-up CT. Primary outcome was NWU. Secondary outcome was a good functional outcome (modified Rankin Scale [mRS] 0-2).580 patients met inclusion criteria. Favorable TLC (beta: 4.23, SE: 0.65; p<0.001) predicted smaller NWU after treatment. Favorable TLC (OR: 2.35, [95% CI: 1.31-4.21]; p<0.001), and decreased NWU (OR: 0.75, [95% CI: 0.70-0.79]; p<0.001) predicted good functional outcome, while controlling for age, glucose, CTA collaterals, baseline NIHSS and good vessel reperfusion status.We conclude that favorable TLC predict less ischemic lesion NWU after treatment in AIS-LVO patients. Favorable TLC and decreased NWU were independent predictors of good functional outcome.

    View details for DOI 10.1177/0271678X21992200

    View details for PubMedID 33557694

  • Shear Wave Elastography of Invasive Ductal Carcinoma: Correlations between Shear Wave Velocity and Histological Prognostic Factors. Current medical science Hu, X., Peng, L., Wintermark, M., Lipson, J. A., Zhang, Y., Gao, Y. 2021; 41 (1): 173–79

    Abstract

    The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.

    View details for DOI 10.1007/s11596-021-2333-2

    View details for PubMedID 33582923

  • Multinational Survey of Current Practice from Imaging to Treatment of Atherosclerotic Carotid Stenosis. Cerebrovascular diseases (Basel, Switzerland) Saba, L., Mossa-Basha, M., Abbott, A., Lanzino, G., Wardlaw, J. M., Hatsukami, T. S., Micheletti, G., Balestrieri, A., Hedin, U., Moody, A. R., Wintermark, M., DeMarco, J. K. 2021: 1–13

    Abstract

    BACKGROUND: In the last 20-30 years, there have been many advances in imaging and therapeutic strategies for symptomatic and asymptomatic individuals with carotid artery stenosis. Our aim was to examine contemporary multinational practice standards.METHODS: Departmental Review Board approval for this study was obtained, and 3 authors prepared the 44 multiple choice survey questions. Endorsement was obtained by the European Society of Neuroradiology, American Society of Functional Neuroradiology, and African Academy of Neurology. A link to the online questionnaire was sent to their respective members and members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS). The questionnaire was open from May 16 to July 16, 2019.RESULTS: The responses from 223 respondents from 46 countries were included in the analyses including 65.9% from academic university hospitals. Neuroradiologists/radiologists comprised 68.2% of respondents, followed by neurologists (15%) and vascular surgeons (12.9%). In symptomatic patients, half (50.4%) the respondents answered that the first exam they used to evaluate carotid bifurcation was ultrasound, followed by computed tomography angiography (CTA, 41.6%) and then magnetic resonance imaging (MRI 8%). In asymptomatic patients, the first exam used to evaluate carotid bifurcation was ultrasound in 88.8% of respondents, CTA in 7%, and MRA in 4.2%. The percent stenosis upon which carotid endarterectomy or stenting was recommended was reduced in the presence of imaging evidence of "vulnerable plaque features" by 66.7% respondents for symptomatic patients and 34.2% for asymptomatic patients with a smaller subset of respondents even offering procedural intervention to patients with <50% symptomatic or asymptomatic stenosis.CONCLUSIONS: We found heterogeneity in current practices of carotid stenosis imaging and management in this worldwide survey with many respondents including vulnerable plaque imaging into their decision analysis despite the lack of proven benefit from clinical trials. This study highlights the need for new clinical trials using vulnerable plaque imaging to select high-risk patients despite maximal medical therapy who may benefit from procedural intervention.

    View details for DOI 10.1159/000512181

    View details for PubMedID 33440369

  • Molecular mechanism study of EGFR allosteric inhibitors using molecular dynamics simulations and free energy calculations JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS Wu, X., Guo, Q., Li, Q., Wan, S., Li, Z., Zhang, J. 2021: 1–10

    Abstract

    ABTRACT The epidermal growth factor receptor (EGFR) kinase inhibitors Gefitinib, Erlotinib, Afatinib and Osimertinib have been approved for the treatments of non-small cell lung cancer patients harboring sensitive EGFR mutations, but resistance arises rapidly. To date all approved EGFR inhibitors are ATP-competitive inhibitors, highlighting the need for therapeutic agents with alternative mechanisms of action. Allosteric kinase inhibitors offer a promising new therapeutic strategy to ATP-competitive inhibitors. The mutant-selective allosteric EGFR inhibitors EAI045 exhibited higher potency for EGFRL858R&T790M compared to WT, which was also effective in EGFR-mutant models including those harboring the C797S mutation. However, it was not effective as a single-agent inhibitor, and require the co-administration of the anti-EGFR antibody Cetuximab. Further efforts produced a more potent analog JBJ-04-125-02, which can inhibit cell proliferation as a single-agent inhibitor. In the present study, molecular dynamics simulations and free energy calculations were performed and revealed the detailed inhibitory mechanism of JBJ-04-125-02 as more potent EGFR inhibitor. Moreover, the energy difference between HOMO and LUMO calculated by DFT implied the higher interaction of JBJ-04-125-02 than EAI045 in the active site of the EGFR. The identified key features obtained from the molecular modeling enabled us to design novel EGFR allosteric inhibitors. Communicated by Ramaswamy H. Sarma.

    View details for DOI 10.1080/07391102.2021.1874530

    View details for Web of Science ID 000608504400001

    View details for PubMedID 33459177

  • Predicted Cost Savings Achieved by the Radiology Support, Communication and Alignment Network from Reducing Medical Imaging Overutilization in the Medicare Population. Journal of the American College of Radiology : JACR Wintermark, M. n., Rosenkrantz, A. B., Rezaii, P. G., Fredericks, N. n., Cerdas, L. C., Burleson, J. n., Haines, G. R., Chatfield, M. n., Thorwarth, W. T., Duszak, R. n., Hughes, D. R. 2021

    Abstract

    The Radiology Support, Communication and Alignment Network (R-SCAN) is a quality improvement program through which patients, referring clinicians, and radiologists collaborate to improve imaging appropriateness based on Choosing Wisely recommendations and ACR Appropriateness Criteria. R-SCAN was shown previously to increase the odds of obtaining an appropriate, higher patient or diagnostic value, imaging study. In the current study, we aimed to estimate the potential imaging cost savings associated with R-SCAN use for the Medicare population.The R-SCAN data set was used to determine the proportion of appropriate and lesser value imaging studies performed, as well as the percent change in the total number of imaging studies performed, before and after an R-SCAN educational intervention. Using a separate CMS data set, we then identified the total number of relevant imaging studies and associated total costs using a 5% sample of Medicare beneficiaries in 2017. We applied R-SCAN proportions to the CMS data set to estimate the potential impact of the R-SCAN interventions across a broader Medicare population.We observed a substantial reduction in the costs associated with lesser value imaging in the R-SCAN cohort, totaling $260,000 over 3.5 months. When extrapolated to the Medicare population, the potential cost reductions associated with the decrease in lesser value imaging totaled $433 million yearly.If expanded broadly, R-SCAN interventions can result in substantial savings to the Medicare program.

    View details for DOI 10.1016/j.jacr.2020.12.011

    View details for PubMedID 33444562

  • Noninvasive disconnection of targeted neuronal circuitry sparing axons of passage and nonneuronal cells. Journal of neurosurgery Wang, Y., Anzivino, M. J., Zhang, Y., Bertram, E. H., Woznak, J., Klibanov, A. L., Dumont, E., Wintermark, M., Lee, K. S. 2021: 1-11

    Abstract

    Surgery can be highly effective for the treatment of medically intractable, neurological disorders, such as drug-resistant focal epilepsy. However, despite its benefits, surgery remains substantially underutilized due to both surgical concerns and nonsurgical impediments. In this work, the authors characterized a noninvasive, nonablative strategy to focally destroy neurons in the brain parenchyma with the goal of limiting collateral damage to nontarget structures, such as axons of passage.Low-intensity MR-guided focused ultrasound (MRgFUS), together with intravenous microbubbles, was used to open the blood-brain barrier (BBB) in a transient and focal manner in rats. The period of BBB opening was exploited to focally deliver to the brain parenchyma a systemically administered neurotoxin (quinolinic acid) that is well tolerated peripherally and otherwise impermeable to the BBB.Focal neuronal loss was observed in targeted areas of BBB opening, including brain regions that are prime objectives for epilepsy surgery. Notably, other structures in the area of neuronal loss, including axons of passage, glial cells, vasculature, and the ventricular wall, were spared with this procedure.These findings identify a noninvasive, nonablative approach capable of disconnecting neural circuitry while limiting the neuropathological consequences that attend other surgical procedures. Moreover, this strategy allows conformal targeting, which could enhance the precision and expand the treatment envelope for treating irregularly shaped surgical objectives located in difficult-to-reach sites. Finally, if this strategy translates to the clinic, the noninvasive nature and specificity of the procedure could positively influence both physician referrals for and patient confidence in surgery for medically intractable neurological disorders.

    View details for DOI 10.3171/2021.7.JNS21123

    View details for PubMedID 34798617

  • CT Perfusion Collateral Index in Assessment of Collaterals in Acute Ischemic Stroke with Delayed Presentation: Comparison to Single Phase CTA. Journal of neuroradiology = Journal de neuroradiologie Nael, K., Sakai, Y., Larson, J., Goldstein, J., Deutsch, J., J Awad, A., Pawha, P., Aggarwal, A., Fifi, J., Deleacy, R., Yaniv, G., Wintermark, M., Liebeskind, D. S., Shoirah, H., Mocco, J. 2021

    Abstract

    Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients.ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS.A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p<0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p=0.001) and good functional outcome (p=0.003).CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging biomarker of collateral status in patients with delayed presentation of AIS.

    View details for DOI 10.1016/j.neurad.2021.11.002

    View details for PubMedID 34800563

  • Multicenter DSC-MRI-Based Radiomics Predict IDH Mutation in Gliomas. Cancers Manikis, G. C., Ioannidis, G. S., Siakallis, L., Nikiforaki, K., Iv, M., Vozlic, D., Surlan-Popovic, K., Wintermark, M., Bisdas, S., Marias, K. 2021; 13 (16)

    Abstract

    To address the current lack of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI)-based radiomics to predict isocitrate dehydrogenase (IDH) mutations in gliomas, we present a multicenter study that featured an independent exploratory set for radiomics model development and external validation using two independent cohorts. The maximum performance of the IDH mutation status prediction on the validation set had an accuracy of 0.544 (Cohen's kappa: 0.145, F1-score: 0.415, area under the curve-AUC: 0.639, sensitivity: 0.733, specificity: 0.491), which significantly improved to an accuracy of 0.706 (Cohen's kappa: 0.282, F1-score: 0.474, AUC: 0.667, sensitivity: 0.6, specificity: 0.736) when dynamic-based standardization of the images was performed prior to the radiomics. Model explainability using local interpretable model-agnostic explanations (LIME) and Shapley additive explanations (SHAP) revealed potential intuitive correlations between the IDH-wildtype increased heterogeneity and the texture complexity. These results strengthened our hypothesis that DSC-MRI radiogenomics in gliomas hold the potential to provide increased predictive performance from models that generalize well and provide understandable patterns between IDH mutation status and the extracted features toward enabling the clinical translation of radiogenomics in neuro-oncology.

    View details for DOI 10.3390/cancers13163965

    View details for PubMedID 34439118

  • Neuroradiologic Evaluation of MRI in High-Contact Sports. Frontiers in neurology McAllister, D., Akers, C., Boldt, B., Mitchell, L. A., Tranvinh, E., Douglas, D., Goubran, M., Rosenberg, J., Georgiadis, M., Karimpoor, M., DiGiacomo, P., Mouchawar, N., Grant, G., Camarillo, D., Wintermark, M., Zeineh, M. M. 2021; 12: 701948

    Abstract

    Background and Purpose: Athletes participating in high-contact sports experience repeated head trauma. Anatomical findings, such as a cavum septum pellucidum, prominent CSF spaces, and hippocampal volume reductions, have been observed in cases of mild traumatic brain injury. The extent to which these neuroanatomical findings are associated with high-contact sports is unknown. The purpose of this study was to determine whether there are subtle neuroanatomic differences between athletes participating in high-contact sports compared to low-contact athletic controls. Materials and Methods: We performed longitudinal structural brain MRI scans in 63 football (high-contact) and 34 volleyball (low-contact control) male collegiate athletes with up to 4 years of follow-up, evaluating a total of 315 MRI scans. Board-certified neuroradiologists performed semi-quantitative visual analysis of neuroanatomic findings, including: cavum septum pellucidum type and size, extent of perivascular spaces, prominence of CSF spaces, white matter hyperintensities, arterial spin labeling perfusion asymmetries, fractional anisotropy holes, and hippocampal size. Results: At baseline, cavum septum pellucidum length was greater in football compared to volleyball controls (p = 0.02). All other comparisons were statistically equivalent after multiple comparison correction. Within football at baseline, the following trends that did not survive multiple comparison correction were observed: more years of prior football exposure exhibited a trend toward more perivascular spaces (p = 0.03 uncorrected), and lower baseline Standardized Concussion Assessment Tool scores toward more perivascular spaces (p = 0.02 uncorrected) and a smaller right hippocampal size (p = 0.02 uncorrected). Conclusion: Head impacts in high-contact sport (football) athletes may be associated with increased cavum septum pellucidum length compared to low-contact sport (volleyball) athletic controls. Other investigated neuroradiology metrics were generally equivalent between sports.

    View details for DOI 10.3389/fneur.2021.701948

    View details for PubMedID 34456852

    View details for PubMedCentralID PMC8385770

  • Cost-effectiveness of endovascular thrombectomy in patients with low Alberta Stroke Program Early CT Scores (< 6) at presentation. Journal of neurosurgery Wu, X. n., Payabvash, S. n., Matouk, C. C., Lev, M. H., Wintermark, M. n., Sanelli, P. n., Gandhi, D. n., Malhotra, A. n. 2021: 1–11

    Abstract

    The utility of endovascular thrombectomy (EVT) in patients with acute ischemic stroke, large vessel occlusion (LVO), and low Alberta Stroke Program Early CT Scores (ASPECTS) remains uncertain. The objective of this study was to determine the health outcomes and cost-effectiveness of EVT versus medical management in patients with ASPECTS < 6.A decision-analytical study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT-treated patients compared to medical management. The study was performed over a lifetime horizon with a societal perspective in the US setting.The incremental cost-effectiveness ratios were $412,411/QALY and $1,022,985/QALY for 55- and 65-year-old groups in the short-term model. EVT was the long-term cost-effective strategy in 96.16% of the iterations and resulted in differences in health benefit of 2.21 QALYs and 0.79 QALYs in the 55- and 65-year-old age groups, respectively, equivalent to 807 days and 288 days in perfect health. EVT remained the more cost-effective strategy when the probability of good outcome with EVT was above 16.8% or as long as the good outcome associated with the procedure was at least 1.6% higher in absolute value than that of medical management. EVT remained cost-effective even when its cost exceeded $100,000 (threshold was $108,036). Although the cost-effectiveness decreased with age, EVT was cost-effective for 75-year-old patients as well.This study suggests that EVT is the more cost-effective approach compared to medical management in patients with ASPECTS < 6 in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with nonreperfusion.

    View details for DOI 10.3171/2020.9.JNS202965

    View details for PubMedID 33962378

  • Non-contrast dual-energy CT virtual ischemia maps accurately estimate ischemic core size in large-vessel occlusive stroke. Scientific reports Wolman, D. N., van Ommen, F. n., Tong, E. n., Kauw, F. n., Dankbaar, J. W., Bennink, E. n., de Jong, H. W., Molvin, L. n., Wintermark, M. n., Heit, J. J. 2021; 11 (1): 6745

    Abstract

    Dual-energy CT (DECT) material decomposition techniques may better detect edema within cerebral infarcts than conventional non-contrast CT (NCCT). This study compared if Virtual Ischemia Maps (VIM) derived from non-contrast DECT of patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are superior to NCCT for ischemic core estimation, compared against reference-standard DWI-MRI. Only patients whose baseline ischemic core was most likely to remain stable on follow-up MRI were included, defined as those with excellent post-thrombectomy revascularization or no perfusion mismatch. Twenty-four consecutive AIS-LVO patients with baseline non-contrast DECT, CT perfusion (CTP), and DWI-MRI were analyzed. The primary outcome measure was agreement between volumetric manually segmented VIM, NCCT, and automatically segmented CTP estimates of the ischemic core relative to manually segmented DWI volumes. Volume agreement was assessed using Bland-Altman plots and comparison of CT to DWI volume ratios. DWI volumes were better approximated by VIM than NCCT (VIM/DWI ratio 0.68 ± 0.35 vs. NCCT/DWI ratio 0.34 ± 0.35; P < 0.001) or CTP (CTP/DWI ratio 0.45 ± 0.67; P < 0.001), and VIM best correlated with DWI (rVIM = 0.90; rNCCT = 0.75; rCTP = 0.77; P < 0.001). Bland-Altman analyses indicated significantly greater agreement between DWI and VIM than NCCT core volumes (mean bias 0.60 [95%AI 0.39-0.82] vs. 0.20 [95%AI 0.11-0.30]). We conclude that DECT VIM estimates the ischemic core in AIS-LVO patients more accurately than NCCT.

    View details for DOI 10.1038/s41598-021-85143-3

    View details for PubMedID 33762589

  • Automatic segmentation, feature extraction and comparison of healthy and stroke cerebral vasculature. NeuroImage. Clinical Deshpande, A. n., Jamilpour, N. n., Jiang, B. n., Michel, P. n., Eskandari, A. n., Kidwell, C. n., Wintermark, M. n., Laksari, K. n. 2021; 30: 102573

    Abstract

    Accurate segmentation of cerebral vasculature and a quantitative assessment of its morphology is critical to various diagnostic and therapeutic purposes and is pertinent to studying brain health and disease. However, this is still a challenging task due to the complexity of the vascular imaging data. We propose an automated method for cerebral vascular segmentation without the need of any manual intervention as well as a method to skeletonize the binary segmented map to extract vascular geometric features and characterize vessel structure. We combine a Hessian-based probabilistic vessel-enhancing filtering with an active-contour-based technique to segment magnetic resonance and computed tomography angiograms (MRA and CTA) and subsequently extract the vessel centerlines and diameters to calculate the geometrical properties of the vasculature. Our method was validated using a 3D phantom of the Circle-of-Willis region, demonstrating 84% mean Dice similarity coefficient (DSC) and 85% mean Pearson's correlation coefficient (PCC) with minimal modified Hausdorff distance (MHD) error (3 surface pixels at most), and showed superior performance compared to existing segmentation algorithms upon quantitative comparison using DSC, PCC and MHD. We subsequently applied our algorithm to a dataset of 40 subjects, including 1) MRA scans of healthy subjects (n = 10, age = 30 ± 9), 2) MRA scans of stroke patients (n = 10, age = 51 ± 15), 3) CTA scans of healthy subjects (n = 10, age = 62 ± 12), and 4) CTA scans of stroke patients (n = 10, age = 68 ± 11), and obtained a quantitative comparison between the stroke and normal vasculature for both imaging modalities. The vascular network in stroke patients compared to age-adjusted healthy subjects was found to have a significantly (p < 0.05) higher tortuosity (3.24 ± 0.88 rad/cm vs. 7.17 ± 1.61 rad/cm for MRA, and 4.36 ± 1.32 rad/cm vs. 7.80 ± 0.92 rad/cm for CTA), higher fractal dimension (1.36 ± 0.28 vs. 1.71 ± 0.14 for MRA, and 1.56 ± 0.05 vs. 1.69 ± 0.20 for CTA), lower total length (3.46 ± 0.99 m vs. 2.20 ± 0.67 m for CTA), lower total volume (61.80 ± 18.79 ml vs. 34.43 ± 22.9 ml for CTA), lower average diameter (2.4 ± 0.21 mm vs. 2.18 ± 0.07 mm for CTA), and lower average branch length (4.81 ± 1.97 mm vs. 8.68 ± 2.03 mm for MRA), respectively. We additionally studied the change in vascular features with respect to aging and imaging modality. While we observed differences between features as a result of aging, statistical analysis did not show any significant differences, whereas we found that the number of branches were significantly different (p < 0.05) between the two imaging modalities (201 ± 73 for MRA vs. 189 ± 69 for CTA). Our segmentation and feature extraction algorithm can be applied on any imaging modality and can be used in the future to automatically obtain the 3D segmented vasculature for diagnosis and treatment planning as well as to study morphological changes due to stroke and other cerebrovascular diseases (CVD) in the clinic.

    View details for DOI 10.1016/j.nicl.2021.102573

    View details for PubMedID 33578323

  • Impact of Clot Shape on Successful M1 Endovascular Reperfusion. Frontiers in neurology Guenego, A., Fahed, R., Sussman, E. S., Leipzig, M., Albers, G. W., Martin, B. W., Marcellus, D. G., Kuraitis, G., Marks, M. P., Lansberg, M. G., Wintermark, M., Heit, J. J. 2021; 12: 642877

    Abstract

    Objectives: The susceptibility-vessel-sign (SVS) allows thrombus visualization, length estimation and composition, and it may impact reperfusion during mechanical thrombectomy (MT). SVS can also describe thrombus shape in the occluded artery: in the straight M1-segment (S-shaped), or in an angulated/traversing a bifurcation segment (A-shaped). We determined whether SVS clot shape influenced reperfusion and outcomes after MT for proximal middle-cerebral-artery (M1) occlusions. Methods: Between May 2015 and March 2018, consecutive patients who underwent MT at one comprehensive stroke center and who had a baseline MRI with a T2* sequence were included. Clinical, procedural and radiographic data, including clot shape on SVS [angulated/bifurcation (A-SVS) vs. straight (S-SVS)] and length were assessed. Primary outcome was successful reperfusion (TICI 2b-3). Secondary outcome were MT complication rates, MT reperfusion time, and clinical outcome at 90-days. Predictors of outcome were assessed with univariate and multivariate analyses. Results: A total of 62 patients were included. 56% (35/62) had an A-SVS. Clots were significantly longer in the A-SVS group (19 mm vs. 8 mm p = 0.0002). Groups were otherwise well-matched with regard to baseline characteristics. There was a significantly lower rate of successful reperfusion in the A-SVS cohort (83%) compared to the S-SVS cohort (96%) in multivariable analysis [OR 0.04 (95% CI, 0.002-0.58), p = 0.02]. There was no significant difference in long term clinical outcome between groups. Conclusion: Clot shape as determined on T2* imaging, in patients presenting with M1 occlusion appears to be a predictor of successful reperfusion after MT. Angulated and bifurcating clots are associated with poorer rates of successful reperfusion.

    View details for DOI 10.3389/fneur.2021.642877

    View details for PubMedID 33597919

  • Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Maralani, P. J., Myrehaug, S. n., Mehrabian, H. n., Chan, A. K., Wintermark, M. n., Heyn, C. n., Conklin, J. n., Ellingson, B. M., Rahimi, S. n., Lau, A. Z., Tseng, C. L., Soliman, H. n., Detsky, J. n., Daghighi, S. n., Keith, J. n., Munoz, D. G., Das, S. n., Atenafu, E. G., Lipsman, N. n., Perry, J. n., Stanisz, G. n., Sahgal, A. n. 2021

    Abstract

    Prediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome.38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2 FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADCT1C, ADCT2-FLAIR) and perfusion fraction (fT1C, fT2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated.Higher ADCT2-FLAIR at baseline [Odds Ratio (OR)=1.06, 95% CI 1.01-1.15, p=0.025], lower fT2-FLAIR at fraction 10 (OR=2.11, 95% CI 1.04-4.27, p=0.018), and lack of increase in ADCT2-FLAIR at fraction 20 compared to baseline (OR=1.12, 95% CI 1.02-1.22, p=0.02) were associated with early progression. Combining ADCT2-FLAIR at baseline, fT2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p=0.001). Using multivariable analysis, neither IVIM metric was associated with OS but higher fT2-FLAIR at fraction 10 (HR=0.72, 95% CI 0.56-0.95, p=0.018) was associated with longer PFS.ADCT2-FLAIR at baseline, or its lack of increase from baseline to fraction 20, and fT2-FLAIR at fraction 10 significantly predicted early progression. fT2-FLAIR at fraction 10 was associated with PFS.

    View details for DOI 10.1016/j.radonc.2020.12.037

    View details for PubMedID 33418005

  • Favorable Venous Outflow Profiles Correlate With Favorable Tissue-Level Collaterals and Clinical Outcome. Stroke Faizy, T. D., Kabiri, R. n., Christensen, S. n., Mlynash, M. n., Kuraitis, G. M., Broocks, G. n., Flottmann, F. n., Marks, M. P., Lansberg, M. G., Albers, G. W., Fiehler, J. n., Wintermark, M. n., Heit, J. J. 2021: STROKEAHA120032242

    Abstract

    Patients with acute ischemic stroke due to large vessel occlusion and favorable tissue-level collaterals (TLCs) likely have robust cortical venous outflow (VO). We hypothesized that favorable VO predicts robust TLC and good clinical outcomes.Multicenter retrospective cohort study of consecutive acute ischemic stroke due to large vessel occlusion patients who underwent thrombectomy triage. Included patients had interpretable prethrombectomy computed tomography, computed tomography angiography, and cerebral perfusion imaging. TLCs were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (volume ratio of brain tissue with [Tmax >10 s/Tmax >6 s]). VO was determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on computed tomography angiography as 0, not visible; 1, moderate opacification; and 2, full. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analyses, we determined the association between VO and (1) favorable TLC status (defined as hypoperfusion intensity ratio ≤0.4) and (2) good functional outcome (modified Rankin Scale score, 0-2).Six hundred forty-nine patients met inclusion criteria. Patients with favorable VO were younger (median age, 72 [interquartile range (IQR), 62-80] versus 77 [IQR, 66-84] years), had a lower baseline National Institutes of Health Stroke Scale (median, 12 [IQR, 7-17] versus 19 [IQR, 13-20]), and had a higher Alberta Stroke Program Early Computed Tomography Score (median, 9 [IQR, 7-10] versus 7 [IQR, 6-9]). Favorable VO strongly predicted favorable TLC (odds ratio, 4.5 [95% CI, 3.1-6.5]; P<0.001) in an adjusted regression analysis. Favorable VO also predicted good clinical outcome (odds ratio, 10 [95% CI, 6.2-16.0]; P<0.001), while controlling for favorable TLC, age, glucose, baseline National Institutes of Health Stroke Scale, and good vessel reperfusion status.In this selective retrospective cohort study of acute ischemic stroke due to large vessel occlusion patients undergoing thrombectomy triage, favorable VO profiles correlated with favorable TLC and were associated with good functional outcomes after treatment. Future prospective studies should independently validate our findings.

    View details for DOI 10.1161/STROKEAHA.120.032242

    View details for PubMedID 33682452

  • Concurrent brain structural and functional alterations in patients with migraine without aura: an fMRI study. The journal of headache and pain Li, Z., Zhou, J., Lan, L., Cheng, S., Sun, R., Gong, Q., Wintermark, M., Zeng, F., Liang, F. 2020; 21 (1): 141

    Abstract

    OBJECTIVES: To explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS).METHODS: Seventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed.RESULTS: Compared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG.CONCLUSIONS: MRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms.TRIAL REGISTRATION: NCT01152632 . Registered 27 June 2010.

    View details for DOI 10.1186/s10194-020-01203-5

    View details for PubMedID 33287704

  • Imaging Predictors of Neurologic Outcome After Pediatric Arterial Ischemic Stroke. Stroke Jiang, B., Hills, N. K., Forsyth, R., Jordan, L. C., Slim, M., Pavlakis, S. G., Freidman, N., Dlamini, N., Farooq, O., Li, Y., Zhu, G., Fullerton, H., Wintermark, M., Lo, W. D., VIPS Investigators, Dowling, M. M., Benedict, S. L., Bernard, T. J., Fox, C. K., deVeber, G., Friedman, N. R., Lo, W., Ichord, R. N., Tan, M., Mackay, M., Kirton, A., Hernandez Chavez, M. I., Humphreys, P., Sultan, S., Rivkin, M. J., Yeh, A., Rafay, M. F., Titomanlio, L., Kovacevic, G. S., Yager, J. Y., Amlie-Lefond, C., Condie, J., Kneen, R., Bjornson, B., Pergami, P., Zou, L. P., Elbers, J., Abdalla, A., Chan, A. K., Carpenter, J. L., Wong, V. C., Kirkham, F. 2020: STROKEAHA120030965

    Abstract

    BACKGROUND AND PURPOSE: To assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients.METHODS: We used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome.RESULTS: Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome.CONCLUSIONS: In the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.120.030965

    View details for PubMedID 33280552

  • Mind Over Magnets - How Magnetic Particle Imaging is Changing the Way We Think About the Future of Neuroscience. Neuroscience V Makela, A., Gaudet, J. M., Murrell, D. H., Mansfield, J. R., Wintermark, M., Contag, C. H. 2020

    Abstract

    Magnetic particle imaging (MPI) is an emerging imaging technique, which has the potential to provide the sensitivity, specificity and temporal resolution necessary for novel imaging advances in neurological applications. MPI relies on the detection of superparamagnetic iron-oxide nanoparticles, which allows for visualization and quantification of iron or iron-labeled cells throughout a subject. The combination of these qualities can be used to image many neurological conditions including cancer, inflammatory processes, vascular-related issues and could even focus on cell therapies and theranostics to treat these problems. This review will provide a basic introduction to MPI, discuss the current use of this technology to image neurological conditions, and touch on future applications including the potential for clinical translation.

    View details for DOI 10.1016/j.neuroscience.2020.10.036

    View details for PubMedID 33197498

  • Collateral Status in Ischemic Stroke: A Comparison of Computed Tomography Angiography, Computed Tomography Perfusion, and Digital Subtraction Angiography. Journal of computer assisted tomography Kauw, F., Dankbaar, J. W., Martin, B. W., Ding, V. Y., Boothroyd, D. B., van Ommen, F., de Jong, H. W., Kappelle, L. J., Velthuis, B. K., Heit, J. J., Wintermark, M. 2020; 44 (6): 984–92

    Abstract

    OBJECTIVE: To compare assessment of collaterals by single-phase computed tomography (CT) angiography (CTA) and CT perfusion-derived 3-phase CTA, multiphase CTA and temporal maximum-intensity projection (tMIP) images to digital subtraction angiography (DSA), and relate collateral assessments to clinical outcome in patients with acute ischemic stroke.METHODS: Consecutive acute ischemic stroke patients who underwent CT perfusion, CTA, and DSA before thrombectomy with occlusion of the internal carotid artery, the M1 or the M2 segments were included. Two observers assessed all CT images and one separate observer assessed DSA (reference standard) with static and dynamic (modified American Society of Interventional and Therapeutic Neuroradiology) collateral grading methods. Interobserver agreement and concordance were quantified with Cohen-weighted kappa and concordance correlation coefficient, respectively. Imaging assessments were related to clinical outcome (modified Rankin Scale, ≤ 2).RESULTS: Interobserver agreement (n = 101) was 0.46 (tMIP), 0.58 (3-phase CTA), 0.67 (multiphase CTA), and 0.69 (single-phase CTA) for static assessments and 0.52 (3-phase CTA) and 0.54 (multiphase CTA) for dynamic assessments. Concordance correlation coefficient (n = 80) was 0.08 (3-phase CTA), 0.09 (single-phase CTA), and 0.23 (multiphase CTA) for static assessments and 0.10 (3-phase CTA) and 0.27 (multiphase CTA) for dynamic assessments. Higher static collateral scores on multiphase CTA (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and tMIP images (OR, 2.0; 95% CI, 1.1-3.4) were associated with modified Rankin Scale of 2 or less as were higher modified American Society of Interventional and Therapeutic Neuroradiology scores on 3-phase CTA (OR, 1.5; 95% CI, 1.1-2.2) and multiphase CTA (OR, 1.7; 95% CI, 1.1-2.6).CONCLUSIONS: Concordance between assessments on CT and DSA was poor. Collateral status evaluated on 3-phase CTA and multiphase CTA, but not on DSA, was associated with clinical outcome.

    View details for DOI 10.1097/RCT.0000000000001090

    View details for PubMedID 33196604

  • Vessel Wall-Imaging Biomarkers of Carotid Plaque Vulnerability in StrokePrevention Trials: A viewpoint from The Carotid Imaging Consensus Group. JACC. Cardiovascular imaging Saba, L., Moody, A. R., Saam, T., Kooi, M. E., Wasserman, B. A., Staub, D., van der Lugt, A., DeMarco, J. K., Saloner, D., Wintermark, M., Gupta, A. 2020; 13 (11): 2445–56

    View details for DOI 10.1016/j.jcmg.2020.07.046

    View details for PubMedID 33153534

  • Blood Biomarkers for Detection of Brain Injury in COVID-19 Patients. Journal of neurotrauma DeKosky, S. T., Kochanek, P. M., Valadka, A., Clark, R. S., Chou, S. H., Au, A., Horvat, C. M., Jha, R. M., Mannix, R., Wisniewski, S. R., Wintermark, M., Rowell, S. E., Welch, R. D., Lewis, L. M., House, S., Tanzi, R. E., Smith, D. R., Vittor, A. Y., Denslow, N. D., Davis, M. D., Glushakova, O. Y., Hayes, R. L. 2020

    Abstract

    The SARS-CoV-2 virus attacks multiple organs of coronavirus disease (COVID-19) patients, including the brain. There are worldwide descriptions of neurologic deficits in COVID-19 patients. CNS symptoms can be present early in the course of the disease. As many as 55% of hospitalized COVID-19 patients have been reported to have neurologic disturbances three months after infection by SARS-CoV-2. The mutability of the SARS-COV-2 virus and its potential to directly affect the CNS highlight the urgency of developing technology to diagnose, manage and treat brain injury in COVID-19 patients. The pathobiology of CNS infection by SARS-CoV-2 and the associated neurologic sequelae of this infection remain poorly understood. In this review we outline the rationale for the use of blood biomarkers (BBs) for diagnosis of brain injury in COVID-19 patients, the research needed to incorporate their use into clinical practice and the improvements in patient management and outcomes that can result. BBs of brain injury could potentially provide tools for detection of brain injury in COVID-19 patients. Elevations of BBs have been reported in CSF and blood of COVID-19 patients. BB proteins have been analyzed in cerebrospinal fluid (CSF) to detect CNS involvement in patients with infectious diseases including human immunodeficiency virus (HIV) and tuberculous meningitis. BBs are approved by the US Food and Drug Administration (FDA) for diagnosis of mild versus moderate traumatic brain injury (TBI) and have identified brain injury following stroke, cardiac arrest, hypoxia and epilepsy. BBs, integrated with other diagnostic tools, could enhance understanding of viral mechanisms of brain injury, predict severity of neurological deficits, guide triage of patients and assignment to appropriate medical pathways and assess efficacy of therapeutic interventions in COVID-19 patients.

    View details for DOI 10.1089/neu.2020.7332

    View details for PubMedID 33115334

  • CT imaging features of carotid artery plaque vulnerability. Annals of translational medicine Murgia, A., Erta, M., Suri, J. S., Gupta, A., Wintermark, M., Saba, L. 2020; 8 (19): 1261

    Abstract

    Despite steady advances in medical care, cardiovascular disease remains one of the main causes of death and long-term morbidity worldwide. Up to 30% of strokes are associated with the presence of carotid atherosclerotic plaques. While the degree of stenosis has long been recognized as the main guiding factor in risk stratification and therapeutical decisions, recent evidence suggests that features of unstable, or 'vulnerable', plaques offer better prognostication capabilities. This paradigmatic shift has motivated researchers to explore the potentialities of non-invasive diagnostic tools to image not only the lumen, but also the vascular wall and the structural characteristics of the plaque. The present review will offer a panoramic on the imaging modalities currently available to characterize carotid atherosclerotic plaques and, in particular, it will focus on the increasingly important role covered by multidetector computed tomographic angiography.

    View details for DOI 10.21037/atm-2020-cass-13

    View details for PubMedID 33178793

  • Can COVID19 trigger the plaque vulnerability-a Kounis syndrome warning for "asymptomatic subjects" CARDIOVASCULAR DIAGNOSIS AND THERAPY Saba, L., Gerosa, C., Wintermark, M., Hedin, U., Fanni, D., Suri, J. S., Balestrieri, A., Faa, G. 2020; 10 (5): 1352–55

    View details for DOI 10.21037/cdt-20-561

    View details for Web of Science ID 000582467900021

    View details for PubMedID 33224760

    View details for PubMedCentralID PMC7666923

  • Synthesize High-Quality Multi-Contrast Magnetic Resonance Imaging From Multi-Echo Acquisition Using Multi-Task Deep Generative Model IEEE TRANSACTIONS ON MEDICAL IMAGING Wang, G., Gong, E., Banerjee, S., Martin, D., Tong, E., Choi, J., Chen, H., Wintermark, M., Pauly, J. M., Zaharchuk, G. 2020; 39 (10): 3089–99

    Abstract

    Multi-echo saturation recovery sequence can provide redundant information to synthesize multi-contrast magnetic resonance imaging. Traditional synthesis methods, such as GE's MAGiC platform, employ a model-fitting approach to generate parameter-weighted contrasts. However, models' over-simplification, as well as imperfections in the acquisition, can lead to undesirable reconstruction artifacts, especially in T2-FLAIR contrast. To improve the image quality, in this study, a multi-task deep learning model is developed to synthesize multi-contrast neuroimaging jointly using both signal relaxation relationships and spatial information. Compared with previous deep learning-based synthesis, the correlation between different destination contrast is utilized to enhance reconstruction quality. To improve model generalizability and evaluate clinical significance, the proposed model was trained and tested on a large multi-center dataset, including healthy subjects and patients with pathology. Results from both quantitative comparison and clinical reader study demonstrate that the multi-task formulation leads to more efficient and accurate contrast synthesis than previous methods.

    View details for DOI 10.1109/TMI.2020.2987026

    View details for Web of Science ID 000574745800010

    View details for PubMedID 32286966

  • White-matter hyperintensities in patients with carotid artery stenosis: An exploratory connectometry study. The neuroradiology journal Porcu, M., Sanfilippo, R., Montisci, R., Balestrieri, A., Suri, J. S., Wintermark, M., Saba, L. 2020: 1971400920959323

    Abstract

    BACKGROUND: White-matter lesions (WMLs) are frequently found in magnetic resonance imaging (MRi), and the WML load tends to be higher in patients affected by cervical internal carotid artery (cICA) stenosis.PURPOSE: This study aimed to investigate whether and how WMLs influence cerebral networking in patients with asymptomatic cICA stenosis eligible for carotid endarterectomy (CEA) by exploiting the connectometry technique.METHODS: The study was designed as a cross-sectional exploratory investigation, and 28 patients with cICA stenosis eligible for CEA were enrolled. All patients received an MRI scan, including a T1-weighted, a FLAIR and a diffusion-weighted (DW) sequence. The T1 and FLAIR sequences were analysed for quantification of WML burden (WMLB) and total number of WMLs (TNWMLs). The DW data were reconstructed in the MNI space using q-space diffeomorphic reconstruction, and were grouped to create a connectometry database. The connectometry analysis evaluated the influence of both the WMLB and TNWMLs to local connectivity in a multiple regression model that included age, WMLB and TNWMLs, adopting three different T-score thresholds (1, 2 and 3). A p-value corrected for false discovery rate of <0.05 was adopted as a threshold to identify statistically significant results.RESULTS: The connectometry analysis identified several white-matter bundles negatively correlated with WMLB; no statistically significant correlation was found for TNWMLs.CONCLUSION: Results of our study suggest that WMLs influence brain connectivity measured by the connectometry technique in patients with cICA stenosis eligible for CEA. Further studies are warranted to understand the role of WMLs better as a marker of disease in patients with cICA stenosis.

    View details for DOI 10.1177/1971400920959323

    View details for PubMedID 32955384

  • COVID-19-induced anosmia associated with olfactory bulb atrophy. Neuroradiology Chiu, A., Fischbein, N., Wintermark, M., Zaharchuk, G., Yun, P. T., Zeineh, M. 2020

    Abstract

    As the global COVID-19 pandemic evolves, our knowledge of the respiratory and non-respiratory symptoms continues to grow. One such symptom, anosmia, may be a neurologic marker of coronavirus infection and the initial presentation of infected patients. Because this symptom is not routinely investigated by imaging, there is conflicting literature on neuroimaging abnormalities related to COVID-19-related anosmia. We present a novel case of COVID-19 anosmia with definitive olfactory bulb atrophy compared with pre-COVID imaging. The patient had prior MR imaging related to a history of prolactinoma that provided baseline volumes of her olfactory bulbs. After a positive diagnosis of COVID-19 and approximately 2 months duration of anosmia, an MRI was performed that showed clear interval olfactory bulb atrophy. This diagnostic finding is of prognostic importance and indicates that the olfactory entry point to the brain should be further investigated to improve our understanding of COVID infectious pathophysiology.

    View details for DOI 10.1007/s00234-020-02554-1

    View details for PubMedID 32930820

  • Carotid plaque imaging and the risk of atherosclerotic cardiovascular disease CARDIOVASCULAR DIAGNOSIS AND THERAPY Zhu, G., Hom, J., Li, Y., Jiang, B., Rodriguez, F., Fleischmann, D., Saloner, D., Porcu, M., Zhang, Y., Saba, L., Wintermark, M. 2020; 10 (4): 1048–67
  • Virtual monochromatic dual-energy CT reconstructions improve detection of cerebral infarct in patients with suspicion of stroke. Neuroradiology van Ommen, F., Dankbaar, J. W., Zhu, G., Wolman, D. N., Heit, J. J., Kauw, F., Bennink, E., de Jong, H. W., Wintermark, M. 2020

    Abstract

    PURPOSE: Early infarcts are hard to diagnose on non-contrast head CT. Dual-energy CT (DECT) may potentially increase infarct differentiation. The optimal DECT settings for differentiation were identified and evaluated.METHODS: One hundred and twenty-five consecutive patients who presented with suspected acute ischemic stroke (AIS) and underwent non-contrast DECT and subsequent DWI were retrospectively identified. The DWI was used as reference standard. First, virtual monochromatic images (VMI) of 25 patients were reconstructed from 40 to 140keV and scored by two readers for acute infarct. Sensitivity, specificity, positive, and negative predictive values for infarct detection were compared and a subset of VMI energies were selected. Next, for a separate larger cohort of 100 suspected AIS patients, conventional non-contrast CT (NCT) and selected VMI were scored by two readers for the presence and location of infarct. The same statistics for infarct detection were calculated. Infarct location match was compared per vascular territory. Subgroup analyses were dichotomized by time from last-seen-well to CT imaging.RESULTS: A total of 80-90keV VMI were marginally more sensitive (36.3-37.3%) than NCT (32.4%; p>0.680), with marginally higher specificity (92.2-94.4 vs 91.1%; p>0.509) for infarct detection. Location match was superior for VMI compared with NCT (28.7-27.4 vs 19.5%; p<0.010). Within 4.5h from last-seen-well, 80keV VMI more accurately detected infarct (58.0 vs 54.0%) and localized infarcts (27.1 vs 11.9%; p=0.004) than NCT, whereas after 4.5h, 90keV VMI was more accurate (69.3 vs 66.3%).CONCLUSION: Non-contrast 80-90keV VMI best differentiates normal from infarcted brain parenchyma.

    View details for DOI 10.1007/s00234-020-02492-y

    View details for PubMedID 32728777

  • Simultaneous FDG-PET/MRI detects hippocampal subfield metabolic differences in AD/MCI. Scientific reports Carlson, M. L., DiGiacomo, P. S., Fan, A. P., Goubran, M., Khalighi, M. M., Chao, S. Z., Vasanawala, M., Wintermark, M., Mormino, E., Zaharchuk, G., James, M. L., Zeineh, M. M. 2020; 10 (1): 12064

    Abstract

    The medial temporal lobe is one of the most well-studied brain regions affected by Alzheimer's disease (AD). Although the spread of neurofibrillary pathology in the hippocampus throughout the progression of AD has been thoroughly characterized and staged using histology and other imaging techniques, it has not been precisely quantified in vivo at the subfield level using simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI). Here, we investigate alterations in metabolism and volume using [18F]fluoro-deoxyglucose (FDG) and simultaneous time-of-flight (TOF) PET/MRI with hippocampal subfield analysis of AD, mild cognitive impairment (MCI), and healthy subjects. We found significant structural and metabolic changes within the hippocampus that can be sensitively assessed at the subfield level in a small cohort. While no significant differences were found between groups for whole hippocampal SUVr values (p=0.166), we found a clear delineation in SUVr between groups in the dentate gyrus (p=0.009). Subfield analysis may be more sensitive for detecting pathological changes using PET-MRI in AD compared to global hippocampal assessment.

    View details for DOI 10.1038/s41598-020-69065-0

    View details for PubMedID 32694602

  • Neuroimaging in Pediatric Patients with Mild Traumatic Brain Injury: Relating the current 2018 CDC guideline and the potential of advanced neuroimaging modalities for research and clinical biomarker development. Journal of neurotrauma Fong, A., Allen, M., Waltzman, D., Sarmiento, K., Yeates, K. O., Suskauer, S. J., Wintermark, M., Lindberg, D., Tate, D. F., Loewen, J., Wilde, E. A. 2020

    Abstract

    CDC's 2018 Guideline for current practices in pediatric mild traumatic brain injury (mTBI; also referred to as concussion herein) systematically identified the best up-to-date practices based on current evidence and, specifically, identified recommended practices regarding CT, MRI, and skull radiograph imaging. In this commentary, we discuss types of neuroimaging not discussed in the guideline in terms of their safety for pediatric populations, their potential application, and the research investigating the future use of certain modalities to aid in the diagnosis and treatment of mTBI in children. The role of neuroimaging in pediatric mTBI cases should be considered for the potential contribution to children's neural and social development, in addition to the immediate clinical value (as in the case of acute structural findings).Selective use of specific neuroimaging modalities in research has already been shown to detect aspects of diffuse brain injury, disrupted cerebral blood flow, and correlate physiological factors with persistent symptoms following mTBI. However, these advanced neuroimaging modalities are currently limited to the research arena, and any future clinical application of advanced imaging modalities in pediatric mTBI will require robust evidence for each modality's ability to provide measurement of the subtle conditions of brain development, disease, damage, or degeneration while accounting for variables at both non-injury and time-post-injury epochs. Continued collaboration and communication between researchers and health care providers is essential to investigate, develop, and validate the potential of advanced imaging modalities in pediatric mTBI diagnostics and management.

    View details for DOI 10.1089/neu.2020.7100

    View details for PubMedID 32640874

  • Generalizable, Reproducible, and Neuroscientifically Interpretable Imaging Biomarkers for Alzheimer's Disease ADVANCED SCIENCE Jin, D., Zhou, B., Han, Y., Ren, J., Han, T., Liu, B., Lu, J., Song, C., Wang, P., Wang, D., Xu, J., Yang, Z., Yao, H., Yu, C., Zhao, K., Wintermark, M., Zuo, N., Zhang, X., Zhou, Y., Zhang, X., Jiang, T., Wang, Q., Liu, Y. 2020
  • Assessment of the Radiology Support, Communication and Alignment Network to Reduce Medical Imaging Overutilization: A Multipractice Cohort Study. Journal of the American College of Radiology : JACR Rezaii, P. G., Fredericks, N., Lincoln, C. M., Hom, J., Willis, M., Burleson, J., Haines, G. R., Chatfield, M., Boothroyd, D., Ding, V. Y., Bello, J. A., McGinty, G. B., Smith, C. D., Yucel, E. K., Hillman, B., Thorwarth, W. T., Wintermark, M. 2020; 17 (5): 597–605

    Abstract

    PURPOSE: The aim of this study was to determine whether participation in Radiology Support, Communication and Alignment Network (R-SCAN) results in a reduction of inappropriate imaging in a wide range of real-world clinical environments.METHODS: This quality improvement study used imaging data from 27 US academic and private practices that completed R-SCAN projects between January 25, 2015, and August 8, 2018. Each project consisted of baseline, educational (intervention), and posteducational phases. Baseline and posteducational imaging cases were rated as high, medium, or low value on the basis of validated ACR Appropriateness Criteria. Four cohorts were generated: a comprehensive cohort that included all eligible practices and three topic-specific cohorts that included practices that completed projects of specific Choosing Wisely topics (pulmonary embolism, adnexal cyst, and low back pain). Changes in the proportion of high-value cases after R-SCAN intervention were assessed for each cohort using generalized estimating equation logistic regression, and changes in the number of low-value cases were analyzed using Poisson regression.RESULTS: Use of R-SCAN in the comprehensive cohort resulted in a greater proportion of high-value imaging cases (from 57% to 79%; odds ratio, 2.69; 95% confidence interval, 1.50-4.86; P= .001) and 345 fewer low-value cases after intervention (incidence rate ratio, 0.45; 95% confidence interval, 0.29-0.70; P < .001). Similar changes in proportion of high-value cases and number of low-value cases were found for the pulmonary embolism, adnexal cyst, and low back pain cohorts.CONCLUSIONS: R-SCAN participation was associated with a reduced likelihood of inappropriate imaging and is thus a promising tool to enhance the quality of patient care and promote wise use of health care resources.

    View details for DOI 10.1016/j.jacr.2020.02.011

    View details for PubMedID 32371000

  • Imaging cancer immunology: Systemic tracking of immune cells in vivo with magnetic particle imaging Mansfield, J., Ren, G., Gaudet, J., Zhang, Y., Gerosa, M., Wintermark, M., Goodwill, P. SOC NUCLEAR MEDICINE INC. 2020
  • Clinical Decision Support: Curse orBlessing? Journal of the American College of Radiology : JACR Wintermark, M., Bruno, M. A. 2020; 17 (5): 566–67

    View details for DOI 10.1016/j.jacr.2020.03.022

    View details for PubMedID 32370996

  • Everything Every Radiologist Always Wanted (and Needs) to Know About Clinical Decision Support. Journal of the American College of Radiology : JACR Wintermark, M., Willis, M. H., Hom, J., Franceschi, A. M., Fotos, J. S., Mosher, T., Cruciata, G., Reuss, T., Horton, R., Fredericks, N., Burleson, J., Haines, B., Bruno, M. 2020; 17 (5): 568–73

    Abstract

    As of January 2020, clinical decision support needs to be implemented across US health systems for advanced diagnostic imaging services. This article reviews the history, importance, and hurdles of clinical decision support and discusses a few pearls and pitfalls regarding its implementation.

    View details for DOI 10.1016/j.jacr.2020.03.016

    View details for PubMedID 32370997

  • Imaging Cancer Immunology: Magnetic Particle Imaging of Immunotherapies in a Murine Breast Cancer Model Ren, G., Gerosa, M., Gaudet, J., Zhang, Y., Mansfield, J., Goodwill, P., Wintermark, M. CELL PRESS. 2020: 496–97
  • Supracardiac atherosclerosis in embolic stroke of undetermined source: the underestimated source. European heart journal Ntaios, G., Wintermark, M., Michel, P. 2020

    Abstract

    The term 'embolic stroke of undetermined source' (ESUS) is used to describe patients with a non-lacunar ischaemic stroke without any identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause. When the ESUS concept was introduced, covert atrial fibrillation was conceived to be the main underlying cause in the majority of ESUS patients. Another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch-collectively described as supracardiac atherosclerosis. There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than it was initially perceived. Advanced imaging methods are available to identify plaques which high embolic risk. The role of novel antithrombotic strategies in these patients needs to be assessed in randomized controlled trials. This review presents the evidence which points towards a major aetiological association between atherosclerotic plaques and ESUS, summarizes the imaging features which may aid to identify plaques more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk, and highlights the rationale for future research in this field.

    View details for DOI 10.1093/eurheartj/ehaa218

    View details for PubMedID 32300781

  • Early magnetic resonance imaging as a predictor of outcome in pediatric traumatic brain injury Janas, A., Threlkeld, Z., Wintermark, M., Lee, S. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Safety and Effectiveness of Neuro-thrombectomy on Single compared to Biplane Angiography Systems. Scientific reports Guenego, A., Mosimann, P. J., Wintermark, M., Heit, J. J., Zuber, K., Dobrocky, T., Lotterie, J. A., Nicholson, P., Marcellus, D. G., Olivot, J. M., Gonzalez, N., Blanc, R., Pereira, V. M., Gralla, J., Kaesmacher, J., Fahed, R., Piotin, M., Cognard, C., RADON Investigators, Piechowiak, E., Mordasini, P., Zibold, F., Ducroux, C., Bonneville, F., Darcourt, J., Vukasinovic, I., Januel, A. C., Monfraix, S., Michelozzi, C., Tall, P., Mazighi, M., Desilles, J., Ciccio, G., Smajda, S., Redjem, H., Maier, B., Martin, B. W., Guenego, E., Carbillet, F. 2020; 10 (1): 4470

    Abstract

    An increasing number of centers not necessarily equipped with biplane (BP) angiosuites are performing mechanical thrombectomy (MT) in acute ischemic stroke patients. We assessed whether MT performed on single-plane (SP) is equivalent in terms of safety, effectiveness, radiation and contrast agent exposure. Consecutive patients treated by MT in four high volume centers between January 2014 and May 2017 were included. Demographic and MT characteristics were assessed and compared between SP and BP. Of 906 patients treated by MT, 576 (64%) were handled on a BP system. After multivariate analysis, contrast load and fluoroscopy duration were significantly lower in the BP group [100vs200mL, relative effect 0.85 (CI: 0.79-0.92), p=0.0002; 22 vs 27min, relative effect 0.84 (CI: 0.76-0.93), p=0.0008, respectively]. There was no difference in recanalization (modified Thrombolysis-In-Cerebral-Infarction 2b-3), good clinical outcome (modified Rankin Scale 0-2), complications rates, procedure duration or radiation exposure. A three-vessel diagnostic angiogram performed prior to MT led to a significant increase in procedure duration (15% increase, p=0.05), radiation exposure (33% increase, p<0.0001) and contrast load (125% increase, p<0.0001). Mechanical neuro-thrombectomy seems equally safe and effective on a single or biplane angiography system despite increased contrast load and fluoroscopy duration on the former.

    View details for DOI 10.1038/s41598-020-60851-4

    View details for PubMedID 32161286

  • The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression. NeuroImage Tozzi, L., Staveland, B., Holt-Gosselin, B., Chesnut, M., Chang, S. E., Choi, D., Shiner, M. L., Wu, H., Lerma-Usabiaga, G., Sporns, O., Barch, D., Gotlib, I. H., Hastie, T. J., Kerr, A. B., Poldrack, R. A., Wandell, B. A., Wintermark, M., Williams, L. M. 2020: 116715

    Abstract

    Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally. Such states of disordered emotion cut across multiple diagnostic categories of mood and anxiety disorders and are compounded by accompanying disruptions in cognitive function. Not surprisingly, these forms of psychopathology are the leading cause of disability worldwide. The Research Domain Criteria (RDoC) initiative spearheaded by NIMH offers a framework for characterizing the relations among connectome dysfunctions, anchored in neural circuits and phenotypic profiles of behavior and self-reported symptoms. Here, we report on our Connectomes Related to Human Disease protocol for integrating an RDoC framework with HCP protocols to characterize connectome dysfunctions in disordered emotional states, and present quality control data from a representative sample of participants. We focus on three RDoC domains and constructs most relevant to depression and anxiety: 1) loss and acute threat within the Negative Valence System (NVS) domain; 2) reward valuation and responsiveness within the Positive Valence System (PVS) domain; and 3) working memory and cognitive control within the Cognitive System (CS) domain. For 29 healthy controls, we present preliminary imaging data: functional magnetic resonance imaging collected in the resting state and in tasks matching our constructs of interest ("Emotion", "Gambling" and "Continuous Performance" tasks), as well as diffusion-weighted imaging. All functional scans demonstrated good signal-to-noise ratio. Established neural networks were robustly identified in the resting state condition by independent component analysis. Processing of negative emotional faces significantly activated the bilateral dorsolateral prefrontal and occipital cortices, fusiform gyrus and amygdalae. Reward elicited a response in the bilateral dorsolateral prefrontal, parietal and occipital cortices, and in the striatum. Working memory was associated with activation in the dorsolateral prefrontal, parietal, motor, temporal and insular cortices, in the striatum and cerebellum. Diffusion tractography showed consistent profiles of fractional anisotropy along known white matter tracts. We also show that results are comparable to those in a matched sample from the HCP Healthy Young Adult data release. These preliminary data provide the foundation for acquisition of 250 subjects who are experiencing disordered emotional states. When complete, these data will be used to develop a neurobiological model that maps connectome dysfunctions to specific behaviors and symptoms.

    View details for DOI 10.1016/j.neuroimage.2020.116715

    View details for PubMedID 32147367

  • Changing the field: Magnetic particle imaging and localized RF hyperthermia in cancer immunology. Mansfield, J. R., Gaudet, J. M., Ren, G., Hensley, D., Goodwill, P., Wintermark, M. AMER ASSOC CANCER RESEARCH. 2020: 89
  • Hypoperfusion Intensity Ratio Correlates With Angiographic Collaterals In Acute Ischemic Stroke With M1 Occlusion. European journal of neurology Guenego, A., Fahed, R., Albers, G. W., Kuraitis, G., Sussman, E. S., Martin, B. W., Marcellus, D. G., Olivot, J., Marks, M. P., Lansberg, M. G., Wintermark, M., Heit, J. J. 2020

    Abstract

    PURPOSE: Among patients with an acute ischemic stroke (AIS) secondary to large-vessel-occlusion, the hypoperfusion-intensity-ratio (HIR, TMax>10 volume / TMax>6 volume) is a strong predictor of infarct growth. We studied the correlation between HIR and collaterals assessed with digital-subtraction-angiography (DSA) before thrombectomy.METHODS: Between January 2014 and March 2018, consecutive patients with an AIS and a M1 middle-cerebral-artery occlusion who underwent perfusion imaging and endovascular treatment at our center were screened. Ischemic core (mL), HIR and perfusion mismatch (TMax>6sec minus core volume) were assessed through MRI or CT perfusion. Collaterals were assessed on pre-intervention DSA using the American-Society of Interventional and Therapeutic-Neuroradiology/Society of Interventional-Radiology (ASITN/SIR) scale. Baseline clinical and perfusion characteristics were compared between patients with good (ASITN/SIR 3-4) and those with poor (ASITN/SIR 0-2) DSA collaterals. Correlation between HIR and ASITN/SIR was evaluated using Pearson's correlation. ROC analysis was performed to determine the optimal HIR threshold for the prediction of good DSA collaterals.RESULTS: Ninety-eight patients were included. 49% (48/98) had good DSA collaterals, those patients had significantly smaller hypoperfusion volumes (TMax >6sec 89mL versus 125mL; p=0.007) and perfusion mismatch volumes (72mL versus 89mL; p=0.016). HIR was significantly correlated with DSA collaterals (-0.327 [IC 95%: -0.494 to -0.138; p=0.01]). A HIR cut-off of <0.4 best predicted good DSA collaterals with an odds ratio of 4.3 (1.8-10.1) (Sensitivity=0.792, Specificity=0.560, AUC=0.708).CONCLUSION: HIR is a robust indicator of angiographic collaterals and might be used as a surrogate of collateral assessment in patients undergoing MRI. HIR<0.4 best predicted good DSA collaterals.

    View details for DOI 10.1111/ene.14181

    View details for PubMedID 32068938

  • Effects of Non-invasive, Targeted, Neuronal Lesions on Seizures in a Mouse Model of Temporal Lobe Epilepsy. Ultrasound in medicine & biology Zhang, Y., Zhou, H., Qu, H., Liao, C., Jiang, H., Huang, S., Ghobadi, S. N., Telichko, A., Li, N., Habte, F. G., Doyle, T., Woznak, J. P., Bertram, E. H., Lee, K. S., Wintermark, M. 2020

    Abstract

    Surgery to treat drug-resistant epilepsy can be quite effective but remains substantially underutilized. A pilot study was undertaken to test the feasibility of using a non-invasive, non-ablative, approach to produce focal neuronal loss to treat seizures in a rodent model of temporal lobe epilepsy. In this study, spontaneous, recurrent seizures were established in a mouse model of pilocarpine-induced status epilepticus. After post-status epilepticus stabilization, baseline behavioral seizures were monitored for 30 d. Non-invasive opening of the blood-brain barrier targeting the hippocampus was then produced by using magnetic resonance-guided, low-intensity focused ultrasound, through which a neurotoxin (quinolinic acid) administered intraperitoneally gained access to the brain parenchyma to produce focal neuronal loss. Behavioral seizures were then monitored for 30 d after this procedure, and brains were subsequently prepared for histologic analysis of the sites of neuronal loss. The average frequency of behavioral seizures in all animals (n = 11) was reduced by 21.2%. Histologic analyses along the longitudinal axis of the hippocampus revealed that most of the animals (n = 8) exhibited neuronal loss located primarily in the intermediate aspect of the hippocampus, while sparing the septal aspect. Two other animals with damage to the intermediate hippocampus also exhibited prominent bilateral damage to the septal aspect of the hippocampus. A final animal had negligible neuronal loss overall. Notably, the site of neuronal loss along the longitudinal axis of the hippocampus influenced seizure outcomes. Animals that did not have bilateral damage to the septal hippocampus displayed a mean decrease in seizure frequency of 27.7%, while those with bilateral damage to the septal hippocampus actually increased seizure frequency by 18.7%. The animal without neuronal loss exhibited an increase in seizure frequency of 19.6%. The findings indicate an overall decrease in seizure frequency in treated animals. And, the site of neuronal loss along the longitudinal axis of the hippocampus appears to play a key role in reducing seizure activity. These pilot data are promising, and they encourage additional and more comprehensive studies examining the effects of targeted, non-invasive, neuronal lesions for the treatment of epilepsy.

    View details for DOI 10.1016/j.ultrasmedbio.2020.01.008

    View details for PubMedID 32081583

  • Brainstem Atrophy in Gulf War Illness. Neurotoxicology Zhang, Y., Avery, T., Vakhtin, A. A., Mathersul, D. C., Tranvinh, E., Wintermark, M., Massaband, P., Ashford, J. W., Bayley, P. J., Furst, A. J. 2020

    Abstract

    BACKGROUND: Gulf War illness (GWI) is a condition that affects about 30% of veterans who served in the 1990-91 Persian Gulf War. Given its broad symptomatic manifestation, including chronic pain, fatigue, neurological, gastrointestinal, respiratory, and skin problems, it is of interest to examine whether GWI is associated with changes in the brain. Existing neuroimaging studies, however, have been limited by small sample sizes, inconsistent GWI diagnosis criteria, and potential comorbidity confounds.OBJECTIVES: Using a large cohort of US veterans with GWI, we assessed regional brain volumes for their associations with GWI, and quantified the relationships between any regional volumetric changes and GWI symptoms.METHODS: Structural magnetic resonance imaging (MRI) scans from 111 veterans with GWI (Age=49±6, 88% Male) and 59 healthy controls (age=51±9, 78% male) were collected at the California War Related Illness and Injury Study Center (WRIISC-CA) and from a multicenter study of the Parkinson's Progression Marker Initiative (PPMI), respectively. Individual MRI volumes were segmented and parcellated using FreeSurfer. Regional volumes of 19 subcortical, 68 cortical, and 3 brainstem structures were evaluated in the GWI cohort relative to healthy controls. The relationships between regional volumes and GWI symptoms were also assessed.RESULTS: We found significant subcortical atrophy, but no cortical differences, in the GWI group relative to controls, with the largest effect detected in the brainstem, followed by the ventral diencephalon and the thalamus. In a subsample of 58 veterans with GWI who completed the Chronic Fatigue Scale (CFS) inventory of Centers for Disease Control and Prevention (CDC), smaller brainstem volumes were significantly correlated with increased severities of fatigue and depressive symptoms.CONCLUSION: The findings suggest that brainstem volume may be selectively affected by GWI, and that the resulting atrophy could in turn mediate or moderate GWI-related symptoms such as fatigue and depression. Consequently, the brain stem should be carefully considered in future research focusing on GWI pathology.

    View details for DOI 10.1016/j.neuro.2020.02.006

    View details for PubMedID 32081703

  • From "Time is Brain" to "Imaging is Brain": A Paradigm Shift in the Management of Acute Ischemic Stroke. Journal of neuroimaging : official journal of the American Society of Neuroimaging Puig, J., Shankar, J., Liebeskind, D., Terceno, M., Nael, K., Demchuk, A. M., Menon, B., Dowlatshahi, D., Leiva-Salinas, C., Wintermark, M., Thomalla, G., Silva, Y., Serena, J., Pedraza, S., Essig, M. 2020

    Abstract

    Arterial recanalization to restore the blood supply and limit the brain damage is the primary goal in the management of acute ischemic stroke (AIS). Since the publication of pivotal randomized clinical trials in 2015, endovascular thrombectomy has become part of the standard of care in selected cases of AIS from large-vessel occlusions up to 6 hours after the onset of symptoms. However, the association between endovascular reperfusion and improved functional outcome is not strictly time dependent. Rather than on rigid time windows, candidates should be selected based on vascular and physiologic information. This approach places imaging data at the center of treatment decisions. Advances in imaging-based management of AIS provide crucial information about vessel occlusion, infarct core, ischemic penumbra, and degree of collaterals. This information is invaluable in identifying patients who are likely to benefit from reperfusion therapies and excluding those who are unlikely to benefit or are at risk of adverse effects. The approach to reperfusion therapies continues to evolve, and imaging is acquiring a greater role in the diagnostic work-up and treatment decisions as shown in recent clinical trials with extended time window. The 2018 American Heart Association/American Stroke Association guidelines reflect a paradigm shift in the management of AIS from "Time is Brain" to "Imaging is Brain." This review discusses the essential role of multimodal imaging developing from recent trials on therapy for AIS.

    View details for DOI 10.1111/jon.12693

    View details for PubMedID 32037629

  • Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment JOURNAL OF NEURORADIOLOGY Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2020; 47 (1): 13–19
  • Interobserver Agreement for the CT Severity Grading Scales for Acute Traumatic Brain Injury (TBI). Journal of neurotrauma Creeden, S., Ding, V., Parker, J. J., Jiang, B., Li, Y., Lanzman, B., Trinh, A., Khalaf, A., Wolman, D., Halpern, C., Boothroyd, D., Wintermark, M. 2020

    Abstract

    PURPOSE: To determine the interobserver variability among providers of different specialties and levels of experience across five established computed tomography (CT) scoring systems for acute traumatic brain injury (TBI).MATERIALS & METHODS: One hundred cases were selected at random from a retrospective population of adult patients transported to our emergency department and subjected to a non-contrast head CT due to suspicion for TBI. Eight neuroradiologists and neurosurgeons in trainee (residents and fellows) and attending roles independently scored each non-contrast head CT scan on the Marshall, Rotterdam, Helsinki, Stockholm and NeuroImaging Radiological Interpretation System (NIRIS) head CT scales. Interobserver variability of scale scores - overall and by specialty and level of training - was quantified using the intraclass correlation coefficient (ICC), and agreement with respect to National Institutes of Health Common Data Elements (NIH CDEs) was assessed using Cohen's kappa.RESULTS: All CT severity scoring systems showed high interobserver agreement as evidenced by high ICCs, ranging from 0.75 - 0.89. For all scoring systems, neuroradiologists (ICC range from 0.81 - 0.94) tended to have higher interobserver agreement than neurosurgeons (ICC range from 0.63 - 0.76). For all scoring systems, attendings (ICC range from 0.76 - 0.89) had similar interobserver agreement to trainees (ICC range from 0.73 - 0.89). Agreement with respect to NIH CDEs was high for ascertaining presence/absence of hemorrhage, skull fracture, and mass effect, with estimated kappa statistics of least 0.89.CONCLUSION: Acute TBI CT scoring systems demonstrate high interobserver agreement. These results provide scientific rigor for future use of these systems for the classification of acute TBI.

    View details for DOI 10.1089/neu.2019.6871

    View details for PubMedID 31996087

  • CT Angiography for Triage of Patients with Acute Minor Stroke: A Cost-effectiveness Analysis. Radiology Wu, X., Hughes, D. R., Gandhi, D., Matouk, C. C., Sheth, K., Schindler, J., Wira, C., Wintermark, M., Sanelli, P., Malhotra, A. 2020: 191238

    Abstract

    Background Minor stroke is common and may represent up to two-thirds of cases of acute ischemic stroke. The cost-effectiveness of CT angiography in patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤6) is not well established. Purpose To evaluate cost-effectiveness of CT angiography in the detection of large-vessel occlusion (LVO) in patients with acute minor stroke (NIHSS score ≤6). Materials and Methods A Markov decision-analytic model with a societal perspective was constructed. Three different management strategies were evaluated: (a) no vascular imaging and best medical management, (b) CT angiography for all patients and immediate thrombectomy for LVO after intravenous thrombolysis, and (c) CT angiography for all and best medical management (including intravenous thrombolysis, with rescue thrombectomy for patients with LVO and neurologic deterioration). One-way, two-way, and probabilistic sensitivity analyses were performed. Results Base-case calculation showed that CT angiography followed by immediate thrombectomy had the lowest cost ($346 007) and highest health benefits (9.26 quality-adjusted life-years [QALYs]). CT angiography followed by best medical management with possible rescue thrombectomy for patients with LVO had a slightly higher cost ($346 500) and lower health benefits (9.09 QALYs). No vascular imaging had the highest cost and lowest health benefits. The difference in health benefits compared with the CT angiography and immediate thrombectomy strategy was 0.39 QALY, which corresponds to 142 days in perfect health per patient. The conclusion was robust in a probabilistic sensitivity analysis. CT angiography was cost-effective when the probability of LVO was greater than 0.16% in patients with acute minor stroke. The net monetary benefit of performing CT angiography was higher in younger patients ($68 950 difference between CT angiography followed by immediate thrombectomy and no vascular imaging in 55-year-old patients compared with $20 931 in 85-year-old patients). Conclusion Screening for large-vessel occlusion with CT angiography in patients with acute minor stroke is cost-effective and associated with improved health outcomes. Undetected large-vessel occlusion in the absence of vascular imaging results in worse health outcomes and higher costs. © RSNA, 2020 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2019191238

    View details for PubMedID 31934828

  • Carotid plaque imaging and the risk of atherosclerotic cardiovascular disease. Cardiovascular diagnosis and therapy Zhu, G. n., Hom, J. n., Li, Y. n., Jiang, B. n., Rodriguez, F. n., Fleischmann, D. n., Saloner, D. n., Porcu, M. n., Zhang, Y. n., Saba, L. n., Wintermark, M. n. 2020; 10 (4): 1048–67

    Abstract

    Carotid artery plaque is a measure of atherosclerosis and is associated with future risk of atherosclerotic cardiovascular disease (ASCVD), which encompasses coronary, cerebrovascular, and peripheral arterial diseases. With advanced imaging techniques, computerized tomography (CT) and magnetic resonance imaging (MRI) have shown their potential superiority to routine ultrasound to detect features of carotid plaque vulnerability, such as intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC), and calcification. The correlation between imaging features and histological changes of carotid plaques has been investigated. Imaging of carotid features has been used to predict the risk of cardiovascular events. Other techniques such as nuclear imaging and intra-vascular ultrasound (IVUS) have also been proposed to better understand the vulnerable carotid plaque features. In this article, we review the studies of imaging specific carotid plaque components and their correlation with risk scores.

    View details for DOI 10.21037/cdt.2020.03.10

    View details for PubMedID 32968660

    View details for PubMedCentralID PMC7487384

  • The aging imageomics study: rationale, design and baseline characteristics of the study population. Mechanisms of ageing and development Puig, J. n., Biarnes, C. n., Pedraza, S. n., Vilanova, J. C., Pamplona, R. n., Fernández-Real, J. M., Brugada, R. n., Ramos, R. n., Coll-de-Tuero, G. n., Calvo-Perxas, L. n., Serena, J. n., Ramió-Torrentà, L. n., Gich, J. n., Gallart, L. n., Portero-Otin, M. n., Alberich-Bayarri, A. n., Jimenez-Pastor, A. n., Camacho-Ramos, E. n., Mayneris-Perxachs, J. n., Pineda, V. n., Font, R. n., Prats-Puig, A. n., Gacto, M. L., Deco, G. n., Escrichs, A. n., Clotet, B. n., Paredes, R. n., Negredo, E. n., Triaire, B. n., Rodríguez, M. n., Heredia-Escámez, A. n., Coronado, R. n., de Graaf, W. n., Prevost, V. n., Mitulescu, A. n., Daunis-I-Estadella, P. n., Thió-Henestrosa, S. n., Miralles, F. n., Ribas-Ripoll, V. n., Puig-Domingo, M. n., Essig, M. n., Figley, C. R., Figley, T. D., Albensi, B. n., Ashraf, A. n., Reiber, J. H., Schifitto, G. n., Md Nasir, U. n., Leiva-Salinas, C. n., Wintermark, M. n., Nael, K. n., Vilalta-Franch, J. n., Barretina, J. n., Garre-Olmo, J. n. 2020: 111257

    Abstract

    Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiomic variables. This study recruited 1030 participants aged ≥ 50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.

    View details for DOI 10.1016/j.mad.2020.111257

    View details for PubMedID 32437737

  • Effect of Oxygen Extraction (Brush-Sign) on Baseline Core Infarct Depends on Collaterals (HIR). Frontiers in neurology Guenego, A., Leipzig, M., Fahed, R., Sussman, E. S., Faizy, T. D., Martin, B. W., Marcellus, D. G., Wintermark, M., Olivot, J., Albers, G. W., Lansberg, M. G., Heit, J. J. 2020; 11: 618765

    Abstract

    Objectives: Baseline-core-infarct volume is a critical factor in patient selection and outcome in acute ischemic stroke (AIS) before mechanical thrombectomy (MT). We determined whether oxygen extraction efficiency and arterial collaterals, two different physiologic components of the cerebral ischemic cascade, interacted to modulate baseline-core-infarct volume in patients with AIS-LVO undergoing MT triage. Methods: Between January 2015 and March 2018, consecutive patients with an AIS and M1 occlusion considered for MT with a baseline MRI and perfusion-imaging were included. Variables such as baseline-core-infarct volume [mL], arterial collaterals (HIR: TMax > 10 s volume/TMax > 6 s), high oxygen extraction (HOE, presence of the brush-sign on T2*) were assessed. A linear-regression was used to test the interaction of HOE and HIR with baseline-core-infarct volume, after including potential confounding variables. Results: We included 103 patients. Median age was 70 (58-78), and 63% were female. Median baseline-core-infarct volume was 32 ml (IQR 8-74.5). Seventy six patients (74%) had HOE. In a multivariate analysis both favorable HIR collaterals (p = 0.02) and HOE (p = 0.038) were associated with lower baseline-core-infarct volume. However, HOE significantly interacted with HIR (p = 0.01) to predict baseline-core-infarct volume, favorable collaterals (low HIR) with HOE was associated with small baseline-core-infarct whereas patients with poor collaterals (high HIR) and HOE had large baseline-core-infarct. Conclusion: While HOE under effective collateral blood-flow has the lowest baseline-core-infarct volume of all patients, the protective effect of HOE reverses under poor collateral blood-flow and may be a maladaptive response to ischemic stroke as measured by core infarctions in AIS-LVO patients undergoing MT triage.

    View details for DOI 10.3389/fneur.2020.618765

    View details for PubMedID 33488506

  • What's new in imaging of acute stroke? Intensive care medicine Shams, M. n., Shams, S. n., Wintermark, M. n. 2020

    View details for DOI 10.1007/s00134-020-06070-x

    View details for PubMedID 32394066

  • MR elastography frequency-dependent and independent parameters demonstrate accelerated decrease of brain stiffness in elder subjects. European radiology Lv, H. n., Kurt, M. n., Zeng, N. n., Ozkaya, E. n., Marcuz, F. n., Wu, L. n., Laksari, K. n., Camarillo, D. B., Pauly, K. B., Wang, Z. n., Wintermark, M. n. 2020

    Abstract

    To analyze the mechanical properties in different regions of the brain in healthy adults in a wide age range: 26 to 76 years old.We used a multifrequency magnetic resonance elastography (MRE) protocol to analyze the effect of age on frequency-dependent (storage and loss moduli, G' and G″, respectively) and frequency-independent parameters (μ1, μ2, and η, as determined by a standard linear solid model) of the cerebral parenchyma, cortical gray matter (GM), white matter (WM), and subcortical GM structures of 46 healthy male and female subjects. The multifrequency behavior of the brain and frequency-independent parameters were analyzed across different age groups.The annual change rate ranged from - 0.32 to - 0.36% for G' and - 0.43 to - 0.55% for G″ for the cerebral parenchyma, cortical GM, and WM. For the subcortical GM, changes in G' ranged from - 0.18 to - 0.23%, and G″ changed - 0.43%. Interestingly, males exhibited decreased elasticity, while females exhibited decreased viscosity with respect to age in some regions of subcortical GM. Significantly decreased values were also found in subjects over 60 years old.Values of G' and G″ at 60 Hz and the frequency-independent μ2 of the caudate, putamen, and thalamus may serve as parameters that characterize the aging effect on the brain. The decrease in brain stiffness accelerates in elderly subjects.• We used a multifrequency MRE protocol to assess changes in the mechanical properties of the brain with age. • Frequency-dependent (storage moduli G' and loss moduli G″) and frequency-independent (μ1, μ2, and η) parameters can bequantitatively measured by our protocol. • The decreased value of viscoelastic properties due to aging varies in different regions of subcortical GM in males and females, and the decrease in brain stiffness is accelerated in elderly subjects over 60 years old.

    View details for DOI 10.1007/s00330-020-07054-7

    View details for PubMedID 32683552

  • Editorial: Posterior Reversible Encephalopathy Syndrome and Associated Diseases. Frontiers in neurology Legriel, S., Lerner, A., Wintermark, M., Rykken, J. B., Gao, B. 2020; 11: 667

    View details for DOI 10.3389/fneur.2020.00667

    View details for PubMedID 32849174

  • Diffusion tensor tractography of brainstem fibers and its application in pain. PloS one Zhang, Y., Vakhtin, A. A., Jennings, J. S., Massaband, P., Wintermark, M., Craig, P. L., Ashford, J. W., Clark, J. D., Furst, A. J. 2020; 15 (2): e0213952

    Abstract

    Evaluation of brainstem pathways with diffusion tensor imaging (DTI) and tractography may provide insights into pathophysiologies associated with dysfunction of key brainstem circuits. However, identification of these tracts has been elusive, with relatively few in vivo human studies to date. In this paper we proposed an automated approach for reconstructing nine brainstem fiber trajectories of pathways that might be involved in pain modulation. We first performed native-space manual tractography of these fiber tracts in a small normative cohort of participants and confirmed the anatomical precision of the results using existing anatomical literature. Second, region-of-interest pairs were manually defined at each extracted fiber's termini and nonlinearly warped to a standard anatomical brain template to create an atlas of the region-of-interest pairs. The resulting atlas was then transformed non-linearly into the native space of 17 veteran patients' brains for automated brainstem tractography. Lastly, we assessed the relationships between the integrity levels of the obtained fiber bundles and pain severity levels. Fractional anisotropy (FA) measures derived using automated tractography reflected the respective tracts' FA levels obtained via manual tractography. A significant inverse relationship between FA and pain levels was detected within the automatically derived dorsal and medial longitudinal fasciculi of the brainstem. This study demonstrates the feasibility of DTI in exploring brainstem circuitries involved in pain processing. In this context, the described automated approach is a viable alternative to the time-consuming manual tractography. The physiological and functional relevance of the measures derived from automated tractography is evidenced by their relationships with individual pain severities.

    View details for DOI 10.1371/journal.pone.0213952

    View details for PubMedID 32069284

  • Longitudinal alteration of cortical thickness and volume in high-impact sports. NeuroImage Mills, B. D., Goubran, M. n., Parivash, S. N., Dennis, E. L., Rezaii, P. n., Akers, C. n., Bian, W. n., Mitchell, L. A., Boldt, B. n., Douglas, D. n., Sami, S. n., Mouchawar, N. n., Wilson, E. W., DiGiacomo, P. n., Parekh, M. n., Do, H. n., Lopez, J. n., Rosenberg, J. n., Camarillo, D. n., Grant, G. n., Wintermark, M. n., Zeineh, M. n. 2020: 116864

    Abstract

    Collegiate football athletes are subject to repeated head impacts. The purpose of this study was to determine whether this exposure can lead to changes in brain structure. This prospective cohort study was conducted with up to 4 years of follow-up on 63 football (high-impact) and 34 volleyball (control) male collegiate athletes with a total of 315 MRI scans (after exclusions: football n=50, volleyball n= 24, total scans=273) using high-resolution structural imaging. Volumetric and cortical thickness estimates were derived using FreeSurfer 5.3's longitudinal pipeline. A linear mixed-effects model assessed the effect of group (football vs. volleyball), time from baseline MRI, and the interaction between group and time. We confirmed an expected developmental decrement in cortical thickness and volume in our cohort (p<0.001). Superimposed on this, total cortical gray matter volume (p = .03) and cortical thickness within the left hemisphere (p=.04) showed a group by time interaction, indicating less age-related volume reduction and thinning in football compared to volleyball athletes. At the regional level, sport by time interactions on thickness and volume were identified in the left orbitofrontal (p=.001), superior temporal (p=.001), and postcentral regions (p< .001). Additional cortical thickness interactions were found in the left temporal pole (p=.003) and cuneus (p=.005). At the regional level, we also found main effects of sport in football athletes characterized by reduced volume in the right hippocampus (p=.003), right superior parietal cortical gray (p<.001) and white matter (p<.001), and increased volume of the left pallidum (p=.002). Within football, cortical thickness was higher with greater years of prior play (left hemisphere p=.013, right hemisphere p=.005), and any history of concussion was associated with less cortical thinning (left hemisphere p=.010, right hemisphere p=.011). Additionally, both position-associated concussion risk (p=.002) and SCAT scores (p=.023) were associated with less of the expected volume decrement of deep gray structures. This prospective longitudinal study comparing football and volleyball athletes shows divergent age-related trajectories of cortical thinning, possibly reflecting an impact-related alteration of normal cortical development. This warrants future research into the underlying mechanisms of impacts to the head on cortical maturation.

    View details for DOI 10.1016/j.neuroimage.2020.116864

    View details for PubMedID 32360690

  • Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry. Journal of visualized experiments : JoVE Wang, W. n., Zhang, Y. n., Anzivino, M. J., Bertram, E. H., Woznak, J. n., Klibanov, A. n., Dumont, E. n., Wintermark, M. n., Lee, K. S. 2020

    Abstract

    Surgical intervention can be quite effective for treating certain types of medically intractable neurological diseases. This approach is particularly useful for disorders in which identifiable neuronal circuitry plays a key role, such as epilepsy and movement disorders. Currently available surgical modalities, while effective, generally involve an invasive surgical procedure, which can result in surgical injury to non-target tissues. Consequently, it would be of value to expand the range of surgical approaches to include a technique that is both non-invasive and neurotoxic. Here, a method is presented for producing focal, neuronal lesions in the brain in a non-invasive manner. This approach utilizes low-intensity focused ultrasound together with intravenous microbubbles to transiently and focally open the Blood Brain Barrier (BBB). The period of transient BBB opening is then exploited to focally deliver a systemically administered neurotoxin to a targeted brain area. The neurotoxin quinolinic acid (QA) is normally BBB-impermeable, and is well-tolerated when administered intraperitoneally or intravenously. However, when QA gains direct access to brain tissue, it is toxic to the neurons. This method has been used in rats and mice to target specific brain regions. Immediately after MRgFUS, successful opening of the BBB is confirmed using contrast enhanced T1-weighted imaging. After the procedure, T2 imaging shows injury restricted to the targeted area of the brain and the loss of neurons in the targeted area can be confirmed post-mortem utilizing histological techniques. Notably, animals injected with saline rather than QA do demonstrate opening of the BBB, but dot not exhibit injury or neuronal loss. This method, termed Precise Intracerebral Non-invasive Guided surgery (PING) could provide a non-invasive approach for treating neurological disorders associated with disturbances in neural circuitry.

    View details for DOI 10.3791/61271

    View details for PubMedID 33044450

  • Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease. Journal of Alzheimer's disease : JAD Shams, M. n., Martola, J. n., Charidimou, A. n., Granberg, T. n., Ferreira, D. n., Westman, E. n., Wintermark, M. n., Iv, M. n., Larvie, M. n., Kristoffersen Wiberg, M. n., Kaijser, M. n., Forsgard, N. n., Zetterberg, H. n., Wahlund, L. O., Shams, S. n. 2020

    Abstract

    Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma.Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels.This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models.No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers.CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.

    View details for DOI 10.3233/JAD-200656

    View details for PubMedID 33104030

  • Emergency department implementation of abbreviated magnetic resonance imaging for pediatric traumatic brain injury. Journal of the American College of Emergency Physicians open Lumba-Brown, A. n., Lee, M. O., Brown, I. n., Cornwell, J. n., Dannenberg, B. n., Fang, A. n., Ghazi-Askar, M. n., Grant, G. n., Imler, D. n., Khanna, K. n., Lowe, J. n., Wang, E. n., Wintermark, M. n. 2020; 1 (5): 994–99

    Abstract

    Pediatric head injury is a common presenting complaint in the emergency department (ED), often requiring neuroimaging or ED observation for diagnosis. However, the traditional diagnostic neuroimaging modality, head computed tomography (CT), is associated with radiation exposure while prolonged ED observation impacts patient flow and resource utilization. Recent scientific literature supports abbreviated, or focused and shorter, brain magnetic resonance imaging (MRI) as a feasible and accurate diagnostic alternative to CT for traumatic brain injury. However, this is a relatively new application and its use is not widespread. The aims of this review are to describe the science and applications of abbreviated brain MRI and report a model protocol's development and ED implementation in the evaluation of children with head injury for replication in other institutions.

    View details for DOI 10.1002/emp2.12055

    View details for PubMedID 33145550

    View details for PubMedCentralID PMC7593499

  • Artificial Intelligence and Stroke Imaging: A West Coast Perspective. Neuroimaging clinics of North America Zhu, G. n., Jiang, B. n., Chen, H. n., Tong, E. n., Xie, Y. n., Faizy, T. D., Heit, J. J., Zaharchuk, G. n., Wintermark, M. n. 2020; 30 (4): 479–92

    Abstract

    Artificial intelligence (AI) advancements have significant implications for medical imaging. Stroke is the leading cause of disability and the fifth leading cause of death in the United States. AI applications for stroke imaging are a topic of intense research. AI techniques are well-suited for dealing with vast amounts of stroke imaging data and a large number of multidisciplinary approaches used in classification, risk assessment, segmentation tasks, diagnosis, prognosis, and even prediction of therapy responses. This article addresses this topic and seeks to present an overview of machine learning and/or deep learning applied to stroke imaging.

    View details for DOI 10.1016/j.nic.2020.07.001

    View details for PubMedID 33038998

  • Viscoelasticity of children and adolescent brains through MR elastography. Journal of the mechanical behavior of biomedical materials Ozkaya, E. n., Fabris, G. n., Macruz, F. n., Suar, Z. M., Abderezaei, J. n., Su, B. n., Laksari, K. n., Wu, L. n., Camarillo, D. B., Pauly, K. B., Wintermark, M. n., Kurt, M. n. 2020; 115: 104229

    Abstract

    Magnetic Resonance Elastography (MRE) is an elasticity imaging technique that allows a safe, fast, and non-invasive evaluation of the mechanical properties of biological tissues in vivo. Since mechanical properties reflect a tissue's composition and arrangement, MRE is a powerful tool for the investigation of the microstructural changes that take place in the brain during childhood and adolescence. The goal of this study was to evaluate the viscoelastic properties of the brain in a population of healthy children and adolescents in order to identify potential age and sex dependencies. We hypothesize that because of myelination, age dependent changes in the mechanical properties of the brain will occur during childhood and adolescence. Our sample consisted of 26 healthy individuals (13 M, 13 F) with age that ranged from 7-17 years (mean: 11.9 years). We performed multifrequency MRE at 40, 60, and 80 Hz actuation frequencies to acquire the complex-valued shear modulus G = G' + iG″ with the fundamental MRE parameters being the storage modulus (G'), the loss modulus (G″), and the magnitude of complex-valued shear modulus (|G|). We fitted a springpot model to these frequency-dependent MRE parameters in order to obtain the parameter α, which is related to tissue's microstructure, and the elasticity parameter k, which was converted to a shear modulus parameter (μ) through viscosity (η). We observed no statistically significant variation in the parameter μ, but a significant increase of the microstructural parameter α of the white matter with increasing age (p < 0.05). Therefore, our MRE results suggest that subtle microstructural changes such as neural tissue's enhanced alignment and geometrical reorganization during childhood and adolescence could result in significant biomechanical changes. In line with previously reported MRE data for adults, we also report significantly higher shear modulus (μ) for female brains when compared to males (p < 0.05). The data presented here can serve as a clinical baseline in the analysis of the pediatric and adolescent brain's viscoelasticity over this age span, as well as extending our understanding of the biomechanics of brain development.

    View details for DOI 10.1016/j.jmbbm.2020.104229

    View details for PubMedID 33387852

  • Image Quality of Virtual Monochromatic Reconstructions of Noncontrast CT on a Dual-Source CT Scanner in Adult Patients. Academic radiology van Ommen, F. n., Kauw, F. n., Bennink, E. n., Heit, J. J., Wolman, D. N., Dankbaar, J. W., de Jong, H. W., Wintermark, M. n. 2020

    Abstract

    To evaluate the image quality of virtual monochromatic images (VMI) reconstructed from dual-energy dual-source noncontrast head CT with different reconstruction kernels.Twenty-five consecutive adult patients underwent noncontrast dual-energy CT. VMI were retrospectively reconstructed at 5-keV increments from 40 to 140 keV using quantitative and head kernels. CT-number, noise levels (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the gray and white matter and artifacts using the posterior fossa artifact index (PFAI) were evaluated.CT-number increased with decreasing VMI energy levels, and SD was lowest at 85 keV. SNR was maximized at 80 keV and 85 keV for the head and quantitative kernels, respectively. CNR was maximum at 40 keV; PFAI was lowest at 90 (head kernel) and 100 (quantitative kernel) keV. Optimal VMI image quality was significantly better than conventional CT.Optimal image quality of VMI energies can improve brain parenchymal image quality compared to conventional CT but are reconstruction kernel dependent and depend on indication for performing noncontrast CT.

    View details for DOI 10.1016/j.acra.2020.05.038

    View details for PubMedID 32616420

  • Generalizable, Reproducible, and Neuroscientifically Interpretable Imaging Biomarkers for Alzheimer's Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Jin, D. n., Zhou, B. n., Han, Y. n., Ren, J. n., Han, T. n., Liu, B. n., Lu, J. n., Song, C. n., Wang, P. n., Wang, D. n., Xu, J. n., Yang, Z. n., Yao, H. n., Yu, C. n., Zhao, K. n., Wintermark, M. n., Zuo, N. n., Zhang, X. n., Zhou, Y. n., Zhang, X. n., Jiang, T. n., Wang, Q. n., Liu, Y. n. 2020; 7 (14): 2000675

    Abstract

    Precision medicine for Alzheimer's disease (AD) necessitates the development of personalized, reproducible, and neuroscientifically interpretable biomarkers, yet despite remarkable advances, few such biomarkers are available. Also, a comprehensive evaluation of the neurobiological basis and generalizability of the end-to-end machine learning system should be given the highest priority. For this reason, a deep learning model (3D attention network, 3DAN) that can simultaneously capture candidate imaging biomarkers with an attention mechanism module and advance the diagnosis of AD based on structural magnetic resonance imaging is proposed. The generalizability and reproducibility are evaluated using cross-validation on in-house, multicenter (n = 716), and public (n = 1116) databases with an accuracy up to 92%. Significant associations between the classification output and clinical characteristics of AD and mild cognitive impairment (MCI, a middle stage of dementia) groups provide solid neurobiological support for the 3DAN model. The effectiveness of the 3DAN model is further validated by its good performance in predicting the MCI subjects who progress to AD with an accuracy of 72%. Collectively, the findings highlight the potential for structural brain imaging to provide a generalizable, and neuroscientifically interpretable imaging biomarker that can support clinicians in the early diagnosis of AD.

    View details for DOI 10.1002/advs.202000675

    View details for PubMedID 32714766

    View details for PubMedCentralID PMC7375255

  • National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond. Stroke Broderick, J. P., Elm, J. J., Janis, L. S., Zhao, W. n., Moy, C. S., Dillon, C. R., Chimowitz, M. I., Sacco, R. L., Cramer, S. C., Wolf, S. L., Johnston, K. C., Saver, J. L., Marshall, R. S., Brown, D. n., Wintermark, M. n., Elkind, M. S., Kamel, H. n., Tirschwell, D. L., Longstreth, W. T., Chervin, R. D., Adeoye, O. M., Barreto, A. D., Grotta, J. C., Ramey, S. L., Lo, W. D., Feng, W. n., Schlaug, G. n., Sheth, K. N., Selim, M. n., Naidech, A. M., Lansberg, M. G., Lazar, R. M., Albers, G. W., Griffin, J. S., Sirline, L. P., Frasure, J. n., Wright, C. B., Khatri, P. n. 2020; 51 (8): 2580–86

    View details for DOI 10.1161/STROKEAHA.120.030417

    View details for PubMedID 32716819

  • Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study BRAIN IMAGING AND BEHAVIOR Porcu, M., Craboledda, D., Garofalo, P., Columbano, G., Barberini, L., Sanfilippo, R., Zaccagna, F., Wintermark, M., Montisci, R., Saba, L. 2019; 13 (6): 1708–18
  • Eligibility for late endovascular treatment using DAWN, DEFUSE-3, and more liberal selection criteria in a stroke center. Journal of neurointerventional surgery Nannoni, S., Strambo, D., Sirimarco, G., Amiguet, M., Vanacker, P., Eskandari, A., Saliou, G., Wintermark, M., Dunet, V., Michel, P. 2019

    Abstract

    BACKGROUND AND PURPOSE: The real-life application of DAWN and DEFUSE-3 trials has been poorly investigated. We aimed to identify the proportion of patients with acute ischemic stroke (AIS) eligible for late endovascular treatment (EVT) in our stroke center based on trial and more liberal selection criteria.METHODS: All consecutive patients in our stroke registry (2003-2017) admitted within 5-23 hours of last proof of good health were selected if they had complete clinical and radiological datasets. We calculated the proportion of patients eligible for late EVT according to trial (DAWN and/or DEFUSE-3) and more liberal clinical/imaging mismatch criteria (including lower admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score for core estimation).RESULTS: Of 1705 patients with AIS admitted to our comprehensive stroke center in the late time window, we identified 925 patients with complete clinical and radiological data. Among them, the proportions of late EVT eligibility were 2.5% (n=23) with DAWN, 5.1% (n=47) with DEFUSE-3, and 11.1% (n=103) with more liberal criteria. Considering late-arriving patients with large vessel occlusion (n=221), the percentages of eligible patients were 10.4%, 21.3%, and 46.6%, respectively. A favorable outcome was observed at comparable rates in treated patients selected by trial or liberal criteria (67% vs 58%, p=0.49).CONCLUSIONS: In a long-term stroke registry, the proportion of late EVT eligibility varied greatly according to selection criteria and referral pattern. Among late-arriving patients referred to our comprehensive stroke center, we found 5.6% eligible according to trial (DAWN/DEFUSE-3) and 11.1% according to liberal criteria. These data indicate that late EVT could be offered to a larger population of patients if more liberal criteria are applied.

    View details for DOI 10.1136/neurintsurg-2019-015382

    View details for PubMedID 31772044

  • Computed Tomography Perfusion Data for Acute Ischemic Stroke Evaluation Using Rapid Software: Pitfalls of Automated Postprocessing. Journal of computer assisted tomography Kauw, F., Heit, J. J., Martin, B. W., van Ommen, F., Kappelle, L. J., Velthuis, B. K., de Jong, H. W., Dankbaar, J. W., Wintermark, M. 2019

    Abstract

    Computed tomography perfusion (CTP) is increasingly used to determine treatment eligibility for acute ischemic stroke patients. Automated postprocessing of raw CTP data is routinely used, but it can fail. In reviewing 176 consecutive acute ischemic stroke patients, failures occurred in 20 patients (11%) during automated postprocessing by the RAPID software. Failures were caused by motion (n = 11, 73%), streak artifacts (n = 2, 13%), and poor contrast bolus arrival (n = 2, 13%). Stroke physicians should review CTP results with care before they are being integrated in their decision-making process.

    View details for DOI 10.1097/RCT.0000000000000946

    View details for PubMedID 31804241

  • Imaging cancer immunology: Systemic tracking of immune cells in vivo with magnetic particle imaging Mansfield, J., Ren, G., Gaudet, J., Zhang, Y., Ghobadi, S., Wintermark, M., Goodwill, P. BMC. 2019
  • Perfusion Computed Tomography in Acute Ischemic Stroke. Radiologic clinics of North America Heit, J. J., Sussman, E. S., Wintermark, M. 2019; 57 (6): 1109–16

    Abstract

    Occlusion of a cervical or cerebral artery may cause acute ischemic stroke (AIS). Recent advances in AIS treatment by endovascular thrombectomy have led to more widespread use of advanced computed tomography (CT) imaging, including perfusion CT (PCT). This article reviews PCT for the evaluation of AIS patients.

    View details for DOI 10.1016/j.rcl.2019.06.003

    View details for PubMedID 31582038

  • Automated CT perfusion imaging for acute ischemic stroke: Pearls and pitfalls for real-world use. Neurology Vagal, A., Wintermark, M., Nael, K., Bivard, A., Parsons, M., Grossman, A. W., Khatri, P. 2019

    Abstract

    Recent positive trials have thrust acute cerebral perfusion imaging into the routine evaluation of acute ischemic stroke. Updated guidelines state that in patients with anterior circulation large vessel occlusions presenting beyond 6 hours from time last known well, advanced imaging selection including perfusion-based selection is necessary. Centers that receive patients with acute stroke must now have the capability to perform and interpret CT or magnetic resonance perfusion imaging or provide rapid transfer to centers with the capability of selecting patients for a highly impactful endovascular therapy, particularly in delayed time windows. Many stroke centers are quickly incorporating the use of automated perfusion processing software to interpret perfusion raw data. As CT perfusion (CTP) is being assimilated in real-world clinical practice, it is essential to understand the basics of perfusion acquisition, quantification, and interpretation. It is equally important to recognize the common technical and clinical diagnostic challenges of automated CTP including ischemic core and penumbral misclassifications that could result in underestimation or overestimation of the core and penumbra volumes. This review highlights the pitfalls of automated CTP along with practical pearls to address the common challenges. This is particularly tailored to aid the acute stroke clinician who must interpret automated perfusion studies in an emergency setting to make time-dependent treatment decisions for patients with acute ischemic stroke.

    View details for DOI 10.1212/WNL.0000000000008481

    View details for PubMedID 31636160

  • White matter asymmetry: a reflection of pathology in traumatic brain injury. Journal of neurotrauma Vakhtin, A. A., Zhang, Y., Wintermark, M., Massaband, P., Robinson, M., Ashford, J. W., Furst, A. J. 2019

    Abstract

    Comparisons of white matter (WM) fractional anisotropy (FA) values between mild traumatic brain injury (mTBI) patients and controls have revealed inconsistencies in the directions of the resulting FA changes. To address these discrepancies, we examined hemispheric FA symmetry levels across WM tracts in 150 mTBI patients relative to 96 military controls. Automated fiber quantification was used to extract 18 WM tracts with 100 FA values, which were used to compute correlation strengths between the 9 bilateral tract pairs. The Fisher z-transformed Pearson's r values were entered into an analysis of covariance examining the effects of group (mTBI and controls) and age on symmetry levels within each tract pair. The mTBI group displayed lower symmetry levels in the cortico-spinal tract and the inferior longitudinal fasciculus. Interactions between age and group were detected in the inferior fronto-occipital (IFOF), uncinate (UF), and superior longitudinal fasciculi (SLF). A similar pattern emerged in the IFOF and the UF, revealing age-related symmetry decreases in the mTBI patients despite stable levels of symmetry across age in controls. In contrast, while the control group's symmetry levels actually increased with age in the SLF, no age-related symmetry changes were detected across the mTBI participants. Here we proposed WM symmetry measures as a potential means of circumventing directional inconsistencies of trauma-related FA changes, as well as capturing more within-tract and within-subject variances of DTI metrics. Further, we demonstrated the method's utility in detecting mTBI-specific effects and their associated interactions with age.

    View details for DOI 10.1089/neu.2019.6487

    View details for PubMedID 31595833

  • Application of FLAIR Vascular Hyperintensity-DWI Mismatch in Ischemic Stroke Depending on Semi-Quantitative DWI-Alberta Stroke Program Early CT Score FRONTIERS IN NEUROLOGY Song, L., Lyu, C., Shen, G., Guo, T., Wang, J., Wang, W., Qiu, X., Lerner, A., Wintermark, M., Gao, B. 2019; 10
  • Anatomic and Thermometric Analysis of Cranial Nerve Palsy after Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy. Operative neurosurgery (Hagerstown, Md.) Huang, Y., Leung, S. A., Parker, J. J., Ho, A. L., Wintermark, M., Patel, S. H., Pauly, K. B., Kakusa, B. W., Beres, S. J., Henderson, J. M., Grant, G. A., Halpern, C. H. 2019

    Abstract

    BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive therapy for treating medication-resistant mesial temporal lobe epilepsy. Cranial nerve (CN) palsy has been reported as a procedural complication, but the mechanism of this complication is not understood.OBJECTIVE: To identify the cause of postoperative CN palsy after LITT.METHODS: Four medial temporal lobe epilepsy patients with CN palsy after LITT were identified for comparison with 22 consecutive patients with no palsy. We evaluated individual variation in the distance between CN III and the uncus, and CN IV and the parahippocampal gyrus using preoperative T1- and T2-weighted magnetic resonance (MR) images. Intraoperative MR thermometry was used to estimate temperature changes.RESULTS: CN III (n=2) and CN IV palsies (n=2) were reported. On preoperative imaging, the majority of identified CN III (54%) and CN IV (43%) were located within 1 to 2 mm of the uncus and parahippocampal gyrus tissue border, respectively. Affected CN III and CN IV were more likely to be found<1 mm of the tissue border (PCNIII=.03, PCNIV<.01; chi-squared test). Retrospective assessment of thermal profile during ablation showed higher temperature rise along the mesial temporal lobe tissue border in affected CNs than unaffected CNs after controlling for distance (12.9°C vs 5.8°C; P=.03; 2-sample t-test).CONCLUSION: CN palsy after LITT likely results from direct heating of the respective CN running at extreme proximity to the mesial temporal lobe. Low-temperature thresholds set at the border of the mesial temporal lobe in patients whose CNs are at close proximity may reduce this risk.

    View details for DOI 10.1093/ons/opz279

    View details for PubMedID 31555820

  • Imaging of Atypical and Complicated Posterior Reversible Encephalopathy Syndrome FRONTIERS IN NEUROLOGY Saad, A. F., Chaudhari, R., Wintermark, M. 2019; 10
  • Comparison of MRI IVIM and MR perfusion imaging in acute ischemic stroke due to large vessel occlusion. International journal of stroke : official journal of the International Stroke Society Zhu, G., Federau, C., Wintermark, M., Chen, H., Marcellus, D. G., Martin, B. W., Heit, J. J. 2019: 1747493019873515

    Abstract

    PURPOSE: Intravoxel incoherent motion is a diffusion-weighted imaging magnetic resonance imaging technique that measures microvascular perfusion from a multi-b value sequence. Intravoxel incoherent motion microvascular perfusion has not been directly compared to conventional dynamic susceptibility contrast perfusion-weighted imaging in the context of acute ischemic stroke. We determined the degree of correlation between perfusion-weighted imaging and intravoxel incoherent motion parameter maps in patients with acute ischemic stroke.METHODS: We performed a retrospective cohort study of acute ischemic stroke patients undergoing thrombectomy treatment triage by magnetic resonance imaging. Intravoxel incoherent motion perfusion fraction maps were derived using two-step voxel-by-voxel post-processing. Ischemic core, penumbra, non-ischemia, and contralateral hemisphere were delineated based upon diffusion-weighted imaging and perfusion-weighted imaging using a Tmax >6s threshold. Signal intensity within different brain compartments were measured on intravoxel incoherent motion (IVIM f, IVIM D*, IVIM fD*) parametric maps and compared the differences using one-way ANOVA. Ischemic volumes were measured on perfusion-weighted imaging and intravoxel incoherent motion parametric maps. Bland-Altman analysis and voxel-based volumetric comparison were used to determine the agreements among ischemic volumes of perfusion-weighted imaging and intravoxel incoherent motion perfusion parameters. Inter-rater reliability on intravoxel incoherent motion maps was also assessed. Significance level was set at alpha<0.05.RESULTS: Twenty patients (11 males, 55%; mean age 67.1±13.8 years) were included. Vessel occlusions involved the internal carotid artery (6 patients, 30%) and M1 segment of the middle cerebral artery (14, 70%). Mean pre-treatment core infarct volume was 19.07±23.56ml. Mean pre-treatment ischemic volumes on perfusion-weighted imaging were 10.90±13.33ml (CBV), 24.83±23.08ml (CBF), 58.87±37.85ml (MTT), and 47.53±26.78ml (Tmax). Mean pre-treatment ischemic volumes on corresponding IVIM parameters were 23.20±25.63ml (IVIM f), 14.01±16.81ml (IVIM D*), and 27.41±40.01ml (IVIM fD*). IVIM f, D, and fD* demonstrated significant differences (P<0.001). The best agreement in term of ischemic volumes and voxel-based overlap was between IVIM fD* and CBF with mean volume difference of 0.5ml and mean dice similarity coefficient (DSC) of 0.630±0.136.CONCLUSION: There are moderate differences in brain perfusion assessment between intravoxel incoherent motion and perfusion-weighted imaging parametric maps, and IVIM fD* and perfusion-weighted imaging CBF show excellent agreement. Intravoxel incoherent motion is promising for cerebral perfusion assessment in acute ischemic stroke patients.

    View details for DOI 10.1177/1747493019873515

    View details for PubMedID 31480940

  • Carotid Artery Imaging Is More Strongly Associated With the 10-Year Atherosclerotic Cardiovascular Disease Score Than Coronary Artery Imaging. Journal of computer assisted tomography Li, Y., Zhu, G., Ding, V., Jiang, B., Boothroyd, D., Rodriguez, F., Fleischmann, D., Desai, M., Saloner, D., Saba, L., Hom, J., Wintermark, M. 2019; 43 (5): 679–85

    Abstract

    PURPOSE: The aim of this study was to compare coronary and carotid artery imaging and determine which one shows the strongest association with atherosclerotic cardiovascular disease (ASCVD) score.PATIENTS AND METHODS: Two separate series patients who underwent either coronary computed tomography angiography (CTA) or carotid CTA were included. We recorded the ASCVD scores and assessed the CTA imaging. Two thirds were used to build predictive models, and the remaining one third generated predicted ASCVD scores. The Bland-Altman analysis analyzed the concordance.RESULTS: A total of 110 patients were included in each group. There was no significant difference between clinical characteristics. Three imaging variables were included in the carotid model. Two coronary models (presence of calcium or Agatston score) were created. The bias between true and predicted ASCVD scores was 0.37 ± 5.72% on the carotid model, and 2.07 ± 7.18% and 2.47 ± 7.82% on coronary artery models, respectively.CONCLUSIONS: Both carotid and coronary artery imaging features can predict ASCVD score. The carotid artery was more associated to the ASCVD score than the coronary artery.

    View details for DOI 10.1097/RCT.0000000000000920

    View details for PubMedID 31609291

  • Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience JOURNAL OF NEUROINTERVENTIONAL SURGERY Lee, S., Heit, J., Albers, G. W., Wintermark, M., Jiang, B., Bernier, E., Fischbein, N. J., Mlynash, M., Marks, M. P., Do, H. M., Dodd, R. L. 2019; 11 (9): 940–46
  • Endovascular versus medical therapy for large-vessel anterior occlusive stroke presenting with mild symptoms. International journal of stroke : official journal of the International Stroke Society Wolman, D. N., Marcellus, D. G., Lansberg, M. G., Albers, G., Guenego, A., Marks, M. P., Dodd, R. L., Do, H. M., Wintermark, M., Martin, B. W., Heit, J. J. 2019: 1747493019873510

    Abstract

    BACKGROUND: Acute ischemic stroke patients with a large-vessel occlusion but mild symptoms (NIHSS≤6) pose a treatment dilemma between medical management and endovascular thrombectomy.AIMS: To evaluate the differences in clinical outcomes of endovascular thrombectomy-eligible patients with target-mismatch perfusion profiles who undergo either medical management or endovascular thrombectomy.METHODS: Forty-seven patients with acute ischemic stroke due to large-vessel occlusion, NIHSS≤6, and a target-mismatch perfusion imaging profile were included. Patients underwent medical management or endovascular thrombectomy following treating neurointerventionalist and neurologist consensus. The primary outcome measure was NIHSS shift. Secondary outcome measures were symptomatic intracranial hemorrhage, in-hospital mortality, and 90-day mRS scores. The primary intention-to-treat and as-treated analyses were compared to determine the impact of crossover patient allocation on study outcome measures.RESULTS: Forty-seven patients were included. Thirty underwent medical management (64%) and 17 underwent endovascular thrombectomy (36%). Three medical management patients underwent endovascular thrombectomy due to early clinical deterioration. Presentation NIHSS (P=0.82), NIHSS shift (P=0.62), and 90-day functional independence (mRS 0-2; P=0.25) were similar between groups. Endovascular thrombectomy patients demonstrated an increased overall rate of intracranial hemorrhage (35.3% vs. 10.0%; P=0.04), but symptomatic intracranial hemorrhage was similar between groups (P=0.25). In-hospital mortality was similar between groups (P=0.46), though all two deaths in the medical management group occurred among crossover patients. Endovascular thrombectomy patients demonstrated a longer length of stay (7.6±7.2 vs. 4.3±3.9 days; P=0.04) and a higher frequency of unfavorable discharge to a skilled-nursing facility (P=0.03) rather than home (P=0.05).CONCLUSIONS: Endovascular thrombectomy may pose an unfavorable risk-benefit profile over medical management for endovascular thrombectomy-eligible acute ischemic stroke patients with mild symptoms, which warrants a randomized trial in this subpopulation.

    View details for DOI 10.1177/1747493019873510

    View details for PubMedID 31474193

  • Applications of Deep Learning to Neuro-Imaging Techniques FRONTIERS IN NEUROLOGY Zhu, G., Jiang, B., Tong, L., Xie, Y., Zaharchuk, G., Wintermark, M. 2019; 10
  • Optimized Combination of b‑values for IVIM Perfusion Imaging in Acute Ischemic Stroke Patients. Clinical neuroradiology Zhu, G., Heit, J. J., Martin, B. W., Marcellus, D. G., Federau, C., Wintermark, M. 2019

    Abstract

    PURPOSE: To determine the optimal combination of low b‑values to generate perfusion information from intravoxel incoherent motion (IVIM) in patients with acute ischemic stroke (AIS) considering the time constraints for these patients.METHODS: A retrospective cohort study of AIS patients with IVIM MRI was performed. A two-step voxel-by-voxel postprocessing was used to derive IVIM perfusion fraction maps with different combinations of bvalues. Signal values within regions of ischemic core, non-infarcted ischemic hemisphere, and contralateral hemisphere were measured on IVIM (f, D*, fD*, D) parameter maps. Bland-Altman analysis and the Dice similarity coefficient were used to determine quantitative and spatial agreements between the reference standard IVIM (IVIM with 6 bvalues of 0, 50, 100, 150, 200, 1000 s/mm2) and other combinations of bvalues. Significance level was set at p <0.05.RESULTS: There were 58 patients (36males, 61.3%; mean age 70.2 ±13.4 years) included. Considering all IVIM parameters, the combination of bvalues of 0, 50, 200, 1000 was the most consistent with our reference standard on Bland-Altman analysis. The best voxel-based overlaps of ischemic regions were on IVIMD, while there were good voxel-based overlaps on IVIMf.CONCLUSION: The IVIM with these four bvalues collects diffusion and perfusion information from asingle short MRI sequence, which may have important implications for the imaging of AIS patients.

    View details for DOI 10.1007/s00062-019-00817-w

    View details for PubMedID 31375894

  • Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain JOURNAL OF NEUROIMAGING Kurt, M., Wu, L., Laksari, K., Ozkaya, E., Suar, Z. M., Lv, H., Epperson, K., Epperson, K., Sawyer, A. M., Camarillo, D., Pauly, K., Wintermark, M. 2019; 29 (4): 440–46

    View details for DOI 10.1111/jon.12619

    View details for Web of Science ID 000488852500003

  • Longitudinal Changes in Hippocampal Subfield Volume Associated with Collegiate Football JOURNAL OF NEUROTRAUMA Parivash, S. N., Goubran, M., Mills, B. D., Rezaii, P., Thaler, C., Wolman, D., Bian, W., Mitchell, L. A., Boldt, B., Douglas, D., Wilson, E. W., Choi, J., Xie, L., Yushkevich, P. A., DiGiacomo, P., Wongsripuemtet, J., Parekh, M., Fiehler, J., Do, H., Lopez, J., Rosenberg, J., Camarillo, D., Grant, G., Wintermark, M., Zeineh, M. 2019
  • Decreasing Stroke Code to CT Time in Patients Presenting with Stroke Symptoms. Radiographics : a review publication of the Radiological Society of North America, Inc Kalnins, A. n., Mickelsen, L. J., Marsh, D. n., Zorich, C. n., Casal, S. n., Tai, W. A., Vora, N. n., Olalia, G. n., Wintermark, M. n., Larson, D. B. ; 37 (5): 1559–68

    Abstract

    Guided quality improvement (QI) programs present an effective means to streamline stroke code to computed tomography (CT) times in a comprehensive stroke center. Applying QI methods and a multidisciplinary team approach may decrease the stroke code to CT time in non-prenotified emergency department (ED) patients presenting with symptoms of stroke. The aim of this project was to decrease this time for non-prenotified stroke code patients from a baseline mean of 20 minutes to one less than 15 minutes during an 18-week period by applying QI methods in the context of a structured QI program. By reducing this time, it was expected that the door-to-CT time guideline of 25 minutes could be met more consistently. Through the structured QI program, we gained an understanding of the process that enabled us to effectively identify key drivers of performance to guide project interventions. As a result of these interventions, the stroke code to CT time for non-prenotified stroke code patients decreased to a mean of less than 14 minutes. This article reports these methods and results so that others can similarly improve the time it takes to perform nonenhanced CT studies in non-prenotified stroke code patients in the ED. (©)RSNA, 2017.

    View details for PubMedID 28820652

  • Imaging biomarkers of vulnerable carotid plaques for stroke risk prediction and their potential clinical implications LANCET NEUROLOGY Saba, L., Saam, T., Jager, H., Yuan, C., Hatsukami, T. S., Saloner, D., Wasserman, B. A., Bonati, L. H., Wintermark, M. 2019; 18 (6): 559–72
  • A statistical approach to identify optimal inclusion criteria: An application to acute stroke clinical trials CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS Ball, R. L., Jiang, B., Desai, M., Michel, P., Eskandari, A., Jovin, T., Wintermark, M. 2019; 14
  • A statistical approach to identify optimal inclusion criteria: An application to acute stroke clinical trials. Contemporary clinical trials communications Ball, R. L., Jiang, B., Desai, M., Michel, P., Eskandari, A., Jovin, T., Wintermark, M. 2019; 14: 100355

    Abstract

    Purpose: To develop a statistical approach that compares patient selection strategies across clinical trials and apply this approach to acute ischemic stroke clinical trials to identify the optimal inclusion criteria.Methods: We developed a statistical approach that compares the number needed to treat to achieve one success (NNT) along with the number needed to screen to achieve one success (NNS) and assesses if there are significant differences in inclusion criteria, treatment course, and clinical outcome among patients that may have been included/excluded in the trials. We applied this approach to the study population from four recent positive acute stroke clinical trials: MR CLEAN, EXTEND-IA, ESCAPE, and SWIFT PRIME, applying published trial criteria to an independent registry of 612 acute stroke patients, since we did not have access to the complete trial data.Results: Although reported NNT were similar for EXTEND-IA, SWIFT PRIME and ESCAPE, and somewhat higher for MR CLEAN, NNS varied across the trials from 21 for EXTEND-IA, 27 for MR CLEAN, to 46 for ESCAPE and 64 for SWIFT PRIME, reflecting less and more stringent inclusion criteria, respectively. Although there were significant differences in imaging biomarkers and other clinical characteristics among patients that may have been included/excluded in the trials, these differences did not translate to significant differences in treatment course or clinical outcomes.Conclusions: Our study proposes a robust statistical approach that can be applied to a larger pooled trial dataset, if made available, to objectively compare across clinical trials and inform inclusion criteria of future trials. Pooled analysis of the acute stroke trial data is needed to determine which imaging biomarker inclusion criteria are critical and which may be relaxed. If this procedure were applied across the pooled trial data, it could decrease costs and refine the design of future trials to be the most efficacious for the greatest number of patients.

    View details for PubMedID 31011658

  • Collaterals are a major determinant of the core but not the penumbra volume in acute ischemic stroke. Neuroradiology Nannoni, S., Cereda, C. W., Sirimarco, G., Lambrou, D., Strambo, D., Eskandari, A., Dunet, V., Wintermark, M., Michel, P. 2019

    Abstract

    PURPOSE: Determinants of early loss of ischemic tissue (core) or its prolonged survival (penumbra) in acute ischemic stroke (AIS) are poorly understood. We aimed to identify radiological associations of core and penumbra volumes on CT perfusion (CTP) in a large cohort of AIS.METHODS: In the ASTRAL registry (2003-2016), we identified consecutive AIS patients with proximal middle cerebral artery (MCA) occlusion. We calculated core and penumbra volumes using established thresholds and the mismatch ratio (MR). We graded collaterals into three categories on CT-angiography. We used clot burden score (CBS) to quantify the clot length. We related CTP volumes to radiological variables in multivariate regression analyses, adjusted for time from stroke onset to first imaging.RESULTS: The median age of the 415 included patients was 69years (IQR=21) and 49% were female. Median admission NIHSS was 16 (11) and median delay to imaging 2.2h (1.9). Lower core volumes were associated with higher ASPECTS (hazard ratio=1.08), absence of hyperdense MCA sign (HR=0.70), higher CBS (i.e., smaller clot, HR=1.10), and better collaterals (HR=1.95). Higher penumbra volumes were related to lower CBS (i.e., longer clot, HR=1.08) and proximal intracranial occlusion (HR=1.47), but not to collaterals. Higher MR was found in absence of hyperdense MCA sign (HR=1.28), absence of distal intracranial occlusion (HR=1.39), and with better collaterals (HR=0.52).CONCLUSIONS: In AIS, better collaterals were associated with lower core volumes, but not with higher penumbra volumes. This suggests a major role of collaterals in early tissue loss and their limited significance as marker of salvageable tissue.

    View details for DOI 10.1007/s00234-019-02224-x

    View details for PubMedID 31123760

  • Common Data Elements for Radiological Imaging of Patients with Subarachnoid Hemorrhage: Proposal of a Multidisciplinary Research Group. Neurocritical care Hackenberg, K. A., Etminan, N., Wintermark, M., Meyers, P. M., Lanzino, G., Rufenacht, D., Krings, T., Huston, J. 3., Rinkel, G., Derdeyn, C., Unruptured Intracranial Aneurysms and SAH CDE Project Investigators, Suarez, J. I., Macdonald, R. L., Amin-Hanjani, S., Brown, R. D., de Oliveira Manoel, A. L., Derdeyn, C. P., Etminan, N., Keller, E., LeRoux, P. D., Mayer, S., Morita, A., Rinkel, G., Rufennacht, D., Stienen, M. N., Torner, J., Vergouwen, M. D., Wong, G. K., Bijlenga, P., Ko, N., McDougall, C. G., Mocco, J., Murayama, Y., Werner, M. J., Damani, R., Broderick, J., Dhar, R., Jauch, E. C., Kirkpatrick, P. J., Martin, R. H., Muehlschlegel, S., Mutoh, T., Nyquist, P., Olson, D., Mejia-Mantilla, J. H., van der Jagt, M., Bambakidis, N., Brophy, G., Bulsara, K., Claassen, J., Sander Connolly, E., Hoffer, S. A., Hoh, B. L., Holloway, R. G., Kelly, A., Nakaji, P., Rabinstein, A., Vajkoczy, P., Vergouwen, M. D., Woo, H., Zipfel, G. J., Chou, S., Dore, S., Dumont, A. S., Gunel, M., Kasuya, H., Roederer, A., Ruigrok, Y., Vespa, P. M., Sarrafzadeh-Khorrasani, A. S., Hackenberg, K. A., Huston, J. 3., Krings, T., Lanzino, G., Meyers, P. M., Wintermark, M., Daly, J., Ogilvy, C., Rhoney, D. H., Roos, Y. B., Siddiqui, A., Algra, A., Frosen, J., Hasan, D., Juvela, S., Langer, D. J., Salman, R. A., Hanggi, D., Schweizer, T., Visser-Meily, J., Amos, L., Ludet, C., Moy, C., Odenkirchen, J., Ala'i, S., Esterlitz, J., Joseph, K., Sheikh, M. 2019

    Abstract

    INTRODUCTION: Lack of homogeneous definitions for imaging data and consensus on their relevance in the setting of subarachnoid hemorrhage and unruptured intracranial aneurysms lead to a difficulty of data pooling and lack of robust data. The aim of the National Institute of Health/National Institute of Neurological Disorders and Stroke, Unruptured Intracranial Aneurysm (UIA) and Subarachnoid Hemorrhage (SAH) Common Data Elements (CDE) Project was to standardize data elements to ultimately facilitate data pooling and establish a more robust data quality in future neurovascular research on UIA and SAH.METHODS: For the subcommittee 'Radiological imaging of SAH,' international cerebrovascular specialists with imaging expertise in the setting of SAH were selected by the steering committee. CDEs were developed after reviewing the literature on neuroradiology and already existing CDEs for other neurological diseases. For prioritization, the CDEs were classified into 'Core,' 'Supplemental-Highly Recommended,' 'Supplemental' and 'Exploratory.'RESULTS: The subcommittee compiled 136 CDEs, 100 out of which were derived from previously established CDEs on ischemic stroke and 36 were newly created. The CDEs were assigned to four main categories (several CDEs were assigned to more than one category): 'Parenchymal imaging' with 42 CDEs, 'Angiography' with 49 CDEs, 'Perfusion imaging' with 20 CDEs, and 'Transcranial doppler' with 55 CDEs. The CDEs were classified into core, supplemental highly recommended, supplemental and exploratory elements. The core CDEs were imaging modality, imaging modality type, imaging modality vessel, angiography type, vessel angiography arterial anatomic site and imaging vessel angiography arterial result.CONCLUSIONS: The CDEs were established based on the current literature and consensus across cerebrovascular specialists. The use of these CDEs will facilitate standardization and aggregation of imaging data in the setting of SAH. However, the CDEs may require reevaluation and periodic adjustment based on current research and improved imaging quality and novel modalities.

    View details for DOI 10.1007/s12028-019-00728-1

    View details for PubMedID 31115823

  • Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke NEUROLOGY Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019; 92 (21): E2462–E2471
  • Stability of Blood Biomarkers of Traumatic Brain Injury JOURNAL OF NEUROTRAUMA Rezaii, P., Grant, G., Zeineh, M., Richardson, K., Coburn, M., Bet, A., Weber, A., Jiang, B., Li, Y., Ubungen, K., Routh, G., Wheatcroft, A., Paulino, A., Hayes, R., Steinberg, G., Wintermark, M. 2019: 1–10
  • Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain. Journal of neuroimaging : official journal of the American Society of Neuroimaging Kurt, M., Wu, L., Laksari, K., Ozkaya, E., Suar, Z. M., Lv, H., Epperson, K., Epperson, K., Sawyer, A. M., Camarillo, D., Pauly, K. B., Wintermark, M. 2019

    Abstract

    BACKGROUND AND PURPOSE: The brain's stiffness measurements from magnetic resonance elastography (MRE) strongly depend on actuation frequencies, which makes cross-study comparisons challenging. We performed a preliminary study to acquire optimal sets of actuation frequencies to accurately obtain rheological parameters for the whole brain (WB), white matter (WM), and gray matter (GM).METHODS: Six healthy volunteers aged between 26 and 72 years old went through MRE with a modified single-shot spin-echo echo planar imaging pulse sequence embedded with motion encoding gradients on a 3T scanner. Frequency-independent brain material properties and best-fit material model were determined from the frequency-dependent brain tissue response data (20 -80 Hz), by comparing four different linear viscoelastic material models (Maxwell, Kelvin-Voigt, Springpot, and Zener). During the material fitting, spatial averaging of complex shear moduli (G*) obtained under single actuation frequency was performed, and then rheological parameters were acquired. Since clinical scan time is limited, a combination of three actuation frequencies that would provide the most accurate approximation and lowest fitting error was determined for WB, WM, and GM by optimizing for the lowest Bayesian information criterion (BIC).RESULTS: BIC scores for the Zener and Springpot models showed these models approximate the multifrequency response of the tissue best. The best-fit frequency combinations for the reference Zener and Springpot models were identified to be 30-60-70 and 30-40-80 Hz, respectively, for the WB.CONCLUSIONS: Optimal sets of actuation frequencies to accurately obtain rheological parameters for WB, WM, and GM were determined from shear moduli measurements obtained via 3-dimensional direct inversion. We believe that our study is a first-step in developing a region-specific multifrequency MRE protocol for the human brain.

    View details for PubMedID 31056818

  • Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke. Neurology Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019

    Abstract

    OBJECTIVE: To determine if intravoxel incoherent motion (IVIM) magnetic resonance perfusion can measure the quality of the collateral blood flow in the penumbra in hyperacute stroke.METHODS: A 6 b values IVIM MRI sequence was acquired in stroke patients with large vessel occlusion imaged <16 hours of last seen well. IVIM perfusion measures were evaluated in regions of interest drawn in the infarct core (D < 600 mm2/s), in the corresponding region in the contralateral hemisphere, and in the dynamic susceptibility contrast penumbra. In patients with a penumbra >15 mL, images were reviewed for the presence of a penumbra perfusion lesion on the IVIM f map, which was correlated with infarct size metrics. Statistical significance was tested using Student t test, Mann-Whitney U test, and Fisher exact test.RESULTS: A total of 34 patients were included. In the stroke core, IVIM f was significantly lower (4.6 ± 3.3%) compared to the healthy contralateral region (6.3 ± 2.2%, p < 0.001). In the 25 patients with a penumbra >15 mL, 9 patients had an IVIM penumbra perfusion lesion (56 ± 76 mL), and 16 did not. Patients with an IVIM penumbra perfusion lesion had a larger infarct core (82 ± 84 mL) at baseline, a larger infarct growth (68 ± 40 mL), and a larger final infarct size (126 ± 81 mL) on follow-up images compared to the patients without (resp. 20 ± 17 mL, p < 0.05; 13 ± 19 mL, p < 0.01; 29 ± 24 mL, p < 0.05). All IVIM penumbra perfusion lesions progressed to infarction despite thrombectomy treatment.CONCLUSIONS: IVIM is a promising tool to assess the quality of the collateral blood flow in hyperacute stroke. IVIM penumbra perfusion lesion may be a marker of nonsalvageable tissue despite treatment with thrombectomy, suggesting that the IVIM penumbra perfusion lesion might be counted to the stroke core, together with the DWI lesion.

    View details for PubMedID 31019105

  • Stability of Blood Biomarkers of Traumatic Brain Injury. Journal of neurotrauma Rezaii, P., Grant, G., Zeineh, M., Richardson, K. J., Coburn, M. L., Bet, A. M., Weber, A., Jiang, B., Li, Y., Ubungen, K., Routh, G., Wheatcroft, A. M., Paulino, A., Hayes, R. L., Steinberg, G. K., Wintermark, M. 2019

    Abstract

    Blood biomarker tests were recently approved for clinical diagnosis of traumatic brain injury (TBI), yet there are still fundamental questions which need attention. One such question is the stability of putative biomarkers in blood over the course of several days after injury if the sample is unable to be processed into serum or plasma and stored at low temperatures. Blood may not be able to be stored at ultra-low temperatures in austere combat or sports environments. In this prospective study of 20 adult patients with positive head computed tomography imaging findings, the stability of three biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], and S100B) in whole blood and in serum stored at 4-5°C was evaluated over the course of 72 hours after blood collection. The amount of time whole blood and serum were refrigerated had no significant effect on GFAP concentration in plasma obtained from whole blood and in serum (p=0.6256 and p=0.3687, respectively), UCH-L1 concentration in plasma obtained from whole blood and in serum (p=0.0611 and p=0.5189, respectively), and S100B concentration in serum (p=0.4663). Concentration levels of GFAP, UCH-L1, and S100B in blood collected from patients with TBI were found to be stable at 4-5°C for at least 3 days after blood draw. This study suggests that the levels of the three diagnostic markers above are still valid for diagnostic TBI tests if the sample is stored in 4-5°C refrigerated conditions.

    View details for PubMedID 30968744

  • Design of a Phase III Study of Intravenous Glibenclamide (BIIB093) for Large Hemispheric Infarction: the CHARM Study Sheth, K. N., Kimberley, W., Albers, G. W., Hinson, H. E., Molyneaux, B. J., Nogueira, R., Saver, J., Steiner, T., Toyoda, K., Wintermark, M., Elkins, J., Deykin, A., Wald, M., Landen, J. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Imaging biomarkers of vulnerable carotid plaques for stroke risk prediction and their potential clinical implications. The Lancet. Neurology Saba, L., Saam, T., Jager, H. R., Yuan, C., Hatsukami, T. S., Saloner, D., Wasserman, B. A., Bonati, L. H., Wintermark, M. 2019

    Abstract

    Stroke represents a massive public health problem. Carotid atherosclerosis plays a fundamental part in the occurence of ischaemic stroke. European and US guidelines for prevention of stroke in patients with carotid plaques are based on quantification of the percentage reduction in luminal diameter due to the atherosclerotic process to select the best therapeutic approach. However, better strategies for prevention of stroke are needed because some subtypes of carotid plaques (eg, vulnerable plaques) can predict the occurrence of stroke independent of the degree of stenosis. Advances in imaging techniques have enabled routine characterisation and detection of the features of carotid plaque vulnerability. Intraplaque haemorrhage is accepted by neurologists and radiologists as one of the features of vulnerable plaques, but other characteristics-eg, plaque volume, neovascularisation, and inflammation-are promising as biomarkers of carotid plaque vulnerability. These biomarkers could change current management strategies based merely on the degree of stenosis.

    View details for PubMedID 30954372

  • Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy STROKE Guenego, A., Marcellus, D. G., Martin, B. W., Christensen, S., Albers, G. W., Lansberg, M. G., Marks, M. P., Wintermark, M., Heit, J. J. 2019; 50 (4): 917–22
  • Proposed achievable levels of dose and impact of dose-reduction systems for thrombectomy in acute ischemic stroke: an international, multicentric, retrospective study in 1096 patients. European radiology Guenego, A., Mosimann, P. J., Pereira, V. M., Nicholson, P., Zuber, K., Lotterie, J. A., Dobrocky, T., Marcellus, D. G., Olivot, J. M., Piotin, M., Gralla, J., Fahed, R., Wintermark, M., Heit, J. J., Cognard, C., RADON Investigators 2019

    Abstract

    BACKGROUND: International dose reference levels are lacking for mechanical thrombectomy in acute ischemic stroke patients with large vessel occlusions. We studied whether radiation dose-reduction systems (RDS) could effectively reduce exposure and propose achievable levels.MATERIALS AND METHODS: We retrospectively included consecutive patients treated with thrombectomy on a biplane angiography system (BP) in five international, high-volume centers between January 2014 and May 2017. Institutional Review Board approvals were obtained. Technical, procedural, and clinical characteristics were assessed. Efficacy, safety, radiation dose, and contrast load were compared between angiography systems with and without RDS. Multivariate analyses were adjusted according to Bonferroni's correction. Proposed international achievable cutoff levels were set at the 75th percentile.RESULTS: Out of the 1096 thrombectomized patients, 520 (47%) were treated on a BP equipped with RDS. After multivariate analysis, RDS significantly reduced dose-area product (DAP) (91 vs 140Gycm2, relative effect 0.74 (CI 0.66; 0.83), 35% decrease, p<0.001) and air kerma (0.46 vs 0.97Gy, relative effect 0.63 (CI 0.56; 0.71), 53% decrease, p<0.001) with 75th percentile levels of 148Gycm2 and 0.73Gy, respectively. There was no difference in contrast load, rates of successful recanalization, complications, or clinical outcome.CONCLUSION: Radiation dose-reduction systems can reduce DAP and air kerma by a third and a half, respectively, without affecting thrombectomy efficacy or safety. The respective thresholds of 148Gycm2 and 0.73Gy represent achievable levels that may serve to optimize current and future radiation exposure in the setting of acute ischemic stroke treatment. As technology evolves, we expect these values to decrease.KEY POINTS: Internationally validated achievable levels may help caregivers and health authorities better assess and reduce radiation exposure of both ischemic stroke patients and treating staff during thrombectomy procedures. Radiation dose-reduction systems can reduce DAP and air kerma by a third and a half, respectively, without affecting thrombectomy efficacy or safety in the setting of acute ischemic stroke due to large vessel occlusion.

    View details for DOI 10.1007/s00330-019-06062-6

    View details for PubMedID 30903333

  • Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy. Stroke Guenego, A., Marcellus, D. G., Martin, B. W., Christensen, S., Albers, G. W., Lansberg, M. G., Marks, M. P., Wintermark, M., Heit, J. J. 2019: STROKEAHA118024134

    Abstract

    Background and Purpose- Hypoperfusion intensity ratio (HIR) is associated with collateral status in acute ischemic stroke patients with anterior circulation large vessel occlusion. We assessed whether HIR was correlated to patient eligibility for mechanical thrombectomy (MT). Methods- We performed a retrospective cohort study of consecutive acute ischemic stroke patients with a proximal middle cerebral artery or internal carotid artery occlusion who underwent MT triage with computed tomography or magnetic resonance perfusion imaging. Clinical data, ischemic core (mL), HIR (defined as time-to-maximum [TMax] >10 seconds/TMax >6 seconds), mismatch volume between core and penumbra, and MT details were assessed. Primary outcome was favorable HIR collateral score (HIR <0.4) between patients who underwent MT (MT+) and those who did not (MT-) according to American Heart Association guidelines both in the <6 hours and 6 to 24 hours windows. Secondary outcomes were favorable HIR score in MT- subgroups (National Institutes of Health Stroke Scale <6 versus core >70 mL) and core-penumbra mismatch volumes. Patients who did not meet guidelines were not included. Results- We included 197 patients (145 MT+ and 52 MT-). MT+ patients had a significantly lower median HIR compared with MT- patients (0.4 [interquartile range, 0.2-0.5] versus 0.6 [interquartile range, 0.5-0.8]; P<0.001) and a higher mismatch volume (96 versus 27 mL, P<0.001). Among MT- patients, 43 had a core >70 mL, and 9 had a National Institutes of Health Stroke Scale <6. MT- patients with National Institutes of Health Stroke Scale <6 had a lower HIR than MT- patients with core >70 mL (0.2 [interquartile range, 0.2-0.3] versus 0.7 [interquartile range, 0.6-0.8], P<0.001) but their HIR was not significantly different that MT+ patients. Conclusions- Patients who meet American Heart Association guidelines for thrombectomy are more likely to have favorable collaterals (low HIR). HIR may be used as a marker of eligibility for MT triage.

    View details for PubMedID 30841821

  • Variation of degree of stenosis quantification using different energy level with dual energy CT scanner NEURORADIOLOGY Saba, L., Argioas, G., Lucatelli, P., Lavra, F., Suri, J. S., Wintermark, M. 2019; 61 (3): 285-291
  • Determining factors of better leptomeningeal collaterals: a study of 857 consecutive acute ischemic stroke patients JOURNAL OF NEUROLOGY Nannoni, S., Sirimarco, G., Cereda, C. W., Lambrou, D., Strambo, D., Eskandari, A., Mosimann, P. J., Wintermark, M., Michel, P. 2019; 266 (3): 582-588
  • Accuracy of detecting enlargement of aneurysms using different MRI modalities and measurement protocols JOURNAL OF NEUROSURGERY Nakagawa, D., Nagahama, Y., Policeni, B. A., Raghavan, M. L., Dillard, S. I., Schumacher, A. L., Sarathy, S., Dlouhy, B. J., Wilson, S., Allan, L., Woo, H. H., Huston, J., Cloft, H. J., Wintermark, M., Torner, J. C., Brown, R. D., Hasan, D. M. 2019; 130 (2): 559–65

    Abstract

    In BriefTo reliably assess the individual and agreement rates of accurately detecting intracranial aneurysm enlargement, the authors performed this study using flow phantom models and generally used MRI modalities. The results of this study suggest that the detection rate of at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or different measurement protocols.

    View details for PubMedID 29521585

  • FDG PET/MRI Coregistration Helps Predict Response to Gamma Knife Radiosurgery in Patients With Brain Metastases AMERICAN JOURNAL OF ROENTGENOLOGY Leiva-Salinas, C., Muttikkal, T., Flors, L., Puig, J., Wintermark, M., Patrie, J. T., Rehm, P. K., Sheehan, J. P., Schiff, D. 2019; 212 (2): 425-430
  • Predictors and Outcome of Eligible Patients for Late Endovascular Treatment: Real Life Analysis From a Comprehensive Stroke Center. Nannoni, S., Strambo, D., Sirimarco, G., Amiguet, M., Vanacker, P., Eskandari, A., Dunet, V., Saliou, G., Wintermark, M., Michel, P. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Inflammatory Biomarkers Correlate With Etiology in Childhood Arterial Ischemic Stroke Fullerton, H. J., Hills, N. K., Wintermark, M., Norris, P., Heitman, J., Keating, S., Owen, R., VIPS Investigators LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Selection Criteria for Thrombectomy in Pediatric Stroke: A Single-Center Series Lee, S., Heit, J. J., Albers, G. W., Wintermark, M., Elbers, J., Bernier, E., Jiang, B., Marks, M. P., Do Huy, M., Dodd, R. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Macrovascular Networks on Contrast-Enhanced Magnetic Resonance Imaging Improves Survival Prediction in Newly Diagnosed Glioblastoma. Cancers Puig, J., Biarnes, C., Daunis-I-Estadella, P., Blasco, G., Gimeno, A., Essig, M., Balana, C., Alberich-Bayarri, A., Jimenez-Pastor, A., Camacho, E., Thio-Henestrosa, S., Capellades, J., Sanchez-Gonzalez, J., Navas-Marti, M., Domenech-Ximenos, B., Del Barco, S., Puigdemont, M., Leiva-Salinas, C., Wintermark, M., Nael, K., Jain, R., Pedraza, S. 2019; 11 (1)

    Abstract

    A higher degree of angiogenesis is associated with shortened survival in glioblastoma. Feasible morphometric parameters for analyzing vascular networks in brain tumors in clinical practice are lacking. We investigated whether the macrovascular network classified by the number of vessel-like structures (nVS) visible on three-dimensional T1-weighted contrast⁻enhanced (3D-T1CE) magnetic resonance imaging (MRI) could improve survival prediction models for newly diagnosed glioblastoma based on clinical and other imaging features. Ninety-seven consecutive patients (62 men; mean age, 58 ± 15 years) with histologically proven glioblastoma underwent 1.5T-MRI, including anatomical, diffusion-weighted, dynamic susceptibility contrast perfusion, and 3D-T1CE sequences after 0.1 mmol/kg gadobutrol. We assessed nVS related to the tumor on 1-mm isovoxel 3D-T1CE images, and relative cerebral blood volume, relative cerebral flow volume (rCBF), delay mean time, and apparent diffusion coefficient in volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter. We also assessed Visually Accessible Rembrandt Images scoring system features. We used ROC curves to determine the cutoff for nVS and univariate and multivariate cox proportional hazards regression for overall survival. Prognostic factors were evaluated by Kaplan-Meier survival and ROC analyses. Lesions with nVS > 5 were classified as having highly developed macrovascular network; 58 (60.4%) tumors had highly developed macrovascular network. Patients with highly developed macrovascular network were older, had higher volumeCEL, increased rCBFCEL, and poor survival; nVS correlated negatively with survival (r = -0.286; p = 0.008). On multivariate analysis, standard treatment, age at diagnosis, and macrovascular network best predicted survival at 1 year (AUC 0.901, 83.3% sensitivity, 93.3% specificity, 96.2% PPV, 73.7% NPV). Contrast-enhanced MRI macrovascular network improves survival prediction in newly diagnosed glioblastoma.

    View details for PubMedID 30646519

  • Determining factors of better leptomeningeal collaterals: a study of 857 consecutive acute ischemic stroke patients. Journal of neurology Nannoni, S., Sirimarco, G., Cereda, C. W., Lambrou, D., Strambo, D., Eskandari, A., Mosimann, P. J., Wintermark, M., Michel, P. 2019

    Abstract

    BACKGROUND: In acute ischemic stroke (AIS) collaterals correlate with infarct size, recanalization rate and clinical outcome. We aimed to identify factors associated with better collateral status in a large series of AIS patients with middle cerebral artery (MCA) occlusion.METHODS: In the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 2003 to 2016, we identified all consecutive AIS with proximal MCA occlusion on CT-angiography performed<24h. Collaterals were scored from 0 (absent) to 3 (≥100%) and related to multiple demographic, clinical, metabolic and radiological variables in a multivariate regression analysis (MVA).RESULTS: The 857 included patients had a median age of 72.3years, 48.4% were female and median admission NIHSS was 16. Better collaterals were associated with younger age (OR 0.99; 95% CI 0.98-1.00), hemineglect (OR 1.35; 95% CI 1.03-1.76), absence of visual field defects (OR 0.64; 95% CI 0.46-0.90), eye deviation (OR 0.58; 95% CI 0.43-0.79) and decreased vigilance (OR 0.62; 95% CI 0.44-0.88). Better collaterals were also associated with dyslipidemia (OR 1.57; 95% CI 1.16-2.13), no previous statin use (OR 0.69; 95% CI 0.50-0.95), and lower creatinine levels (OR 0.99; 95% CI 0.99-1.00). On neuroimaging, better collaterals related to higher ASPECTS score (OR 1.27; 95% CI 1.20-1.35) and higher clot burden score (OR 1.09; 95% CI 1.03-1.14).CONCLUSIONS: Younger age, dyslipidemia and lower creatinine levels were predictors of better collaterals in AIS patients from proximal MCA occlusions. Greater degree of collaterals related to lower stroke severity on admission. On neuroimaging, better collaterals were independently associated with minor early ischemic changes and lower clot burden. These data may add knowledge on pathophysiology of collaterals development and may help to identify patients with better collaterals for late or aggressive recanalization treatments.

    View details for PubMedID 30610425

  • Longitudinal changes in hippocampal subfield volume associated with collegiate football. Journal of neurotrauma Parivash, S. N., Goubran, M. n., Mills, B. D., Rezaii, P. n., Thaler, C. n., Wolman, D. n., Bian, W. n., Mitchell, L. A., Boldt, B. n., Douglas, D. n., Wilson, E. n., Choi, J. n., Xie, L. n., Yushkevich, P. n., Digiacomo, P. n., Wongsripuemtet, J. n., Parekh, M. n., Fiehler, J. n., Do, H. n., Lopez, J. n., Rosenerg, J. n., Camarillo, D. B., Grant, G. n., Wintermark, M. n., Zeineh, M. n. 2019

    Abstract

    Collegiate football athletes are subject to repeated head impacts that may cause brain injury. The hippocampus is composed of several distinct subfields with possible differential susceptibility to injury. The purpose of this study is to determine whether there are longitudinal changes in hippocampal subfield volume in collegiate football. A prospective cohort study was conducted over a 5-year period tracking 63 football and 34 volleyball male collegiate athletes. Athletes underwent high-resolution structural magnetic resonance imaging, and automated segmentation provided hippocampal subfield volumes. At baseline, football athletes demonstrated a smaller subiculum volume than volleyball athletes (-67.77 mm3, P=.012). A regression analysis performed within football athletes similarly demonstrated a smaller subiculum volume among those at increased concussion risk based on athlete position (P=.001). For the longitudinal analysis, a linear mixed-effects model assessed the interaction between sport and time, revealing a significant decrease in CA1 volume in football athletes without an in-study concussion compared to volleyball athletes (volume difference per year=-35.22 mm3, P=.005). This decrease in CA1 volume over time was significant when football athletes were examined in isolation from volleyball athletes (P=.011). Thus, this prospective longitudinal study showed a decrease in CA1 volume over time in football athletes, in addition to baseline differences that were identified in the downstream subiculum. Hippocampal changes may have important implications for high-contact sports.

    View details for PubMedID 31044639

  • Imaging Evaluation of the Adult Presenting With New-Onset Seizure AMERICAN JOURNAL OF ROENTGENOLOGY Tranvinh, E., Lanzman, B., Provenzale, J., Wintermark, M. 2019; 212 (1): 15-25
  • Reorganization of brain networks following carotid endarterectomy: an exploratory study using resting state functional connectivity with a focus on the changes in Default Mode Network connectivity EUROPEAN JOURNAL OF RADIOLOGY Porcu, M., Craboledda, D., Garofalo, P., Barberini, L., Sanfilippo, R., Zaccagna, F., Wintermark, M., Montisci, R., Saba, L. 2019; 110: 233-241
  • Assessing the Relationship between Atherosclerotic Cardiovascular Disease Risk Score and Carotid Artery Imaging Findings JOURNAL OF NEUROIMAGING Li, Y., Zhu, G., Ding, V., Huang, Y., Jiang, B., Ball, R. L., Rodriguez, F., Fleischmann, D., Desai, M., Saloner, D., Saba, L., Hom, J., Wintermark, M. 2019; 29 (1): 119–25

    View details for DOI 10.1111/jon.12573

    View details for Web of Science ID 000454959000014

  • Macrovascular Networks on Contrast-Enhanced Magnetic Resonance Imaging Improves Survival Prediction in Newly Diagnosed Glioblastoma CANCERS Puig, J., Biarnes, C., Daunis-i-Estadella, P., Blasco, G., Gimeno, A., Essig, M., Balana, C., Alberich-Bayarri, A., Jimenez-Pastor, A., Camacho, E., Thio-Henestrosa, S., Capellades, J., Sanchez-Gonzalez, J., Navas-Marti, M., Domenech-Ximenos, B., Del Barco, S., Puigdemont, M., Leiva-Salinas, C., Wintermark, M., Nael, K., Jain, R., Pedraza, S. 2019; 11 (1)
  • Use of Gradient Boosting Machine Learning to Predict Patient Outcome in Acute Ischemic Stroke on the Basis of Imaging, Demographic, and Clinical Information AMERICAN JOURNAL OF ROENTGENOLOGY Xie, Y., Jiang, B., Gong, E., Li, Y., Zhu, G., Michel, P., Wintermark, M., Zaharchuk, G. 2019; 212 (1): 44–51
  • TESTING DIFFERENT COMBINATIONS OF ACOUSTIC PRESSURE AND DOSES OF QUINOLINIC ACID FOR INDUCTION OF FOCAL NEURON LOSS IN MICE USING TRANSCRANIAL LOW-INTENSITY FOCUSED ULTRASOUND ULTRASOUND IN MEDICINE AND BIOLOGY Zhang, Y., Liao, C., Qu, H., Huang, S., Jiang, H., Zhou, H., Abrams, E., Habte, F. G., Yuan, L., Bertram, E. H., Lee, K. S., Pauly, K., Buckmaster, P. S., Wintermark, M. 2019; 45 (1): 129–36
  • Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study RADIOLOGY Iv, M., Samghabadi, P., Holdsworth, S., Gentles, A., Rezaii, P., Harsh, G., Li, G., Thomas, R., Moseley, M., Daldrup-Link, H. E., Vogel, H., Wintermark, M., Cheshier, S., Yeom, K. W. 2019; 290 (1): 198–206
  • Seizures and Outcome One Year After Neonatal and Childhood Cerebral Sinovenous Thrombosis. Pediatric neurology Mineyko, A. n., Kirton, A. n., Billinghurst, L. n., Tatishvili, N. N., Wintermark, M. n., deVeber, G. n., Fox, C. n. 2019

    Abstract

    Pediatric cerebral sinovenous thrombosis is a treatable cause of brain injury, acute symptomatic seizures, and remote epilepsy. Our objective was to prospectively study epilepsy and outcomes in neonates and children one year after cerebral sinovenous thrombosis diagnosis.Patients with cerebral sinovenous thrombosis were enrolled prospectively from 21 international sites through the Seizures in Pediatric Stroke Study. Clinical data including acute symptomatic seizures and cerebral sinovenous thrombosis risk factors were collected at diagnosis. A neuroradiologist who was unaware of the diagnosis reviewed acute imaging. At one year, outcomes including seizure recurrence, epilepsy diagnosis, antiepileptic drug use, and modified Engel score were collected. Outcomes were assessed using the modified Rankin score and the King's Outcome Scale for Childhood Head Injury.Twenty-four participants with cerebral sinovenous thrombosis were enrolled (67% male, 21% neonates). Headache was the most common presenting symptom in non-neonates (47%, nine of 19). Nine (37.5%) presented with acute symptomatic seizures. Six (25%; 95% confidence interval, 10% to 47%) developed epilepsy by one-year follow-up. No clinical predictors associated with epilepsy were identified. King's Outcome Scale for Childhood Head Injury and modified Rankin scores at one year were favorable in 71%. Half of the patients who developed epilepsy (three of six) did not have infarcts, hemorrhage, or seizures identified during the acute hospitalization.Our study provides a prospective estimate that epilepsy occurs in approximately one-quarter of patients by one year after diagnosis of cerebral sinovenous thrombosis. Later epilepsy can develop in the absence of acute seizures or parenchymal injury associated with the acute presentation.

    View details for DOI 10.1016/j.pediatrneurol.2019.08.012

    View details for PubMedID 31882182

  • Imaging of Atypical and Complicated Posterior Reversible Encephalopathy Syndrome. Frontiers in neurology Saad, A. F., Chaudhari, R. n., Wintermark, M. n. 2019; 10: 964

    Abstract

    Posterior reversible encephalopathy syndrome (PRES) is a condition clinically characterized by headache, altered mental status, seizures, and visual loss and may be associated with systemic hypertension, preeclampsia/eclampsia, chemotherapy, immunosuppressive therapies in the setting of organ transplantation, and uremic encephalopathy. While brain imaging in patients with PRES typically reveals symmetric vasogenic edema within the parietal and occipital lobes, PRES may present with atypical imaging findings such as central brainstem and deep gray involvement without subcortical edema, and even spinal cord involvement. Additionally, PRES may be complicated in some cases by the presence of cytotoxic edema and hemorrhage. This review will serve to summarize the pathophysiologic theories and controversies underlying PRES, imaging features encountered in atypical and complicated PRES, and the implications these findings may have on patient prognosis.

    View details for DOI 10.3389/fneur.2019.00964

    View details for PubMedID 31551919

    View details for PubMedCentralID PMC6738024

  • Effect of Electronic Clinical Decision Support on Imaging for the Evaluation of Acute Low Back Pain in the Ambulatory Care Setting. World neurosurgery Chen, D. n., Bhambhvani, H. P., Hom, J. n., Mahoney, M. n., Wintermark, M. n., Sharp, C. n., Ratliff, J. n., Chen, Y. R. 2019

    Abstract

    To assess the effectiveness of a clinical decision support tool consisting of an electronic medical record Best Practice Alert (BPA) on the frequency of lumbar imaging in patients with acute low back pain (LBP) in the ambulatory care setting. To understand why providers order imaging outside of clinical guidelines.We implemented a BPA pop-up alert on 3/23/16 that informed the ordering physician of the Choosing Wisely recommendation to not order imaging within the first 6 weeks of low back pain in the absence of red flags. We measured imaging rates 1 year before and after implementation of the BPA. To override the BPA, providers could ignore the alert or explain their rationale for ordering imaging using either pre-set options or free-text submission. We tracked pre-set options and manually reviewed 125 free-text submissions.Significant decreases in both total imaging rate (9.6% decrease, p = 0.02) and MRI rate (14.9% decrease, p < 0.01) were observed after implementation of the BPA. No change was found in the rates of x-ray or CT ordering. 64% of providers used pre-set options in overriding the BPA, while 36% of providers entered a free-text submission. Among those providers using a free-text submission, 56% entered a non-guideline supported rationale.The present study demonstrates the effectiveness of a simple, low-cost clinical decision support tool in reducing imaging rates for patients with acute low back pain. We additionally identify reasons providers order imaging outside of clinical guidelines.

    View details for DOI 10.1016/j.wneu.2019.11.031

    View details for PubMedID 31733384

  • Reorganization of brain networks following carotid endarterectomy: an exploratory study using resting state functional connectivity with a focus on the changes in Default Mode Network connectivity. European journal of radiology Porcu, M., Craboledda, D., Garofalo, P., Barberini, L., Sanfilippo, R., Zaccagna, F., Wintermark, M., Montisci, R., Saba, L. 2019; 110: 233–41

    Abstract

    OBJECTIVES: To assess whether there is mid-term reorganization in brain networks connectivity after Carotid Endarterectomy (CEA) using resting state functional connectivity Magnetic Resonance (fc-rsMR), with a special focus on the Default Mode Network (DMN).MATERIALS AND METHODS: In this prospective exploratory study, 14 asymptomatic consecutive patients (10 males and 4 females, mean age 73.5) with unilateral, significant ICA stenosis eligible for CEA according to European Society for Vascular Surgery guidelines were prospectively recruited. The week before CEA procedure, each patient underwent both neurocognitive and rs-fcMR evaluations on the same day; the neurocognitive test consisted on a Mini Mental State Examination (MMSE). The same neurocognitive test and rs-fcMR examination were repeated on follow-up between 3-6 months after CEA. MMSE scores were compared using paired T-Student Test. Rs-fcMR Region Of Interest (ROI-to-ROI) and Seed-to-voxel group analysis were conducted using the CONN toolbox v18 and the SPM 12 software.RESULTS: Patients showed improvements in MMSE scores from before to after CEA (p-value=0.0001). ROI-to-ROI analysis revealed several statistically significant connectivity changes following CEA, both in terms of positive and negative correlations; Seed-to-Voxel focusing on DMN revealed increased connectivity between medial prefrontal cortex (mPFC) and three different clusters of voxels.CONCLUSIONS: CEA procedure is associated with an improvement in neurocognitive performance (according to MMSE testing) and reorganization of functional connectivity, including the DMN. These results represent a starting point in order to design further studies for a better understanding of the reorganization of brain networks following CEA, and to investigate the potential role of CEA as a therapeutic procedure for cognitive impairments in selected patients with critical ICA stenosis.

    View details for PubMedID 30599866

  • Arterial-Spin Labeling MRI Identifies Residual Cerebral Arteriovenous Malformation Following Stereotactic Radiosurgery Treatment. Journal of neuroradiology. Journal de neuroradiologie Heit, J. J., Thakur, N. H., Iv, M. n., Fischbein, N. J., Wintermark, M. n., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. n. 2019

    Abstract

    Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment.We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow - up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal.15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k = 0.92; 95% CI: 0.8-1.0; p < 0.0001).ASL is highly sensitive and specific in the detection of residual cerebral AVM following SRS treatment.

    View details for PubMedID 30658138

  • Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience. Journal of neurointerventional surgery Lee, S. n., Heit, J. J., Albers, G. W., Wintermark, M. n., Jiang, B. n., Bernier, E. n., Fischbein, N. J., Mlynash, M. n., Marks, M. P., Do, H. M., Dodd, R. L. 2019

    Abstract

    The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.We performed a retrospective cohort study of patients aged <18 years presenting within 24 hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher's exact test, t-test, or Mann-Whitney U-test.Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10-14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

    View details for PubMedID 31097548

  • Factors influencing infarct growth including collateral status assessed using computed tomography in acute stroke patients with large artery occlusion. International journal of stroke : official journal of the International Stroke Society Jiang, B. n., Ball, R. L., Michel, P. n., Li, Y. n., Zhu, G. n., Ding, V. n., Su, B. n., Naqvi, Z. n., Eskandari, A. n., Desai, M. n., Wintermark, M. n. 2019: 1747493019851278

    Abstract

    In major ischemic stroke caused by a large artery occlusion, neuronal loss varies considerably across individuals without revascularization. This study aims to identify which patient characteristics are most highly associated with this variability. Demographic and clinical information were retrospectively collected on a registry of 878 patients. Imaging biomarkers including Alberta Stroke Program Early CT score, noncontrast head computed tomography infarct volume, perfusion computed tomography infarct core and penumbra, occlusion site, collateral score, and recanalization status were evaluated on the baseline and early follow-up computed tomography images. Infarct growth rates were calculated by dividing infarct volumes by the time elapsed between the computed tomography scan and the symptom onset. Collateral score was graded into four levels (0, 1, 2, and 3) in comparison with the normal side. Correlation of perfusion computed tomography and noncontrast head computed tomography infarct volumes and infarct growth rates were estimated with the nonparametric Spearman's rank correlation. Conditional inference trees were used to identify the clinical and imaging biomarkers that were most highly associated with the infarct growth rate and modified Rankin Scale at 90 days. Two hundred and thirty-two patients met the inclusion criteria for this study. The median infarct growth rates for perfusion computed tomography and noncontrast head computed tomography were 11.2 and 6.2 ml/log(min) in logarithmic model, and 18.9 and 10.4 ml/h in linear model, respectively. Noncontrast head computed tomography and perfusion computed tomography infarct volumes and infarct growth rates were significantly correlated (rho=0.53; P < 0.001). Collateral status was the strongest predictor for infarct growth rates. For collateral=0, the perfusion computed tomography and noncontrast head computed tomography infarct growth rate were 31.56 and 16.86 ml/log(min), respectively. Patients who had collateral >0 and penumbra volumes>92 ml had the lowest predicted perfusion computed tomography infarct growth rates (6.61 ml/log(min)). Collateral status was closely related to the diversity of infarct growth rates, poor collaterals were associated with a faster infarct growth rates and vice versa.

    View details for DOI 10.1177/1747493019851278

    View details for PubMedID 31096871

  • Deep Learning Convolutional Neural Networks for the Automatic Quantification of Muscle Fat Infiltration Following Whiplash Injury. Scientific reports Weber, K. A., Smith, A. C., Wasielewski, M. n., Eghtesad, K. n., Upadhyayula, P. A., Wintermark, M. n., Hastie, T. J., Parrish, T. B., Mackey, S. n., Elliott, J. M. 2019; 9 (1): 7973

    Abstract

    Muscle fat infiltration (MFI) of the deep cervical spine extensors has been observed in cervical spine conditions using time-consuming and rater-dependent manual techniques. Deep learning convolutional neural network (CNN) models have demonstrated state-of-the-art performance in segmentation tasks. Here, we train and test a CNN for muscle segmentation and automatic MFI calculation using high-resolution fat-water images from 39 participants (26 female, average = 31.7 ± 9.3 years) 3 months post whiplash injury. First, we demonstrate high test reliability and accuracy of the CNN compared to manual segmentation. Then we explore the relationships between CNN muscle volume, CNN MFI, and clinical measures of pain and neck-related disability. Across all participants, we demonstrate that CNN muscle volume was negatively correlated to pain (R = -0.415, p = 0.006) and disability (R = -0.286, p = 0.045), while CNN MFI tended to be positively correlated to disability (R = 0.214, p = 0.105). Additionally, CNN MFI was higher in participants with persisting pain and disability (p = 0.049). Overall, CNN's may improve the efficiency and objectivity of muscle measures allowing for the quantitative monitoring of muscle properties in disorders of and beyond the cervical spine.

    View details for DOI 10.1038/s41598-019-44416-8

    View details for PubMedID 31138878

  • Semiautomated Characterization of Carotid Artery Plaque Features From Computed Tomography Angiography to Predict Atherosclerotic Cardiovascular Disease Risk Score. Journal of computer assisted tomography Zhu, G. n., Li, Y. n., Ding, V. n., Jiang, B. n., Ball, R. L., Rodriguez, F. n., Fleischmann, D. n., Desai, M. n., Saloner, D. n., Gupta, A. n., Saba, L. n., Hom, J. n., Wintermark, M. n. 2019

    Abstract

    To investigate whether selected carotid computed tomography angiography (CTA) quantitative features can predict 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores.One hundred seventeen patients with calculated ASCVD risk scores were considered. A semiautomated imaging analysis software was used to segment and quantify plaque features. Eighty patients were randomly selected to build models using 14 imaging variables and the calculated ASCVD risk score as the end point (continuous and binarized). The remaining 37 patients were used as the test set to generate predicted ASCVD scores. The predicted and observed ASCVD risk scores were compared to assess properties of the predictive model.Nine of 14 CTA imaging variables were included in a model that considered the plaque features in a continuous fashion (model 1) and 6 in a model that considered the plaque features dichotomized (model 2). The predicted ASCVD risk scores were 18.87% ± 13.26% and 18.39% ± 11.6%, respectively. There were strong correlations between the observed ASCVD and the predicted ASCVDs, with r = 0.736 for model 1 and r = 0.657 for model 2. The mean biases between observed ASCVD and predicted ASCVDs were -1.954% ± 10.88% and -1.466% ± 12.04%, respectively.Selected quantitative imaging carotid features extracted from the semiautomated carotid artery analysis can predict the ASCVD risk scores.

    View details for PubMedID 31082978

  • The influence of the volumetric composition of the intracranial space on neural activity in healthy subjects: a resting-state functional magnetic resonance study. The European journal of neuroscience Porcu, M. n., Wintermark, M. n., Suri, J. S., Saba, L. n. 2019

    Abstract

    Brain atrophy is a condition observed both with healthy aging and in association with neurologic pathological conditions. We investigated the role of the volumetric composition of the intracranial space (VOCICS) in terms of relative brain volume (BV%) and relative cerebrospinal fluid volume (CSFV%) on the neural activity measured by resting-state functional Magnetic Resonance Imaging (rs-fMRI). We performed a group rs-fMRI analysis of a dataset of 192 healthy subjects derived by the publicly available Functional Connectome Project. Automatic volumetric analysis of structural data was performed in order to obtain BV% and CSFV% for every subject. Two fractional Amplitude of Low Frequency Fluctuations (fALFF) and two Region of interest to Region of interest (ROI-to-ROI) analyses were then performed using BV% and CSFV% as second level covariates, adopting a multiple regression statistic test in order to evaluate the effects of BV% and CSFV% on brain networks. The analyses revealed that VOCICS broadly influence brain networks. In conclusion, VOCICS significantly influences brain activity measured by rs-fMRI, and this parameter could represent an easy marker of brain connectivity in healthy young subjects.

    View details for DOI 10.1111/ejn.14627

    View details for PubMedID 31782842

  • Application of FLAIR Vascular Hyperintensity-DWI Mismatch in Ischemic Stroke Depending on Semi-Quantitative DWI-Alberta Stroke Program Early CT Score. Frontiers in neurology Song, L. n., Lyu, C. n., Shen, G. n., Guo, T. n., Wang, J. n., Wang, W. n., Qiu, X. n., Lerner, A. n., Wintermark, M. n., Gao, B. n. 2019; 10: 994

    Abstract

    Objective: Diffusion-weighted imaging (DWI)-Alberta Stroke Program Early CT Score (ASPECTS) is a simple, widely used method to estimate the size of the infarct. Our aim is to determine whether there is a relationship between DWI-ASPECTS and fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH)-DWI mismatch and to better quantify FVH-DWI mismatch to assess the prognosis of cerebral infarction. Materials and Methods: A retrospective analysis of 109 patients with MCA stenosis or occlusion with cerebral infarction was performed by dividing this cohort into FVH-DWI match group and FVH-DWI mismatch group based on FVH and DWI results. The clinical and imaging data of these two groups of patients were reviewed and analyzed to identify associations between FVH-DWI mismatch and prognosis of patients for preservation of neurological function. Correlation between DWI-ASPECTS and FVH-DWI mismatch was also performed. Results: FVH-DWI mismatch was present in 66/109 (60.55%) patients, and FVH-DWI match was present in 43/109 (39.45%). Patients with FVH-DWI mismatch had higher DWI-ASPECTS (7.0 vs. 4.0, P < 0.001) and lower mRS at 3 months (3.0 vs. 4.0, P < 0.001) than patients without FVH-DWI mismatch. Multiple regression analysis suggested that DWI-ASPECTS (OR = 4.7, 95% CI = 2.5-9.2, P < 0.001) remained significantly associated with FVH-DWI mismatch. Two threshold points for DWI-ASPECTS of 3 and 8 can be used to distinguish whether there is a mismatch in FVH-DWI by smooth curve fitting. Conclusions: The DWI-ASPECTS score was an independent predictor of FVH-DWI mismatch. At DWI-ASPECTS ≤ 3, the FVH-DWI mismatch offers no prognostic value; whereas, at DWI-ASPECTS ≥ 8, the FVH-DWI mismatch had the highest prognostic value. DWI-ASPECTS can roughly determine whether there is a FVH-DWI mismatch in order to select optimal clinical treatment and accurately assess prognosis.

    View details for DOI 10.3389/fneur.2019.00994

    View details for PubMedID 31611838

    View details for PubMedCentralID PMC6776088

  • Demographics and Clinical Characteristics of Acute Traumatic Brain Injury Patients in the Different Neuroimaging Radiological Interpretation System (NIRIS) Categories. Journal of neuroradiology. Journal de neuroradiologie Chen, H. n., Li, Y. n., Jiang, B. n., Zhu, G. n., Rezaii, P. G., Gang, L. n., Wintermark, M. n. 2019

    Abstract

    - To characterize the demographics, clinical and imaging findings, and outcomes of traumatic brain injury (TBI) patients in each of NeuroImaging Radiological Interpretation System (NIRIS) categories.- We considered all consecutive patients transported to Stanford Hospital's emergency department by ambulance or helicopter between November 2015 and April 2017. We retained adult patients (> 18 years old) for whom a trauma alert was triggered and who underwent a non-contrast head computer tomography (CT) because of suspected TBI. We reviewed the non-contrast CT scans in these patients for the NIH TBI common data elements (CDEs). We recorded, then assessed differences in terms of demographics, clinical characteristics, imaging CDEs, and outcomes in patients from the different NIRIS categories.- 1,152 patients were included in this study. Patients with NIRIS 0 imaging findings were significantly younger than patients in other NIRIS categories (p<0.001). Motor vehicle accidents and falls from height were the most common mechanisms of injury across NIRIS categories. GCS scores decreased with increasing NIRIS category imaging findings and were significantly lower in patients with NIRIS 4 imaging findings (p<0.001). Significant differences in NIRIS categories were observed for all imaging CDEs (p<0.001), in agreement with the definition of the different NIRIS categories. Mortality increased progressively with increasing NIRIS severity.- TBI patients in different NIRIS categories have different clinical characteristics, hospital courses and outcomes. This natural history assessment of patients from different NIRIS categories could thus serve as a reference standard for future TBI clinical trials.

    View details for DOI 10.1016/j.neurad.2019.07.002

    View details for PubMedID 31323305

  • Stereotactic laser ablation for completion corpus callosotomy. Journal of neurosurgery. Pediatrics Huang, Y. n., Yecies, D. n., Bruckert, L. n., Parker, J. J., Ho, A. L., Kim, L. H., Fornoff, L. n., Wintermark, M. n., Porter, B. n., Yeom, K. W., Halpern, C. H., Grant, G. A. 2019: 1–9

    Abstract

    Completion corpus callosotomy can offer further remission from disabling seizures when a prior partial corpus callosotomy has failed and residual callosal tissue is identified on imaging. Traditional microsurgical approaches to section residual fibers carry risks associated with multiple craniotomies and the proximity to the medially oriented motor cortices. Laser interstitial thermal therapy (LITT) represents a minimally invasive approach for the ablation of residual fibers following a prior partial corpus callosotomy. Here, the authors report clinical outcomes of 6 patients undergoing LITT for completion corpus callosotomy and characterize the radiological effects of ablation.A retrospective clinical review was performed on a series of 6 patients who underwent LITT completion corpus callosotomy for medically intractable epilepsy at Stanford University Medical Center and Lucile Packard Children's Hospital at Stanford between January 2015 and January 2018. Detailed structural and diffusion-weighted MR images were obtained prior to and at multiple time points after LITT. In 4 patients who underwent diffusion tensor imaging (DTI), streamline tractography was used to reconstruct and evaluate tract projections crossing the anterior (genu and rostrum) and posterior (splenium) parts of the corpus callosum. Multiple diffusion parameters were evaluated at baseline and at each follow-up.Three pediatric (age 8-18 years) and 3 adult patients (age 30-40 years) who underwent completion corpus callosotomy by LITT were identified. Mean length of follow-up postoperatively was 21.2 (range 12-34) months. Two patients had residual splenium, rostrum, and genu of the corpus callosum, while 4 patients had residual splenium only. Postoperative complications included asymptomatic extension of ablation into the left thalamus and transient disconnection syndrome. Ablation of the targeted area was confirmed on immediate postoperative diffusion-weighted MRI in all patients. Engel class I-II outcomes were achieved in 3 adult patients, whereas all 3 pediatric patients had Engel class III-IV outcomes. Tractography in 2 adult and 2 pediatric patients revealed time-dependent reduction of fractional anisotropy after LITT.LITT is a safe, minimally invasive approach for completion corpus callosotomy. Engel outcomes for completion corpus callosotomy by LITT were similar to reported outcomes of open completion callosotomy, with seizure reduction primarily observed in adult patients. Serial DTI can be used to assess the presence of tract projections over time but does not classify treatment responders or nonresponders.

    View details for DOI 10.3171/2019.5.PEDS19117

    View details for PubMedID 31374542

  • Validation of the NeuroImaging Radiological Interpretation System for Acute Traumatic Brain Injury. Journal of computer assisted tomography Zhou, B. n., Ding, V. Y., Li, Y. n., Ball, R. L., Jiang, B. n., Zhu, G. n., Boothroyd, D. n., Zeineh, M. n., Gean, A. n., Wintermark, M. n. 2019

    Abstract

    The aim of the study was to refine and validate the NeuroImaging Radiological Interpretation System (NIRIS), which was developed to predict management and clinical outcome based on noncontrast head computerized tomography findings in patients suspected of acute traumatic brain injury (TBI).We assessed the performance of the NIRIS score in a prospective, single-center cohort of patients suspected of TBI (n = 648) and compared the performance of NIRIS with that of the Marshall and Rotterdam scoring systems. We also revised components of the NIRIS scoring system using decision tree methodologies implemented on pooled data from the retrospective and prospective studies (N = 1190).The NIRIS performed similarly to the Marshall and Rotterdam scoring systems in predicting mortality and markedly better in terms of predicting more granular elements of disposition and management of TBI patients, such as admission, follow-up imaging, intensive care unit stay, and neurosurgical procedures. The revised NIRIS classification correctly predicted disposition and outcome in 91.2% (331/363) after excluding patients with other major extracranial traumatic injuries or intracranial nontraumatic injuries.The present study further demonstrates the predictive value of NIRIS in guiding standardized clinical management and decision-making regarding treatment options for TBI patients.

    View details for DOI 10.1097/RCT.0000000000000913

    View details for PubMedID 31490891

  • Large-scale ensemble simulations of biomathematical brain arteriovenous malformation models using graphics processing unit computation. Computers in biology and medicine Jain, M. S., Do, H. M., Wintermark, M. n., Massoud, T. F. 2019; 113: 103416

    Abstract

    Theoretical modeling allows investigations of cerebral arteriovenous malformation (AVM) hemodynamics, but current models are too simple and not clinically representative. We developed a more realistic AVM model based on graphics processing unit (GPU) computing, to replicate highly variable and complex nidus angioarchitectures with vessel counts in the thousands-orders of magnitude greater than current models.We constructed a theoretical electrical circuit AVM model with a nidus described by a stochastic block model (SBM) of 57 nodes and an average of 1000 plexiform and fistulous vessels. We sampled and individually simulated 10,000 distinct nidus morphologies from this SBM, constituting an ensemble simulation. We assigned appropriate biophysical values to all model vessels, and known values of mean intravascular pressure (Pmean) to extranidal vessels. We then used network analysis to calculate Pmean and volumetric flow rate within each nidus vessel, and mapped these values onto a graphic representation of the nidus network. We derived an expression for nidus rupture risk and conducted a model parameter sensitivity analysis.Simulations revealed a total intranidal volumetric blood flow ranging from 268 mL/min to 535 mL/min, with an average of 463 mL/min. The maximum percentage rupture risk among all vessels in the nidus ranged from 0% to 60%, with an average of 29%.This easy to implement biomathematical AVM model, allowed by parallel data processing using advanced GPU computing, will serve as a useful tool for theoretical investigations of AVM therapies and their hemodynamic sequelae.

    View details for DOI 10.1016/j.compbiomed.2019.103416

    View details for PubMedID 31494430

  • Neuroimaging of Traumatic Brain Injury. Medical sciences (Basel, Switzerland) Douglas, D. B., Ro, T., Toffoli, T., Krawchuk, B., Muldermans, J., Gullo, J., Dulberger, A., Anderson, A. E., Douglas, P. K., Wintermark, M. 2018; 7 (1)

    Abstract

    The purpose of this article is to review conventional and advanced neuroimaging techniques performed in the setting of traumatic brain injury (TBI). The primary goal for the treatment of patients with suspected TBI is to prevent secondary injury. In the setting of a moderate to severe TBI, the most appropriate initial neuroimaging examination is a noncontrast head computed tomography (CT), which can reveal life-threatening injuries and direct emergent neurosurgical intervention. We will focus much of the article on advanced neuroimaging techniques including perfusion imaging and diffusion tensor imaging and discuss their potentials and challenges. We believe that advanced neuroimaging techniques may improve the accuracy of diagnosis of TBI and improve management of TBI.

    View details for PubMedID 30577545

  • Variation of degree of stenosis quantification using different energy level with dual energy CT scanner. Neuroradiology Saba, L., Argioas, G. M., Lucatelli, P., Lavra, F., Suri, J. S., Wintermark, M. 2018

    Abstract

    PURPOSE: To investigate the variation in the quantification of the carotid degree of stenosis (DoS) with a dual energy computed tomography (CT), using different energy levels during the image reconstruction.METHODS: In this retrospective study, 53 subjects (37 males; mean age 67±11years; age range 47-83years) studied with a multi-energy CT scanner were included. Datasets were reconstructed on a dedicated workstation and from the CT raw data multiple datasets were generated at the following monochromatic energy levels: 66, 70, 77, and 86kilo-electronvolt (keV). Two radiologists independently performed all measurements for quantification of the degree of stenosis. Wilcoxon test was used to test the differences between the Hounsifield unit (HU) values in the plaques at different keV.RESULTS: The Wilcoxon analysis showed a statistically significant difference (p=0.001) in the DoS assessment among the different keVs selected. The Bland-Altman analysis showed that the DoS difference had a linear relation with the keV difference (the bigger is the difference in keV, the bigger is the variation in DoS) and that for different keVs, the difference in DoS is reduced with its increase.CONCLUSION: A standardization in the use of the energy level during the image reconstruction should be considered.

    View details for PubMedID 30554271

  • Connectometry evaluation in patients undergoing carotid endarterectomy: an exploratory study. Brain imaging and behavior Porcu, M., Craboledda, D., Garofalo, P., Columbano, G., Barberini, L., Sanfilippo, R., Zaccagna, F., Wintermark, M., Montisci, R., Saba, L. 2018

    Abstract

    This research investigated local brain connectivity changes following Carotid Endarterectomy (CEA) by connectometry. Seventeen subjects (15 males and 2 females, mean age 74.1years), all eligible for CEA, were prospectively recruited in this exploratory study. On the same day within the week before the CEA, each patient underwent a cognitive evaluation with a Mini Mental State Examination (MMSE) and a Magnetic Resonance Imaging (MRI) exam that included a DTI sequence for the connectometry analysis. A second MMSE and the same MRI protocol were performed on follow-up, 3-6months after CEA. The MMSE scores were analyzed using T-Student tests. The connectometry analysis was performed using a multiple regression model to consider the effect of CEA, choosing three different T-score threshold (T-threshold) values (1, 2 and 3). Results were considered statistically valid for p value adjusted for False Discovery Rate (p-FDR)<0.05. Comparison of pre-CEA and post-CEA MMSE scores showed improvement of MMSE scores after CEA. Connectometry analysis revealed no areas of statistically significant increased connectivity related to CEA for T-threshold value=1 and 2, but showed statistically significant increase of connectivity after CEA in both cerebellar hemispheres and corpus callosum for T-threshold value=3 (p-FDR=0.0106667). The network property analysis showed improved small worldness (2.14%), clustering coefficient (1.64%), local (1.94%) and global efficiency (0.56%), and reduced characteristic path length (-0.52%) after CEA. These results suggest that CEA is associated both with cognitive performance improvement and changes in interhemispheric local connectivity in the corpus callosum and cerebellum.

    View details for PubMedID 30535626

  • Response by Vagal et al to Letter Regarding Article, "Collateral Clock Is More Important Than Time Clock for Tissue Fate: A Natural History Study of Acute Ischemic Strokes". Stroke Vagal, A., Aviv, R., Wintermark, M. 2018; 49 (12): e340

    View details for PubMedID 30571445

  • Response by Vagal et al to Letter Regarding Article, "Collateral Clock Is More Important Than Time Clock for Tissue Fate: A Natural History Study of Acute Ischemic Strokes" STROKE Vagal, A., Aviv, R., Wintermark, M. 2018; 49 (12): E340
  • Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? JOURNAL OF NEUROINTERVENTIONAL SURGERY Wolman, D. N., Iv, M., Wintermark, M., Zaharchuk, G., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018; 10 (12): 1132-+
  • FDG PET/MRI Coregistration Helps Predict Response to Gamma Knife Radiosurgery in Patients With Brain Metastases. AJR. American journal of roentgenology Leiva-Salinas, C., Muttikkal, T. J., Flors, L., Puig, J., Wintermark, M., Patrie, J. T., Rehm, P. K., Sheehan, J. P., Schiff, D. 2018: 1–6

    Abstract

    OBJECTIVE: The purpose of this study was to determine whether relative standardized uptake value (SUV) measurements at FDG PET/MRI coregistration are predictive of local tumor control in patients with brain metastases treated with stereotactic radiosurgery (SRS).MATERIALS AND METHODS: A retrospective review was conducted of the images and clinical characteristics of a cohort of patients with brain metastases from non-CNS neoplasms treated with gamma knife radiosurgery (GKRS) who underwent posttherapy FDG PET because of MRI findings concerning for progression. The PET and contrast-enhanced MR images were fused. Relative SUV measurements were calculated from ROIs placed in the area of highest FDG uptake within the enhancing lesion and in the contralateral normal-appearing white matter. Relative SUV was defined as the ratio of maximum SUV in the tumor to maximum SUV in healthy white matter. Two independent readers evaluated response to GKRS using serial posttherapy MRI performed at least 3 months after GKRS completion. The relation between relative SUV and local tumor progression was evaluated with respect to treatment effect.RESULTS: Eighty-five patients (48 [56.5%] women, 37 [43.5%] men; mean age at diagnosis, 60.5 ± 11.3 years) met the inclusion criteria. Thirty-three (38.8%) lesions progressed after SRS. There was a significant association between relative SUV and local tumor control (p = 0.035). Relative SUV provided a diagnostic ROC AUC of 0.67 (95% CI, 0.55-0.79).CONCLUSION: Quantitative relative SUV at posttherapy FDG PET serves as a biomarker of response to SRS in patients with brain metastases in cases in which lesion growth is identified at follow-up MRI. This prognostic data may affect management, supporting the need for further therapeutic actions for selected patients.

    View details for PubMedID 30422717

  • Focal Cerebral Arteriopathy of Childhood. Stroke Fullerton, H. J., Stence, N., Hills, N. K., Jiang, B., Amlie-Lefond, C., Bernard, T. J., Friedman, N. R., Ichord, R., Mackay, M. T., Rafay, M. F., Chabrier, S., Steinlin, M., Elkind, M. S., deVeber, G. A., Wintermark, M., VIPS Investigators 2018; 49 (11): 2590–96

    Abstract

    Background and Purpose- Focal cerebral arteriopathy (FCA)-a common cause of arterial ischemic stroke in previously healthy children-often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods- The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010-2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results- The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2-6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5-9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5-35.5) days poststroke; their median FCASS increase was 4 (2.5-6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P=0.037). Conclusions- Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development.

    View details for PubMedID 30355212

  • Impact of Neuroradiology Staffing on Academic Hospital Level Quality and Cost Measures for the Neuroscience Service Line JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Wintermark, M., Lee, Y., Kerr, A., Hess, C., Dillon, W. P., Mukherji, S. K., Norbash, A., Seidenwurm, D., Law, M. 2018; 15 (11): 1609-1612
  • Assessing the Relationship Between American Heart Association Atherosclerotic Cardiovascular Disease Risk Score and Coronary Artery Imaging Findings JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Li, Y., Zhu, G., Ding, V., Jiang, B., Ball, R. L., Ahuja, N., Rodriguez, F., Fleischmann, D., Desai, M., Saloner, D., Saba, L., Wintermark, M., Hom, J. 2018; 42 (6): 898–905
  • Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History STROKE Fullerton, H. J., Stence, N., Hills, N. K., Jiang, B., Amlie-Lefond, C., Bernard, T. J., Friedman, N. R., Ichord, R., Mackay, M. T., Rafay, M. F., Chabrier, S., Steinlin, M., Elkind, M. V., deVeber, G. A., Wintermark, M., VIPS Investigators 2018; 49 (11): 2590–96
  • Advanced Neuroimaging of Acute Ischemic Stroke: Penumbra and Collateral Assessment. Neuroimaging clinics of North America Heit, J. J., Zaharchuk, G., Wintermark, M. 2018; 28 (4): 585–97

    Abstract

    Acute ischemic stroke (AIS) occurs when there is a sudden loss in cerebral blood flow due to embolic or thromboembolic occlusion of a cerebral or cervical artery. Patients with AIS require emergent neuroimaging to guide treatment, which includes intravenous thrombolysis and endovascular mechanical thrombectomy (EMT). Recent advances in AIS treatment by EMT has been driven in part by advances in computed tomography (CT) and MR imaging neuroimaging evaluation of ischemic penumbra and pial collateral vessels. The authors review advanced noninvasive brain imaging by CT and MR imaging for the evaluation of AIS focusing on penumbral and collateral imaging.

    View details for DOI 10.1016/j.nic.2018.06.004

    View details for PubMedID 30322595

  • Computed Tomography, Computed Tomography Angiography, and Perfusion Computed Tomography Evaluation of Acute Ischemic Stroke NEUROIMAGING CLINICS OF NORTH AMERICA Leiva-Salinas, C., Jiang, B., Wintermark, M. 2018; 28 (4): 565–72
  • Use of Gradient Boosting Machine Learning to Predict Patient Outcome in Acute Ischemic Stroke on the Basis of Imaging, Demographic, and Clinical Information. AJR. American journal of roentgenology Xie, Y., Jiang, B., Gong, E., Li, Y., Zhu, G., Michel, P., Wintermark, M., Zaharchuk, G. 2018: 1–7

    Abstract

    OBJECTIVE: When treatment decisions are being made for patients with acute ischemic stroke, timely and accurate outcome prediction plays an important role. The optimal rehabilitation strategy also relies on long-term outcome predictions. The decision-making process involves numerous biomarkers including imaging features and demographic information. The objective of this study was to integrate common stroke biomarkers using machine learning methods and predict patient recovery outcome at 90 days.MATERIALS AND METHODS: A total of 512 patients were enrolled in this retrospective study. Extreme gradient boosting (XGB) and gradient boosting machine (GBM) models were used to predict modified Rankin scale (mRS) scores at 90 days using biomarkers available at admission and 24 hours. Feature selections were performed using a greedy algorithm. Fivefold cross validation was applied to estimate model performance.RESULTS: For binary prediction of an mRS score of greater than 2 using biomarkers available at admission, XGB and GBM had an AUC of 0.746 and 0.748, respectively. Adding the National Institutes of Health Stroke Score at 24 hours and performing feature selection improved the AUC of XGB to 0.884 and the AUC of GBM to 0.877. With the addition of the recanalization outcome, XGB's AUC improved to 0.807 for nonrecanalized patients and dropped to 0.670 for recanalized patients. GBM's AUC improved to 0.781 for nonrecanalized patients and dropped to 0.655 for recanalized patients.CONCLUSION: Decision tree-based GBMs can predict the recovery outcome of stroke patients at admission with a high AUC. Breaking down the patient groups on the basis of recanalization and nonrecanalization can potentially help with the treatment decision process.

    View details for PubMedID 30354266

  • Imaging Evaluation of the Adult Presenting With New-Onset Seizure. AJR. American journal of roentgenology Tranvinh, E., Lanzman, B., Provenzale, J., Wintermark, M. 2018: 1–11

    Abstract

    OBJECTIVE: The purpose of this study is to discuss the evidence supporting the use of neuroimaging in adult patients presenting with new-onset seizure.CONCLUSION: Unenhanced CT should be the initial imaging examination performed for adults presenting with first unprovoked seizure in the acute setting to exclude conditions requiring urgent or emergent intervention. MRI has added benefits and should be considered for adults presenting acutely for whom the initial CT is negative and for those presenting with new-onset seizure in the nonacute setting.

    View details for PubMedID 30299997

  • Testing Different Combinations of Acoustic Pressure and Doses of Quinolinic Acid for Induction of Focal Neuron Loss in Mice Using Transcranial Low-Intensity Focused Ultrasound. Ultrasound in medicine & biology Zhang, Y., Liao, C., Qu, H., Huang, S., Jiang, H., Zhou, H., Abrams, E., Habte, F. G., Yuan, L., Bertram, E. H., Lee, K. S., Pauly, K. B., Buckmaster, P. S., Wintermark, M. 2018

    Abstract

    The goal of this study was to test different combinations of acoustic pressure and doses of quinolinic acid (QA) for producing a focal neuronal lesion in the murine hippocampus without causing unwanted damage to adjacent brain structures. Sixty male CD-1 mice were divided into 12 groups that underwent magnetic resonance-guided focused ultrasound at high (0.67 MPa), medium (0.5 MPa) and low (0.33 MPa) acoustic peak negative pressures and received QA at high (0.012 mmol), medium (0.006 mmol) and low (0.003 mmol) dosages. Neuronal loss occurred only when magnetic resonance-guided focused ultrasound with adequate acoustic power (0.67 or 0.5 MPa) was combined with QA. The animals subjected to the highest acoustic power had larger lesions than those treated with medium acoustic power, but two mice had evidence of bleeding. When the intermediate acoustic power was used, medium andhigh dosages of QA produced lesions larger than those produced by the low dosage.

    View details for PubMedID 30309748

  • Intracranial Hemorrhage Imaging. Seminars in ultrasound, CT, and MR Saad, A. F., Chaudhari, R., Fischbein, N. J., Wintermark, M. 2018; 39 (5): 441–56

    Abstract

    Intracranial hemorrhage is a medical event frequently encountered in the clinical practice of radiology that has significant potential for patient morbidity and mortality. The expedient and accurate identification of intracranial hemorrhage as well as elucidation of the underlying cause can assist in optimizing the care of these patients. In this review, we attempt to familiarize the reader with the imaging appearance of multiple types of intracranial hemorrhage, both intra-axial and extra-axial and utilizing both computed tomography and magnetic resonance imaging, as well as to provide a framework for assessment of the underlying cause of the hemorrhage.

    View details for PubMedID 30244759

  • Intracranial Hemorrhage Imaging SEMINARS IN ULTRASOUND CT AND MRI Saad, A. F., Chaudhari, R., Fischbein, N. J., Wintermark, M. 2018; 39 (5): 441-456
  • Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome After Acute Stroke STROKE Puig, J., Blasco, G., Alberich-Bayarri, A., Schlaug, G., Deco, G., Biarnes, C., Navas-Marti, M., Rivero, M., Gich, J., Figueras, J., Torres, C., Daunis-i-Estadella, P., Oramas-Requejo, C. L., Serena, J., Stinear, C. M., Kuceyeski, A., Soriano-Mas, C., Thomalla, G., Essig, M., Figley, C. R., Menon, B., Demchuk, A., Nael, K., Wintermark, M., Liebeskind, D. S., Pedraza, S. 2018; 49 (10): 2353-2360
  • Investigating the effects of subconcussion on functional connectivity using mass-univariate and multivariate approaches BRAIN IMAGING AND BEHAVIOR Reynolds, B. B., Stanton, A. N., Soldozy, S., Goodkin, H. P., Wintermark, M., Druzgal, T. 2018; 12 (5): 1332–45

    Abstract

    There are concerns about the effects of subconcussive head impacts in sport, but the effects of subconcussion on brain connectivity are not well understood. We hypothesized that college football players experience changes in brain functional connectivity not found in athletes competing in lower impact sports or healthy controls. These changes may be spatially heterogeneous across participants, requiring analysis methods that go beyond mass-univariate approaches commonly used in functional MRI (fMRI). To test this hypothesis, we analyzed resting-state fMRI data from college football (n = 15), soccer (n = 12), and lacrosse players (n = 16), and controls (n = 29) collected at preseason and postseason time points. Regional homogeneity (ReHo) and degree centrality (DC) were calculated as measures of local and long-range functional connectivity, respectively. Standard voxel-wise analysis and paired support vector machine (SVM) classification studied subconcussion's effects on local and global functional connectivity. Voxel-wise analyses yielded minimal findings, but SVM classification had high accuracy for college football's ReHo (87%, p = 0.009) and no other group. The findings suggest subconcussion results in spatially heterogeneous changes in local functional connectivity that may only be detectible with multivariate analyses. To determine if voxel-wise and SVM analyses had similar spatial patterns, region-average t-statistic and SVM weight values were compared using a measure of ranking distance. T-statistic and SVM weight rankings exhibited significantly low ranking distance values for all groups and metrics, demonstrating that the analyses converged on a similar underlying effect. Overall, this research suggests that subconcussion in football may produce local functional connectivity changes similar to concussion.

    View details for PubMedID 29188492

    View details for PubMedCentralID PMC6141348

  • Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome After Acute Stroke. Stroke Puig, J., Blasco, G., Alberich-Bayarri, A., Schlaug, G., Deco, G., Biarnes, C., Navas-Marti, M., Rivero, M., Gich, J., Figueras, J., Torres, C., Daunis-I-Estadella, P., Oramas-Requejo, C. L., Serena, J., Stinear, C. M., Kuceyeski, A., Soriano-Mas, C., Thomalla, G., Essig, M., Figley, C. R., Menon, B., Demchuk, A., Nael, K., Wintermark, M., Liebeskind, D. S., Pedraza, S. 2018; 49 (10): 2353–60

    Abstract

    Background and Purpose- Physiological effects of stroke are best assessed over entire brain networks rather than just focally at the site of structural damage. Resting-state functional magnetic resonance imaging can map functional-anatomic networks by analyzing spontaneously correlated low-frequency activity fluctuations across the brain, but its potential usefulness in predicting functional outcome after acute stroke remains unknown. We assessed the ability of resting-state functional magnetic resonance imaging to predict functional outcome after acute stroke. Methods- We scanned 37 consecutive reperfused stroke patients (age, 69±14 years; 14 females; 3-day National Institutes of Health Stroke Scale score, 6±5) on day 3 after symptom onset. After imaging preprocessing, we used a whole-brain mask to calculate the correlation coefficient matrices for every paired region using the Harvard-Oxford probabilistic atlas. To evaluate functional outcome, we applied the modified Rankin Scale at 90 days. We used region of interest analyses to explore the functional connectivity between regions and graph-computation analysis to detect differences in functional connectivity between patients with good functional outcome (modified Rankin Scale score ≤2) and those with poor outcome (modified Rankin Scale score >2). Results- Patients with good outcome had greater functional connectivity than patients with poor outcome. Although 3-day National Institutes of Health Stroke Scale score was the most accurate independent predictor of 90-day modified Rankin Scale (84.2%), adding functional connectivity increased accuracy to 94.7%. Preserved bilateral interhemispheric connectivity between the anterior inferior temporal gyrus and superior frontal gyrus and decreased connectivity between the caudate and anterior inferior temporal gyrus in the left hemisphere had the greatest impact in favoring good prognosis. Conclusions- These data suggest that information about functional connectivity from resting-state functional magnetic resonance imaging may help predict 90-day stroke outcome.

    View details for PubMedID 30355087

  • Consensus statement on current and emerging methods for the diagnosis and evaluation of cerebrovascular disease JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Donahue, M. J., Achten, E., Cogswell, P. M., De Leeuw, F., Derdeyn, C. P., Dijkhuizen, R. M., Fan, A. P., Ghaznawi, R., Heit, J. J., Ikram, M., Jezzard, P., Jordan, L. C., Jouvent, E., Knutsson, L., Leigh, R., Liebeskind, D. S., Lin, W., Okell, T. W., Qureshi, A. I., Stagg, C. J., van Osch, M. P., van Zijl, P. M., Watchmaker, J. M., Wintermark, M., Wu, O., Zaharchuk, G., Zhou, J., Hendrikse, J. 2018; 38 (9): 1391–1417

    Abstract

    Cerebrovascular disease (CVD) remains a leading cause of death and the leading cause of adult disability in most developed countries. This work summarizes state-of-the-art, and possible future, diagnostic and evaluation approaches in multiple stages of CVD, including (i) visualization of sub-clinical disease processes, (ii) acute stroke theranostics, and (iii) characterization of post-stroke recovery mechanisms. Underlying pathophysiology as it relates to large vessel steno-occlusive disease and the impact of this macrovascular disease on tissue-level viability, hemodynamics (cerebral blood flow, cerebral blood volume, and mean transit time), and metabolism (cerebral metabolic rate of oxygen consumption and pH) are also discussed in the context of emerging neuroimaging protocols with sensitivity to these factors. The overall purpose is to highlight advancements in stroke care and diagnostics and to provide a general overview of emerging research topics that have potential for reducing morbidity in multiple areas of CVD.

    View details for PubMedID 28816594

  • New developments in clinical ischemic stroke prevention and treatment and their imaging implications JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Heit, J. J., Wintermark, M. 2018; 38 (9): 1533–50
  • Pediatric Stroke Imaging PEDIATRIC NEUROLOGY Khalaf, A., Iv, M., Fullerton, H., Wintermark, M. 2018; 86: 5–18
  • Optimal Delay Time of CT Perfusion for Predicting Cerebral Parenchymal Hematoma After Intra-Arterial tPA Treatment FRONTIERS IN NEUROLOGY Wu, B., Liu, N., Wintermark, M., Parsons, M. W., Chen, H., Lin, L., Zhou, S., Hui, G., Zhang, Y., Hui, J., Li, Y., Su, Z., Wu, X., Zhu, G. 2018; 9
  • Double diffusion encoding MRI for the clinic MAGNETIC RESONANCE IN MEDICINE Yang, G., Tian, Q., Leuze, C., Wintermark, M., McNab, J. A. 2018; 80 (2): 507–20

    Abstract

    The purpose of this study is to develop double diffusion encoding (DDE) MRI methods for clinical use. Microscopic diffusion anisotropy measurements from DDE promise greater specificity to changes in tissue microstructure compared with conventional diffusion tensor imaging, but implementation of DDE sequences on whole-body MRI scanners is challenging because of the limited gradient strengths and lengthy acquisition times.A custom single-refocused DDE sequence was implemented on a 3T whole-body scanner. The DDE gradient orientation scheme and sequence parameters were optimized based on a Gaussian diffusion assumption. Using an optimized 5-min DDE acquisition, microscopic fractional anisotropy (μFA) maps were acquired for the first time in multiple sclerosis patients.Based on simulations and in vivo human measurements, six parallel and six orthogonal diffusion gradient pairs were found to be the minimum number of diffusion gradient pairs necessary to produce a rotationally invariant measurement of μFA. Simulations showed that optimal precision and accuracy of μFA measurements were obtained using b-values between 1500 and 3000 s/mm2 . The μFA maps showed improved delineation of multiple sclerosis lesions compared with conventional fractional anisotropy and distinct contrast from T2 -weighted fluid attenuated inversion recovery and T1 -weighted imaging.The μFA maps can be measured using DDE in a clinical setting and may provide new opportunities for characterizing multiple sclerosis lesions and other types of tissue degeneration. Magn Reson Med 80:507-520, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for PubMedID 29266375

    View details for PubMedCentralID PMC5910247

  • Neuroimaging of brain trauma CURRENT OPINION IN NEUROLOGY Douglas, D. B., Muldermans, J. L., Wintermark, M. 2018; 31 (4): 362-370
  • Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Gong, E., Pauly, J. M., Wintermark, M., Zaharchuk, G. 2018; 48 (2): 330–40

    View details for DOI 10.1002/jmri.25970

    View details for Web of Science ID 000440926000003

  • Impact of Neuroradiology Staffing on Academic Hospital Level Quality and Cost Measures for the Neuroscience Service Line. Journal of the American College of Radiology : JACR Wintermark, M., Lee, Y., Kerr, A., Hess, C., Dillon, W. P., Mukherji, S. K., Norbash, A., Seidenwurm, D., Law, M. 2018

    View details for PubMedID 30057242

  • Neuroimaging Radiological Interpretation System for Acute Traumatic Brain Injury JOURNAL OF NEUROTRAUMA Wintermark, M., Li, Y., Ding, V. Y., Xu, Y., Jiang, B., Ball, R. L., Zeineh, M., Gean, A., Sanelli, P. 2018; 35 (22): 2665–72
  • Management of Incidental Pituitary Findings on CT, MRI, and F-18-Fluorodeoxyglucose PET: A White Paper of the ACR Incidental Findings Committee JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Hoang, J. K., Hoffman, A. R., Gonzalez, R., Wintermark, M., Glenn, B. J., Pandharipande, P. V., Berland, L. L., Seidenwurm, D. J. 2018; 15 (7): 966–72

    Abstract

    The ACR Incidental Findings Committee presents recommendations for managing pituitary findings that are incidentally detected on CT, MRI and 18F-fluorodeoxyglucose PET. The Pituitary Subcommittee, which included radiologists practicing neuroradiology and an endocrinologist, developed this algorithm. The recommendations draw from published evidence and expert opinion and were finalized by informal iterative consensus. Algorithm branches successively categorize pituitary findings on the basis of imaging features. They terminate with an ascertainment of an indolent lesion (with sufficient confidence to discontinue follow-up) or a management recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. The goal is to improve the quality of care by providing guidance on how to manage incidentally detected pituitary findings.

    View details for PubMedID 29735244

  • Neuroimaging of brain trauma. Current opinion in neurology Douglas, D. B., Muldermans, J. L., Wintermark, M. 2018

    Abstract

    PURPOSE OF REVIEW: The purpose of this review is to provide an update on advanced neuroimaging techniques in traumatic brain injury (TBI). We will focus this review on recent literature published within the last 18 months and the advanced neuroimaging techniques of perfusion imaging and diffusion tensor imaging (DTI).RECENT FINDINGS: In the setting of a moderate or severe acute closed head injury (Glasgow Coma Scale <13), the most appropriate neuroimaging study is a noncontrast computed tomography (CT) scan. In the setting of mild TBI, the indication for neuroimaging can be determined using the New Orleans Criteria or Canadian CT Head Rules or National Emergency X-Ray Utilization Study-II clinical criteria. Two advanced neuroimaging techniques that are currently being researched in TBI include perfusion imaging and DTI. Perfusion CT has a higher sensitivity for detecting cerebral contusions than noncontrast CT examinations. DTI is a sensitive at detecting TBI at the group level (TBI-group versus control group), but there is insufficient evidence to suggest that DTI plays a clinical role for diagnosing mild TBI at the individual patient level.SUMMARY: Future research in advanced neuroimaging techniques including perfusion imaging and DTI may improve the accuracy of the diagnosis and prognosis as well as improve the management of TBI.

    View details for PubMedID 29878909

  • The vast potential and bright future of neuroimaging. The British journal of radiology Wintermark, M., Colen, R., Whitlow, C. T., Zaharchuk, G. 2018: 20170505

    Abstract

    Significant advances in anatomical and functional neuroimaging techniques have allowed researchers and clinicians to visualize the brain in action. The field of neuroimaging currently includes newer and faster scanners, improved image quality, higher spatial and temporal resolution and diverse methods of acquisition and analysis. Beyond simply imaging brain structures, these developments enable quantitative assessment of the microstructural and functional architecture, perfusion and metabolism of the brain. The resultant highly granular data have the potential to greatly improve characterization of neurological, neurosurgical and psychiatric disorders without invasive neurosurgery. However, the surge in neuroimaging data that can be collected over a relatively short acquisition period has led to a "big data" problem, where novel methods are needed to appropriately extract and analyze information and integrate data with other types of big data, such as genomic and proteomic data. Another challenge is the translation of these new technologies from basic science into clinical practice, so that they can be leveraged to improve patient outcomes and alleviate human disease. Critical to this endeavor is research comparing the effectiveness and outcomes of these advancements to allow widespread acceptance in the modern, economically constrained healthcare system. This review aims to illustrate the different facets of cutting edge neuroimaging techniques, as well as the potential role of these methods as clinical tools for evaluating the breadth of diseases that affect the brain.

    View details for PubMedID 29848016

  • A spiral-based volumetric acquisition for MR temperature imaging MAGNETIC RESONANCE IN MEDICINE Fielden, S. W., Feng, X., Zhao, L., Miller, G., Geeslin, M., Dallapiazza, R. F., Elias, W., Wintermark, M., Pauly, K., Meyer, C. H. 2018; 79 (6): 3122–27

    Abstract

    To develop a rapid pulse sequence for volumetric MR thermometry.Simulations were carried out to assess temperature deviation, focal spot distortion/blurring, and focal spot shift across a range of readout durations and maximum temperatures for Cartesian, spiral-out, and retraced spiral-in/out (RIO) trajectories. The RIO trajectory was applied for stack-of-spirals 3D imaging on a real-time imaging platform and preliminary evaluation was carried out compared to a standard 2D sequence in vivo using a swine brain model, comparing maximum and mean temperatures measured between the two methods, as well as the temporal standard deviation measured by the two methods.In simulations, low-bandwidth Cartesian trajectories showed substantial shift of the focal spot, whereas both spiral trajectories showed no shift while maintaining focal spot geometry. In vivo, the 3D sequence achieved real-time 4D monitoring of thermometry, with an update time of 2.9-3.3 s.Spiral imaging, and RIO imaging in particular, is an effective way to speed up volumetric MR thermometry. Magn Reson Med 79:3122-3127, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for PubMedID 29115692

  • NeuroImaging Radiological Interpretation System (NIRIS) for Acute Traumatic Brain Injury (TBI). Journal of neurotrauma Wintermark, M., Li, Y., Ding, V. Y., Xu, Y., Jiang, B., Ball, R. L., Zeineh, M., Gean, A., Sanelli, P. 2018

    Abstract

    To develop an outcome-based NeuroImaging Radiological Interpretation System (NIRIS) for acute traumatic brain injury (TBI) patients that would standardize the interpretation of non-contrast head CTs and consolidate imaging findings into ordinal severity categories that would inform specific patient management actions and that could be used as a clinical decision support tool. We retrospectively identified all patients transported to our emergency department by ambulance or helicopter, for whom a trauma alert was triggered per established criteria and who underwent a non-contrast head CT due to suspicion of TBI, between November 2015 and April 2016. Two neuroradiologists reviewed the non-contrast head CTs and assessed the TBI imaging common data elements (CDEs), as defined by the National Institutes of Health (NIH). Using descriptive statistics and receiver operating characteristic curve analyses to identify imaging characteristics and associated thresholds that best distinguished among outcomes, we classified patients into five mutually exclusive categories: 0-discharge from the emergency department; 1-follow-up brain imaging and/or admission; 2-admission to an advanced care unit; 3-neurosurgical procedure; 4-death up to 6 months after TBI. Sensitivity of NIRIS with respect to each patient's true outcome was then evaluated and compared to that of the Marshall and Rotterdam scoring systems for TBI. In our cohort of 542 TBI patients, NIRIS was developed to predict discharge (182 patients), follow-up brain imaging/admission (187 patients), need for advanced care unit (151 patients). neurosurgical procedures (10 patients) and death (12 patients). NIRIS performed similarly to the Marshall and Rotterdam scoring systems in terms of predicting mortality. We developed an interpretation system for neuroimaging using the CDEs that informs specific patient management actions and could be used as a clinical decision support tool for patients with TBI. Our NIRIS classification, with evidence-based grouping of the CDEs into actionable categories, will need to be validated in different TBI populations.

    View details for PubMedID 29665763

  • Improved operative efficiency using a real-time MRI-guided stereotactic platform for laser amygdalohippocampotomy JOURNAL OF NEUROSURGERY Ho, A. L., Sussman, E. S., Pendharkar, A. V., Le, S., Mantovani, A., Keebaugh, A. C., Drover, D. R., Grant, G. A., Wintermark, M., Halpern, C. H. 2018; 128 (4): 1165–72

    Abstract

    OBJECTIVE MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive method for thermal destruction of benign or malignant tissue that has been used for selective amygdalohippocampal ablation for the treatment of temporal lobe epilepsy. The authors report their initial experience adopting a real-time MRI-guided stereotactic platform that allows for completion of the entire procedure in the MRI suite. METHODS Between October 2014 and May 2016, 17 patients with mesial temporal sclerosis were selected by a multidisciplinary epilepsy board to undergo a selective amygdalohippocampal ablation for temporal lobe epilepsy using MRgLITT. The first 9 patients underwent standard laser ablation in 2 phases (operating room [OR] and MRI suite), whereas the next 8 patients underwent laser ablation entirely in the MRI suite with the ClearPoint platform. A checklist specific to the real-time MRI-guided laser amydalohippocampal ablation was developed and used for each case. For both cohorts, clinical and operative information, including average case times and accuracy data, was collected and analyzed. RESULTS There was a learning curve associated with using this real-time MRI-guided system. However, operative times decreased in a linear fashion, as did total anesthesia time. In fact, the total mean patient procedure time was less in the MRI cohort (362.8 ± 86.6 minutes) than in the OR cohort (456.9 ± 80.7 minutes). The mean anesthesia time was significantly shorter in the MRI cohort (327.2 ± 79.9 minutes) than in the OR cohort (435.8 ± 78.4 minutes, p = 0.02). CONCLUSIONS The real-time MRI platform for MRgLITT can be adopted in an expedient manner. Completion of MRgLITT entirely in the MRI suite may lead to significant advantages in procedural times.

    View details for PubMedID 28665249

  • Radiation dose and image quality of computed tomography of the supra-aortic arteries: A comparison between single-source and dual-source CT Scanners JOURNAL OF NEURORADIOLOGY Saba, L., di Martino, M., Siotto, P., Anzidei, M., Argiolas, G., Porcu, M., Suri, J. S., Wintermark, M. 2018; 45 (2): 136–41

    Abstract

    The purpose of this work was to compare the image quality and radiation dose delivered to patients during computed tomography (CT) angiography (CTA) of the supra-aortic arteries using two single-source (SS) and two dual-energy (DE) CT scanners.In this retrospective study, 120 patients who underwent CTA of supra-aortic arteries were studied using four different types of CT scanners: a sixteen and forty-detector-row SS and two DE CT scanners. Seventy milliters of contrast medium were injected at a flow rate of 4mL/s using a power injector. For each patient the dose-length product (DLP), the volume computed tomography dose index (CDTIvol), the length of the scan and the effective dose (ED) were calculated. Qualitative and quantitative [image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] image quality assessment was performed.A statistically significant lower value of the DE compared to the SS technology (P<0.0001) for the CDTI, DLP and ED was found, whereas we did not find any statistically significant difference between the four scanners for the measurements of the image noise, SNR and CNR.DS CT scanners allow performing CTAs with a reduced dose compared to SS CT scanner with comparable image quality.

    View details for DOI 10.1016/j.neurad.2017.09.007

    View details for Web of Science ID 000430906700008

    View details for PubMedID 28987274

  • Early administration of pyrrolidine dithiocarbamate extends the therapeutic time window of tissue plasminogen activator in a male rat model of embolic stroke JOURNAL OF NEUROSCIENCE RESEARCH Wang, Z., Shan, W., Cao, J., Wintermark, M., Huang, W., Zuo, Z. 2018; 96 (3): 449–58

    Abstract

    Tissue plasminogen activator (tPA) is used in fewer than 4% of patients after ischemic stroke because of its narrow therapeutic time window. We tested whether pyrrolidine dithiocarbamate (PDTC), a drug with multiple mechanisms to provide neuroprotection, can be used to extend the therapeutic time window of tPA. Three-month-old male Sprague-Dawley rats were subjected to embolic stroke in the area supplied by the right middle cerebral artery. tPA at 10 mg/kg was given intravenously 4 h after the onset of stroke. PDTC at 50 mg/kg was given via gastric gavage at 30 min or 4 h after the onset of stroke. Two days after the stroke, neurological outcome was evaluated and the right frontal cortex area 1 (Fr1), an ischemic penumbral region, was harvested for analysis. PDTC given at 30 min after the stroke reduced infarct volumes and improved neurological functions no matter whether the rats received tPA. PDTC also reduced tPA-increased hemorrhagic volumes. Consistent with these results, PDTC in the presence or absence of tPA treatment attenuated the increase of proinflammatory cytokines, oxidative stress and matrix metalloprotease 2 activity in the right Fr1. However, PDTC given at 4 h after the onset of stroke did not improve the neurological outcome of rats treated with or without tPA. Our results suggest that PDTC given at an early time point but not in a delayed phase provides neuroprotection against embolic stroke and may be used to extend the therapeutic time window of tPA.

    View details for DOI 10.1002/jnr.24186

    View details for Web of Science ID 000419987300014

    View details for PubMedID 28976017

    View details for PubMedCentralID PMC5766379

  • Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI. Journal of magnetic resonance imaging : JMRI Gong, E., Pauly, J. M., Wintermark, M., Zaharchuk, G. 2018

    Abstract

    BACKGROUND: There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration.PURPOSE: To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method.STUDY TYPE: Retrospective, crossover.POPULATION: Sixty patients receiving clinically indicated contrast-enhanced brain MRI.SEQUENCE: 3D T1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma.ASSESSMENT: For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images.STATISTICAL ANALYSIS: Results were assessed using paired t-tests and noninferiority tests.RESULTS: The proposed deep learning method yielded significant (n=50, P<0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n=20, P=0.003) and contrast enhancement (n=20, P<0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n=20, P=0.083) and contrast enhancement (n=20, P=0.068). Slightly better (n=20, P=0.039) motion-artifact suppression was noted in the synthesized images. The noninferiority test rejects the inferiority of the synthesized to true full-dose images for image quality (95% CI: -14-9%), artifacts suppression (95% CI: -5-20%), and contrast enhancement (95% CI: -13-6%).DATA CONCLUSION: With the proposed deep learning method, gadolinium dose can be reduced 10-fold while preserving contrast information and avoiding significant image quality degradation.LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

    View details for PubMedID 29437269

  • Clinical Evaluation of Silent T1-Weighted MRI and Silent MR Angiography of the Brain AMERICAN JOURNAL OF ROENTGENOLOGY Holdsworth, S. J., Macpherson, S. J., Yeom, K. W., Wintermark, M., Zaharchuk, G. 2018; 210 (2): 404–11

    Abstract

    New MRI sequences based on rapid radial acquisition have reduced gradient noise. The purpose of this study was to compare Silent T1-weighted and unenhanced MR angiography (MRA) against conventional sequences in a clinical population.The study cohort consisted of 40 patients with suspected brain metastases (median age, 60 years; range, 23-91 years) who underwent T1-weighted contrast-enhanced MRI and 51 patients with suspected vascular lesions or cerebral ischemia (median age, 60 years; range, 16-94 years) who underwent unenhanced intracranial MRA. Three neuroradiologists reviewed the images blindly and rated several measures of image quality on a 5-point Likert scale. Reviewers recorded the number of enhancing lesions and whether Silent images were better than, worse than, or equivalent to conventional images.For T1-weighted MR images, ratings were slightly lower for Silent versus conventional images, except for diagnostic confidence. Although more lesions were detected on conventional images, this difference was not statistically significant; agreement was seen in 88% of cases. In 48% of cases, T1-weighted scans were deemed equivalent, but when a preference existed, it was usually for conventional images (38% vs 14%). Conventional MRA images were rated higher on all image quality metrics and were strongly preferred (reviewers preferred conventional images in 69% of cases, rated the images as equivalent in 27% of cases, and preferred Silent images in 4% of cases). In some cases, artifacts on Silent images caused reduced vessel caliber, vessel irregularities, and even absent vessels.Although conventional T1-weighted images were preferred overall, most Silent T1-weighted images were rated as equivalent to or better than conventional images and represent a potential alternative for imaging of noise-averse patients. Silent MRA scored significantly worse and could not be recommended at this time, suggesting that it requires additional refinement before routine clinical use.

    View details for PubMedID 29112472

  • A review of potential applications of MR-guided focused ultrasound for targeting brain tumor therapy NEUROSURGICAL FOCUS Lamsam, L., Johnson, E., Connolly, I. D., Wintermark, M., Gephart, M. 2018; 44 (2): E10

    Abstract

    Magnetic resonance-guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.

    View details for PubMedID 29385922

  • Perfusion Imaging in Acute Traumatic Brain Injury NEUROIMAGING CLINICS OF NORTH AMERICA Douglas, D. B., Chaudhari, R., Zhao, J. M., Gullo, J., Kirkland, J., Douglas, P. K., Wolin, E., Walroth, J., Wintermark, M. 2018; 28 (1): 55-+

    Abstract

    Traumatic brain injury (TBI) is a significant problem worldwide and neuroimaging plays a critical role in diagnosis and management. Recently, perfusion neuroimaging techniques have been explored in TBI to determine and characterize potential perfusion neuroimaging biomarkers to aid in diagnosis, treatment, and prognosis. In this article, computed tomography (CT) bolus perfusion, MR imaging bolus perfusion, MR imaging arterial spin labeling perfusion, and xenon CT are reviewed with a focus on their applications in acute TBI. Future research directions are also discussed.

    View details for PubMedID 29157853

  • Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization NEUROIMAGE-CLINICAL Rosen, A. C., Soman, S., Bhat, J., Laird, A. R., Stephens, J., Eickhoff, S. B., Fox, P., Long, B., Dinishak, D., Ortega, M., Lane, B., Wintermark, M., Hitchner, E., Zhou, W. 2018; 18: 553–59

    Abstract

    Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

    View details for PubMedID 29868451

  • Intraoperative Imaging for Arteriovenous Malformations and Dural Arteriovenous Fistulas BRAIN ARTERIOVENOUS MALFORMATIONS AND ARTERIOVENOUS FISTULAS Wintermark, M., Heit, J. J., Dumont, A., Lanzino, G., Sheehan, J. 2018: 67–74
  • The vast potential and bright future of neuroimaging BRITISH JOURNAL OF RADIOLOGY Wintermark, M., Colen, R., Whitlow, C. T., Zaharchuk, G. 2018; 91 (1087)
  • Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor NEUROIMAGE-CLINICAL Tian, Q., Wintermark, M., Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K., McNab, J. A. 2018; 19: 572–80
  • Assessing the Relationship Between American Heart Association Atherosclerotic Cardiovascular Disease Risk Score and Coronary Artery Imaging Findings. Journal of computer assisted tomography Li, Y. n., Zhu, G. n., Ding, V. n., Jiang, B. n., Ball, R. L., Ahuja, N. n., Rodriguez, F. n., Fleischmann, D. n., Desai, M. n., Saloner, D. n., Saba, L. n., Wintermark, M. n., Hom, J. n. 2018

    Abstract

    The aim of this study was to characterize the relationship between computed tomography angiography imaging characteristics of coronary artery and atherosclerotic cardiovascular disease (ASCVD) score.We retrospectively identified all patients who underwent a coronary computed tomography angiography at our institution from December 2013 to July 2016, then we calculated the 10-year ASCVD score. We characterized the relationship between coronary artery imaging findings and ASCVD risk score.One hundred fifty-one patients met our inclusion criteria. Patients with a 10-year ASCVD score of 7.5% or greater had significantly more arterial segments showing stenosis (46.4%, P = 0.008) and significantly higher maximal plaque thickness (1.25 vs 0.53, P = 0.001). However, among 56 patients with a 10-year ASCVD score of 7.5% or greater, 30 (53.6%) had no arterial stenosis. Furthermore, among the patients with a 10-year ASCVD score of less than 7.5%, 24 (25.3%) had some arterial stenosis.There is some concordance but not a perfect overlap between 10-year ASCVD risk scores and coronary artery imaging findings.

    View details for PubMedID 30407249

  • Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study. Radiology Iv, M. n., Samghabadi, P. n., Holdsworth, S. n., Gentles, A. n., Rezaii, P. n., Harsh, G. n., Li, G. n., Thomas, R. n., Moseley, M. n., Daldrup-Link, H. E., Vogel, H. n., Wintermark, M. n., Cheshier, S. n., Yeom, K. W. 2018: 181204

    Abstract

    Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

    View details for PubMedID 30398435

  • Optimal Delay Time of CT Perfusion for Predicting Cerebral Parenchymal Hematoma After Intra-Arterial tPA Treatment. Frontiers in neurology Wu, B. n., Liu, N. n., Wintermark, M. n., Parsons, M. W., Chen, H. n., Lin, L. n., Zhou, S. n., Hu, G. n., Zhang, Y. n., Hu, J. n., Li, Y. n., Su, Z. n., Wu, X. n., Zhu, G. n. 2018; 9: 680

    Abstract

    Background and Purpose: Cerebral hemorrhage is a serious potential complication of stroke revascularization, especially in patients receiving intra-arterial tissue-type plasminogen activator (tPA) therapy. We investigated the optimal pre-intervention delay time (DT) of computed tomography perfusion (CTP) measurement to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke (AIS) patients after intra-arterial tissue plasminogen activator (tPA) treatment. Methods: The study population consisted of a series of patients with AIS who received intra-arterial tPA treatment and had CTP and follow-up computed tomography/magnetic resonance imaging (CT/MRI) to identify hemorrhagic transformation. The association of increasing DT thresholds (>2, >4, >6, >8, and >10 s) with PH was examined using receiver operating characteristic (ROC) analysis and logistic regression. Results: Of 94 patients, 23 developed PH on follow-up imaging. Receiver operating characteristic analysis revealed that the greatest area under the curve for predicting PH occurred at DT > 4 s (area under the curve, 0.66). At this threshold of > 4 s, DT lesion volume ≥ 30.85 mL optimally predicted PH with 70% sensitivity and 59% specificity. DT > 4 s volume was independently predictive of PH in a multivariate logistic regression model (P < 0.05). Conclusions: DT > 4 s was the parameter most strongly associated with PH. The volume of moderate, not severe, hypo-perfusion on DT is more strongly associated and may allow better prediction of PH after intra-arterial tPA thrombolysis.

    View details for PubMedID 30186221

  • Dual-Energy Computed Tomography Applications in Neurointervention. Journal of computer assisted tomography Wolman, D. N., Patel, B. P., Wintermark, M. n., Heit, J. J. 2018

    Abstract

    Dual-energy computed tomography (CT) combines the high spatial resolution of standard CT with the ability to improve contrast resolution, reduce artifact, and separate materials of different atomic weights and energy-based attenuation through postprocessing. We review the underlying physical principles and applications of dual-energy CT within the context of patients undergoing preprocedural and postprocedural evaluation for neurointerventional therapies. The broad imaging categories of cerebral ischemia and hemorrhage, head and neck angiography, and the spine are reviewed.

    View details for PubMedID 30052616

  • Computed Tomography, Computed Tomography Angiography, and Perfusion Computed Tomography Evaluation of Acute Ischemic Stroke. Neuroimaging clinics of North America Leiva-Salinas, C. n., Jiang, B. n., Wintermark, M. n. 2018; 28 (4): 565–72

    Abstract

    This review outlines the current role of the individual components of multimodal computed tomography (computed tomography, computed tomography angiography, and perfusion computed tomography) in the evaluation of patients with acute ischemic stroke.

    View details for PubMedID 30322593

  • Collateral Clock Is More Important Than Time Clock for Tissue Fate. Stroke Vagal, A. n., Aviv, R. n., Sucharew, H. n., Reddy, M. n., Hou, Q. n., Michel, P. n., Jovin, T. n., Tomsick, T. n., Wintermark, M. n., Khatri, P. n. 2018; 49 (9): 2102–7

    Abstract

    Background and Purpose- Although perfusion abnormality is an increasingly important therapeutic target, the natural history of tissue at risk without reperfusion treatment is understudied. Our objective was to determine how time affects penumbral salvage and infarct growth in untreated acute ischemic stroke patients and whether collateral status affects this relationship. Methods- We used a prospectively collected, multicenter acute stroke registry to assess acute stroke patients who were not treated with intravenous thrombolysis or endovascular treatment. We analyzed baseline computed tomography angiogram and computed tomography perfusion within 24 hours of stroke onset along with follow-up imaging and assessed time from stroke onset to baseline imaging, ASPECTS (Alberta Stroke Program Early CT Score), vessel occlusion, collaterals, ischemic core, and penumbra. Penumbral salvage and infarct growth were calculated. Correlations between time and penumbral salvage and infarct growth were evaluated with Spearman correlation. Penumbral salvage and infarct growth were compared between subjects with good versus poor collateral status using the Wilcoxon rank-sum test. Clinical and imaging factors affecting penumbral salvage and infarct growth were evaluated by linear regression. Results- Among 94 untreated stroke patients eligible for this analysis, the mean age was 65 years, median National Institutes of Health Stroke Scale score was 13, and median (range) time from stroke onset to baseline imaging was 2.9 (0.4-23) hours. There was no correlation between time and salvaged penumbra ( r=0.06; P=0.56) or infarct growth ( r=-0.05; P=0.61). Infarct growth was higher among those with poor collaterals versus those with good collaterals (median, 52.3 versus 0.9 cm3; P<0.01). Penumbral salvage was lower among those with poor collaterals compared with those with good collaterals (poor, 0 [0-0]; good, 5.9 cm3 [0-29.4]; P<0.01). Multivariable linear regression demonstrated that collaterals, but not time, were significantly associated with infarct growth and penumbral salvage. Conclusions- In this natural history study, penumbral salvage and infarct growth were less time dependent and more a measure of collateral flow.

    View details for PubMedID 30354992

    View details for PubMedCentralID PMC6206882

  • Assessing the Relationship between Atherosclerotic Cardiovascular Disease Risk Score and Carotid Artery Imaging Findings. Journal of neuroimaging : official journal of the American Society of Neuroimaging Li, Y. n., Zhu, G. n., Ding, V. n., Huang, Y. n., Jiang, B. n., Ball, R. L., Rodriguez, F. n., Fleischmann, D. n., Desai, M. n., Saloner, D. n., Saba, L. n., Hom, J. n., Wintermark, M. n. 2018

    Abstract

    To characterize the relationship between computed tomography angiography (CTA) imaging characteristics of carotid artery and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) score.We retrospectively identified all patients who underwent a cervical CTA at our institution from January 2013 to July 2016, extracted clinical information, and calculated the 10-year ASCVD score using the Pooled Cohort Equations from the 2013 ACC/AHA guidelines. We compared the imaging features of artery atherosclerosis derived from the CTAs between low and high risk.One hundred forty-six patients met our inclusion criteria. Patients with an ASCVD score ≥7.5% (64.4%) had significantly more arterial stenosis than patients with an ASCVD score <7.5% (35.6%, P < .001). Maximal plaque thickness was significantly higher (mean 2.33 vs. .42 mm, P < .001) and soft plaques (55.3% vs. 13.5%, P < .001) were significantly more frequent in patients with an ASCVD score ≥7.5%. However, among patients with a 10-year ASCVD score ≥7.5%, 33 (35.1%) had no arterial stenosis, 35 (37.2%) had a maximal plaque thickness less than. 9 mm, and 42 (44.7%) had no soft plaque. Furthermore, among the patients with a 10-year ASCVD score <7.5%, 8 (15.4%) had some arterial stenosis, 8 (15.4%) had a maximal plaque thickness more than. 9 mm, and 7 (13.5%) had soft plaque.There is some concordance but not a perfect overlap between the 10-year ASCVD risk scores calculated from clinical and blood assessment and carotid artery imaging findings.

    View details for PubMedID 30357980

  • Pediatric Stroke Imaging. Pediatric neurology Khalaf, A. n., Iv, M. n., Fullerton, H. n., Wintermark, M. n. 2018

    Abstract

    Pediatric stroke is a distinct clinical entity as compared with that in adults due to its unique and diverse set of etiologies. Furthermore, the role and application of diagnostic imaging has specific constraints and considerations. The intention of this article is to review these concepts in a thorough manner to offer a pediatric stroke imaging framework that providers can employ when taking care of these patients.A comprehensive primary and secondary literature review was performed with specific attention to the common causes of pediatric stroke, appropriate use of neuroimaging, specific imaging findings, and developing techniques which may improve our ability to accurately diagnose these patients.Findings from this literature review were synthesized and summarized in order to thoroughly review the aforementioned concepts and outline the current consensus-based approach to diagnostic imaging in pediatric stroke. Furthermore, imaging findings drawn from cases which presented to our institution are demonstrated to familiarize readers with pediatric stroke neuroimaging.The challenges posed by pediatric stroke can be mitigated, in part by the thoughtful application of diagnostic imaging, with the ultimate hope of improving outcomes for these vulnerable patients.

    View details for PubMedID 30122281

  • Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor. NeuroImage. Clinical Tian, Q., Wintermark, M., Jeffrey Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K. B., McNab, J. A. 2018; 19: 572–80

    Abstract

    Purpose: To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET).Materials and methods: Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment.Results: The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = -0.929, -0.75, -0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = -0.719, -0.976, -0.707, -0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively).Conclusion: Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

    View details for PubMedID 29984165

  • Magnetic resonance elastography of the brain: A comparison between pigs and humans JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Weickenmeier, J., Kurt, M., Ozkaya, E., Wintermark, M., Pauly, K., Kuhl, E. 2018; 77: 702–10

    Abstract

    Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of μ1=1.3kPa, μ2=2.1kPa, and η=0.025kPas and porcine values of μ1=2.0kPa, μ2=4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance elastography as a whole.

    View details for PubMedID 28919161

  • Reducing Inappropriate Lumbar Spine MRI for Low Back Pain: Radiology Support, Communication and Alignment Network JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Wang, K., Yen, C., Chen, M., Variyam, D., Acosta, T., Reed, B., Wintermark, M., Lincoln, C. 2018; 15 (1): 116–22

    Abstract

    The aim of this study is to evaluate the impact of educational sessions on reducing lumbar spine MRI inappropriateness for uncomplicated low back pain and to present our institutional experience on the use of ACR's Radiology Support, Communication and Alignment Network (R-SCAN) program toward achieving appropriateness.The R-SCAN web portal was accessed to register a project. Using order entry data, the number of lumbar spine MRI orders placed per month at three family medicine clinics was assessed over a 10-month period. After educational presentations were given at those three clinics highlighting the American College of Physicians and Choosing Wisely campaign imaging guidelines, the number of MRI orders placed was reassessed over an additional 10 months. For a subset of these exams, the ACR Appropriateness Criteria rating of the lumbar spine MRIs were compared between the pre- and posteducation periods. A P value < .05 was considered statistically significant.The average number of monthly MRIs ordered from all three clinics combined was 6.3 during the posteducation period, which was significantly less than during the pre-education period of 10.0 (P = .009). The combined average ACR Appropriateness Criteria rating made at all three clinics was 5.8 after educational sessions, which was significantly higher than the rating of 4.7 before educational sessions (P = .014).Clinician education, facilitated by R-SCAN, resulted in a reduced number of MRI lumbar spine studies performed for uncomplicated low back pain and improved appropriateness of those studies as measured by the ACR Appropriateness Criteria rating.

    View details for PubMedID 28969974

  • Janus Iron Oxides @ Semiconducting Polymer Nanoparticle Tracer for Cell Tracking by Magnetic Particle Imaging NANO LETTERS Song, G., Chen, M., Zhang, Y., Cui, L., Qu, H., Zheng, X., Wintermark, M., Liu, Z., Rao, J. 2018; 18 (1): 182–89

    Abstract

    Iron oxides nanoparticles tailored for magnetic particle imaging (MPI) have been synthesized, and their MPI signal intensity is three-times that of commercial MPI contrast (Ferucarbotran, also called Vivotrax) and seven-times that of MRI contrast (Feraheme) at the same Fe concentration. MPI tailored iron oxide nanoparticles were encapsulated with semiconducting polymers to produce Janus nanoparticles that possessed optical and magnetic properties for MPI and fluorescence imaging. Janus particles were applied to cancer cell labeling and in vivo tracking, and as few as 250 cells were imaged by MPI after implantation, corresponding to an amount of 7.8 ng of Fe. Comparison with MRI and fluorescence imaging further demonstrated the advantages of our Janus particles for MPI-super sensitivity, unlimited tissue penetration, and linear quantitativity.

    View details for PubMedID 29232142

  • Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M. n., Wintermark, M. n., Zaharchuk, G. n., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

    Abstract

    Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

    View details for PubMedID 29555872

  • Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture. Stroke Heit, J. J., Wintermark, M. n., Martin, B. W., Zhu, G. n., Marks, M. P., Zaharchuk, G. n., Dodd, R. L., Do, H. M., Steinberg, G. K., Lansberg, M. G., Albers, G. W., Federau, C. n. 2018

    Abstract

    Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.Sixteen patients (11 females, 69%;P=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI- group). Compared with DCI- patients, DCI+ patients had decreased IVIM perfusion fractionf(0.09±0.03 versus 0.13±0.01;P=0.03), reduced diffusion coefficientD(0.82±0.05 versus 0.92±0.07×10-3mm2/s;P=0.003), and reduced blood flow-related parameterfD* (1.18±0.40 versus 1.83±0.40×10-3mm2/s;P=0.009). IVIM pseudodiffusion coefficientD* did not differ between DCI- (0.011±0.002) and DCI+ (0.013±0.005 mm2/s;P=0.4) patients. No differences in mortality or clinical outcome were identified.Decreased IVIM perfusion fractionfand blood flow-related parameterfD* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.

    View details for DOI 10.1161/STROKEAHA.117.020395

    View details for PubMedID 29439196

  • Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man. Proceedings of the National Academy of Sciences of the United States of America Wu, H. n., Miller, K. J., Blumenfeld, Z. n., Williams, N. R., Ravikumar, V. K., Lee, K. E., Kakusa, B. n., Sacchet, M. D., Wintermark, M. n., Christoffel, D. J., Rutt, B. K., Bronte-Stewart, H. n., Knutson, B. n., Malenka, R. C., Halpern, C. H. 2018; 115 (1): 192–97

    Abstract

    Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.

    View details for PubMedID 29255043

  • Current Clinical State of Advanced Magnetic Resonance Imaging for Brain Tumor Diagnosis and Follow Up. Seminars in roentgenology Iv, M. n., Yoon, B. C., Heit, J. J., Fischbein, N. n., Wintermark, M. n. 2018; 53 (1): 45–61

    View details for PubMedID 29405955

  • IVIM perfusion fraction is prognostic for survival in brain glioma CLINICAL NEURORADIOLOGY Federau, C., Cerny, M., Roux, M., Mosimann, P. J., Maeder, P., Meuli, R., Wintermark, M. 2017; 27 (4): 485–92
  • High-permeability region size on perfusion CT predicts hemorrhagic transformation after intravenous thrombolysis in stroke PLOS ONE Puig, J., Blasco, G., Daunis-i-Estadella, P., van Eendendburg, C., Carrillo-Garcia, M., Aboud, C., Hernandez-Perez, M., Serena, J., Biarnes, C., Nael, K., Liebeskind, D. S., Thomalla, G., Menon, B. K., Demchuk, A., Wintermark, M., Pedraza, S., Castellanos, M. 2017; 12 (11): e0188238

    Abstract

    Blood-brain barrier (BBB) permeability has been proposed as a predictor of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) administration; however, the reliability of perfusion computed tomography (PCT) permeability imaging for predicting HT is uncertain. We aimed to determine the performance of high-permeability region size on PCT (HPrs-PCT) in predicting HT after intravenous tPA administration in patients with acute stroke.We performed a multimodal CT protocol (non-contrast CT, PCT, CT angiography) to prospectively study patients with middle cerebral artery occlusion treated with tPA within 4.5 hours of symptom onset. HT was graded at 24 hours using the European-Australasian Acute Stroke Study II criteria. ROC curves selected optimal volume threshold, and multivariate logistic regression analysis identified predictors of HT.The study included 156 patients (50% male, median age 75.5 years). Thirty-seven (23,7%) developed HT [12 (7,7%), parenchymal hematoma type 2 (PH-2)]. At admission, patients with HT had lower platelet values, higher NIHSS scores, increased ischemic lesion volumes, larger HPrs-PCT, and poorer collateral status. The negative predictive value of HPrs-PCT at a threshold of 7mL/100g/min was 0.84 for HT and 0.93 for PH-2. The multiple regression analysis selected HPrs-PCT at 7mL/100g/min combined with platelets and baseline NIHSS score as the best model for predicting HT (AUC 0.77). HPrs-PCT at 7mL/100g/min was the only independent predictor of PH-2 (OR 1, AUC 0.68, p = 0.045).HPrs-PCT can help predict HT after tPA, and is particularly useful in identifying patients at low risk of developing HT.

    View details for PubMedID 29182658

  • Time-resolved CT assessment of collaterals as imaging biomarkers to predict clinical outcomes in acute ischemic stroke NEURORADIOLOGY Tong, E., Patrie, J., Tong, S., Evans, A., Michel, P., Eskandari, A., Wintermark, M. 2017; 59 (11): 1101-1109

    Abstract

    Collateral circulation plays a pivotal role in the pathophysiology of acute ischemic stroke and is increasingly recognized as a promising biomarker for predicting the clinical outcome. However, there is no single established grading system. We designed a novel machine-learning software that allows non-invasive, objective, and quantitative assessment of collaterals according to their vascular territories. Our goal is to investigate the prognostic and predictive value of this collateral score for the prediction of acute stroke outcome.This is a retrospective study of 135 patients with anterior circulation stroke treated with IV TPA. An equation using this collateral score (adjusting for age, baseline NIHSS, and recanalization) was derived to predict the clinical outcome (90-day mRS). The primary analyses focused on determining the prognostic value of our newly developed collateral scores. Secondary analyses examined the interrelationships between the collateral score and other variables.The collateral score emerged as a statistically significant prognostic biomarker for good clinical outcome (p < 0.033) among recanalized patients, but not among non-recanalized patients (p < 0.497). Our results also showed that collateral score was a predictive biomarker (p < 0.044). These results suggest that (1) patients with good collateral score derive more benefit from successful recanalization than patients with poor collateral score and (2) collateral status is inconsequential if recanalization is not achieved.Our data results reinforce the importance of careful patient selection for recanalization therapy to avoid futile recanalization. The paucity of collaterals predicts poor clinical outcome despite recanalization. On the other hand, robust collaterals warrant consideration for recanalization therapy given the better odds of good clinical outcome.

    View details for DOI 10.1007/s00234-017-1914-z

    View details for Web of Science ID 000412758900009

    View details for PubMedID 28864854

  • Parvovirus B19 Infection in Children With Arterial Ischemic Stroke STROKE Fullerton, H. J., Luna, J. M., Wintermark, M., Hills, N. K., Tokarz, R., Li, Y., Glaser, C., DeVeber, G. A., Lipkin, W., Elkind, M. V., VIPS Investigators 2017; 48 (10): 2875-+

    Abstract

    Case-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases.The multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens.Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries.Using MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.

    View details for PubMedID 28864597

    View details for PubMedCentralID PMC5614850

  • MULTIVARIATE APPROACH TO STUDYING THE EFFECTS OF SUBCONCUSSION ON FUNCTIONAL CONNECTIVITY Reynolds, B., Stanton, A., Soldozy, S., Goodkin, H., Wintermark, M., Druzgal, J. MARY ANN LIEBERT, INC. 2017: A112
  • Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials. Stroke Jiang, B., Ball, R. L., Michel, P., Jovin, T., Desai, M., Eskandari, A., Naqvi, Z., Wintermark, M. 2017; 48 (6): 1675-1677

    Abstract

    Imaging biomarkers are increasingly used as selection criteria for stroke clinical trials. The goal of our study was to determine the prevalence of commonly studied imaging biomarkers in different time windows after acute ischemic stroke onset to better facilitate the design of stroke clinical trials using such biomarkers for patient selection.This retrospective study included 612 patients admitted with a clinical suspicion of acute ischemic stroke with symptom onset no more than 24 hours before completing baseline imaging. Patients with subacute/chronic/remote infarcts and hemorrhage were excluded from this study. Imaging biomarkers were extracted from baseline imaging, which included a noncontrast head computed tomography (CT), perfusion CT, and CT angiography. The prevalence of dichotomized versions of each of the imaging biomarkers in several time windows (time since symptom onset) was assessed and statistically modeled to assess time dependence (not lack thereof).We created tables showing the prevalence of the imaging biomarkers pertaining to the core, the penumbra and the arterial occlusion for different time windows. All continuous imaging features vary over time. The dichotomized imaging features that vary significantly over time include: noncontrast head computed tomography Alberta Stroke Program Early CT (ASPECT) score and dense artery sign, perfusion CT infarct volume, and CT angiography collateral score and visible clot. The dichotomized imaging features that did not vary significantly over time include the thresholded perfusion CT penumbra volumes.As part of the feasibility analysis in stroke clinical trials, this analysis and the resulting tables can help investigators determine sample size and the number needed to screen.

    View details for DOI 10.1161/STROKEAHA.117.016759

    View details for PubMedID 28386041

  • Number needed to screen for acute revascularization trials in stroke: Prognostic and predictive imaging biomarkers INTERNATIONAL JOURNAL OF STROKE Hou, Q., Patrie, J. L., Xin, W., Michel, P., Jovin, T., Eskandari, A., Wintermark, M. 2017; 12 (4): 356-367

    Abstract

    To systematically assess imaging biomarkers on CT-based multimodal imaging for their being predictive versus prognostic biomarkers for intravenous and endovascular (IA) revascularization therapy, and for their prevalence.Our retrospective study included patients suspected of acute ischemic stroke with admission work-up including a non-contrast head CT, perfusion CT, and CT angiography. Modified Rankin scores at 90 days were used as outcomes. For each imaging biomarker, the effect size of the test of interaction between the presence of the biomarker and the treatment effect was calculated, allowing the inference of a total sample size. The total sample size required was combined with the prevalence of the biomarker to determine the number needed to screen.In the 0-4.5-h time window, the two predictive biomarkers associated with the smallest number needed to screen were perfusion CT penumbra ≥ 20% (404 NNS) and CT angiography collateral score ≥ 2 (581 NNS). In the 3-9-h time window, the four predictive biomarkers associated with the smallest number needed to screen were clot burden score (CBS) on CT angiography (1181 NNS), clot length ≥ 10 mm (1924 NNS), CBS and clot length ≥ 10 mm (1132 NNS), and CBS and perfusion CT penumbra ≥ 100% (1374 NNS). Perfusion CT ischemic core was a prognostic biomarker in both time windows.Predictive biomarkers need to be differentiated from prognostic biomarkers when being considered to select patients for a trial, and their prevalence should be assessed to determine the number needed to screen and overall feasibility of the trials.

    View details for DOI 10.1177/1747493016677978

    View details for Web of Science ID 000401153900006

  • R-SCAN: Imaging for Pediatric Simple Febrile Seizures. Journal of the American College of Radiology Lee, S., Fisher, P., Grant, G. A., Porter, B., Dannenberg, B., Wintermark, M. 2017

    View details for DOI 10.1016/j.jacr.2017.04.007

    View details for PubMedID 28551342

  • CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy MOLECULAR NEUROBIOLOGY Liu, N., Chen, H., Wu, B., Li, Y., Wintermark, M., Jackson, A., Hu, J., Zhang, Y., Su, Z., Zhu, G., Zhang, W. 2017; 54 (4): 2539-2546

    Abstract

    In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K (trans)) as a biomarker for blood-brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K (trans) (K (trans)-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K (trans)-PIV, and smaller FIV (P < 0.001). K (trans)-PIV showed good correlation with FIV (P < 00.001, R (2) = 0.6997). In the regression analyses, K (trans)-PIV was the best predictor of clinical outcomes (P = 0.009, odds ratio (OR) = 1.960) and also the best predictor for FIV (F = 75.590, P < 0.0001). In conclusion, combining PCT and K (trans) maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.

    View details for DOI 10.1007/s12035-016-9838-x

    View details for Web of Science ID 000399303300016

  • Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Movement disorders Ravikumar, V. K., Parker, J. J., Hornbeck, T. S., Santini, V. E., Pauly, K. B., Wintermark, M., Ghanouni, P., Stein, S. C., Halpern, C. H. 2017

    Abstract

    Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options.Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques.Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery.Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.

    View details for DOI 10.1002/mds.26997

    View details for PubMedID 28370272

  • Relationship between white matter hyperintensities volume and the circle of Willis configurations in patients with carotid artery pathology. European journal of radiology Saba, L., Sanfilippo, R., Porcu, M., Lucatelli, P., Montisci, R., Zaccagna, F., Suri, J., Anzidei, M., Wintermark, M. 2017; 89: 111-116

    Abstract

    We aimed to assess if there is a difference of distribution and volume of white matter hyperintensities (WMH) in the brain according to the Circle of Willis (CoW) configuration in patients with carotid artery pathology.One-hundred consecutive patients (79 males, 21 females; mean age 70 years; age range 46-84 years) that underwent brain MRI before carotid endarterectomy (CEA) were included. FLAIR-WMH lesion volume was performed using a semi-automated segmentation technique and the status of the circle of Willis was assessed by two neuroradiologists in consensus.We found a prevalence of 55% of variants in the CoW configuration; 22 cases had one variants (40%); 25 cases had two variants (45.45%) and 8 cases showed 3 variants (14.55%). The configuration that was associated with the biggest WMH volume and number of lesions was the A1+PcoA+PcoA. The PcoA variants were the most prevalent and there was no statistically significant difference in number of lesions and WMH for each vascular territory assessed and the same results were found for AcoA and A1 variants.Results of our study suggest that the more common CoW variants are not associated with the presence of an increased WMH or number of lesions whereas uncommon configurations, in particular when 2 or more segment are missing increase the WMH volume and number of lesions. The WHM volume of the MCA territory seems to be more affected by the CoW configuration.

    View details for DOI 10.1016/j.ejrad.2017.01.031

    View details for PubMedID 28267525

  • Transcarotid Artery Revascularization With Flow Reversal: The PROOF Study JOURNAL OF ENDOVASCULAR THERAPY Alpaslan, A., Wintermark, M., Pinter, L., Macdonald, S., Ruedy, R., Kolvenbach, R. 2017; 24 (2): 265-270

    Abstract

    To report a study evaluating the safety and efficacy of stenting via direct carotid access with flow reversal using the ENROUTE Transcarotid Neuroprotection System.Between March 2009 and June 2012, 75 patients (mean age 72.6 years; 45 men) underwent carotid artery stenting with the ENROUTE System; the majority of patients (63, 84%) were asymptomatic. The primary safety endpoint was the composite of major stroke, myocardial infarction, or death at 30 days. Efficacy outcomes included acute device success, procedure success, and tolerance to flow reversal. Fifty-six (74.7%) patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) before and after the procedure to assess the development of new ischemic brain lesions.Acute device and procedure success were achieved in 68 (90.6%) patients. The reverse flow circuit was established in 71 (94.6%) patients; only 5 patients demonstrated transient intolerance to flow reversal that did not interfere with completion of the procedure. The mean time on flow reversal was 19.1 minutes. In the DW-MRI substudy, 10 (17.9%) of 56 patients had ipsilateral new white lesions with a mean volume of 0.17 mL. At 30 days, no major stroke, myocardial infarction, or death occurred; 1 patient had experienced a minor stroke that was adjudicated as not related to either the device or procedure.Results of the PROOF study demonstrate the safety and efficacy of transcarotid revascularization with the ENROUTE Transcarotid Neuroprotection System.

    View details for DOI 10.1177/1526602817693607

    View details for Web of Science ID 000397861400017

  • Transcarotid Artery Revascularization With Flow Reversal. Journal of endovascular therapy Alpaslan, A., Wintermark, M., Pintér, L., Macdonald, S., Ruedy, R., Kolvenbach, R. 2017; 24 (2): 265-270

    Abstract

    To report a study evaluating the safety and efficacy of stenting via direct carotid access with flow reversal using the ENROUTE Transcarotid Neuroprotection System.Between March 2009 and June 2012, 75 patients (mean age 72.6 years; 45 men) underwent carotid artery stenting with the ENROUTE System; the majority of patients (63, 84%) were asymptomatic. The primary safety endpoint was the composite of major stroke, myocardial infarction, or death at 30 days. Efficacy outcomes included acute device success, procedure success, and tolerance to flow reversal. Fifty-six (74.7%) patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) before and after the procedure to assess the development of new ischemic brain lesions.Acute device and procedure success were achieved in 68 (90.6%) patients. The reverse flow circuit was established in 71 (94.6%) patients; only 5 patients demonstrated transient intolerance to flow reversal that did not interfere with completion of the procedure. The mean time on flow reversal was 19.1 minutes. In the DW-MRI substudy, 10 (17.9%) of 56 patients had ipsilateral new white lesions with a mean volume of 0.17 mL. At 30 days, no major stroke, myocardial infarction, or death occurred; 1 patient had experienced a minor stroke that was adjudicated as not related to either the device or procedure.Results of the PROOF study demonstrate the safety and efficacy of transcarotid revascularization with the ENROUTE Transcarotid Neuroprotection System.

    View details for DOI 10.1177/1526602817693607

    View details for PubMedID 28335706

  • Diffusion tensor imaging as a prognostic biomarker for motor recovery and rehabilitation after stroke NEURORADIOLOGY Puig, J., Blasco, G., Schlaug, G., Stinear, C. M., Daunis-i-Estadella, P., Biarnes, C., Figueras, J., Serena, J., Hernandez-Perez, M., Alberich-Bayarri, A., Castellanos, M., Liebeskind, D. S., Demchuk, A. M., Menon, B. K., Thomalla, G., Nael, K., Wintermark, M., Pedraza, S. 2017; 59 (4): 343-351

    Abstract

    Despite improved acute treatment and new tools to facilitate recovery, most patients have motor deficits after stroke, often causing disability. However, motor impairment varies considerably among patients, and recovery in the acute/subacute phase is difficult to predict using clinical measures alone, particularly in severely impaired patients. Accurate early prediction of recovery would help rationalize rehabilitation goals and improve the design of trials testing strategies to facilitate recovery.We review the role of diffusion tensor imaging (DTI) in predicting motor recovery after stroke, in monitoring treatment response, and in evaluating white matter remodeling. We critically appraise DTI studies and discuss their limitations, and we explore directions for future study.Growing evidence suggests that combining clinical scores with information about corticospinal tract (CST) integrity can improve predictions about motor outcome. The extent of CST damage on DTI and/or the overlap between the CST and a lesion are key prognostic factor that determines motor performance and outcome. Three main strategies to quantify stroke-related CST damage have been proposed: (i) measuring FA distal to the stroke area, (ii) measuring the number of fibers that go through the stroke with tractography, and (iii) measuring the overlap between the stroke and a CST map derived from healthy age- and gender-matched controls.Recovery of motor function probably involves remodeling of the CST proper and/or a greater reliance on alternative motor tracts through spontaneous and treatment-induced plasticity. DTI-metrics represent promising clinical biomarkers to predict motor recovery and to monitor and predict the response to neurorehabilitative interventions.

    View details for DOI 10.1007/s00234-017-1816-0

    View details for Web of Science ID 000399690900005

    View details for PubMedID 28293701

  • Understanding the Neurophysiology and Quantification of Brain Perfusion. Topics in magnetic resonance imaging Tong, E., Sugrue, L., Wintermark, M. 2017; 26 (2): 57-65

    Abstract

    Newer neuroimaging technology has moved beyond pure anatomical imaging and ventured into functional and physiological imaging. Perfusion magnetic resonance imaging (PWI), which depicts hemodynamic conditions of the brain at the microvascular level, has an increasingly important role in clinical central nervous system applications. This review provides an overview of the established role of PWI in brain tumor and cerebrovascular imaging, as well as some emerging applications in neuroimaging. PWI allows better characterization of brain tumors, grading, and monitoring. In acute stroke imaging, PWI is utilized to distinguish penumbra from infarcted tissue. PWI is a promising tool in the assessment of neurodegenerative and neuropsychiatric diseases, although its clinical role is not yet defined.

    View details for DOI 10.1097/RMR.0000000000000128

    View details for PubMedID 28277465

  • Effects of Sex and Event Type on Head Impact in Collegiate Soccer. Orthopaedic journal of sports medicine Reynolds, B. B., Patrie, J., Henry, E. J., Goodkin, H. P., Broshek, D. K., Wintermark, M., Druzgal, T. J. 2017; 5 (4): 2325967117701708-?

    Abstract

    The effects of head impact in sports are of growing interest for clinicians, scientists, and athletes. Soccer is the most popular sport worldwide, but the burden of head impact in collegiate soccer is still unknown.To quantify head impact associated with practicing and playing collegiate soccer using wearable accelerometers.Descriptive epidemiological study.Mastoid patch accelerometers were used to quantify head impact in soccer, examining differences in head impact as a function of sex and event type (practice vs game). Seven female and 14 male collegiate soccer players wore mastoid patch accelerometers that measured head impacts during team events. Data were summarized for each athletic exposure, and statistical analyses evaluated the mean number of impacts, mean peak linear acceleration, mean peak rotational acceleration, and cumulative linear and rotational acceleration, each grouped by sex and event type.There were no differences in the frequency or severity of head impacts between men's and women's soccer practices. For men's soccer, games resulted in 285% more head impacts than practices, but there were no event-type differences in mean impact severity. Men's soccer games resulted in more head impacts than practices across nearly all measured impact severities, which also resulted in men's soccer games producing a greater cumulative impact burden.Similar to other sports, men's soccer games have a greater impact burden when compared with practices, and this effect is driven by the quantity rather than severity of head impacts. In contrast, there were no differences in the quantity or severity of head impacts in men's and women's soccer practices. These data could prompt discussions of practical concern to collegiate soccer, such as understanding sex differences in head impact and whether games disproportionately contribute to an athlete's head impact burden.

    View details for DOI 10.1177/2325967117701708

    View details for PubMedID 28491885

  • Pathways for Neuroimaging of Childhood Stroke PEDIATRIC NEUROLOGY Mirsky, D. M., Beslow, L. A., Amlie-Lefond, C., Krishnan, P., Laughlin, S., Lee, S., Lehman, L., Rafay, M., Shaw, D., Rivkin, M. J., Wintermark, M. 2017; 69: 11-23

    Abstract

    The purpose of this article is to aid practitioners in choosing appropriate neuroimaging for children who present with symptoms that could be caused by stroke.The Writing Group members participated in one or more pediatric stroke neuroimaging symposiums hosted by the Stroke Imaging Laboratory for Children housed at the Hospital for Sick Children in Toronto, Ontario, Canada. Through collaboration, literature review, and discussion among child neurologists with expertise diagnosing and treating childhood stroke and pediatric neuroradiologists and neuroradiologists with expertise in pediatric neurovascular disease, suggested imaging protocols are presented for children with suspected stroke syndromes including arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke.This article presents information about the epidemiology and classification of childhood stroke with definitions based on the National Institutes of Health Common Data Elements. The role of imaging for the diagnosis of childhood stroke is examined in depth, with separate sections for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke. Abbreviated neuroimaging protocols for rapid diagnosis are discussed. The Writing Group provides suggestions for optimal neuroimaging investigation of various stroke types in the acute setting and suggestions for follow-up neuroimaging. Advanced sequences such as diffusion tensor imaging, perfusion imaging, and vessel wall imaging are also discussed.This article provides protocols for the imaging of children who present with suspected stroke.

    View details for DOI 10.1016/j.pediatrneurol.2016.12.004

    View details for Web of Science ID 000398648400003

    View details for PubMedID 28274641

  • Contemporary Imaging of Cerebral Arteriovenous Malformations. AJR. American journal of roentgenology Tranvinh, E., Heit, J. J., Hacein-Bey, L., Provenzale, J., Wintermark, M. 2017: 1-11

    Abstract

    Brain arteriovenous malformation (AVM) rupture results in substantial morbidity and mortality. The goal of AVM treatment is eradication of the AVM, but the risk of treatment must be weighed against the risk of future hemorrhage.Imaging plays a vital role by providing the information necessary for AVM management. Here, we discuss the background, natural history, clinical presentation, and imaging of AVMs. In addition, we explain advances in techniques for imaging AVMs.

    View details for DOI 10.2214/AJR.16.17306

    View details for PubMedID 28267351

  • Multiparametric Magnetic Resonance Imaging for Prediction of Parenchymal Hemorrhage in Acute Ischemic Stroke After Reperfusion Therapy. Stroke Nael, K., Knitter, J. R., Jahan, R., Gornbein, J., Ajani, Z., Feng, L., Meyer, B. C., Schwamm, L. H., Yoo, A. J., Marshall, R. S., Meyers, P. M., Yavagal, D. R., Wintermark, M., Liebeskind, D. S., Guzy, J., Starkman, S., Saver, J. L., Kidwell, C. S. 2017; 48 (3): 664-670

    Abstract

    Patients with acute ischemic stroke are at increased risk of developing parenchymal hemorrhage (PH), particularly in the setting of reperfusion therapies. We have developed a predictive model to examine the risk of PH using combined magnetic resonance perfusion and diffusion parameters, including cerebral blood volume (CBV), apparent diffusion coefficient, and microvascular permeability (K2).Voxel-based values of CBV, K2, and apparent diffusion coefficient from the ischemic core were obtained using pretreatment magnetic resonance imaging data from patients enrolled in the MR RESCUE clinical trial (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy). The associations between PH and extreme values of imaging parameters were assessed in univariate and multivariate analyses. Receiver-operating characteristic curve analysis was performed to determine the optimal parameter(s) and threshold for predicting PH.In 83 patients included in this analysis, 20 developed PH. Univariate analysis showed significantly lower 10th percentile CBV and 10th percentile apparent diffusion coefficient values and significantly higher 90th percentile K2 values within the infarction core of patients with PH. Using classification tree analysis, the 10th percentile CBV at threshold of 0.47 and 90th percentile K2 at threshold of 0.28 resulted in overall predictive accuracy of 88.7%, sensitivity of 90.0%, and specificity of 87.3%, which was superior to any individual or combination of other classifiers.Our results suggest that combined 10th percentile CBV and 90th percentile K2 is an independent predictor of PH in patients with acute ischemic stroke with diagnostic accuracy superior to individual classifiers alone. This approach may allow risk stratification for patients undergoing reperfusion therapies.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00389467.

    View details for DOI 10.1161/STROKEAHA.116.014343

    View details for PubMedID 28138001

    View details for PubMedCentralID PMC5325250

  • R-SCAN: Admission and Preoperative Chest X-Rays for Ambulatory Patients With Unremarkable History and Physical Examination. Journal of the American College of Radiology Jacobson, F. L., Bader, A. M., Smith, C. D., Weinberger, S. E., Triveri, C. M., Wintermark, M., Hunsaker, A. R. 2017; 14 (3): 380-382

    View details for DOI 10.1016/j.jacr.2016.11.026

    View details for PubMedID 28259327

  • Volume of subclinical embolic infarct correlates to long-term cognitive changes after carotid revascularization. Journal of vascular surgery Zhou, W., Baughman, B. D., Soman, S., Wintermark, M., Lazzeroni, L. C., Hitchner, E., Bhat, J., Rosen, A. 2017; 65 (3): 686-694

    Abstract

    Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts.The study recruited 119 patients including 46% symptomatic patients who underwent carotid revascularization. Neuropsychological testing was administered preoperatively and at 1 month, 6 months, and 12 months postoperatively. Rey Auditory Verbal Learning Test (RAVLT) was the primary cognitive measure with parallel forms to avoid practice effect. All patients also received 3T brain magnetic resonance imaging with a diffusion-weighted imaging (DWI) sequence preoperatively and within 48 hours postoperatively to identify procedure-related new embolic lesions. Each DWI lesion was manually traced and input into a neuroimaging program to define volume. Embolic infarct volumes were correlated with cognitive measures. Regression models were used to identify relationships between infarct volumes and cognitive measures.A total of 587 DWI lesions were identified on 3T magnetic resonance imaging in 81.7% of carotid artery stenting (CAS) and 36.4% of carotid endarterectomy patients with a total volume of 29,327 mm(3). Among them, 54 DWI lesions were found in carotid endarterectomy patients and 533 in the CAS patients. Four patients had transient postoperative neurologic symptoms and one had a stroke. CAS was an independent predictor of embolic infarction (odds ratio, 6.6 [2.1-20.4]; P < .01) and infarct volume (P = .004). Diabetes and contralateral carotid severe stenosis or occlusion had a trend of positive association with infarct volume, whereas systolic blood pressure ≥140 mm Hg had a negative association (P = .1, .09, and .1, respectively). There was a trend of improved RAVLT scores overall after carotid revascularization. Significantly higher infarct volumes were observed among those with RAVLT decline. Within the CAS cohort, infarct volume was negatively correlated with short- and long-term RAVLT changes (P < .05).Cognitive assessment of procedure-related subclinical microemboli is challenging. Volumes of embolic infarct correlate with long-term cognitive changes, suggesting that microembolization should be considered a surrogate measure for carotid disease management.

    View details for DOI 10.1016/j.jvs.2016.09.057

    View details for PubMedID 28024850

  • Stroke Recovery and Rehabilitation Research: Issues, Opportunities, and the National Institutes of Health StrokeNet. Stroke Cramer, S. C., Wolf, S. L., Adams, H. P., Chen, D., Dromerick, A. W., Dunning, K., Ellerbe, C., Grande, A., Janis, S., Lansberg, M. G., Lazar, R. M., Palesch, Y. Y., Richards, L., Roth, E., Savitz, S. I., Wechsler, L. R., Wintermark, M., Broderick, J. P. 2017; 48 (3): 813-819

    View details for DOI 10.1161/STROKEAHA.116.015501

    View details for PubMedID 28174324

    View details for PubMedCentralID PMC5330812

  • The "White Gray Sign" Identifies the Central Sulcus on 3T High-Resolution T1-Weighted Images AMERICAN JOURNAL OF NEURORADIOLOGY Kaneko, O. F., Fischbein, N. J., Rosenberg, J., Wintermark, M., Zeineh, M. M. 2017; 38 (2): 276-280

    Abstract

    The central sulcus is an important anatomic landmark, but most methods of identifying it rely on variable gyral and sulcal patterns. We describe and assess the accuracy of reduced gray-white contrast along the central sulcus, an observation we term the "white gray sign."We conducted a retrospective review of 51 fMRIs with a T1-weighted 3D inversion recovery fast-spoiled gradient-echo and concomitant hand-motor fMRI, which served as confirmation for the location of the central sulcus. To measure gray-white contrast across the central and adjacent sulci, we performed a quantitative analysis of 25 normal hemispheres along the anterior and posterior cortices and intervening white matter of the pre- and postcentral gyri. 3D inversion recovery fast-spoiled gradient-echo axial images from 51 fMRIs were then evaluated by 2 raters for the presence of the white gray sign as well as additional established signs of the central sulcus: the bracket, cortical thickness, omega, and T signs.The mean gray-white contrast along the central sulcus was 0.218 anteriorly and 0.237 posteriorly, compared with 0.320 and 0.295 along the posterior precentral and anterior postcentral sulci, respectively (P < .001). Both raters correctly identified the central sulcus in all 35 normal and 16 abnormal hemispheres. The white gray sign had the highest agreement of all signs between raters and was rated as present the most often among all the signs.Reduced gray-white contrast around the central sulcus is a reliable sign for identification of the central sulcus on 3D inversion recovery fast-spoiled gradient-echo images.

    View details for DOI 10.3174/ajnr.A5014

    View details for Web of Science ID 000393170100016

    View details for PubMedID 27932507

  • R-SCAN: Imaging for Pediatric Minor Head Trauma. Journal of the American College of Radiology Lee, S., Grant, G. A., Fisher, P. G., Imler, D., Padrez, R., Avery, C., Sharp, A. L., Wintermark, M. 2017; 14 (2): 294-297

    View details for DOI 10.1016/j.jacr.2016.10.006

    View details for PubMedID 28017272

  • Pathways for Neuroimaging of Neonatal Stroke. Pediatric neurology Lee, S., Mirsky, D. M., Beslow, L. A., Amlie-Lefond, C., Danehy, A. R., Lehman, L., Stence, N. V., Vossough, A., Wintermark, M., Rivkin, M. J. 2017

    Abstract

    To provide consensus-based, suggested imaging protocols to facilitate the accurate and timely diagnosis of a neonate with symptoms concerning for stroke.The Writing Group, an international collaboration of pediatric neurologists and neuroradiologists with expertise in perinatal and childhood stroke, participated in a series of pediatric stroke neuroimaging symposia. These discussions, in conjunction with extensive literature review, led to a consensus for imaging protocols to guide practitioners in the diagnosis of neonatal stroke subtypes as defined by the National Institute of Neurological Disorders and Stroke Common Data Elements. The epidemiology, clinical presentation, and associated risk factors for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke are reviewed, with a focused discussion regarding the role of neuroimaging for each subtype.In a neonate with suspected stroke, magnetic resonance imaging is the preferred modality, given the lack of X-irradiation, superior anatomic resolution, and sensitivity for acute ischemia. Core recommended sequences include diffusion-weighted imaging and apparent diffusion coefficient mapping to diagnose acute ischemia, gradient-recalled echo or susceptibility-weighted imaging to detect intracranial blood and its breakdown products, and T1- and T2-weighted imaging to assess for myelination, extra-axial blood, and edema. Magnetic resonance angiography of the brain may be useful to detect vascular abnormalities, with venography if venous sinus thrombosis is suspected. The application of more novel sequences, as well as the utility of follow up-imaging, is also discussed.

    View details for DOI 10.1016/j.pediatrneurol.2016.12.008

    View details for PubMedID 28262550

  • Harnessing Neuroimaging Capability in Pediatric Stroke: Proceedings of the Stroke Imaging Laboratory for Children Workshop. Pediatric neurology Dlamini, N., Wintermark, M., Fullerton, H., Strother, S., Lee, W., Bjornson, B., Guilliams, K. P., Miller, S., Kirton, A., Filippi, C. G., Linds, A., Askalan, R., DeVeber, G. 2017

    Abstract

    On June 5, 2015 the International Pediatric Stroke Study and the Stroke Imaging Laboratory for Children cohosted a unique workshop focused on developing neuroimaging research in pediatric stroke. Pediatric neurologists, neuroradiologists, interventional neuroradiologists, physicists, nurse practitioners, neuropsychologists, and imaging research scientists from around the world attended this one-day meeting. Our objectives were to (1) establish a group of experts to collaborate in advancing pediatric neuroimaging for stroke, (2) develop consensus clinical and research magnetic resonance imaging protocols for pediatric stroke patients, and (3) develop imaging-based research strategies in pediatric ischemic stroke. This article provides a summary of the meeting proceedings focusing on identified challenges and solutions and outcomes from the meeting. Further details on the workshop contents and outcomes are provided in three additional articles in the current issue of Pediatric Neurology.

    View details for DOI 10.1016/j.pediatrneurol.2017.01.006

    View details for PubMedID 28259513

  • Imaging of Intracranial Hemorrhage. Journal of stroke Heit, J. J., Iv, M., Wintermark, M. 2017; 19 (1): 11-27

    Abstract

    Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage.

    View details for DOI 10.5853/jos.2016.00563

    View details for PubMedID 28030895

  • Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma. Oncoscience Lehrer, M. n., Bhadra, A. n., Ravikumar, V. n., Chen, J. Y., Wintermark, M. n., Hwang, S. N., Holder, C. A., Huang, E. P., Fevrier-Sullivan, B. n., Freymann, J. B., Rao, A. n. 2017; 4 (5-6): 57–66

    Abstract

    Lower grade gliomas (LGGs), lesions of WHO grades II and III, comprise 10-15% of primary brain tumors. In this first-of-a-kind study, we aim to carry out a radioproteomic characterization of LGGs using proteomics data from the TCGA and imaging data from the TCIA cohorts, to obtain an association between tumor MRI characteristics and protein measurements. The availability of linked imaging and molecular data permits the assessment of relationships between tumor genomic/proteomic measurements with phenotypic features.Multiple-response regression of the image-derived, radiologist scored features with reverse-phase protein array (RPPA) expression levels generated correlation coefficients for each combination of image-feature and protein or phospho-protein in the RPPA dataset. Significantly-associated proteins for VASARI features were analyzed with Ingenuity Pathway Analysis software. Hierarchical clustering of the results of the pathway analysis was used to determine which feature groups were most strongly correlated with pathway activity and cellular functions.The multiple-response regression approach identified multiple proteins associated with each VASARI imaging feature. VASARI features were found to be correlated with expression of IL8, PTEN, PI3K/Akt, Neuregulin, ERK/MAPK, p70S6K and EGF signaling pathways.Radioproteomics analysis might enable an insight into the phenotypic consequences of molecular aberrations in LGGs.

    View details for PubMedID 28781988

  • R-SCAN: CT Angiographic Imaging for Pulmonary Embolism. Journal of the American College of Radiology : JACR Frigini, L. A., Hoxhaj, S. n., Wintermark, M. n., Gibby, C. n., De Rosen, V. L., Willis, M. H. 2017; 14 (5): 637–40

    View details for PubMedID 28284675

  • Imaging-based selection of patients for acute stroke treatment: Is it ready for prime time? Neurology Carrera, E. n., Wintermark, M. n. 2017; 88 (24): 2242–43

    View details for PubMedID 28515271

  • Patient-centered Radiology: Where Are We, Where Do We Want to Be, and How Do We Get There? Radiology Kemp, J. L., Mahoney, M. C., Mathews, V. P., Wintermark, M. n., Yee, J. n., Brown, S. D. 2017; 285 (2): 601–8

    Abstract

    Purpose The objectives of the Radiological Society of North America (RSNA) Patient-Centered Radiology Steering Committee survey were to (a) assess RSNA members' general attitudes and experiences concerning patient-centered radiology, with specific attention paid to radiologist-to-patient communication; (b) examine the members' barriers to communicating more directly with patients; and (c) explore their perceptions of how such barriers can be overcome. Materials and Methods A total of 5999 radiologists were invited by e-mail to complete an anonymous electronic survey developed by the Steering Committee and the RSNA Department of Research. Participants were asked to identify aspects of patient-centered care important to their practice, report on their interactions with patients, and share their opinions on radiologist-patient communication. Statistical analyses were performed by using the χ2 test and analysis of variance. Results The response rate was 12% (n = 694, 109 invitations were undeliverable). Most respondents (89%, 611 of 684) agreed that promoting awareness of the role of radiology in patients' overall health care is important to how they practice. The majority (73%, 421 of 575) reported that time or workload frequently prevented them from communicating directly with patients. The majority (74%, 423 of 572) reported that a personal sense of satisfaction was likely to motivate them to communicate more directly with patients, but many commented that changes to reimbursement and compensation would help them communicate with patients more directly. Conclusion Many radiologists support the concept of communicating more directly with patients but report they are constrained by time or workload. Changes to reimbursement schemes may help mitigate these barriers to one crucial aspect of patient-centered care. © RSNA, 2017 Online supplemental material is available for this article.

    View details for PubMedID 28631981

  • Dual Energy Computed Tomography Applications for the Evaluation of the Spine. Neuroimaging clinics of North America Komlosi, P. n., Wintermark, M. n. 2017; 27 (3): 483–87

    Abstract

    Capturing the energy-dependent x-ray attenuation of different tissues, dual-energy computed tomography offers multiple benefits in the imaging of the spine, such as bone and iodinated contrast removal, monosodium urate imaging, and robust reduction of beam-hardening artifacts. The emerging new applications of this technique include bone marrow imaging in acute trauma and myeloinfiltrative disorders, improved bone density determination, and noninvasive assessment of spinal gout.

    View details for PubMedID 28711207

  • Method for decreasing CT simulation time of complex phantoms and systems through separation of material specific projection data SPIE Medical Imaging 2017: Physics of Medical Imaging Divel, S. E., Christensen, S., Wintermark, M., Lansberg, M. G., Pelc, N. J. 2017: 1013259

    View details for DOI 10.1117/12.2254076

  • Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome. Journal of magnetic resonance imaging : JMRI Federau, C. n., Goubran, M. n., Rosenberg, J. n., Henderson, J. n., Halpern, C. H., Santini, V. n., Wintermark, M. n., Butts Pauly, K. n., Ghanouni, P. n. 2017

    Abstract

    Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor.To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor.Retrospective.Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T.T2 -weighted images were acquired immediately and at 1 year posttreatment at 3T.An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year.Statistical significance was assessed using the Wilcoxon two-tailed rank test.The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure - posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure.In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS.1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.

    View details for PubMedID 29076274

  • Venous imaging-based biomarkers in acute ischaemic stroke JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Munuera, J., Blasco, G., Hernandez-Perez, M., Daunis-i-Estadella, P., Davalos, A., Liebeskind, D. S., Wintermark, M., Demchuk, A., Menon, B. K., Thomalla, G., Nael, K., Pedraza, S., Puig, J. 2017; 88 (1): 62-69

    Abstract

    Vascular neuroimaging plays a decisive role in selecting the best therapy in patients with acute ischaemic stroke. However, compared with the arterial system, the role of veins has not been thoroughly studied. In this review, we present the major venous imaging-based biomarkers in ischaemic stroke. First, the presence of hypodense veins in the monophasic CT angiography ipsilateral to the arterial occlusion. Second, the asymmetry of venous drainage in the pathological cerebral hemisphere on CT and MRI dynamic angiography. Finally, the presence of hypodense veins on T2* -based MRI. From the physiological point of view, the venous imaging-based biomarkers would detect the alteration of brain perfusion (flow), as well as the optimisation of extraction oxygen mechanisms (misery perfusion). Several studies have correlated the venous imaging-based biomarkers with grade of collateral circulation, the ischaemic penumbra and clinical functional outcome. Although venous imaging-based biomarkers still have to be validated, growing evidence highlights a potential complementary role in the acute stroke clinical decision-making process.

    View details for DOI 10.1136/jnnp-2016-314814

    View details for Web of Science ID 000393747500011

  • Reducing Functional MR Imaging Acquisition Times by Optimizing Workflow RADIOGRAPHICS Chwang, W. B., Iv, M., Smith, J., Kalnins, A., Mickelsen, J., Bammer, R., Fleischmann, D., Larson, D. B., Wintermark, M., Zeineh, M. 2017; 37 (1): 315-321

    Abstract

    Functional magnetic resonance (MR) imaging is a complex, specialized examination that is able to noninvasively measure information critical to patient care such as hemispheric language lateralization ( 1 ). Diagnostic functional MR imaging requires extensive patient interaction as well as the coordinated efforts of the entire health care team. We observed in our practice at an academic center that the times to perform functional MR imaging examinations were excessively lengthy, making scheduling of the examination difficult. The purpose of our project was to reduce functional MR imaging acquisition times by increasing the efficiency of our workflow, using specific quality tools to drive improvement of functional MR imaging. We assembled a multidisciplinary team and retrospectively reviewed all functional MR imaging examinations performed at our institution from January 2013 to August 2015. We identified five key drivers: (a) streamlined protocols, (b) consistent patient monitoring, (c) clear visual slides and audio, (d) improved patient understanding, and (e) minimized patient motion. We then implemented four specific interventions over a period of 10 months: (a) eliminating intravenous contrast medium, (b) reducing repeated language paradigms, (c) updating technologist and physician checklists, and (d) updating visual slides and audio. Our mean functional MR imaging acquisition time was reduced from 76.3 to 53.2 minutes, while our functional MR imaging examinations remained of diagnostic quality. As a result, we reduced our routine scheduling time for functional MR imaging from 2 hours to 1 hour, improving patient comfort and satisfaction as well as saving time for additional potential MR imaging acquisitions. Our efforts to optimize functional MR imaging workflow constitute a practice quality improvement project that is beneficial for patient care and can be applied broadly to other functional MR imaging practices. (©)RSNA, 2017.

    View details for DOI 10.1148/rg.2017160035

    View details for Web of Science ID 000397205200021

  • Altered Microstructural Caudate Integrity in Posttraumatic Stress Disorder but Not Traumatic Brain Injury. PloS one Waltzman, D., Soman, S., Hantke, N. C., Fairchild, J. K., Kinoshita, L. M., Wintermark, M., Ashford, J. W., Yesavage, J., Williams, L., Adamson, M. M., Furst, A. J. 2017; 12 (1)

    Abstract

    Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI.We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls).While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls.The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders.

    View details for DOI 10.1371/journal.pone.0170564

    View details for PubMedID 28114393

    View details for PubMedCentralID PMC5256941

  • Severe cerebral hypovolemia on perfusion CT and lower body weight are associated with parenchymal haemorrhage after thrombolysis NEURORADIOLOGY Tsetsou, S., Amiguet, M., Eskandari, A., Meuli, R., Maeder, P., Jiang, B., Wintermark, M., Michel, P. 2017; 59 (1): 23-29

    Abstract

    Haemorrhagic transformation of acute ischemic stroke (AIS) and particularly parenchymal haemorrhage (PH) remains a feared complication of intravenous thrombolysis (IVT). We aimed to identify clinical and perfusion CT (PCT) variables which are independently associated with PHs.In this observational cohort study, based on the Acute Stroke Registry Analysis of Lausanne (ASTRAL) from 2003 to December 2013, we selected patients with AIS involving the middle cerebral artery (MCA) territory who were thrombolysed within 4.5 h of symptoms' onset and who had a good quality baseline PCT at the beginning of IVT. In addition to demographic, clinical, laboratory and non-contrast CT data, volumes of salvageable tissue and ischemic core on PCT, as well as absolute CBF and CBV values within the ischemic regions were compared in patients with and without PH in multivariate analysis.Of the 190 included patients, 24 (12.6%) presented a PH (11 had PH1 and 13 had PH2). In multivariate analysis of the clinical and radiological variables, the lowest CBV in the core and lower body weight was both significantly associated with PH (p = 0.009 and p = 0.024, respectively).In thrombolysed MCA strokes, maximal hypoperfusion severity depicted by lowest CBV values in the core region and lower body weight are independently correlated with PH. This information, if confirmed in other case series, may add to the stratification of revascularisation decisions in patients with a perceived high PH risk.

    View details for DOI 10.1007/s00234-016-1775-x

    View details for Web of Science ID 000392306400005

    View details for PubMedID 28028565

  • Added value of multimodal computed tomography imaging: analysis of 1994 acute ischaemic strokes EUROPEAN JOURNAL OF NEUROLOGY Bill, O., Faouzi, M., Meuli, R., Maeder, P., Wintermark, M., Michel, P. 2017; 24 (1): 167-174

    View details for DOI 10.1111/ene.13173

    View details for Web of Science ID 000392806700014

  • Reducing Functional MR Imaging Acquisition Times by Optimizing Workflow. Radiographics Chwang, W. B., Iv, M., Smith, J., Kalnins, A., Mickelsen, J., Bammer, R., Fleischmann, D., Larson, D. B., Wintermark, M., Zeineh, M. 2017; 37 (1): 316-322

    Abstract

    Functional magnetic resonance (MR) imaging is a complex, specialized examination that is able to noninvasively measure information critical to patient care such as hemispheric language lateralization ( 1 ). Diagnostic functional MR imaging requires extensive patient interaction as well as the coordinated efforts of the entire health care team. We observed in our practice at an academic center that the times to perform functional MR imaging examinations were excessively lengthy, making scheduling of the examination difficult. The purpose of our project was to reduce functional MR imaging acquisition times by increasing the efficiency of our workflow, using specific quality tools to drive improvement of functional MR imaging. We assembled a multidisciplinary team and retrospectively reviewed all functional MR imaging examinations performed at our institution from January 2013 to August 2015. We identified five key drivers: (a) streamlined protocols, (b) consistent patient monitoring, (c) clear visual slides and audio, (d) improved patient understanding, and (e) minimized patient motion. We then implemented four specific interventions over a period of 10 months: (a) eliminating intravenous contrast medium, (b) reducing repeated language paradigms, (c) updating technologist and physician checklists, and (d) updating visual slides and audio. Our mean functional MR imaging acquisition time was reduced from 76.3 to 53.2 minutes, while our functional MR imaging examinations remained of diagnostic quality. As a result, we reduced our routine scheduling time for functional MR imaging from 2 hours to 1 hour, improving patient comfort and satisfaction as well as saving time for additional potential MR imaging acquisitions. Our efforts to optimize functional MR imaging workflow constitute a practice quality improvement project that is beneficial for patient care and can be applied broadly to other functional MR imaging practices. (©)RSNA, 2017.

    View details for DOI 10.1148/rg.2017160035

    View details for PubMedID 28076003

  • New developments in clinical ischemic stroke prevention and treatment and their imaging implications. Journal of cerebral blood flow and metabolism Heit, J. J., Wintermark, M. 2017: 271678X17694046-?

    Abstract

    Acute ischemic stroke results from blockage of a cerebral artery or impaired cerebral blood flow due to cervical or intracranial arterial stenosis. Ischemic stroke prevention seeks to minimize the risk of developing impaired cerebral perfusion by controlling vascular and cardiac disease risk factors. Similarly, ischemic stroke treatment aims to restore cerebral blood flow through recanalization of an occluded artery or dilation of a severely narrowed artery that supplies cerebral tissue. Stroke prevention and treatment are increasingly informed by imaging studies, and neurovascular and cerebral perfusion imaging has become essential in in guiding ischemic stroke prevention and treatment. Here we review the latest advances in ischemic stroke prevention and treatment with an emphasis on the neuroimaging principles emphasized in recent randomized trials. Future research directions that should be explored in ischemic stroke prevention and treatment are also discussed.

    View details for DOI 10.1177/0271678X17694046

    View details for PubMedID 28195500

  • Comparative Analysis of Head Impact in Contact and Collision Sports JOURNAL OF NEUROTRAUMA Reynolds, B. B., Patrie, J., Henry, E. J., Goodkin, H. P., Broshek, D. K., Wintermark, M., Druzgal, T. J. 2017; 34 (1): 38-49

    Abstract

    As concerns about head impact in American football have grown, similar concerns have started to extend to other sports thought to experience less head impact, such as soccer and lacrosse. However, the amount of head impact experienced in soccer and lacrosse is relatively unknown, particularly compared with the substantial amount of data from football. This pilot study quantifies and compares head impact from four different types of sports teams: college football, high school football, college soccer, and college lacrosse. During the 2013 and 2014 seasons, 61 players wore mastoid patch accelerometers to quantify head impact during official athletic events (i.e., practices and games). In both practices and games, college football players experienced the most or second-most impacts per athletic event, highest average peak resultant linear and rotational acceleration per impact, and highest cumulative linear and rotational acceleration per athletic event. For average peak resultant linear and rotational acceleration per individual impact, college football was followed by high school football, then college lacrosse, and then college soccer, with similar trends in both practices and games. In the four teams under study, college football players experienced a categorically higher burden of head impact. However, for cumulative impact burden, the high school football cohort was not significantly different from the college soccer cohort. The results suggest that head impact in sport substantially varies by both the type of sport (football vs. soccer vs. lacrosse) and level of play (college vs. high school).

    View details for DOI 10.1089/neu.2015.4308

    View details for PubMedID 27541183

  • Relationship between leukoaraiosis, carotid intima-media thickness and intima-media thickness variability: Preliminary results EUROPEAN RADIOLOGY Lucatelli, P., Raz, E., Saba, L., Argiolas, G. M., Montisci, R., Wintermark, M., King, K. S., Molinari, F., Ikeda, N., Siotto, P., Suri, J. S. 2016; 26 (12): 4423-4431

    Abstract

    To assess the relationship between the degree of leukoaraiosis (LA), carotid intima-media thickness (IMT) and intima-media thickness variability (IMTV).Sixty-one consecutive patients, who underwent a brain MRI examination and a carotid artery ultrasound, were included in this retrospective study, which conformed with the Declaration of Helsinki. Written informed consent was waived. In each patient, right/left carotid arteries and brain hemispheres were assessed using automated software for IMT, IMTV and LA volume.The mean hemispheric LA volume was 2,224 mm(3) (SD 2,702 mm(3)) and there was no statistically significant difference in LA volume between the right and left hemispheres (p value = 0.628). The mean IMT and IMTV values were 0.866 mm (SD 0.170) and 0.143 mm (SD 0.100), respectively, without significant differences between the right and left sides (p values 0.733 and 0.098, respectively). The correlation coefficient between IMTV and LA volume was 0.41 (p value = 0.0001), and 0.246 (p value = 0.074) between IMT and LA volume.IMTV significantly correlates with LA volume. Further studies are warranted to verify whether this parameter can be used clinically as a marker of cerebrovascular risk.• Intima-media thickness variability (IMTV) significantly correlates with leukoaraiosis volume. • IMTV could be used as a marker for cerebrovascular risk. • IMTV seems to be a better predictor of weighted mean difference than IMT.

    View details for DOI 10.1007/s00330-016-4296-4

    View details for PubMedID 27027314

  • A Simplified Model for Intravoxel Incoherent Motion Perfusion Imaging of the Brain AMERICAN JOURNAL OF NEURORADIOLOGY Conklin, J., Heyn, C., Roux, M., Cerny, M., Wintermark, M., Federau, C. 2016; 37 (12): 2251-2257

    Abstract

    Despite a recent resurgence, intravoxel incoherent motion MRI faces practical challenges, including limited SNR and demanding acquisition and postprocessing requirements. A simplified approach using linear fitting of a subset of higher b-values has seen success in other organ systems. We sought to validate this method for evaluation of brain pathology by comparing perfusion measurements using simplified linear fitting to conventional biexponential fitting.Forty-nine patients with gliomas and 17 with acute strokes underwent 3T MRI, including DWI with 16 b-values (range, 0-900 s/mm(2)). Conventional intravoxel incoherent motion was performed using nonlinear fitting of the standard biexponential equation. Simplified intravoxel incoherent motion was performed using linear fitting of the log-normalized signal curves for subsets of b-values >200 s/mm(2). Comparisons between ROIs (tumors, strokes, contralateral brain) and between models (biexponential and simplified linear) were performed by using 2-way ANOVA. The root mean square error and coefficient of determination (R(2)) were computed for the simplified model, with biexponential fitting as the reference standard.Perfusion maps using simplified linear fitting were qualitatively similar to conventional biexponential fitting. The perfusion fraction was elevated in high-grade (n = 33) compared to low-grade (n = 16) gliomas and was reduced in strokes compared to the contralateral brain (P < .001 for both main effects). Decreasing the number of b-values used for linear fitting resulted in reduced accuracy (higher root mean square error and lower R(2)) compared with full biexponential fitting.Intravoxel incoherent motion perfusion imaging of common brain pathology can be performed by using simplified linear fitting, with preservation of clinically relevant perfusion information.

    View details for DOI 10.3174/ajnr.A4929

    View details for Web of Science ID 000390082800014

    View details for PubMedID 27561834

  • Number needed to screen for acute revascularization trials in stroke: Prognostic and predictive imaging biomarkers. International journal of stroke Hou, Q., Patrie, J. L., Xin, W., Michel, P., Jovin, T., Eskandari, A., Wintermark, M. 2016

    Abstract

    To systematically assess imaging biomarkers on CT-based multimodal imaging for their being predictive versus prognostic biomarkers for intravenous and endovascular (IA) revascularization therapy, and for their prevalence.Our retrospective study included patients suspected of acute ischemic stroke with admission work-up including a non-contrast head CT, perfusion CT, and CT angiography. Modified Rankin scores at 90 days were used as outcomes. For each imaging biomarker, the effect size of the test of interaction between the presence of the biomarker and the treatment effect was calculated, allowing the inference of a total sample size. The total sample size required was combined with the prevalence of the biomarker to determine the number needed to screen.In the 0-4.5-h time window, the two predictive biomarkers associated with the smallest number needed to screen were perfusion CT penumbra ≥ 20% (404 NNS) and CT angiography collateral score ≥ 2 (581 NNS). In the 3-9-h time window, the four predictive biomarkers associated with the smallest number needed to screen were clot burden score (CBS) on CT angiography (1181 NNS), clot length ≥ 10 mm (1924 NNS), CBS and clot length ≥ 10 mm (1132 NNS), and CBS and perfusion CT penumbra ≥ 100% (1374 NNS). Perfusion CT ischemic core was a prognostic biomarker in both time windows.Predictive biomarkers need to be differentiated from prognostic biomarkers when being considered to select patients for a trial, and their prevalence should be assessed to determine the number needed to screen and overall feasibility of the trials.

    View details for PubMedID 27807278

  • Venous imaging-based biomarkers in acute ischaemic stroke. Journal of neurology, neurosurgery, and psychiatry Munuera, J., Blasco, G., Hernández-Pérez, M., Daunis-i-Estadella, P., Dávalos, A., Liebeskind, D. S., Wintermark, M., Demchuk, A., Menon, B. K., Thomalla, G., Nael, K., Pedraza, S., Puig, J. 2016

    Abstract

    Vascular neuroimaging plays a decisive role in selecting the best therapy in patients with acute ischaemic stroke. However, compared with the arterial system, the role of veins has not been thoroughly studied. In this review, we present the major venous imaging-based biomarkers in ischaemic stroke. First, the presence of hypodense veins in the monophasic CT angiography ipsilateral to the arterial occlusion. Second, the asymmetry of venous drainage in the pathological cerebral hemisphere on CT and MRI dynamic angiography. Finally, the presence of hypodense veins on T2* -based MRI. From the physiological point of view, the venous imaging-based biomarkers would detect the alteration of brain perfusion (flow), as well as the optimisation of extraction oxygen mechanisms (misery perfusion). Several studies have correlated the venous imaging-based biomarkers with grade of collateral circulation, the ischaemic penumbra and clinical functional outcome. Although venous imaging-based biomarkers still have to be validated, growing evidence highlights a potential complementary role in the acute stroke clinical decision-making process.

    View details for DOI 10.1136/jnnp-2016-314814

    View details for PubMedID 27807197

  • Prevalence of dural venous sinus stenosis and hypoplasia in a generalized population. Journal of neurointerventional surgery Durst, C. R., Ornan, D. A., Reardon, M. A., Mehndiratta, P., Mukherjee, S., Starke, R. M., Wintermark, M., Evans, A., Jensen, M. E., Crowley, R. W., Gaughen, J., Liu, K. C. 2016; 8 (11): 1173-1177

    Abstract

    While recent literature has described the prevalence of transverse sinus stenosis in patients with idiopathic intracranial hypertension, tinnitus, and refractory headaches, it is unclear what the prevalence is in the general population. This study evaluates the prevalence of venous sinus stenosis and hypoplasia in the general patient population.355 of 600 consecutive patients who underwent CT angiography of the head met the inclusion criteria. The diameters of the dural venous sinuses were recorded. Each study was evaluated by a neuroradiologist for the presence of stenoses. Univariate and multivariate statistical analyses were performed by a statistician.The prevalence of unilateral transverse sinus stenosis or hypoplasia in a sample of patients representing the general population was 33%, the prevalence of bilateral transverse sinus stenosis was 5%, and the prevalence of unilateral stenosis with contralateral hypoplasia was 1%. A multivariate analysis identified arachnoid granulations as a predictor of stenosis (p<0.001). Gender trended toward significance (p=0.094). Race was not a significant predictor of stenosis (p=0.745).The prevalence of bilateral transverse sinus stenosis in the general population is not trivial. These data may be used as a reference for understanding the mechanistic role of stenoses in idiopathic intracranial hypertension, tinnitus, and refractory headaches.

    View details for DOI 10.1136/neurintsurg-2015-012147

    View details for PubMedID 26747875

  • Detection of parathyroid adenomas using a monophasic dual-energy computed tomography acquisition: diagnostic performance and potential radiation dose reduction NEURORADIOLOGY Leiva-Salinas, C., Flors, L., Durst, C. R., Hou, Q., Patrie, J. T., Wintermark, M., Mukherjee, S. 2016; 58 (11): 1135-1141

    Abstract

    The aims of the study were to compare the diagnostic performance of a combination of virtual non-contrast (VNC) images and arterial images obtained from a single-phase dual-energy CT (DECT) acquisition and standard non-contrast and arterial images from a biphasic protocol and to study the potential radiation dose reduction of the former approach.All DECT examinations performed for evaluation of parathyroid adenomas during a 13-month period were retrospectively reviewed. An initial single-energy unenhanced acquisition was followed by a dual-energy arterial phase acquisition. "Virtual non-contrast images" were generated from the dual-energy acquisition. Two independent and blinded radiologists evaluated three different sets of images during three reading sessions: single arterial phase, single-phase DECT (virtual non-contrast and arterial phase), and standard biphasic protocol (true non-contrast and arterial phase). The accuracy of interpretation in lateralizing an adenoma to the side of the neck and localizing it to a quadrant in the neck was evaluated.Sixty patients (mean age, 65.5 years; age range, 38-87 years) were included in the study. The lateralization and localization accuracy, sensitivity, and positive predicted value (PPV) and negative predicted value (NPV) of the different image datasets were comparable. The combination of VNC and arterial images was more specific than arterial images alone to lateralize a parathyroid lesion (OR = 1.93, p = 0.043). The use of the single-phase protocol resulted in a calculated radiation exposure reduction of 52.8 %.Virtual non-contrast and arterial images from a single DECT acquisition showed similar diagnostic accuracy than a biphasic protocol, providing a significant dose reduction.

    View details for DOI 10.1007/s00234-016-1736-4

    View details for Web of Science ID 000388690700010

    View details for PubMedID 27590748

  • Quantifying Head Impacts in Collegiate Lacrosse AMERICAN JOURNAL OF SPORTS MEDICINE Reynolds, B. B., Patrie, J., Henry, E. J., Goodkin, H. P., Broshek, D. K., Wintermark, M., Druzgal, T. J. 2016; 44 (11): 2947-2956

    Abstract

    Concussion and repetitive head impact in sports has increased interest and concern for clinicians, scientists, and athletes. Lacrosse is the fastest growing sport in the United States, but the burden of head impact in lacrosse is unknown.The goal of this pilot study was to quantify head impact associated with practicing and playing collegiate lacrosse while subjects were fitted with wearable accelerometers.Descriptive epidemiology study.In a single year, a collegiate cohort of 14 women's and 15 men's lacrosse players wore mastoid-patch accelerometers to measure the frequency and severity of head impacts during official practices and games. Average impact severity, mean number of impacts, and cumulative acceleration were evaluated, stratified by sport and event type.Men's and women's collegiate lacrosse players did not significantly differ in the number of head impacts received during games (11.5 for men vs 9.2 for women) or practices (3.1 vs 3.1). Men's lacrosse players had significantly higher average head acceleration per impact during games compared with women (21.1g vs 14.7g) but not during practices (21.3g vs 18.1g). For both men and women, more impacts occurred during games than during practices (men, 11.5 vs 3.1; women, 9.2 vs 3.1), but impact severity did not significantly differ between events for either sport (men, 21.1g vs 21.3g; women, 14.7g vs 18.1g).The study data suggest a higher impact burden during games compared with practices, but this effect is driven by the quantity rather than severity of impacts. In contrast, sex-based effects in impact burden are driven by average impact severity rather than quantity. Data collected from larger multisite trials and/or different age groups could be used to inform ongoing debates, including headgear and practice regulations, that might appreciably affect the burden of head impacts in lacrosse.While most head impacts do not result in a clinical diagnosis of concussion, evidence indicates that subconcussive head impacts may increase susceptibility to concussion and contribute to long-term neurodegeneration.

    View details for DOI 10.1177/0363546516648442

    View details for Web of Science ID 000387359900006

    View details for PubMedID 27281278

  • Added value of multimodal computed tomography imaging: analysis of 1994 acute ischaemic strokes. European journal of neurology BILL, O., Faouzi, M., Meuli, R., Maeder, P., Wintermark, M., Michel, P. 2016

    Abstract

    Multimodal computed tomography (CT) based imaging (MCTI) is widely used in acute ischaemic stroke. It was postulated that the use of MCTI is associated with improved patient outcome without causing harm.All patients with an acute ischaemic stroke and CT-based imaging within 24 h from the ASTRAL (Acute Stroke Registry and Analysis of Lausanne) registry were included. Preceding demographic, clinical, biological, radiological and follow-up data were collected. Significant predictors of MCTI use were identified retrospectively to go on to fit a multivariable analysis. Then, patients undergoing additional CT angiography (CTA) or CTA and perfusion CT (CTP) were compared with non-contrast CT only patients with regard to 3-month favourable outcome (modified Rankin Scale score ≤2), 12-month mortality, stroke mechanism, short-term renal failure, use of ancillary diagnostic tests, duration of hospitalization and 12-month stroke recurrence.Of the 1994 included patients, 273 had only non-contrast CT, 411 had both non-contrast CT and CTA and 1310 had all three examinations. Factors independently associated with MCTI were younger age, low pre-stroke modified Rankin Scale score, low creatinine value, known stroke onset, anterior circulation stroke, anticoagulation or antihypertensive therapy (CTA only) and higher National Institutes of Health Stroke Scale scores (CTP only). After adjustment, MCTI was associated with a 50% reduction of 12-month mortality and a lower likelihood of unknown stroke mechanism. No association was found between MCTI and 3-month outcome, contrast-induced nephropathy, hospitalization duration, number of ancillary diagnostic tests or with stroke recurrence.Our study shows an association of MCTI use with lower adjusted 12-month mortality, better identification of the stroke mechanism and no signs of harm.

    View details for DOI 10.1111/ene.13173

    View details for PubMedID 27801538

  • R-SCAN: Imaging for Low Back Pain. Journal of the American College of Radiology Hom, J., Smith, C. D., Ahuja, N., Wintermark, M. 2016; 13 (11): 1385-1386 e1

    View details for DOI 10.1016/j.jacr.2016.06.043

    View details for PubMedID 27595195

  • R-SCAN: Imaging for Uncomplicated Acute Rhinosinusitis. Journal of the American College of Radiology Kroll, H., Hom, J., Ahuja, N., Smith, C. D., Wintermark, M. 2016

    View details for DOI 10.1016/j.jacr.2016.08.018

    View details for PubMedID 27744010

  • A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Cereda, C. W., Christensen, S., Campbell, B. C., Mishra, N. K., Mlynash, M., Levi, C., Straka, M., Wintermark, M., Bammer, R., Albers, G. W., Parsons, M. W., Lansberg, M. G. 2016; 36 (10): 1780-1789

    Abstract

    Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

    View details for DOI 10.1177/0271678X15610586

    View details for Web of Science ID 000385349400011

    View details for PubMedID 26661203

    View details for PubMedCentralID PMC5076783

  • Stroke Treatment Academic Industry Roundtable: The Next Generation of Endovascular Trials. Stroke; a journal of cerebral circulation Jovin, T. G., Albers, G. W., Liebeskind, D. S. 2016; 47 (10): 2656-2665

    Abstract

    The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. In pursuit of this goal and building on recently available level I evidence of benefit from endovascular therapy (ET) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in ET.Three key directions for advancing the field were identified: (1) development of systems of care for ET in large vessel occlusion stroke, (2) development of therapeutic approaches adjunctive to ET, and (3) exploring clinical benefit of ET in patient population insufficiently studied in recent trials. Methodological issues such as optimal trial design and outcome measures have also been addressed.Development of systems of care strategies should be geared both toward ensuring broad access to ET for eligible patients and toward shortening time to reperfusion to the minimum possible. Adjunctive therapy development includes neuroprotective approaches, adjuvant microcirculatory/collateral enhancing strategies, and periprocedural management. Future research priorities seeking to expand the eligible patient population are to determine benefit of ET in patients presenting beyond conventional time windows, in patients with large baseline ischemic core lesions, and in other important subgroups.Research priorities in ET for large vessel occlusion stroke are to improve systems of care, investigate effective adjuvant therapies, and explore whether patient eligibility could be expanded.

    View details for DOI 10.1161/STROKEAHA.116.013578

    View details for PubMedID 27586682

  • R-SCAN: Why We Should Care! Journal of the American College of Radiology Wintermark, M., Fredericks, N., Burleson, J., Bello, J. A., McGinty, G., Smith, C. D., Weinberger, S. E., Thorwarth, W. T., Haines, G. R. 2016; 13 (10): 1247-1248 e1

    View details for DOI 10.1016/j.jacr.2016.06.035

    View details for PubMedID 27601198

  • Utilizing dual energy CT to improve CT diagnosis of posterior fossa ischemia. Journal of neuroradiology. Journal de neuroradiologie Hixson, H. R., Leiva-Salinas, C., Sumer, S., Patrie, J., Xin, W., Wintermark, M. 2016; 43 (5): 346-352

    Abstract

    Evaluation of posterior fossa ischemia on conventional CT is limited. The goal of our study was to determine if virtual monochromatic CT increases the diagnostic accuracy for the detection of posterior infarcts relative to standard CT while using diffusion-weighted MRI as a reference standard.Thirty consecutive subjects who meet the following inclusion criteria were retrospectively enrolled: (1) symptoms of posterior fossa stroke (e.g. vertigo, fainting, and dizziness), (2) unenhanced dual-energy CT of the head performed upon admission to the emergency department, and (3) MRI of the brain within 7 days following the CT. Eight of the 30 subjects were determined to have MRI diffusion-weighted imaging findings consistent with acute posterior fossa ischemia. Monochromatic energy reconstructions at 60, 80, 100, 120keV and the clinical CT were interpreted independently by two fellowship-trained neuroradiologists, who assessed the images for posterior fossa infarcts and for imaging quality.Reconstructions obtained at 80keV provided the best artifact reduction and overall maximization of image quality and were statistically significantly better than standard head CT (P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were at least not less than standard CT, and there was a trend toward better values at 100keV (P=0.096).Monoenergetic 80 or 100keV reconstructions may improve the detection of posterior fossa ischemia compared to conventional CT. However, if clinical suspicion for posterior fossa ischemia warrants, a brain MRI with diffusion-weighted imaging should still be obtained, even in the presence of a negative dual energy CT of the brain.

    View details for DOI 10.1016/j.neurad.2016.04.001

    View details for PubMedID 27255679

  • Non-Invasive, Focal Disconnection of Brain Circuitry Using Magnetic Resonance-Guided Low-Intensity Focused Ultrasound to Deliver a Neurotoxin. Ultrasound in medicine and biology Zhang, Y., Tan, H., Bertram, E. H., Aubry, J., Lopes, M., Roy, J., Dumont, E., Xie, M., Zuo, Z., Klibanov, A. L., Lee, K. S., Wintermark, M. 2016; 42 (9): 2261-2269

    Abstract

    Disturbances in the function of neuronal circuitry contribute to most neurologic disorders. As knowledge of the brain's connectome continues to improve, a more refined understanding of the role of specific circuits in pathologic states will also evolve. Tools capable of manipulating identified circuits in a targeted and restricted manner will be essential not only to expand our understanding of the functional roles of such circuits, but also to therapeutically disconnect critical pathways contributing to neurologic disease. This study took advantage of the ability of low-intensity focused ultrasound (FUS) to transiently disrupt the blood-brain barrier (BBB) to deliver a neurotoxin with poor BBB permeability (quinolinic acid [QA]) in a guided manner to a target region in the brain parenchyma. Ten male Sprague-Dawley rats were divided into two groups receiving the following treatments: (i) magnetic resonance-guided FUS + microbubbles + saline (n = 5), or (ii) magnetic resonance-guided FUS + microbubbles + QA (n = 5). Systemic administration of QA was well tolerated. However, when QA and microbubbles were systemically administered in conjunction with magnetic resonance-guided FUS, the BBB was disrupted and primary neurons were destroyed in the targeted subregion of the hippocampus in all QA-treated animals. Administration of vehicle (saline) together with microbubbles and FUS also disrupted the BBB but did not produce neuronal injury. These findings indicate the feasibility of non-invasively destroying a targeted region of the brain parenchyma using low-intensity FUS together with systemic administration of microbubbles and a neurotoxin. This approach could be of therapeutic value in various disorders in which disturbances of neural circuitry contribute to neurologic disease.

    View details for DOI 10.1016/j.ultrasmedbio.2016.04.019

    View details for PubMedID 27260243

  • Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke: Correlates of Stroke Cause and Recurrence. Stroke; a journal of cerebral circulation Fullerton, H. J., deVeber, G. A., Hills, N. K., Dowling, M. M., Fox, C. K., Mackay, M. T., Kirton, A., Yager, J. Y., Bernard, T. J., Hod, E. A., Wintermark, M., Elkind, M. S. 2016; 47 (9): 2221-2228

    Abstract

    Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS.In an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS.Median age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3-10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies.Among children with AIS, specific inflammatory biomarkers correlate with cause and-in the arteriopathy group-risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

    View details for DOI 10.1161/STROKEAHA.116.013719

    View details for PubMedID 27491741

  • Safety of Computed Tomographic Angiography in the Evaluation of Patients With Acute Stroke: A Single-Center Experience. Stroke; a journal of cerebral circulation Ehrlich, M. E., Turner, H. L., Currie, L. J., Wintermark, M., Worrall, B. B., Southerland, A. M. 2016; 47 (8): 2045-2050

    Abstract

    Noncontrasted head computed tomography (NCHCT) has long been the standard of care for acute stroke imaging. New guidelines recommending advanced vascular imaging to identify eligible patients for endovascular therapy have renewed safety concerns on the use of contrast in the emergent setting without laboratory confirmation of renal function.We compared computed tomographic angiography (CTA) versus NCHCT alone during acute stroke evaluation with focus on renal safety and timeliness of therapy delivery. We reviewed data on all emergency department patients for whom the Acute Stroke Intervention Team was activated between December 2013 and September 2014. Primary outcomes included acute kidney injury and change in serum creatinine from presentation to 24 to 48 hours (Δ serum creatinine [Cr]). We assessed therapy delay using door-to-CT and door-to-needle times.Of 289 patients requiring Acute Stroke Intervention Team activation, 157 received CTA and 132 NCHCT only. There was no difference between groups in mean Cr at 24 to 48 hours (1.06 CTA; 1.40 NCHCT; P=0.059), ΔCr (-0.07 CTA, -0.11 NCHCT, P=0.489), or rates of acute kidney injury (5 CTA, 7 NCHCT, P=0.422). There was no significant difference in mean intravenous tissue plasminogen activator treatment times (68.11 minutes CTA, 81.36 minutes NCHCT; P=0.577). In the 157 patients who underwent CTA, 16 (10.2%) vascular anomalies and 55 (35.0%) high-grade stenoses or occlusions were identified.CTA acquisition during acute stroke evaluation was safe with regards to renal function and did not delay appropriate therapy delivery. Acute CTA acquisition offers additional clinical value in rapid identification of vascular abnormalities.

    View details for DOI 10.1161/STROKEAHA.116.013973

    View details for PubMedID 27364528

  • Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma PLOS ONE Puig, J., Sanchez-Gonzalez, J., Blasco, G., Daunis-i-Estadella, P., Federau, C., Alberich-Bayarri, A., Biarnes, C., Nael, K., Essig, M., Jain, R., Wintermark, M., Pedraza, S. 2016; 11 (7)

    Abstract

    Intravoxel incoherent motion (IVIM) is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma.Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were generated for contrast-enhancing regions (CER) and non-enhancing regions (NCER). Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses.We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10-3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively). Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031); fCER combined with treatment predicted survival with 100% accuracy.The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

    View details for DOI 10.1371/journal.pone.0158887

    View details for Web of Science ID 000379811500059

    View details for PubMedID 27387822

    View details for PubMedCentralID PMC4936699

  • Non-Relative Value Unit-Generating Activities Represent One-Fifth of Academic Neuroradiologist Productivity. AJNR. American journal of neuroradiology Wintermark, M., Zeineh, M., Zaharchuk, G., Srivastava, A., Fischbein, N. 2016; 37 (7): 1206-1208

    Abstract

    A neuroradiologist's activity includes many tasks beyond interpreting relative value unit-generating imaging studies. Our aim was to test a simple method to record and quantify the non-relative value unit-generating clinical activity represented by consults and clinical conferences, including tumor boards.Four full-time neuroradiologists, working an average of 50% clinical and 50% academic activity, systematically recorded all the non-relative value unit-generating consults and conferences in which they were involved during 3 months by using a simple, Web-based, computer-based application accessible from smartphones, tablets, or computers. The number and type of imaging studies they interpreted during the same period and the associated relative value units were extracted from our billing system.During 3 months, the 4 neuroradiologists working an average of 50% clinical activity interpreted 4241 relative value unit-generating imaging studies, representing 8152 work relative value units. During the same period, they recorded 792 non-relative value unit-generating study reviews as part of consults and conferences (not including reading room consults), representing 19% of the interpreted relative value unit-generating imaging studies.We propose a simple Web-based smartphone app to record and quantify non-relative value unit-generating activities including consults, clinical conferences, and tumor boards. The quantification of non-relative value unit-generating activities is paramount in this time of a paradigm shift from volume to value. It also represents an important tool for determining staffing levels, which cannot be performed on the basis of relative value unit only, considering the importance of time spent by radiologists on non-relative value unit-generating activities. It may also influence payment models from medical centers to radiology departments or practices.

    View details for DOI 10.3174/ajnr.A4701

    View details for PubMedID 26939630

  • Evolution of Volume and Signal Intensity on Fluid-attenuated Inversion Recovery MR Images after Endovascular Stroke Therapy RADIOLOGY Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Lansberg, M. G., Wintermark, M., Albers, G. W. 2016; 280 (1): 184-192

    Abstract

    Purpose To analyze both volume and signal evolution on magnetic resonance (MR) fluid-attenuated inversion recovery (FLAIR) images between the images after endovascular therapy and day 5 (which was the prespecified end point for infarct volume in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution [DEFUSE 2] trial) in a subset of patients enrolled in the DEFUSE 2 study. Materials and Methods This study was approved by the local ethics committee at all participating sites. Informed written consent was obtained from all patients. In this post hoc analysis of the DEFUSE 2 study, 35 patients with FLAIR images acquired both after endovascular therapy (median time after symptom onset, 12 hours) and at day 5 were identified. Patients were separated into two groups based on the degree of reperfusion achieved on time to maximum greater than 6-second perfusion imaging (≥90% vs <90%). After coregistration and signal normalization, lesion volumes and signal intensity were assessed by using FLAIR imaging for the initial lesion (ie, visible after endovascular therapy) and the recruited lesion (the additional lesion visible on day 5, but not visible after endovascular therapy). Statistical significance was assessed by using Wilcoxon signed-rank, Mann-Whitney U, and Fisher exact tests. Results All 35 patients had FLAIR lesion growth between the after-revascularization examination and day 5. Median lesion growth was significantly larger in patients with <90% reperfusion (27.85 mL) compared with ≥90% (8.12 mL; P = .003). In the initial lesion, normalized signal did not change between after endovascular therapy (median, 1.60) and day 5 (median, 1.58) in the ≥90% reperfusion group (P = .97), but increased in the <90% reperfusion group (from 1.60 to 1.73; P = .01). In the recruited lesion, median normalized signal increased significantly in both groups between after endovascular therapy and day 5 (after endovascular therapy, from 1.19 to 1.56, P < .001; and day 5, from 1.18 to 1.63, P < .001). Conclusion Patients with ≥90% reperfusion after endovascular therapy have significantly less lesion growth on FLAIR images between after therapy and day 5 compared with patients who have <90% reperfusion. Therefore, the effect of reperfusion therapies on lesion volumes are likely more apparent at day 5 than after therapy. (©) RSNA, 2016.

    View details for DOI 10.1148/radiol.2015151586

    View details for Web of Science ID 000378721900020

    View details for PubMedID 26761721

  • Same-Day Sinus and Brain CT Imaging in the Medicare Population: Are Practice Patterns Changing in Association with Medicare Policy Initiatives? AMERICAN JOURNAL OF NEURORADIOLOGY Kroll, H., Duszak, R., Hemingway, J., Hughes, D., Wintermark, M. 2016; 37 (6): 1000-1004

    Abstract

    Monitoring the frequency of same-day sinus and brain CT (Outpatient Measure 14, "OP-14") is part of a recent large Centers for Medicare and Medicaid Services hospital outpatient quality initiative to improve imaging efficiency. This study investigates patient-level claims data in the Medicare population focusing on where same-day sinus and brain CT imaging is performed and how the frequency of same-day studies changed with time before and during OP-14 measure program implementation.Research Identifiable Files were used to identify all sinus and brain CT examinations from 2004 through 2012 for a 5% random patient sample of Medicare fee-for-service beneficiaries. Overall and site of service use rates were calculated for same- and non-same-day examinations. Changes were mapped to policy initiative timetables.The number of same-day sinus and brain CT studies from 2004 to 2012 increased 67% from 1.85 (95% CI, 1.78-1.91) per 1000 Medicare beneficiaries in 2004 to 3.08 (95% CI, 3.00-3.15) in 2012. The biggest driver of increased same-day studies was the emergency department setting, from 0.56 (95% CI, 0.53-0.60) per 1000 to 1.78 (95% CI, 1.72-1.84; +215.7%). Overall use of brain CT from 146.0 (95% CI, 145.1-146.9) per 1000 to 176.3 (95% CI, 175.4-177.2; +21%) and sinus CT from 12.6 (95% CI, 12.4-12.8) per 1000 to 15.4 (95% CI, 15.2-15.6; +22%) increased until 2009 and remained stable through 2012.Previously increasing same-day sinus and brain CT in Medicare beneficiaries plateaued in 2009, coinciding with the implementation of targeted measures by the Centers for Medicare and Medicaid Services. Same-day imaging continues to increase in the emergency department setting.

    View details for DOI 10.3174/ajnr.A4670

    View details for Web of Science ID 000377633100005

    View details for PubMedID 26822731

  • ACR Appropriateness Criteria Head Trauma JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Shetty, V. S., Reis, M. N., Aulino, J. M., Berger, K. L., Broder, J., Choudhri, A. F., Kendi, A. T., Kessler, M. M., Kirsch, C. F., Luttrull, M. D., Mechtler, L. L., Prall, J. A., Raksin, P. B., Roth, C. J., Sharma, A., West, O. C., Wintermark, M., Cornelius, R. S., Bykowski, J. 2016; 13 (6): 668-679

    Abstract

    Neuroimaging plays an important role in the management of head trauma. Several guidelines have been published for identifying which patients can avoid neuroimaging. Noncontrast head CT is the most appropriate initial examination in patients with minor or mild acute closed head injury who require neuroimaging as well as patients with moderate to severe acute closed head injury. In short-term follow-up neuroimaging of acute traumatic brain injury, CT and MRI may have complementary roles. In subacute to chronic traumatic brain injury, MRI is the most appropriate initial examination, though CT may have a complementary role in select circumstances. Advanced neuroimaging techniques are areas of active research but are not considered routine clinical practice at this time. In suspected intracranial vascular injury, CT angiography or venography or MR angiography or venography is the most appropriate imaging study. In suspected posttraumatic cerebrospinal fluid leak, high-resolution noncontrast skull base CT is the most appropriate initial imaging study to identify the source, with cisternography reserved for problem solving. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

    View details for DOI 10.1016/j.jacr.2016.02.023

    View details for PubMedID 27262056

  • Volume of Subclinical Microembolization Correlates to Long-term Cognitive Changes Following Carotid Revascularization Zhou, W., Hitchner, E., Bhat, J., Baughman, B., Soman, S., Wintermark, M., Rosen, A., Yesavage, J. MOSBY-ELSEVIER. 2016: 141S–142S
  • Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398

    Abstract

    The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

    View details for DOI 10.1161/STROKEAHA.115.012364

    View details for PubMedID 27073243

  • Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis? STROKE Wei, F., Diedrich, K. T., Fullerton, H. J., de Veber, G., Wintermark, M., Hodge, J., Kirton, A. 2016; 47 (5): 1265-1270

    Abstract

    Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.

    View details for DOI 10.1161/STROKEAHA.115.011331

    View details for Web of Science ID 000375049700025

    View details for PubMedID 27006453

  • IVIM perfusion fraction is prognostic for survival in brain glioma. Clinical neuroradiology Federau, C., Cerny, M., Roux, M., Mosimann, P. J., Maeder, P., Meuli, R., Wintermark, M. 2016: -?

    Abstract

    The interest in measuring brain perfusion with intravoxel incoherent motion (IVIM) MRI has significantly increased in the last 3 years. Our aim was to evaluate the prognostic value for survival of intravoxel incoherent motion perfusion fraction in patients with gliomas, and compare it to dynamic susceptibility contrast relative cerebral blood volume and apparent diffusion coefficient.Images were acquired in 27 patients with brain gliomas (16 high grades, 11 low grades), before any relevant treatment. Region of maximal perfusion fraction, maximal relative cerebral blood volume, and minimal apparent diffusion coefficient were obtained. The accuracy of all three methods for 2‑year survival prognosis was compared using the area under the receiver operating characteristic curve and Kaplan-Meier survival curves.Death or survival for at least 2 years after imaging could be documented in 22/27 patients. The cutoff values of 0.112 for the perfusion fraction, of 3.01 for the relative cerebral blood volume, and 1033 × 10(-6) mm(2)/s for apparent diffusion coefficient led to an identical sensitivity of 0.889, and a specificity of 0.833, 0.517, and 0.750, respectively for 2 year survival prognosis. The corresponding areas under the receiver operating characteristic curves were 0.84, 076, and 0.86, respectively. All three methods had a significant log rank test considering overall survival (p = 0.001, p = 0.028, and p = 0.002).In this relatively small cohort, maximal IVIM perfusion fraction, similarly to maximal relative cerebral blood volume and minimal apparent diffusion coefficient, was prognostic for survival in patients with gliomas. Maximal IVIM perfusion fraction and minimal apparent diffusion coefficient performed similarly in predicting survival, and both slightly outperformed maximal relative cerebral blood volume.

    View details for PubMedID 27116215

  • A combinatorial radiographic phenotype may stratify patient survival and be associated with invasion and proliferation characteristics in glioblastoma JOURNAL OF NEUROSURGERY Rao, A., Rao, G., Gutman, D. A., Flanders, A. E., Hwang, S. N., Rubin, D. L., Colen, R. R., Zinn, P. O., Jain, R., Wintermark, M., Kirby, J. S., Jaffe, C. C., Freymann, J. 2016; 124 (4): 1008-1017

    Abstract

    Individual MRI characteristics (e.g., volume) are routinely used to identify survival-associated phenotypes for glioblastoma (GBM). This study investigated whether combinations of MRI features can also stratify survival. Furthermore, the molecular differences between phenotype-induced groups were investigated.Ninety-two patients with imaging, molecular, and survival data from the TCGA (The Cancer Genome Atlas)-GBM collection were included in this study. For combinatorial phenotype analysis, hierarchical clustering was used. Groups were defined based on a cutpoint obtained via tree-based partitioning. Furthermore, differential expression analysis of microRNA (miRNA) and mRNA expression data was performed using GenePattern Suite. Functional analysis of the resulting genes and miRNAs was performed using Ingenuity Pathway Analysis. Pathway analysis was performed using Gene Set Enrichment Analysis.Clustering analysis reveals that image-based grouping of the patients is driven by 3 features: volume-class, hemorrhage, and T1/FLAIR-envelope ratio. A combination of these features stratifies survival in a statistically significant manner. A cutpoint analysis yields a significant survival difference in the training set (median survival difference: 12 months, p = 0.004) as well as a validation set (p = 0.0001). Specifically, a low value for any of these 3 features indicates favorable survival characteristics. Differential expression analysis between cutpoint-induced groups suggests that several immune-associated (natural killer cell activity, T-cell lymphocyte differentiation) and metabolism-associated (mitochondrial activity, oxidative phosphorylation) pathways underlie the transition of this phenotype. Integrating data for mRNA and miRNA suggests the roles of several genes regulating proliferation and invasion.A 3-way combination of MRI phenotypes may be capable of stratifying survival in GBM. Examination of molecular processes associated with groups created by this combinatorial phenotype suggests the role of biological processes associated with growth and invasion characteristics.

    View details for DOI 10.3171/2015.4.JNS142732

    View details for Web of Science ID 000372669100015

    View details for PubMedCentralID PMC4990448

  • A combinatorial radiographic phenotype may stratify patient survival and be associated with invasion and proliferation characteristics in glioblastoma. Journal of neurosurgery Rao, A., Rao, G., Gutman, D. A., Flanders, A. E., Hwang, S. N., Rubin, D. L., Colen, R. R., Zinn, P. O., Jain, R., Wintermark, M., Kirby, J. S., Jaffe, C. C., Freymann, J. 2016; 124 (4): 1008-1017

    Abstract

    Individual MRI characteristics (e.g., volume) are routinely used to identify survival-associated phenotypes for glioblastoma (GBM). This study investigated whether combinations of MRI features can also stratify survival. Furthermore, the molecular differences between phenotype-induced groups were investigated.Ninety-two patients with imaging, molecular, and survival data from the TCGA (The Cancer Genome Atlas)-GBM collection were included in this study. For combinatorial phenotype analysis, hierarchical clustering was used. Groups were defined based on a cutpoint obtained via tree-based partitioning. Furthermore, differential expression analysis of microRNA (miRNA) and mRNA expression data was performed using GenePattern Suite. Functional analysis of the resulting genes and miRNAs was performed using Ingenuity Pathway Analysis. Pathway analysis was performed using Gene Set Enrichment Analysis.Clustering analysis reveals that image-based grouping of the patients is driven by 3 features: volume-class, hemorrhage, and T1/FLAIR-envelope ratio. A combination of these features stratifies survival in a statistically significant manner. A cutpoint analysis yields a significant survival difference in the training set (median survival difference: 12 months, p = 0.004) as well as a validation set (p = 0.0001). Specifically, a low value for any of these 3 features indicates favorable survival characteristics. Differential expression analysis between cutpoint-induced groups suggests that several immune-associated (natural killer cell activity, T-cell lymphocyte differentiation) and metabolism-associated (mitochondrial activity, oxidative phosphorylation) pathways underlie the transition of this phenotype. Integrating data for mRNA and miRNA suggests the roles of several genes regulating proliferation and invasion.A 3-way combination of MRI phenotypes may be capable of stratifying survival in GBM. Examination of molecular processes associated with groups created by this combinatorial phenotype suggests the role of biological processes associated with growth and invasion characteristics.

    View details for DOI 10.3171/2015.4.JNS142732

    View details for PubMedID 26473782

  • Perfusion Computed Tomography for the Evaluation of Acute Ischemic Stroke Strengths and Pitfalls STROKE Heit, J. J., Wintermark, M. 2016; 47 (4): 1153-1158
  • CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy. Molecular neurobiology Liu, N., Chen, H., Wu, B., Li, Y., Wintermark, M., Jackson, A., Hu, J., Zhang, Y., Su, Z., Zhu, G., Zhang, W. 2016: -?

    Abstract

    In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K (trans)) as a biomarker for blood-brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K (trans) (K (trans)-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K (trans)-PIV, and smaller FIV (P < 0.001). K (trans)-PIV showed good correlation with FIV (P < 00.001, R (2) = 0.6997). In the regression analyses, K (trans)-PIV was the best predictor of clinical outcomes (P = 0.009, odds ratio (OR) = 1.960) and also the best predictor for FIV (F = 75.590, P < 0.0001). In conclusion, combining PCT and K (trans) maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.

    View details for PubMedID 26988262

  • Recent Endovascular Trials: Implications for Radiology Departments, Radiology Residency, and Neuroradiology Fellowship Training at Comprehensive Stroke Centers. Radiology Goyal, M., Derdeyn, C. P., Fiorella, D., Ross, J., Schaefer, P., Tarr, R., Willson, M. C., Bartlett, E., Wintermark, M., Kallmes, D. 2016; 278 (3): 642-645

    View details for DOI 10.1148/radiol.2015151965

    View details for PubMedID 26885731

  • Pediatric Traumatic Brain Injury JOURNAL OF PEDIATRIC NEURORADIOLOGY Kadom, N., Wintermark, M. 2016; 5 (1): 1
  • Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time. Stroke; a journal of cerebral circulation Dowlatshahi, D., Brouwers, H. B., Demchuk, A. M., Hill, M. D., Aviv, R. I., Ufholz, L., Reaume, M., Wintermark, M., Hemphill, J. C., Murai, Y., Wang, Y., Zhao, X., Wang, Y., Li, N., Sorimachi, T., Matsumae, M., Steiner, T., Rizos, T., Greenberg, S. M., Romero, J. M., Rosand, J., Goldstein, J. N., Sharma, M. 2016; 47 (3): 695-700

    Abstract

    Hematoma expansion after acute intracerebral hemorrhage is common and is associated with early deterioration and poor clinical outcome. The computed tomographic angiography (CTA) spot sign is a promising predictor of expansion; however, frequency and predictive values are variable across studies, possibly because of differences in onset-to-CTA time. We performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and frequency and predictive ability of the spot sign.We completed a systematic review for studies of CTA spot sign and hematoma expansion. We subsequently pooled patient-level data on the frequency and predictive values for significant hematoma expansion according to 5 predefined categorized onset-to-CTA times. We calculated spot-sign frequency both as raw and frequency-adjusted rates.Among 2051 studies identified, 12 met our inclusion criteria. Baseline hematoma volume, spot-sign status, and time-to-CTA were available for 1176 patients, and 1039 patients had follow-up computed tomographies for hematoma expansion analysis. The overall spot sign frequency was 26%, decreasing from 39% within 2 hours of onset to 13% beyond 8 hours (P<0.001). There was a significant decrease in hematoma expansion in spot-positive patients as onset-to-CTA time increased (P=0.004), with positive predictive values decreasing from 53% to 33%.The frequency of the CTA spot sign is inversely related to intracerebral hemorrhage onset-to-CTA time. Furthermore, the positive predictive value of the spot sign for significant hematoma expansion decreases as time-to-CTA increases. Our results offer more precise risk stratification for patients with acute intracerebral hemorrhage and will help refine clinical prediction rules for intracerebral hemorrhage expansion.

    View details for DOI 10.1161/STROKEAHA.115.012012

    View details for PubMedID 26846857

    View details for PubMedCentralID PMC4766058

  • Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study. Circulation Elkind, M. S., Hills, N. K., Glaser, C. A., Lo, W. D., Amlie-Lefond, C., Dlamini, N., Kneen, R., Hod, E. A., Wintermark, M., deVeber, G. A., Fullerton, H. J. 2016; 133 (8): 732-741

    Abstract

    Epidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS.We enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) years for controls (P=0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic.Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

    View details for DOI 10.1161/CIRCULATIONAHA.115.018595

    View details for PubMedID 26813104

    View details for PubMedCentralID PMC4766042

  • Prediction of Early Arterial Recanalization and Tissue Fate in the Selection of Patients With the Greatest Potential to Benefit From Intravenous Tissue-Type Plasminogen Activator. Stroke; a journal of cerebral circulation Leiva-Salinas, C., Patrie, J. T., Xin, W., Michel, P., Jovin, T., Wintermark, M. 2016; 47 (2): 397-403

    Abstract

    Our objective is to determine the performance of the combination of likelihood of arterial recanalization and tissue fate to predict functional clinical outcome in patients with acute stroke.Clinical, imaging, and outcome data were collected in 173 patients with acute ischemic stroke who presented within 4.5 hours from symptom onset, in the time window eligible for intravenous tissue-type plasminogen activator. Imaging data included Alberta Score Program Early Computed Tomographic Score (ASPECTS), site of occlusion, volume of ischemic core and penumbra, and recanalization. Outcome data consisted of modified Rankin Scale score at 90 days. We classified patients based on their baseline imaging characteristics and treatment with intravenous tissue-type plasminogen activator (yes/no) according to 5 different hypothetical prognostic algorithms: (1) based on whether patients received intravenous tissue-type plasminogen activator, (2) based on ASPECTS, (3) based on the site of occlusion, (4) based on volume of ischemic core and penumbra, and (5) based on a matrix of predicted recanalization and volume of ischemic core and penumbra. We compared the performance of such algorithms to predict good clinical outcome, defined as modified Rankin Scale score of ≤2 at 90 days.One hundred and twenty-four patients received intravenous tissue-type plasminogen activator; 49 did not. In the group that was treated, 46 (37%) had good outcome as opposed to 38.7% in the nontreated. The algorithm that combined the prediction of recanalization with the volume of ischemic core and penumbra showed the highest accuracy to predict good outcome (77.7%) as opposed to others (range, 43.9%-57.2%)The combination of predicted recanalization and tissue fate proved superior to prognosticate good clinical outcome when compared with other usual predictors.

    View details for DOI 10.1161/STROKEAHA.115.011066

    View details for PubMedID 26696647

  • Modern Neuroimaging: Deciphering the Developing Brain JOURNAL OF PEDIATRICS Wintermark, M. 2016; 169: 6-7

    View details for DOI 10.1016/j.jpeds.2015.11.038

    View details for Web of Science ID 000368595300002

    View details for PubMedID 26681475

  • Prediction of Thrombolysis-induced Parenchymal Hemorrhage in Patients With Acute Ischemic Stroke: Use of MR Perfusion and Diffusion Biomarkers Nael, K., Knitter, J., Jahan, R., Alger, J. R., Nenov, V., Ajani, Z., Feng, L., Meyer, B. C., Olson, S., Schwamm, L. H., Yoo, A. J., Marshall, R. S., Meyers, P. M., Yavagal, D. R., Wintermark, M., Liebeskind, D. S., Guzy, J., Saver, J. L., Kidwell, C. S. LIPPINCOTT WILLIAMS & WILKINS. 2016
  • Evolution of FLAIR Volume and Signal Intensity Following Endovascular Stroke Therapy Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Wintermark, M., Lansberg, M., Albers, G., DEFUSE 2 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2016
  • Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making. International journal of stroke Luby, M., Warach, S. J., Albers, G. W., Baron, J., Cognard, C., Dávalos, A., Donnan, G. A., Fiebach, J. B., Fiehler, J., Hacke, W., Lansberg, M. G., Liebeskind, D. S., Mattle, H. P., Oppenheim, C., Schellinger, P. D., Wardlaw, J. M., Wintermark, M. 2016; 11 (2): 180-190

    Abstract

    For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials.STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials.We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy.Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.

    View details for DOI 10.1177/1747493015616634

    View details for PubMedID 26783309

    View details for PubMedCentralID PMC4762013

  • Practice type effects on head impact in collegiate football. Journal of neurosurgery Reynolds, B. B., Patrie, J., Henry, E. J., Goodkin, H. P., Broshek, D. K., Wintermark, M., Druzgal, T. J. 2016; 124 (2): 501-510

    Abstract

    OBJECT IVE: This study directly compares the number and severity of subconcussive head impacts sustained during helmet-only practices, shell practices, full-pad practices, and competitive games in a National Collegiate Athletic Association (NCAA) Division I-A football team. The goal of the study was to determine whether subconcussive head impact in collegiate athletes varies with practice type, which is currently unregulated by the NCAA.Over an entire season, a cohort of 20 collegiate football players wore impact-sensing mastoid patches that measured the linear and rotational acceleration of all head impacts during a total of 890 athletic exposures. Data were analyzed to compare the number of head impacts, head impact burden, and average impact severity during helmet-only, shell, and full-pad practices, and games.Helmet-only, shell, and full-pad practices and games all significantly differed from each other (p ≤ 0.05) in the mean number of impacts for each event, with the number of impacts being greatest for games, then full-pad practices, then shell practices, and then helmet-only practices. The cumulative distributions for both linear and rotational acceleration differed between all event types (p < 0.01), with the acceleration distribution being similarly greatest for games, then full-pad practices, then shell practices, and then helmet-only practices. For both linear and rotational acceleration, helmet-only practices had a lower average impact severity when compared with other event types (p < 0.001). However, the average impact severity did not differ between any comparisons of shell and full-pad practices, and games.Helmet-only, shell, and full-pad practices, and games result in distinct head impact profiles per event, with each succeeding event type receiving more impacts than the one before. Both the number of head impacts and cumulative impact burden during practice are categorically less than in games. In practice events, the number and cumulative burden of head impacts per event increases with the amount of equipment worn. The average severity of individual impacts is relatively consistent across event types, with the exception of helmet-only practices. The number of hits experienced during each event type is the main driver of event type differences in impact burden per athletic exposure, rather than the average severity of impacts that occur during the event. These findings suggest that regulation of practice equipment could be a fair and effective way to substantially reduce subconcussive head impact in thousands of collegiate football players.

    View details for DOI 10.3171/2015.5.JNS15573

    View details for PubMedID 26238972

  • Cerebral amyloid angiopathy-related inflammation: A potentially reversible cause of dementia with characteristic imaging findings. Journal of neuroradiology. Journal de neuroradiologie Raghavan, P., Looby, S., Bourne, T. D., Wintermark, M. 2016; 43 (1): 11-17

    Abstract

    Cerebral amyloid angiopathy with inflammation (CAA-I) is a less well-recognized clinically and radiologically distinct subtype of CAA. We aim to describe the imaging manifestations of this uncommon entity.A retrospective review of the medical records and imaging database yielded 9 patients with clinical and radiological findings compatible with CAA-I. The neurological findings at presentation, MRI findings including the presence of white matter involvement, mass effect, microhemorrhages and contrast enhancement, treatment provided and outcome were evaluated. Brain biopsy specimens, when available were also reviewed.All patients presented with subacute cognitive decline. In all 9 patients, confluent white matter lesions with mass effect were observed. Eight out of 9 patients demonstrated foci of microhemorrhage, while in 1, the microhemorrhages appeared 12 weeks after the initial examination. No significant parenchymal or meningeal enhancement was present in any patient. In 4 patients, brain biopsy was consistent with CAA-I. Immunosuppressive therapy was initiated in all patients, leading to full recovery in 5.CAA-I is characterized by the subacute onset of dementia, a distinct pattern of confluent white matter signal abnormality with mass effect and response to immunosuppressive therapy. Prompt recognition may help obviate brain biopsy and initiation of treatment.

    View details for DOI 10.1016/j.neurad.2015.07.004

    View details for PubMedID 26471406

  • Mismatch of Low Perfusion and High Permeability Predicts Hemorrhagic Transformation Region in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolysis. Scientific reports Chen, H., Liu, N., Li, Y., Wintermark, M., Jackson, A., Wu, B., Su, Z., Chen, F., Hu, J., Zhang, Y., Zhu, G. 2016; 6: 27950-?

    Abstract

    This study sought to determine whether the permeability related parameter K(trans), derived from computed tomography perfusion (CTP) imaging, can predict hemorrhagic transformation (HT) in patients with acute ischemic stroke who receive intra-arterial thrombolysis. Data from patients meeting the criterion were examined. CTP was performed and K(trans) maps were used to assess the permeability values in HT and non-HT regions. A receiver operating characteristic (ROC) curve was calculated, showing the sensitivity and specificity of K(trans) for predicting HT risk. Composite images were produced to illustrate the spatial correlations among perfusion, permeability changes and HT. This study examined 41 patients. Twenty-six patients had hemorrhagic infarction and 15 had parenchymal hemorrhage. The mean K(trans) value in HT regions was significantly lower than that in the non-HT regions (0.26 ± 0.21/min vs. 0.78 ± 0.64/min; P < 0.001). The ROC curve analysis identified an optimal cutoff value of 0.334/min for K(trans) to predict HT risk. Composite images suggested ischemic regions with low permeability, or the mismatch area of low perfusion and high permeability, more likely have HT. HT regions after intra-arterial thrombolysis had lower permeability values on K(trans) maps. The mismatch area of lower perfusion and higher permeability are more likely to develop HT.

    View details for DOI 10.1038/srep27950

    View details for PubMedID 27302077

    View details for PubMedCentralID PMC4908417

  • Central Nervous System Infarction HANDBOOK OF NEURO-ONCOLOGY NEUROIMAGING, 2ND EDITION Vagal, A., Vossough, A., Lev, M. H., Wintermark, M., Newton, H. B. 2016: 89-98
  • Imaging of Epidural Spinal Cord Compression HANDBOOK OF NEURO-ONCOLOGY NEUROIMAGING, 2ND EDITION Rizvi, T., Wintermark, M., Schiff, D., Newton, H. B. 2016: 723-744
  • R-SCAN: Imaging for Headache. Journal of the American College of Radiology : JACR Hom, J. n., Ahuja, N. n., Smith, C. D., Wintermark, M. n. 2016; 13 (12 Pt A): 1534–35.e1

    View details for PubMedID 28341311

  • Volume of subclinical embolic infarct correlates to long-term cognitive changes after carotid revascularization. Journal of vascular surgery Zhou, W. n., Baughman, B. D., Soman, S. n., Wintermark, M. n., Lazzeroni, L. C., Hitchner, E. n., Bhat, J. n., Rosen, A. n. 2016

    Abstract

    Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts.The study recruited 119 patients including 46% symptomatic patients who underwent carotid revascularization. Neuropsychological testing was administered preoperatively and at 1 month, 6 months, and 12 months postoperatively. Rey Auditory Verbal Learning Test (RAVLT) was the primary cognitive measure with parallel forms to avoid practice effect. All patients also received 3T brain magnetic resonance imaging with a diffusion-weighted imaging (DWI) sequence preoperatively and within 48 hours postoperatively to identify procedure-related new embolic lesions. Each DWI lesion was manually traced and input into a neuroimaging program to define volume. Embolic infarct volumes were correlated with cognitive measures. Regression models were used to identify relationships between infarct volumes and cognitive measures.A total of 587 DWI lesions were identified on 3T magnetic resonance imaging in 81.7% of carotid artery stenting (CAS) and 36.4% of carotid endarterectomy patients with a total volume of 29,327 mm(3). Among them, 54 DWI lesions were found in carotid endarterectomy patients and 533 in the CAS patients. Four patients had transient postoperative neurologic symptoms and one had a stroke. CAS was an independent predictor of embolic infarction (odds ratio, 6.6 [2.1-20.4]; P < .01) and infarct volume (P = .004). Diabetes and contralateral carotid severe stenosis or occlusion had a trend of positive association with infarct volume, whereas systolic blood pressure ≥140 mm Hg had a negative association (P = .1, .09, and .1, respectively). There was a trend of improved RAVLT scores overall after carotid revascularization. Significantly higher infarct volumes were observed among those with RAVLT decline. Within the CAS cohort, infarct volume was negatively correlated with short- and long-term RAVLT changes (P < .05).Cognitive assessment of procedure-related subclinical microemboli is challenging. Volumes of embolic infarct correlate with long-term cognitive changes, suggesting that microembolization should be considered a surrogate measure for carotid disease management.

    View details for PubMedID 28024850

  • High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study. Neuroradiology Puig, J. n., Blasco, G. n., Daunis-I-Estadella, J. n., Alberich-Bayarri, A. n., Essig, M. n., Jain, R. n., Remollo, S. n., Hernández, D. n., Puigdemont, M. n., Sánchez-González, J. n., Mateu, G. n., Wintermark, M. n., Pedraza, S. n. 2016; 58 (1): 17–26

    Abstract

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas.Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model.Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001).Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival.

    View details for PubMedID 26438560

  • Perfusion Computed Tomography for the Evaluation of Acute Ischemic Stroke: Strengths and Pitfalls. Stroke; a journal of cerebral circulation Heit, J. J., Wintermark, M. n. 2016

    View details for PubMedID 26965849

  • High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study NEURORADIOLOGY Puig, J., Blasco, G., Daunis-i-Estadella, J., Alberich-Bayarri, A., Essig, M., Jain, R., Remollo, S., Hernandez, D., Puigdemont, M., Sanchez-Gonzalez, J., Mateu, G., Wintermark, M., Pedraza, S. 2016; 58 (1): 17-26

    Abstract

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas.Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model.Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001).Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival.

    View details for DOI 10.1007/s00234-015-1599-0

    View details for Web of Science ID 000368810700004

  • Risk of Recurrent Arterial Ischemic Stroke in Childhood A Prospective International Study STROKE Fullerton, H. J., Wintermark, M., Hills, N. K., Dowling, M. M., Tan, M., Rafay, M. F., Elkind, M. S., Barkovich, A. J., deVeber, G. A. 2016; 47 (1): 53-59

    Abstract

    Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

    View details for DOI 10.1161/STROKEAHA.115.011173

    View details for PubMedID 26556824

  • Correlation between arterial spin labeling MRI and dynamic FDG on PET-MR in Alzheimer's disease and non-Alzhiemer's disease patients. EJNMMI physics Douglas, D., Goubran, M., Wilson, E., Xu, G., Tripathi, P., Holley, D., Chao, S., Wintermark, M., Quon, A., Zeineh, M., Vasanawala, M., Zaharchuk, G. 2015; 2: A83-?

    View details for DOI 10.1186/2197-7364-2-S1-A83

    View details for PubMedID 26956345

  • One-stop-shop stroke imaging with functional CT EUROPEAN JOURNAL OF RADIOLOGY Tong, E., Komlosi, P., Wintermark, M. 2015; 84 (12): 2425-2431

    Abstract

    Advanced imaging techniques have extended beyond traditional anatomic imaging and progressed to dynamic, physiologic and functional imaging. Neuroimaging is no longer a mere diagnostic tool. Multimodal functional CT, comprising of NCCT, PCT and CTA, provides a one-stop-shop for rapid stroke imaging. Integrating those imaging findings with pertinent clinical information can help guide subsequent treatment decisions, medical management and follow-up imaging selection. This review article will briefly discuss the indication and utility of each modality in acute stroke imaging.

    View details for DOI 10.1016/j.ejrad.2014.11.027

    View details for Web of Science ID 000367357700011

  • Effect of Collaterals on Clinical Presentation, Baseline Imaging, Complications, and Outcome in Acute Stroke AMERICAN JOURNAL OF NEURORADIOLOGY Fanou, E. M., Knight, J., Aviv, R. I., Hojjat, S., Symons, S. P., Zhang, L., Wintermark, M. 2015; 36 (12): 2285-2291

    View details for DOI 10.3174/ajnr.A4453

    View details for Web of Science ID 000366952700014

    View details for PubMedID 26471754

  • Outcomes after endovascular treatment for anterior circulation stroke presenting as wake-up strokes are not different than those with witnessed onset beyond 8hours JOURNAL OF NEUROINTERVENTIONAL SURGERY Aghaebrahim, A., Leiva-Salinas, C., Jadhav, A. P., Jankowitz, B., Zaidi, S., Jumaa, M., Urra, X., Amorim, E., Zhu, G., Giurgiutiu, D., Horev, A., Reddy, V., Hammer, M., Wechsler, L., Wintermark, M., Jovin, T. 2015; 7 (12): 875-880

    Abstract

    Previous studies have suggested that patients with wake-up stroke (WUS) may have superior outcomes compared with patients with a witnessed late time of onset after revascularization. We sought to test this hypothesis in patients with anterior circulation large vessel occlusion stroke (ACLVOS) treated with endovascular therapy beyond 8 h from time last seen well (TLSW).A single center retrospective review of a prospectively acquired database of consecutive patients was performed to identify patients presenting beyond 8 h of TLSW with radiographic evidence of ACLVOS, small core, and large penumbra who subsequently underwent endovascular treatment.We identified 206 patients. Patients were divided into two groups: (1) patients with WUS (38%, n=78) and (2) patients with witnessed onset beyond 8 h (62%, n=128). The groups were similar in age, baseline National Institutes of Health Stroke Scale score, TLSW to reperfusion, baseline infarct volume, and rate of successful recanalization. Rates of good outcome (modified Rankin Scale score of 0-2 at 90 days, 43% vs. 50%, p=0.3), parenchymal hematoma (9% vs. 5.5%, p=0.3), and final infarct volume (75.2 vs. 61.4 mL, p=0.6) were comparable. Multivariate analysis identified age (OR=0.95, 95% CI 0.91 to 0.99, p<0.042), successful recanalization (OR 6.0, 95% CI 1.5 to 23.5, p=0.009), and final infarct volume (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) but not mode of presentation as predictors of favorable outcomes.Rates of good outcomes, parenchymal hematoma, and final infarct volumes following endovascular treatment may not be different in patients with WUS compared with patients with witnessed onset of symptoms beyond 8 h.

    View details for DOI 10.1136/neurintsurg-2014-011316

    View details for Web of Science ID 000365851700007

    View details for PubMedID 25326003

  • Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival. Neuro-oncology Wangaryattawanich, P., Hatami, M., Wang, J., Thomas, G., Flanders, A., Kirby, J., Wintermark, M., Huang, E. S., Bakhtiari, A. S., Luedi, M. M., Hashmi, S. S., Rubin, D. L., Chen, J. Y., Hwang, S. N., Freymann, J., Holder, C. A., Zinn, P. O., Colen, R. R. 2015; 17 (11): 1525-1537

    Abstract

    Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM.We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas. Qualitative imaging assessments were based on the Visually Accessible Rembrandt Images feature-set criteria. Volumetric parameters were obtained of the specific tumor components: contrast enhancement, necrosis, and edema/invasion. Cox regression was used to assess prognostic and survival significance of each image.Univariable Cox regression analysis demonstrated 10 imaging features and 2 clinical variables to be significantly associated with overall survival. Multivariable Cox regression analysis showed that tumor-enhancing volume (P = .03) and eloquent brain involvement (P < .001) were independent prognostic indicators of overall survival. In the multivariable Cox analysis of the volumetric features, the edema/invasion volume of more than 85 000 mm(3) and the proportion of enhancing tumor were significantly correlated with higher mortality (Ps = .004 and .003, respectively).Preoperative MRI parameters have a significant prognostic role in predicting survival in patients with GBM, thus making them useful for patient stratification and endpoint biomarkers in clinical trials.

    View details for DOI 10.1093/neuonc/nov117

    View details for PubMedID 26203066

  • Rapid 3D dynamic arterial spin labeling with a sparse model-based image reconstruction NEUROIMAGE Zhao, L., Fielden, S. W., Feng, X., Wintermark, M., Mugler, J. P., Meyer, C. H. 2015; 121: 205-216

    Abstract

    Dynamic arterial spin labeling (ASL) MRI measures the perfusion bolus at multiple observation times and yields accurate estimates of cerebral blood flow in the presence of variations in arterial transit time. ASL has intrinsically low signal-to-noise ratio (SNR) and is sensitive to motion, so that extensive signal averaging is typically required, leading to long scan times for dynamic ASL. The goal of this study was to develop an accelerated dynamic ASL method with improved SNR and robustness to motion using a model-based image reconstruction that exploits the inherent sparsity of dynamic ASL data. The first component of this method is a single-shot 3D turbo spin echo spiral pulse sequence accelerated using a combination of parallel imaging and compressed sensing. This pulse sequence was then incorporated into a dynamic pseudo continuous ASL acquisition acquired at multiple observation times, and the resulting images were jointly reconstructed enforcing a model of potential perfusion time courses. Performance of the technique was verified using a numerical phantom and it was validated on normal volunteers on a 3-Tesla scanner. In simulation, a spatial sparsity constraint improved SNR and reduced estimation errors. Combined with a model-based sparsity constraint, the proposed method further improved SNR, reduced estimation error and suppressed motion artifacts. Experimentally, the proposed method resulted in significant improvements, with scan times as short as 20s per time point. These results suggest that the model-based image reconstruction enables rapid dynamic ASL with improved accuracy and robustness.

    View details for DOI 10.1016/j.neuroimage.2015.07.018

    View details for Web of Science ID 000363122000019

    View details for PubMedID 26169322

  • Introduction: Neuroimaging of degenerative and traumatic encephalopathies. Neurosurgical focus Law, M., Wintermark, M., Liu, C., Van Horn, J. D. 2015; 39 (5): E1-?

    View details for DOI 10.3171/2015.8.FOCUS15424

    View details for PubMedID 26646925

  • Infection, vaccination, and childhood arterial ischemic stroke Results of the VIPS study NEUROLOGY Fullerton, H. J., Hills, N. K., Elkind, M. S., Dowling, M. M., Wintermark, M., Glaser, C. A., Tan, M., Rivkin, M. J., Titomanlio, L., Barkovich, A. J., deVeber, G. A. 2015; 85 (17): 1459-1466

    Abstract

    Minor infection can trigger adult arterial ischemic stroke (AIS) and is common in childhood. We tested the hypotheses that infection transiently increases risk of AIS in children, regardless of stroke subtype, while vaccination against infection is protective.The Vascular Effects of Infection in Pediatric Stroke study is an international case-control study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years old) and 354 stroke-free controls. To determine prior exposure to infections and vaccines, we conducted parental interviews and chart review.Median (interquartile range) age was 7.6 years for cases and 9.3 for controls (p = 0.44). Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk of AIS (p < 0.0001); upper respiratory infections were most common. Prevalence of preceding infection was similar across stroke subtypes: arteriopathic, cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly low in both groups. Children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most (odds ratio [OR] 7.3, p = 0.0002). In an age-adjusted multivariate logistic regression model, independent risk factors for AIS included infection in the prior week (OR 6.3, p < 0.0001), undervaccination (OR 8.2, p = 0.0004), black race (compared to white; OR 1.9, p = 0.009), and rural residence (compared to urban; OR 3.0, p = 0.0003).Infection may act as a trigger for childhood AIS, while routine vaccinations appear protective. Hence, efforts to reduce the spread of common infections might help prevent stroke in children.

    View details for DOI 10.1212/WNL.0000000000002065

    View details for Web of Science ID 000363968900007

    View details for PubMedID 26423434

    View details for PubMedCentralID PMC4631070

  • The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) IEEE TRANSACTIONS ON MEDICAL IMAGING Menze, B. H., Jakab, A., Bauer, S., Kalpathy-Cramer, J., Farahani, K., Kirby, J., Burren, Y., Porz, N., Slotboom, J., Wiest, R., Lanczi, L., Gerstner, E., Weber, M., Arbel, T., Avants, B. B., Ayache, N., Buendia, P., Collins, D. L., Cordier, N., Corso, J. J., Criminisi, A., Das, T., Delingette, H., Demiralp, C., Durst, C. R., Dojat, M., Doyle, S., Festa, J., Forbes, F., Geremia, E., Glocker, B., Golland, P., Guo, X., Hamamci, A., Iftekharuddin, K. M., Jena, R., John, N. M., Konukoglu, E., Lashkari, D., Mariz, J. A., Meier, R., Pereira, S., Precup, D., Price, S. J., Raviv, T. R., Reza, S. M., Ryan, M., Sarikaya, D., Schwartz, L., Shin, H., Shotton, J., Silva, C. A., Sousa, N., Subbanna, N. K., Szekely, G., Taylor, T. J., Thomas, O. M., Tustison, N. J., Unal, G., Vasseur, F., Wintermark, M., Ye, D. H., Zhao, L., Zhao, B., Zikic, D., Prastawa, M., Reyes, M., Van Leemput, K. 2015; 34 (10): 1993-2024

    Abstract

    In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

    View details for DOI 10.1109/TMI.2014.2377694

    View details for Web of Science ID 000362358000001

    View details for PubMedID 25494501

    View details for PubMedCentralID PMC4833122

  • CTP in Transient Global Amnesia: A Single-Center Experience of 30 Patients AMERICAN JOURNAL OF NEURORADIOLOGY Meyer, I. A., Wintermark, M., Demonet, J., Michel, P. 2015; 36 (10): 1830-1833

    View details for DOI 10.3174/ajnr.A4370

    View details for Web of Science ID 000362700900008

    View details for PubMedID 26045576

  • Accuracy of MRI for the diagnosis of metastatic cervical lymphadenopathy in patients with thyroid cancer RADIOLOGIA MEDICA Chen, Q., Raghavan, P., Mukherjee, S., Jameson, M. J., Patrie, J., Xin, W., Xian, J., Wang, Z., Levine, P. A., Wintermark, M. 2015; 120 (10): 959-966

    Abstract

    The aim of this study was to systematically compare a comprehensive array of magnetic resonance (MR) imaging features in terms of their sensitivity and specificity to diagnose cervical lymph node metastases in patients with thyroid cancer.The study included 41 patients with thyroid malignancy who underwent surgical excision of cervical lymph nodes and had preoperative MR imaging ≤4weeks prior to surgery. Three head and neck neuroradiologists independently evaluated all the MR images. Using the pathology results as reference, the sensitivity, specificity and interobserver agreement of each MR imaging characteristic were calculated.On multivariate analysis, no single imaging feature was significantly correlated with metastasis. In general, imaging features demonstrated high specificity, but poor sensitivity and moderate interobserver agreement at best.Commonly used MR imaging features have limited sensitivity at correctly identifying cervical lymph node metastases in patients with thyroid cancer. A negative neck MR scan should not dissuade a surgeon from performing a neck dissection in patients with thyroid carcinomas.

    View details for DOI 10.1007/s11547-014-0474-0

    View details for Web of Science ID 000361491400009

    View details for PubMedID 25725789

  • Diffusion Tensor Imaging of TBI: Potentials and Challenges. Topics in magnetic resonance imaging Douglas, D. B., Iv, M., Douglas, P. K., Anderson, A., Vos, S. B., Bammer, R., Zeineh, M., Wintermark, M. 2015; 24 (5): 241-251

    Abstract

    Neuroimaging plays a critical role in the setting in traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging technique that is capable of providing rich information on the brain's neuroanatomic connectome. The purpose of this article is to systematically review the role of DTI and advanced diffusion techniques in the setting of TBI, including diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging, diffusion spectrum imaging, and q-ball imaging. We discuss clinical applications of DTI and review the DTI literature as it pertains to TBI. Despite the continued advancements in DTI and related diffusion techniques over the past 20 years, DTI techniques are sensitive for TBI at the group level only and there is insufficient evidence that DTI plays a role at the individual level. We conclude by discussing future directions in DTI research in TBI including the role of machine learning in the pattern classification of TBI.

    View details for DOI 10.1097/RMR.0000000000000062

    View details for PubMedID 26502306

  • Computed Tomography Perfusion in Acute Ischemic Stroke: Is It Ready for Prime Time? Stroke; a journal of cerebral circulation Liebeskind, D. S., Parsons, M. W., Wintermark, M., Selim, M., Molina, C. A., Lev, M. H., González, R. G. 2015; 46 (8): 2364-2367

    View details for DOI 10.1161/STROKEAHA.115.009179

    View details for PubMedID 26159791

  • Effective time window in reducing pituitary adenoma size by gamma knife radiosurgery PITUITARY Mak, H. K., Lai, S., Qian, W., Xu, S., Tong, E., Vance, M. L., Oldfield, E., Jane, J., Sheehan, J., Yau, K. K., Wintermark, M. 2015; 18 (4): 509-517

    Abstract

    Although the effectiveness of gamma knife radiosurgery (GKRS) in controlling the size of pituitary adenomas has been well demonstrated in many studies, the time period in which significant changes in tumor size occurs has been investigated in a limited fashion. It is important to determine the therapeutic window of GKRS in treating pituitary adenomas, i.e., the effective timeframe during which significant size reduction of these tumors occurs, so that alternative treatments such as further GKRS or microsurgery might be prescribed in a timely manner if clinically indicated.This was a nested sample of an ongoing local cohort study on GKRS for pituitary adenomas at the University of Virginia. Magnetic resonance imaging (MRI) using dedicated sequences was employed. Only patients with a baseline MRI (TP0) and at least 1 follow-up study performed in the University Hospital after GKRS were included. The follow-up scans were performed at five time-points (TP1-TP5) which were 6, 12, 24, 36 and 48 months after GKRS. The dimensional indices of the tumors were measured in three orthogonal planes, i.e., transverse (TR), antero-posterior (AP) and cranio-caudal (CC). The volumes of the tumors were estimated by using the following formula: [Formula: see text]. Tumor volume decrease by more than 25% from baseline was considered as 'shrinkage', <25% tumor size increase or decrease was considered 'static', and more than 25% increase as 'increment'. Our cohort consisted of 21 patients, with functioning adenomas in 13 subjects i.e. six adrenocorticotrophic hormone (ACTH)-secreting and seven growth hormone (GH)-secreting, and non-functioning (NF) adenomas in eight subjects.In 26 adenomas (8 ACTH, 9 GH and 9 NF), tumor control (tumor shrinkage or static) were achieved in 21 tumors (80.8%); 89, 75, and 78% for GH-secreting, ACTH-secreting and NF adenomas respectively, at the end of the 4-year follow-up period. Analysis of variance showed significant differences of GKRS margin dose among different types of tumors (p = 0.013), but not of baseline tumor volumes (p = 0.240). Logistic regression analysis showed no significant association of margin dose, baseline volume or tumor type with the tumor control outcome. Comparison of tumor change using dimensional indices relative to the base time point (TP0) showed that in the sample there was an average reduction of 1.290 mm at TP1 (6 months) with p values 0.155 (parametric t test) and 0.098 (non-parametric Wilcoxon signed-ranked test) respectively, showing a moderate reduction in tumor dimensional indices. The change in dimensional indices at later time points (TP2-TP5) showed an average reduction ranging from 1.930 to 2.471 mm. Significant reduction in the mean dimensional indices was firstly observed at TP2 (1 year) with p values 0.013 (t test) and 0.018 (Wilcoxon signed-rank test). Such scale of reduction in the dimensional indices appeared to be maintained along the time axis (from TP2 to TP5).Significant decrease in tumor dimensional indices tended to occur at 1 year post-GKRS. Although to a lesser extent, such decrease in dimensional indices continued up to the end of our follow-up period.

    View details for DOI 10.1007/s11102-014-0603-8

    View details for Web of Science ID 000356824300011

    View details for PubMedID 25261330

  • Final infarct volume discriminates outcome in mild strokes. The neuroradiology journal Vagal, A. S., Sucharew, H., Prabhakaran, S., Khatri, P., Jovin, T., Michel, P., Wintermark, M. 2015; 28 (4): 404-408

    Abstract

    Knowledge of whether final infarct volume (FIV) predicts disability after mild stroke is limited. We sought to determine if FIV could differentiate good versus poor outcome after mild stroke.We retrospectively identified 65 patients with mild stroke (National Institutes of Health Stroke Scale≤5) in a multicenter registry of 2453 patients. We evaluated associations between FIV and clinical outcome and evaluated the optimal FIV threshold that discriminated favorable (modified Rankin scale (mRS) 0-1) versus poor (mRS 2-6) outcome.The FIV cut-point of 20 mL differentiated favorable and poor outcomes (area under curve (AUC) 0.73, 95% confidence interval: 0.58-0.88). Favorable outcome was observed in 37/45 (82%) with FIV<20 mL, compared to 5/14 (36%) with FIV≥20 mL (p<0.01). FIV≥20 mL remained strongly associated with poor outcome independent of age, gender, stroke severity, Alberta Stroke Program Early CT Score (ASPECTS), and proximal arterial occlusion.In our small sample size, an FIV of 20 mL best differentiated between the likelihood of good versus poor outcome in patients with mild stroke. Further validation of infarct volume as a surrogate marker in mild stroke is warranted.

    View details for DOI 10.1177/1971400915609347

    View details for PubMedID 26427891

    View details for PubMedCentralID PMC4757309

  • Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients. Journal of neuroradiology. Journal de neuroradiologie Nicolasjilwan, M., Hu, Y., Yan, C., Meerzaman, D., Holder, C. A., Gutman, D., Jain, R., Colen, R., Rubin, D. L., Zinn, P. O., Hwang, S. N., Raghavan, P., Hammoud, D. A., Scarpace, L. M., Mikkelsen, T., Chen, J., Gevaert, O., Buetow, K., Freymann, J., Kirby, J., Flanders, A. E., Wintermark, M. 2015; 42 (4): 212-221

    Abstract

    The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type.The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients' clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis.The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679±0.068, Akaike's information criterion 566.7, P<0.001).A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM.

    View details for DOI 10.1016/j.neurad.2014.02.006

    View details for PubMedID 24997477

  • Intraventricular migration of silicone oil: A mimic of traumatic and neoplastic pathology. Journal of clinical neuroscience Chiao, D., Ksendzovsky, A., Buell, T., Sheehan, J., Newman, S., Wintermark, M. 2015; 22 (7): 1205-1207

    Abstract

    We describe an 80-year-old woman with intraventricular silicone oil mimicking traumatic pathology upon presentation to the emergency department after a ground-level fall. Intraventricular migration of silicone oil from prior intraocular endotamponade is rare having only been described in a handful of case reports. While it has a unique and characteristic appearance on imaging, intraventricular silicone oil can be confused with intraventricular hemorrhage or calcified ventricular neoplasms. Recognition and differentiation of intraventricular silicone oil from more sinister pathology is essential for the radiologist, neurologist and neurosurgeon and can be done with routine head CT scan. We discuss the imaging findings of intraventricular silicone oil and review the current understanding of this unusual phenomenon.

    View details for DOI 10.1016/j.jocn.2015.02.003

    View details for PubMedID 25863996

  • International survey of acute Stroke imaging used to make revascularization treatment decisions INTERNATIONAL JOURNAL OF STROKE Wintermark, M., Luby, M., Bornstein, N. M., Demchuk, A., Fiehler, J., Kudo, K., Lees, K. R., Liebeskind, D. S., Michel, P., Nogueira, R. G., Parsons, M. W., Sasaki, M., Wardlaw, J. M., Wu, O., Zhang, W., Zhu, G., Warach, S. J. 2015; 10 (5): 759-762

    Abstract

    To assess the differences across continental regions in terms of stroke imaging obtained for making acute revascularization therapy decisions, and to identify obstacles to participating in randomized trials involving multimodal imaging.STroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA)-Imaging circulated an online survey through its website, through the websites of national professional societies from multiple countries as well as through email distribution lists from STIR and the above mentioned societies.We received responses from 223 centers (2 from Africa, 38 from Asia, 10 from Australia, 101 from Europe, 4 from Middle East, 55 from North America, 13 from South America). In combination, the sites surveyed administered acute revascularization therapy to a total of 25 326 acute stroke patients in 2012. Seventy-three percent of these patients received intravenous (IV) tissue plasminogen activator (tPA), and 27%, endovascular therapy. Vascular imaging was routinely obtained in 79% (152/193) of sites for endovascular therapy decisions, and also as part of standard IV tPA treatment decisions at 46% (92/198) of sites. Modality, availability and use of acute vascular and perfusion imaging before revascularization varied substantially between geographical areas. The main obstacles to participate in randomized trials involving multimodal imaging included: mainly insufficient research support and staff (50%, 79/158) and infrequent use of multimodal imaging (27%, 43/158) .There were significant variations among sites and geographical areas in terms of stroke imaging work-up used tomake decisions both for intravenous and endovascular revascularization. Clinical trials using advanced imaging as a selection tool for acute revascularization therapy should address the need for additional resources and technical support, and take into consideration the lack of routine use of such techniques in trial planning.

    View details for DOI 10.1111/ijs.12491

    View details for PubMedID 25833105

  • The predictive value of magnetic resonance imaging in evaluating intracranial arteriovenous malformation obliteration after stereotactic radiosurgery. Journal of neurosurgery Lee, C., Reardon, M. A., Ball, B. Z., Chen, C., Yen, C., Xu, Z., Wintermark, M., Sheehan, J. 2015; 123 (1): 136-144

    Abstract

    OBJECT The current gold standard for diagnosing arteriovenous malformation (AVM) and assessing its obliteration after stereotactic radiosurgery (SRS) is digital subtraction angiography (DSA). Recently, MRI and MR angiography (MRA) have become increasingly popular imaging modalities for the follow-up of patients with an AVM because of their convenient setup and noninvasiveness. In this study, the authors assessed the sensitivity and specificity of MRI/MRA in evaluating AVM nidus obliteration as assessed by DSA. METHODS The authors study a consecutive series of 136 patients who underwent SRS between January 2000 and December 2012 and who underwent regular clinical examinations, several MRI studies, and at least 1 post-SRS DSA follow- up evaluation at the University of Virginia. The average follow-up time was 47.3 months (range 10.1-165.2 months). Two blinded observers were enrolled to interpret the results of MRI/MRA compared with those of DSA. The sensitivity, specificity, positive predictive value, and negative predictive value for the obliteration of AVM were reported. RESULTS On the basis of DSA, 73 patients (53.7%) achieved final angiographic obliteration in a median of 28.8 months. The sensitivity (the probability of finding obliteration on MRI/MRA among those for whom complete obliteration was shown on DSA) was 84.9% for one observer (Observer 1) and 76.7% for the other (Observer 2). The specificity was 88.9% and 95.2%, respectively. The false-negative interpretations were significantly related to the presence of draining veins, perinidal edema on T2-weighted images, and the interval between the MRI/MRA and DSA studies. CONCLUSIONS MRI/MRA predicted AVM obliteration after SRS in most patients and can be used in their follow-up. However, because the specificity of MRI/MRA is not perfect, DSA should still be performed to confirm AVM nidus obliteration after SRS.

    View details for DOI 10.3171/2014.10.JNS141565

    View details for PubMedID 25839923

  • Imaging in StrokeNet Realizing the Potential of Big Data STROKE Liebeskind, D. S., Albers, G. W., Crawford, K., Derdeyn, C. P., George, M. S., Palesch, Y. Y., Toga, A. W., Warach, S., Zhao, W., Brott, T. G., Sacco, R. L., Khatri, P., Saver, J. L., Cramer, S. C., Wolf, S. L., Broderick, J. P., Wintermark, M. 2015; 46 (7): 2000-2006

    View details for DOI 10.1161/STROKEAHA.115.009479

    View details for PubMedID 26045600

  • Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications AMERICAN JOURNAL OF ROENTGENOLOGY Ghanouni, P., Pauly, K. B., Elias, W. J., Henderson, J., Sheehan, J., Monteith, S., Wintermark, M. 2015; 205 (1): 150-159

    Abstract

    This article reviews the physical principles of MRI-guided focused ultra-sound and discusses current and potential applications of this exciting technology.MRI-guided focused ultrasound is a new minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors.

    View details for DOI 10.2214/AJR.14.13632

    View details for PubMedID 26102394

  • Delay-sensitive and delay-insensitive deconvolution perfusion-CT: similar ischemic core and penumbra volumes if appropriate threshold selected for each NEURORADIOLOGY Man, F., Patrie, J. T., Xin, W., Zhu, G., Hou, Q., Michel, P., Eskandari, A., Jovin, T., Xian, J., Wang, Z., Wintermark, M. 2015; 57 (6): 573-581

    Abstract

    Perfusion-CT (PCT) processing involves deconvolution, a mathematical operation that computes the perfusion parameters from the PCT time density curves and an arterial curve. Delay-sensitive deconvolution does not correct for arrival delay of contrast, whereas delay-insensitive deconvolution does. The goal of this study was to compare delay-sensitive and delay-insensitive deconvolution PCT in terms of delineation of the ischemic core and penumbra.We retrospectively identified 100 patients with acute ischemic stroke who underwent admission PCT and CT angiography (CTA), a follow-up vascular study to determine recanalization status, and a follow-up noncontrast head CT (NCT) or MRI to calculate final infarct volume. PCT datasets were processed twice, once using delay-sensitive deconvolution and once using delay-insensitive deconvolution. Regions of interest (ROIs) were drawn, and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in these ROIs were recorded and compared. Volume and geographic distribution of ischemic core and penumbra using both deconvolution methods were also recorded and compared.MTT and CBF values are affected by the deconvolution method used (p < 0.05), while CBV values remain unchanged. Optimal thresholds to delineate ischemic core and penumbra are different for delay-sensitive (145 % MTT, CBV 2 ml × 100 g(-1) × min(-1)) and delay-insensitive deconvolution (135 % MTT, CBV 2 ml × 100 g(-1) × min(-1) for delay-insensitive deconvolution). When applying these different thresholds, however, the predicted ischemic core (p = 0.366) and penumbra (p = 0.405) were similar with both methods.Both delay-sensitive and delay-insensitive deconvolution methods are appropriate for PCT processing in acute ischemic stroke patients. The predicted ischemic core and penumbra are similar with both methods when using different sets of thresholds, specific for each deconvolution method.

    View details for DOI 10.1007/s00234-015-1507-7

    View details for Web of Science ID 000354806900004

    View details for PubMedID 25749851

  • Noninvasive evaluation of the regional variations of GABA using magnetic resonance spectroscopy at 3 Tesla. Magnetic resonance imaging Durst, C. R., Michael, N., Tustison, N. J., Patrie, J. T., Raghavan, P., Wintermark, M., Sendhil Velan, S. 2015; 33 (5): 611-617

    Abstract

    Rapid regional fluctuations in GABA may result in inhomogeneous concentrations throughout the brain parenchyma. The goal of this study is to provide further insight into the natural distribution of GABA throughout the brain and thus determine if a surrogate site may be used for spectroscopy when evaluating motor diseases, neurological disorders, or psychiatric dysfunction.In this prospective study, eight healthy volunteers underwent spectroscopic evaluation of the frontal lobe, occipital lobe, lateral temporal lobe, basal ganglia, and both hippocampi using a spin echo variant of a J-difference editing method. Knowledge of the relative peak intensities of the macromolecule peaks at 3ppm and 0.9ppm was used to correct the contribution of co-edited macromolecules to the GABA peak at 3ppm. The GABA values were internally referenced to NAA. Linear regression was used to normalize the effect of regional tissue-fraction variation on the GABA/NAA values. A one-way ANOVA was performed with Tukey's multiple comparison test to compare the normalized GABA/NAA values in each pair of locations.After accounting for the macromolecule contribution to the GABA signal and correction for tissue fraction variation, the normalized GABA/NAA ratios differ significantly between the six brain locations (p<0.001). Pairwise comparisons of the corrected normalized GABA/NAA ratios show statistically significant variation between the frontal lobe and the basal ganglia, frontal and lateral temporal lobes, and frontal lobe and right hippocampus. Variations in the normalized GABA/NAA ratios trend toward significance between the frontal lobe and left hippocampus, occipital lobe and the frontal lobe, occipital lobe and basal ganglia, and occipital lobe and right hippocampus.Our study suggests that GABA concentration is inhomogeneous throughout the parenchyma. Studies evaluating the role of GABA must carefully consider voxel placement when incorporating spectroscopy.

    View details for DOI 10.1016/j.mri.2015.02.015

    View details for PubMedID 25708260

  • Noninvasive evaluation of the regional variations of GABA using magnetic resonance spectroscopy at 3 Tesla MAGNETIC RESONANCE IMAGING Durst, C. R., Michael, N., Tustison, N. J., Patrie, J. T., Raghavan, P., Wintermark, M., Velan, S. S. 2015; 33 (5): 611-617
  • ASFNR Recommendations for Clinical Performance of MR Dynamic Susceptibility Contrast Perfusion Imaging of the Brain AMERICAN JOURNAL OF NEURORADIOLOGY Welker, K., Boxerman, J., Kalnin, A., Kaufmann, T., Shiroishi, M., Wintermark, M. 2015; 36 (6): E41-E51

    Abstract

    MR perfusion imaging is becoming an increasingly common means of evaluating a variety of cerebral pathologies, including tumors and ischemia. In particular, there has been great interest in the use of MR perfusion imaging for both assessing brain tumor grade and for monitoring for tumor recurrence in previously treated patients. Of the various techniques devised for evaluating cerebral perfusion imaging, the dynamic susceptibility contrast method has been employed most widely among clinical MR imaging practitioners. However, when implementing DSC MR perfusion imaging in a contemporary radiology practice, a neuroradiologist is confronted with a large number of decisions. These include choices surrounding appropriate patient selection, scan-acquisition parameters, data-postprocessing methods, image interpretation, and reporting. Throughout the imaging literature, there is conflicting advice on these issues. In an effort to provide guidance to neuroradiologists struggling to implement DSC perfusion imaging in their MR imaging practice, the Clinical Practice Committee of the American Society of Functional Neuroradiology has provided the following recommendations. This guidance is based on review of the literature coupled with the practice experience of the authors. While the ASFNR acknowledges that alternate means of carrying out DSC perfusion imaging may yield clinically acceptable results, the following recommendations should provide a framework for achieving routine success in this complicated-but-rewarding aspect of neuroradiology MR imaging practice.

    View details for DOI 10.3174/ajnr.A4341

    View details for Web of Science ID 000355831700001

    View details for PubMedID 25907520

  • Using standard first-pass perfusion computed tomographic data to evaluate collateral flow in acute ischemic stroke. Stroke; a journal of cerebral circulation Chen, H., Wu, B., Liu, N., Wintermark, M., Su, Z., Li, Y., Hu, J., Zhang, Y., Zhang, W., Zhu, G. 2015; 46 (4): 961-967

    Abstract

    The study aims to determine whether volume transfer constant (K(trans)) maps calculated from first-pass perfusion computed tomographic data are a biomarker of cerebral collateral circulation and predict the clinical outcome in acute ischemic stroke caused by proximal arterial occlusion.Consecutive patients with acute occlusion of the middle cerebral artery who received endovascular treatment were enrolled. Digital subtraction angiography, computed tomographic angiography with maximum intensity projection, and K(trans) maps were used to assess their collateral circulation. Agreement between different methods was evaluated using the χ(2) tests. The correlations of various radiological and clinical outcomes with the collateral flow score, as determined from K(trans) maps, were calculated.Seventy-five patients were included, comprising 39 women and 36 men, with a mean age of 65.3±14.6 years. Collateral flow score on K(trans) maps had the highest correlation with digital subtraction angiography (κ=0.8101; P=0.9796). Twenty-five patients had poor collateral circulation on K(trans) maps, 25 had intermediate collateral flow, 20 had good collateral flow, and 5 had excellent collateral flow. Better collateral circulation was associated with better clinical outcome (P<0.0001).K(trans) maps extracted from standard first-pass perfusion computed tomography are correlated with collateral circulation status after acute proximal arterial occlusion and predictive of outcome.

    View details for DOI 10.1161/STROKEAHA.114.008015

    View details for PubMedID 25669309

  • Stenting of symptomatic intracranial stenosis using balloon mounted coronary stents: a single center experience JOURNAL OF NEUROINTERVENTIONAL SURGERY Durst, C. R., Geraghty, S. R., Southerland, A. M., Starke, R. M., Rembold, K., Malik, S., Wintermark, M., Liu, K. C., Crowley, R. W., Gaughen, J., Jensen, M. E., Evans, A. J. 2015; 7 (4): 245-249

    Abstract

    Intracranial atherosclerotic disease is the cause of up to 10% of ischemic strokes and transient ischemic attacks. Intracranial stenting with off-label balloon mounted coronary stents (BMCS) may be a viable alternative for patients with symptomatic intracranial stenosis who fail best medical therapy.Between December 2005 and June 2012, 42 symptomatic intracranial stenoses were treated with a BMCS after failing medical management. Procedural records, clinical outcomes, and imaging follow-up were reviewed. Outcome measurements included technical success rate, morbidity and mortality, long term stent patency, and clinical outcomes, as measured by the modified Rankin Scale.The technical success rate was 98% (41 of 42 lesions). Morbidity within the first 30 days was 7.1% (three of 42 lesions). Overall morbidity, including both periprocedural and long term evaluation, was 9.5% (four of 42 lesions). There were no deaths. Follow-up imaging was available for 30 stents (71%) with an average follow-up time of 35.1 months. Restenosis (>50%) and retreatment were observed in 20% and 10% of cases, respectively. Clinical evaluation by a neurologist ≥ 30 days postprocedure was available in 40 of 42 cases (95%) with an average of 32.1 months. At presentation, 55% of patients had a modified Rankin Scale (mRS) score of ≤ 2. At follow-up, 74% of patients were found to have an mRS score of ≤ 2.This study suggests that BMCS may benefit patients with symptomatic intracranial stenosis who experience stroke or transient ischemic attack in spite of best medical therapy.

    View details for DOI 10.1136/neurintsurg-2014-011185

    View details for Web of Science ID 000351619400009

    View details for PubMedID 24646693

  • Optimal Symmetric Multimodal Templates and Concatenated Random Forests for Supervised Brain Tumor Segmentation (Simplified) with ANTsR NEUROINFORMATICS Tustison, N. J., Shrinidhi, K. L., Wintermark, M., Durst, C. R., Kandel, B. M., Gee, J. C., Grossman, M. C., Avants, B. B. 2015; 13 (2): 209-225

    Abstract

    Segmenting and quantifying gliomas from MRI is an important task for diagnosis, planning intervention, and for tracking tumor changes over time. However, this task is complicated by the lack of prior knowledge concerning tumor location, spatial extent, shape, possible displacement of normal tissue, and intensity signature. To accommodate such complications, we introduce a framework for supervised segmentation based on multiple modality intensity, geometry, and asymmetry feature sets. These features drive a supervised whole-brain and tumor segmentation approach based on random forest-derived probabilities. The asymmetry-related features (based on optimal symmetric multimodal templates) demonstrate excellent discriminative properties within this framework. We also gain performance by generating probability maps from random forest models and using these maps for a refining Markov random field regularized probabilistic segmentation. This strategy allows us to interface the supervised learning capabilities of the random forest model with regularized probabilistic segmentation using the recently developed ANTsR package--a comprehensive statistical and visualization interface between the popular Advanced Normalization Tools (ANTs) and the R statistical project. The reported algorithmic framework was the top-performing entry in the MICCAI 2013 Multimodal Brain Tumor Segmentation challenge. The challenge data were widely varying consisting of both high-grade and low-grade glioma tumor four-modality MRI from five different institutions. Average Dice overlap measures for the final algorithmic assessment were 0.87, 0.78, and 0.74 for "complete", "core", and "enhanced" tumor components, respectively.

    View details for DOI 10.1007/s12021-014-9245-2

    View details for Web of Science ID 000355263700008

    View details for PubMedID 25433513

  • Using Standard First-Pass Perfusion Computed Tomographic Data to Evaluate Collateral Flow in Acute Ischemic Stroke STROKE Chen, H., Wu, B., Liu, N., Wintermark, M., Su, Z., Li, Y., Hu, J., Zhang, Y., Zhang, W., Zhu, G. 2015; 46 (4): 961-?

    Abstract

    The study aims to determine whether volume transfer constant (K(trans)) maps calculated from first-pass perfusion computed tomographic data are a biomarker of cerebral collateral circulation and predict the clinical outcome in acute ischemic stroke caused by proximal arterial occlusion.Consecutive patients with acute occlusion of the middle cerebral artery who received endovascular treatment were enrolled. Digital subtraction angiography, computed tomographic angiography with maximum intensity projection, and K(trans) maps were used to assess their collateral circulation. Agreement between different methods was evaluated using the χ(2) tests. The correlations of various radiological and clinical outcomes with the collateral flow score, as determined from K(trans) maps, were calculated.Seventy-five patients were included, comprising 39 women and 36 men, with a mean age of 65.3±14.6 years. Collateral flow score on K(trans) maps had the highest correlation with digital subtraction angiography (κ=0.8101; P=0.9796). Twenty-five patients had poor collateral circulation on K(trans) maps, 25 had intermediate collateral flow, 20 had good collateral flow, and 5 had excellent collateral flow. Better collateral circulation was associated with better clinical outcome (P<0.0001).K(trans) maps extracted from standard first-pass perfusion computed tomography are correlated with collateral circulation status after acute proximal arterial occlusion and predictive of outcome.

    View details for DOI 10.1161/STROKEAHA.114.008015

    View details for Web of Science ID 000351669000021

    View details for PubMedID 25669309

  • Permeability Imaging as a Biomarker of Leptomeningeal Collateral Flow in Patients with Intracranial Arterial Stenosis CELL BIOCHEMISTRY AND BIOPHYSICS Chen, H., Wu, B., Zhu, G., Wintermark, M., Wu, X., Su, Z., Xu, X., Tian, C., Ma, L., Zhang, W., Lou, X. 2015; 71 (3): 1273-1279

    Abstract

    Different methods of angiography are of great clinical utility; however, it still remains unstandardized as which method would be suitable to determine cerebral collateral circulation. Here we compared digital subtraction angiography (DSA), computer tomography angiography (CTA) and dynamic contrast-enhanced T1-weighted imaging magnetic resonance imaging (MRI) findings in seven patients with severe intracranial arterial stenosis, and determine whether volume transfer constant (K(trans)) maps of permeability imaging could be used as the biomarkers of cerebral collateral circulation. We retrospectively reviewed seven adult patients with severe intracranial arterial stenosis or occlusion with a complete parenchymal and vascular imaging work-up. DSA, CTA source imaging (CTA-SI), arterial spin labeling (ASL), and K(trans) maps were used to assess their collateral flow. Cohen's Kappa coefficient was calculated to test the consistency of their collateral scores. A reasonable agreement was found between DSA and K(trans) maps (Kappa = 0.502, P < 0.001) when all 15 regional vascular sites were included, and a better agreement found after exclusion of perforating artery territories (N = 10 sites, Kappa = 0.766, P < 0.001). The agreement between CTA-SI and DSA was moderate on all 15 sites (Kappa = 0.413, P < 0.001) and 10 sites (Kappa = 0.329, P < 0.001). The agreement between ASL and DSA was least favorable, no matter for all 15 sites (Kappa = 0.270, P < 0.001) or 10 sites (Kappa = 0.205, P = 0.002). K(trans) maps are useful and promising for leptomeningeal collateral assessment, when compared to CTA-SI or ASL. Further studies are requited for verify its validity in a large registry of patients.

    View details for DOI 10.1007/s12013-014-0343-4

    View details for Web of Science ID 000355342900002

  • Traumatic Brain Injury Imaging Research Roadmap AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Coombs, L., Druzgal, T. J., Field, A. S., Filippi, C. G., Hicks, R., Horton, R., Lui, Y. W., Law, M., Mukherjee, P., Norbash, A., Riedy, G., Sanelli, P. C., Stone, J. R., Sze, G., Tilkin, M., Whitlow, C. T., Wilde, E. A., York, G., Provenzale, J. M. 2015; 36 (3): E12-E23

    Abstract

    The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic Disorders and Stroke, industry representatives, and other traumatic brain injury stakeholders to attempt to reach consensus on issues related to and develop consensus recommendations in terms of creating both a well-characterized normative data base of comprehensive imaging and ancillary data to serve as a reference for tools that will allow interpretation of advanced neuroimaging tests at an individual level of a patient with traumatic brain injury. The workshop involved discussions concerning the following: 1) designation of the policies and infrastructure needed for a normative data base, 2) principles for characterizing normal control subjects, and 3) standardizing research neuroimaging protocols for traumatic brain injury. The present article summarizes these recommendations and examines practical steps to achieve them.

    View details for DOI 10.3174/ajnr.A4254

    View details for Web of Science ID 000350990900001

    View details for PubMedID 25655872

  • Imaging selection for reperfusion therapy in acute ischemic stroke. Current treatment options in neurology Heit, J. J., Wintermark, M. 2015; 17 (2): 332-?

    Abstract

    Neuroimaging is essential in the evaluation of the acute stroke patient. Computed tomography (CT) or magnetic resonance imaging (MRI) should be used to confirm the diagnosis of acute stroke, exclude stroke mimics, and triage patients for intravenous tissue plasminogen activator and endovascular revascularization therapies. Advanced neuroimaging techniques, including CT-angiography, MR-angiography, CT-perfusion, and MR-perfusion should be used to further inform acute stroke treatment decisions. Patients considered for endovascular stroke therapy should have (1) a vascular occlusion that can be reached by an endovascular approach; (2) a small area of core cerebral infarction; and (3) viable tissue at risk of infarction if prompt revascularization is not achieved (penumbra).

    View details for DOI 10.1007/s11940-014-0332-3

    View details for PubMedID 25619536

  • Imaging selection for reperfusion therapy in acute ischemic stroke. Current treatment options in neurology Heit, J. J., Wintermark, M. 2015; 17 (2): 332-?

    View details for DOI 10.1007/s11940-014-0332-3

    View details for PubMedID 25619536

  • Association between internal carotid artery dissection and arterial tortuosity NEURORADIOLOGY Saba, L., Argiolas, G. M., Sumer, S., Siotto, P., Raz, E., Sanfilippo, R., Montisci, R., Piga, M., Wintermark, M. 2015; 57 (2): 149-153

    Abstract

    Carotid artery dissection is an important cause of ischemic stroke in all age groups, particularly in young patients. The purpose of this work was to assess whether there is an association between the presence of an internal carotid artery dissection (ICAD) and the arterial tortuosity.This study considered 124 patients (72 males and 52 females; median age 57 years) with CT/MR diagnosis of ICAD of the internal carotid artery were considered in this multi-centric retrospective study. The arterial tortuosity was evaluated and, when present, was categorized as elongation, kinking, or coiling. For each patient, both the right and left sides were considered for a total number of 248 arteries in order to have the same number of cases and controls. Fisher's exact test was applied to test the association between elongation, kinking, coiling, dissection, and the side affected by CAD.Fisher's exact test showed a statistically significant association between the ICAD and kinking (p = 0.0089) and coiling (p = 0.0251) whereas no statistically significant difference was found with arterial vessel elongation (p = 0.444). ICAD was more often seen on the left side compared to the right (p = 0.0001). These results were confirmed using both carotid arteries of the same patient as dependent parameter with p = 0.0012, 0.0129, and 0.3323 for kinking, coiling, and elongation, respectively.The presence of kinking and coiling is associated with ICAD.

    View details for DOI 10.1007/s00234-014-1436-x

    View details for Web of Science ID 000350369300003

    View details for PubMedID 25326167

  • Principles of T-2*- Weighted Dynamic Susceptibility Contrast MRI Technique in Brain Tumor Imaging JOURNAL OF MAGNETIC RESONANCE IMAGING Shiroishi, M. S., Castellazzi, G., Boxerman, J. L., d'Amore, F., Essig, M., Nguyen, T. B., Provenzale, J. M., Enterline, D. S., Anzalone, N., Doerfler, A., Rovira, A., Wintermark, M., Law, M. 2015; 41 (2): 296-313

    Abstract

    Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) is used to track the first pass of an exogenous, paramagnetic, nondiffusible contrast agent through brain tissue, and has emerged as a powerful tool in the characterization of brain tumor hemodynamics. DSC-MRI parameters can be helpful in many aspects, including tumor grading, prediction of treatment response, likelihood of malignant transformation, discrimination between tumor recurrence and radiation necrosis, and differentiation between true early progression and pseudoprogression. This review aims to provide a conceptual overview of the underlying principles of DSC-MRI of the brain for clinical neuroradiologists, scientists, or students wishing to improve their understanding of the technical aspects, pitfalls, and controversies of DSC perfusion MRI of the brain. Future consensus on image acquisition parameters and postprocessing of DSC-MRI will most likely allow this technique to be evaluated and used in high-quality multicenter studies and ultimately help guide clinical care.

    View details for DOI 10.1002/jmri.24648

    View details for Web of Science ID 000348850600004

    View details for PubMedID 24817252

  • DEFINING THE OPTIMAL AGE FOR FOCAL LESIONING IN A RAT MODEL OF TRANSCRANIAL HIFU ULTRASOUND IN MEDICINE AND BIOLOGY Zhang, Y., Aubry, J., Zhang, J., Wang, Y., Roy, J., Mata, J. F., Miller, W., Dumont, E., Xie, M., Lee, K., Zuo, Z., Wintermark, M. 2015; 41 (2): 449-455

    Abstract

    This study aimed at determining the optimal age group for high-intensity focused ultrasound (HIFU) experiments for producing lesions in rats. Younger rats have thinner skulls, allowing for the acoustic waves to propagate easily through the skull without causing burns of the skin and brain surface. Younger rats however, have a smaller brain that can make HIFU focusing in the brain parenchyma challenging because of the focus size. In this study, we conducted transcranial HIFU sonications in rat pups of different ages (from 9 to 43 d) with a 1.5MHz MR compatible transducer. The electric power was selected to always reach a target temperature of at least 50°C in the parenchyma. The thickness of the skull and of the brain parenchyma was measured using T2-weighted MR imaging. Results showed that the thickness of the brain parenchyma increased quickly from P9 to P12, reaching 8.5 mm at P16, and then increasing gradually along with age. The skull thickness increased gradually from P9 to P26, and then more quickly after P30. The ratio between brain parenchyma thickness and skull thickness decreased gradually with age. For the pups at 30 d, the temperature in the brain tissue adjacent to the skull increased to 48.9°C, and those from the rodents older than 33 d reached 60°C or higher, which can produce undesired irreversible damage in this location. We conclude that young rats aged 16-26 d are optimal for experiments producing transcranial HIFU lesions in rats with an intact skull.

    View details for DOI 10.1016/j.ultrasmedbio.2014.09.029

    View details for Web of Science ID 000347899300011

    View details for PubMedID 25542495

  • Imaging evidence and recommendations for traumatic brain injury: advanced neuro- and neurovascular imaging techniques. AJNR. American journal of neuroradiology Wintermark, M., Sanelli, P. C., Anzai, Y., Tsiouris, A. J., Whitlow, C. T. 2015; 36 (2): E1-E11

    Abstract

    Neuroimaging plays a critical role in the evaluation of patients with traumatic brain injury, with NCCT as the first-line of imaging for patients with traumatic brain injury and MR imaging being recommended in specific settings. Advanced neuroimaging techniques, including MR imaging DTI, blood oxygen level-dependent fMRI, MR spectroscopy, perfusion imaging, PET/SPECT, and magnetoencephalography, are of particular interest in identifying further injury in patients with traumatic brain injury when conventional NCCT and MR imaging findings are normal, as well as for prognostication in patients with persistent symptoms. These advanced neuroimaging techniques are currently under investigation in an attempt to optimize them and substantiate their clinical relevance in individual patients. However, the data currently available confine their use to the research arena for group comparisons, and there remains insufficient evidence at the time of this writing to conclude that these advanced techniques can be used for routine clinical use at the individual patient level. TBI imaging is a rapidly evolving field, and a number of the recommendations presented will be updated in the future to reflect the advances in medical knowledge.

    View details for DOI 10.3174/ajnr.A4181

    View details for PubMedID 25424870

  • Perfusion CT and acute stroke imaging: Foundations, applications, and literature review JOURNAL OF NEURORADIOLOGY Donahue, J., Wintermark, M. 2015; 42 (1): 21-29

    Abstract

    Multimodal CT features prominently in the rapidly evolving field of acute stroke triage, with perfusion CT applications at the forefront of many clinical research efforts. Perfusion CT offers a time sensitive and widely practicable assessment of cerebral hemodynamics and parenchymal viability that is key in acute stroke management. The following article reviews perfusion CT foundations and technical considerations while highlighting recent modality advances and frontline clinical applications. Ischemic penumbra and other prognostic imaging biomarkers are discussed in the context of results of recent clinical trials (MR-RESCUE, IMS III, Tenecteplase, etc.), with an emphasis on evidence based image guided stroke triage.

    View details for DOI 10.1016/j.neurad.2014.11.003

    View details for PubMedID 25636991

  • Imaging evidence and recommendations for traumatic brain injury: conventional neuroimaging techniques. Journal of the American College of Radiology Wintermark, M., Sanelli, P. C., Anzai, Y., Tsiouris, A. J., Whitlow, C. T. 2015; 12 (2): e1-e14

    Abstract

    Imaging plays an essential role in identifying intracranial injury in patients with traumatic brain injury (TBI). The goals of imaging include (1) detecting injuries that may require immediate surgical or procedural intervention, (2) detecting injuries that may benefit from early medical therapy or vigilant neurologic supervision, and (3) determining the prognosis of patients to tailor rehabilitative therapy or help with family counseling and discharge planning. In this article, the authors perform a review of the evidence on the utility of various imaging techniques in patients presenting with TBI to provide guidance for evidence-based, clinical imaging protocols. The intent of this article is to suggest practical imaging recommendations for patients presenting with TBI across different practice settings and to simultaneously provide the rationale and background evidence supporting their use. These recommendations should ultimately assist referring physicians faced with the task of ordering appropriate imaging tests in particular patients with TBI for whom they are providing care. These recommendations should also help radiologists advise their clinical colleagues on appropriate imaging utilization for patients with TBI.

    View details for DOI 10.1016/j.jacr.2014.10.014

    View details for PubMedID 25456317

  • Trends in Lumbar Puncture Over 2 Decades: A Dramatic Shift to Radiology AMERICAN JOURNAL OF ROENTGENOLOGY Kroll, H., Duszak, R., Nsiah, E., Hughes, D. R., Sumer, S., Wintermark, M. 2015; 204 (1): 15-19

    Abstract

    The purpose of this study is to evaluate national trends in lumbar puncture (LP) procedures and the relative roles of specialty groups providing this service.Aggregated claims data for LPs were extracted from Medicare Physician Supplier Procedure Summary master files annually from 1991 through 2011. LP procedure volumes by specialty group and place of service were studied.Between 1991 and 2011, the overall numbers of LP procedures increased, with a slight increase in diagnostic LP procedures (90,460 vs 90,785) and a marked increase in therapeutic LP procedures (2868 vs 6461) in Medicare fee-for-service beneficiaries. Although radiologists performed 11.3% (n = 10,533) of all LP procedures in 1991, they performed 46.6% (n = 45,338) in 2011. For diagnostic LPs, radiology (11.4% [n = 10,272] in 1991 and 48.0% [n = 43,601] in 2011) now exceeds emergency medicine, neurosciences, and all others as the dominant provider group. For therapeutic LP procedures, radiology now performs the second greatest number of LP procedures (9.0% [n = 261] in 1991 and 26.9% [n = 1737] in 2011). Although volumes remain small (< 10% of all procedures), midlevel practitioners have experienced over 100-fold growth for most services. The inpatient hospital setting remains the dominant site of service (71,385 in 1991 vs 44,817 in 2011: -37%), followed by procedures performed in the emergency department (297 in 1991 vs 26,117 in 2011: 8794%).Over the last 2 decades, LP procedures on Medicare beneficiaries have increased, with radiology now the dominant overall provider. Although this trend may have relatively negative financial implications for radiology practices in current fee-for-service payment models, it has the potential to cement radiology's more central position through direct involvement in patient care in emerging accountable care organizations.

    View details for DOI 10.2214/AJR.14.12622

    View details for Web of Science ID 000348562300025

    View details for PubMedID 25539231

  • Permeability Imaging as a Biomarker of Leptomeningeal Collateral Flow in Patients with Intracranial Arterial Stenosis. Cell biochemistry and biophysics Chen, H. n., Wu, B. n., Zhu, G. n., Wintermark, M. n., Wu, X. n., Su, Z. n., Xu, X. n., Tian, C. n., Ma, L. n., Zhang, W. n., Lou, X. n. 2015; 71 (3): 1273–79

    Abstract

    Different methods of angiography are of great clinical utility; however, it still remains unstandardized as which method would be suitable to determine cerebral collateral circulation. Here we compared digital subtraction angiography (DSA), computer tomography angiography (CTA) and dynamic contrast-enhanced T1-weighted imaging magnetic resonance imaging (MRI) findings in seven patients with severe intracranial arterial stenosis, and determine whether volume transfer constant (K(trans)) maps of permeability imaging could be used as the biomarkers of cerebral collateral circulation. We retrospectively reviewed seven adult patients with severe intracranial arterial stenosis or occlusion with a complete parenchymal and vascular imaging work-up. DSA, CTA source imaging (CTA-SI), arterial spin labeling (ASL), and K(trans) maps were used to assess their collateral flow. Cohen's Kappa coefficient was calculated to test the consistency of their collateral scores. A reasonable agreement was found between DSA and K(trans) maps (Kappa = 0.502, P < 0.001) when all 15 regional vascular sites were included, and a better agreement found after exclusion of perforating artery territories (N = 10 sites, Kappa = 0.766, P < 0.001). The agreement between CTA-SI and DSA was moderate on all 15 sites (Kappa = 0.413, P < 0.001) and 10 sites (Kappa = 0.329, P < 0.001). The agreement between ASL and DSA was least favorable, no matter for all 15 sites (Kappa = 0.270, P < 0.001) or 10 sites (Kappa = 0.205, P = 0.002). K(trans) maps are useful and promising for leptomeningeal collateral assessment, when compared to CTA-SI or ASL. Further studies are requited for verify its validity in a large registry of patients.

    View details for PubMedID 25504074

  • One-stop-shop stroke imaging with functional CT. European journal of radiology Tong, E. n., Komlosi, P. n., Wintermark, M. n. 2015; 84 (12): 2425–31

    Abstract

    Advanced imaging techniques have extended beyond traditional anatomic imaging and progressed to dynamic, physiologic and functional imaging. Neuroimaging is no longer a mere diagnostic tool. Multimodal functional CT, comprising of NCCT, PCT and CTA, provides a one-stop-shop for rapid stroke imaging. Integrating those imaging findings with pertinent clinical information can help guide subsequent treatment decisions, medical management and follow-up imaging selection. This review article will briefly discuss the indication and utility of each modality in acute stroke imaging.

    View details for PubMedID 25554006

  • Multiphase CT Angiography: A Poor Man's Perfusion CT? Radiology Aviv, R. I., Parsons, M. n., Bivard, A. n., Jahromi, B. n., Wintermark, M. n. 2015; 277 (3): 922–24

    View details for PubMedID 26599931

  • Feasibility and Safety of MR-Guided Focused Ultrasound Lesioning in the Setting of Deep Brain Stimulation STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Dallapiazza, R., Khaled, M., Eames, M., Snell, J., Lopes, M. B., Wintermark, M., Elias, W. J. 2015; 93 (2): 140-146

    View details for DOI 10.1159/000368908

    View details for Web of Science ID 000351486500010

  • Prediction of recanalization in acute stroke patients receiving intravenous and endovascular revascularization therapy INTERNATIONAL JOURNAL OF STROKE Zhu, G., Michel, P., Jovin, T., Patrie, J. T., Xin, W., Eskandari, A., Zhang, W., Wintermark, M. 2015; 10 (1): 28-36

    Abstract

    The study aims to assess the recanalization rate in acute ischemic stroke patients who received no revascularization therapy, intravenous thrombolysis, and endovascular treatment, respectively, and to identify best clinical and imaging predictors of recanalization in each treatment group.Clinical and imaging data were collected in 103 patients with acute ischemic stroke caused by anterior circulation arterial occlusion. We recorded demographics and vascular risk factors. We reviewed the noncontrast head computed tomographies to assess for hyperdense middle cerebral artery and its computed tomography density. We reviewed the computed tomography angiograms and the raw images to determine the site and degree of arterial occlusion, collateral score, clot burden score, and the density of the clot. Recanalization status was assessed on recanalization imaging using Thrombolysis in Myocardial Ischemia. Multivariate logistic regressions were utilized to determine the best predictors of outcome in each treatment group.Among the 103 study patients, 43 (42%) received intravenous thrombolysis, 34 (33%) received endovascular thrombolysis, and 26 (25%) did not receive any revascularization therapy. In the patients with intravenous thrombolysis or no revascularization therapy, recanalization of the vessel was more likely with intravenous thrombolysis (P = 0·046) and when M1/A1 was occluded (P = 0·001). In this subgroup of patients, clot burden score, cervical degree of stenosis (North American Symptomatic Carotid Endarterectomy Trial), and hyperlipidemia status added information to the aforementioned likelihood of recanalization at the patient level (P < 0·001). In patients with endovascular thrombolysis, recanalization of the vessel was more likely in the case of a higher computed tomography angiogram clot density (P = 0·012), and in this subgroup of patients gender added information to the likelihood of recanalization at the patient level (P = 0·044).The overall likelihood of recanalization was the highest in the endovascular group, and higher for intravenous thrombolysis compared with no revascularization therapy. However, our statistical models of recanalization for each individual patient indicate significant variability between treatment options, suggesting the need to include this prediction in the personalized treatment selection.

    View details for DOI 10.1111/ijs.12312

    View details for Web of Science ID 000346156500014

    View details for PubMedID 24975168

  • Evaluation of monoenergetic imaging to reduce metallic instrumentation artifacts in computed tomography of the cervical spine JOURNAL OF NEUROSURGERY-SPINE Komlosi, P., Grady, D., Smith, J. S., Shaffrey, C. I., Goode, A. R., Judy, P. G., Shaffrey, M., Wintermark, M. 2015; 22 (1): 34-38

    Abstract

    Monoenergetic imaging with dual-energy CT has been proposed to reduce metallic artifacts in comparison with conventional polychromatic CT. The purpose of this study is to systematically evaluate and define the optimal dual-energy CT imaging parameters for specific cervical spinal implant alloy compositions.Spinal fixation rods of cobalt-chromium or titanium alloy inserted into the cervical spine section of an Alderson Rando anthropomorphic phantom were imaged ex vivo with fast-kilovoltage switching CT at 80 and 140 peak kV. The collimation width and field of view were varied between 20 and 40 mm and medium to large, respectively. Extrapolated monoenergetic images were generated at 70, 90, 110, and 130 kiloelectron volts (keV). The standard deviation of voxel intensities along a circular line profile around the spine was used as an index of the magnitude of metallic artifact.The metallic artifact was more conspicuous around the fixation rods made of cobalt-chromium than those of titanium alloy. The magnitude of metallic artifact seen with titanium fixation rods was minimized at monoenergies of 90 keV and higher, using a collimation width of 20 mm and large field of view. The magnitude of metallic artifact with cobalt-chromium fixation rods was minimized at monoenergies of 110 keV and higher; collimation width or field of view had no effect.Optimization of acquisition settings used with monoenergetic CT studies might yield reduced metallic artifacts.

    View details for DOI 10.3171/2014.10.SPINE14463

    View details for Web of Science ID 000346817000005

    View details for PubMedID 25380537

  • Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke Results of the Vascular Effects of Infection in Pediatric Stroke Study STROKE Wintermark, M., Hills, N. K., deVeber, G. A., Barkovich, A. J., Elkind, M. S., Sear, K., Zhu, G., Leiva-Salinas, C., Hou, Q., Dowling, M. M., Bernard, T. J., Friedman, N. R., Ichord, R. N., Fullerton, H. J. 2014; 45 (12): 3597-?

    Abstract

    Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78).Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.114.007404

    View details for PubMedID 25388419

  • Carotid artery dissection on non-contrast CT: Does color improve the diagnostic confidence? EUROPEAN JOURNAL OF RADIOLOGY Saba, L., Argiolas, G. M., Raz, E., Sannia, S., Suri, J. S., Siotto, P., Sanfilippo, R., Montisci, R., Piga, M., Wintermark, M. 2014; 83 (12): 2288-2293

    Abstract

    The purpose of this work was to evaluate if the use of color maps, instead of conventional grayscale images, would improve the observer's diagnostic confidence in the non-contrast CT evaluation of internal carotid artery dissection (ICAD).One hundred patients (61 men, 39 women; mean age, 51 years; range, 25-78 years), 40 with and 60 without ICAD, underwent non-contrast CT and were included in this the retrospective study. In this study, three groups of patients were considered: patients with MR confirmation of ICAD, n=40; patients with MR confirmation of ICAD absence, n=20; patients who underwent CT of the carotid arteries because of atherosclerotic disease, n=40. Four blinded observers with different levels of expertise (expert, intermediate A, intermediate B and trainee) analyzed the non-contrast CT datasets using a cross model (one case grayscale and the following case using the color scale). The presence of ICAD was scored on a 5-point scale in order to assess the observer's diagnostic confidence. After 3 months the four observers evaluated the same datasets by using the same cross-model for the alternate readings (one case color scale and the following case using the grayscale). Statistical analysis included receiver operating characteristics (ROC) curve analysis, the Cohen weighted test and sensitivity, specificity, PPV, NPV, accuracy, LR+ and LR-.The ROC curve analysis showed that, for all observers, the use of color scale resulted in an improved diagnostic confidence with AUC values increasing from 0.896 to 0.936, 0.823 to 0.849, 0.84 to 0.909 and 0.749 to 0.861 for expert, intermediate A, intermediate B and trainee observers, respectively. The increase in diagnostic confidence (between the AUC areas) was statistically significant (p=0.036) for the trainee. Accuracy as well as sensitivity, specificity, PPV, NPV, LR+ and LR- were improved using the color scale.Our study suggests that the use of a color scale instead the conventional grayscale improves the diagnostic confidence, accuracy and inter-observer agreement of the readers, in particular of junior ones, in the diagnosis of ICAD on non-contrast CT.

    View details for DOI 10.1016/j.ejrad.2014.09.001

    View details for Web of Science ID 000344940600024

    View details for PubMedID 25306107

  • Dental Flat Panel Conebeam CT in the Evaluation of Patients with Inflammatory Sinonasal Disease: Diagnostic Efficacy and Radiation Dose Savings AMERICAN JOURNAL OF NEURORADIOLOGY Leiva-Salinas, C., Flors, L., Gras, P., Mas-Estelles, F., Lemercier, P., Patrie, J. T., Wintermark, M., Marti-Bonmati, L. 2014; 35 (11): 2052-2057

    Abstract

    CT is the imaging modality of choice to study the paranasal sinuses; unfortunately, it involves significant radiation dose. Our aim was to assess the diagnostic validity, image quality, and radiation-dose savings of dental conebeam CT in the evaluation of patients with suspected inflammatory disorders of the paranasal sinuses.We prospectively studied 40 patients with suspected inflammatory disorders of the sinuses with dental conebeam CT and standard CT. Two radiologists analyzed the images independently, blinded to clinical information. The image quality of both techniques and the diagnostic validity of dental conebeam CT compared with the reference standard CT were assessed by using 3 different scoring systems. Image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated for both techniques. The absorbed radiation dose to the lenses and thyroid and parotid glands was measured by using a phantom and dosimeter chips. The effective radiation dose for CT was calculated.All dental conebeam CT scans were judged of diagnostic quality. Compared with CT, the conebeam CT image noise was 37.3% higher (P < .001) and the SNR of the bone was 75% lower (P < .001). The effective dose of our conebeam CT protocol was 23 μSv. Compared with CT, the absorbed radiation dose to the lenses and parotid and thyroid glands with conebeam CT was 4%, 7.8%, and 7.3% of the dose delivered to the same organs by conventional CT (P < .001).Dental conebeam CT is a valid imaging procedure for the evaluation of patients with inflammatory sinonasal disorders.

    View details for DOI 10.3174/ajnr.A4019

    View details for Web of Science ID 000345197700006

    View details for PubMedID 24970545

  • CTA-enhanced perfusion CT: an original method to perform ultra-low-dose CTA-enhanced perfusion CT NEURORADIOLOGY Tong, E., Wintermark, M. 2014; 56 (11): 955-964

    Abstract

    Utilizing CT angiography enhances image quality in PCT, thereby permitting acquisition at ultra-low dose.Dynamic CT acquisitions were obtained at 80 kVp with decreasing tube current-time product [milliamperes × seconds (mAs)] in patients suspected of ischemic stroke, with concurrent CTA of the cervical and intracranial arteries. By utilizing fast Fourier transformation, high spatial frequencies of CTA were combined with low spatial frequencies of PCT to create a virtual PCT dataset. The real and virtual PCT datasets with decreasing mAs were compared by assessing contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and noise and PCT values and by visual inspection of PCT parametric maps.Virtual PCT attained CNR and SNR three- to sevenfold superior to real PCT and noise reduction by a factor of 4-6 (p < 0.05). At 20 mAs, virtual PCT achieved diagnostic parametric maps, while the quality of real PCT maps was inadequate. At 10 mAs, both real and virtual PCT maps were nondiagnostic. Virtual PCT (but not real PCT) maps regained diagnostic quality at 10 mAs by applying 40 % adaptive statistical iterative reconstruction (ASIR) and improved further with 80 % ASIR.Our new method of creating virtual PCT by combining ultra-low-dose PCT with CTA information yields diagnostic perfusion parametric maps from PCT acquired at 20 or 10 mAs with 80 % ASIR. Effective dose is approximately 0.20 mSv, equivalent to two chest radiographs.

    View details for DOI 10.1007/s00234-014-1416-1

    View details for Web of Science ID 000344345800005

    View details for PubMedID 25085013

  • Acute imaging does not improve ASTRAL score's accuracy despite having a prognostic value INTERNATIONAL JOURNAL OF STROKE Ntaios, G., Papavasileiou, V., Faouzi, M., Vanacker, P., Wintermark, M., Michel, P. 2014; 9 (7): 926-931

    Abstract

    The ASTRAL score was recently shown to reliably predict three-month functional outcome in patients with acute ischemic stroke.The study aims to investigate whether information from multimodal imaging increases ASTRAL score's accuracy.All patients registered in the ASTRAL registry until March 2011 were included. In multivariate logistic-regression analyses, we added covariates derived from parenchymal, vascular, and perfusion imaging to the 6-parameter model of the ASTRAL score. If a specific imaging covariate remained an independent predictor of three-month modified Rankin score>2, the area-under-the-curve (AUC) of this new model was calculated and compared with ASTRAL score's AUC. We also performed similar logistic regression analyses in arbitrarily chosen patient subgroups.When added to the ASTRAL score, the following covariates on admission computed tomography/magnetic resonance imaging-based multimodal imaging were not significant predictors of outcome: any stroke-related acute lesion, any nonstroke-related lesions, chronic/subacute stroke, leukoaraiosis, significant arterial pathology in ischemic territory on computed tomography angiography/magnetic resonance angiography/Doppler, significant intracranial arterial pathology in ischemic territory, and focal hypoperfusion on perfusion-computed tomography. The Alberta Stroke Program Early CT score on plain imaging and any significant extracranial arterial pathology on computed tomography angiography/magnetic resonance angiography/Doppler were independent predictors of outcome (odds ratio: 0·93, 95% CI: 0·87-0·99 and odds ratio: 1·49, 95% CI: 1·08-2·05, respectively) but did not increase ASTRAL score's AUC (0·849 vs. 0·850, and 0·8563 vs. 0·8564, respectively). In exploratory analyses in subgroups of different prognosis, age or stroke severity, no covariate was found to increase ASTRAL score's AUC, either.The addition of information derived from multimodal imaging does not increase ASTRAL score's accuracy to predict functional outcome despite having an independent prognostic value. More selected radiological parameters applied in specific subgroups of stroke patients may add prognostic value of multimodal imaging.

    View details for DOI 10.1111/ijs.12304

    View details for Web of Science ID 000342581900024

    View details for PubMedID 24894405

  • Assessment of collateral flow in patients with cerebrovascular disorders JOURNAL OF NEURORADIOLOGY Donahue, J., Sumer, S., Wintermark, M. 2014; 41 (4): 234-242

    Abstract

    The ability to maintain cerebral parenchymal perfusion during states of acute or chronic ischemic insult depends largely on the capacity of the cerebral collateral circulation. Perfusion techniques, including perfusion-CT and arterial spin labeling, may not only describe the overall status of the collateral network, but can also quantify the pathophysiologic collateral reserve, which is occult to conventional imaging techniques. The following review details advanced imaging modalities capable of resolving pathophysiologic collateral circulation in a functional and dynamic manner, with regards to the evaluation of both acute ischemic penumbra and chronic cerebral vascular reserve. Specifically, the applications of perfusion-CT, arterial spin labeling MRI techniques, and transcranial Doppler are reviewed in the context of collateral circulation with emphasis on perfusion techniques and proposed clinical utility.

    View details for DOI 10.1016/j.neurad.2013.11.002

    View details for Web of Science ID 000342728000004

    View details for PubMedID 24388564

  • Effect of neoadjuvant temozolomide upon volume reduction and resection of diffuse low-grade glioma JOURNAL OF NEURO-ONCOLOGY Jo, J., Williams, B., Smolkin, M., Wintermark, M., Shaffrey, M. E., Lopes, M. B., Schiff, D. 2014; 120 (1): 155-161

    Abstract

    Maximal safe resection is associated with prolonged survival in patients with low-grade glioma (LGG). It has been suggested that neoadjuvant temozolomide may provide sufficient tumor shrinkage to facilitate aggressive surgical debulking. We examined the impact of temozolomide upon volume reduction and resectability of LGG. We retrospectively identified 20 adult patients with biopsy-proven, deemed not totally resectable LGGs, treated initially with temozolomide. Volumetric 3D (calculated from serial FLAIR images) and 2D tumor measurements were obtained prior to treatment and at 3 months post-treatment. The anticipated extent of resection (EOR) at the 2 time points was measured based on anatomical limitations, calculated as: [(total tumor volume - unresectable tumor volume)/total tumor volume] ×100. Eloquent cortex, deep structures and corpus callosum were considered unresectable. Mean tumor volume was 68.4 cm(3) pre-treatment and 49.5 cm(3) at 3 months post-treatment. The mean change from baseline to 3 months after treatment was -32.5 % (p < 0.001). Mean 2D pre-treatment area was 28.6 and 23.3 cm(2) at 3 months post-treatment. The 2D change was also significant, with mean change of -17% (p < 0.001). 5% had partial response; 40% minor response; 45% stable disease; and 10% progressive disease by RANO criteria. Mean pre-treatment anticipated EOR was 67.2 and 71.5% at 3 months post-treatment. The mean change from baseline was 4.3% (p = 0.10). Our findings demonstrate significant volumetric and 2D reduction of LGG with temozolomide. Although this tumor shrinkage might facilitate radical surgical resection in some cases, our data failed to show statistically significant improvement in anticipated EOR.

    View details for DOI 10.1007/s11060-014-1538-7

    View details for Web of Science ID 000342456600018

    View details for PubMedID 25038848

  • Dynamic CT for Parathyroid Disease: Are Multiple Phases Necessary? AMERICAN JOURNAL OF NEURORADIOLOGY Raghavan, P., Durst, C. R., Ornan, D. A., Mukherjee, S., Wintermark, M., Patrie, J. T., Xin, W., Shada, A. L., Hanks, J. B., Smith, P. W. 2014; 35 (10): 1959-1964

    Abstract

    A 4D CT protocol for detection of parathyroid lesions involves obtaining unenhanced, arterial, early, and delayed venous phase images. The aim of the study was to determine the ideal combination of phases that would minimize radiation dose without sacrificing diagnostic accuracy.With institutional review board approval, the records of 29 patients with primary hyperparathyroidism who had undergone surgical exploration were reviewed. Four neuroradiologists who were blinded to the surgical outcome reviewed the imaging studies in 5 combinations (unenhanced and arterial phase; unenhanced, arterial, and early venous; all 4 phases; arterial alone; arterial and early venous phases) with an interval of at least 7 days between each review. The accuracy of interpretation in lateralizing an abnormality to the side of the neck (right, left, ectopic) and localizing it to a quadrant in the neck (right or left upper, right or left lower) was evaluated.The lateralization and localization accuracy (90.5% and 91.5%, respectively) of the arterial phase alone was comparable with the other combinations of phases. There was no statistically significant difference among the different combinations of phases in their ability to lateralize or localize adenomas to a quadrant (P = .976 and .996, respectively).Assessment of a small group of patients shows that adequate diagnostic accuracy for parathyroid adenoma localization may be achievable by obtaining arterial phase images alone. If this outcome can be validated prospectively in a larger group of patients, then the radiation dose can potentially be reduced to one-fourth of what would otherwise be administered.

    View details for DOI 10.3174/ajnr.A3978

    View details for Web of Science ID 000342885700020

    View details for PubMedID 24904051

  • Correlation of diffusion tensor tractography and intraoperative macrostimulation during deep brain stimulation for Parkinson disease JOURNAL OF NEUROSURGERY Said, N., Elias, W. J., Raghavan, P., Cupino, A., Tustison, N., Frysinger, R., Patrie, J., Xin, W., Wintermark, M. 2014; 121 (4): 929-935

    Abstract

    The purpose of this study was to investigate whether diffusion tensor imaging (DTI) of the corticospinal tract (CST) is a reliable surrogate for intraoperative macrostimulation through the deep brain stimulation (DBS) leads. The authors hypothesized that the distance on MRI from the DBS lead to the CST as determined by DTI would correlate with intraoperative motor thresholds from macrostimulations through the same DBS lead.The authors retrospectively reviewed pre- and postoperative MRI studies and intraoperative macrostimulation recordings in 17 patients with Parkinson disease (PD) treated by DBS stimulation. Preoperative DTI tractography of the CST was coregistered with postoperative MRI studies showing the position of the DBS leads. The shortest distance and the angle from each contact of each DBS lead to the CST was automatically calculated using software-based analysis. The distance measurements calculated for each contact were evaluated with respect to the intraoperative voltage thresholds that elicited a motor response at each contact.There was a nonsignificant trend for voltage thresholds to increase when the distances between the DBS leads and the CST increased. There was a significant correlation between the angle and the voltage, but the correlation was weak (coefficient of correlation [R] = 0.36).Caution needs to be exercised when using DTI tractography information to guide DBS lead placement in patients with PD. Further studies are needed to compare DTI tractography measurements with other approaches such as microelectrode recordings and conventional intraoperative MRI-guided placement of DBS leads.

    View details for DOI 10.3171/2014.6.JNS131673

    View details for Web of Science ID 000342973300025

    View details for PubMedID 25061862

  • Demographic and Clinical Predictors of Leptomeningeal Collaterals in Stroke Patients JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Malik, N., Hou, Q., Vagal, A., Patrie, J., Xin, W., Michel, P., Eskandari, A., Jovin, T., Wintermark, M. 2014; 23 (8): 2018-2022

    Abstract

    Leptomeningeal collaterals improve outcome after stroke, including reduction of hemorrhagic complications after thrombolytic or endovascular therapy, smaller infarct size, and reduction in symptoms at follow-up evaluation. The purpose of this study was to determine the demographic and clinical variables that are associated with a greater degree of cerebral collaterals.Clinical data of patients presenting with M1 occlusions of the middle cerebral artery (MCA) and associated computed tomography angiography studies after admission from 3 separate institutions were retrospectively compiled (n = 82). Occluded hemispheres were evaluated against the intact hemisphere for degree of collateralization in the MCA territory. Regression analysis of variance was conducted between clinical variables and collateral score to determine which variables associate with greater collateral development.Smaller infarct size corresponded to greater collateral scores, whereas older age and statin use corresponded to lower collateral scores (P < .001).Cerebral collateralization is influenced by age and statin use and influences infarct size.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2014.02.018

    View details for Web of Science ID 000341484900014

    View details for PubMedID 25088172

  • Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor RADIOLOGY Jain, R., Poisson, L. M., Gutman, D., Scarpace, L., Hwang, S. N., Holder, C. A., Wintermark, M., Rao, A., Colen, R. R., Kirby, J., Freymann, J., Jaffe, C. C., Mikkelsen, T., Flanders, A. 2014; 272 (2): 484-493

    Abstract

    Purpose To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. Materials and Methods An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Results Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). Conclusion Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features. © RSNA, 2014 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.14131691

    View details for Web of Science ID 000340035100018

    View details for PubMedID 24646147

  • Intravoxel incoherent motion perfusion imaging in acute stroke: initial clinical experience NEURORADIOLOGY Federau, C., Sumer, S., Becce, F., Maeder, P., O'Brien, K., Meuli, R., Wintermark, M. 2014; 56 (8): 629-635

    Abstract

    Intravoxel incoherent motion (IVIM) imaging is an MRI perfusion technique that uses a diffusion-weighted sequence with multiple b values and a bi-compartmental signal model to measure the so-called pseudo-diffusion of blood caused by its passage through the microvascular network. The goal of the current study was to assess the feasibility of IVIM perfusion fraction imaging in patients with acute stroke.Images were collected in 17 patients with acute stroke. Exclusion criteria were onset of symptoms to imaging >5 days, hemorrhagic transformation, infratentorial lesions, small lesions <0.5 cm in minimal diameter and hemodynamic instability. IVIM imaging was performed at 3 T, using a standard spin-echo Stejskal-Tanner pulsed gradients diffusion-weighted sequence, using 16 b values from 0 to 900 s/mm(2). Image quality was assessed by two radiologists, and quantitative analysis was performed in regions of interest placed in the stroke area, defined by thresholding the apparent diffusion coefficient maps, as well as in the contralateral region.IVIM perfusion fraction maps showed an area of decreased perfusion fraction f in the region of decreased apparent diffusion coefficient. Quantitative analysis showed a statistically significant decrease in both IVIM perfusion fraction f (0.026 ± 0.019 vs. 0.056 ± 0.025, p=2.2 · 10(-6)) and diffusion coefficient D compared with the contralateral side (3.9 ± 0.79 · 10(-4) vs. 7.5 ± 0.86 · 10(-4) mm(2)/s, p=1.3 · 10(-20)).IVIM perfusion fraction imaging is feasible in acute stroke. IVIM perfusion fraction is significantly reduced in the visible infarct. Further studies should evaluate the potential for IVIM to predict clinical outcome and treatment response.

    View details for DOI 10.1007/s00234-014-1370-y

    View details for Web of Science ID 000340479900003

    View details for PubMedID 24838807

  • T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound PHYSICS IN MEDICINE AND BIOLOGY Wintermark, M., Tustison, N. J., Elias, W. J., Patrie, J. T., Xin, W., Demartini, N., Eames, M., Sumer, S., Lau, B., Cupino, A., Snell, J., Hananel, A., Kassell, N., Aubry, J. 2014; 59 (13): 3599-3614

    Abstract

    Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE), proton density weighted 3D sampling perfection with applications optimized contrasts using different flip angle evolution and 3D true fast imaging with steady state precision T2-weighted imaging) on patients who have already had a CT scan performed. We made detailed measurements of the calvarial structure based on the MRI data and compared those so-called 'virtual CT' to detailed measurements of the calvarial structure based on the CT data, used as a reference standard. We then loaded both standard and virtual CT in a TcMRgFUS device and compared the calculated phase correction values, as well as the temperature elevation in a phantom. A series of Bland-Altman measurement agreement analyses showed T1 3D VIBE as the optimal MRI sequence, with respect to minimizing the measurement discrepancy between the MRI derived total skull thickness measurement and the CT derived total skull thickness measurement (mean measurement discrepancy: 0.025; 95% CL (-0.22-0.27); p = 0.825). The T1-weighted sequence was also optimal in estimating skull CT density and skull layer thickness. The mean difference between the phase shifts calculated with the standard CT and the virtual CT reconstructed from the T1 dataset was 0.08 ± 1.2 rad on patients and 0.1 ± 0.9 rad on phantom. Compared to the real CT, the MR-based correction showed a 1 °C drop on the maximum temperature elevation in the phantom (7% relative drop). Without any correction, the maximum temperature was down 6 °C (43% relative drop). We have developed an approach that allows for a reconstruction of a virtual CT dataset from MRI to perform phase correction in TcMRgFUS.

    View details for DOI 10.1088/0031-9155/59/13/3599

    View details for Web of Science ID 000338424800024

    View details for PubMedID 24909357

  • Thalamic Connectivity in Patients with Essential Tremor Treated with MR Imaging-guided Focused Ultrasound: In Vivo Fiber Tracking by Using Diffusion-Tensor MR Imaging RADIOLOGY Wintermark, M., Huss, D. S., Shah, B. B., Tustison, N., Druzgal, T. J., Kassell, N., Elias, W. J. 2014; 272 (1): 202-209

    Abstract

    To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement.With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. DT MR imaging studies at 3.0 T were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation.Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the centrum semiovale, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001).DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor.

    View details for DOI 10.1148/radiol.14132112

    View details for Web of Science ID 000340034300021

    View details for PubMedID 24620914

  • Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and metabolic dysfunction: a TCGA glioma phenotype research group project BMC MEDICAL GENOMICS Colen, R. R., Vangel, M., Wang, J., Gutman, D. A., Hwang, S. N., Wintermark, M., Jain, R., Jilwan-Nicolas, M., Chen, J. Y., Raghavan, P., Holder, C. A., Rubin, D., Huang, E., Kirby, J., Freymann, J., Jaffe, C. C., Flanders, A., Zinn, P. O. 2014; 7

    Abstract

    Invasion of tumor cells into adjacent brain parenchyma is a major cause of treatment failure in glioblastoma. Furthermore, invasive tumors are shown to have a different genomic composition and metabolic abnormalities that allow for a more aggressive GBM phenotype and resistance to therapy. We thus seek to identify those genomic abnormalities associated with a highly aggressive and invasive GBM imaging-phenotype.We retrospectively identified 104 treatment-naïve glioblastoma patients from The Cancer Genome Atlas (TCGA) whom had gene expression profiles and corresponding MR imaging available in The Cancer Imaging Archive (TCIA). The standardized VASARI feature-set criteria were used for the qualitative visual assessments of invasion. Patients were assigned to classes based on the presence (Class A) or absence (Class B) of statistically significant invasion parameters to create an invasive imaging signature; imaging genomic analysis was subsequently performed using GenePattern Comparative Marker Selection module (Broad Institute).Our results show that patients with a combination of deep white matter tracts and ependymal invasion (Class A) on imaging had a significant decrease in overall survival as compared to patients with absence of such invasive imaging features (Class B) (8.7 versus 18.6 months, p < 0.001). Mitochondrial dysfunction was the top canonical pathway associated with Class A gene expression signature. The MYC oncogene was predicted to be the top activation regulator in Class A.We demonstrate that MRI biomarker signatures can identify distinct GBM phenotypes associated with highly significant survival differences and specific molecular pathways. This study identifies mitochondrial dysfunction as the top canonical pathway in a very aggressive GBM phenotype. Thus, imaging-genomic analyses may prove invaluable in detecting novel targetable genomic pathways.

    View details for DOI 10.1186/1755-8794-7-30

    View details for Web of Science ID 000338464600001

    View details for PubMedCentralID PMC4057583

  • Application of diffusion-weighted magnetic resonance imaging to predict the intracranial metastatic tumor response to gamma knife radiosurgery JOURNAL OF NEURO-ONCOLOGY Lee, C., Wintermark, M., Xu, Z., Yen, C., Schlesinger, D., Sheehan, J. P. 2014; 118 (2): 351-361

    Abstract

    To evaluate the effect of stereotactic radiosurgery (SRS) on intracranial metastases with diffusion-weighted imaging/apparent diffusion coefficient maps. A total of 107 patients with 144 metastases larger than 1 cm in diameter were retrospectively reviewed. We calculated the DWI(Tumor/white matter) ratios (DWI(T/WM) ratio) between the metastases and the normal, contralateral frontal white matter at each time point. We also recorded the ADC values for metastases (ADCT values). The DWI(T/WM) ratio and ADCT values were assessed for correlation with the patients' tumor response, brain edema, and survival. A decrease in DWI(T/WM) ratios was seen in the controlled metastases, and an increase in the DWI(T/WM) ratio were seen in the metastases with poor tumor control. On the other hand, an increase in ADCT values was seen in the controlled metastases, and a decrease in ADCT values was seen in the metastases with poor control. The differences were significant (p value: 0.001 and 0.002, respectively). Sensitivity of a decrease in the DWI(T/WM) ratio to make an early prediction of tumor control was 83.9%, and specificity was 88.5%. When using the initial ADCT values of metastases to predict tumor response, sensitivity and specificity were 85.5 and 72.7%, respectively. DWI/ADC is a practical method for studying the efficacy of SRS and predicting early metastases response progression. A decrease signal on DWI and increased ADC values are indicators of good tumor control, and reflect the beneficial effect of SRS.

    View details for DOI 10.1007/s11060-014-1439-9

    View details for Web of Science ID 000337024300016

    View details for PubMedID 24760414

  • Imaging of the Carotid Artery Vulnerable Plaque CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY Saba, L., Anzidei, M., Marincola, B. C., Piga, M., Raz, E., Bassareo, P. P., Napoli, A., Mannelli, L., Catalano, C., Wintermark, M. 2014; 37 (3): 572-585

    Abstract

    Atherosclerosis involving the carotid arteries has a high prevalence in the population worldwide. This condition is significant because accidents of the carotid artery plaque are associated with the development of cerebrovascular events. For this reason, carotid atherosclerotic disease needs to be diagnosed and those determinants that are associated to an increased risk of stroke need to be identified. The degree of stenosis typically has been considered the parameter of choice to determine the therapeutical approach, but several recently published investigations have demonstrated that the degree of luminal stenosis is only an indirect indicator of the atherosclerotic process and that direct assessment of the plaque structure and composition may be key to predict the development of future cerebrovascular ischemic events. The concept of "vulnerable plaque" was born, referring to those plaque's parameters that concur to the instability of the plaque making it more prone to the rupture and distal embolization. The purpose of this review is to describe the imaging characteristics of "vulnerable carotid plaques."

    View details for DOI 10.1007/s00270-013-0711-2

    View details for Web of Science ID 000336331300002

    View details for PubMedID 23912494

  • Optimal Perfusion Computed Tomographic Thresholds for Ischemic Core and Penumbra Are Not Time Dependent in the Clinically Relevant Time Window STROKE Qiao, Y., Zhu, G., Patrie, J., Xin, W., Michel, P., Eskandari, A., Jovin, T., Wintermark, M. 2014; 45 (5): 1355-1362

    Abstract

    This study aims to determine whether perfusion computed tomographic (PCT) thresholds for delineating the ischemic core and penumbra are time dependent or time independent in patients presenting with symptoms of acute stroke.Two hundred seventeen patients were evaluated in a retrospective, multicenter study. Patients were divided into those with either persistent occlusion or recanalization. All patients received admission PCT and follow-up imaging to determine the final ischemic core, which was then retrospectively matched to the PCT images to identify optimal thresholds for the different PCT parameters. These thresholds were assessed for significant variation over time since symptom onset.In the persistent occlusion group, optimal PCT parameters that did not significantly change with time included absolute mean transit time, relative mean transit time, relative cerebral blood flow, and relative cerebral blood volume when time was restricted to 15 hours after symptom onset. Conversely, the recanalization group showed no significant time variation for any PCT parameter at any time interval. In the persistent occlusion group, the optimal threshold to delineate the total ischemic area was the relative mean transit time at a threshold of 180%. In patients with recanalization, the optimal parameter to predict the ischemic core was relative cerebral blood volume at a threshold of 66%.Time does not influence the optimal PCT thresholds to delineate the ischemic core and penumbra in the first 15 hours after symptom onset for relative mean transit time and relative cerebral blood volume, the optimal parameters to delineate ischemic core and penumbra.

    View details for DOI 10.1161/STROKEAHA.113.003362

    View details for Web of Science ID 000335578100039

    View details for PubMedID 24627117

  • Imaging Findings in MR Imaging-Guided Focused Ultrasound Treatment for Patients with Essential Tremor AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Druzgal, J., HUSS, D. S., Khaled, M. A., Monteith, S., Raghavan, P., Huerta, T., Schweickert, L. C., Burkholder, B., Loomba, J. J., Zadicario, E., Qiao, Y., Shah, B., Snell, J., Eames, M., Frysinger, R., Kassell, N., Elias, W. J. 2014; 35 (5): 891-896

    Abstract

    MR imaging-guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging-guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging-guided focused sonography.Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging-guided focused sonography. MR imaging studies were obtained on a 3T scanner before the procedure and 24 hours, 1 week, 1 month, and 3 months following the procedure.On T2-weighted imaging, 3 time-dependent concentric zones were seen at the site of the focal spot. The inner 2 zones showed reduced ADC values at 24 hours in all patients except one. Diffusion had pseudonormalized by 1 month in all patients, when the cavity collapsed. Very mild postcontrast enhancement was seen at 24 hours and again at 1 month after MR imaging-guided focused sonography. The total lesion size and clinical response evolved inversely compared with each other (coefficient of correlation = 0.29, P value = .02).MR imaging-guided focused sonography can accurately ablate a precisely delineated target, with typical imaging findings seen in the days, weeks, and months following the treatment. Tremor control was optimal early when the lesion size and perilesional edema were maximal and was less later when the perilesional edema had resolved.

    View details for DOI 10.3174/ajnr.A3808

    View details for Web of Science ID 000337308700015

    View details for PubMedID 24371027

  • Recommendations for the Management of Cerebral and Cerebellar Infarction With Swelling A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Wijdicks, E. F., Sheth, K. N., Carter, B. S., Greer, D. M., Kasner, S. E., Kimberly, W. T., Schwab, S., Smith, E. E., Tamargo, R. J., Wintermark, M. 2014; 45 (4): 1222-1238

    Abstract

    There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere.The writing group used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review.Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may include early loss of corneal reflexes and the development of miosis. Standardized definitions should be established to facilitate multicenter and population-based studies of incidence, prevalence, risk factors, and outcomes. Identification of patients at high risk for brain swelling should include clinical and neuroimaging data. If a full resuscitative status is warranted in a patient with a large territorial stroke, admission to a unit with neurological monitoring capabilities is needed. These patients are best admitted to intensive care or stroke units attended by skilled and experienced physicians such as neurointensivists or vascular neurologists. Complex medical care includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but decompressive craniectomy with dural expansion should be considered in patients who continue to deteriorate neurologically. There is uncertainty about the efficacy of decompressive craniectomy in patients ≥60 years of age. In swollen cerebellar stroke, suboccipital craniectomy with dural expansion should be performed in patients who deteriorate neurologically. Ventriculostomy to relieve obstructive hydrocephalus after a cerebellar infarct should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement. In swollen hemispheric supratentorial infarcts, outcome can be satisfactory, but one should anticipate that one third of patients will be severely disabled and fully dependent on care even after decompressive craniectomy. Surgery after a cerebellar infarct leads to acceptable functional outcome in most patients.Swollen cerebral and cerebellar infarcts are critical conditions that warrant immediate, specialized neurointensive care and often neurosurgical intervention. Decompressive craniectomy is a necessary option in many patients. Selected patients may benefit greatly from such an approach, and although disabled, they may be functionally independent.

    View details for DOI 10.1161/01.str.0000441965.15164.d6

    View details for Web of Science ID 000333303400062

    View details for PubMedID 24481970

  • Validation of FDG Uptake in the Arterial Wall as an Imaging Biomarker of Atherosclerotic Plaques with F-18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG-PET/CT) JOURNAL OF NEUROIMAGING Bucci, M., Aparici, C. M., Hawkins, R., Bacharach, S., Schrek, C., Cheng, S., Tong, E., Arora, S., Parati, E., Wintermark, M. 2014; 24 (2): 117-123

    Abstract

    From the literature, the prevalence of fluorodeoxyglucose (FDG) uptake in large artery atherosclerotic plaques shows great heterogeneity. We retrospectively reviewed 100 consecutive patients who underwent FDG-positron emission tomography-computed tomography (PET/CT) imaging of their whole body, to evaluate FDG uptake in the arterial wall.We retrospectively evaluated 100 whole-body PET-CT scans. The PET images coregistered with CT were reviewed for abnormal 18F-FDG uptake. The mean standard uptake value (SUV) was measured in regions of interest (ROIs). The prevalence of PET+ plaques was determined based on the qualitative PET review, used as the gold standard in a receiver-operating characteristic (ROC) curve analysis to determine an optimal threshold for the quantitative PET analysis.The qualitative, visual assessment demonstrated FDG uptake in the arterial walls of 26 patients. A total of 85 slices exhibited FDG uptake within the arterial wall of 37 artery locations. 11, 17, and 2 patients exhibited FDG uptake within the wall of carotid arteries, of the aorta, and of the iliac arteries, respectively. Only 4 of the 26 patients had positive FDG uptake in more than one artery location. In terms of quantitative analysis, a threshold of 2.8 SUV was associated with a negative predictive value of 99.4% and a positive predictive value of 100% to predict qualitative PET+ plaques. A threshold of 1.8 SUV was associated with a negative predictive value of 100% and a positive predictive value of 99.4%. Area under the ROC curve was .839.The prevalence of PET uptake in arterial walls in a consecutive population of asymptomatic patients is low and usually confined to one type of artery, and its clinical relevance in terms of vulnerability to ischemic events remains to be determined.

    View details for DOI 10.1111/j.1552-6569.2012.00740.x

    View details for Web of Science ID 000332095700003

    View details for PubMedID 22928741

  • Adaptive statistical iterative reconstruction reduces patient radiation dose in neuroradiology CT studies NEURORADIOLOGY Komlosi, P., Zhang, Y., Leiva-Salinas, C., Ornan, D., Patrie, J. T., Xin, W., Grady, D., Wintermark, M. 2014; 56 (3): 187-193

    Abstract

    Adaptive statistical iterative reconstruction (ASIR) can decrease image noise, thereby generating CT images of comparable diagnostic quality with less radiation. The purpose of this study is to quantify the effect of systematic use of ASIR versus filtered back projection (FBP) for neuroradiology CT protocols on patients' radiation dose and image quality.We evaluated the effect of ASIR on six types of neuroradiologic CT studies: adult and pediatric unenhanced head CT, adult cervical spine CT, adult cervical and intracranial CT angiography, adult soft tissue neck CT with contrast, and adult lumbar spine CT. For each type of CT study, two groups of 100 consecutive studies were retrospectively reviewed: 100 studies performed with FBP and 100 studies performed with ASIR/FBP blending factor of 40 %/60 % with appropriate noise indices. The weighted volume CT dose index (CTDIvol), dose-length product (DLP) and noise were recorded. Each study was also reviewed for image quality by two reviewers. Continuous and categorical variables were compared by t test and free permutation test, respectively.For adult unenhanced brain CT, CT cervical myelography, cervical and intracranial CT angiography and lumbar spine CT both CTDIvol and DLP were lowered by up to 10.9 % (p < 0.001), 17.9 % (p = 0.005), 20.9 % (p < 0.001), and 21.7 % (p = 0.001), respectively, by using ASIR compared with FBP alone. Image quality and noise were similar for both FBP and ASIR.We recommend routine use of iterative reconstruction for neuroradiology CT examinations because this approach affords a significant dose reduction while preserving image quality.

    View details for DOI 10.1007/s00234-013-1313-z

    View details for Web of Science ID 000332460500002

    View details for PubMedID 24384672

  • Clinical application of perfusion computed tomography in neurosurgery Clinical article JOURNAL OF NEUROSURGERY Huang, A. P., Tsai, J., Kuo, L., Lee, C., Lai, H., Tsai, L., Huang, S., Chen, C., Chen, Y., Chuang, H., Wintermark, M. 2014; 120 (2): 473-488
  • Multimodal MR imaging model to predict tumor infiltration in patients with gliomas NEURORADIOLOGY Durst, C. R., Raghavan, P., Shaffrey, M. E., Schiff, D., Lopes, M. B., Sheehan, J. P., Tustison, N. J., Patrie, J. T., Xin, W., Elias, W. J., Liu, K. C., Helm, G. A., Cupino, A., Wintermark, M. 2014; 56 (2): 107-115

    Abstract

    Gliomas remain difficult to treat, in part, due to our inability to accurately delineate the margins of the tumor. The goal of our study was to evaluate if a combination of advanced MR imaging techniques and a multimodal imaging model could be used to predict tumor infiltration in patients with diffuse gliomas.Institutional review board approval and written consent were obtained. This prospective pilot study enrolled patients undergoing stereotactic biopsy for a suspected de novo glioma. Stereotactic biopsy coordinates were coregistered with multiple standard and advanced neuroimaging sequences in 10 patients. Objective imaging values were assigned to the biopsy sites for each of the imaging sequences. A principal component analysis was performed to reduce the dimensionality of the imaging dataset without losing important information. A univariate analysis was performed to identify the statistically relevant principal components. Finally, a multivariate analysis was used to build the final model describing nuclear density.A univariate analysis identified three principal components as being linearly associated with the observed nuclear density (p values 0.021, 0.016, and 0.046, respectively). These three principal component composite scores are predominantly comprised of DTI (mean diffusivity or average diffusion coefficient and fractional anisotropy) and PWI data (rMTT, Ktrans). The p value of the model was <0.001. The correlation between the predicted and observed nuclear density was 0.75.A multi-input, single output imaging model may predict the extent of glioma invasion with significant correlation with histopathology.

    View details for DOI 10.1007/s00234-013-1308-9

    View details for Web of Science ID 000330946300003

    View details for PubMedID 24337609

  • Imaging genomic mapping of an invasive MRI phenotype predicts patient outcome and metabolic dysfunction: a TCGA glioma phenotype research group project. BMC medical genomics Colen, R. R., Vangel, M., Wang, J., Gutman, D. A., Hwang, S. N., Wintermark, M., Jain, R., Jilwan-Nicolas, M., Chen, J. Y., Raghavan, P., Holder, C. A., Rubin, D., Huang, E., Kirby, J., Freymann, J., Jaffe, C. C., Flanders, A., Zinn, P. O. 2014; 7: 30-?

    Abstract

    Invasion of tumor cells into adjacent brain parenchyma is a major cause of treatment failure in glioblastoma. Furthermore, invasive tumors are shown to have a different genomic composition and metabolic abnormalities that allow for a more aggressive GBM phenotype and resistance to therapy. We thus seek to identify those genomic abnormalities associated with a highly aggressive and invasive GBM imaging-phenotype.We retrospectively identified 104 treatment-naïve glioblastoma patients from The Cancer Genome Atlas (TCGA) whom had gene expression profiles and corresponding MR imaging available in The Cancer Imaging Archive (TCIA). The standardized VASARI feature-set criteria were used for the qualitative visual assessments of invasion. Patients were assigned to classes based on the presence (Class A) or absence (Class B) of statistically significant invasion parameters to create an invasive imaging signature; imaging genomic analysis was subsequently performed using GenePattern Comparative Marker Selection module (Broad Institute).Our results show that patients with a combination of deep white matter tracts and ependymal invasion (Class A) on imaging had a significant decrease in overall survival as compared to patients with absence of such invasive imaging features (Class B) (8.7 versus 18.6 months, p < 0.001). Mitochondrial dysfunction was the top canonical pathway associated with Class A gene expression signature. The MYC oncogene was predicted to be the top activation regulator in Class A.We demonstrate that MRI biomarker signatures can identify distinct GBM phenotypes associated with highly significant survival differences and specific molecular pathways. This study identifies mitochondrial dysfunction as the top canonical pathway in a very aggressive GBM phenotype. Thus, imaging-genomic analyses may prove invaluable in detecting novel targetable genomic pathways.

    View details for DOI 10.1186/1755-8794-7-30

    View details for PubMedID 24889866

  • The role of imaging in acute ischemic stroke NEUROSURGICAL FOCUS Tong, E., Hou, Q., Fiebach, J. B., Wintermark, M. 2014; 36 (1)

    Abstract

    Neuroimaging has expanded beyond its traditional diagnostic role and become a critical tool in the evaluation and management of stroke. The objectives of imaging include prompt accurate diagnosis, treatment triage, prognosis prediction, and secondary preventative precautions. While capitalizing on the latest treatment options and expanding upon the "time is brain" doctrine, the ultimate goal of imaging is to maximize the number of treated patients and improve the outcome of one the most costly and morbid disease. A broad overview of comprehensive multimodal stroke imaging is presented here to affirm its utilization.

    View details for DOI 10.3171/2013.10.FOCUS13396

    View details for Web of Science ID 000329171100004

    View details for PubMedID 24380480

  • Evolution of CT Imaging Features of Carotid Atherosclerotic Plaques in a 1-Year Prospective Cohort Study JOURNAL OF NEUROIMAGING Adraktas, D. D., Tong, E., Furtado, A. D., Cheng, S., Wintermark, M. 2014; 24 (1): 1-6

    Abstract

    The purpose of this study was to identify imaging markers and clinical risk factors that significantly predict the evolution of computed tomography (CT) imaging features of carotid artery atherosclerotic disease over a 1-year period.Our prospective study involved 120 consecutive patients undergoing emergent CT evaluation for symptoms of acute stroke. These patients were asked to consent to a follow-up CT exam in 1 year. To evaluate for atherosclerotic plaque, both at baseline and on follow-up, we employed a comprehensive computed tomography angiography (CTA) protocol that captured the carotid, vertebral, aortic, and coronary arteries. To further evaluate carotid artery plaque components, we used an automated classifier computer algorithm that distinguishes among the histological components of the carotid artery wall (lipids, calcium, fibrous tissue) based on appropriate thresholds of CT density. Baseline values of carotid imaging features and clinical variables were assessed for their ability to significantly predict changes in these imaging features over 1 year.Of these 120 consecutive patients, 17 received both a baseline and a follow-up CTA exam. Wall volume increased more when the largest lipid cluster was located close to the lumen (coefficient -7.61, -13.83 to -1.40, P = .016). The volume of lipid increased with age (coefficient .36, .21 to .50, P = .000), in smokers (coefficient 8.89, 6.82 to 10.95, P = .000) and when fewer lipid clusters were present at baseline (coefficient -0.11, -0.17 to -.04, P = .001). The volume of calcium increased with greater volume of lipid at baseline (coefficient .35, .02 to .68, P = .035) and in patients on statins (coefficient 4.79, 1.73 to 7.86, P = .002).There are a number of imaging markers and risk factors that significantly predict the evolution of CT imaging features of carotid artery atherosclerotic disease over a 1-year period.

    View details for DOI 10.1111/j.1552-6569.2012.00705.x

    View details for Web of Science ID 000329509100001

    View details for PubMedID 22985127

  • Influence of Chronic Hyperglycemia on Cerebral Microvascular Remodeling An In Vivo Study Using Perfusion Computed Tomography in Acute Ischemic Stroke Patients STROKE Hou, Q., Zuo, Z., Michel, P., Zhang, Y., Eskandari, A., Man, F., Gao, Q., Johnston, K. C., Wintermark, M. 2013; 44 (12): 3557-3560

    Abstract

    To investigate the effect of chronic hyperglycemia on cerebral microvascular remodeling using perfusion computed tomography.We retrospectively identified 26 patients from our registry of 2453 patients who underwent a perfusion computed tomographic study and had their hemoglobin A1c (HbA1c) measured. These 26 patients were divided into 2 groups: those with HbA1c>6.5% (n=15) and those with HbA1c≤6.5% (n=11). Perfusion computed tomographic studies were processed using a delay-corrected, deconvolution-based software. Perfusion computed tomographic values were compared between the 2 patient groups, including mean transit time, which relates to the cerebral capillary architecture and length.Mean transit time values in the nonischemic cerebral hemisphere were significantly longer in the patients with HbA1c>6.5% (P=0.033), especially in the white matter (P=0.005). Significant correlation (R=0.469; P=0.016) between mean transit time and HbA1c level was observed.Our results from a small sample suggest that chronic hyperglycemia may be associated with cerebral microvascular remodeling in humans. Additional prospective studies with larger sample size are required to confirm this observation.

    View details for DOI 10.1161/STROKEAHA.113.003150

    View details for Web of Science ID 000327386300335

    View details for PubMedID 24029632

  • Stroke Treatment Academic Industry Roundtable Research Priorities in the Assessment of Neurothrombectomy Devices STROKE Saver, J. L., Jovin, T. G., Smith, W. S., Albers, G. W. 2013; 44 (12): 3596-3601

    Abstract

    The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke.Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue.Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

    View details for DOI 10.1161/STROKEAHA.113.002769

    View details for PubMedID 24193797

  • Imaging recommendations for acute stroke and transient ischemic attack patients: A joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery. AJNR. American journal of neuroradiology Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J., Derdeyn, C., Hetts, S. W., Johnson, M. H., Kidwell, C., Lev, M. H., Liebeskind, D. S., Rowley, H., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 34 (11): E117-27

    Abstract

    Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

    View details for DOI 10.3174/ajnr.A3690

    View details for PubMedID 23907247

  • IMAGING GENOMIC CORRELATION OF INVASIVE GENOMIC COMPOSITION AND PATIENT SURVIVAL DEMONSTRATES METABOLIC DYSFUNCTION: A TCGA GLIOMA PHENOTYPE RESEARCH GROUP PROJECT Colen, R., Vangel, M., Gutman, D., Hwang, S., Wintermark, M., Jain, R., Jilwan-Nicolas, M., Chen, J., Raghavan, P., Holder, C., Rubin, D., Huang, E., Kirby, J., Freymann, J., Jaffe, C., Flanders, A., Zinn, P. OXFORD UNIV PRESS INC. 2013: 193
  • Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery. Journal of the American College of Radiology Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J. A., Derdeyn, C. P., Hetts, S. W., Johnson, M. H., Kidwell, C. S., Lev, M. H., Liebeskind, D. S., Rowley, H. A., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 10 (11): 828-832

    Abstract

    In the article entitled "Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution.

    View details for DOI 10.1016/j.jacr.2013.06.019

    View details for PubMedID 23948676

  • Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J., Derdeyn, C., Hetts, S. W., Johnson, M. H., Kidwell, C., Lev, M. H., Liebeskind, D. S., Rowley, H., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 34 (11): E117-E127

    View details for DOI 10.3174/ajnr.A3690

    View details for Web of Science ID 000330234700001

    View details for PubMedID 23907247

  • Acute Stroke Imaging Research Roadmap II STROKE Wintermark, M., Albers, G. W., Broderick, J. P., Demchuk, A. M., Fiebach, J. B., Fiehler, J., Grotta, J. C., Houser, G., Jovin, T. G., Lees, K. R., Lev, M. H., Liebeskind, D. S., Luby, M., Muir, K. W., Parsons, M. W., von Kummer, R., Wardlaw, J. M., Wu, O., Yoo, A. J., Alexandrov, A. V., Alger, J. R., Aviv, R. I., Bammer, R., Baron, J., Calamante, F., Campbell, B. C., Carpenter, T. C., Christensen, S., Copen, W. A., Derdeyn, C. P., Haley, C., Khatri, P., Kudo, K., Lansberg, M. G., Latour, L. L., Lee, T., Leigh, R., Lin, W., Lyden, P., Mair, G., Menon, B. K., Michel, P., Mikulik, R., Nogueira, R. G., Ostergaard, L., Pedraza, S., Riedel, C. H., Rowley, H. A., Sanelli, P. C., Sasaki, M., Saver, J. L., Schaefer, P. W., Schellinger, P. D., Tsivgoulis, G., Wechsler, L. R., White, P. M., Zaharchuk, G., Zaidat, O. O., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Kang, D., Kidwell, C., Thijs, V. N., Thomalla, G., Warach, S. J. 2013; 44 (9): 2628-2639

    View details for DOI 10.1161/STROKEAHA.113.002015

    View details for Web of Science ID 000329982500063

    View details for PubMedID 23860298

  • Perfusion MRI: The Five Most Frequently Asked Clinical Questions AMERICAN JOURNAL OF ROENTGENOLOGY Essig, M., Thanh Binh Nguyen, T. B., Shiroishi, M. S., Saake, M., Provenzale, J. M., Enterline, D. S., Anzalone, N., Doerfler, A., Rovira, A., Wintermark, M., Law, M. 2013; 201 (3): W495-W510

    Abstract

    This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging.Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of per-fusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.

    View details for DOI 10.2214/AJR.12.9544

    View details for Web of Science ID 000323601500016

    View details for PubMedID 23971482

  • Recommendations on Angiographic Revascularization Grading Standards for Acute Ischemic Stroke A Consensus Statement STROKE Zaidat, O. O., Yoo, A. J., Khatri, P., Tomsick, T. A., von Kummer, R., Saver, J. L., Marks, M. P., Prabhakaran, S., Kallmes, D. F., Fitzsimmons, B. M., Mocco, J., Wardlaw, J. M., Barnwell, S. L., Jovin, T. G., Linfante, I., Siddiqui, A. H., Alexander, M. J., Hirsch, J. A., Wintermark, M., Albers, G., Woo, H. H., Heck, D. V., Lev, M., Aviv, R., Hacke, W., Warach, S., Broderick, J., Derdeyn, C. P., Furlan, A., Nogueira, R. G., Yavagal, D. R., Goyal, M., Demchuk, A. M., Bendszus, M., Liebeskind, D. S. 2013; 44 (9): 2650-2663

    View details for DOI 10.1161/STROKEAHA.113.001972

    View details for Web of Science ID 000329982500066

    View details for PubMedID 23920012

  • A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor NEW ENGLAND JOURNAL OF MEDICINE Elias, W. J., Huss, D., Voss, T., Loomba, J., Khaled, M., Zadicario, E., Frysinger, R. C., Sperling, S. A., Wylie, S., Monteith, S. J., Druzgal, J., Shah, B. B., Harrison, M., Wintermark, M. 2013; 369 (7): 640-648

    Abstract

    Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor.From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability).Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001).In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

    View details for DOI 10.1056/NEJMoa1300962

    View details for Web of Science ID 000326354500010

    View details for PubMedID 23944301

  • A magnetic resonance imaging, histological, and dose modeling comparison of focused ultrasound, radiofrequency, and Gamma Knife radiosurgery lesions in swine thalamus Laboratory investigation JOURNAL OF NEUROSURGERY Elias, W. J., Khaled, M., Hilliard, J. D., Aubry, J., Frysinger, R. C., Sheehan, J. P., Wintermark, M., Lopes, M. B. 2013; 119 (2): 307-317
  • A magnetic resonance imaging, histological, and dose modeling comparison of focused ultrasound, radiofrequency, and Gamma Knife radiosurgery lesions in swine thalamus. Journal of neurosurgery Elias, W. J., Khaled, M., Hilliard, J. D., Aubry, J., Frysinger, R. C., Sheehan, J. P., Wintermark, M., Lopes, M. B. 2013; 119 (2): 307-317

    Abstract

    The purpose of this study was to use MRI and histology to compare stereotactic lesioning modalities in a large brain model of thalamotomy.A unilateral thalamotomy was performed in piglets utilizing one of 3 stereotactic lesioning modalities: focused ultrasound (FUS), radiofrequency, and radiosurgery. Standard clinical lesioning parameters were used for each treatment; and clinical, MRI, and histological assessments were made at early (< 72 hours), subacute (1 week), and later (1-3 months) time intervals.Histological and MRI assessment showed similar development for FUS and radiofrequency lesions. T2-weighted MRI revealed 3 concentric lesional zones at 48 hours with resolution of perilesional edema by 1 week. Acute ischemic infarction with macrophage infiltration was most prominent at 72 hours, with subsequent resolution of the inflammatory reaction and coalescence of the necrotic zone. There was no apparent difference in ischemic penumbra or "sharpness" between FUS or radiofrequency lesions. The radiosurgery lesions presented differently, with latent effects, less circumscribed lesions at 3 months, and apparent histological changes seen in white matter beyond the thalamic target. Additionally, thermal and radiation lesioning gradients were compared with modeling by dose to examine the theoretical penumbra.In swine thalamus, FUS and radiosurgery lesions evolve similarly as determined by MRI, histological examination, and theoretical modeling. Radiosurgery produces lesions with more delayed effects and seemed to result in changes in the white matter beyond the thalamic target.

    View details for DOI 10.3171/2013.5.JNS122327

    View details for PubMedID 23746105

  • Tissue at risk in acute stroke patients treated beyond 8 h after symptom onset NEURORADIOLOGY Leiva-Salinas, C., Aghaebrahim, A., Zhu, G., Patrie, J. T., Xin, W., LAU, B. C., Jovin, T., Wintermark, M. 2013; 55 (7): 807-812

    Abstract

    The decision on thrombolytics administration is usually based on a generalized, rigid time-based rule rather than an individualized evaluation of the "tissue at risk of infarction" which is the target of the recanalization therapies. The goals of our article are to assess whether there is tissue at risk of infarction in a group of acute stroke patients treated beyond 8 h after symptom onset and to investigate the baseline imaging and clinical features that predict the fate of this tissue at risk.We retrospectively reviewed a series of patients with acute ischemic stroke treated with endovascular recanalization therapies beyond 8 h after symptom onset. The tissue at risk was calculated as the difference between the infarct volumes on baseline and follow-up imaging (infarct growth). We analyzed the epidemiological distribution of infarct growth, and we performed a multivariate regression analysis to identify the baseline variables that predict infarct growth.Our study group included 75 patients (65 ± 13.8 years, baseline National Institutes of Health Stroke Scale 14 ± 4.9, time to treatment 15.2 ± 8.7 h). The mean infarct growth was 78.6 ± 95.0 cc (p < 0.001), and, overall, the infarct growth was greater when the baseline volume of infarct tissue was small (p < 0.001) and in the case of a unsuccessful arterial recanalization (p = 0.001).There is potentially salvageable ischemic tissue at risk in acute stroke patients treated beyond 8 h after symptom onset.

    View details for DOI 10.1007/s00234-013-1164-7

    View details for Web of Science ID 000321919900002

    View details for PubMedID 23559400

  • Acute type A aortic dissection intimal tears by 64-slice computed tomography: a role for endovascular stent-grafting? JOURNAL OF CARDIOVASCULAR SURGERY Jaussaud, N., Chitsaz, S., Meadows, A., Wintermark, M., Cambronero, N., Azadani, A. N., Saloner, D. A., Chuter, T. A., Tseng, E. E. 2013; 54 (3): 373-381

    Abstract

    The goal of this study was to identify physical characteristics of primary intimal tears in patients arriving to the hospital alive with acute type A aortic dissection using 64-multislice computerized tomography (MSCT) in order to determine anatomic feasibility of endovascular stent-grafting (ESG) for future treatment.Radiology database was screened for acute type A aortic dissection since the time of acquisition of the 64-slice CT scanner and cross-referenced with surgical database. Seventeen patients met inclusion criteria. Images were reviewed for number, location, and size of intimal tears and aortic dimensions. Potential obstacles for ESG were determined.Ascending aorta (29%) and sinotubular junction (29%) were the most frequent regions where intimal tears originated. Location of intimal tears in nearly 75% of patients was inappropriate for ESG, and 94% of patients did not have sufficient proximal or distal landing zone required for secure fixation. Only 71% of patients underwent surgical aortic dissection repair after imaging and 86% of entry tears detected on MSCT were confirmed on intraoperative documentation. Only one patient would have met all technical criteria for ESG using currently available devices.Location of intimal tear, aortic valve insufficiency, aortic diameter>38 mm are major factors limiting use of ESG for acute type A dissection. Available stents used to treat type B aortic dissection do not address anatomic constraints present in type A aortic dissection in the majority of cases, such that development of new devices would be required.

    View details for Web of Science ID 000320743200008

    View details for PubMedID 22820738

  • MR Imaging Predictors of Molecular Profile and Survival: Multi-institutional Study of the TCGA Glioblastoma Data Set RADIOLOGY Gutman, D. A., Cooper, L. A., Hwang, S. N., Holder, C. A., Gao, J., Aurora, T. D., Dunn, W. D., Scarpace, L., Mikkelsen, T., Jain, R., Wintermark, M., Jilwan, M., Raghavan, P., Huang, E., Clifford, R. J., Mongkolwat, P., Kleper, V., Freymann, J., Kirby, J., Zinn, P. O., Moreno, C. S., Jaffe, C., Colen, R., Rubin, D. L., Saltz, J., Flanders, A., Brat, D. J. 2013; 267 (2): 560-569

    Abstract

    To conduct a comprehensive analysis of radiologist-made assessments of glioblastoma (GBM) tumor size and composition by using a community-developed controlled terminology of magnetic resonance (MR) imaging visual features as they relate to genetic alterations, gene expression class, and patient survival.Because all study patients had been previously deidentified by the Cancer Genome Atlas (TCGA), a publicly available data set that contains no linkage to patient identifiers and that is HIPAA compliant, no institutional review board approval was required. Presurgical MR images of 75 patients with GBM with genetic data in the TCGA portal were rated by three neuroradiologists for size, location, and tumor morphology by using a standardized feature set. Interrater agreements were analyzed by using the Krippendorff α statistic and intraclass correlation coefficient. Associations between survival, tumor size, and morphology were determined by using multivariate Cox regression models; associations between imaging features and genomics were studied by using the Fisher exact test.Interrater analysis showed significant agreement in terms of contrast material enhancement, nonenhancement, necrosis, edema, and size variables. Contrast-enhanced tumor volume and longest axis length of tumor were strongly associated with poor survival (respectively, hazard ratio: 8.84, P = .0253, and hazard ratio: 1.02, P = .00973), even after adjusting for Karnofsky performance score (P = .0208). Proneural class GBM had significantly lower levels of contrast enhancement (P = .02) than other subtypes, while mesenchymal GBM showed lower levels of nonenhanced tumor (P < .01).This analysis demonstrates a method for consistent image feature annotation capable of reproducibly characterizing brain tumors; this study shows that radiologists' estimations of macroscopic imaging features can be combined with genetic alterations and gene expression subtypes to provide deeper insight to the underlying biologic properties of GBM subsets.

    View details for DOI 10.1148/radiol.13120118

    View details for Web of Science ID 000318069700028

    View details for PubMedID 23392431

    View details for PubMedCentralID PMC3632807

  • Dorsal Thoracic Arachnoid Web and the "Scalpel Sign": A Distinct Clinical-Radiologic Entity AMERICAN JOURNAL OF NEURORADIOLOGY REARDON, M. A., Raghavan, P., Carpenter-Bailey, K., Mukherjee, S., Smith, J. S., Matsumoto, J. A., Yen, C., Shaffrey, M. E., Lee, R. R., Shaffrey, C. I., Wintermark, M. 2013; 34 (5): 1104-1110

    Abstract

    Arachnoid webs are intradural extramedullary bands of arachnoid tissue that can extend to the pial surface of the spinal cord, causing a focal dorsal indentation of the cord. These webs tend to occur in the upper thoracic spine and may produce a characteristic deformity of the cord that we term the "scalpel sign." We describe 14 patients whose imaging studies demonstrated the scalpel sign. Ten of 13 patients who underwent MR imaging demonstrated T2WI cord signal-intensity changes, and 7 of these patients also demonstrated syringomyelia adjacent to the level of indentation. Seven patients underwent surgery, with 5 demonstrating an arachnoid web as the cause of the dorsal indentation demonstrated on preoperative imaging. Although the webs themselves are rarely demonstrated on imaging, we propose that the scalpel sign is a reliable indicator of their presence and should prompt consideration of surgical lysis, which is potentially curative.

    View details for DOI 10.3174/ajnr.A3432

    View details for Web of Science ID 000330536900041

    View details for PubMedID 23348759

  • A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor GLOBAL PUBLIC HEALTH Elias, W. J., Huss, D., Voss, T., Loomba, J., Khaled, M., Zadicario, E., Frysinger, R. C., Sperling, S. A., Wylie, S., Monteith, S. J., Druzgal, J., Shah, B. B., Harrison, M., Wintermark, M. 2013; 8 (5): 640-648
  • Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound. Journal of neurosurgery Monteith, S. J., Harnof, S., Medel, R., Popp, B., Wintermark, M., Lopes, M. B., Kassell, N. F., Elias, W. J., Snell, J., Eames, M., Zadicario, E., Moldovan, K., Sheehan, J. 2013; 118 (5): 1035-1045

    Abstract

    Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube.In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance.The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

    View details for DOI 10.3171/2012.12.JNS121095

    View details for PubMedID 23330996

  • Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound Laboratory investigation JOURNAL OF NEUROSURGERY Monteith, S. J., Harnof, S., Medel, R., Popp, B., Wintermark, M., Lopes, M. B., Kassell, N. F., Elias, W. J., Snell, J., Eames, M., Zadicario, E., Moldovan, K., Sheehan, J. 2013; 118 (5): 1035-1045
  • Genomic Mapping and Survival Prediction in Glioblastoma: Molecular Subclassification Strengthened by Hemodynamic Imaging Biomarkers RADIOLOGY Jain, R., Poisson, L., Narang, J., Gutman, D., Scarpace, L., Hwang, S. N., Holder, C., Wintermark, M., Colen, R. R., Kirby, J., Freymann, J., Brat, D. J., Jaffe, C., Mikkelsen, T. 2013; 267 (1): 212-220

    Abstract

    To correlate tumor blood volume, measured by using dynamic susceptibility contrast material-enhanced T2*-weighted magnetic resonance (MR) perfusion studies, with patient survival and determine its association with molecular subclasses of glioblastoma (GBM).This HIPAA-compliant retrospective study was approved by institutional review board. Fifty patients underwent dynamic susceptibility contrast-enhanced T2*-weighted MR perfusion studies and had gene expression data available from the Cancer Genome Atlas. Relative cerebral blood volume (rCBV) (maximum rCBV [rCBV(max)] and mean rCBV [rCBV(mean)]) of the contrast-enhanced lesion as well as rCBV of the nonenhanced lesion (rCBV(NEL)) were measured. Patients were subclassified according to the Verhaak and Phillips classification schemas, which are based on similarity to defined genomic expression signature. We correlated rCBV measures with the molecular subclasses as well as with patient overall survival by using Cox regression analysis.No statistically significant differences were noted for rCBV(max), rCBV(mean) of contrast-enhanced lesion or rCBV(NEL) between the four Verhaak classes or the three Phillips classes. However, increased rCBV measures are associated with poor overall survival in GBM. The rCBV(max) (P = .0131) is the strongest predictor of overall survival regardless of potential confounders or molecular classification. Interestingly, including the Verhaak molecular GBM classification in the survival model clarifies the association of rCBV(mean) with patient overall survival (hazard ratio: 1.46, P = .0212) compared with rCBV(mean) alone (hazard ratio: 1.25, P = .1918). Phillips subclasses are not predictive of overall survival nor do they affect the predictive ability of rCBV measures on overall survival.The rCBV(max) measurements could be used to predict patient overall survival independent of the molecular subclasses of GBM; however, Verhaak classifiers provided additional information, suggesting that molecular markers could be used in combination with hemodynamic imaging biomarkers in the future.

    View details for DOI 10.1148/radiol.12120846

    View details for Web of Science ID 000316565000022

    View details for PubMedID 23238158

  • Optimal Imaging of In Vitro Clot Sonothrombolysis by MR-Guided Focused Ultrasound JOURNAL OF NEUROIMAGING Durst, C., Monteith, S., Sheehan, J., Moldovan, K., Snell, J., Eames, M., Huerta, T., Walker, W., Viola, F., Kassell, N., Wintermark, M. 2013; 23 (2): 187-191

    Abstract

    As magnetic resonance-guided focused ultrasound (MRgFUS) sonothrombolysis relies on mechanical rather than thermal mechanisms to achieve clot lysis, thermometry is not useful for the intraoperative monitoring of clot breakdown by MRgFUS. Therefore, the purpose of this study was to evaluate the optimum imaging sequence for sonothrombolysis.In vitro blood drawn from 6 healthy volunteers was imaged using T1, T2 spin-echo, and T2 gradient-echo (GRE) sequences both before and after sonication using an Insightec ExAblate 4000 FUS transducer. Signal intensities of the three MR imaging sequences were measured and normalized to background signal for each time point. Representative samples of the pre- and postsonication clot were also sent to pathology for hematologic analysis.After sonication, the clot in the treatment tube was fully lysed as evidenced by physical and hematologic evaluation. The difference between pre- and postsonicated normalized signal intensity ratios demonstrated statistical significance only on T2 and GRE sequences (P < .001). However, significant blooming artifact limited interpretation on all GRE images.T2 is the most appropriate sequence for the evaluation of mechanical MRgFUS sonothrombolysis of an in vitro clot. These findings are consistent across the oxidative states of clot up to 48 hours.

    View details for DOI 10.1111/j.1552-6569.2011.00662.x

    View details for Web of Science ID 000317617800008

    View details for PubMedID 22082153

  • Accuracy and Reliability Assessment of CT and MR Perfusion Analysis Software Using a Digital Phantom RADIOLOGY Kudo, K., Christensen, S., Sasaki, M., Ostergaard, L., Shirato, H., Ogasawara, K., Wintermark, M., Warach, S. 2013; 267 (1): 201-211

    Abstract

    To design a digital phantom data set for computed tomography (CT) perfusion and perfusion-weighted imaging on the basis of the widely accepted tracer kinetic theory in which the true values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and tracer arrival delay are known and to evaluate the accuracy and reliability of postprocessing programs using this digital phantom.A phantom data set was created by generating concentration-time curves reflecting true values for CBF (2.5-87.5 mL/100 g per minute), CBV (1.0-5.0 mL/100 g), MTT (3.4-24 seconds), and tracer delays (0-3.0 seconds). These curves were embedded in human brain images. The data were analyzed by using 13 algorithms each for CT and magnetic resonance (MR), including five commercial vendors and five academic programs. Accuracy was assessed by using the Pearson correlation coefficient (r) for true values. Delay-, MTT-, or CBV-dependent errors and correlations between time to maximum of residue function (Tmax) were also evaluated.In CT, CBV was generally well reproduced (r > 0.9 in 12 algorithms), but not CBF and MTT (r > 0.9 in seven and four algorithms, respectively). In MR, good correlation (r > 0.9) was observed in one-half of commercial programs, while all academic algorithms showed good correlations for all parameters. Most algorithms had delay-dependent errors, especially for commercial software, as well as CBV dependency for CBF or MTT calculation and MTT dependency for CBV calculation. Correlation was good in Tmax except for one algorithm.The digital phantom readily evaluated the accuracy and characteristics of the CT and MR perfusion analysis software. All commercial programs had delay-induced errors and/or insufficient correlations with true values, while academic programs for MR showed good correlations with true values.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112618/-/DC1.

    View details for DOI 10.1148/radiol.12112618

    View details for Web of Science ID 000316565000021

    View details for PubMedID 23220899

  • Computed Tomography Workup of Patients Suspected of Acute Ischemic Stroke Perfusion Computed Tomography Adds Value Compared With Clinical Evaluation, Noncontrast Computed Tomography, and Computed Tomography Angiogram in Terms of Predicting Outcome STROKE Zhu, G., Michel, P., Aghaebrahim, A., Patrie, J. T., Xin, W., Eskandari, A., Zhang, W., Wintermark, M. 2013; 44 (4): 1049-?

    Abstract

    To determine whether perfusion computed tomography (PCT) adds value to noncontrast head CT (NCT), CT angiogram (CTA), and clinical assessment in patients suspected of acute ischemic stroke.We retrospectively reviewed 165 patients with acute ischemic stroke. PCT was used to calculate the volumes of infarct core and ischemic penumbra on admission. Other imaging data included Alberta Score Program Early CT Score, site of occlusion, and collateral flow. Clinical data included age, time, National Institutes of Health Stroke Scale at baseline, treatment type, and modified Rankin score (mRS) at 90 days. Recanalization status was assessed on follow-up imaging. In a first multivariate regression analysis, we assessed whether volumes of PCT penumbra and infarct core could be predicted from clinical variables, NCT, or CTA, or whether they represented independent information. In a second multivariate regression analysis, we used mRS at 90 days as outcome and determined which variables predicted it best.Of 165 patients identified, 76 had a mRS score of 0 to 2 at 90 days, 89 had a mRS score >2. PCT infarct could be predicted by clinical data, NCT, CTA, and combinations of this data (P<0.05). PCT penumbra could not be predicted by clinical data, NCT, and CTA. All of the variables but NCT and CTA were significantly associated with 90-day mRS outcome. The single most important predictor was recanalization status (P<0.001). PCT penumbra volume (P=0.001) was also a predictor of clinical outcome, especially when considered in conjunction with recanalization through an interaction term (P<0.001).PCT penumbra represents independent information, which cannot be predicted by clinical, NCT, and CTA data. PCT penumbra is an important determinant of clinical outcome and adds relevant clinical information compared with a stroke CT workup, including NCT and CTA.

    View details for DOI 10.1161/STROKEAHA.111.674705

    View details for Web of Science ID 000316673900030

    View details for PubMedID 23404718

  • Prediction of Recanalization Trumps Prediction of Tissue Fate The Penumbra: A Dual-edged Sword STROKE Zhu, G., Michel, P., Aghaebrahim, A., Patrie, J. T., Xin, W., Eskandari, A., Zhang, W., Wintermark, M. 2013; 44 (4): 1014-1019

    Abstract

    To determine whether infarct core or penumbra is the more significant predictor of outcome in acute ischemic stroke, and whether the results are affected by the statistical method used.Clinical and imaging data were collected in 165 patients with acute ischemic stroke. We reviewed the noncontrast head computed tomography (CT) to determine the Alberta Score Program Early CT score and assess for hyperdense middle cerebral artery. We reviewed CT-angiogram for site of occlusion and collateral flow score. From perfusion-CT, we calculated the volumes of infarct core and ischemic penumbra. Recanalization status was assessed on early follow-up imaging. Clinical data included age, several time points, National Institutes of Health Stroke Scale at admission, treatment type, and modified Rankin score at 90 days. Two multivariate regression analyses were conducted to determine which variables predicted outcome best. In the first analysis, we did not include recanalization status among the potential predicting variables. In the second, we included recanalization status and its interaction between perfusion-CT variables.Among the 165 study patients, 76 had a good outcome (modified Rankin score ≤2) and 89 had a poor outcome (modified Rankin score >2). In our first analysis, the most important predictors were age (P<0.001) and National Institutes of Health Stroke Scale at admission (P=0.001). The imaging variables were not important predictors of outcome (P>0.05). In the second analysis, when the recanalization status and its interaction with perfusion-CT variables were included, recanalization status and perfusion-CT penumbra volume became the significant predictors (P<0.001).Imaging prediction of tissue fate, more specifically imaging of the ischemic penumbra, matters only if recanalization can also be predicted.

    View details for DOI 10.1161/STROKEAHA.111.000229

    View details for Web of Science ID 000316673900024

    View details for PubMedID 23463751

  • A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke NEW ENGLAND JOURNAL OF MEDICINE Kidwell, C. S., Jahan, R., Gornbein, J., Alger, J. R., Nenov, V., Ajani, Z., Feng, L., Meyer, B. C., Olson, S., Schwamm, L. H., Yoo, A. J., Marshall, R. S., Meyers, P. M., Yavagal, D. R., Wintermark, M., Guzy, J., Starkman, S., Saver, J. L. 2013; 368 (10): 914-923

    Abstract

    Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear.In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14).A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.).

    View details for DOI 10.1056/NEJMoa1212793

    View details for Web of Science ID 000315669100007

    View details for PubMedID 23394476

  • Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Jauch, E. C., Saver, J. L., Adams, H. P., Bruno, A., Connors, J. J., Demaerschalk, B. M., Khatri, P., McMullan, P. W., Qureshi, A. I., Rosenfield, K., Scott, P. A., Summers, D. R., Wang, D. Z., Wintermark, M., Yonas, H. 2013; 44 (3): 870-947

    Abstract

    The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates.Members of the writing committee were appointed by the American Stroke Association Stroke Council's Scientific Statement Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise, reviewed the stroke literature with emphasis on publications since the prior guidelines, and drafted recommendations in accordance with the American Heart Association Stroke Council's Level of Evidence grading algorithm.The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care, as well as ischemic stroke, specific interventions such as reperfusion strategies, and general physiological optimization for cerebral resuscitation.Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke remains urgently needed.

    View details for DOI 10.1161/STR.0b013e318284056a

    View details for Web of Science ID 000315447400060

    View details for PubMedID 23370205

  • Guidelines for the Early Management of Patients With Acute Ischemic Stroke: Executive Summary A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Jauch, E. C., Saver, J. L., Adams, H. P., Bruno, A., Connors, J. J., Demaerschalk, B. M., Khatri, P., McMullan, P. W., Qureshi, A. I., Rosenfield, K., Scott, P. A., Summers, D. R., Wang, D. Z., Wintermark, M., Yonas, H. 2013; 44 (3)
  • Demographics of carotid atherosclerotic plaque features imaged by computed tomography JOURNAL OF NEURORADIOLOGY Chien, J. D., Furtado, A., Cheng, S., Lam, J., Schaeffer, S., Chun, K., Wintermark, M. 2013; 40 (1): 1-10

    Abstract

    This was a prospective, cross-sectional study to evaluate the risk factors and symptoms associated with specific carotid wall and atherosclerotic plaque features as seen on computed tomography-angiography (CTA) studies.A total of 120 consecutive consenting patients admitted to the emergency department with suspected cerebrovascular ischemia, and receiving standard-of-care CTA of the brain and neck on a 64-slice CT scanner, were prospectively enrolled in the study. The carotid wall features observed on CT were quantitatively analyzed with customized software using different radiodensities for contrast-phase acquisition of the carotids. Clinical datasets, including a complete medical history and examination, were obtained by research physicians or specially trained associates blinded to any findings on CT. Univariate and multivariate analyses were performed to assess the degree of association between clinical indicators and quantitative CT features of carotid atherosclerotic plaques.Men tended to have increased carotid lumen (coefficient: 608.7; 95% CI: 356.9-860.6; P<0.001) and wall volumes (209.2; 54.5-364.0; P=0.008), and hypertension was associated with increased wall volume (260.6; 88.7-432.6; P=0.003). Advanced age was associated with increases in maximum wall thickness (0.02; 0.003-0.05; P=0.029), fibrous cap thickness (0.005; 0.001-0.008; P=0.016) and number of calcium voxels (2.7; 1.25-4.2; P<0.001), and the presence of a carotid bruit was associated with carotid stenosis length (21.0; 5.38-37.8; P=0.009). Exercise was inversely related to the number of calcium (-37.1; -71.5 - -2.7; P=0.035) and lipid (-7.9; -15.1 - -0.7; P=0.032) voxels. ACE inhibitor use was associated with fibrous cap thickness (0.1; 0.04-0.23; P=0.005).Significant associations were found between clinical descriptors and carotid atherosclerotic plaque features as revealed by CT. Future studies are needed to validate our findings, and to continue investigations into whether CT features of carotid plaques can be used as biomarkers to quantify the impact of strategies aiming to correct vascular risk factors.

    View details for DOI 10.1016/j.neurad.2012.05.008

    View details for Web of Science ID 000317092100001

    View details for PubMedID 23428245

  • Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study JOURNAL OF NEUROSURGERY Monteith, S. J., Medel, R., Kassell, N. F., Wintermark, M., Eames, M., Snell, J., Zadicario, E., Grinfeld, J., Sheehan, J. P., Elias, W. J. 2013; 118 (2): 319-328

    Abstract

    Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as a treatment modality in neurosurgery. Until now, the trigeminal nerve was believed to be beyond the treatment envelope of existing high-frequency transcranial MRgFUS systems. In this study, the authors explore the feasibility of targeting the trigeminal nerve in a cadaveric model with temperature assessments using computer simulations and an in vitro skull phantom model fitted with thermocouples.Six trigeminal nerves from 4 unpreserved cadavers were targeted in the first experiment. Preprocedural CT scanning of the head was performed to allow for a skull correction algorithm. Three-Tesla, volumetric, FIESTA MRI sequences were performed to delineate the trigeminal nerve and any vascular structures of the cisternal segment. The cadaver was positioned in a focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that the focus of the transducer was centered at the proximal trigeminal nerve, allowing for targeting of the root entry zone (REZ) and the cisternal segment. Real-time, 2D thermometry was performed during the 10- to 30-second sonication procedures. Post hoc MR thermometry was performed on a computer workstation at the conclusion of the procedure to analyze temperature effects at neuroanatomical areas of interest. Finally, the region of the trigeminal nerve was targeted in a gel phantom encased within a human cranium, and temperature changes in regions of interest in the skull base were measured using thermocouples.The trigeminal nerves were clearly identified in all cadavers for accurate targeting. Sequential sonications of 25-1500 W for 10-30 seconds were successfully performed along the length of the trigeminal nerve starting at the REZ. Real-time MR thermometry confirmed the temperature increase as a narrow focus of heating by a mean of 10°C. Postprocedural thermometry calculations and thermocouple experiments in a phantom skull were performed and confirmed minimal heating of adjacent structures including the skull base, cranial nerves, and cerebral vessels. For targeting, inclusion of no-pass regions through the petrous bone decreased collateral heating in the internal acoustic canal from 16.7°C without blocking to 5.7°C with blocking. Temperature at the REZ target decreased by 3.7°C with blocking. Similarly, for midcisternal targeting, collateral heating at the internal acoustic canal was improved from a 16.3°C increase to a 4.9°C increase. Blocking decreased the target temperature increase by 4.4°C for the same power settings.This study demonstrates focal heating of up to 18°C in a cadaveric trigeminal nerve at the REZ and along the cisternal segment with transcranial MRgFUS. Significant heating of the skull base and surrounding neural structures did not occur with implementation of no-pass regions. However, in vivo studies are necessary to confirm the safety and efficacy of this potentially new, noninvasive treatment.

    View details for DOI 10.3171/2012.10.JNS12186

    View details for Web of Science ID 000313937900015

    View details for PubMedID 23157185

  • Clinical Risk Factors and CT Imaging Features of Carotid Atherosclerotic Plaques as Predictors of New Incident Carotid Ischemic Stroke: A Retrospective Cohort Study AMERICAN JOURNAL OF NEURORADIOLOGY Magge, R., LAU, B. C., Soares, B. P., Fischette, S., Arora, S., Tong, E., Cheng, S., Wintermark, M. 2013; 34 (2): 402-409

    Abstract

    Parameters other than luminal narrowing are needed to predict the risk of stroke more reliably, particularly in patients with <70% stenosis. The goal of our study was to identify clinical risk factors and CT features of carotid atherosclerotic plaques, in a retrospective cohort of patients free of stroke at baseline, that are independent predictors of incident stroke on follow-up.We identified a retrospective cohort of patients admitted to our emergency department with suspected stroke between 2001-2007 who underwent a stroke work-up including a CTA of the carotid arteries that was subsequently negative for acute stroke. All patients also had to receive a follow-up brain study at least 2 weeks later. From a random sample, we reviewed charts and imaging studies of patients with subsequent new stroke on follow-up as well as those who remained stroke-free. All patients were classified either as "new carotid infarct patients" or "no-new carotid infarct patients" based on the Causative Classification for Stroke. Independently, the baseline CTA studies were processed using a custom, CT-based automated computer classifier algorithm that quantitatively assesses a set of carotid CT features (wall thickness, plaque ulcerations, fibrous cap thickness, lipid-rich necrotic core, and calcifications). Univariate and multivariate statistical analyses were used to identify any significant differences in CT features between the patient groups in the sample. Subsequent ROC analysis allowed comparison to the classic NASCET stenosis rule in identifying patients with incident stroke on follow-up.We identified a total of 315 patients without a new carotid stroke between baseline and follow-up, and 14 with a new carotid stroke between baseline and follow-up, creating the main comparison groups for the study. Statistical analysis showed age and use of antihypertensive drugs to be the most significant clinical variables, and maximal carotid wall thickness was the most relevant imaging variable. The use of age ≥ 75 years, antihypertensive medication use, and a maximal carotid wall thickness of at least 4 mm was able to successfully identify 10 of the 14 patients who developed a new incident infarct on follow-up. ROC analysis showed an area under the ROC curve of 0.706 for prediction of new stroke with this new model.Our new paradigm of using age ≥ 75 years, history of hypertension, and carotid maximal wall thickness of >4 mm identified most of the patients with subsequent new carotid stroke in our study. It is simple and may help clinicians choose the patients at greatest risk of developing a carotid infarct, warranting validation with a prospective observational study.

    View details for DOI 10.3174/ajnr.A3228

    View details for Web of Science ID 000329210300029

    View details for PubMedID 22859283

  • Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery JOURNAL OF NEUROSURGERY Monteith, S., Sheehan, J., Medel, R., Wintermark, M., Eames, M., Snell, J., Kassell, N. F., Elias, W. J. 2013; 118 (2): 215-221

    Abstract

    Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

    View details for DOI 10.3171/2012.10.JNS12449

    View details for Web of Science ID 000313937900001

    View details for PubMedID 23176339

  • Radiation-induced imaging changes following Gamma Knife surgery for cerebral arteriovenous malformations Clinical article JOURNAL OF NEUROSURGERY Yen, C., Matsumoto, J. A., Wintermark, M., Schwyzer, L., Evans, A. J., Jensen, M. E., Shaffrey, M. E., Sheehan, J. P. 2013; 118 (1): 63-73
  • Radiation-induced imaging changes following Gamma Knife surgery for cerebral arteriovenous malformations Clinical article NEUROSURGICAL FOCUS Yen, C., Matsumoto, J. A., Wintermark, M., Schwyzer, L., Evans, A. J., Jensen, M. E., Shaffrey, M. E., Sheehan, J. P. 2013; 34 (1): 63-73
  • Multiparametric MRI and CT Models of Infarct Core and Favorable Penumbral Imaging Patterns in Acute Ischemic Stroke STROKE Kidwell, C. S., Wintermark, M., De Silva, D. A., Schaewe, T. J., Jahan, R., Starkman, S., Jovin, T., Hom, J., Jumaa, M., Schreier, J., Gornbein, J., Liebeskind, D. S., Alger, J. R., Saver, J. L. 2013; 44 (1): 73-79

    Abstract

    Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were (1) to develop magnetic resonance imaging (MRI) and computed tomography (CT) multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and (2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization.An analysis of imaging and clinical data was performed on 2 cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified.The MRI and CT models were developed and validated from 34 and 32 patients, using 943 320 and 1 236 917 voxels, respectively. The derivation MRI and 2-branch CT models had an overall accuracy of 74% and 80%, respectively, and were independently validated with an accuracy of 71% and 79%, respectively. The imaging criteria of (1) predicted infarct core ≤90 mL and (2) ratio of predicted infarct tissue within the at-risk region ≤70% identified patients as having a favorable penumbral pattern with 78% to 100% accuracy.Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate.

    View details for DOI 10.1161/STROKEAHA.112.670034

    View details for Web of Science ID 000312883800014

    View details for PubMedID 23233383

  • Perfusion MRI: The Five Most Frequently Asked Technical Questions AMERICAN JOURNAL OF ROENTGENOLOGY Essig, M., Shiroishi, M. S., Thanh Binh Nguyen, T. B., Saake, M., Provenzale, J. M., Enterline, D., Anzalone, N., Doerfler, A., Rovira, A., Wintermark, M., Law, M. 2013; 200 (1): 24-34

    Abstract

    This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging.Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.

    View details for DOI 10.2214/AJR.12.9543

    View details for Web of Science ID 000312772200020

    View details for PubMedID 23255738

  • Radiation-induced imaging changes following Gamma Knife surgery for cerebral arteriovenous malformations. Journal of neurosurgery Yen, C., Matsumoto, J. A., Wintermark, M., Schwyzer, L., Evans, A. J., Jensen, M. E., Shaffrey, M. E., Sheehan, J. P. 2013; 118 (1): 63-73

    Abstract

    The objective of this study was to evaluate the incidence, severity, clinical manifestations, and risk factors of radiation-induced imaging changes (RIICs) following Gamma Knife surgery (GKS) for cerebral arteriovenous malformations (AVMs).A total of 1426 GKS procedures performed for AVMs with imaging follow-up available were analyzed. Radiation-induced imaging changes were defined as newly developed increased T2 signal surrounding the treated AVM nidi. A grading system was developed to categorize the severity of RIICs. Grade I RIICs were mild imaging changes imposing no mass effect on the surrounding brain. Grade II RIICs were moderate changes causing effacement of the sulci or compression of the ventricles. Grade III RIICs were severe changes causing midline shift of the brain. Univariate and multivariate logistic regression analyses were applied to test factors potentially affecting the occurrence, severity, and associated symptoms of RIICs.A total of 482 nidi (33.8%) developed RIICs following GKS, with 281 classified as Grade I, 164 as Grade II, and 37 as Grade III. The median duration from GKS to the development of RIICs was 13 months (range 2-124 months). The imaging changes disappeared completely within 2-128 months (median 22 months) following the development of RIICs. The RIICs were symptomatic in 122 patients, yielding an overall incidence of symptomatic RIICs of 8.6%. Twenty-six patients (1.8%) with RIICs had permanent deficits. A negative history of prior surgery, no prior hemorrhage, large nidus, and a single draining vein were associated with a higher risk of RIICs.Radiation-induced imaging changes are the most common adverse effects following GKS. Fortunately, few of the RIICs are symptomatic and most of the symptoms are reversible. Patients with a relatively healthy brain and nidi that are large, or with a single draining vein, are more likely to develop RIICs.

    View details for DOI 10.3171/2012.10.JNS12402

    View details for PubMedID 23140155

  • Use of Computed Tomography to Identify Atrial Fibrillation Associated Differences in Left Atrial Wall Thickness and Density PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Dewland, T. A., Wintermark, M., Vaysman, A., Smith, L. M., Tong, E., Vittinghoff, E., Marcus, G. M. 2013; 36 (1): 55-62

    Abstract

    Left atrial (LA) tissue characteristics may play an important role in atrial fibrillation (AF) induction and perpetuation. Although frequently used in clinical practice, computed tomography (CT) has not been employed to describe differences in LA wall properties between AF patients and controls. We sought to noninvasively characterize AF-associated differences in LA tissue using CT.CT images of the LA were obtained in 98 consecutive patients undergoing AF ablation and in 89 controls. A custom software algorithm was used to measure wall thickness and density in four prespecified regions of the LA.On average, LA walls were thinner (-15.5%, 95% confidence interval [CI] -23.2 to -7.8%, P < 0.001) and demonstrated significantly lower density (-19.7 Hounsfield Units [HU], 95% CI -27.0 to -12.5 HU, P < 0.001) in AF patients compared to controls. In linear mixed models adjusting for demographics, clinical variables, and other CT measurements, the average LA, interatrial septum, LA appendage, and anterior walls remained significantly thinner in AF patients. After adjusting for the same potential confounders, history of AF was associated with reduced density in the LA anterior wall and increased density below the right inferior pulmonary vein and in the LA appendage.Application of an automated measurement algorithm to CT imaging of the atrium identified significant thinning of the LA wall and regional alterations in tissue density in patients with a history of AF. These findings suggest differences in LA tissue composition can be noninvasively identified and quantified using CT.

    View details for DOI 10.1111/pace.12028

    View details for Web of Science ID 000314658600018

    View details for PubMedID 23106219

  • MRI Blood-Brain Barrier Permeability Measurements to Predict Hemorrhagic Transformation in a Rat Model of Ischemic Stroke TRANSLATIONAL STROKE RESEARCH Hoffmann, A., Bredno, J., Wendland, M. F., Derugin, N., Hom, J., Schuster, T., Zimmer, C., Su, H., Ohara, P. T., Young, W. L., Wintermark, M. 2012; 3 (4): 508-516
  • Perfusion-CT assessment of blood-brain barrier permeability in patients with aneurysmal subarachnoid hemorrhage JOURNAL OF NEURORADIOLOGY Kishore, S., Ko, N., Soares, B. P., Higashida, R. T., Tong, E., Bhogal, S., Bredno, J., Cheng, S., Wintermark, M. 2012; 39 (5): 317-325

    Abstract

    The goal of this study was to determine which clinical and radiographic variables in patients with subarachnoid hemorrhage (SAH) are associated with in vivo blood-brain barrier permeability (BBBP) assessments obtained using perfusion-CT (PCT) technology.SAH patients with confirmed aneurysm etiology and with PCT and angiogram within 24 hours of each other were included, and relationships between clinical and imaging variables were analyzed using random-effects generalized linear models.One thousand one hundred and sixty two vascular territories from 83 patients were evaluated in this study. The mean BBBP increased by severity of vasospasm on DSA, however, in multivariate analysis, only mean transit time (MTT), cerebral blood volume (CBV), and severity of hydrocephalus were significantly associated with BBBP. Increased BBBP was not associated with angiographic vasospasm severity in multivariate analysis.Perfusion-CT assessment of BBBP may serve as a unique and useful biomarker in conjunction with angiography, additional perfusion-CT parameters, and clinical assessments, especially in characterizing microvascular dysfunction, or even in targeting treatments. However, future prospective studies will be required to definitively establish its clinical utility in the care of SAH patients.

    View details for DOI 10.1016/j.neurad.2011.11.004

    View details for Web of Science ID 000313298800006

    View details for PubMedID 22197406

  • Magnetic Resonance-Guided Focused Ultrasound Surgery: Part 2: A Review of Current and Future Applications NEUROSURGERY Medel, R., Monteith, S. J., Elias, W. J., Eames, M., Snell, J., Sheehan, J. P., Wintermark, M., Jolesz, F. A., Kassell, N. F. 2012; 71 (4): 755-763

    Abstract

    Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact.

    View details for DOI 10.1227/NEU.0b013e3182672ac9

    View details for Web of Science ID 000309117200020

    View details for PubMedID 22791029

  • A Pictorial Essay of Brain Perfusion-CT: Not Every Abnormality Is a Stroke! JOURNAL OF NEUROIMAGING Keedy, A., Soares, B., Wintermark, M. 2012; 22 (4): E20-E33

    Abstract

    Perfusion-CT (PCT) of the brain is a rapidly evolving imaging technique used to assess blood supply to the brain parenchyma. PCT is readily available at most imaging centers, resulting in steadily increasing use of this imaging technique. Though PCT was initially introduced and still most widely used to evaluate patients with acute ischemic stroke, a wide variety of other pathologic processes demonstrate abnormal perfusion maps. Therefore, it is important for the radiologist to recognize altered perfusion patterns observed in diseases other than typical ischemic stroke. The goal of this article is to show the perfusion maps and review the perfusion patterns observed in some subtypes of atypical stroke and in neurological entities other than stroke, so that they are recognized and not confused with the PCT patterns observed in patients with typical ischemic stroke.

    View details for DOI 10.1111/j.1552-6569.2012.00716.x

    View details for Web of Science ID 000310563200001

    View details for PubMedID 22985169

  • Refinement of the Magnetic Resonance Diffusion-Perfusion Mismatch Concept for Thrombolytic Patient Selection Insights From the Desmoteplase in Acute Stroke Trials STROKE Warach, S., Al-Rawi, Y., Furlan, A. J., Fiebach, J. B., Wintermark, M., Lindsten, A., Smyej, J., Bharucha, D. B., Pedraza, S., Rowley, H. A. 2012; 43 (9): 2313-?

    Abstract

    The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted.In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2.In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size.Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.

    View details for DOI 10.1161/STROKEAHA.111.642348

    View details for Web of Science ID 000308416300023

    View details for PubMedID 22738918

  • The alphabet soup of perfusion CT and MR imaging: terminology revisited and clarified in five questions NEURORADIOLOGY Leiva-Salinas, C., Provenzale, J. M., Kudo, K., Sasaki, M., Wintermark, M. 2012; 54 (9): 907-918

    Abstract

    The five questions answered in this article revolve around the different parameters resulting from perfusion imaging processing, and this clarifies the frequently confusing terminology used to describe these parameters. More specifically, the article discusses the different imaging techniques and main mathematical models behind perfusion imaging, reviews the perfusion attributes of brain tissue, and proposes a standardized parameter terminology to facilitate understanding and avoid common misinterpretations.

    View details for DOI 10.1007/s00234-012-1028-6

    View details for Web of Science ID 000308534600001

    View details for PubMedID 22488209

  • Do Microemboli Reach the Brain Penetrating Arteries? JOURNAL OF SURGICAL RESEARCH Zhu, L., Hoffmann, A., Wintermark, M., Pan, X., Tu, R., Rapp, J. H. 2012; 176 (2): 679-683

    Abstract

    As they are "end arteries," microembolic obstruction of brain penetrating arteries would be expected to create ischemia. Yet the mammalian brain appears to have an impressive tolerance to experimental microembolization with ischemia occurring only after the injection of large numbers of particulates. Potential explanations could be that the majority of these particulates marginate along the pial vasculature or escape the cerebral circulation via arteriovenous (AV) fistulae.To test these theories, we first established the level of injury created by the injection of 20, 45, and 90 μm fluorescent microspheres in Sprague-Dawley rats. Brains were examined by immunohistochemistry for injury and for infarction. We then injected 1000 size 20 μm, 500 size 45 μm, and 150 size 90 μm and harvested the brains and lungs for assays of fluorescence. The location of microemboli within the brain was established by determining the percent of 20 and 45 μm fluorescent microspheres entering the superficial versus deeper layers of the brain. The location of larger microemboli was established by 2T-MRI after injection of 60-100 μm microthrombi labeled with supraparamagnetic iron oxide (SPIO) particles.With 20 μm microspheres there were no areas of injury or infarction after injection of 500 and rare areas of injury and no infarctions after injection of 1000 microspheres. With either 250 or 500 size 45 μm microspheres there were a few (≤ 6) small areas of injury per animal with ≤ 2 areas of infarction. After injection, 93%-96% of injected microspheres remained in the brain. Approximately 40% of either fluorescent or SPIO labeled microthrombi were found on the brain surface.As in humans, the rat brain has an impressive tolerance to microemboli, although this clearly varies with emboli size and number. Wash out of particulates through AV connections is not a major factor in brain tolerance in this model. Approximately 40% of microemboli remain in the larger pial vasculature where the more extensive collateralization may limit their effects on distal perfusion. However, the remaining 60% enter penetrating arteries but few create ischemia.

    View details for DOI 10.1016/j.jss.2011.09.059

    View details for Web of Science ID 000306488700049

    View details for PubMedID 22261594

  • Vascular Occlusion Enables Selecting Acute Ischemic Stroke Patients for Treatment With Desmoteplase STROKE Fiebach, J. B., Al-Rawi, Y., Wintermark, M., Furlan, A. J., Rowley, H. A., Lindsten, A., Smyej, J., Eng, P., Warach, S., Pedraza, S. 2012; 43 (6): 1561-1566

    Abstract

    Desmoteplase is a novel and highly fibrin-specific thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute Ischemic Stroke [DEDAS]). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post hoc analyses were performed with the aim of predicting treatment responders based on CTA and MRA.Patients were grouped according to vessel status (Thrombolysis In Myocardial Infarction [TIMI] grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2.In DIAS-2, a substantial number of mismatch-selected patients (126/179; 70%) presented with a normal flow/low-grade stenosis (TIMI 2-3) at screening, with the majority having a favorable outcome at day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0-1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect based on the pooled data from DIAS, DEDAS, and DIAS-2 was favorable for desmoteplase-treated patients presenting with TIMI 0 to 1 at baseline (OR, 4.144; 95% CI, 1.40-12.23; P=0.010). There was no desmoteplase treatment benefit in patients presenting with TIMI 2 to 3 (OR, 1.109).In this sample of patients with a mismatch diagnosed, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CTA or MRA in clinical trials of thrombolytic therapy is justifiable.

    View details for DOI 10.1161/STROKEAHA.111.642322

    View details for Web of Science ID 000304523800026

    View details for PubMedID 22474060

  • Standardization of Stroke Perfusion CT for Reperfusion Therapy TRANSLATIONAL STROKE RESEARCH Zhu, G., Michel, P., Zhang, W., Wintermark, M. 2012; 3 (2): 221-227

    Abstract

    With the advances in terms of perfusion imaging, the "time is brain" approach used for acute reperfusion therapy in ischemic stroke patients is slowly being replaced by a "penumbra is brain" or "imaging is brain" approach. But the concept of penumbra-guided reperfusion therapy has not been validated. The lack of standardization in penumbral imaging is one of the main contributing factors for this absence of validation. This article reviews the issues underlying the lack of standardization of perfusion-CT for penumbra imaging, and offers avenues to remedy this situation.

    View details for DOI 10.1007/s12975-012-0156-y

    View details for Web of Science ID 000304625200007

    View details for PubMedID 24323777

  • Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial NEURORADIOLOGY Michel, P., Ntaios, G., Reichhart, M., Schindler, C., Bogousslavsky, J., Maeder, P., Meuli, R., Wintermark, M. 2012; 54 (6): 579-588

    Abstract

    Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset.Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9 mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2 h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria.At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm(3) in the treatment arm and 29 (8-105) cm(3) in the placebo arm.This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be established.

    View details for DOI 10.1007/s00234-011-0944-1

    View details for Web of Science ID 000304399700006

    View details for PubMedID 21808985

  • Subependymal seeding of low-grade oligodendroglial neoplasms: a case series JOURNAL OF NEURO-ONCOLOGY Nicolasjilwan, M., Lopes, M. B., Larner, J., Wintermark, M., Schiff, D. 2012; 108 (1): 99-108

    Abstract

    The CSF dissemination of low-grade glial tumors is a known albeit rare entity. Few cases have been reported in the literature. We describe a unique series of six patients with supratentorial low-grade gliomas who presented to our institution at ages 20-41 years, and developed signal abnormality along the margin of the fourth ventricle without enhancement at variable times during their disease course (0 to 95 months). MR spectroscopy and perfusion-weighted imaging through the region of abnormality in two of these patients were consistent with a low-grade glial tumor. We hypothesize that this finding represents dissemination of the supratentorial low-grade glioma along the ventricular ependyma or through the ventricular CSF. Although the small size of our series does not allow us to draw statistically significant conclusions, this abnormality correlates with progression of the supratentorial disease with or without features of a higher grade malignancy. Additional variables that were present in all six patients include the presence of an oligodendroglial component within the supratentorial tumor, mutated IDH1, and the supratentorial tumor contacting the ventricular margin. All six patients were males.

    View details for DOI 10.1007/s11060-012-0800-0

    View details for Web of Science ID 000303469600011

    View details for PubMedID 22311105

  • Contrast Delay on Perfusion CT as a Predictor of New, Incident Infarct A Retrospective Cohort Study STROKE Keedy, A. W., Fischette, S., Soares, B. P., Arora, S., Lau, B. C., Magge, R., Bredno, J., Cheng, S., Wintermark, M. 2012; 43 (5): 1295-1301

    Abstract

    The purpose of this study was to determine if the assessment of intracranial collateral circulation by CT angiography and/or perfusion CT (PCT) can predict the risk of future ischemic stroke in a large, retrospective cohort study.We identified 135 consecutive patients who underwent CT angiography of the head and neck and PCT of the brain at baseline and with subsequent follow-up brain imaging. Clinical and demographic information and carotid wall features were collected. Collateral circulation was assessed anatomically at CT angiography and functionally by measuring the mean transit time delay at PCT. The clinical, carotid, CT angiography, and PCT variables were compared between those with and without new incident infarct at follow-up imaging using mixed effect logistic statistical models.During the follow-up period, 15 patients developed a new infarct and 120 patients did not. Clinical features associated with the stroke risk were age, hypertension, hyperlipidemia, and atrial fibrillation. The carotid features associated with stroke risk were wall thickness. Anatomic assessment of collaterals on CT angiography was not associated with stroke risk, whereas the functional assessment of collaterals (mean transit time delay on PCT) was associated with stroke risk. In a multivariate model, age, atrial fibrillation, and mean transit time delay (OR, 22.8; P<0.001) were the only covariates that were independent predictors of future ischemic stroke.The mean transit time delay on PCT contains important physiological information and should not be discarded. Along with age and atrial fibrillation, this functional assessment of intracranial collateral circulation predicts the risk of future hemispheric infarct.

    View details for DOI 10.1161/STROKEAHA.111.639229

    View details for Web of Science ID 000303602700029

    View details for PubMedID 22363062

  • Advanced neuroimaging in stroke patients: prediction of tissue fate and hemorrhagic transformation. Expert review of cardiovascular therapy Hoffmann, A., Zhu, G., Wintermark, M. 2012; 10 (4): 515-524

    Abstract

    Stroke is the second greatest cause of mortality worldwide after ischemic heart disease. It is also the leading cause of disability in industrialized countries. According to the WHO, 15 million people worldwide suffer a stroke annually. It is very difficult to distinguish between an ischemic and a hemorrhagic stroke on a clinical basis, therefore imaging (computed tomography or MRI) plays a central role in the evaluation of patients with acute stroke symptoms. Because of significant advances over the last decade, imaging now provides information beyond the mere presence or absence of intracerebral hemorrhage. Comprehensive neurovascular imaging protocols using computed tomography or MRI can be acquired within minutes, helping to distinguish stroke etiology and guiding treatment decisions for acute reperfusion therapies. The purpose of this article is to give an overview of diagnostic information provided by neuroimaging in the setting of acute stroke, especially ischemic stroke, including information about brain tissue viability status and blood-brain barrier permeability. We will discuss the indications of the current treatment options for stroke, and how imaging influences treatment decision. We will organize our discussion around the concept of the 'four Ps' (parenchyma, pipes, penumbra and permeability) proposed by Howard Rowley, which is an excellent guide for understanding the underlying causes and pathophysiology of ischemic stroke.

    View details for DOI 10.1586/erc.12.30

    View details for PubMedID 22458583

  • Neonatal non-ketotic hyperglycinemia JOURNAL OF NEURORADIOLOGY Nicolasjilwan, M., Ozer, H., Wintermark, M., Matsumoto, J. 2011; 38 (4): 246-250

    Abstract

    The typical imaging findings of neonatal non-ketotic hyperglycinemia have rarely been described in the radiologic literature with only few individual cases or small series reported. In this article, we present a case of neonatal onset non-ketotic hyperglycinemia, imaged at 6 days of age, and discuss characteristic MRI and MR spectroscopic findings.

    View details for DOI 10.1016/j.neurad.2010.11.005

    View details for Web of Science ID 000296268800008

    View details for PubMedID 21354623

  • Comparison of Computed Tomography Angiography and Transesophageal Echocardiography for Evaluating Aortic Arch Disease JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Barazangi, N., Wintermark, M., Lease, K., Rao, R., Smith, W., Josephson, S. A. 2011; 20 (5): 436-442

    Abstract

    Aortic arch (AA) atheroma is a common source of artery-to-artery embolism. Identification of AA atherosclerotic disease is an important component of the embolic stroke workup. Transesophageal echocardiography (TEE) is the gold standard for AA evaluation, but it has associated risks and is not always readily available. Computed tomography angiography (CTA) is a rapid and noninvasive alternative. This study was conducted to compare the sensitivity and specificity of CTA and TEE for detecting AA disease. We performed a retrospective review of 250 consecutive patients at a tertiary stroke center who underwent both TEE and CTA within a 90-day period. We compared the presence and characteristics of AA plaques using a predetermined grading system for plaques in the ascending, transverse, and descending arch for both modalities (grades 1-4). Out of 750 AA segments (ascending, transverse, and descending AA in 250 patients), 494 were adequately imaged by CTA and TEE. The sensitivity of CTA in detecting grade 1-4 AA atheromas was 53%, and the specificity was 89%. For only high-grade atheromas, the specificity improved to 99%, but the sensitivity decreased to 23%. The negative predictive value of CTA for detection of AA atheromas was 60% (range 54%-65%) for all grades and 95% (range 92%-96%) for high-grade atheromas. CTA has a high negative predictive value for AA atheromas, especially for higher-grade atheromas, and thus may be a useful screening tool to exclude high-grade plaques, indicating a possible complementary role for CTA in detecting AA atheromas.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2010.02.016

    View details for Web of Science ID 000294981100008

    View details for PubMedID 20813553

  • Stroke Treatment Academic Industry Roundtable (STAIR) Recommendations for Maximizing the Use of Intravenous Thrombolytics and Expanding Treatment Options With Intra-arterial and Neuroprotective Therapies STROKE Albers, G. W., Goldstein, L. B., Hess, D. C., Wechsler, L. R., Furie, K. L., Gorelick, P. B., Hurn, P., Liebeskind, D. S., Nogueira, R. G., Saver, J. L. 2011; 42 (9): 2645-2650

    Abstract

    The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of acute and restorative stroke therapies. Summary of Review- At the STAIR VII recommendations for strategies to maximize the use of intravenous thrombolytics through targeting public education, and the refinement of current treatment exclusion criteria were proposed. Increased utilization of mechanical devices for intra-arterial recanalization can be achieved by obtaining more definitive evidence of efficacy in randomized clinical trials, identification of patient characteristics associated with treatment efficacy, optimization of technical approaches, clarification of effective time windows, and development of approaches to limit complications. Neuroprotective strategies remain viable; recommendations for further study of these agents include an emphasis on rapid administration, consideration of the systemic effects of ischemic stroke, prevention of complications associated with early reperfusion, a focus on agents with multiple mechanisms of action, and consideration of possible interactions between neuroprotective and thrombolytic therapies.Extending intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies, and further development of neuroprotective therapies were the key recommendations from STAIR VII.

    View details for DOI 10.1161/STROKEAHA.111.618850

    View details for Web of Science ID 000294342800061

    View details for PubMedID 21852620

  • The Vascular Effects of Infection in Pediatric Stroke (VIPS) Study JOURNAL OF CHILD NEUROLOGY Fullerton, H. J., Elkind, M. S., Barkovich, A. J., Glaser, C., Glidden, D., Hills, N. K., Leiva-Salinas, C., Wintermark, M., deVeber, G. A. 2011; 26 (9): 1101-1110

    Abstract

    Understanding the vascular injury pathway is crucial to developing rational strategies for secondary stroke prevention in children. The multicenter Vascular Effects of Infection in Pediatric Stroke (VIPS) cohort study will test the hypotheses that (1) infection can lead to childhood arterial ischemic stroke by causing vascular injury and (2) resultant arteriopathy and inflammatory markers predict recurrent stroke. The authors are prospectively enrolling 480 children (aged 1 month through 18 years) with arterial ischemic stroke and collecting extensive infectious histories, blood and serum samples (and cerebrospinal fluid, when clinically obtained), and standardized brain and cerebrovascular imaging studies. Laboratory assays include serologies (acute and convalescent) and molecular assays for herpesviruses and levels of inflammatory markers. Participants are followed prospectively for recurrent ischemic events (minimum of 1 year). The analyses will measure association between markers of infection and cerebral arteriopathy and will assess whether cerebral arteriopathy and inflammatory markers predict recurrent stroke.

    View details for DOI 10.1177/0883073811408089

    View details for Web of Science ID 000293892500003

    View details for PubMedID 21616922

  • Delay correction for the assessment of blood-brain barrier permeability using first-pass dynamic perfusion CT. AJNR. American journal of neuroradiology Schneider, T., Hom, J., Bredno, J., Dankbaar, J. W., Cheng, S., Wintermark, M. 2011; 32 (7): E134-8

    Abstract

    Hemorrhagic transformation is a serious potential complication of ischemic stroke with damage to the BBB as one of the contributing mechanisms. BBB permeability measurements extracted from PCT by using the Patlak model can provide a valuable assessment of the extent of BBB damage. Unfortunately, Patlak assumptions require extended PCT acquisition, increasing the risk of motion artifacts. A necessary correction is presented for obtaining accurate BBB permeability measurements from first-pass PCT.

    View details for DOI 10.3174/ajnr.A2152

    View details for PubMedID 20538824

  • Validation of In Vivo Magnetic Resonance Imaging Blood-Brain Barrier Permeability Measurements by Comparison With Gold Standard Histology STROKE Hoffmann, A., Bredno, J., Wendland, M. F., Derugin, N., Hom, J., Schuster, T., Su, H., Ohara, P. T., Young, W. L., Wintermark, M. 2011; 42 (7): 2054-2060

    Abstract

    We sought to validate the blood-brain barrier permeability measurements extracted from perfusion-weighted MRI through a relatively simple and frequently applied model, the Patlak model, by comparison with gold standard histology in a rat model of ischemic stroke.Eleven spontaneously hypertensive rats and 11 Wistar rats with unilateral 2-hour filament occlusion of the right middle cerebral artery underwent imaging during occlusion at 4 hours and 24 hours after reperfusion. Blood-brain barrier permeability was imaged by gradient echo imaging after the first pass of the contrast agent bolus and quantified by a Patlak analysis. Blood-brain barrier permeability was shown on histology by the extravasation of Evans blue on fluorescence microscopy sections matching location and orientation of MR images. Cresyl-violet staining was used to detect and characterize hemorrhage. Landmark-based elastic image registration allowed a region-by-region comparison of permeability imaging at 24 hours with Evans blue extravasation and hemorrhage as detected on histological slides obtained immediately after the 24-hour image set.Permeability values in the nonischemic tissue (marginal mean ± SE: 0.15 ± 0.019 mL/min 100 g) were significantly lower compared to all permeability values in regions of Evans blue extravasation or hemorrhage. Permeability values in regions of weak Evans blue extravasation (0.23 ± 0.016 mL/min 100 g) were significantly lower compared to permeability values of in regions of strong Evans blue extravasation (0.29 ± 0.020 mL/min 100 g) and macroscopic hemorrhage (0.35 ± 0.049 mL/min 100 g). Permeability values in regions of microscopic hemorrhage (0.26 ± 0.024 mL/min 100 g) only differed significantly from values in regions of nonischemic tissue (0.15 ± 0.019 mL/min 100 g).Areas of increased permeability measured in vivo by imaging coincide with blood-brain barrier disruption and hemorrhage observed on gold standard histology.

    View details for DOI 10.1161/STROKEAHA.110.597997

    View details for Web of Science ID 000292090900054

    View details for PubMedID 21636816

  • Dynamic perfusion-CT assessment of early changes in blood brain barrier permeability of acute ischaemic stroke patients JOURNAL OF NEURORADIOLOGY Dankbaar, J. W., Hom, J., Schneider, T., Cheng, S., Bredno, J., LAU, B. C., van der Schaaf, I. C., Wintermark, M. 2011; 38 (3): 161-166

    Abstract

    Damage to the blood brain barrier (BBB) may lead to haemorrhagic transformation after ischaemic stroke. The purpose of this study was to evaluate the effect of patient characteristics and stroke severity on admission BBB permeability (BBBP) values measured with perfusion-CT (PCT) in acute ischaemic stroke patients.We retrospectively identified 65 patients with proven ischaemic stroke admitted within 12 hours after symptom onset. Patients' charts were reviewed for demographic variables and vascular risk factors. The Patlak's model was applied to calculate BBBP values from the PCT data in the infarct core, penumbra and non-ischaemic tissue in the contralateral hemisphere. Mean BBBP values and their 95% confidence intervals (CI) were calculated in the different tissue types. Effects of demographic variables and risk factors on BBBP were analyzed using a multivariate, generalized estimating equations (GEE) model.BBBP values in the infarct core (mean [95%CI]: 2.48 [2.16-2.85]) and penumbra (2.48 [2.21-2.79]) were significantly higher than in non-ischaemic tissue (2.12 [1.88-2.39]). Multivariate analysis demonstrated that collateral filling has effect on BBBP. Less elevated BBBP values were associated with more than 50% collateral filling.BBBP values are increased in ischaemic brain tissue on the admission PCT scan of acute ischaemic stroke patients. Less abnormally elevated BBBP values were observed in patients with more than 50% collateral filling, possibly explaining why there is a relationship between more collateral filling and a lower incidence of haemorrhagic transformation.

    View details for DOI 10.1016/j.neurad.2010.08.001

    View details for Web of Science ID 000293209800005

    View details for PubMedID 20950860

  • CT Perfusion Imaging in Acute Stroke NEUROIMAGING CLINICS OF NORTH AMERICA Konstas, A. A., Wintermark, M., Lev, M. H. 2011; 21 (2): 215-?

    Abstract

    Computed tomographic perfusion (CTP) imaging is an advanced modality that provides important information about capillary-level hemodynamics of the brain parenchyma. CTP can aid in diagnosis, management, and prognosis of acute stroke patients by clarifying acute cerebral physiology and hemodynamic status, including distinguishing severely hypoperfused but potentially salvageable tissue from both tissue likely to be irreversibly infarcted ("core") and hypoperfused but metabolically stable tissue ("benign oligemia"). A qualitative estimate of the presence and degree of ischemia is typically required for guiding clinical management. Radiation dose issues with CTP imaging, a topic of much current concern, are also addressed in this review.

    View details for DOI 10.1016/j.nic.2011.01.008

    View details for Web of Science ID 000292007900004

    View details for PubMedID 21640296

  • Stroke Imaging Research Road Map NEUROIMAGING CLINICS OF NORTH AMERICA Leiva-Salinas, C., Hom, J., Warach, S., Wintermark, M. 2011; 21 (2): 239-?

    Abstract

    Although acute stroke imaging has made significant progress in the last few years, several improvements and validation steps are needed to make stroke-imaging techniques fully operational and appropriate in daily clinical practice. This review outlines the needs in the stroke-imaging field and describes a consortium that was founded to provide them.

    View details for DOI 10.1016/j.nic.2011.01.009

    View details for Web of Science ID 000292007900005

    View details for PubMedID 21640297

  • The distribution and size of ischemic lesions after carotid artery angioplasty and stenting: Evidence for microembolization to terminal arteries JOURNAL OF VASCULAR SURGERY Zhu, L., Wintermark, M., Saloner, D., Fandel, M., Pan, X. M., Rapp, J. H. 2011; 53 (4): 971-976

    Abstract

    Much of the brain is perfused by penetrating arteries that are the "single source" of blood to their surrounding tissues. These tissues should be equally vulnerable to ischemia from embolic occlusion, but there are questions about whether emboli have access to the penetrating arteries serving the deep brain tissues. To examine this issue in humans we recorded the number and distribution of new ischemic lesions on diffusion-weighted magnetic resonance imaging (DWMRI) after carotid artery stenting (CAS), a procedure producing showers of numerous small atheroemboli.Twenty-nine men (aged 62-81) underwent 30 CAS procedures with distal protection in place, and DWMRI 48 hours after the procedure documented new lesions had developed. Thirteen patients were asymptomatic, and 16 had experienced recent symptoms ipsilateral to the treated carotid stenosis. A DWMRI study was done in each patient ≤72 hours before the procedure. All MRI studies were read by the same neuroradiologist.One patient sustained a minor stroke, which resolved. DWNRI found 131 new lesions (median, 3; range, 1-17; interquartile range, 2-4). Lesion size was <5 mm in 96.6% and 5 to 10 mm in 3.1%. Lesions were ipsilateral in 83.1% and contralateral in 16.9%. Lesions were in the distribution of the middle cerebral artery (91.6%), posterior cerebral artery (6.1%), and superior cerebellar artery subclavian artery (2.0%). Most lesions were in the cortex but at a depth where they were best described as cortical/subcortical (90.8%). The rest were in the periventricular white matter (6.1%) and deep gray matter (3.0%).The ischemic areas developing after CAS were predominately in the deeper layers of the cortex in the distribution of the middle cerebral artery, but lesions were seen throughout the brain. The distribution of lesions caused by CAS-induced embolization coincided with estimates of blood flow to the respective areas of the brain. These data add to the evidence implicating microemboli in ischemic pathologies throughout the brain.

    View details for DOI 10.1016/j.jvs.2010.10.091

    View details for Web of Science ID 000289012600012

    View details for PubMedID 21215560

  • High and Low Molecular Weight Fluorescein Isothiocyanate (FITC)-Dextrans to Assess Blood-Brain Barrier Disruption: Technical Considerations TRANSLATIONAL STROKE RESEARCH Hoffmann, A., Bredno, J., Wendland, M., Derugin, N., Ohara, P., Wintermark, M. 2011; 2 (1): 106-111

    Abstract

    This note is to report how histological preparation techniques influence the extravasation pattern of the different molecular sizes of fluorescein isothiocyanate (FITC)-dextrans, typically used as markers for blood-brain barrier leakage. By using appropriate preparation methods, false negative results can be minimized. Wistar rats underwent a 2-h middle cerebral artery occlusion and magnetic resonance imaging. After the last imaging scan, Evans blue and FITC-dextrans of 4, 40, and 70 kDa molecular weight were injected. Different histological preparation methods were used. Sites of blood-brain barrier leakage were analyzed by fluorescence microscopy. Extravasation of Evans blue and high molecular FITC-dextrans (40 and 70 kDa) in the infarcted region could be detected with all preparation methods used. If exposed directly to saline, the signal intensity of these FITC-dextrans decreased. Extravasation of the 4-kDa low molecular weight FITC-dextran could only be detected using freshly frozen tissue sections. Preparations involving paraformaldehyde and sucrose resulted in the 4-kDa FITC-dextran dissolving in these reactants and being washed out, giving the false negative result of no extravasation. FITC-dextrans represent a valuable tool to characterize altered blood-brain barrier permeability in animal models. Diffusion and washout of low molecular weight FITC-dextran can be avoided by direct immobilization through immediate freezing of the tissue. This pitfall needs to be known to avoid the false impression that there was no extravasation of low molecular weight FITC-dextrans.

    View details for DOI 10.1007/s12975-010-0049-x

    View details for Web of Science ID 000304162800014

    View details for PubMedID 21423333

  • Causes of Misinterpretation of Cross-Sectional Imaging Studies for Dissection of the Craniocervical Arteries AMERICAN JOURNAL OF ROENTGENOLOGY Provenzale, J. M., Sarikaya, B., Hacein-Bey, L., Wintermark, M. 2011; 196 (1): 45-52

    Abstract

    This review presents some of the more common causes of false-positive and false-negative interpretations of cross-sectional imaging studies showing, or designed to show, dissection of the carotid or vertebral arteries.Dissection of the craniocervical arteries is a diagnosis that can be very difficult on cross-sectional imaging studies such as CT angiography, MRI, and MR angiography.

    View details for DOI 10.2214/AJR.10.5384

    View details for Web of Science ID 000286018800006

    View details for PubMedID 21178045

  • Ischemic Stroke: Etiologic Work-up with Multidetector CT of Heart and Extra- and Intracranial Arteries RADIOLOGY Boussel, L., Cakmak, S., Wintermark, M., Nighoghossian, N., Loffroy, R., Coulon, P., Derex, L., Cho, T. H., Douek, P. C. 2011; 258 (1): 206-212

    Abstract

    To assess the potential of a single-session multidetector computed tomography (CT) protocol, as compared with established methods, for the etiologic work-up of acute ischemic stroke.Patients found to have recently experienced an ischemic stroke were recruited for this prospective study after institutional review board approval was obtained. Each patient was scheduled for two evaluation strategies: (a) a standard approach involving transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE), duplex ultrasonography (US) of the neck vessels, and magnetic resonance (MR) angiography of the neck and brain vessels; and (b) a protocol involving single-session multidetector CT of the heart, neck, and brain vessels. The authors sought to determine the major etiologic factors of stroke, including cardiac sources of embolism and atheroma of the aortic arch and the extra- and intracranial vessels, by using both strategies.Multidetector CT, MR imaging, and duplex US were performed in 46 patients, 39 of whom also underwent TEE. The sensitivity and specificity of multidetector CT were 72% (18 of 25 cases) and 95% (20 of 21 cases), respectively, for detection of cardiac sources and 100% (24 of 24 cases) and 91% (20 of 22 cases), respectively, for detection of major arterial atheroma. For the 46 cases of stroke, the final etiologic classifications determined by using the standard combination approach were cardiac sources in 20 (44%) cases, major arterial atheroma in nine (20%), multiple sources in four (9%), and cryptogenic sources in 13 (28%). Multidetector CT facilitated correct etiologic classification for 38 (83%) of the 46 patients.Multidetector CT is a promising tool for etiologic assessment of ischemic stroke, although the identification of minor cardiac sources with this examination requires the establishment of robust criteria.

    View details for DOI 10.1148/radiol.10100804

    View details for Web of Science ID 000285574200024

    View details for PubMedID 21062925

  • Responses to the 10 Most Frequently Asked Questions About Perfusion CT AMERICAN JOURNAL OF ROENTGENOLOGY Leiva-Salinas, C., Provenzale, J. M., Wintermark, M. 2011; 196 (1): 53-60

    Abstract

    The objective of this article is to address the 10 most frequently asked questions radiologists face when planning, performing, processing, and interpreting a perfusion CT study in a patient with clinical suspicion of acute ischemic stroke.It is important for radiologists using PCT for stroke imaging to be familiar with the perfusion software used at their institution, with the parameters that can be selected during the post-processing and how these may influence the PCT results.

    View details for DOI 10.2214/AJR.10.5705

    View details for Web of Science ID 000286018800007

    View details for PubMedID 21178046

  • Neuroimaging of Cerebral Ischemia and Infarction NEUROTHERAPEUTICS Leiva-Salinas, C., Wintermark, M., Kidwell, C. S. 2011; 8 (1): 19-27

    Abstract

    The imaging workup for patients with suspected acute ischemic stroke has advanced significantly over the past few years. Evaluation is no longer limited to noncontrast computed tomography, but now frequently also includes vascular and perfusion imaging. Although acute stroke imaging has made significant progress in the last few decades with the development of multimodal approaches, there are still many unanswered questions regarding their appropriate use in the setting of daily patient care. It is important for all physicians taking care of stroke patients to be familiar with current multimodal computed tomography and magnetic resonance imaging techniques, including their strengths, limitations, and their role in guiding therapy.

    View details for DOI 10.1007/s13311-010-0004-2

    View details for Web of Science ID 000289566500004

    View details for PubMedID 21274682

  • Blood-Brain Barrier Permeability Assessed by Perfusion CT Predicts Symptomatic Hemorrhagic Transformation and Malignant Edema in Acute Ischemic Stroke AMERICAN JOURNAL OF NEURORADIOLOGY Hom, J., Dankbaar, J. W., Soares, B. P., Schneider, T., Cheng, S., Bredno, J., LAU, B. C., Smith, W., Dillon, W. P., Wintermark, M. 2011; 32 (1): 41-48

    Abstract

    SHT and ME are feared complications in patients with acute ischemic stroke. They occur >10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in predicting the development of SHT and ME in patients with acute ischemic stroke.We retrospectively analyzed a dataset consisting of 32 consecutive patients with acute ischemic stroke with appropriate admission and follow-up imaging. We calculated admission BBBP by using delayed-acquisition PCT data and the Patlak model. Collateral flow was assessed on the admission CTA, while recanalization and reperfusion were assessed on the follow-up CTA and PCT, respectively. SHT and ME were defined according to ECASS III criteria. Clinical data were obtained from chart review. In our univariate and forward selection-based multivariate analysis for predictors of SHT and ME, we incorporated both clinical and imaging variables, including age, admission NIHSS score, admission blood glucose level, admission blood pressure, time from symptom onset to scanning, treatment type, admission PCT-defined infarct volume, admission BBBP, collateral flow, recanalization, and reperfusion. Optimal sensitivity and specificity for SHT and ME prediction were calculated by using ROC analysis.In our sample of 32 patients, 3 developed SHT and 3 developed ME. Of the 3 patients with SHT, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device; of the 3 patients with ME, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device. Admission BBBP measurements above the threshold were 100% sensitive and 79% specific in predicting SHT and ME. Furthermore, all patients with SHT and ME--and only those with SHT and ME--had admission BBBP measurements above the threshold, were older than 65 years of age, and received tPA. Admission BBBP, age, and tPA were the independent predictors of SHT and ME in our forward selection-based multivariate analysis. Of these 3 variables, only BBBP measurements and age were known before making the decision of administering tPA and thus are clinically meaningful.Admission BBBP, a pretreatment measurement, was 100% sensitive and 79% specific in predicting SHT and ME.

    View details for DOI 10.3174/ajnr.A2244

    View details for Web of Science ID 000287016200008

    View details for PubMedID 20947643

  • The pre-requisite of a second-generation glioma PET biomarker JOURNAL OF THE NEUROLOGICAL SCIENCES Borbely, K., Wintermark, M., Martos, J., Fedorcsak, I., Bognar, L., Kasler, M. 2010; 298 (1-2): 11-16

    Abstract

    Since the introduction of FDG into the field of molecular imaging with positron emission tomography (PET) more than three decades ago, FDG has been the tracer of choice for oncology PET imaging. Despite the relative disadvantages of FDG and the relative benefits of its challengers, FDG remains the most commonly used glioma tracer nowadays. The present article surveys the expectations of the field and gives a concise summary of recent developments; including the issues pertaining to the continued search for an optimal second-generation PET biomarker for glioma.The present article gives a concise summary of recent developments; including the issues pertaining to the continued search for an optimal PET biomarker for glioma.

    View details for DOI 10.1016/j.jns.2010.07.024

    View details for Web of Science ID 000284441200002

    View details for PubMedID 20739034

  • Common Data Elements in Radiologic Imaging of Traumatic Brain Injury ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Duhaime, A., Gean, A. D., Haacke, E. M., Hicks, R., Wintermark, M., Mukherjee, P., Brody, D., Latour, L., Riedy, G. 2010; 91 (11): 1661-1666

    Abstract

    Radiologic brain imaging is the most useful means of visualizing and categorizing the location, nature, and degree of damage to the central nervous system sustained by patients with traumatic brain injury (TBI). In addition to determining acute patient management and prognosis, imaging is crucial for the characterization and classification of injuries for natural history studies and clinical trials. This article is the initial result of a workshop convened by multiple national health care agencies in March 2009 to begin to make recommendations for potential data elements dealing with specific radiologic features and definitions needed to characterize injuries, as well as specific techniques and parameters needed to optimize radiologic data acquisition. The neuroimaging work group included professionals with expertise in basic imaging research and physics, clinical neuroradiology, neurosurgery, neurology, physiatry, psychiatry, TBI research, and research database formation. This article outlines the rationale and overview of their specific recommendations. In addition, we review the contributions of various imaging modalities to the understanding of TBI and the general principles needed for database flexibility and evolution over time to accommodate technical advances.

    View details for DOI 10.1016/j.apmr.2010.07.238

    View details for Web of Science ID 000284346400005

    View details for PubMedID 21044709

  • Imaging of Acute Ischemic Stroke NEUROIMAGING CLINICS OF NORTH AMERICA Leiva-Salinas, C., Wintermark, M. 2010; 20 (4): 455-?

    Abstract

    In this article the individual components of multimodal computed tomography and multimodal magnetic resonance imaging are discussed, the current status of neuroimaging for the evaluation of the acute ischemic stroke is presented, and the potential role of a combined multimodal stroke protocol is addressed.

    View details for DOI 10.1016/j.nic.2010.07.002

    View details for Web of Science ID 000284504300003

    View details for PubMedID 20974371

  • The Acute STroke Registry and Analysis of Lausanne (ASTRAL) Design and Baseline Analysis of an Ischemic Stroke Registry Including Acute Multimodal Imaging STROKE Michel, P., Odier, C., Rutgers, M., Reichhart, M., Maeder, P., Meuli, R., Wintermark, M., Maghraoui, A., Faouzi, M., Croquelois, A., Ntaios, G. 2010; 41 (11): 2491-2498

    Abstract

    Stroke registries are valuable tools for obtaining information about stroke epidemiology and management. The Acute STroke Registry and Analysis of Lausanne (ASTRAL) prospectively collects epidemiological, clinical, laboratory and multimodal brain imaging data of acute ischemic stroke patients in the Centre Hospitalier Universitaire Vaudois (CHUV). Here, we provide design and methods used to create ASTRAL and present baseline data of our patients (2003 to 2008).All consecutive patients admitted to CHUV between January 1, 2003 and December 31, 2008 with acute ischemic stroke within 24 hours of symptom onset were included in ASTRAL. Patients arriving beyond 24 hours, with transient ischemic attack, intracerebral hemorrhage, subarachnoidal hemorrhage, or cerebral sinus venous thrombosis, were excluded. Recurrent ischemic strokes were registered as new events.Between 2003 and 2008, 1633 patients and 1742 events were registered in ASTRAL. There was a preponderance of males, even in the elderly. Cardioembolic stroke was the most frequent type of stroke. Most strokes were of minor severity (National Institute of Health Stroke Scale [NIHSS] score ≤ 4 in 40.8% of patients). Cardioembolic stroke and dissections presented with the most severe clinical picture. There was a significant number of patients with unknown onset stroke, including wake-up stroke (n=568, 33.1%). Median time from last-well time to hospital arrival was 142 minutes for known onset and 759 minutes for unknown-onset stroke. The rate of intravenous or intraarterial thrombolysis between 2003 and 2008 increased from 10.8% to 20.8% in patients admitted within 24 hours of last-well time. Acute brain imaging was performed in 1695 patients (97.3%) within 24 hours. In 1358 patients (78%) who underwent acute computed tomography angiography, 717 patients (52.8%) had significant abnormalities. Of the 1068 supratentorial stroke patients who underwent acute perfusion computed tomography (61.3%), focal hypoperfusion was demonstrated in 786 patients (73.6%).This hospital-based prospective registry of consecutive acute ischemic strokes incorporates demographic, clinical, metabolic, acute perfusion, and arterial imaging. It is characterized by a high proportion of minor and unknown-onset strokes, short onset-to-admission time for known-onset patients, rapidly increasing thrombolysis rates, and significant vascular and perfusion imaging abnormalities in the majority of patients.

    View details for DOI 10.1161/STROKEAHA.110.596189

    View details for Web of Science ID 000283443500029

    View details for PubMedID 20930152

  • Perfusion-CT of developmental venous anomalies: typical and atypical hemodynamic patterns JOURNAL OF NEURORADIOLOGY Kroll, H., Soares, B. P., Saloner, D., Dillon, W. P., Wintermark, M. 2010; 37 (4): 239-242

    Abstract

    This article reports perfusion-CT patterns that can be observed in patients with DVAs. In atypical DVAs, an abnormal venous congestion pattern with increased CBV, CBF and MTT can be observed in the vicinity of a DVA, and needs to be recognized and differentiated from other entities such as cerebral neoplasms or stroke. This pattern might help to stratify risks of associated complications such as hemorrhage.

    View details for DOI 10.1016/j.neurad.2009.09.002

    View details for Web of Science ID 000283706500005

    View details for PubMedID 19959233

  • The Future of Stroke Imaging What We Need and How to Get to It STROKE Leiva-Salinas, C., Wintermark, M. 2010; 41 (10): S152-S153

    Abstract

    Clinical trials of reperfusion therapies for acute ischemic stroke patients in an extended time window have shown mixed results. Advanced neuroimaging for stroke, more specifically vascular imaging and perfusion/penumbral imaging, have been hypothesized to be powerful selection tools in this setting. However, a number of improvements and validation steps are needed to make these imaging techniques operational and accurate in the stroke community in general. This article briefly describes the needs in this field and recommends future steps to achieve them.

    View details for DOI 10.1161/STROKEAHA.110.595116

    View details for Web of Science ID 000282224300041

    View details for PubMedID 20876493

  • Perfusion Computed Tomographic Imaging and Surgical Selection With Patients After Poor-Grade Aneurysmal Subarachnoid Hemorrhage NEUROSURGERY Huang, A. P., Arora, S., Wintermark, M., Ko, N., Tu, Y., Lawton, M. T. 2010; 67 (4): 964-974

    Abstract

    Patients with ruptured aneurysms who present in coma have already experienced significant brain injury, require intensive resuscitation, have aneurysms that are difficult to treat, and generally fare poorly despite aggressive intervention.To determine whether surgical outcomes in comatose patients with ruptured aneurysms in a modern series might be better than previously reported because of changing surgical indications and multidisciplinary management, and to determine whether perfusion computed tomography (PCT) imaging might help select patients for surgery.A consecutive series of 78 patients with poor-grade aneurysms treated surgically was reviewed. Management consisted of resuscitation, early surgery, intracranial pressure control, comprehensive intensive care, and endovascular therapy for vasospasm. Cerebral blood flow (CBF), volume (CBV), and mean transit time (MTT) were measured on admission PCT studies and correlated with outcomes.Among 58 grade IV patients (74%) and 20 grade V patients (26%), 44 patients (56%) had favorable outcomes (Glasgow Outcome Scale 5 and 4), and 34 patients (44%) had unfavorable outcomes. Favorable outcomes among grade IV patients were observed in 71%, whereas mortality among grade V patients was 60%. Sixteen patients (89%) with normal cerebral perfusion had favorable outcomes and all 13 patients with hemispheric or global hypoperfusion had unfavorable outcomes.PCT provides physiological data that are immediately applicable and can guide decisions to aggressively manage comatose patients with ruptured aneurysms. Grade IV patients with normal or focally abnormal perfusion are good candidates for treatment, whereas grade V patients with hemispheric or global hypoperfusion are poor candidates. Surgery effectively excludes aneurysms with complex anatomy and relieves increased intracranial pressure with hematoma evacuation, lobectomy, and/or hemicraniectomy. Modern neurosurgical, endovascular, and neurointensive critical care produces favorable outcomes in a substantial percentage of carefully selected patients.

    View details for DOI 10.1227/NEU.0b013e3181ee359c

    View details for Web of Science ID 000282197900034

    View details for PubMedID 20881562

  • Common Data Elements in Radiologic Imaging of Traumatic Brain Injury JOURNAL OF MAGNETIC RESONANCE IMAGING Haacke, E. M., Duhaime, A. C., Gean, A. D., Riedy, G., Wintermark, M., Mukherjee, P., Brody, D. L., DeGraba, T., Duncan, T. D., Elovic, E., Hurley, R., Latour, L., Smirniotopoulos, J. G., Smith, D. H. 2010; 32 (3): 516-543

    Abstract

    Traumatic brain injury (TBI) has a poorly understood pathology. Patients suffer from a variety of physical and cognitive effects that worsen as the type of trauma worsens. Some noninvasive insights into the pathophysiology of TBI are possible using magnetic resonance imaging (MRI), computed tomography (CT), and many other forms of imaging as well. A recent workshop was convened to evaluate the common data elements (CDEs) that cut across the imaging field and given the charge to review the contributions of the various imaging modalities to TBI and to prepare an overview of the various clinical manifestations of TBI and their interpretation. Technical details regarding state-of-the-art protocols for both MRI and CT are also presented with the hope of guiding current and future research efforts as to what is possible in the field. Stress was also placed on the potential to create a database of CDEs as a means to best record information from a given patient from the reading of the images.

    View details for DOI 10.1002/jmri.22259

    View details for Web of Science ID 000281532700002

    View details for PubMedID 20815050

  • Carotid Atherosclerosis Does Not Predict Coronary, Vertebral, or Aortic Atherosclerosis in Patients With Acute Stroke Symptoms STROKE Adraktas, D. D., Brasic, N., Furtado, A. D., Cheng, S., Ordovas, K., Chun, K., Chien, J. D., Schaeffer, S., Wintermark, M. 2010; 41 (8): 1604-1609

    Abstract

    The purpose of this study was to determine whether significant atherosclerotic disease in the carotid arteries predicts significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke.Atherosclerotic disease was imaged using CT angiography in a prospective study of 120 consecutive patients undergoing emergent CT evaluation for symptoms of stroke. Using a comprehensive CT angiography protocol that captured the carotid arteries, coronary arteries, vertebral arteries, and aorta, we evaluated these arteries for the presence and severity of atherosclerotic disease. Significant atherosclerotic disease was defined as >50% stenosis in the carotid, coronary, and vertebral arteries, or >or=4 mm thickness and encroaching in the aorta. Presence of any and significant atherosclerotic disease was compared in the different types of arteries assessed.Of these 120 patients, 79 had CT angiography examinations of adequate image quality and were evaluated in this study. Of these 79 patients, 33 had significant atherosclerotic disease. In 26 of these 33 patients (79%), significant disease was isolated to 1 type of artery, most often to the coronary arteries (N=14; 54%). Nonsignificant atherosclerotic disease was more systemic and involved multiple arteries.Significant atherosclerotic disease in the carotid arteries does not predict significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. Significant atherosclerotic disease is most often isolated to 1 type of artery in these patients, whereas nonsignificant atherosclerotic disease tends to be more systemic.

    View details for DOI 10.1161/STROKEAHA.109.577437

    View details for Web of Science ID 000280330700005

    View details for PubMedID 20595672

  • The Triple Rule-Out for Acute Ischemic Stroke: Imaging the Brain, Carotid Arteries, Aorta, and Heart AMERICAN JOURNAL OF NEURORADIOLOGY Furtado, A. D., Adraktas, D. D., Brasic, N., Cheng, S., Ordovas, K., Smith, W. S., Lewin, M. R., Chun, K., Chien, J. D., Schaeffer, S., Wintermark, M. 2010; 31 (7): 1290-1296

    Abstract

    Ischemic stroke is commonly embolic, either from carotid atherosclerosis or from cardiac origin. These potential sources of emboli need to be investigated to accurately prescribe secondary stroke prevention. Moreover, the mortality in ischemic stroke patients due to ischemic heart disease is greater than that of age-matched controls, thus making evaluation for coronary artery disease important in this patient population. The purpose of this study was to evaluate the image quality of a comprehensive CTA protocol in patients with acute stroke that expands the standard CTA coverage to include all 4 chambers of the heart and the coronary arteries.One hundred twenty patients consecutively admitted to the emergency department with suspected cerebrovascular ischemia undergoing standard-of-care CTA were prospectively enrolled in our study. We used an original tailored acquisition protocol using a 64-section CT scanner, consisting of a dual-phase intravenous injection of iodinated contrast and saline flush, in conjunction with a dual-phase CT acquisition, ascending from the top of the aortic arch to the vertex of the head, then descending from the top of the aortic arch to the diaphragm. No beta blockers were administered. The image quality, attenuation, and CNRs of the carotid, aortic, vertebral, and coronary arteries were assessed.Carotid, aorta, and vertebral artery image quality was 100% diagnostic (rated good or excellent) in all patients. Coronary artery image quality was diagnostic in 58% of RCA segments, 73% of LAD segments, and 63% of LCX segments. When we considered proximal segments only, the diagnostic quality rose to 71% in the RCA, 83% in the LAD, and 74% in the LCX.Our stroke protocol achieved excellent opacification of the left heart chambers, the cervical arteries, and each coronary artery, in addition to adequate carotid and coronary artery image quality.

    View details for DOI 10.3174/ajnr.A2075

    View details for Web of Science ID 000281106700026

    View details for PubMedID 20360341

  • Carotid Atheroma Rupture Observed In Vivo and FSI-Predicted Stress Distribution Based on Pre-rupture Imaging ANNALS OF BIOMEDICAL ENGINEERING Leach, J. R., Rayz, V. L., Soares, B., Wintermark, M., Mofrad, M. R., Saloner, D. 2010; 38 (8): 2748-2765

    Abstract

    Atherosclerosis at the carotid bifurcation is a major risk factor for stroke. As mechanical forces may impact lesion stability, finite element studies have been conducted on models of diseased vessels to elucidate the effects of lesion characteristics on the stresses within plaque materials. It is hoped that patient-specific biomechanical analyses may serve clinically to assess the rupture potential for any particular lesion, allowing better stratification of patients into the most appropriate treatments. Due to a sparsity of in vivo plaque rupture data, the relationship between various mechanical descriptors such as stresses or strains and rupture vulnerability is incompletely known, and the patient-specific utility of biomechanical analyses is unclear. In this article, we present a comparison between carotid atheroma rupture observed in vivo and the plaque stress distribution from fluid-structure interaction analysis based on pre-rupture medical imaging. The effects of image resolution are explored and the calculated stress fields are shown to vary by as much as 50% with sub-pixel geometric uncertainty. Within these bounds, we find a region of pronounced elevation in stress within the fibrous plaque layer of the lesion with a location and extent corresponding to that of the observed site of plaque rupture.

    View details for DOI 10.1007/s10439-010-0004-8

    View details for Web of Science ID 000279682000023

    View details for PubMedID 20232151

  • Simulation Model for Contrast Agent Dynamics in Brain Perfusion Scans MAGNETIC RESONANCE IN MEDICINE Bredno, J., Olszewski, M. E., Wintermark, M. 2010; 64 (1): 280-290

    Abstract

    Standardization efforts are currently under way to reduce the heterogeneity of quantitative brain perfusion methods. A brain perfusion simulation model is proposed to generate test data for an unbiased comparison of these methods. This model provides realistic simulated patient data and is independent of and different from any computational method. The flow of contrast agent solute and blood through cerebral vasculature with disease-specific configurations is simulated. Blood and contrast agent dynamics are modeled as a combination of convection and diffusion in tubular networks. A combination of a cerebral arterial model and a microvascular model provides arterial-input and time-concentration curves for a wide range of flow and perfusion statuses. The model is configured to represent an embolic stroke in one middle cerebral artery territory and provides physiologically plausible vascular dispersion operators for major arteries and tissue contrast agent retention functions. These curves are fit to simpler template curves to allow the use of the simulation results in multiple validation studies. A gamma-variate function with fit parameters is proposed as the vascular dispersion operator, and a combination of a boxcar and exponential decay function is proposed as the retention function. Such physiologically plausible operators should be used to create test data that better assess the strengths and the weaknesses of various analysis methods.

    View details for DOI 10.1002/mrm.22431

    View details for Web of Science ID 000279301500032

    View details for PubMedID 20572155

  • Magnetic resonance angiography to evaluate septocutaneous perforators in free fibula flap transfer JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY Fukaya, E., Saloner, D., Leon, P., Wintermark, M., Grossman, R. F., Nozaki, M. 2010; 63 (7): 1099-1104

    Abstract

    In harvesting free fibula composite flaps, preoperative knowledge of the lower limb vascular anatomy is essential to prevent ischaemic complications or flap failure. Magnetic resonance angiography (MRA) allows imaging of the septocutaneous perforators (< or = 1-2mm diameter) of the peroneal artery used in the free fibula flap.We investigated seven patients undergoing the free fibula flap preoperatively with high-resolution MRA images to study the following: 1) tibio-peroneal anatomy, 2) peripheral artery disease, 3) the positions of the perforator vessels on the peroneal artery and their course in the posterolateral intermuscular septum and 4) the cutaneous distribution of the perforators, and to compare them to surgical findings.MRA demonstrated tibio-peroneal anatomy in sufficient detail to exclude anatomic variants and significant peripheral vascular disease, detected septocutaneous perforators arising from the peroneal artery coursing in the posterolateral intermuscular septum and determined the skin terminus of the septocutaneous perforators. All septocutaneous perforators found during surgery were detected prospectively on high-resolution MRA.Lower leg vascular anatomy assessment with high-resolution MRA determined the location of the septocutaneous perforators of the peroneal artery preoperatively with accuracy and precision. This anatomical knowledge provides for a safer procedure and the opportunity to plan surgical details preoperatively.

    View details for DOI 10.1016/j.bjps.2009.06.002

    View details for Web of Science ID 000278656200005

    View details for PubMedID 19577973

  • Optimal carotid artery coverage for carotid plaque CT-imaging in predicting ischemic stroke JOURNAL OF NEURORADIOLOGY Arora, S., Chien, J. D., Cheng, S., Chun, K. A., Wintermark, M. 2010; 37 (2): 98-103

    Abstract

    To determine the optimal spatial coverage for CT-imaging of carotid atherosclerosis, allowing the most accurate prediction of the associated risk of ischemic stroke.In a cross-sectional study, we retrospectively identified 136 consecutive patients admitted to our emergency department with suspected stroke who underwent a CT-angiogram (CTA) of the cervical and intracranial carotid arteries. CTA studies of the carotid arteries were processed using a custom, CT-based automated computer classifier algorithm that quantitatively assesses a battery of carotid CT features. We used this algorithm to individually analyze different lengths of the common and internal carotid arteries for carotid wall features previously shown to be significantly associated with the risk of stroke. Acute stroke patients were categorized into "acute carotid stroke patients" and "non-acute carotid stroke patients" independently of carotid wall CT features. Univariate and multivariate analyses were used to compare the different spatial coverages in terms of their ability to distinguish between the carotid stroke patients and the noncarotid stroke patients using a receiver-operating characteristic curve (ROC) approach.The carotid wall volume was excellent at distinguishing between carotid stroke patients and noncarotid stroke patients, especially for coverages 20mm or less. The number and location of lipid clusters had a good discrimination power, mainly for coverages 15mm or greater. Measurement of minimal fibrous cap thickness was most associated with carotid stroke when assessed using intermediate coverages. Typically, a 20mm coverage on each side of the carotid bifurcation offered the optimal compromise between the individual carotid features.We recommend assessment of 20mm of each side of the carotid bifurcation to best characterize carotid atherosclerotic disease and the associated risk of ischemic stroke.

    View details for DOI 10.1016/j.neurad.2009.04.002

    View details for Web of Science ID 000278330200004

    View details for PubMedID 19573923

  • Cerebral perfusion-CT patterns following seizure EUROPEAN JOURNAL OF NEUROLOGY Gelfand, J. M., Wintermark, M., Josephson, S. A. 2010; 17 (4): 594-601

    Abstract

    Cerebral perfusion-CT (PCT) is commonly used to image patients with suspected stroke, but PCT may also be useful in detecting abnormalities following seizure.We retrospectively identified patients who presented to our stroke center between 2000 and 2008 with acute, transient neurological deficits because of seizure and received PCT imaging within 72 h. We compared the group of seizure patients with abnormal post-ictal PCT to a group of seizure patients with normal post-ictal PCT. Patients were excluded from analysis if the seizure occurred secondary to an acute process known to alter cerebral perfusion.Of 27 patients with acute post-ictal neurological deficits, PCT was abnormal in 10 (37%) and normal in 17 (63%). The most common post-ictal perfusion abnormality, seen in eight of 10 patients, was focal hypoperfusion, with prolonged mean transit time (MTT) and decreased cerebral blood flow and cerebral blood volume, in a cortical ribbon pattern, multi-lobar or holo-hemispheric distribution, sparing the basal ganglia. CT Angiography (CTA) showed no corresponding large vessel pathology. Two other PCT abnormalities--focal hyperperfusion and an isolated prolonged MTT--were also observed in single patients. Imaging within 2 h after seizure termination was significantly associated with finding a post-ictal PCT abnormality (P < 0.039).Post-ictal cerebral PCT abnormalities are relatively common in patients early after seizure. When PCT abnormalities occur in atypical vascular distributions--and the CTA shows no corresponding large vessel occlusions--seizure should be considered as a diagnostic possibility prior to giving acute stroke therapy.

    View details for DOI 10.1111/j.1468-1331.2009.02869.x

    View details for Web of Science ID 000275635800018

    View details for PubMedID 19968701

  • Optimal Brain Perfusion CT Coverage in Patients with Acute Middle Cerebral Artery Stroke AMERICAN JOURNAL OF NEURORADIOLOGY Furtado, A. D., LAU, B. C., Vittinghoff, E., Dillon, W. P., Smith, W. S., Rigby, T., Boussel, L., Wintermark, M. 2010; 31 (4): 691-695

    Abstract

    PCT has emerged as an alternative to MR imaging for the assessment of patients with suspected acute stroke. However, 1 disadvantage of PCT is its limited anatomic coverage, which may impact the characterization of hemispheric ischemic strokes. The purpose of this study was to determine the optimal brain CT coverage required to accurately estimate the size of the infarct core relative to the MCA territory and the infarct-penumbra mismatch, by using a criterion standard of these parameters measured on PCT with 80-mm z-axis coverage.Fifty-one patients with acute ischemic hemispheric stroke underwent PCT scanning (2 boluses, total coverage of 80 mm, 16 x 5 mm sections) within the first 24 hours of symptom onset and a follow-up NCCT of the brain between 3 days and 3 months after the initial stroke CT study. The volumes of PCT infarct and penumbra for each possible extent of z-axis coverage derived from the individual PCT sections were recorded (beginning with 5 mm of z-axis coverage above the orbits and then increasing the coverage in 5-mm increments in the z-axis up to 80 mm above the orbits). The infarct-penumbra mismatch and the size of the infarction relative to the MCA territory were calculated for each extent of z-axis coverage. Using the 80-mm z-axis coverage as the criterion standard, we calculated the accuracy of the values of the relative PCT infarct size and mismatch that were obtained by using more limited z-axis coverage. The impact of different levels of PCT z-axis coverage on the eligibility for reperfusion treatment was assessed.On the admission PCT, by using 80-mm of z-axis coverage, the mean perfusion infarct core volume was 45.9 +/- 44.0 cm(3) (range, 0-170 cm(3)) and the mean penumbra volume was 64.5 +/- 64.4 cm(3) (range, 0-226 cm(3)). The mean perfusion infarct core/MCA territory ratio was 19.6% +/- 16.2% (range, 0.1%-56%). The penumbra / (infarct + penumbra) ratio was 68.6% +/- 23.6% (range, 16.4%-100%). The final infarct volume on follow-up NCCT was 115.4 +/- 157.3 cm(3) (range, 1.79-647.4 cm(3)). The minimal z-axis PCT coverage required to obtain values similar to those obtained with 80-mm z-axis coverage was 75 mm for a mismatch of 0.5, fifty millimeters for a mismatch of 0.2, and 55 mm for a size of PCT infarct relative to the MCA territory.Seventy-five millimeters is the minimal PCT coverage required to use PCT as a tool to select patients with acute stroke for reperfusion therapy by using a mismatch of 0.5. A z-axis coverage of 50 mm was sufficient for a mismatch of 0.2; and 55 mm, for the size of PCT infarct relative to MCA territory (one-third or more).

    View details for DOI 10.3174/ajnr.A1880

    View details for Web of Science ID 000277000500021

    View details for PubMedID 19942712

  • Early profiles of clinical evolution after intravenous thrombolysis in an unselected stroke population JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Delgado, M. G., Michel, P., Naves, M., Maeder, P., Reichhart, M., Wintermark, M., Bogousslavsky, J. 2010; 81 (3): 282-285

    Abstract

    Intravenous recombinant tissular plasminogen activator (rt-PA) is the only approved pharmacological treatment for acute ischaemic stroke. The authors aimed to analyse potential causes of the variable effect on early course and late outcome.136 patients (42% women, 58% men) treated with intravenous rt-PA within 3 h of stroke onset in an acute stroke unit over a 3-year period, were included. Early clinical profiles of evolution at 48 h were divided into clinical improvement (CI) (decrease >4 points in the National Institute of Health Stroke Scale (NIHSS)); clinical worsening (CW) (increase >4 points NIHSS); clinical worsening after initial improvement (CWFI) (variations of >4 points in the NIHSS). Patients with clinical stability (no NIHSS modification or <4 points) were excluded. The patients showed in 66.9% CI, 13.2% CW 8.1 % CWFI and 11.8% remained stable. Female sex, no hyperlipaemia and peripheral arterial disease were associated with CW. Male sex and smoking were associated with CI. Absence of arterial occlusion on admission (28.4%) and arterial recanalisation at 24 h were associated with CI. Main causes of clinical deterioration included symptomatic intracranial haemorrhage (sICH), persistent occlusion and cerebral oedema. 23.5% developed ICH, 6.6% of which had sICH. At 3 months, 15.5% had died. Mortality was increased in CW, mainly related to sICH and cerebral oedema. The outcome of CWFI was intermediate between CW and CI.Early clinical profiles of evolution in thrombolysed patients vary considerably. Even with CI, it is critical to maintain vessel permeability to avoid subsequent CW.

    View details for DOI 10.1136/jnnp.2009.185363

    View details for Web of Science ID 000274974300012

    View details for PubMedID 19850577

  • Acute stroke magnetic resonance imaging: current status and future perspective NEURORADIOLOGY Kloska, S. P., Wintermark, M., Engelhorn, T., Fiebach, J. B. 2010; 52 (3): 189-201

    Abstract

    Cerebral stroke is one of the most frequent causes of permanent disability or death in the western world and a major burden in healthcare system. The major portion is caused by acute ischemia due to cerebral artery occlusion by a clot. The minority of strokes is related to intracerebral hemorrhage or other sources. To limit the permanent disability in ischemic stroke patients resulting from irreversible infarction of ischemic brain tissue, major efforts were made in the last decade. To extend the time window for thrombolysis, which is the only approved therapy, several imaging parameters in computed tomography and magnetic resonance imaging (MRI) have been investigated. However, the current guidelines neglect the fact that the portion of potentially salvageable ischemic tissue (penumbra) is not dependent on the time window but the individual collateral blood flow. Within the last years, the differentiation of infarct core and penumbra with MRI using diffusion-weighted images (DWI) and perfusion imaging (PI) with parameter maps was established. Current trials transform these technical advances to a redefined patient selection based on physiological parameters determined by MRI. This review article presents the current status of MRI for acute stroke imaging. A special focus is the ischemic stroke. In dependence on the pathophysiology of cerebral ischemia, the basic principle and diagnostic value of different MRI sequences are illustrated. MRI techniques for imaging of the main differential diagnoses of ischemic stroke are mentioned. Moreover, perspectives of MRI for imaging-based acute stroke treatment as well as monitoring of restorative stroke therapy from recent trials are discussed.

    View details for DOI 10.1007/s00234-009-0637-1

    View details for Web of Science ID 000274657000004

    View details for PubMedID 19967531

  • Interobserver Variability in the Assessment of CT Imaging Features of Traumatic Brain Injury JOURNAL OF NEUROTRAUMA Chun, K. A., Manley, G. T., Stiver, S. I., Aiken, A. H., Phan, N., Wang, V., Meeker, M., Cheng, S., Gean, A. D., Wintermark, M. 2010; 27 (2): 325-330

    Abstract

    The goal of our study was to determine the interobserver variability between observers with different backgrounds and experience when interpreting computed tomography (CT) imaging features of traumatic brain injury (TBI). We retrospectively identified a consecutive series of 50 adult patients admitted at our institution with a suspicion of TBI, and displaying a Glasgow Coma Scale score < or =12. Noncontrast CT (NCT) studies were anonymized and sent to five reviewers with different backgrounds and levels of experience, who independently reviewed each NCT scan. Each reviewer assessed multiple CT imaging features of TBI and assigned every NCT scan a Marshall and a Rotterdam grading score. The interobserver agreement and coefficient of variation were calculated for individual CT imaging features of TBI as well as for the two scores. Our results indicated that the imaging review by both neuroradiologists and neurosurgeons were consistent with each other. The kappa coefficient of agreement for all CT characteristics showed no significant difference in interpretation between the neurosurgeons and neuroradiologists. The average Bland and Altman coefficients of variation for the Marshall and Rotterdam classification systems were 12.7% and 21.9%, respectively, which indicates acceptable agreement among all five reviewers. In conclusion, there is good interobserver reproducibility between neuroradiologists and neurosurgeons in the interpretation of CT imaging features of TBI and calculation of Marshall and Rotterdam scores.

    View details for DOI 10.1089/neu.2009.1115

    View details for Web of Science ID 000274664800005

    View details for PubMedID 19895192

  • The Role of CT and MRI in the Emergency Evaluation of Persons with Suspected Stroke CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Kidwell, C. S., Wintermark, M. 2010; 10 (1): 21-28

    Abstract

    As a growing number of therapeutic treatment options for acute stroke are being introduced, multimodal acute neuroimaging is assuming a growing role in the initial evaluation and management of patients. Multimodal neuroimaging, using either a CT or MRI approach, can identify the type, location, and severity of the lesion (ischemia or hemorrhage); the status of the cerebral vasculature; the status of cerebral perfusion; and the existence and extent of the ischemic penumbra. Both acute and long-term treatment decisions for stroke patients can then be optimally guided by this information.

    View details for DOI 10.1007/s11910-009-0075-9

    View details for Web of Science ID 000274940400002

    View details for PubMedID 20425222

  • Reperfusion Is a More Accurate Predictor of Follow-Up Infarct Volume Than Recanalization A Proof of Concept Using CT in Acute Ischemic Stroke Patients STROKE Soares, B. P., Tong, E., Hom, J., Cheng, S., Bredno, J., Boussel, L., Smith, W. S., Wintermark, M. 2010; 41 (1): E34-E40