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


  • Chair, Research Committee, American Society of Functional Neuroradiology (2013 - Present)
  • 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


  • Board Certification: Neuroradiology, American Board of Radiology (2011)
  • Board Certification: Diagnostic Radiology, American Board of Radiology (2009)
  • Fellowship:University of California, San Francisco (2005) CA
  • Internship:GHOL - Hospital of Nyon (2000) Switzerland
  • Medical Education:University of Lausanne School of Medicine (1998) Switzerland
  • Residency:CHUV - University Hospital of Lausanne - Department of RadiologySwitzerland
  • 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

2017-18 Courses


Graduate and Fellowship Programs


  • Neuroradiology (Fellowship Program)

All Publications


  • 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
  • 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
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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
  • 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

  • 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 Web of Science ID 000390420100006

    View details for PubMedID 27541183

  • 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
  • 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

  • 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

  • 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 Web of Science ID 000387810700025

    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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 Web of Science ID 000375049700044

    View details for PubMedID 27073243

  • 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
  • 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

    View details for PubMedCentralID PMC4990448

  • Perfusion Computed Tomography for the Evaluation of Acute Ischemic Stroke Strengths and Pitfalls STROKE Heit, J. J., Wintermark, M. 2016; 47 (4): 1153-1158
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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
  • 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

    View details for DOI 10.1161/STROKEAHA.115.011173

    View details for Web of Science ID 000367136500009

    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

    View details for PubMedCentralID PMC4798659

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

    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

    View details for DOI 10.1212/WNL.0000000000002065

    View details for Web of Science ID 000363968900007

    View details for PubMedID 26423434

  • 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

    View details for DOI 10.1109/TMI.2014.2377694

    View details for Web of Science ID 000362358000001

    View details for PubMedID 25494501

  • 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

  • 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

  • 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 Web of Science ID 000356718000030

    View details for PubMedID 25833105

  • 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

  • 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 Web of Science ID 000356672800039

    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 Web of Science ID 000356781000041

    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-?

    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
  • 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 Web of Science ID 000350901900004

    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

  • 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 Web of Science ID 000345516600250

    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
  • 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

  • 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 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
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

    Abstract

    The purpose of this study was to compare recanalization and reperfusion in terms of their predictive value for imaging outcomes (follow-up infarct volume, infarct growth, salvaged penumbra) and clinical outcome in acute ischemic stroke patients. Material andTwenty-two patients admitted within 6 hours of stroke onset were retrospectively included in this study. These patients underwent a first stroke CT protocol including CT-angiography (CTA) and perfusion-CT (PCT) on admission, and similar imaging after treatment, typically around 24 hours, to assess recanalization and reperfusion. Recanalization was assessed by comparing arterial patency on admission and posttreatment CTAs; reperfusion, by comparing the volumes of CBV, CBF, and MTT abnormality on admission and posttreatment PCTs. Collateral flow was graded on the admission CTA. Follow-up infarct volume was measured on the discharge noncontrast CT. The groups of patients with reperfusion, no reperfusion, recanalization, and no recanalization were compared in terms of imaging and clinical outcomes.Reperfusion (using an MTT reperfusion index >75%) was a more accurate predictor of follow-up infarct volume than recanalization. Collateral flow and recanalization were not accurate predictors of follow-up infarct volume. An interaction term was found between reperfusion and the volume of the admission penumbra >50 mL.Our study provides evidence that reperfusion is a more accurate predictor of follow-up infarct volume in acute ischemic stroke patients than recanalization. We recommend an MTT reperfusion index >75% to assess therapy efficacy in future acute ischemic stroke trials that use perfusion-CT.

    View details for DOI 10.1161/STROKEAHA.109.568766

    View details for Web of Science ID 000273093400042

    View details for PubMedID 19910542

  • Sixty-Four-Section Multidetector CT Angiography of Carotid Arteries: A Systematic Analysis of Image Quality and Artifacts AMERICAN JOURNAL OF NEURORADIOLOGY Kim, J. J., Dillon, W. P., Glastonbury, C. M., Provenzale, J. M., Wintermark, M. 2010; 31 (1): 91-99

    Abstract

    Sixty-four-section CT scanners have recently been introduced for vascular imaging. Before such scanners reach widespread use, scanning protocol should be optimized and image quality assessed. The goals of this study were to systematically measure image quality and determine the prevalence of various types of artifacts produced by a 64-section scanner.We retrospectively reviewed CT angiography (CTA) scans obtained on a 64-section CT scanner in 100 consecutive patients presenting to the emergency department during a 2-month period with a suspected acute cerebrovascular event. We evaluated scan quality by using 2 different methods: First, we quantitatively assessed arterial opacification by measuring attenuation values in 9 arterial segments from the aortic arch to the distal cervical internal carotid artery, by using a threshold of 150 HU as an indicator of good opacification. Second, we assessed image contrast between arteries and veins by measuring attenuation within venous segments and recording the number of artery-vein-segment pairs in which the attenuation difference was 150 HU). Image contrast between artery and vein segments was also good, with 714 of 763 analyzable segment pairs (85.6%) having >50 HU difference. Artifacts obscuring arterial evaluation included streak from contrast material in the subclavian/brachiocephalic vein (32% of patients), attenuation of the x-ray beam between the shoulders (28%), beam-hardening from metallic hardware (26%), and contrast material reflux into neck veins (16%). The most clinically relevant artifacts were flow artifacts, mimicking dissection or vascular occlusion; they were seen in 14% of patients and likely are related to the rapid data acquisition for CTA on 64-section scanners (compared with the circulation of contrast material in the cervical arteries). None of the patients in our historical control group who underwent 16-section CT had flow artifacts on their CTA studies; the incidence of the other types of artifacts in this group was similar to that in patients imaged with 64-section CT.The 64-section CTA imaging protocol for carotid arteries yields high-quality studies in >95% of cases.

    View details for DOI 10.3174/ajnr.A1768

    View details for Web of Science ID 000273943700018

    View details for PubMedID 19729539

  • Age- and anatomy-related values of blood-brain barrier permeability measured by perfusion-CT in non-stroke patients JOURNAL OF NEURORADIOLOGY Dankbaar, J. W., Hom, J., Schneider, T., Cheng, S., LAU, B. C., van der Schaaf, I., Virmani, S., Pohlman, S., Wintermark, M. 2009; 36 (4): 219-227

    Abstract

    The goal of this study was to determine blood-brain barrier permeability (BBBP) values extracted from perfusion-CT (PCT) using the Patlak model and possible variations related to age, gender, race, vascular risk factors and their treatment and anatomy in non-stroke patients.We retrospectively identified 96 non-stroke patients who underwent a PCT study using a prolonged acquisition time up to 3 minutes. Patients' charts were reviewed for demographic data, vascular risk factors and their treatment. The Patlak model was applied to calculate BBBP values in regions of interest drawn within the basal ganglia and the gray and white matter of the different cerebral lobes. Differences in BBBP values were analyzed using a multivariate analysis considering clinical variables and anatomy.Mean absolute BBBP values were 1.2 ml 100 g(-1) min(-1) and relative BBBP/CBF values were 3.5%. Statistical differences between gray and white matter were not clinically relevant. BBBP values were influenced by age, history of diabetes and/or hypertension and aspirin intake.This study reports ranges of BBBP values in non-stroke patients calculated from delayed phase PCT data using the Patlak model. These ranges will be useful to detect abnormal BBBP values when assessing patients with cerebral infarction for the risk of hemorrhagic transformation.

    View details for DOI 10.1016/j.neurad.2009.01.001

    View details for Web of Science ID 000271524500005

    View details for PubMedID 19251320

  • Optimal Duration of Acquisition for Dynamic Perfusion CT Assessment of Blood-Brain Barrier Permeability Using the Patlak Model AMERICAN JOURNAL OF NEURORADIOLOGY Hom, J., Dankbaar, J. W., Schneider, T., Cheng, S., Bredno, J., Wintermark, M. 2009; 30 (7): 1366-1370

    Abstract

    A previous study demonstrated the need to use delayed acquisition rather than first-pass data for accurate blood-brain barrier permeability surface product (BBBP) calculation from perfusion CT (PCT) according to the Patlak model, but the optimal duration of the delayed acquisition has not been established. Our goal was to determine the optimal duration of the delayed PCT acquisition to obtain accurate BBBP measurements while minimizing potential motion artifacts and radiation dose.We retrospectively identified 23 consecutive patients with acute ischemic anterior circulation stroke who underwent a PCT study with delayed acquisition. The Patlak model was applied for the full delayed acquisition (90-240 seconds) and also for truncated analysis windows (90-210, 90-180, 90-150, 90-120 seconds). Linear regression of Patlak plots was performed separately for the full and truncated analysis windows, and the slope of these regression lines was used to indicate BBBP. The full and truncated analysis windows were compared in terms of the resulting BBBP values and the quality of the Patlak fitting.BBBP values in the infarct and penumbra were similar for the full 90- to 240-second acquisition (95% confidence intervals for the infarct and penumbra: 1.62-2.47 and 1.75-2.41 mL x100 g(-1) x min(-1), respectively) and the 90- to 210-second analysis window (1.82-2.76 and 2.01-2.74 mL x 100 g(-1) x min(-1), respectively). BBBP values increased significantly with shorter acquisitions. The quality of the Patlak fit was excellent for the full 90- to 240-second and 90- to 210-second acquisitions, but it degraded with shorter acquisitions.The duration for the delayed PCT acquisition should be at least 210 seconds, because acquisitions shorter than 210 seconds lead to significantly overestimated BBBP values.

    View details for DOI 10.3174/ajnr.A1592

    View details for Web of Science ID 000269169600020

    View details for PubMedID 19369610

  • Difference in Disease Burden and Activity in Pediatric Patients on Brain Magnetic Resonance Imaging at Time of Multiple Sclerosis Onset vs Adults ARCHIVES OF NEUROLOGY Waubant, E., Chabas, D., Okuda, D. T., Glenn, O., Mowry, E., Henry, R. G., Strober, J. B., Soares, B., Wintermark, M., Pelletier, D. 2009; 66 (8): 967-971

    Abstract

    To compare initial brain magnetic resonance imaging (MRI) characteristics of children and adults at multiple sclerosis (MS) onset.Retrospective analysis of features of first brain MRI available at MS onset in patients with pediatric-onset and adult-onset MS.A pediatric and an adult MS center.Patients with pediatric-onset <18 years) and adult-onset (> or =18 years) MS.We evaluated initial and second (when available) brain MRI scans obtained at the time of first MS symptoms for lesions that were T2-bright, ovoid and well defined, large (> or =1cm), or enhancing.We identified 41 patients with pediatric-onset MS and 35 patients with adult-onset MS. Children had a higher number of total T2- (median, 21 vs 6; P < .001) and large T2-bright areas (median, 4 vs 0; P < .001) than adults. Children more frequently had T2-bright foci in the posterior fossa (68.3% vs 31.4%; P = .001) and enhancing lesions (68.4% vs 21.2%; P < .001) than adults. On the second brain MRI, children had more new T2-bright (median, 2.5 vs 0; P < .001) and gadolinium-enhancing foci (P < .001) than adults. Except for corpus callosum involvement, race/ethnicity was not strongly associated with disease burden or lesion location on the first scan, although other associations cannot be excluded because of the width of the confidence intervals.While it is unknown whether the higher disease burden, posterior fossa involvement, and rate of new lesions in pediatric-onset MS are explained by age alone, these characteristics have been associated with worse disability progression in adults.

    View details for Web of Science ID 000268848100007

    View details for PubMedID 19667217

  • Automated versus manual post-processing of perfusion-CT data in patients with acute cerebral ischemia: influence on interobserver variability NEURORADIOLOGY Soares, B. P., Dankbaar, J. W., Bredno, J., Cheng, S., Bhogal, S., Dillon, W. P., Wintermark, M. 2009; 51 (7): 445-451

    Abstract

    The purpose of this study is to compare the variability of PCT results obtained by automatic selection of the arterial input function (AIF), venous output function (VOF) and symmetry axis versus manual selection.Imaging data from 30 PCT studies obtained as part of standard clinical stroke care at our institution in patients with suspected acute hemispheric ischemic stroke were retrospectively reviewed. Two observers performed the post-processing of 30 CTP datasets. Each observer processed the data twice, the first time employing manual selection of AIF, VOF and symmetry axis, and a second time using automated selection of these same parameters, with the user being allowed to adjust them whenever deemed appropriate. The volumes of infarct core and of total perfusion defect were recorded. The cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and blood-brain barrier permeability (BBBP) values in standardized regions of interest were recorded. Interobserver variability was quantified using the Bland and Altman's approach.Automated post-processing yielded lower coefficients of variation for the volume of the infarct core and the volume of the total perfusion defect (15.7% and 5.8%, respectively) compared to manual post-processing (31.0% and 12.2%, respectively). Automated post-processing yielded lower coefficients of variation for PCT values (11.3% for CBV, 9.7% for CBF, and 9.5% for MTT) compared to manual post-processing (23.7% for CBV, 32.8% for CBF, and 16.7% for MTT).Automated post-processing of PCT data improves interobserver agreement in measurements of CBV, CBF and MTT, as well as volume of infarct core and penumbra.

    View details for DOI 10.1007/s00234-009-0516-9

    View details for Web of Science ID 000266927000002

    View details for PubMedID 19274457

  • Modern imaging of the infarct core and the ischemic penumbra in acute stroke patients: CT versus MRI. Expert review of cardiovascular therapy Ledezma, C. J., Fiebach, J. B., Wintermark, M. 2009; 7 (4): 395-403

    Abstract

    Thrombolysis has become an approved therapy for acute stroke. However, many stroke patients do not benefit from such treatment, since the presently used criteria are very restrictive, notably with respect to the accepted time window. Even so, a significant rate of intracranial hemorrhage still occurs. Conventional cerebral computed tomography (CT) without contrast has been proposed as a selection tool for acute stroke patients. However, more-modern MRI and CT techniques, referred to as diffusion- and perfusion-weighted imaging and perfusion-CT, have been introduced, which afford a comprehensive noninvasive survey of acute stroke patients as soon as their emergency admission, with accurate demonstration of the site of arterial occlusion and its hemodynamic and pathophysiological repercussions for the brain parenchyma. The objective of this article is to present the advantages and drawbacks of CT and MRI in the evaluation of acute stroke patients.

    View details for DOI 10.1586/erc.09.7

    View details for PubMedID 19379068

  • MR and CT Monitoring of Recanalization, Reperfusion, and Penumbra Salvage Everything That Recanalizes Does Not Necessarily Reperfuse! STROKE Soares, B. P., Chien, J. D., Wintermark, M. 2009; 40 (3): S24-S27

    Abstract

    Revascularization therapies for acute stroke patients aim to rescue the ischemic penumbra by restoring the patency of the occluded artery ("recanalization") and the downstream capillary blood flow ("reperfusion"). This article reviews the definition of recanalization and reperfusion used in stroke clinical trials and their limitations and proposes a study design to determine the relative importance of recanalization, reperfusion, and collateral flow in evaluating the efficacy of revascularization therapies for acute ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.108.526814

    View details for Web of Science ID 000263594200008

    View details for PubMedID 19064812

  • Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study LANCET NEUROLOGY Hacke, W., Furlan, A. J., Al-Rawi, Y., Davalos, A., Fiebach, J. B., Gruber, F., Kaste, M., Lipka, L. J., Pedraza, S., Ringleb, P. A., Rowley, H. A., Schneider, D., Schwamm, L. H., Leal, J. S., Soehngen, M., Teal, P. A., Wilhelm-Ogunbiyi, K., Wintermark, M., Warach, S. 2009; 8 (2): 141-150

    Abstract

    Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI).In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 microg/kg desmoteplase, 125 microg/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT00111852.Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 microg/kg desmoteplase; 66 received 125 microg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6-14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 microg/kg desmoteplase, 36% (24 of 66) for 125 microg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 microg/kg desmoteplase 14.0% (0.5 cm(3)); 125 microg/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9 cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for 90 microg/kg desmoteplase, 4.5% (3 of 66) for 125 microg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 microg/kg desmoteplase; 21% [14 of 66] for 125 microg/kg desmoteplase; and 6% [4 of 63] for placebo).The DIAS-2 study did not show a benefit of desmoteplase given 3-9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase.PAION Deutschland GmbH; Forest Laboratories.

    View details for DOI 10.1016/S1474-4422(08)70267-9

    View details for Web of Science ID 000262752000012

    View details for PubMedID 19097942

  • Imaging of brain parenchyma in stroke. Handbook of clinical neurology Wintermark, M., Fiebach, J. 2009; 94: 1011-1019

    View details for DOI 10.1016/S0072-9752(08)94049-5

    View details for PubMedID 18793886

  • Multimodal CT in Stroke Imaging: New Concepts RADIOLOGIC CLINICS OF NORTH AMERICA Ledezma, C. J., Wintermark, M. 2009; 47 (1): 109-?

    Abstract

    A multimodal CT protocol provides a comprehensive noninvasive survey of acute stroke patients with accurate demonstration of the site of arterial occlusion and its hemodynamic tissue status. It combines widespread availability with the ability to provide functional characterization of cerebral ischemia, and could potentially allow more accurate selection of candidates for acute stroke reperfusion therapy. This article discusses the individual components of multimodal CT and addresses the potential role of a combined multimodal CT stroke protocol in acute stroke therapy.

    View details for DOI 10.1016/j.rcl.2008.10.008

    View details for Web of Science ID 000263843900009

    View details for PubMedID 19195537

  • Morphological and functional MR imaging of Lhermitte-Duclos disease with pathology correlate JOURNAL OF NEURORADIOLOGY Cianfoni, A., Wintermark, M., Pitudu, F., D'Alessandris, Q. G., Lauriola, L., Visocchi, M., Colosimo, C. 2008; 35 (5): 297-300

    Abstract

    Lhermitte-Duclos disease (LDD) is a rare benign lesion of uncertain pathogenesis characterised by distortion of the normal cerebellar laminar cytoarchitecture. We report a case of LDD thoroughly characterized by advanced magnetic resonance imaging techniques, with diffusion-weighted, perfusion-weighted and post-gadolinium sequences. Imaging showed restricted diffusion consistent with high cellularity, high degree of vascularity and preserved blood-brain barrier permeability, correlating with pathology.

    View details for DOI 10.1016/j.neurad.2008.05.002

    View details for Web of Science ID 000261970400008

    View details for PubMedID 18692898

  • Cerebral perfusion CT: Technique and clinical applications JOURNAL OF NEURORADIOLOGY Wintermark, M., Sincic, R., Sridhar, D., Chien, J. D. 2008; 35 (5): 253-260

    Abstract

    Perfusion computed tomography (PCT) is an imaging technique that allows rapid, noninvasive, quantitative evaluation of cerebral perfusion by generating maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The concepts behind this imaging technique were developed in the 1980s', but its widespread clinical use was allowed by the recent introduction of rapid, large-coverage multidetector-row CT scanners. Key clinical applications for PCT include the diagnosis of cerebral ischemia and infarction, and evaluation of vasospasm after subarachnoid hemorrhage. PCT measurements of cerebrovascular reserve after acetazolamide challenges in patients with vascular stenoses permit evaluation of candidacy for bypass surgery and endovascular treatment. PCT has also been used to assess cerebral perfusion after head trauma and microvascular permeability in the setting of intracranial neoplasm. Some controversy exists regarding this technique, including questions regarding correct selection of an arterial input vessel, the accuracy of quantitative results, and the reproducibility of results. This article provides an overview of PCT, including details of technique, major clinical applications, and limitations.

    View details for DOI 10.1016/j.neurad.2008.03.005

    View details for Web of Science ID 000261970400001

    View details for PubMedID 18466974

  • Computer-Aided Assessment of Head Computed Tomography (CT) Studies in Patients with Suspected Traumatic Brain Injury JOURNAL OF NEUROTRAUMA Yuh, E. L., Gean, A. D., Manley, G. T., Callen, A. L., Wintermark, M. 2008; 25 (10): 1163-1172

    Abstract

    In this study, we sought to determine the accuracy of a computer algorithm that automatically assesses head computed tomography (CT) studies in patients with suspected traumatic brain injury (TBI) for features of intracranial hemorrhage and mass effect, employing a neuroradiologist's interpretation as the gold standard. To this end, we designed a suite of computer algorithms that evaluates in a fully automated fashion the presence of intracranial blood and/or mass effect based on the following CT findings: (1) presence or absence of a subdural or epidural hematoma, (2) presence or absence of subarachnoid hemorrhage, (3) presence or absence of an intraparenchymal hematoma, (4) presence or absence of clinically significant midline shift (>or=5 mm), and (5) normal, partly effaced, or completely effaced basal cisterns. The algorithm displays abnormal findings as color overlays on the original head CT images, and calculates the volume of each type of blood collection, the midline shift, and the volume of the basal cisterns, based on the above-described features. Thresholds and parameters yielding optimal accuracy of the computer algorithm were determined using a development sample of 33 selected, nonconsecutive patients. The software was then applied to a validation sample of 250 consecutive patients evaluated for suspicion of acute TBI at our institution in 2006-2007. Software detection of the presence of at least one noncontrast CT (NCT) feature of acute TBI demonstrated high sensitivity of 98% and high negative predictive value (NPV) of 99%. There was actually only one false negative case, where a very subtle subdural hematoma, extending exclusively along the falx, was diagnosed by the neuroradiologist, while the case was considered as normal by the computer algorithm. The software was excellent at detecting the presence of mass effect and intracranial hemorrhage, but showed some disagreements with the neuroradiologist in quantifying the degree of mass effect and characterizing the type of intracranial hemorrhage. In summary, we have developed a fully automated computer algorithm that demonstrated excellent sensitivity for acute intracranial hemorrhage and clinically significant midline shift, while maintaining intermediate specificity. Further studies are required to evaluate the potential favorable impact of this software on facilitating workflow and improving diagnostic accuracy when used as a screening aid by physicians with different levels of experience.

    View details for DOI 10.1089/neu.2008.0590

    View details for Web of Science ID 000260796200004

    View details for PubMedID 18986221

  • Dynamic Perfusion CT Assessment of the Blood-Brain Barrier Permeability: First Pass versus Delayed Acquisition AMERICAN JOURNAL OF NEURORADIOLOGY Dankbaar, J. W., Hom, J., Schneider, T., Cheng, S., LAU, B. C., van der Schaaf, I., Virmani, S., Pohlman, S., Dillon, W. P., Wintermark, M. 2008; 29 (9): 1671-1676

    Abstract

    The Patlak model has been applied to first-pass perfusion CT (PCT) data to extract information on blood-brain barrier permeability (BBBP) to predict hemorrhagic transformation in patients with acute stroke. However, the Patlak model was originally described for the delayed steady-state phase of contrast circulation. The goal of this study was to assess whether the first pass or the delayed phase of a contrast bolus injection better respects the assumptions of the Patlak model for the assessment of BBBP in patients with acute stroke by using PCT.We retrospectively identified 125 consecutive patients (29 with acute hemispheric stroke and 96 without) who underwent a PCT study by using a prolonged acquisition time up to 3 minutes. The Patlak model was applied to calculate BBBP in ischemic and nonischemic brain tissue. Linear regression of the Patlak plot was performed separately for the first pass and for the delayed phase of the contrast bolus injection. Patlak linear regression models for the first pass and the delayed phase were compared in terms of their respective square root mean squared errors (square root MSE) and correlation coefficients (R) by using generalized estimating equations with robust variance estimation.BBBP values calculated from the first pass were significantly higher than those from the delayed phase, both in nonischemic brain tissue (2.81 mL x 100 g(-1) x min(-1) for the first pass versus 1.05 mL x 100 g(-1) x min(-1) for the delayed phase, P < .001) and in ischemic tissue (7.63 mL x 100 g(-1) x min(-1) for the first pass versus 1.31 mL x 100 g(-1) x min(-1) for the delayed phase, P < .001). Compared with regression models from the first pass, Patlak regression models obtained from the delayed data were of better quality, showing significantly lower square root MSE and higher R.Only the delayed phase of PCT acquisition respects the assumptions of linearity of the Patlak model in patients with and without stroke.

    View details for DOI 10.3174/ajnr.A1203

    View details for Web of Science ID 000260023800015

    View details for PubMedID 18635616

  • Identification of residual ischemia, infarction, and microvascular impairment in revascularized myocardial infarction using 64-slice MDCT CONTRAST MEDIA & MOLECULAR IMAGING Furtado, A. D., Carlsson, M., Wintermark, M., Ordovas, K., Saeed, M. 2008; 3 (5): 198-206

    Abstract

    This study aimed to assess the potential of 64-slice MDCT in characterizing revascularized infarcted myocardium at the cellular and microvascular levels. Pigs (n = 7) underwent 2 h left anterior descending coronary artery occlusion/reperfusion. In acute (2-4 h) and subacute (1 week) infarction, first-pass perfusion (FPP) (1 ml/kg of 300 mg/ml Omnipaque) was performed using a cine (rotation time 60 s/bpm) non-ECG gated sequence (mAS/kV = 100/120). Delayed contrast enhanced images (DE) (mAS/kV = 650/120) were acquired every 2 min for 10 min to determine the kinetics of Omnipaque and to define infarcted myocardium and microvascular impairment (representing microvascular obstruction and/or no- or low-reflow phenomenon). Maximum upslope, maximum attenuation and time to the peak were measured from FPP plots. 2,3,5-Triphenyltetrazolium-chloride (TTC) was used to define true infarction in the excised hearts. Hyperenhanced myocardium on DE was measured and compared with TTC. The contrast media caused minor beam hardening and X-ray scatter on FPP. The above-mentioned perfusion parameters significantly differed between remote and acute infarction. Infarcted myocardium showed two patterns of enhancement on DE, hyperenhanced rim representing the perfused infarction and hypoenhanced core representing a microvascular impaired region, with significantly different attenuation. The extent of infarction on DE-MDCT decreased over the course of 1 week and did not differ from TTC. Post-processed FPP semi-quantitative images showed a decline in myocardial blood volume and flow in acute revascularized infarction. In conclusion, modern MDCT has the potential to identify residual ischemia on FPP and microvascular impairment and infarction on DE images.

    View details for DOI 10.1002/cmmi.253

    View details for Web of Science ID 000261387900007

    View details for PubMedID 18973214

  • Focal Lesions in Acute Mild Traumatic Brain Injury and Neurocognitive Outcome: CT versus 3T MRI JOURNAL OF NEUROTRAUMA Lee, H., Wintermark, M., Gean, A. D., Ghajar, J., Manley, G. T., Mukherjee, P. 2008; 25 (9): 1049-1056

    Abstract

    Mild traumatic brain injury (mTBI) is associated with long-term cognitive deficits. This study compared the detection rate of acute post-traumatic focal lesions on computed tomography (CT) and 3T (Tesla) magnetic resonance (MR) imaging with neurocognitive outcomes. Adults (n = 36; age range, 19-52 years) with a single episode of mTBI (Glasgow Coma Scale 13-15, as well as loss of consciousness and post-traumatic amnesia) were prospectively enrolled and had CT within 24 h of injury and 3T MR within 2 weeks of injury. The CT and MR scans were reviewed by two neuroradiologists who were blinded to clinical information. Twenty-eight of these mTBI subjects and 18 matched healthy volunteers also underwent serial neurocognitive testing. Of the 36 mTBI cases, intraparenchymal lesions were detected in 18 CT and 27 acute MR exams, consisting of hemorrhagic traumatic axonal injury (TAI) (eight CT, 17 MR), non-hemorrhagic TAI (zero CT, four MR), and cerebral contusions (13 CT, 21 MR). Mild TBI patients had significantly worse performance on working memory tasks than matched controls at the acute time point (<2 weeks), and at 1 month and at 1 year post-injury; yet there was no significant correlation of imaging findings with working memory impairment. In conclusion, 3T MR detected parenchymal lesions in 75% of this mTBI cohort with loss of consciousness and post-traumatic amnesia, a much higher rate than CT. However, the CT and 3T MR imaging findings did not account for cognitive impairment, suggesting that newer imaging techniques such as diffusion tensor imaging are needed to provide biomarkers for neurocognitive and functional outcome in mTBI.

    View details for DOI 10.1089/neu.2008.0566

    View details for Web of Science ID 000260054900001

    View details for PubMedID 18707244

  • Perfusion CT compared to (H2O)-O-15/(OO)-O-15 PET in patients with chronic cervical carotid artery occlusion NEURORADIOLOGY Kamath, A., Smith, W. S., Powers, W. J., Cianfoni, A., Chien, J. D., Videen, T., Lawton, M. T., Finley, B., Dillon, W. P., Wintermark, M. 2008; 50 (9): 745-751

    Abstract

    The purpose of this study was to compare the results of perfusion computed tomography (PCT) with those of (15)O(2)/H(2) (15)O positron emission tomography (PET) in a subset of Carotid Occlusion Surgery Study (COSS) patients.Six patients enrolled in the COSS underwent a standard-of-care PCT in addition to the (15)O(2)/H(2) (15)O PET study used for selection for extracranial-intracranial bypass surgery. PCT and PET studies were coregistered and then processed separately by different radiologists. Relative measurement of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were calculated from PET. PCT datasets were processed using different arterial input functions (AIF). Relative PCT and PET CBF values from matching regions of interest were compared using linear regression model to determine the most appropriate arterial input function for PCT. Also, PCT measurements using the most accurate AIF were evaluated for linear regression with respect to relative PET OEF values.The most accurate PCT relative CBF maps with respect to the gold standard PET CBF were obtained when CBF values for each arterial territory are calculated using a dedicated AIF for each territory (R (2) = 0.796, p < 0.001). PCT mean transit time (MTT) is the parameter that showed the best correlation with the count-based PET OEF ratios (R (2) = 0.590, p < 0.001).PCT relative CBF compares favorably to PET relative CBF in patients with chronic carotid occlusion when processed using a dedicated AIF for each territory. The PCT MTT parameter correlated best with PET relative OEF.

    View details for DOI 10.1007/s00234-008-0403-9

    View details for Web of Science ID 000259008400001

    View details for PubMedID 18509627

  • Carotid plaque computed tomography imaging in stroke and nonstroke patients ANNALS OF NEUROLOGY Wintermark, M., Arora, S., Tong, E., Vittinghoff, E., Lau, B. C., Chien, J. D., Dillon, W. P., Saloner, D. 2008; 64 (2): 149-157

    Abstract

    To identify a set of computed tomographic (CT) features of carotid atherosclerotic plaques that is significantly associated with 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 of the carotid arteries. CT-angiographic studies of the carotid arteries were processed automatically using automated computer classifier algorithm that quantitatively assesses a battery of carotid CT features. Acute stroke patients were categorized into "acute carotid stroke patients" and "nonacute carotid stroke patients" independent of carotid wall CT features, using the Causative Classification System for Ischemic Stroke, which includes the neuroradiologist's review of the imaging studies of the brain parenchyma and of the degree of carotid stenosis, and charted test results (such as electrocardiogram). Univariate followed by multivariate analyses were used to build models to differentiate between these patient groups and to differentiate between the infarct and unaffected sides in the "acute carotid stroke patients."Forty "acute carotid stroke" patients and 50 "nonacute carotid stroke" patients were identified. Multivariate modeling identified a small number of the carotid wall CT features that were significantly associated with acute carotid stroke, including wall volume, fibrous cap thickness, number and location of lipid clusters, and number of calcium clusters.Patients with acute carotid stroke demonstrate significant differences in the appearance of their carotid wall ipsilateral to the side of their infarct, when compared with either nonacute carotid stroke patients or the carotid wall contralateral with the infarct side.

    View details for DOI 10.1002/ana.21424

    View details for Web of Science ID 000258921800006

    View details for PubMedID 18756475

  • Reversible monoparesis following decompressive hemicraniectomy for traumatic brain injury JOURNAL OF NEUROSURGERY Stiver, S. I., Wintermark, M., Manley, G. T. 2008; 109 (2): 245-254

    Abstract

    The "syndrome of the trephined" is an uncommon and poorly understood disorder of delayed neurological deficit following craniectomy. From the authors' extensive experience with decompressive hemicraniectomy for traumatic brain injury (TBI), they have encountered a number of patients who developed delayed motor deficits, also called "motor trephine syndrome," and reversal of the weakness following cranioplasty repair. The authors set out to study motor function systematically in this patient population to define the incidence, contributing factors, and outcome of patients with motor trephine syndrome.The authors evaluated patient demographics, injury characteristics, detailed motor examinations, and CT scans in 38 patients with long-term follow-up after decompressive hemicraniectomy for TBI.Ten patients (26%) experienced delayed contralateral upper-extremity weakness, beginning 4.9 +/- 0.4 months (mean +/- standard error) after decompressive hemicraniectomy. Motor deficits improved markedly within 72 hours of cranioplasty repair, and all patients recovered full motor function. The CT perfusion scans, performed in 2 patients, demonstrated improvements in cerebral blood flow commensurate with resolution of cerebrospinal fluid flow disturbances on CT scanning and return of motor strength. Comparisons between 10 patients with and 20 patients (53%) without delayed motor deficits identified 3 factors--ipsilateral contusions, abnormal cerebrospinal fluid circulation, and longer intervals to cranioplasty repair--to be strongly associated with delayed, reversible monoparesis following decompressive hemicraniectomy.Delayed, reversible monoparesis, also called motor trephine syndrome, is common following decompressive hemicraniectomy for TBI. The results of this study suggest that close follow-up of motor strength with early cranioplasty repair may prevent delayed motor complications of decompressive hemicraniectomy.

    View details for DOI 10.3171/JNS/2008/109/8/0245

    View details for Web of Science ID 000257958400012

    View details for PubMedID 18671636

  • Perfusion-CT assessment of the cerebrovascular reserve: A revisit to the acetazolamide challenges JOURNAL OF NEURORADIOLOGY Smith, L. M., Elkins, J. S., Dillon, W. P., Schaeffer, S., Wintermark, M. 2008; 35 (3): 157-164

    Abstract

    Imaging techniques utilizing acetazolamide challenges classically measure cerebral blood flow (CBF). In addition to measuring CBF, Perfusion-CT (PCT) can also assess cerebral blood volume (CBV) and mean transit time (MTT), expanding but also complicating the results of acetazolamide challenges performed using PCT. The goal of this study is to clarify the interpretation of PCT studies obtained during acetazolamide challenges.Four consecutive patients were referred for evaluation of their cerebrovascular reserve because of suspected or known large vessel stenosis or occlusion. In one patient, the potential stenosis was found to be artifactual, and this subject was considered as a normal control. The remaining three patients had clinical histories clearly suggestive of a worsening in cerebrovascular reserve (no.1 with a single transient ischemic attack (TIA), no.2 with several TIAs, no.3 with multiple, prolonged TIAs). All patients underwent a baseline PCT scan, followed by intravenous injection of 1g acetazolamide and, 20 min postinjection, by a second PCT scan at exactly the same locations as the first. PCT cerebral blood flow, volume, and mean transit time values were measured in regions of interest (ROIs) encompassing the brain tissue at-risk and the normal brain tissue, defined based on the site of occlusion and the anatomy of the Circle of Willis. Changes in PCT parameters were calculated in corresponding ROIs on pre- and postacetazolamide PCT maps.As compared to the normal control patient, baseline CBF values in the at-risk regions were similar in patients nos.1 and 2, and lower in patient no.3. After acetazolamide administration, CBF increased by 32% in the normal patient and decreased by 11, 11, and 9% in the at-risk regions in patients nos.1, 2, and 3, respectively; CBV was stable for all patients except no.3, who showed a 36% increase; MTT was the PCT parameter whose change best differentiated the four patients (-17% in the normal patient, +9% in patient no.1, +24% in patient no.2, +48% in patient no.3). Interestingly, the baseline MTT values, measured before acetazolamide injection, showed a similar, gradual increase in the four patients, ranging from 4.5 to 8.1s.The degree of impairment in cerebrovascular reserve, as assessed by clinical history, correlated most closely with the change in MTT in response to acetazolamide. Increased baseline MTT values may be a static, quantitative indicator of compromised cerebrovascular reserve in at-risk territories.

    View details for DOI 10.1016/j.neurad.2007.11.002

    View details for Web of Science ID 000258305200005

    View details for PubMedID 18242708

  • Semi-automated computer assessment of the degree of carotid artery stenosis compares favorably to visual evaluation JOURNAL OF THE NEUROLOGICAL SCIENCES Wintermark, M., Glastonbury, C., Tong, E., Lau, B. C., Schaeffer, S., Chien, J. D., Haar, P. J., Saloner, D. 2008; 269 (1-2): 74-79

    Abstract

    To validate a semi-automated computer approach for the assessment of the degree of carotid artery luminal narrowing by comparing it to the visual evaluation by a neuroradiologist.In a retrospective cross-sectional study, consecutive emergency department patients who underwent computed tomography angiography (CTA) of the carotid arteries were identified. CTA studies were reviewed by a neuroradiologist, and also independently processed with a computer algorithm that automatically measures the degree of luminal narrowing at the level of the internal carotid artery bulb. The findings of the neuroradiologist and computer assessment were compared using Chi2 tests/kappa calculations and linear regression for categorical and continuous measurements of carotid stenosis, respectively.The study population consisted of 125 patients (74 no stroke/TIA, 18TIA, and 33 stroke). 201 carotid arteries showed no significant stenosis; 33 showed > or =70% stenosis, 5 showed 95-99% stenosis, and 11 showed complete occlusion. There was excellent agreement between the neuroradiologist's visual assessment and the automated computer evaluation of the category of carotid stenosis (kappa=0.918, p<0.001).The automated computer algorithm for quantifying the degree of carotid stenosis is reliable and shows high concordance with the interpretation of an experienced neuroradiologist.

    View details for DOI 10.1016/j.jns.2007.12.023

    View details for Web of Science ID 000256208500012

    View details for PubMedID 18234230

  • Spinal arterial anatomy and risk factors for lower extremity weakness following endovascular thoracoabdominal aortic aneurysm repair with branched stent-grafts JOURNAL OF ENDOVASCULAR THERAPY Chang, C. K., Chuter, T. A., Reilly, L. M., Ota, M. K., Furtado, A., Bucci, M., Wintermark, M., Hiramoto, J. S. 2008; 15 (3): 356-362

    Abstract

    To evaluate spinal arterial anatomy and identify risk factors for lower extremity weakness (LEW) following endovascular thoracoabdominal aortic aneurysm (TAAA) repair.A retrospective review was conducted of 37 patients (27 men; mean age 74.8+/-7.1 years, range 58-86) undergoing endovascular TAAA repair with branched stent-grafts at a single academic institution from July 2005 to December 2007. Data were collected on preoperative comorbidities, duration of operation, blood loss, type of anesthesia, extent of aortic coverage, blood pressure, cerebrospinal fluid (CSF) pressure and drainage, and postoperative development of LEW. Pre- and postoperative contrast-enhanced computed tomographic angiograms (CTA) in a 26-patient subset were analyzed to evaluate the number of patent intercostal and lumbar arteries before and after repair.All patients were neurologically intact at the end of the operation. Seven (19%) patients developed LEW postoperatively: 6 perioperatively and 1 after discharge. LEW was associated with postoperative hypotension, internal iliac artery (IIA) occlusion, and fewer patent segmental arteries on preoperative CTA. Lowest mean systolic blood pressure was <90 mmHg in all 6 (100%) patients who developed LEW in hospital compared to 12 (44%) of the 27 patients who did not develop LEW (p = 0.02). Complete resolution of LEW (n = 4) followed prompt measures to raise blood pressure and lower CSF pressure. Persistent LEW (n = 3) was associated with sustained hypotension from sepsis, postoperative bleeding, and hemodialysis, respectively. Two (29%) of 7 patients with LEW either lost prograde flow to an IIA during repair or had bilaterally occluded IIAs preoperatively compared to 2 (7%) of 30 patients without LEW (p = 0.16). Comparison of pre- and postoperative CTAs showed no reduction in the mean number of patent segmental arteries in patients with or without LEW.Endovascular TAAA repair inevitably occludes direct inflow to lumbar and intercostal arteries. The distal segments of these arteries to the spine, however, are seen to remain patent through collaterals. Measures to preserve collateral pathways and increase perfusion pressure may help prevent or treat LEW.

    View details for Web of Science ID 000257093100015

    View details for PubMedID 18540712

  • Acute stroke imaging research roadmap STROKE Wintermark, M., Albers, G. W., Alexandrov, A. V., Alger, J. R., Bammer, R., Baron, J., Davis, S., Demaerschalk, B. M., Derdeyn, C. P., Donnan, G. A., Eastwood, J. D., Fiebach, J. B., Fisher, M., Furie, K. L., Goldmakher, G. V., Hacke, W., Kidwell, C. S., Kloska, S. P., Koehrmann, M., Koroshetz, W., Lee, T., Lees, K. R., Lev, M. H., Liebeskind, D. S., Ostergaard, L., Powers, W. J., Provenzale, J., Schellinger, P., Silbergleit, R., Sorensen, A. G., Wardlaw, J., Warach, S. 2008; 39 (5): 1621-1628

    Abstract

    The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.

    View details for DOI 10.1161/STROKEAHA.107.512319

    View details for Web of Science ID 000255393100043

    View details for PubMedID 18403743

  • High-resolution CT imaging of carotid artery atherosclerotic plaques AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Jawadi, S. S., Rapp, J. H., Tihan, T., Tong, E., Glidden, D. V., Abedin, S., Schaeffer, S., Acevedo-Bolton, G., Boudignon, B., Orwoll, B., Pan, X., Saloner, D. 2008; 29 (5): 875-882

    Abstract

    Plaque morphologic features have been suggested as a complement to luminal narrowing measurements for assessing the risk of stroke associated with carotid atherosclerotic disease, giving rise to the concept of "vulnerable plaque." The purpose of this study was to evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard.Eight patients with transient ischemic attacks who underwent carotid CTA and "en bloc" endarterectomy were enrolled in a prospective study. An ex vivo micro-CT study of each endarterectomy specimen was obtained, followed by histologic examination. A systematic comparison of CTA images with histologic sections and micro-CT images was performed to determine the CT attenuation associated with each component of the atherosclerotic plaques. A computer algorithm was subsequently developed that automatically identifies the components of the carotid atherosclerotic plaques, based on the density of each pixel. A neuroradiologist's reading of this computer analysis was compared with the interpretation of the histologic slides by a pathologist with respect to the types and characteristics of the carotid plaques.There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (kappa = 0.796; P < .001) and large hemorrhages (kappa = 0.712; P = .102). CTA performed well in detecting ulcerations (kappa = 0.855) and in measuring the fibrous cap thickness (R(2) = 0.77; P < .001).The composition of carotid atherosclerotic plaques determined by CTA reflects plaque composition defined by histologic examination.

    View details for DOI 10.3174/ajnr.A0950

    View details for Web of Science ID 000255966800010

    View details for PubMedID 18272562

  • Local cortical hypoperfusion imaged with CT perfusion during postictal Todd's paresis NEURORADIOLOGY Mathews, M. S., Smith, W. S., Wintermark, M., Dillon, W. P., Binder, D. K. 2008; 50 (5): 397-401

    Abstract

    Postictal ("Todd's") paralysis, or "epileptic hemiplegia," is a well-known complication of focal or generalized epileptic seizures. However, it is unclear whether the pathophysiology of Todd's paralysis is related to alterations in cerebral perfusion. We report CT perfusion findings in a patient presenting with postictal aphasia and right hemiparesis.A 62-year-old woman with a history of alcohol abuse, closed head injury and posttraumatic epilepsy, presented with acute onset aphasia and right hemiparesis. A non-contrast head CT scan demonstrated no acute hemorrhage. Left hemispheric ischemia was suspected, and the patient was considered for acute thrombolytic therapy. MRI revealed a subtle increase in signal intensity involving the left medial temporal, hippocampal and parahippocampal regions on both T2-weighted FLAIR and diffusion-weighted sequences. CT angiography and CT perfusion study were performed. The CT perfusion study and CT angiography demonstrated a dramatic reduction in cerebral blood flow and blood volume involving the entire left hemisphere, but with relative symmetry of mean transit time, ruling out a large vessel occlusion.Clinical resolution of the aphasia and hemiparesis occurred within a few hours, and correlated with normalization of perfusion to the left hemisphere (detected by MR perfusion).This unique case is the first in which clinical evidence of Todd's paralysis has been correlated with reversible postictal hemispheric changes on CT and MR perfusion studies. This is important because CT perfusion study is being used more and more in the diagnosis of acute stroke, and one needs to be careful to not misinterpret the data.

    View details for DOI 10.1007/s00234-008-0362-1

    View details for Web of Science ID 000255256500003

    View details for PubMedID 18278489

  • Radiation dose reduction strategy for CT protocols: Successful implementation in neuroradiology section RADIOLOGY Smith, A. B., Dillon, W. P., Lau, B. C., Gould, R., Verdun, F. R., Lopez, E. B., Wintermark, M. 2008; 247 (2): 499-506

    Abstract

    To retrospectively quantify the effect of systematic use of tube current modulation for neuroradiology computed tomographic (CT) protocols on patient dose and image quality.This HIPAA-compliant study had institutional review board approval, with waiver of informed consent. The authors evaluated the effect of dose modulation on four types of neuroradiologic CT studies: brain CT performed without contrast material (unenhanced CT) in adult patients, unenhanced brain CT in pediatric patients, adult cervical spine CT, and adult cervical and intracranial CT angiography. For each type of CT study, three series of 100 consecutive studies were reviewed: 100 studies performed without dose modulation, 100 studies performed with z-axis dose modulation, and 100 studies performed with x-y-z-axis dose modulation. For each examination, the weighted volume CT dose index (CTDI(vol)) and dose-length product (DLP) were recorded and noise was measured. Each study was also reviewed for image quality. Continuous variables (CTDI(vol), DLP, noise) were compared by using t tests, and categorical variables (image quality) were compared by using Wilcoxon rank-sum tests.For unenhanced CT of adult brains, the CTDI(vol) and DLP, respectively, were reduced by 60.9% and 60.3%, respectively, by using z-axis dose modulation and by 50.4% and 22.4% by using x-y-z-axis dose modulation. Significant dose reductions (P < .001) were also observed for pediatric unenhanced brain CT, cervical spine CT, and adult cervical and intracranial CT angiography performed with each dose modulation technique. Image quality and noise were unaffected by the use of either dose modulation technique (P > .05).Use of dose-modulation techniques for neuroradiology CT examinations affords significant dose reduction while image quality is maintained.

    View details for DOI 10.1148/radiol.2472071054

    View details for Web of Science ID 000255289700024

    View details for PubMedID 18372456

  • How accurate is CT angiography in evaluating intracranial atherosclerotic disease? STROKE Nguyen-Huynh, M. N., Wintermark, M., English, J., Lam, J., Vittinghoff, E., Smith, W. S., Johnston, S. C. 2008; 39 (4): 1184-1188

    Abstract

    Digital subtraction angiography (DSA) is regarded as the gold standard in assessing degree of stenosis in intracranial vessels. However, it is invasive and can only be carried out at specialized centers. We sought to compare CT angiography (CTA) to DSA for detection and measurement of stenosis in large intracranial arteries.We identified all subjects admitted with ischemic stroke or transient ischemic attack and with CTA and DSA studies of good quality completed within 30 days of each other between April 2000 and May 2006 at a single medical center. Two readers blinded to clinical information reviewed each CTA and DSA independently. Each reader located and measured stenosis of 15 prespecified large intracranial arterial segments per study at the same level of magnification. These stenotic lesions were most likely atherosclerotic in etiology. All measurements were made with Wiha digiMax 6" digital calipers. The degree of stenosis was calculated using the published method for the Warfarin-Aspirin Symptomatic Intracranial Disease study. All disagreements of greater than 10% were reviewed by a third reader who decided between the 2 prior measurements. Segments were excluded from analyses if they were judged to be congenitally hypoplastic or seen only through collaterals or cross-filling. Intraclass correlation, sensitivity, and specificity were calculated using DSA as the reference standard.Forty-one pairs of CTA and DSAs from 41 patients were reviewed. CTAs were completed within 28 days before 13 days after DSA, with a median of 1 day. A total of 475 pairs of major intracranial arterial segment were analyzed. Intraclass correlation between degree of stenosis based on CTA and DSA for all segments was 0.98 (P=0.001). CTA detected large arterial occlusion with 100% sensitivity and specificity. For detection of >or=50% stenosis, CTA had 97.1% sensitivity and 99.5% specificity. To detect all lesions >or=50% as determined by DSA, the cut off point on CTA appeared to be at >or=30%, with a false-positive rate of 2.4%.Compared to DSA, CTA has high sensitivity and specificity for detecting >or=50% stenosis of large intracranial arterial segments. CTA is minimally invasive and may be a useful screening tool for intracranial arterial disease and occlusion.

    View details for DOI 10.1161/STROKEAHA.107.502906

    View details for Web of Science ID 000254632900022

    View details for PubMedID 18292376

  • The anterior cerebral artery is an appropriate arterial input function for perfusion-CT processing in patients with acute stroke NEURORADIOLOGY Wintermark, M., Lau, B. C., Chien, J., Arora, S. 2008; 50 (3): 227-236

    Abstract

    Dynamic perfusion-CT (PCT) with deconvolution requires an arterial input function (AIF) for postprocessing. In clinical settings, the anterior cerebral artery (ACA) is often chosen for simplicity. The goals of this study were to determine how the AIF selection influences PCT results in acute stroke patients and whether the ACA is an appropriate default AIF.We retrospectively identified consecutive patients suspected of hemispheric stroke of less than 48 h duration who were evaluated on admission by PCT. PCT datasets were postprocessed using multiple AIF, and cerebral blood volume (CBV) and flow (CBF), and mean transit time (MTT) values were measured in the corresponding territories. Results from corresponding territories in the same patients were compared using paired t-tests. The volumes of infarct core and tissue at risk obtained with different AIFs were compared to the final infarct volume.Of 113 patients who met the inclusion criteria, 55 with stroke were considered for analysis. The MTT values obtained with an "ischemic" AIF tended to be shorter (P=0.055) and the CBF values higher (P=0.108) than those obtained using a "nonischemic" AIF. CBV values were not influenced by the selection of the AIF. No statistically significant difference was observed between the size of the PCT infarct core (P=0.121) and tissue at risk (P=0.178), regardless of AIF selection.In acute stroke patients, the selection of the AIF has no statistically significant impact of the PCT results; standardization of the PCT postprocessing using the ACA as the default AIF is adequate.

    View details for DOI 10.1007/s00234-007-0336-8

    View details for Web of Science ID 000253522800005

    View details for PubMedID 18057929

  • Contrast extravasation on CT predicts mortality in primary intracerebral hemorrhage AMERICAN JOURNAL OF NEURORADIOLOGY Kim, J., Smith, A., Hemphill, J. C., Smith, W. S., Lu, Y., Dillon, W. P., Wintermark, M. 2008; 29 (3): 520-525

    Abstract

    Recent studies of intracerebral hemorrhage (ICH) treatments have highlighted the need to identify reliable predictors of hematoma expansion. The goal of this study was to determine whether contrast extravasation on multisection CT angiography (CTA) and/or contrast-enhanced CT (CECT) of the brain is associated with hematoma expansion and increased mortality in patients with primary ICH.All patients with primary ICH who underwent CTA and CECT, as well as follow-up noncontrast CT (NCCT) before discharge/death from January 1, 2003, to September 30, 2005, were retrospectively identified. One neuroradiologist reviewed admission and follow-up NCCT for hematoma size and growth. A second neuroradiologist independently reviewed CTA and CECT for active contrast extravasation. Univariate and multivariate logistic regression analyses were performed to evaluate the significance of clinical and radiologic variables in predicting 30-day mortality, designated as the primary outcome. Hematoma growth was considered as a secondary outcome.Of 56 patients, contrast extravasation was seen in 17.9% of patients on initial CTA and in 23.2% of patients on initial CECT following CTA. Univariate analysis showed that the presence of extravasation on CT, large initial hematoma size (>30 mL), the presence of "swirl sign" on NCCT, the Glasgow Coma Scale and ICH scores, and international normalized ratio were associated with increased mortality. On multivariate analysis, only contrast extravasation on CT (P = .017) independently predicted mortality. Contrast extravasation on CT (P < .001) was also an independent predictor of hematoma growth on multivariate analysis.Active contrast extravasation on CT in patients with primary ICH independently predicts mortality and hematoma growth.

    View details for DOI 10.3174/ajnr.A0859

    View details for Web of Science ID 000254066700021

    View details for PubMedID 18065505

  • Imaging of intracranial haemorrhage LANCET NEUROLOGY Kidwell, C. S., Wintermark, M. 2008; 7 (3): 256-267

    Abstract

    Intracranial haemorrhage can be a devastating disorder that requires rapid diagnosis and management. Neuroimaging studies are not only required for diagnosis but also provide important insights into the type of haemorrhage, the underlying aetiology, and the accompanying pathophysiology. Historically, CT has been the diagnostic imaging study of choice; however, there is a growing body of data that suggest that MRI is at least as sensitive as CT to detect haemorrhage in the hyperacute setting, and superior to CT in the subacute and chronic settings. Blood has characteristic appearances on both imaging modalities at each stage (acute, subacute, and chronic) and it is important that physicians are familiar with the appearance of various types of intracranial haemorrhage on CT and MRI and their clinical implications. In addition, new imaging applications, such as magnetic resonance spectroscopy and diffusion tensor imaging, are promising research techniques that have the potential to enhance our understanding of the tissue injury and recovery that result from intracranial haemorrhage.

    View details for Web of Science ID 000253580000017

    View details for PubMedID 18275927

  • Monitoring serial change in the lumen and outer wall of vertebrobasilar aneurysms AMERICAN JOURNAL OF NEURORADIOLOGY Boussel, L., Wintermark, M., Martin, A., Dispensa, B., VanTijen, R., Leach, J., Rayz, V., Acevedo-Bolton, G., Lawton, M., Higashicla, R., Smith, W. S., Young, W. L., Saloner, D. 2008; 29 (2): 259-264

    Abstract

    Estimation of the stability of fusiform aneurysms of the basilar artery requires precise monitoring of the luminal and outer wall volumes. In this report we describe the use of MR imaging and 3D postprocessing methods to study the evolution of those aneurysms.Nine patients with fusiform basilar artery aneurysms underwent MR imaging studies covering at least 2 different time points (mean delay between studies, 7.1 +/- 4.6 months). Imaging included multisection 2D T1-weighted fast spin-echo and/or 3D steady-state imaging to assess the outer wall and contrast-enhanced MR angiography to study the lumen. The outer and inner walls were extracted using, respectively, a manual delineation (made by 2 observers) and a thresholding technique. The 2 studies were subsequently coregistered at each time point, as well as between differing time points. Volumes of each vessel component were calculated.Mean volume was 6760 +/- 6620 mm(3) for the outer wall and 2060 +/- 1200 mm(3) for the lumen. Evolution of the lumen and outer wall was highly variable from 1 patient to another, with a trend toward increase of the vessel wall for the largest aneurysms. Interobserver reproducibility for outer wall delineation was on the order of 90%.Combining MR imaging methods to study both the outer wall and lumen with 3D registration tools provides a powerful method for progression of fusiform basilar aneurysmal disease.

    View details for DOI 10.3174/ajnr.A0796

    View details for Web of Science ID 000253345200016

    View details for PubMedID 17974611

  • Accuracy and Anatomical Coverage of Perfusion CT Assessment of the Blood-Brain Barrier Permeability: One Bolus versus Two Boluses CEREBROVASCULAR DISEASES Dankbaar, J. W., Hom, J., Schneider, T., Cheng, S., Lau, B. C., van der Schaaf, I., Virmani, S., Pohlman, S., Dillon, W. P., Wintermark, M. 2008; 26 (6): 600-605

    Abstract

    To assess whether blood-brain barrier permeability (BBBP) values, extracted with the Patlak model from the second perfusion CT (PCT) contrast bolus, are significantly lower than the values extracted from the first bolus in the same patient.125 consecutive patients (29 with acute hemispheric stroke and 96 without stroke) who underwent a PCT study using a prolonged acquisition time up to 3 min were retrospectively identified. The Patlak model was applied to calculate the rate of contrast leakage out of the vascular compartment. Patlak plots were created from the arterial and parenchymal time enhancement curves obtained in multiple regions of interest drawn in ischemic brain tissue and in nonischemic brain tissue. The slope of a regression line fit to the Patlak plot was used as an indicator of BBBP. Square roots of the mean squared errors and correlation coefficients were used to describe the quality of the linear regression model. This was performed separately for the first and the second PCT bolus. Results from the first and the second bolus were compared in terms of BBBP values and the quality of the linear model fitted to the Patlak plot, using generalized estimating equations with robust variance estimation.BBBP values from the second bolus were not lower than BBBP values from the first bolus in either nonischemic brain tissue [estimated mean with 95% confidence interval: 1.42 (1.10-1.82) ml x 100 g(-1) x min(-1) for the first bolus versus 1.64 (1.31-2.05) ml x 100 g(-1) x min(-1) for the second bolus, p = 1.00] or in ischemic tissue [1.04 (0.97-1.12) ml x 100 g(-1) x min(-1) for the first bolus versus 1.19 (1.11-1.28) ml x 100 g(-1)min(-1) for the second bolus, p = 0.79]. Compared to regression models from the first bolus, the Patlak regression models obtained from the second bolus were of similar or slightly better quality. This was true both in nonischemic and ischemic brain tissue.The contrast material from the first bolus of contrast for PCT does not negatively influence measurements of BBBP values from the second bolus. The second bolus can thus be used to increase anatomical coverage of BBBP assessment using PCT.

    View details for DOI 10.1159/000165113

    View details for Web of Science ID 000261132400005

    View details for PubMedID 18946215

  • Visual grading system for vasospasm based on perfusion CT imaging: Comparisons with conventional angiography and quantitative perfusion CT CEREBROVASCULAR DISEASES Wintermark, M., Dillon, W. P., Smith, W. S., Lau, B. C., Chaudhary, S., Liu, S., Yu, M., Fitch, M., Chien, J. D., Higashida, R. T., Ko, N. U. 2008; 26 (2): 163-170

    Abstract

    The purpose of this study was to compare simple visual grading of perfusion CT (PCT) maps to a more quantitative, threshold-based interpretation of PCT parameters in the characterization of presence and severity of vasospasm.Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 paired PCT and digital subtraction angiography (DSA) examinations. A neuroradiologist and a neurologist reviewed the PCT mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume maps independently; they evaluated five anatomical regions (frontal, temporal, parietal, occipital/thalami, and basal ganglia/insula) and graded them for abnormality (0 if normal, 1 if abnormal in <50% of the region, and 2 if abnormal in >or=50% of the region). A third neuroradiologist blinded to the PCT results reviewed the DSA examinations and assessed 19 segments for the presence or absence of vasospasm. Correlation between PCT and DSA scores was assessed, as well as the sensitivity and specificity of PCT compared to DSA used as a gold standard.MTT (R(2) = 0.939) and CBF (R(2) = 0.907) scores correlated best with DSA scores (p < 0.001). MTT scoring had a sensitivity of 92% and a specificity of 86% compared to DSA; CBF scoring had a sensitivity of 75% and a specificity of 95%. The interobserver agreement between neuroradiologist and neurologist was found to have kappa = 0.789 for MTT and 0.658 for CBF.We propose a user-friendly visual grading system for PCT maps in patients with suspected vasospasm. This visual approach compares favorably to the results of DSA. Sensitive MTT maps should be used for screening, and specific CBF maps for confirmation of vasospasm.

    View details for DOI 10.1159/000139664

    View details for Web of Science ID 000259725400010

    View details for PubMedID 18560220

  • Perfusion CT imaging follows clinical severity in left hemispheric strokes EUROPEAN NEUROLOGY Furtado, A. D., Smith, W. S., Koroshetz, W., Dillon, W. P., Furie, K. L., Lev, M. H., Vittinghoff, E., Schaeffer, S., Biagini, T., Hazarika, O., Wintermark, M. 2008; 60 (5): 244-252

    Abstract

    The purpose of this study was to assess how imaging findings on admission perfusion CT (PCT) and follow-up noncontrast CT (NCT), and their changes over time, correlate with clinical scores of stroke severity measured on admission, at discharge and at 6-month follow-up.Fifty-two patients with suspected hemispheric acute ischemic stroke underwent a PCT within the first 24 h of symptom onset and a follow-up NCT of the brain between 24 h and 3 months after the initial stroke CT study. NIH Stroke Scale (NIHSS) scores were recorded for each patient at admission, discharge and 6 months; modified Rankin scores were determined at discharge and 6 months. Baseline PCT and follow-up NCT were analyzed quantitatively (volume of ischemic/infarcted tissue) and semiquantitatively (anatomical grading score derived from the Alberta Stroke Program Early CT Score). The correlation between imaging volumes/scores and clinical scores was assessed. Analysis was performed for all patients considered together and separately for those with right and left hemispheric strokes.Significant correlations were found between clinical scores and both quantitative and semiquantitative imaging. The volume of the acute PCT mean transit time lesion showed best correlation with admission NIHSS scores (R2 = 0.61, p < 0.001). This association was significantly better for left hemispheric strokes (R(2) = 0.80, p < 0.001) than for right hemispheric strokes (R2 = 0.39, p = 0.131). Correlation between imaging and NIHSS scores was better than correlation between imaging and modified Rankin scores (p = 0.047). The correlation with discharge clinical scores was better than that with 6-month clinical scores (p = 0.012).Baseline PCT and follow-up NCT volumes predict stroke severity at baseline, discharge and, to a lesser extent, 6 months. The correlation is stronger for left-sided infarctions. This finding supports the use of PCT as a surrogate stroke outcome measure.

    View details for DOI 10.1159/000151700

    View details for Web of Science ID 000259725000005

    View details for PubMedID 18756089

  • Prospective evaluation of multidetector-row CT angiography for the diagnosis of vasospasm following subarachnoid hemorrhage: A comparison with digital subtraction angiography CEREBROVASCULAR DISEASES Chaudhary, S. R., Ko, N., Dillon, W. P., Yu, M. B., Liu, S., Criqui, G. I., Higashida, R. T., Smith, W. S., Wintermark, M. 2008; 25 (1-2): 144-150

    Abstract

    To evaluate the accuracy of multidetector-row CT angiography (CTA) for the diagnosis of large-vessel vasospasm following subarachnoid hemorrhage by comparison to digital subtraction angiography (DSA).Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 CTA and DSA examinations within 24 h of each other. Two neuroradiologists reviewed the CTA examinations independently. A third neuroradiologist blinded to the CTA results reviewed the DSA examinations. In each patient, for both techniques, 23 arterial segments were evaluated for their degree of narrowing; the reviewers were asked to attribute every narrowing to 'vasospasm' or 'hypoplasia'. Agreement between CTA and DSA for the degree of narrowing, and agreement between the two CTA readers, were calculated using weighted kappa-coefficients. Sensitivity, specificity, accuracy, positive and negative predictive value (NPV) of CTA to detect large-vessel vasospasm were calculated considering DSA as the gold standard.Substantial correlation (kappa = 0.638) was found between CTA and DSA for the detection of arterial narrowing. Interobserver agreement between the two CTA reviewers for the degree of luminal narrowing was substantial (kappa = 0.712).CTA was 87% accurate for the diagnosis of large-vessel vasospasm; the NPV of CTA was 95%. CTA was more accurate, and interobserver agreement higher, for the proximal arterial segments (basilar and vertebral arteries) than for the distal ones (P2 segments). Using CTA as a screening modality, 83% of unnecessary DSA would have been avoided.Compared to the gold standard of DSA, CTA is accurate for the detection of large-vessel vasospasm, and has a very high NPV.

    View details for DOI 10.1159/000112325

    View details for Web of Science ID 000253911700021

    View details for PubMedID 18073468

  • Motor trephine syndrome: A mechanistic hypothesis INTRACRANIAL PRESSURE AND BRAIN MONITORING XIII: MECHANISMS AND TREATMENT Stiver, S. I., Wintermark, M., Manley, G. T. 2008; 102: 273-277

    Abstract

    In our neurotrauma practice, "motor trephine syndrome" was defined as a contralateral monoparesis that developed as a delayed and reversible complication in patients treated with decompressive hemicraniectomy for traumatic brain injury (TBI). The goal of this study was to define causal factors associated with this syndrome.We retrospectively reviewed clinical records and imaging studies of all patients undergoing decompressive hemicraniectomy followed by cranioplasty repair in our comprehensive database of TBI patients. Detailed analysis of motor function from the time of injury to 6 months following cranioplasty repair identified three patterns of motor recovery.Blossoming of contusions, CSF circulation dysfunction, and longer times to cranioplasty repair were strongly associated with "motor trephine syndrome". We hypothesize that "motor trephine syndrome" arises from decompensated CSF flow with transgression of CSF fluid and edema into brain parenchyma, together with associated decrements in cerebral blood flow.Prior contusion injury, decreased skull resistance with large hemispheric decompressions, and longer intervals to cranioplasty repair facilitate transparenchymal flow of CSF and edema. "Motor trephine syndrome" is rapidly reversible following cranioplasty repair. CSF and edema fluid changes within the parenchyma and CBF normalize, coincident with improvements in the patient's motor function, upon replacement of the bone.

    View details for Web of Science ID 000264168500051

    View details for PubMedID 19388328

  • Brain perfusion CT: principles, technique and clinical applications RADIOLOGIA MEDICA Cianfoni, A., Colosimo, C., Basile, M., Wintermark, M., Bonomo, L. 2007; 112 (8): 1225-1243

    Abstract

    The imaging of brain haemodynamics and its applications are generating growing interest. By providing quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), dynamic perfusion computed tomography (p-CT) allows visualisation of cerebral autoregulation mechanisms and represents a fast, available and reliable imaging option for assessing cerebral perfusion. Thanks to its feasibility in emergency settings, p-CT is considered most useful, in combination with CT angiography, in acute ischaemic patients, as it is able to provide a fast and noninvasive assessment of cerebral perfusion impairment. In addition, p-CT can play a diagnostic role in other types of cerebrovascular disease to assess functional reserve, and in intracranial neoplasms, where it has a role in diagnosis, grading, biopsy guidance, and follow-up during treatment. This article illustrates the principles, technique and clinical applications of p-CT cerebral perfusion studies.

    View details for DOI 10.1007/s11547-007-0219-4

    View details for Web of Science ID 000252151900011

    View details for PubMedID 18074193

  • Radiation dose-reduction strategies for neuroradiology CT protocols AMERICAN JOURNAL OF NEURORADIOLOGY Smith, A. B., Dillon, W. P., Gould, R., Wintermark, M. 2007; 28 (9): 1628-1632

    Abstract

    Within the past 2 decades, the number of CT examinations performed has increased almost 10-fold. This is in large part due to advances in multidetector-row CT technology, which now allows faster image acquisition and improved isotropic imaging. The increased use, along with multidetector technique, has led to a significantly increased radiation dose to the patient from CT studies. This places increased responsibility on the radiologist to ensure that CT examinations are indicated and that the "as low as reasonably achievable" concept is adhered to. Neuroradiologists are familiar with factors that affect patient dose such as pitch, milliamperes, kilovolt peak (kVp), collimation, but with increasing attention being given to dose reduction, they are looking for additional ways to further reduce the radiation associated with their CT protocols. In response to increasing concern, CT manufacturers have developed dose-reduction tools, such as dose modulation, in which the tube current is adjusted along with the CT acquisition, according to patient's attenuation. This review will describe the available techniques for reducing dose associated with neuroradiologic CT imaging protocols.

    View details for DOI 10.3174/ajnr.A0814

    View details for Web of Science ID 000250312200005

    View details for PubMedID 17893208

  • Systematic comparison of perfusion-CT and CT-angiography in acute stroke patients ANNALS OF NEUROLOGY Tan, J. C., Dillon, W. P., Liu, S., Adler, F., Smith, W. S., Wintermark, M. 2007; 61 (6): 533-543

    Abstract

    To systematically evaluate the accuracy of noncontrast computed tomography (NCT), perfusion computed tomography (PCT), and computed tomographic angiography (CTA) in determining site of occlusion, infarct core, salvageable brain tissue, and collateral flow in a large series of patients suspected of acute stroke.We retrospectively identified all consecutive patients with signs and symptoms suggesting hemispheric stroke of < 48 hours in duration who were evaluated on admission by NCT, PCT, and CTA, and underwent a follow-up CT/CTA or magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) within 6 months of initial imaging. Two neuroradiologists evaluated NCT for hypodensity, PCT for infarct core and salvageable brain tissue, and CTA source images and maximal intensity projections for site of occlusion, infarct core, and collateral flow. Follow-up CTA and MRA were assessed for persistent arterial occlusion or recanalization. Follow-up CT and MRI were reviewed for final infarct location and volume, and used as a gold standard to calculate sensitivity (SE) and specificity (SP) of initial imaging.A total of 113 patients were considered for analysis, including 55 patients with a final diagnosis of stroke. CTA source images were the most accurate technique in the detection of the site of occlusion (SE = 95%; SP = 100%). Decreased cerebral blood volume on PCT was the most accurate predictor of final infarct volume (SE = 80%; SP = 97%), Increased mean transit time on PCT was predictive of the tissue at risk for infarction in patients with persistent arterial occlusion. CTA maximal intensity projections was the best technique to quantify the degree of collateral circulation.The most accurate assessment of the site of occlusion, infarct core, salvageable brain tissue, and collateral circulation in patients suspected of acute stroke is afforded by a combination of PCT and CTA.

    View details for DOI 10.1002/ana.21130

    View details for Web of Science ID 000248021500006

    View details for PubMedID 17431875

  • Comparison of CT perfusion and angiography and MRI in selecting stroke patients for acute treatment NEUROLOGY Wintermark, M., Meuli, R., Browaeys, P., Reichhart, M., Bogousslavsky, J., Schnyder, P., Michel, P. 2007; 68 (9): 694-697

    Abstract

    Forty-two stroke patients successively underwent perfusion CT (PCT)/CT angiography (CTA) and MRI examinations within 3 to 9 hours following symptom onset; 14 would have been suitable candidates for reperfusion treatment based on MRI findings. Correlation between PCT/CTA and MRI was excellent for infarct size, cortical involvement, and internal cerebral artery occlusion and substantial for penumbra/infarct ratio. Relying on MRI or PCT/CTA would have led to the same treatment decisions in all cases but one.

    View details for Web of Science ID 000244482400014

    View details for PubMedID 17325279

  • MRI of geometric and compositional features of vulnerable carotid plaque STROKE Saloner, D., Acevedo-Bolton, G., Wintermark, M., Rapp, J. H. 2007; 38 (2): 637-641

    Abstract

    Noninvasive imaging of atherosclerotic disease provides a powerful opportunity to gain insight into the complex chain of events underlying atherogenesis, plaque progression, and ultimately those processes that result in atherothrombosis with accompanying clinical symptoms. MRI is particularly attractive because it is noninvasive and is capable of providing a rich array of information on vascular disease. MR methods have been demonstrated to provide information on important features of vascular disease, including the geometric morphology of the flow lumen and the vessel wall, the composition of atheroma, measurement of flow velocities through vessels independent of overlying structures, and more recently insights into the presence and activity of specific molecules that are considered to be important participants in the inflammatory processes and that might differentiate the stable plaque from the vulnerable plaque.

    View details for DOI 10.1161/01.STR.0000254127.52214.2b

    View details for Web of Science ID 000244122600798

    View details for PubMedID 17261706

  • Restricted diffusion in bilateral optic nerves and retinas as an indicator of venous ischemia caused by cavernous sinus thrombophlebitis AMERICAN JOURNAL OF NEURORADIOLOGY Chen, J. S., Mukherjee, P., Dillon, W. P., Wintermark, M. 2006; 27 (9): 1815-1816

    Abstract

    A 44-year-old man developed bilateral blindness following severe periorbital cellulitis and pansinusitis. CT and MR imaging demonstrated bilateral cavernous sinus thrombosis. Diffusion-weighted imaging revealed reduced apparent diffusion coefficient in bilateral optic nerves, suggesting optic nerve ischemia caused by the cavernous sinus thrombophlebitis (CST). Following surgical debridement of pansinusitis, antimicrobial therapy, and anticoagulation, the patient recovered from the infectious episode but sustained permanent bilateral blindness. This case shows that both retinal and optic nerve ischemia can be the cause of blindness after CST. Arguments supporting an arterial-versus-venous origin for the ischemia are discussed.

    View details for Web of Science ID 000241316400007

    View details for PubMedID 17032847

  • Unmasking complicated atherosclerotic plaques on carotid magnetic resonance angiography: A report of three cases JOURNAL OF VASCULAR SURGERY Wintermark, M., Rapp, J. H., Tan, J., Saloner, D. 2006; 44 (4): 884-887

    Abstract

    In stenotic lesions of the extracranial carotid arteries, the presence of intraplaque hemorrhage or thrombosed ulceration is considered to pose an additional risk. Although contrast-enhanced magnetic resonance angiography (MRA) is a powerful means for looking at the vascular lumen, it provides little information on the vessel wall, particularly when mask subtraction methods are used. We report three cases in which the maximal intensity projections obtained from gadolinium-enhanced MRA source images showed only internal carotid artery stenoses, whereas source images revealed a focal increased T1 signal in the wall of the internal carotid artery, representing either intraplaque hemorrhage or thrombosed ulceration. Hence, the physicians interpreting an MRA in an acute stroke patient should not limit themselves to the synthetic maximal intensity projections but should also always review the source partitions, which can contain information related to an acute intraplaque accident.

    View details for DOI 10.1016/j.jvs.2006.06.011

    View details for Web of Science ID 000240960000036

    View details for PubMedID 17012014

  • Quantitative measurement of blood-brain barrier permeability using perfusion-CT in extra-axial brain tumors JOURNAL OF NEURORADIOLOGY Cianfoni, A., Cha, S., Bradley, W. G., Dillon, W. P., Wintermark, M. 2006; 33 (3): 164-168

    Abstract

    Non-invasive assessment of vascular permeability is of main importance in the diagnosis, treatment and follow-up of intracranial tumors. Perfusion-CT is one of the imaging options available, which affords quantitative assessment of cerebral blood volume and blood-brain barrier permeability. Herein we report two cases of extra-axial tumors studied with perfusion-CT. Comparison with perfusion-MRI was available in one case. High permeability values, as measured by perfusion-CT, reflected the absence of blood-brain barrier in these extra-axial tumors.

    View details for Web of Science ID 000239129200004

    View details for PubMedID 16840958

  • Perfusion-CT assessment of infarct core and penumbra - Receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke STROKE Wintermark, M., Flanders, A. E., Velthuis, B., Meuli, R., van Leeuwen, M., Goldsher, D., Pineda, C., Serena, J., van der Schaaf, I., Waaijer, A., Anderson, J., Nesbit, G., Gabriely, I., Medina, V., Quiles, A., Pohlman, S., Quist, M., Schnyder, P., Bogousslavsky, J., Dillon, W. P., Pedraza, S. 2006; 37 (4): 979-985

    Abstract

    Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra.One hundred and thirty patients with symptoms suggesting hemispheric stroke < or =12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard.The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml x 100 g(-1).In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

    View details for DOI 10.1161/01.STR.0000209238.61459.39

    View details for Web of Science ID 000236292100015

    View details for PubMedID 16514093

  • Association between extrinsic and intrinsic carpal ligament injuries at MR arthrography and carpal instability at radiography: Initial observations RADIOLOGY Theumann, N. H., Etechami, G., Duvoisin, B., Wintermark, M., Schnyder, P., Favarger, N., Gilula, L. A. 2006; 238 (3): 950-957

    Abstract

    To retrospectively compare the presence or absence of carpal instability on radiographs with the findings of magnetic resonance (MR) arthrographic evaluation of intrinsic and extrinsic ligament tears in patients with chronic wrist pain.The institutional review board approved this study and did not require informed consent. Signs of carpal instability were assessed on static and dynamic radiographs of the wrist obtained in 72 patients (24 female, 48 male; mean age, 36 years; age range, 14-59 years) with posttraumatic wrist pain. MR arthrography was subsequently performed. Two musculoskeletal radiologists independently analyzed the radiographs and MR images. Each intrinsic and extrinsic ligament was individually evaluated for the presence of a ligament tear. The extent of the tear also was recorded. Interobserver agreement regarding MR arthrographic findings was tested by calculating kappa statistics. Statistical comparison between radiography and MR arthrography was performed by using the Fisher exact test.Twenty-five triangular fibrocartilage complex, 18 (five partial, 13 complete) scapholunate ligament, and 25 (10 partial, 15 complete) lunotriquetral ligament tears were visualized. Twenty-two (all complete) extrinsic ligament tears were detected: two radial collateral ligament, 10 radioscaphocapitate ligament, and 10 radiolunotriquetral ligament tears. Interobserver agreement regarding intrinsic and extrinsic ligament tear detection at MR arthrography was excellent (kappa = 0.80). Nineteen patients had evidence of carpal instability on radiographs. Fourteen (52%) of 27 patients with at least one complete intrinsic lesion had no sign of carpal instability. On the other hand, the association of scapholunate ligament and/or lunotriquetral ligament and extrinsic ligament tears was significantly correlated (P < .001) with carpal instability at radiography.The presence or absence of carpal instability on radiographs depends on the association between intrinsic and extrinsic ligament tears-even partial ones-rather than on the presence of intrinsic ligament tears alone, even when the tears are complete.

    View details for DOI 10.1148/radiol.2383050013

    View details for Web of Science ID 000235520100023

    View details for PubMedID 16424247

  • Cerebral vascular autoregulation assessed by perfusion-CT in severe head trauma patients JOURNAL OF NEURORADIOLOGY Wintermark, M., Chiolero, R., Van Melle, G., Revelly, J. P., Porchet, F., Regli, L., Maeder, P., Meuli, R., Schnyder, P. 2006; 33 (1): 27-37

    Abstract

    To use perfusion-CT technique in order to characterize cerebral vascular autoregulation in a population of severe head trauma patients with features of cerebral edema either on the admission or on the follow-up conventional noncontrast cerebral CT.A total of 80 perfusion-CT examinations were obtained in 42 severe head trauma patients with features of cerebral edema on conventional noncontrast cerebral CT, either on admission or during follow-up. Perfusion-CT results, i.e. the regional cerebral blood volume (rCBV) and flow (rCBF), were correlated with the mean arterial pressure (MAP) measured during each perfusion-CT examination. Ratios were defined to integrate the concept of cerebral vascular autoregulation, and cluster analysis performed, which allowed identification of different subgroups of patients. MAP values and perfusion-CT results in these groups were compared using Kruskal-Wallis and Wilcoxon (Mann-Whitney) tests. Moreover, the functional outcome of the 42 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale (GOS) score and similarly compared between groups.Three main groups of patients were identified: 1) 22 perfusion-CT examinations were collected in 13 patients, characterized by high rCBV and rCBF values and by significant dependence of perfusion-CT rCBV and rCBF results on MAP values (p<0.001), 2) 23 perfusion-CT examinations collected in 19 patients showing perfusion-CT results similar to control trauma subjects, and 3) 33 perfusion-CT collected in 16 patients, with low rCBV and rCBF values and near-independence of perfusion-CT results with respect to MAP values. The first group was interpreted as showing impaired cerebral vascular autoregulation, which was preserved in the third group. The second group was associated with the best functional outcome; it was linked to the first group, because eight patients went from one group to the other from admission to follow-up.Perfusion-CT in severe head trauma patients was able to provide direct and quantitative assessment of cerebral vascular autoregulation with a single measurement. It could hence be used as a guide for brain edema therapy, as well as to monitor the treatment efficiency.

    View details for Web of Science ID 000236062000003

    View details for PubMedID 16528203

  • Imaging and CFD in the analysis of vascular disease progression MEDICAL IMAGING 2006: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES PTS 1 AND 2 Saloner, D., Acevedo-Bolton, G., Rayz, V., Wintermark, M., Martin, A., Dispensa, B., Young, W., Lawton, M., Rapp, J., Jou, L. 2006; 6143

    View details for DOI 10.1117/12.662791

    View details for Web of Science ID 000237637000016

  • Iodinated and gadolinium contrast media in computed tomography (CT) and magnetic resonance (MR) stroke imaging CURRENT MEDICINAL CHEMISTRY Wintermark, M., Fiebach, J. 2006; 13 (22): 2717-2723

    Abstract

    Thrombolysis has become an approved therapy for acute stroke. However, many stroke patients do not benefit from such treatment, since the presently used criteria are very restrictive, notably with respect to the accepted time window. Even so, a significant rate of intracranial hemorrhage still occurs. Conventional cerebral computed tomography (CT) without contrast has been proposed as a selection tool for acute stroke patients. Recently, more modern magnetic resonance imaging (MRI) and CT techniques, referred to as diffusion- and perfusion-weighted imaging, and perfusion-CT, have been introduced. They afford a comprehensive noninvasive survey of acute stroke patients as soon as their emergency admission, with accurate demonstration of the site of arterial occlusion and its hemodynamic and pathophysiological repercussions of the brain parenchyma. The objective of this review article is to present the advantages and drawbacks of CT, using iodinated contrast, and MRI, using gadolinium, in the evaluation of acute stroke patients.

    View details for Web of Science ID 000240122600011

    View details for PubMedID 17017923

  • Vasospasm after subarachnoid hemorrhage: Utility of perfusion CT and CT angiography on diagnosis and management AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Ko, N. U., Smith, W. S., Liu, S., Higashida, R. T., Dillon, W. P. 2006; 27 (1): 26-34

    Abstract

    To evaluate the utility of perfusion CT (PCT) combined with CT angiography (CTA) for the diagnosis and management of vasospasm, by using conventional digital subtraction angiography (DSA) as the gold standard.We retrospectively identified 27 patients with acute subarachnoid hemorrhage who had undergone CTA/PCT, DSA, and transcranial Doppler (TCD) ultrasonography within a time interval of 12 hours of one another. The patients' charts were reviewed for treatment of vasospasm. CTA, PCT, TCD, and DSA examinations were independently reviewed and quantified for vasospasm. PCT thresholds, CTA findings, noncontrast CT (NCT) hypodensities, and TCD thresholds were evaluated for accuracy, sensitivity, and specificity, as well as for negative (NPV) and positive predictive values (PPV) in the prediction of angiographic vasospasm and endovascular treatment, considering DSA as the gold standard.Thirty-five CTA/PCT, TCD, and DSA examinations were performed on these 27 patients. A total of 123 arterial territories in 11 patients demonstrated angiographic vasospasm. Six patients underwent endovascular therapy. CTA qualitative assessment and PCT-derived mean transit time (MTT) with a threshold at 6.4 seconds represented the most accurate (93%) combination for the diagnosis of vasospasm, whereas MTT considered alone represented the most sensitive parameter (NPV, 98.7%). A cortical regional cerebral blood flow value

    View details for Web of Science ID 000234779600017

    View details for PubMedID 16418351

  • Hyperplastic anterior choroidal artery identified using magnetic resonance angiography: A report of two cases CEREBROVASCULAR DISEASES Antonietti, L. C., Glastonbury, C. M., Adler, F., Wintermark, M. 2006; 22 (5-6): 450-452

    View details for DOI 10.1159/000095382

    View details for Web of Science ID 000243592400022

    View details for PubMedID 16940717

  • Comparative overview of brain perfusion imaging techniques. Stroke; a journal of cerebral circulation Wintermark, M., Sesay, M., Barbier, E., Borbély, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J., Nariai, T., Zaharchuk, G., Caillé, J., Dousset, V., Yonas, H. 2005; 36 (9): e83-99

    Abstract

    Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks.This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques.For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting.

    View details for PubMedID 16100027

  • Comparative overview of brain perfusion imaging techniques STROKE Wintermark, M., Sesay, M., Barbier, E., Borbely, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J. F., Nariai, T., Zaharchuk, G., Caille, J. M., Dousset, V., Yonas, H. 2005; 36 (9): E83-E99
  • Comparative overview of brain perfusion imaging techniques STROKE Wintermark, M., Sesay, M., Barbier, E., Borbely, K., Dillon, W. P., Eastwood, J. D., Glenn, T. C., Grandin, C. B., Pedraza, S., Soustiel, J. F., Nariai, T., Zaharchuk, G., Caille, J. M., Dousset, V., Yonas, H. 2005; 36 (9): 2032-2033
  • Posttraumatic pseudolipoma: MRI appearances EUROPEAN RADIOLOGY Theumann, N., Abdelmoumene, A., Wintermark, M., Schnyder, P., Gailloud, M. C., Resnick, D. 2005; 15 (9): 1876-1880

    Abstract

    The goal of this study was to describe the MRI characteristics of posttraumatic pseudolipomas. Ten patients with previous history of blunt trauma or local surgery were investigated with MRI at the level of their deformity. The etiology was blunt trauma in eight patients and postoperative trauma in two. For all patients medical documentation, in the form of clinical history and physical examination, confirmed that a visible hematoma was present acutely at the same location following the injury and that the contour deformity subsequently appeared. All patients underwent liposuction. Preoperative bilateral MRI examinations were performed on all patients. The mean clinical follow-up was 17.8 months. MRI examinations were interpreted in consensus by two experienced musculoskeletal radiologists with attention to fatty extension (subcutaneous fatty thickness and anatomical extension), asymmetry compared with the asymptomatic side, the presence or absence of fibrous septae or nonfatty components, and patterns of contrast enhancement. Ten posttraumatic pseudolipomas were identified. Clinically, they showed as subcutaneous masses with the consistency of normal adipose tissue. Their locations were the abdomen (n=1), hip (n=1), the upper thigh (n=6), the knee (n=1), and the ankle (n=1). On MRI examinations, using the contralateral side as a control, pseudolipomas appeared as focal fatty masses without a capsule or contrast enhancement. Posttraumatic pseudolipomas may develop at a site of blunt trauma or surgical procedures often antedated by a soft tissue hematoma. Characteristic MRI findings are unencapsulated subcutaneous fatty masses without contrast enhancement.

    View details for DOI 10.1007/s00330-005-2757-2

    View details for Web of Science ID 000231162000012

    View details for PubMedID 15841381

  • Acute brain perfusion disorders in children assessed by quantitative perfusion computed tomography in the emergency setting PEDIATRIC EMERGENCY CARE Wintermark, M., Cotting, J., Roulet, E., Lepori, D., Meuli, R., Maeder, P., Regli, L., Deonna, T., Schnyder, P., Gudinchet, F. 2005; 21 (3): 149-160

    Abstract

    Perfusion computed tomography (CT) is a simple imaging technique that allows accurate quantitative assessment of brain perfusion. Perfusion CT is an ideal imaging technique to be used in the emergency setting and has thus gained recognition in the early management of adult acute stroke patients. Perfusion CT can be applied to children successfully by using adequate imaging protocols. The goal of this article is to provide a pictorial essay of the perfusion CT features of diseases that affect brain perfusion as depicted in a population of children who were evaluated in the emergency CT unit of our institution.During the period of September 2001 to October 2002, all the children, who were evaluated in the emergency CT unit of our institution and who were prescribed with a cerebral CT and an intravenous administration of iodinated contrast material, underwent a perfusion-CT examination. Perfusion-CT maps were reviewed in the patients diagnosed as abnormal on the basis of follow-up clinical/radiological examinations and correlated with the results of these tests.Brain perfusion-CT examinations have been performed in 77 children. Fifty-three patients were considered as normal, based on normal conventional cerebral CT and normal clinical/radiological follow-up. Perfusion-CT results showed major abnormalities in 14 cases among the 24 remaining patients, related to brain ischemia in 2, head trauma in 9, brain infection in 2, and sickle cell disease in 1. These abnormalities consisted in low regional cerebral blood flow and volume values, and in high mean transit time values. They demonstrated typical anatomical distribution, depending on the considered pathological condition.Perfusion CT provides quantitative assessment of child brain perfusion disorders. Its ability to be easily performed upon admission makes it an ideal emergency tool that advantageously competes with other imaging techniques such as perfusion-weighted magnetic resonance imaging, despite its limited spatial coverage. Its usefulness with respect to the impact on treatment and outcome, however, remains to be established in further studies.

    View details for Web of Science ID 000227653100002

    View details for PubMedID 15744192

  • An explanation for putaminal CT, MR, and diffusion abnormalities secondary to nonketotic hyperglycemia - Reply AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Fischbein, N. J., Mukherjee, P., Yuh, E. L., Dillon, W. P. 2005; 26 (1): 195-195
  • Accuracy of dynamic perfusion CT with deconvolution in detecting acute hemispheric stroke AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Fischbein, N. J., Smith, W. S., Ko, N. U., Quist, M., Dillon, W. P. 2005; 26 (1): 104-112

    Abstract

    Dynamic perfusion CT (PCT) with deconvolution produces maps of time-to-peak (TTP), mean transit time (MTT), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV), with a computerized automated map of the infarct and penumbra. We determined the accuracy of these maps in patients with suspected acute hemispheric stroke.Forty-six patients underwent nonenhanced CT and dynamic PCT, with follow-up CT or MR imaging. Two observers reviewed the nonenhanced studies for signs of stroke and read the PCT maps for TTP, MTT, rCBF, and rCBV abnormalities. Sensitivity, specificity, accuracy, and interobserver agreement were compared (Wilcoxon tests). Nonenhanced CT and PCT data were reviewed for stroke extent according to previously reported methods. Sensitivity, specificity, and accuracy of the computerized maps in detecting ischemia and its extent were determined.Compared with nonenhanced CT, PCT maps were significantly more accurate in detecting stroke (75.7-86.0% vs. 66.2%; P <.01), MTT maps were significantly more sensitive (77.6% vs. 69.2%; P <.01), and rCBF and rCBV maps were significantly more specific (90.9% and 92.7%, respectively, vs. 65.0%; P <.01). Regarding stroke extent, PCT maps were significantly more sensitive than nonenhanced CT (up to 94.4% vs. 42.9%; P <.01) and had higher interobserver agreement (up to 0.763). For the computerized map, sensitivity, specificity, and accuracy, respectively, were 68.2%, 92.3%, and 88.1% in detecting ischemia and 72.2%, 91.8%, and 87.9% in showing the extent.Dynamic PCT maps are more accurate than nonenhanced CT in detecting hemispheric strokes. Despite limited spatial coverage, PCT is highly reliable to assess the stroke extent.

    View details for Web of Science ID 000226729300025

    View details for PubMedID 15661711

  • Admission perfusion CT: Prognostic value in patients with severe head trauma RADIOLOGY Wintermark, M., Van Melle, G., Schnyder, P., Revelly, J. P., Porchet, F., Regli, L., Meuli, R., Maeder, P., Chiolero, R. 2004; 232 (1): 211-220

    Abstract

    To assess the prognostic value of admission perfusion computed tomography (CT) in patients with severe head trauma.This prospective study included 130 patients with severe trauma, aged 19-86 years, admitted with a Glasgow Coma Scale score of 8 or less. They underwent perfusion CT as part of their admission CT survey. Clinical data, unenhanced cerebral CT findings, and perfusion CT scans were evaluated with respect to the Glasgow Outcome Scale (GOS) score at 3 months. Perfusion CT features were evaluated in patients with intracranial hypertension, cerebral contusions, and juxtadural hematomas. Ordered logistic regression was used to determine risk factors for an unfavorable GOS score at 3 months.Perfusion CT was more sensitive than conventional unenhanced CT in the detection of cerebral contusions. Perfusion CT featured specific patterns with respect to patient outcome, with normal brain perfusion or hyperemia in patients with favorable outcome, and oligemia in patients with unfavorable outcome. The number of arterial territories with low regional cerebral blood volume at perfusion CT was an independent prognostic factor (P =.008), as were mean arterial pressure at the scene of accident (P =.083), base excess at admission (P =.002), presence of skull fractures (P =.041), and signs of herniation (P =.013) at admission unenhanced cerebral CT. Perfusion CT also showed a range of brain perfusion alterations in patients with juxtadural collections, cerebral edema, or intracranial hypertension.Perfusion CT in patients with severe head trauma provides independent prognostic information regarding functional outcome.

    View details for DOI 10.1148/radiol.2321030824

    View details for Web of Science ID 000222161300029

    View details for PubMedID 15220504

  • Relationship between brain perfusion computed tomography variables and cerebral perfusion pressure in severe head trauma patients CRITICAL CARE MEDICINE Wintermark, M., Chiolero, R., Van Melle, G., Revelly, J. P., Porchet, F., Regli, L., Meuli, R., Schnyder, P., Maeder, P. 2004; 32 (7): 1579-1587

    Abstract

    To compare brain perfusion-computed tomography (CT) results with invasive cerebral perfusion pressure (CPP) monitoring in severe head trauma patients.Prospective cohort study.Emergency room and surgical intensive care unit of our hospital.Sixty-one severe head trauma patients.We prospectively collected 103 perfusion-CT examinations with simultaneous measurement of mean arterial pressure and intracranial pressure, affording calculation of CPP. The statistical relationship between perfusion-CT results and the corresponding CPP values was evaluated using Wilcoxon (Mann-Whitney) and generalized F-tests. The functional outcome of the 61 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale score and compared between groups using Fisher's exact tests.Perfusion-CT enabled us to distinguish between two groups of patients. Within each group, a significant correlation (p <.001) between the CPP values and the corresponding perfusion-CT results was demonstrated. There was also a significant correlation (p <.001) between the CPP values and the extent of the abnormal perfusion-CT areas (R up to.817). The first group was characterized by a weak dependence of perfusion-CT results on the corresponding CPP values (low slope) and the second group by a strong dependence (steep slope). These groups were interpreted as having preserved (or pseudo) and impaired cerebral vascular autoregulation, respectively. The functional outcome was better in the second group of patients.Intermittent perfusion-CT measurements plus continuous CPP measurement provide more information than continuous CPP alone. Perfusion-CT gives unique information regarding regional heterogeneity of brain perfusion. It might allow clinicians to distinguish between patients with preserved auto-regulation (or pseudoautoregulation) and those with impaired autoregulation and could therefore guide interpretation of CPP measurements and therapy.

    View details for DOI 10.1097/01.CCM.0000130171.08842.72

    View details for Web of Science ID 000222651800018

    View details for PubMedID 15241105

  • Brain perfusion in children: Evolution with age assessed by quantitative perfusion computed tomography PEDIATRICS Wintermark, M., Lepori, D., Cotting, J., Roulet, E., Van Melle, G., Meuli, R., Maeder, P., Regli, L., Verdun, F. R., Deonna, T., Schnyder, P., Gudinchet, F. 2004; 113 (6): 1642-1652

    Abstract

    The objective of this study was to assess the age-related variations of brain perfusion through quantitative cerebral perfusion computed tomography (CT) results in children without brain abnormality.Brain perfusion CT examinations were performed in 77 children, aged 7 days to 18 years. These patients were admitted at our institution for both noncontrast and contrast-enhanced cerebral CT. Only children whose conventional cerebral CT and clinical/radiologic follow-up, including additional investigations, were normal were taken into account for this study (53 of 77).The average regional rCBF amounts to 40 (mL/100 g per minute) for the first 6 months of life, peaks at approximately 130 (mL/100 g per minute) at approximately 2 to 4 years of age, and finally stabilizes at approximately 50 (mL/100 g per minute) at approximately 7 to 8 years of age, with a small increase of rCBF values at approximately 12 years of age. The rCBF in the gray matter averages 3 times that in the white matter, except for the first 6 months of life. The global CBF represents 10% to 20% of the global cardiac output for the first 6 months of life, peaks at approximately 55% by 2 to 4 years of age, and finally stabilizes at approximately 15% by 7 to 8 years of age. Specific age-related evolution patterns were identified in the different anatomic areas of the cerebral parenchyma, which could be related to the development of neuroanatomic structures and to the emergence of corresponding cognitive functions.Quantitative perfusion CT characterization of brain perfusion shows specific age variations. Brain perfusion of each cortical area evolves according to a specific time course, in close correlation with the psychomotor development.

    View details for Web of Science ID 000221781500013

    View details for PubMedID 15173485

  • Unilateral putaminal CT, MR, and diffusion abnormalities secondary to nonketotic hyperglycemia in the setting of acute neurologic symptoms mimicking stroke AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Fischbein, N. J., Mukherjee, P., Yuh, E. L., Dillon, W. P. 2004; 25 (6): 975-976

    Abstract

    A 75-year-old Asian man presented with two episodes of chorea associated with nonketotic hyperglycemia. His chorea rapidly resolved after restitution of a normal serum glucose level, although an MR image obtained at the time of acute symptoms demonstrated high signal intensity on T1-weighted images, low signal intensity on T2-weighted images, and restricted diffusion, all involving the left putamen. A CT scan obtained 1 month later demonstrated faint hyperattenuation of the involved putamen. The reported pathophysiologic considerations for these imaging features are reviewed, and an original explanation is proposed.

    View details for Web of Science ID 000222067600015

    View details for PubMedID 15205134

  • Dynamic perfusion CT: Optimizing the temporal resolution and contrast volume for calculation of perfusion CT parameters in stroke patients AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Smith, W. S., Ko, N. U., Quist, M., Schnyder, P., Dillon, W. P. 2004; 25 (5): 720-729

    Abstract

    Numerous parameters are involved in dynamic perfusion CT (PCT). We assessed the influence of the temporal sampling rate and the volume of contrast material.Sixty patients with ischemic hemispheric stroke lasting > or = 12 hours underwent PCT. Groups of 15 patients each received 30, 40, 50, or 60 mL of contrast agent. Regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), mean transit time (MTT), and time-to-peak (TTP) maps were calculated for temporal sampling intervals of 0.5, 1, 2, 3, 4, 5, and 6 seconds. Results were statistically compared. Signal-to-noise ratios (SNRs), duration of arterial entrance to venous exit, and radiation dose were also assessed.Increasing temporal sampling intervals lead to significant overestimation of rCBV, rCBF, and TTP and significant underestimation of MTT compared with values for an interval of 1 second. Maximal allowable intervals to avoid these effects were 2, 3, 3, and 4 seconds for 30, 40, 50, and 60-mL boluses, respectively. Venous exit of contrast material occurred in 97.5% of patients after 36, 42, 42, and 48 seconds, respectively, for the four volumes. SNRs did not differ with volume. The effective radiation dose varied between 0.852 and 1.867 mSv, depending on the protocol. The cine mode with two 40-mL boluses and the toggling-table technique with one 60-mL bolus had the lowest doses.Temporal sampling intervals greater than 1 second can be used without altering the quantitative accuracy of PCT. Increased sampling intervals reduce the radiation dose and may allow for increased spatial coverage.

    View details for Web of Science ID 000221503500009

    View details for PubMedID 15140710

  • [Perfusion-CT guided acute stroke management]. Rinsho¯ shinkeigaku = Clinical neurology Michel, P., Reichhart, M., Wintermark, M., Meuli, R., Bogousslavsky, J. 2003; 43 (11): 728-731

    Abstract

    The easily accessible and available PCT reliably identifies reversible and irreversible ischaemia in acute stroke patients. These knowledge will allow treatment strategies to become more appropriate and individualized. Patients with significant penumbra may be candidates for treatment with dangerous or costly medication, and patients without may not, independently of duration of stroke symptoms. Furthermore, PCT also has the scientific potential to identify appropriate patients for therapeutic trials. Finally, salvage of PCT-defined penumbra could be used as a surrogate marker for effectiveness of interventions.

    View details for PubMedID 15152451

  • Correlation of early dynamic CT perfusion imaging with whole-brain MR diffusion and perfusion imaging in acute hemispheric stroke AMERICAN JOURNAL OF NEURORADIOLOGY Eastwood, J. D., Lev, M. H., Wintermark, M., Fitzek, C., Barboriak, D. P., DeLong, D. M., Lee, T. Y., Azhari, T., Herzau, M., Chilukuri, V. R., Provenzale, J. M. 2003; 24 (9): 1869-1875

    Abstract

    Compared with MR imaging, dynamic CT perfusion imaging covers only a fraction of the whole brain. An important assumption is that CT perfusion abnormalities correlate with total ischemic volume. The purpose of our study was to measure the degree of correlation between abnormalities seen on CT perfusion scans and the volumes of abnormality seen on MR diffusion and perfusion images in patients with acute large-vessel stroke.Fourteen patients with acute hemispheric stroke symptoms less than 12 hours in duration were studied with single-slice CT perfusion imaging and multislice MR diffusion and perfusion imaging. CT and MR perfusion studies were completed within 2.5 hours of one another (mean, 77 minutes) and were reviewed independently by two neuroradiologists. Hemodynamic parameters included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Extents of abnormality on images were compared by using Kendall correlation.Statistically significant correlation was found between CT-CBF and MR-CBF abnormalities (tau = 0.60, P =.003) and CT-MTT and MR-MTT abnormalities (tau = 0.65, P =.001). Correlation of CT-CBV with MR-CBV approached significance (tau = 0.39, P =.06). Extent of initial hyperintensity on diffusion-weighted images correlated best with extent of MR-CBV abnormality (tau = 0.69, P =.001), extent of MR-MTT abnormality (tau = 0.67, P =.002), and extent of CT-CBV abnormality (tau = 0.47, P =.02).Good correlation was seen between CT and MR for CBF and MTT abnormalities. It remains uncertain whether CT perfusion CBV abnormalities correspond well to whole-brain abnormalities.

    View details for Web of Science ID 000186022800027

    View details for PubMedID 14561618

  • Aphasia in hyperacute stroke: Language follows brain penumbra dynamics 2 ANNALS OF NEUROLOGY Croquelois, A., Wintermark, M., Reichhart, M., Meuli, R., Bogousslavsky, J. 2003; 54 (3): 321-329

    Abstract

    During the first few hours after onset, stroke symptoms may evolve rapidly. We studied the correlation between brain perfusion and aphasia changes during the hyperacute phase of stroke using a new technique of perfusion computed tomography (P-CT). Using an aphasia score developed for each language modality, language was evaluated within 6 hours after onset, then sequentially during the first week. Maps of the penumbra and infarct obtained from P-CT images and definite infarct size evaluated using T2 and diffusion-weighted MRI (DWI) on day 3 were rated by a neuroradiologist, blinded to the clinical deficit. Within 6 hours, deficits in all language modalities were present in 13 out of 24 consecutive patients, corresponding to large anterior-posterior perfusion deficits of the left middle cerebral artery (MCA) territory. The aphasia score correlated with a corresponding perfusion deficit in specific areas of the MCA territory, and showed significantly less improvement when the penumbra evolved toward infarction than when at least part of the penumbra was rescued. Our findings suggest a particularly good correlation between the evolution of aphasic symptoms and penumbra dynamics. Further studies on the relevance of penumbra dynamics in function-specific brain areas to decision taking in hyperacute stroke management are required.

    View details for DOI 10.1002/ana.10657

    View details for Web of Science ID 000185158100006

    View details for PubMedID 12953264

  • Thoracolumbar spine fractures in patients who have sustained severe trauma: Depiction with multi-detector row CT RADIOLOGY Wintermark, M., Mouhsine, E., Theumann, N., Morclasini, P., Van Melle, G., Leyvraz, P. F., Schnyder, P. 2003; 227 (3): 681-689

    Abstract

    To determine if multi-detector row computed tomography (CT) can replace conventional radiography and be performed alone in severe trauma patients for the depiction of thoracolumbar spine fractures.One hundred consecutive severe trauma patients who underwent conventional radiography of the thoracolumbar spine as well as thoracoabdominal multi-detector row CT were prospectively identified. Conventional radiographs were reviewed independently by three radiologists and two orthopedic surgeons; CT images were reviewed by three radiologists. Reviewers were blinded both to one another's reviews and to the results of initial evaluation. Presence, location, and stability of fractures, as well as quality of reviewed images, were assessed. Statistical analysis was performed to determine sensitivity and interobserver agreement for each procedure, with results of clinical and radiologic follow-up as the standard of reference. The time to perform each examination and the radiation dose involved were evaluated. A resource cost analysis was performed.Sixty-seven fractured vertebrae were diagnosed in 26 patients. Twelve patients had unstable spine fractures. Mean sensitivity and interobserver agreement, respectively, for detection of unstable fractures were 97.2% and 0.951 for multi-detector row CT and 33.3% and 0.368 for conventional radiography. The median times to perform a conventional radiographic and a multi-detector row CT examination, respectively, were 33 and 40 minutes. Effective radiation doses at conventional radiography of the spine and thoracoabdominal multi-detector row CT, respectively, were 6.36 mSv and 19.42 mSv. Multi-detector row CT enabled identification of 146 associated traumatic lesions. The costs of conventional radiography and multi-detector row CT, respectively, were 145 and 880 US dollars per patient.Multi-detector row CT is a better examination for depicting spine fractures than conventional radiography. It can replace conventional radiography and be performed alone in patients who have sustained severe trauma.

    View details for DOI 10.1148/

    View details for Web of Science ID 000182924800012

    View details for PubMedID 12702827

  • Multislice computerized tomography angiography in the evaluation of intracranial aneurysms: a comparison with intraarterial digital subtraction angiography JOURNAL OF NEUROSURGERY Wintermark, M., Uske, A., Chalaron, M., Regli, L., Maeder, P., Meuli, R., Schnyder, P., Binaghi, S. 2003; 98 (4): 828-836

    Abstract

    The goal of this study was to assess the diagnostic accuracy of computerized tomography (CT) angiography performed with the aid of multislice technology (MSCT angiography) in the investigation of intracranial aneurysms, by comparing this method with intraarterial digital subtraction (IADS) angiography.Fifty consecutive adult patients, who successively underwent MSCT angiography (four rows) and IADS angiography of intracranial vessels, were prospectively identified. The MSCT angiography studies consisted of 1.25-mm slices, with 0.8-mm reconstruction intervals, a pitch of 0.75, and timing determined by a test bolus. Two neuroradiologists, who were blinded to the initial interpretation of the MSCT angiograms as well as to those of the IADS angiograms, independently reviewed the MSCT angiograms for the detection and characterization of intracranial aneurysms. Forty-nine intracranial aneurysms were identified in 40 patients; 33 of these lesions were responsible for subarachnoid hemorrhage. The sensitivity, specificity, and accuracy of MSCT angiography in the detection of intracranial aneurysms were 94.8, 95.2, and 94.9%, respectively, on a per-aneurysm basis and 99, 95.2, and 98.3%, respectively, on a per-patient basis. Interobserver agreement was 98%. There was an excellent correlation between aneurysm size assessed using MSCT angiography and that determined by IADS angiography (slope = 0.916, r = 0.877, p < 0.001); however, 2 mm stood as the cutoff size below which the sensitivity of MSCT angiography was statistically lower. That method displayed great accuracy in characterizing the morphological characteristics of the aneurysm.Multislice CT angiography is an accurate and robust noninvasive screening test for intracranial aneurysms. It performs better than that reported for single-slice CT angiography. Introduction of eight- and especially 16-row MSCT angiography will provide further progression through thinner slices, a lower pitch, and a purely arterial phase.

    View details for Web of Science ID 000181922400016

    View details for PubMedID 12691409

  • Imaging of acute ischemic brain injury: the return of computed tomography CURRENT OPINION IN NEUROLOGY Wintermark, M., Bogousslavsky, J. 2003; 16 (1): 59-63

    Abstract

    Classical and modern computed tomography imaging techniques, including conventional computed tomography, perfusion-computed tomography and computed tomography-angiography for acute stroke are reviewed.Thrombolysis has become an approved therapy for acute stroke. However, many stroke patients do not benefit from such treatment, since the presently used criteria are very restrictive, notably with respect to the accepted time-window. Even so, a significant rate of intracranial hemorrhage still occurs. Conventional cerebral computed tomography has been proposed as a selection tool for acute stroke patients. Recently, more modern computed tomography techniques, referred to as functional computed tomography or perfusion-computed tomography, have been introduced. Such perfusion-computed tomography techniques are competing favorably with diffusion-weighted/perfusion-weighted magnetic resonance imaging in the delineation of the penumbra. They are more easy to perform, because they are readily available and accessible in emergency settings, and less time-consuming. Furthermore, perfusion-computed tomography combined with computed tomography-angiography affords a comprehensive non-invasive survey of acute stroke patients as early as at the time of their emergency admission, with accurate demonstration of the site of arterial occlusion and its hemodynamic and pathophysiological repercussions for the brain parenchyma.A renewal of computed tomography in the field of stroke has been afforded by the introduction of functional techniques such as perfusion-computed tomography, which provides promising insights into cerebral tissue viability and can be used as a guidance tool for therapy when combined with computed tomography-angiography.

    View details for DOI 10.1097/01.wco.0000053589.70044.13

    View details for Web of Science ID 000181004000008

    View details for PubMedID 12544858

  • Investigation by perfusion CT and diffusion-weighted MR imaging. Advances in neurology Meuli, R., Bogousslavsky, J., Wintermark, M. 2003; 92: 389-400

    View details for PubMedID 12760205

  • Comparison of admission perfusion computed tomography and qualitative diffusion- and perfusion-weighted magnetic resonance imaging in acute stroke patients STROKE Wintermark, M., Reichhart, M., Cuisenaire, O., Maeder, P., Thiran, J. P., Schnyder, P., Bogousslavsky, J., Meuli, R. 2002; 33 (8): 2025-2031

    Abstract

    Besides classic criteria, cerebral perfusion imaging could improve patient selection for thrombolytic therapy. The purpose of this study was to compare quantitative perfusion CT imaging and qualitative diffusion- and perfusion-weighted MRI (DWI and PWI) in acute stroke patients at the time of their emergency evaluation.Thirteen acute stroke patients underwent perfusion CT and DWI or PWI on admission. The size of infarct and ischemic lesion (infarct plus penumbra) on the admission perfusion CT was compared with that of the MR abnormalities as shown on the DWI trace and on the relative cerebral blood volume, cerebral blood flow, time to peak, and mean transit time maps calculated from PWI studies.The most significant correlation was found between infarct size on the admission perfusion CT and abnormality size on the admission DWI map (r=0.968, P<0.001). A significant correlation was also observed between the size of the ischemic lesion (infarct plus penumbra) on the admission perfusion CT and the abnormality size on the mean transit time map calculated from admission PWI (r=0.946, P<0.001). Information about cerebral infarct and total ischemia (infarct plus penumbra) carried by both imaging techniques was similar, with slopes of 0.913 and 0.905, respectively.An imaging technique may be helpful in the identification of cerebral penumbra in acute stroke patients and thus in the selection of patients for thrombolytic therapy. Perfusion CT and DWI/PWI are equivalent in this task.

    View details for Web of Science ID 000177320100027

    View details for PubMedID 12154257

  • Intraluminal aortic fat as an unusual presentation of blunt traumatic aortic rupture JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE Wintermark, M., Schnyder, P. 2002; 52 (6): 1222-1222

    View details for Web of Science ID 000176195700043

    View details for PubMedID 12045658

  • MR pattern of hyperacute cerebral hemorrhage JOURNAL OF MAGNETIC RESONANCE IMAGING Wintermark, M., Maeder, P., Reichhart, M., Schnyder, P., Bogousslavsky, J., Meuli, R. 2002; 15 (6): 705-709

    Abstract

    Magnetic resonance (MR) pattern of cerebral hemorrhage relates mainly to the relaxation and susceptibility effects of iron-containing hemoglobin degradation products, as well as to their intra- or extracellular location. The purpose of this article is to report two acute stroke patients who underwent thrombolytic therapy and developed hyperacute cerebral hemorrhage during their admission cerebral MR survey. They constitute the earliest MR appearance of hyperacute intracerebral bleeding reported in the literature, featuring increased diffusion properties and persistent susceptibility effect on perfusion-weighted imaging (PWI)-series.

    View details for DOI 10.1002/jmri.10122

    View details for Web of Science ID 000175918300011

    View details for PubMedID 12112521

  • Traumatic injuries: organization and ergonomics of imaging in the emergency environment EUROPEAN RADIOLOGY Wintermark, M., Poletti, P. A., Becker, C. D., Schnyder, P. 2002; 12 (5): 959-968

    Abstract

    Management of trauma patients relies on a simple but obvious concept: Time is life! This is a challenge to the emergency radiologist in his evaluation of the radiological admission survey of severe trauma patients, since the latter need a quick and thorough survey of craniocerebral, cervical, thoracic, abdominal, and limb lesions. This article reviews the architectural design and the management strategies required to fulfill this purpose. Whereas plain films and ultrasonography have precise but limited indications, multislice spiral CT (MSCT) shows an increasingly preponderant role in the imaging evaluation of trauma patients, as demonstrated through three examples (aortic, spine, and craniocerebral trauma). Multislice CT affords a comprehensive assessment of trauma patients' injuries and allows for their categorization according to the severity of traumatic lesions. With respect to the MSCT data volume, the emergency radiologists have to modify the strategies in their examination reading and result transmission, with a growing role attributed to two- and three-dimensional reconstructions. The emergency radiologist's role is thus of prime importance in the management of trauma patients, and this all the more so since development of interventional radiology affords therapeutic procedures alternative to surgery. Trauma radiology and emergency radiology on the whole will assert themselves as consistent and thorough areas of subspecialization.

    View details for DOI 10.1007/s00330-002-1385-3

    View details for Web of Science ID 000175613700002

    View details for PubMedID 11976840

  • Traumatic injuries: role of imaging in the management of the polytrauma victim (conservative expectation) EUROPEAN RADIOLOGY Poletti, P. A., Wintermark, M., Schnyder, P., Becker, C. D. 2002; 12 (5): 969-978

    Abstract

    Abdominal US and CT play an important role in the initial management of blunt trauma in adults. Ultrasound is an excellent method for detection of free intra-abdominal fluid. It is the modality of choice for initial screening and enables selection of hemodynamically unstable trauma victims with severe hemoperitoneum for immediate surgery. However, even in experienced hands, US is not sufficient to rule out organ injuries reliably. Computed tomography, and particularly multislice CT (MSCT), has several major advantages over US and is currently unsurpassed for the detection of blunt visceral injuries in the abdomen. Computed tomography has a high sensitivity for the detection of parenchymal splenic and hepatic injuries. Injuries of the gastrointestinal tract may be detected with good sensitivity provided that adequate examination technique and careful diagnostic interpretation are combined. The value of CT-based injury-grading systems for predicting the outcome of conservative treatment remains unproven; however, demonstration of direct vascular injuries with CT, e.g., the intrasplenic "contrast blush" sign, may indicate a high likelihood that conservative treatment will fail, thus warranting angiographic embolization or surgery. Monitoring of conservatively treated trauma victims by means of repeat CT studies enables early detection of a variety of delayed, clinically silent complications of trauma, e.g., posttraumatic biloma or bowel devascularization. Catheter angiography may be reserved to selected cases with vascular injuries proven on CT.

    View details for DOI 10.1007/s00330-002-1353-y

    View details for Web of Science ID 000175613700003

    View details for PubMedID 11976841

  • Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients ANNALS OF NEUROLOGY Wintermark, M., Reichhart, M., Thiran, J. P., Maeder, P., Chalaron, M., Schnyder, P., Bogousslavsky, J., Meuli, R. 2002; 51 (4): 417-432

    Abstract

    The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.

    View details for DOI 10.1002/ana.10136

    View details for Web of Science ID 000174597600002

    View details for PubMedID 11921048

  • Imaging of patients post blunt trauma to the chest JOURNAL DE RADIOLOGIE Wintermark, M., Schnyder, P. 2002; 83 (2): 123-132

    Abstract

    Blunt chest traumas are a major concern in the setting of high-speed deceleration accidents, since they are associated with a high mortality rate. However, their prompt diagnosis and treatment allows for significant improvement of blunt chest trauma patient's clinical prognosis. If chest radiograph remains the initial screening test, the role of CT is increasing since it provides fast, sensitive, accurate and exhaustive survey of blunt chest trauma patients. The purpose of this article is to review the various radiological and CT patterns of blunt chest lesions.

    View details for Web of Science ID 000174562500005

    View details for PubMedID 11965159

  • Imaging of acute traumatic injuries of the thoracic aorta EUROPEAN RADIOLOGY Wintermark, M., Wicky, S., Schnyder, P. 2002; 12 (2): 431-442

    Abstract

    Blunt traumatic aortic injuries are a major concern in the settings of high-speed deceleration accidents, since they are associated with a very high mortality rate; however, with prompt diagnosis and surgery, 70% of the patients with a blunt aortic lesion who reach the hospital alive will survive. This statement challenges the emergency radiologist in charge to evaluate the admission radiological survey in a severe chest trauma patient. With a 95% negative predictive value for the identification of blunt traumatic aortic lesions, plain chest film represents an adequate screening test. If aortography remains the gold standard, it tends, at least in hemodynamically stable trauma patients, to be replaced by spiral-CT angiography (SCTA), which demonstrates a 96.2% sensitivity, a 99.8% specificity, and a 99.7% accuracy. In unstable patients, trans-esophageal echography (TEE) plays a major diagnostic role. Knowledge of advantages and pitfalls of these imaging techniques, as reviewed in this article, will help the emergency radiologist to choose the appropriate algorithm in the diagnosis of traumatic aortic injury, for each trauma patient.

    View details for DOI 10.1007/s003300100971

    View details for Web of Science ID 000174127700026

    View details for PubMedID 11870446

  • CT perfusion scanning with deconvolution analysis: Pilot study in patients with acute middle cerebral artery stroke RADIOLOGY Eastwood, J. D., Lev, M. H., Azhari, T., Lee, T. Y., Barboriak, D. P., DeLong, D. M., Fitzek, C., Herzau, M., Wintermark, M., Meuli, R., Brazier, D., Provenzale, J. M. 2002; 222 (1): 227-236

    Abstract

    To measure mean cerebral blood flow (CBF) in ischemic and nonischemic territories and in low-attenuation regions in patients with acute stroke by using deconvolution-derived hemodynamic imaging.Twelve patients with acute middle cerebral artery stroke and 12 control patients were examined by using single-section computed tomography (CT) perfusion scanning. Analysis was performed with a deconvolution-based algorithm. Comparisons of mean CBF, cerebral blood volume (CBV), and mean transit time (MTT) were determined between hemispheres in all patients and between low- and normal-attenuation regions in patients with acute stroke. Two independent readers examined the images for extent of visually apparent regional perfusion abnormalities. The data were compared with extent of final infarct in seven patients with acute stroke who underwent follow-up CT or magnetic resonance imaging.Significant decreases in CBF (-50%, P =.001) were found in the affected hemispheres of patients with acute stroke. Significant changes in CBV (-26%, P =.03) and MTT (+111%, P =.004) were also seen. Significant alterations in perfusion were also seen in low- compared with normal-attenuation areas. Pearson correlation between readers for extent of CBF abnormality was 0.94 (P =.001). Intraobserver variation was 8.9% for CBF abnormalities.Deconvolution analysis of CT perfusion data is a promising method for evaluation of cerebral hemodynamics in patients with acute stroke.

    View details for Web of Science ID 000172884800034

    View details for PubMedID 11756730

  • The Macklin effect - A frequent etiology for pneumomediastinum in severe blunt chest trauma CHEST Wintermark, M., Schnyder, P. 2001; 120 (2): 543-547

    Abstract

    To review the etiology and pathophysiology of pneumomediastinum in severe blunt trauma, with a special interest in one of its possible origins, the Macklin effect. The Macklin effect relates to a three-step pathophysiologic process: blunt traumatic alveolar ruptures, air dissection along bronchovascular sheaths, and spreading of this blunt pulmonary interstitial emphysema into the mediastinum. The clinical relevance of the Macklin effect was also evaluated.A university hospital serving as a reference trauma center.A selection of 51 patients with severe blunt trauma between 1995 and 2000.Severe trauma or high-speed deceleration justifying chest CT; if chest CT demonstrated a pneumomediastinum, bronchoscopy and esophagoscopy were performed to rule out tracheobronchial or esophageal injury.Retrospective analysis of patients' clinical files, chest CT, and bronchoscopy and esophagoscopy reports. The Macklin effect was diagnosed when an air collection adjacent to a bronchus and a pulmonary vessel could be clearly identified on the chest CT. Clinical relevance of the Macklin effect was statistically evaluated regarding its repercussions on the pulmonary gas exchange function, the respective durations of intensive care and total hospital stay, and the associated injuries.Twenty (39%) Macklin effects and 5 tracheobronchial injuries (10%) were identified. One tracheobronchial injury occurred simultaneously with the Macklin effect. The presence of the Macklin effect affected neither the clinical profile nor the result of pulmonary gas analysis on hospital admission, but was associated with a significant (p < 0.001) lengthening of the intensive care stay.The Macklin effect is present in 39% of severe blunt traumatic pneumomediastinum detected by CT. Its identification does not rule out a tracheobronchial injury. The Macklin effect reflects severe trauma, since it is associated with significantly prolonged intensive care stay.

    View details for Web of Science ID 000170405500037

    View details for PubMedID 11502656

  • Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: A validation study 86th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) Wintermark, M., Thiran, J. P., Maeder, P., Schnyder, P., Meuli, R. AMER SOC NEURORADIOLOGY. 2001: 905–14

    Abstract

    Knowledge of cerebral blood flow (CBF) alterations in cases of acute stroke could be valuable in the early management of these cases. Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT studies involve sequential acquisition of cerebral CT sections obtained in an axial mode during the IV administration of iodinated contrast material. They are thus very easy to perform in emergency settings. Perfusion CT values of CBF have proved to be accurate in animals, and perfusion CT affords plausible values in humans. The purpose of this study was to validate perfusion CT studies of CBF by comparison with the results provided by stable xenon CT, which have been reported to be accurate, and to evaluate acquisition and processing modalities of CT data, notably the possible deconvolution methods and the selection of the reference artery.Twelve stable xenon CT and perfusion CT cerebral examinations were performed within an interval of a few minutes in patients with various cerebrovascular diseases. CBF maps were obtained from perfusion CT data by deconvolution using singular value decomposition and least mean square methods. The CBF were compared with the stable xenon CT results in multiple regions of interest through linear regression analysis and bilateral t tests for matched variables.Linear regression analysis showed good correlation between perfusion CT and stable xenon CT CBF values (singular value decomposition method: R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83). Bilateral t tests for matched variables did not identify a significant difference between the two imaging methods (P >.1). Both deconvolution methods were equivalent (P >.1). The choice of the reference artery is a major concern and has a strong influence on the final perfusion CT CBF map.Perfusion CT studies of CBF achieved with adequate acquisition parameters and processing lead to accurate and reliable results.

    View details for Web of Science ID 000168681600020

    View details for PubMedID 11337336

  • Quantitative assessment of regional cerebral blood flows by perfusion CT studies at low injection rates: a critical review of the underlying theoretical models EUROPEAN RADIOLOGY Wintermark, M., Maeder, P., Thiran, J. P., Schnyder, P., Meuli, R. 2001; 11 (7): 1220-1230

    Abstract

    Viability of the cerebral parenchyma is dependent on cerebral blood flow (CBF), which is usually kept in a very narrow range due to efficient autoregulation processes and can be altered in a variety of pathological conditions. An accurate method allowing for a quantitative assessment of regional cerebral blood flows (rCBF) and available for the routine clinical practice would, for sure, greatly contribute to improving the management of patients with cerebrovascular diseases. Different imaging techniques are now available to evaluate rCBF: positron emission tomography; single photon emission CT; stable-xenon CT; perfusion CT; and perfusion MRI. Each of these imaging techniques uses an indicator, with specific biological properties, and is supported by a model, which consists of a few simplifying assumptions, necessary to state and solve the equations giving access to rCBF. The obtained results are more or less reliable, depending on whether modeling hypotheses are fulfilled by the used indicator. The purpose of this article is to review the various supporting models in the assessment of rCBF, with special emphasis on perfusion CT studies at low injection rates and on iodinated contrast material used as an indicator.

    View details for Web of Science ID 000169752900021

    View details for PubMedID 11471616

  • Blunt traumatic rupture of a mainstem bronchus: spiral CT demonstration of the "fallen lung" sign EUROPEAN RADIOLOGY Wintermark, M., Schnyder, P., Wicky, S. 2001; 11 (3): 409-411

    Abstract

    Tracheo-bronchial injuries occur in less than 1 % of blunt chest trauma patients. Indirect signs, such as pneumomediastinum, pneumothorax, and/or subcutaneous emphysema, are revealed on admission plain films and chest CT survey. In most instances, however, tracheobronchoscopy is mandatory in assessing the definite diagnosis of tracheo-bronchial lesion. Occasionally, an abnormal course of a mainstem bronchus or a "fallen lung" sign, featuring a collapsed lung in a dependent position, hanging on the hilum only by its vascular attachments, may allow for CT diagnosis of a blunt traumatic bronchial injury.

    View details for Web of Science ID 000167273600005

    View details for PubMedID 11288843

  • Blunt trauma of the heart: CT pattern of atrial appendage ruptures EUROPEAN RADIOLOGY Wintermark, M., Delabays, A., Bettex, D., Schnyder, P. 2001; 11 (1): 113-116

    Abstract

    Blunt trauma patients with myocardial ruptures rarely survive long enough to reach a trauma center; however, for the survivors, prompt diagnosis and surgery are mandatory and save up to 80% of patients. Preoperative diagnosis of myocardial ruptures is assessed by echocardiography or, more rarely, by angiocardiography. We report two cases of blunt trauma patients with an atrial appendage rupture which could be retrospectively identified on admission CT survey.

    View details for Web of Science ID 000166064500017

    View details for PubMedID 11194901

  • Using 80 kVp versus 120 kVp in perfusion CT measurement of regional cerebral blood flow AMERICAN JOURNAL OF NEURORADIOLOGY Wintermark, M., Maeder, P., Verdun, F. R., Thiran, J. P., Valley, J. F., Schnyder, P., Meuli, R. 2000; 21 (10): 1881-1884

    Abstract

    Perfusion CT studies of regional cerebral blood flow (rCBF), involving sequential acquisition of cerebral CT sections during IV contrast material administration, have classically been reported to be achieved at 120 kVp. We hypothesized that using 80 kVp should result in the same image quality while significantly lowering the patient's radiation dose, and we evaluated this assumption. In five patients undergoing cerebral CT survey, one section level was imaged at 120 kVp and 80 kVp, before and after IV administration of iodinated contrast material. These four cerebral CT sections obtained in each patient were analyzed with special interest to contrast, noise, and radiation dose. Contrast enhancement at 80 kVp is significantly increased (P < .001), as well as contrast between gray matter and white matter after contrast enhancement (P < .001). Mean noise at 80 kVp is not statistically different (P = .042). Finally, performance of perfusion CT studies at 80 kVp, keeping mAs constant, lowers the radiation dose by a factor of 2.8. We, thus, conclude that 80 kVp acquisition of perfusion CT studies of rCBF will result in increased contrast enhancement and should improve rCBF analysis, with a reduced patient's irradiation.

    View details for Web of Science ID 000165547500019

    View details for PubMedID 11110541

  • Imaging of blunt chest trauma EUROPEAN RADIOLOGY Wicky, S., Wintermark, M., Schnyder, P., Capasso, P., Denys, A. 2000; 10 (10): 1524-1538

    Abstract

    In western European countries most blunt chest traumas are associated with motor vehicle and sport-related accidents. In Switzerland, 39 of 10,000 inhabitants were involved and severely injured in road accidents in 1998. Fifty two percent of them suffered from blunt chest trauma. According to the Swiss Federal Office of Statistics, traumas represented in men the fourth major cause of death (4%) after cardiovascular disease (38%), cancer (28%), and respiratory disease (7%) in 1998. The outcome of chest trauma patients is determined mainly by the severity of the lesions, the prompt appropriate treatment delivered on the scene of the accident, the time needed to transport the patient to a trauma center, and the immediate recognition of the lesions by a trained emergency team. Other determining factors include age as well as coexisting cardiac, pulmonary, and renal diseases. Our purpose was to review the wide spectrum of pathologies related to blunt chest trauma involving the chest wall, pleura, lungs, trachea and bronchi, aorta, aortic arch vessels, and diaphragm. A particular focus on the diagnostic impact of CT is demonstrated.

    View details for Web of Science ID 000089606600002

    View details for PubMedID 11044920

  • Blunt traumatic pneumomediastinum: Using CT to reveal the Macklin effect AMERICAN JOURNAL OF ROENTGENOLOGY Wintermark, M., Wicky, S., Schnyder, P., Capasso, P. 1999; 172 (1): 129-130

    View details for Web of Science ID 000077743000027

    View details for PubMedID 9888752