Dr. Michael Iv received his medical degree from the David Geffen School of Medicine at UCLA. He completed his radiology residency training at Santa Clara Valley Medical Center and neuroradiology fellowship at Stanford University. He is board certified in Diagnostic Radiology and also holds a Certificate of Added Qualification in Neuroradiology. His primary research interest focuses on the use of advanced MRI techniques to probe the brain tumor microenvironment and improve our diagnostic capability to effectively monitor a tumor’s response to treatment. Examples include using ferumoxytol-enhanced MRI to image tumor associated macrophages and MR perfusion-based fractional tumor burden to image tumor vascularity and neoangiogenesis. He has received multiple intramural and extramural grants including the Radiological Society of North America Research Scholar Grant and Musella Foundation for Brain Tumor Research Grant to support his work. He was also a co-editor of a published two volume book set entitled “Glioblastoma: State-of-the-Art Clinical Neuroimaging.” In addition to research, he is actively involved in the clinical care of patients and regularly participates in multi-disciplinary conferences. He currently serves as the Director of Brain Tumor Imaging at the Stanford Brain Tumor Center.

Clinical Focus

  • Neuroradiology
  • Brain Tumor Imaging
  • Vascular Imaging
  • Diagnostic Neuroimaging

Academic Appointments

Administrative Appointments

  • Director of Brain Tumor Imaging, Stanford Brain Tumor Center (2020 - Present)
  • Co-director, Medical Student Neuroradiology Clerkship (2015 - 2024)
  • Associate Program Director, Radiology Residency (2016 - 2019)
  • Senator, School of Medicine, Faculty Senate (2015 - 2017)

Honors & Awards

  • Research Scholar Grant, RSNA (2015-2017)
  • Grant, Musella Foundation for Brain Tumor Research (2015)
  • Angel Grant, Stanford Radiology (2013)
  • Chief Resident, Santa Clara Valley Medical Center (2009)
  • Dean’s Scholar for Outstanding Medical Student Thesis in Radiology, UCLA (2006)
  • Ceslo Gonzalez/Lopo Family Fellowship Award for Academic Excellence and Leadership, UCLA (2003)
  • Leadership Academy Scholarship, California Medical Association (2003)
  • Magna Cum Laude, UCR (2003)

Boards, Advisory Committees, Professional Organizations

  • Editorial Board (Assistant Editor), Neurosurgery (2022 - Present)
  • Member, Western Neuroradiological Society (WNRS) (2022 - Present)
  • Editorial Board (Associate Editor), Frontiers in Radiology (2021 - Present)
  • Member, American Society of Functional Neuroradiology (ASFNR) (2017 - Present)
  • Member, International Society for Magnetic Resonance in Medicine (ISMRM) (2013 - Present)
  • Member, American Society of Neuroradiology (ASNR) (2011 - Present)
  • Member, American College of Radiology (ACR) (2007 - Present)
  • Member, Radiological Society of North America (RSNA) (2006 - Present)

Professional Education

  • Fellowship: Stanford University Neuroradiology Fellowship (2013) CA
  • Internship: Cedars Sinai Medical Center Internal Medicine Residency (2007) CA
  • Medical Education: UCLA David Geffen School Of Medicine Registrar (2006) CA
  • Residency: Santa Clara Valley Medical Center (2011) CA
  • Board Certification, Neuroradiology, American Board of Radiology (2013)
  • Board Certification: American Board of Radiology, Diagnostic Radiology (2011)

Current Research and Scholarly Interests

My clinical and research interests include brain tumor and vascular imaging in both the adult and pediatric populations, incorporating advanced MR imaging techniques and analyses using qualitative and quantitative methods.

Clinical Trials

  • Study Assessing QBS72S For Treating Brain Metastases Recruiting

    This study is to evaluate the efficacy and safety of QBS72S in participants with advanced, relapsed, metastatic breast cancer with CNS involvement.

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  • BPM31510 in Treating Patients With Recurrent High-Grade Glioma Previously Treated With Bevacizumab Not Recruiting

    This phase I trial studies the side effects and best dose of ubidecarenone injectable nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma or glioblastoma) that has come back and have been previously treated with bevacizumab. BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sophie Bertrand, 650-723-4467.

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  • In Vivo Characterization of Macrophages in Pediatric Patients With Malignant Brain Tumors Using Ferumoxytol-enhanced MRI Not Recruiting

    This pilot early phase I trial studies how well ferumoxytol-enhanced magnetic resonance imaging (MRI) correlates with inflammatory (macrophage) responses in pediatric patients with malignant brain tumors. If there is good correlation, ferumoxytol-enhanced MRI can serve as a noninvasive imaging biomarker of inflammation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Paymon Rezaii, 650-721-6188.

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  • Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS Not Recruiting

    This pilot clinical trial study will assess the inflammatory response of brain tumors or other central nervous system conditions in pediatric and adult patients using ferumoxytol-enhanced MRI. Imaging features will be correlated with the number of inflammatory cells (macrophages) at histopathology. Determining the extent of inflammation associated with pathologies in the central nervous system may be helpful for diagnostic and prognostic purposes as well as monitoring treatment response of current and future immunotherapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michael Iv, 650-723-4527.

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2023-24 Courses

All Publications

  • Arterial Spin-Labeling and DSC Perfusion Metrics Improve Agreement in Neuroradiologists' Clinical Interpretations of Posttreatment High-Grade Glioma Surveillance MR Imaging-An Institutional Experience. AJNR. American journal of neuroradiology Yamin, G., Tranvinh, E., Lanzman, B. A., Tong, E., Hashmi, S. S., Patel, C. B., Iv, M. 2024


    MR perfusion has shown value in the evaluation of posttreatment high-grade gliomas, but few studies have shown its impact on the consistency and confidence of neuroradiologists' interpretation in routine clinical practice. We evaluated the impact of adding MR perfusion metrics to conventional contrast-enhanced MR imaging in posttreatment high-grade glioma surveillance imaging.This retrospective study included 45 adults with high-grade gliomas who had posttreatment perfusion MR imaging. Four neuroradiologists assigned Brain Tumor Reporting and Data System scores for each examination on the basis of the interpretation of contrast-enhanced MR imaging and then after the addition of arterial spin-labeling-CBF, DSC-relative CBV, and DSC-fractional tumor burden. Interrater agreement and rater agreement with a multidisciplinary consensus group were assessed with κ statistics. Raters used a 5-point Likert scale to report confidence scores. The frequency of clinically meaningful score changes resulting from the addition of each perfusion metric was determined.Interrater agreement was moderate for contrast-enhanced MR imaging alone (κ = 0.63) and higher with perfusion metrics (arterial spin-labeling-CBF, κ = 0.67; DSC-relative CBV, κ = 0.66; DSC-fractional tumor burden, κ = 0.70). Agreement between raters and consensus was highest with DSC-fractional tumor burden (κ = 0.66-0.80). Confidence scores were highest with DSC-fractional tumor burden. Across all raters, the addition of perfusion resulted in clinically meaningful interpretation changes in 2%-20% of patients compared with contrast-enhanced MR imaging alone.Adding perfusion to contrast-enhanced MR imaging improved interrater agreement, rater agreement with consensus, and rater confidence in the interpretation of posttreatment high-grade glioma MR imaging, with the highest agreement and confidence scores seen with DSC-fractional tumor burden. Perfusion MR imaging also resulted in interpretation changes that could change therapeutic management in up to 20% of patients.

    View details for DOI 10.3174/ajnr.A8190

    View details for PubMedID 38453410

  • Brain Tumor Imaging: Review of Conventional and Advanced Techniques. Seminars in neurology Campion, A., Iv, M. 2023


    Approaches to central nervous system (CNS) tumor classification and evaluation have undergone multiple iterations over the past few decades, in large part due to our growing understanding of the influence of genetics on tumor behavior and our refinement of brain tumor imaging techniques. Computed tomography and magnetic resonance imaging (MRI) both play a critical role in the diagnosis and monitoring of brain tumors, although MRI has become especially important due to its superior soft tissue resolution. The purpose of this article will be to briefly review the fundamentals of conventional and advanced techniques used in brain tumor imaging. We will also highlight the applications of these imaging tools in the context of commonly encountered tumors based on the most recently updated 2021 World Health Organization (WHO) classification of CNS tumors framework.

    View details for DOI 10.1055/s-0043-1776765

    View details for PubMedID 37963581

  • Tumor treating fields increases blood-brain barrier permeability and relative cerebral blood volume in patients with glioblastoma. The neuroradiology journal Iv, M., Naya, L., Sanan, S., Van Buskirk, S. L., Nagpal, S., Thomas, R. P., Recht, L. D., Patel, C. B. 2023: 19714009231207083


    200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans.Each patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (Vp), volume of extravascular extracellular space (EES) per volume of tissue (Ve), blood-brain barrier (BBB) permeability (Ktrans), and time constant for gadolinium reflux from EES back into the vascular system (Kep). Between-group comparisons were performed using rank-sum analysis, and bootstrapping evaluated likely reproducibility of the results.Among 13 pMRI datasets (11 nGBM, 2 recurrent GBM), therapies included temozolomide-only (n = 9) and temozolomide + TTFields (n = 4). No significant differences were found in patient or tumor characteristics. Compared to temozolomide-only, temozolomide + TTFields did not significantly affect the percent-change in pMRI metrics from baseline to 2 months. But during the 2- to 6-month period, temozolomide + TTFields significantly increased the percent-change in nRCBV (+26.9% [interquartile range 55.1%] vs -39.1% [37.0%], p = 0.049), sRCBV (+9.5% [39.7%] vs -30.5% [39.4%], p = 0.049), Ktrans (+54.6% [1768.4%] vs -26.9% [61.2%], p = 0.024), Ve (+111.0% [518.1%] vs -13.0% [22.5%], p = 0.048), and Vp (+98.8% [2172.4%] vs -24.6% [53.3%], p = 0.024) compared to temozolomide-only.Using pMRI, we provide initial in-human validation of pre-clinical studies regarding the effects of TTFields on tumor blood volume and BBB permeability in GBM.

    View details for DOI 10.1177/19714009231207083

    View details for PubMedID 37931176

  • DSC Perfusion MRI-Derived Fractional Tumor Burden and Relative CBV Differentiate Tumor Progression and Radiation Necrosis in Brain Metastases Treated with Stereotactic Radiosurgery. AJNR. American journal of neuroradiology Kuo, F., Ng, N. N., Nagpal, S., Pollom, E. L., Soltys, S., Hayden-Gephart, M., Li, G., Born, D. E., Iv, M. 2022


    Differentiation between tumor and radiation necrosis in patients with brain metastases treated with stereotactic radiosurgery is challenging. We hypothesized that MR perfusion and metabolic metrics can differentiate radiation necrosis from progressive tumor in this setting.We retrospectively evaluated MRIs comprising DSC, dynamic contrast-enhanced, and arterial spin-labeling perfusion imaging in subjects with brain metastases previously treated with stereotactic radiosurgery. For each lesion, we obtained the mean normalized and standardized relative CBV and fractional tumor burden, volume transfer constant, and normalized maximum CBF, as well as the maximum standardized uptake value in a subset of subjects who underwent FDG-PET. Relative CBV thresholds of 1 and 1.75 were used to define low and high fractional tumor burden.Thirty subjects with 37 lesions (20 radiation necrosis, 17 tumor) were included. Compared with radiation necrosis, tumor had increased mean normalized and standardized relative CBV (P = .002) and high fractional tumor burden (normalized, P = .005; standardized, P = .003) and decreased low fractional tumor burden (normalized, P = .03; standardized, P = .01). The area under the curve showed that relative CBV (normalized = 0.80; standardized = 0.79) and high fractional tumor burden (normalized = 0.77; standardized = 0.78) performed the best to discriminate tumor and radiation necrosis. For tumor prediction, the normalized relative CBV cutoff of ≥1.75 yielded a sensitivity of 76.5% and specificity of 70.0%, while the standardized cutoff of ≥1.75 yielded a sensitivity of 41.2% and specificity of 95.0%. No significance was found with the volume transfer constant, normalized CBF, and standardized uptake value.Increased relative CBV and high fractional tumor burden (defined by a threshold relative CBV of ≥1.75) best differentiated tumor from radiation necrosis in subjects with brain metastases treated with stereotactic radiosurgery. Performance of normalized and standardized approaches was similar.

    View details for DOI 10.3174/ajnr.A7501

    View details for PubMedID 35483909

  • Conventional and Advanced Imaging Techniques in Post-treatment Glioma Imaging Frontiers in Radiology Li, A. Y., Iv, M. 2022
  • Clinical Review of Computed Tomography and MR Perfusion Imaging in Neuro-Oncology. Radiologic clinics of North America Trinh, A., Wintermark, M., Iv, M. 2021; 59 (3): 323–34


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

    View details for DOI 10.1016/j.rcl.2021.01.002

    View details for PubMedID 33926680

  • Handling missing MRI sequences in deep learning segmentation of brain metastases: a multicenter study. NPJ digital medicine Grøvik, E. n., Yi, D. n., Iv, M. n., Tong, E. n., Nilsen, L. B., Latysheva, A. n., Saxhaug, C. n., Jacobsen, K. D., Helland, Å. n., Emblem, K. E., Rubin, D. L., Zaharchuk, G. n. 2021; 4 (1): 33


    The purpose of this study was to assess the clinical value of a deep learning (DL) model for automatic detection and segmentation of brain metastases, in which a neural network is trained on four distinct MRI sequences using an input-level dropout layer, thus simulating the scenario of missing MRI sequences by training on the full set and all possible subsets of the input data. This retrospective, multicenter study, evaluated 165 patients with brain metastases. The proposed input-level dropout (ILD) model was trained on multisequence MRI from 100 patients and validated/tested on 10/55 patients, in which the test set was missing one of the four MRI sequences used for training. The segmentation results were compared with the performance of a state-of-the-art DeepLab V3 model. The MR sequences in the training set included pre-gadolinium and post-gadolinium (Gd) T1-weighted 3D fast spin echo, post-Gd T1-weighted inversion recovery (IR) prepped fast spoiled gradient echo, and 3D fluid attenuated inversion recovery (FLAIR), whereas the test set did not include the IR prepped image-series. The ground truth segmentations were established by experienced neuroradiologists. The results were evaluated using precision, recall, Intersection over union (IoU)-score and Dice score, and receiver operating characteristics (ROC) curve statistics, while the Wilcoxon rank sum test was used to compare the performance of the two neural networks. The area under the ROC curve (AUC), averaged across all test cases, was 0.989 ± 0.029 for the ILD-model and 0.989 ± 0.023 for the DeepLab V3 model (p = 0.62). The ILD-model showed a significantly higher Dice score (0.795 ± 0.104 vs. 0.774 ± 0.104, p = 0.017), and IoU-score (0.561 ± 0.225 vs. 0.492 ± 0.186, p < 0.001) compared to the DeepLab V3 model, and a significantly lower average false positive rate of 3.6/patient vs. 7.0/patient (p < 0.001) using a 10 mm3 lesion-size limit. The ILD-model, trained on all possible combinations of four MRI sequences, may facilitate accurate detection and segmentation of brain metastases on a multicenter basis, even when the test cohort is missing input MRI sequences.

    View details for DOI 10.1038/s41746-021-00398-4

    View details for PubMedID 33619361

  • Neuroimaging in the Era of the Evolving WHO Classification of Brain Tumors, From the AJR Special Series on Cancer Staging. AJR. American journal of roentgenology Iv, M. n., Bisdas, S. n. 2021


    The inclusion of molecular and genetic information, along with histopathology, now defines the framework for brain tumor classification and grading. This framework is reflected in the major restructuring of the WHO brain tumor classification system in 2016, as well as in numerous subsequent proposed updates reflecting ongoing developments in understanding of the impact of tumor genotype on classification and grading. This incorporation of molecular and genetic features allows for improved tumor diagnosis and prediction of tumor behavior and response to treatment. Neuroimaging is essential for the noninvasive assessment of pre-treatment tumor grading and identification and determination of therapeutic efficacy. Conventional neuroimaging as well as physiologic imaging techniques such as diffusion- and perfusion- weighted MRI can increase the diagnostic confidence in the pre-treatment and post-treatment settings. While the use of neuroimaging to consistently determine tumor genetics is not yet robust, promising developments are on the horizon. Given the complexity of the brain tumor microenvironment, the development and implementation of a standardized reporting system can aid in conveying important information about brain tumor response to treatment to radiologists, referring providers, and patients. This article reviews the current state and role of neuroimaging in this continuously evolving field.

    View details for DOI 10.2214/AJR.20.25246

    View details for PubMedID 33502214

  • Advanced Imaging of Brain Metastases: From Augmenting Visualization and Improving Diagnosis to Evaluating Treatment Response. Frontiers in neurology Tong, E. n., McCullagh, K. L., Iv, M. n. 2020; 11: 270


    Early detection of brain metastases and differentiation from other neuropathologies is crucial. Although biopsy is often required for definitive diagnosis, imaging can provide useful information. After treatment commences, imaging is also performed to assess the efficacy of treatment. Contrast-enhanced magnetic resonance imaging (MRI) is the traditional imaging method for the evaluation of brain metastases, as it provides information about lesion size, morphology, and macroscopic properties. Newer MRI sequences have been developed to increase the conspicuity of detecting enhancing metastases. Other advanced MRI techniques, that have the capability to probe beyond the anatomic structure, are available to characterize micro-structures, cellularity, physiology, perfusion, and metabolism. Artificial intelligence provides powerful computational tools for detection, segmentation, classification, prediction, and prognosis. We highlight and review a few advanced MRI techniques for the assessment of brain metastases-specifically for (1) diagnosis, including differentiating between malignancy types and (2) evaluation of treatment response, including the differentiation between radiation necrosis and disease progression.

    View details for DOI 10.3389/fneur.2020.00270

    View details for PubMedID 32351445

    View details for PubMedCentralID PMC7174761

  • Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study. Radiology Iv, M. n., Ng, N. N., Nair, S. n., Zhang, Y. n., Lavezo, J. n., Cheshier, S. H., Holdsworth, S. J., Moseley, M. E., Rosenberg, J. n., Grant, G. A., Yeom, K. W. 2020: 200378


    Background Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results Seventeen participants (mean age ± standard deviation, 13 years ± 5; nine male) were in the ferumoxytol-exposed (case) group, 21 (mean age, 14 years ± 5; 11 male) were in the control group, and nine (mean age, 12 years ± 6; four male) were in the subgroup. The mean number of ferumoxytol administrations was 2 ± 1 (range, one to four). Mean susceptibility (in parts per million [ppm]) and R2* (in inverse seconds [sec-1]) values of the dentate (case participants: 0.06 ppm ± 0.04 and 23.87 sec-1 ± 4.13; control participants: 0.02 ppm ± 0.03 and 21.7 sec-1 ± 5.26), substantia nigrae (case participants: 0.08 ppm ± 0.06 and 27.46 sec-1 ± 5.58; control participants: 0.04 ppm ± 0.05 and 24.96 sec-1 ± 5.3), globus pallidi (case participants: 0.14 ppm ± 0.05 and 30.75 sec-1 ± 5.14; control participants: 0.08 ppm ± 0.07 and 28.82 sec-1 ± 6.62), putamina (case participants: 0.03 ppm ± 0.02 and 20.63 sec-1 ± 2.44; control participants: 0.02 ppm ± 0.02 and 19.65 sec-1 ± 3.6), caudate (case participants: -0.1 ppm ± 0.04 and 18.21 sec-1 ± 3.1; control participants: -0.06 ppm ± 0.05 and 18.83 sec-1 ± 3.32), and thalami (case participants: 0 ppm ± 0.03 and 16.49 sec-1 ± 3.6; control participants: 0.02 ppm ± 0.02 and 18.38 sec-1 ± 2.09) did not differ between groups (susceptibility, P = .21; R2*, P = .24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months ± 8 (range, 1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm ± 0.05 and 25.78 sec-1 ± 5.9; last MRI: 0.06 ppm ± 0.02 and 25.55 sec-1 ± 4.71), substantia nigrae (first MRI: 0.06 ppm ± 0.06 and 28.26 sec-1 ± 9.56; last MRI: 0.07 ppm ± 0.06 and 25.65 sec-1 ± 6.37), globus pallidi (first MRI: 0.13 ppm ± 0.07 and 27.53 sec-1 ± 8.88; last MRI: 0.14 ppm ± 0.06 and 29.78 sec-1 ± 6.54), putamina (first MRI: 0.03 ppm ± 0.03 and 19.78 sec-1 ± 3.51; last MRI: 0.03 ppm ± 0.02 and 19.73 sec-1 ± 3.01), caudate (first MRI: -0.09 ppm ± 0.05 and 21.38 sec-1 ± 4.72; last MRI: -0.1 ppm ± 0.05 and 18.75 sec-1 ± 2.68), and thalami (first MRI: 0.01 ppm ± 0.02 and 17.65 sec-1 ± 5.16; last MRI: 0 ppm ± 0.02 and 15.32 sec-1 ± 2.49) did not differ between the first and last MRI examinations (susceptibility, P = .95; R2*, P = .54). Conclusion No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. © RSNA, 2020.

    View details for DOI 10.1148/radiol.2020200378

    View details for PubMedID 32930651

  • Deep Learning Enables Automatic Detection and Segmentation of Brain Metastases on Multisequence MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Grovik, E., Yi, D., Iv, M., Tong, E., Rubin, D., Zaharchuk, G. 2020; 51 (1): 175–82

    View details for DOI 10.1002/jmri.26766

    View details for Web of Science ID 000530627200017

  • Perfusion MRI-Based Fractional Tumor Burden Differentiates between Tumor and Treatment Effect in Recurrent Glioblastomas and Informs Clinical Decision-Making. AJNR. American journal of neuroradiology Iv, M. n., Liu, X. n., Lavezo, J. n., Gentles, A. J., Ghanem, R. n., Lummus, S. n., Born, D. E., Soltys, S. G., Nagpal, S. n., Thomas, R. n., Recht, L. n., Fischbein, N. n. 2019


    Fractional tumor burden better correlates with histologic tumor volume fraction in treated glioblastoma than other perfusion metrics such as relative CBV. We defined fractional tumor burden classes with low and high blood volume to distinguish tumor from treatment effect and to determine whether fractional tumor burden can inform treatment-related decision-making.Forty-seven patients with high-grade gliomas (primarily glioblastoma) with recurrent contrast-enhancing lesions on DSC-MR imaging were retrospectively evaluated after surgical sampling. Histopathologic examination defined treatment effect versus tumor. Normalized relative CBV thresholds of 1.0 and 1.75 were used to define low, intermediate, and high fractional tumor burden classes in each histopathologically defined group. Performance was assessed with an area under the receiver operating characteristic curve. Consensus agreement among physician raters reporting hypothetic changes in treatment-related decisions based on fractional tumor burden was compared with actual real-time treatment decisions.Mean low fractional tumor burden, high fractional tumor burden, and relative CBV of the contrast-enhancing volume were significantly different between treatment effect and tumor (P = .002, P < .001, and P < .001), with tumor having significantly higher fractional tumor burden and relative CBV and lower fractional tumor burden. No significance was found with intermediate fractional tumor burden. Performance of the area under the receiver operating characteristic curve was the following: high fractional tumor burden, 0.85; low fractional tumor burden, 0.7; and relative CBV, 0.81. In comparing treatment decisions, there were disagreements in 7% of tumor and 44% of treatment effect cases; in the latter, all disagreements were in cases with scattered atypical cells.High fractional tumor burden and low fractional tumor burden define fractions of the contrast-enhancing lesion volume with high and low blood volume, respectively, and can differentiate treatment effect from tumor in recurrent glioblastomas. Fractional tumor burden maps can also help to inform clinical decision-making.

    View details for DOI 10.3174/ajnr.A6211

    View details for PubMedID 31515215

  • Arterial Spin-Labeling MRI Identifies Hypervascular Meningiomas. AJR. American journal of roentgenology Mayercik, V. n., Ma, M. n., Holdsworth, S. n., Heit, J. n., Iv, M. n. 2019: 1–5


    OBJECTIVE. Preoperative identification of hypervascular meningiomas can potentially detect those that may benefit from presurgical embolization, which may help to minimize intraoperative blood loss. In this study, we investigate if increased blood flow within meningiomas seen on arterial spin-labeling (ASL) MRI correlates with increased tumor vascularity seen on digital subtraction angiography (DSA). MATERIALS AND METHODS. A retrospective study was performed of 39 meningiomas in 34 patients who underwent ASL MRI and DSA between January 2008 and January 2017. Two raters independently calculated normalized tumor blood flow (TBF) on postprocessed ASL images using ROI analysis. They also recorded the presence or absence of tumor blush on DSA in each case. Interrater agreement was assessed with intraclass correlation coefficient (ICC). Performance of ASL MRI to identify tumor blush was determined with area under the ROC curve (AUC). RESULTS. In 27 female and seven male patients (mean age, 62.8 years), mean normalized TBF for meningiomas with tumor blush on DSA was significantly higher than those without tumor blush (p < 0.001). Mean normalized TBF for the group with tumor blush and the group without tumor blush group was 4.7 ± 1.1 and 1.5 ± 1.1, respectively, for rater 1 and 4.9 ± 5.3 and 1.5 ± 1.1, respectively, for rater 2. ICC was excellent (0.91). AUC for using normalized TBF to identify tumor vascularity on DSA was 0.82 (95% CI, 0.72-0.91), and a normalized TBF cut point of 2.7 yielded 88% sensitivity and 67% specificity. CONCLUSION. ASL MRI shows potential as a noninvasive screening tool for identifying hypervascular meningiomas.

    View details for DOI 10.2214/AJR.18.21026

    View details for PubMedID 31361532

  • MR Imaging-Based Radiomic Signatures of Distinct Molecular Subgroups of Medulloblastoma. AJNR. American journal of neuroradiology Iv, M., Zhou, M., Shpanskaya, K., Perreault, S., Wang, Z., Tranvinh, E., Lanzman, B., Vajapeyam, S., Vitanza, N. A., Fisher, P. G., Cho, Y. J., Laughlin, S., Ramaswamy, V., Taylor, M. D., Cheshier, S. H., Grant, G. A., Young Poussaint, T., Gevaert, O., Yeom, K. W. 2018


    Distinct molecular subgroups of pediatric medulloblastoma confer important differences in prognosis and therapy. Currently, tissue sampling is the only method to obtain information for classification. Our goal was to develop and validate radiomic and machine learning approaches for predicting molecular subgroups of pediatric medulloblastoma.In this multi-institutional retrospective study, we evaluated MR imaging datasets of 109 pediatric patients with medulloblastoma from 3 children's hospitals from January 2001 to January 2014. A computational framework was developed to extract MR imaging-based radiomic features from tumor segmentations, and we tested 2 predictive models: a double 10-fold cross-validation using a combined dataset consisting of all 3 patient cohorts and a 3-dataset cross-validation, in which training was performed on 2 cohorts and testing was performed on the third independent cohort. We used the Wilcoxon rank sum test for feature selection with assessment of area under the receiver operating characteristic curve to evaluate model performance.Of 590 MR imaging-derived radiomic features, including intensity-based histograms, tumor edge-sharpness, Gabor features, and local area integral invariant features, extracted from imaging-derived tumor segmentations, tumor edge-sharpness was most useful for predicting sonic hedgehog and group 4 tumors. Receiver operating characteristic analysis revealed superior performance of the double 10-fold cross-validation model for predicting sonic hedgehog, group 3, and group 4 tumors when using combined T1- and T2-weighted images (area under the curve = 0.79, 0.70, and 0.83, respectively). With the independent 3-dataset cross-validation strategy, select radiomic features were predictive of sonic hedgehog (area under the curve = 0.70-0.73) and group 4 (area under the curve = 0.76-0.80) medulloblastoma.This study provides proof-of-concept results for the application of radiomic and machine learning approaches to a multi-institutional dataset for the prediction of medulloblastoma subgroups.

    View details for DOI 10.3174/ajnr.A5899

    View details for PubMedID 30523141

  • Evaluation of Thick-Slab Overlapping MIP Images of Contrast-Enhanced 3D T1-Weighted CUBE for Detection of Intracranial Metastases: A Pilot Study for Comparison of Lesion Detection, Interpretation Time, and Sensitivity with Nonoverlapping CUBE MIP, CUBE, and Inversion-Recovery-Prepared Fast-Spoiled Gradient Recalled Brain Volume. AJNR. American journal of neuroradiology Yoon, B. C., Saad, A. F., Rezaii, P., Wintermark, M., Zaharchuk, G., Iv, M. 2018


    Early and accurate identification of cerebral metastases is important for prognostication and treatment planning although this process is often time consuming and labor intensive, especially with the hundreds of images associated with 3D volumetric imaging. This study aimed to evaluate the benefits of thick-slab overlapping MIPs constructed from contrast-enhanced T1-weighted CUBE (overlapping CUBE MIP) for the detection of brain metastases in comparison with traditional CUBE and inversion-recovery prepared fast-spoiled gradient recalled brain volume (IR-FSPGR-BRAVO) and nonoverlapping CUBE MIP.A retrospective review of 48 patients with cerebral metastases was performed at our institution from June 2016 to October 2017. Brain MRIs, which were acquired on multiple 3T scanners, included gadolinium-enhanced T1-weighted IR-FSPGR-BRAVO and CUBE, with subsequent generation of nonoverlapping CUBE MIP and overlapping CUBE MIP. Two blinded radiologists identified the total number and location of metastases on each image type. The Cohen κ was used to determine interrater agreement. Sensitivity, interpretation time, and lesion contrast-to-noise ratio were assessed.Interrater agreement for identification of metastases was fair-to-moderate for all image types (κ = 0.222-0.598). The total number of metastases identified was not significantly different across the image types. Interpretation time for CUBE MIPs was significantly shorter than for CUBE and IR-FSPGR-BRAVO, saving at least 50 seconds per case on average (P < .001). The mean lesion contrast-to-noise ratio for both CUBE MIPs was higher than for IR-FSPGR-BRAVO. The mean contrast-to-noise ratio for small lesions (<4 mm) was lower for nonoverlapping CUBE MIP (1.55) than for overlapping CUBE MIP (2.35). For both readers, the sensitivity for lesion detection was high for all image types but highest for overlapping CUBE MIP and CUBE (0.93-0.97).This study suggests that the use of overlapping CUBE MIP or nonoverlapping CUBE MIP for the detection of brain metastases can reduce interpretation time without sacrificing sensitivity, though the contrast-to-noise ratio of lesions is highest for overlapping CUBE MIP.

    View details for DOI 10.3174/ajnr.A5747

    View details for PubMedID 30093483

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

    View details for PubMedID 29405955

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


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

    View details for PubMedID 30398435

  • Radiomics in Brain Tumor: Image Assessment, Quantitative Feature Descriptors, and Machine-Learning Approaches. AJNR. American journal of neuroradiology Zhou, M. n., Scott, J. n., Chaudhury, B. n., Hall, L. n., Goldgof, D. n., Yeom, K. W., Iv, M. n., Ou, Y. n., Kalpathy-Cramer, J. n., Napel, S. n., Gillies, R. n., Gevaert, O. n., Gatenby, R. n. 2017


    Radiomics describes a broad set of computational methods that extract quantitative features from radiographic images. The resulting features can be used to inform imaging diagnosis, prognosis, and therapy response in oncology. However, major challenges remain for methodologic developments to optimize feature extraction and provide rapid information flow in clinical settings. Equally important, to be clinically useful, predictive radiomic properties must be clearly linked to meaningful biologic characteristics and qualitative imaging properties familiar to radiologists. Here we use a cross-disciplinary approach to highlight studies in radiomics. We review brain tumor radiologic studies (eg, imaging interpretation) through computational models (eg, computer vision and machine learning) that provide novel clinical insights. We outline current quantitative image feature extraction and prediction strategies with different levels of available clinical classes for supporting clinical decision-making. We further discuss machine-learning challenges and data opportunities to advance radiomic studies.

    View details for DOI 10.3174/ajnr.A5391

    View details for PubMedID 28982791

  • Clinical applications of iron oxide nanoparticles for magnetic resonance imaging of brain tumors NANOMEDICINE Iv, M., Telischak, N., Feng, D., Holdsworth, S. J., Yeom, K. W., Daldrup-Link, H. E. 2015; 10 (6): 993-1018


    Current neuroimaging provides detailed anatomic and functional evaluation of brain tumors, allowing for improved diagnostic and prognostic capabilities. Some challenges persist even with today's advanced imaging techniques, including accurate delineation of tumor margins and distinguishing treatment effects from residual or recurrent tumor. Ultrasmall superparamagnetic iron oxide nanoparticles are an emerging tool that can add clinically useful information due to their distinct physiochemical features and biodistribution, while having a good safety profile. Nanoparticles can be used as a platform for theranostic drugs, which have shown great promise for the treatment of CNS malignancies. This review will provide an overview of clinical ultrasmall superparamagnetic iron oxides and how they can be applied to the diagnostic and therapeutic neuro-oncologic setting.

    View details for DOI 10.2217/NNM.14.203

    View details for Web of Science ID 000352806000009

    View details for PubMedID 25867862

  • Detecting High-Dose Methotrexate-Induced Brain Changes in Pediatric and Young Adult Cancer Survivors Using [18F]FDG PET/MRI: A Pilot Study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Singh, S. B., Williams, S. E., Spunt, S. L., Rosenberg, J., Adams, L., Suryadevara, V., Iv, M., Daldrup-Link, H. 2024


    Significant improvements in treatments for children with cancer have resulted in a growing population of childhood cancer survivors who may face long-term adverse outcomes. Here, we aimed to diagnose high-dose methotrexate-induced brain injury on [18F]FDG PET/MRI and correlate the results with cognitive impairment identified by neurocognitive testing in pediatric cancer survivors. Methods: In this prospective, single-center pilot study, 10 children and young adults with sarcoma (n = 5), lymphoma (n = 4), or leukemia (n = 1) underwent dedicated brain [18F]FDG PET/MRI and a 2-h expert neuropsychologic evaluation on the same day, including the Wechsler Abbreviated Scale of Intelligence, second edition, for intellectual functioning; Delis-Kaplan Executive Function System (DKEFS) for executive functioning; and Wide Range Assessment of Memory and Learning, second edition (WRAML), for verbal and visual memory. Using PMOD software, we measured the SUVmean, cortical thickness, mean cerebral blood flow (CBFmean), and mean apparent diffusion coefficient of 3 different cortical regions (prefrontal cortex, cingulate gyrus, and hippocampus) that are routinely involved during the above-specified neurocognitive testing. Standardized scores of different measures were converted to z scores. Pairs of multivariable regression models (one for z scores < 0 and one for z scores > 0) were fitted for each brain region, imaging measure, and test score. Heteroscedasticity regression models were used to account for heterogeneity in variances between brain regions and to adjust for clustering within patients. Results: The regression analysis showed a significant correlation between the SUVmean of the prefrontal cortex and cingulum and DKEFS-sequential tracking (DKEFS-TM4) z scores (P = 0.003 and P = 0.012, respectively). The SUVmean of the hippocampus did not correlate with DKEFS-TM4 z scores (P = 0.111). The SUVmean for any evaluated brain regions did not correlate significantly with WRAML-visual memory (WRAML-VIS) z scores. CBFmean showed a positive correlation with SUVmean (r = 0.56, P = 0.01). The CBFmean of the cingulum, hippocampus, and prefrontal cortex correlated significantly with DKEFS-TM4 (all P < 0.001). In addition, the hippocampal CBFmean correlated significantly with negative WRAML-VIS z scores (P = 0.003). Conclusion: High-dose methotrexate-induced brain injury can manifest as a reduction in glucose metabolism and blood flow in specific brain areas, which can be detected with [18F]FDG PET/MRI. The SUVmean and CBFmean of the prefrontal cortex and cingulum can serve as quantitative measures for detecting executive functioning problems. Hippocampal CBFmean could also be useful for monitoring memory problems.

    View details for DOI 10.2967/jnumed.123.266760

    View details for PubMedID 38575193

  • A rare non-gadolinium enhancing sarcoma brain metastasis with microenvironment dominated by tumor-associated macrophages. Acta neuropathologica communications Rogawski, D., Wheeler, J., Nie, E., Zhu, W., Villanueva, E., Coffey, G., Ma, Q., Ganjoo, K., Fischbein, N., Iv, M., Vogel, H., Nagpal, S. 2024; 12 (1): 15


    Brain metastases occur in 1% of sarcoma cases and are associated with a median overall survival of 6 months. We report a rare case of a brain metastasis with unique radiologic and histopathologic features in a patient with low grade fibromyxoid sarcoma (LGFMS) previously treated with immune checkpoint inhibitor (ICI) therapy. The lone metastasis progressed in the midbrain tegmentum over 15 months as a non-enhancing, T2-hyperintense lesion with peripheral diffusion restriction, mimicking a demyelinating lesion. Histopathology of the lesion at autopsy revealed a rich infiltrate of tumor-associated macrophages (TAMs) with highest density at the leading edge of the metastasis, whereas there was a paucity of lymphocytes, suggestive of an immunologically cold environment. Given the important immunosuppressive and tumor-promoting functions of TAMs in gliomas and carcinoma/melanoma brain metastases, this unusual case provides an interesting example of a dense TAM infiltrate in a much rarer sarcoma brain metastasis.

    View details for DOI 10.1186/s40478-023-01713-8

    View details for PubMedID 38254244

    View details for PubMedCentralID 5021195

  • Investigating the value of radiomics stemming from DSC quantitative biomarkers in IDH mutation prediction in gliomas. Frontiers in neurology Ioannidis, G. S., Pigott, L. E., Iv, M., Surlan-Popovic, K., Wintermark, M., Bisdas, S., Marias, K. 2023; 14: 1249452


    This study aims to assess the value of biomarker based radiomics to predict IDH mutation in gliomas. The patient cohort consists of 160 patients histopathologicaly proven of primary glioma (WHO grades 2-4) from 3 different centers.To quantify the DSC perfusion signal two different mathematical modeling methods were used (Gamma fitting, leakage correction algorithms) considering the assumptions about the compartments contributing in the blood flow between the extra- and intra vascular space.The Mean slope of increase (MSI) and the K1 parameter of the bidirectional exchange model exhibited the highest performance with (ACC 74.3% AUROC 74.2%) and (ACC 75% AUROC 70.5%) respectively.The proposed framework on DSC-MRI radiogenomics in gliomas has the potential of becoming a reliable diagnostic support tool exploiting the mathematical modeling of the DSC signal to characterize IDH mutation status through a more reproducible and standardized signal analysis scheme for facilitating clinical translation.

    View details for DOI 10.3389/fneur.2023.1249452

    View details for PubMedID 38046592

    View details for PubMedCentralID PMC10690367

  • Disagreement Among Neuroradiologists Detecting Change in Multiple Sclerosis Disease Activity Leyden, K., Bajus, L., Iv, M., Tong, E., Siebenborn, N. S., Granziera, C. SAGE PUBLICATIONS LTD. 2023: 257-258
  • Erratum: "MRI pulse sequence integration for deep-learning-based brain metastases segmentation". Medical physics Yi, D., Grøvik, E., Tong, E., Iv, M., Emblem, K. E., Nilsen, L. B., Saxhaug, C., Latysheva, A., Jacobsen, K. D., Helland, Å., Zaharchuk, G., Rubin, D. 2023; 50 (8): 5294

    View details for DOI 10.1002/mp.16594

    View details for PubMedID 37573581

  • Generative Editing via Convolutional Obscuring (GECO): A Generative Adversarial Network for MRI de-artifacting Bagley, B., Petrov, S., Cheng, G., Armanasu, M., Fischbein, N., Jiang, B., Iv, M., Tranvinh, E., Zeineh, M., Gevaert, O. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Correction: Macrophage Exclusion after Radiation Therapy (MERT): A First-in-Human Phase I/II Trial using a CXCR4 Inhibitor in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Thomas, R. P., Nagpal, S., Iv, M., Soltys, S. G., Bertrand, S., Pelpola, J. S., Ball, R., Yang, J., Sundaram, V., Chernikova, S. B., Lavezo, J., Born, D., Vogel, H., Brown, J. M., Recht, L. D. 2023; 29 (2): 502

    View details for DOI 10.1158/1078-0432.CCR-22-3712

    View details for PubMedID 36647675

  • Retinal artery and vein occlusion in calciphylaxis. American journal of ophthalmology case reports Naranjo, A., Rayess, N., Ryan, E., Iv, M., Mahajan, V. B. 2022; 26: 101433


    To report a case of branch retinal artery occlusion (BRAO) followed by branch retinal vein occlusion (BRVO) and paracentral acute middle maculopathy (PAMM) in a patient with confirmed calciphylaxis.A 52-year-old female with a history of BRAO in the right eye one-year prior presented with decreased vision and a new inferotemporal scotoma. Computed tomography angiography of the head and neck demonstrated vascular calcifications at the origin of both ophthalmic arteries, which were otherwise poorly visualized. Ophthalmic examination demonstrated retinal whitening superiorly with intraretinal hemorrhages inferiorly. Optical coherence tomography (OCT) demonstrated middle retinal hyperreflectivity and a mild epiretinal membrane. Fluorescein angiography (FFA) demonstrated delayed perfusion of superior retinal arcade. On further questioning, patient was found to have a history of IgA nephropathy with end-stage renal disease, secondary hyperparathyroidism and calciphylaxis. Calciphylaxis is a systemic disease, characterized by high levels of calcium and progressive calcification of the vascular medial layer leading to ischemia. Anterior ischemic optic neuropathy (AION) and crystalline retinopathy have been reported as ocular manifestations of calciphylaxis, however, there are very few reports on ophthalmic manifestations of calciphylaxis.Clinical manifestations of calciphylaxis are variable and a detailed clinical history is important to suspect calciphylaxis. Calciphylaxis should be considered in the differential diagnosis of BRAO, BRVO, PAMM or any ophthalmic vascular manifestation in patients with end-stage renal disease.

    View details for DOI 10.1016/j.ajoc.2022.101433

    View details for PubMedID 35372715

    View details for PubMedCentralID PMC8968009

  • Deep learning-based brain tumor segmentation on limited sequences of magnetic resonance imaging Huang, J., Molleti, P., Iv, M., Lee, R., Itakura, H. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • 2.5D and 3D segmentation of brain metastases with deep learning on multinational MRI data. Frontiers in neuroinformatics Ottesen, J. A., Yi, D., Tong, E., Iv, M., Latysheva, A., Saxhaug, C., Jacobsen, K. D., Helland, Å., Emblem, K. E., Rubin, D. L., Bjørnerud, A., Zaharchuk, G., Grøvik, E. 2022; 16: 1056068


    Management of patients with brain metastases is often based on manual lesion detection and segmentation by an expert reader. This is a time- and labor-intensive process, and to that end, this work proposes an end-to-end deep learning segmentation network for a varying number of available MRI available sequences.We adapt and evaluate a 2.5D and a 3D convolution neural network trained and tested on a retrospective multinational study from two independent centers, in addition, nnU-Net was adapted as a comparative benchmark. Segmentation and detection performance was evaluated by: (1) the dice similarity coefficient, (2) a per-metastases and the average detection sensitivity, and (3) the number of false positives.The 2.5D and 3D models achieved similar results, albeit the 2.5D model had better detection rate, whereas the 3D model had fewer false positive predictions, and nnU-Net had fewest false positives, but with the lowest detection rate. On MRI data from center 1, the 2.5D, 3D, and nnU-Net detected 79%, 71%, and 65% of all metastases; had an average per patient sensitivity of 0.88, 0.84, and 0.76; and had on average 6.2, 3.2, and 1.7 false positive predictions per patient, respectively. For center 2, the 2.5D, 3D, and nnU-Net detected 88%, 86%, and 78% of all metastases; had an average per patient sensitivity of 0.92, 0.91, and 0.85; and had on average 1.0, 0.4, and 0.1 false positive predictions per patient, respectively.Our results show that deep learning can yield highly accurate segmentations of brain metastases with few false positives in multinational data, but the accuracy degrades for metastases with an area smaller than 0.4 cm2.

    View details for DOI 10.3389/fninf.2022.1056068

    View details for PubMedID 36743439

    View details for PubMedCentralID PMC9889663

  • EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Theranostics Zhou, Q., van den Berg, N. S., Rosenthal, E. L., Iv, M., Zhang, M., Vega Leonel, J. C., Walters, S., Nishio, N., Granucci, M., Raymundo, R., Yi, G., Vogel, H., Cayrol, R., Lee, Y. J., Lu, G., Hom, M., Kang, W., Hayden Gephart, M., Recht, L., Nagpal, S., Thomas, R., Patel, C., Grant, G. A., Li, G. 2021; 11 (15): 7130-7143


    Rationale: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods: Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo, to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results: No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions: Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.

    View details for DOI 10.7150/thno.60582

    View details for PubMedID 34158840

    View details for PubMedCentralID PMC8210618

  • Imaging Chemotherapy-Induced Brain Damage in Pediatric Cancer Survivors Baratto, L., Garcia, D., Rashidi, A., Iv, M., Hawk, K., Daldrup-Link, H. SOC NUCLEAR MEDICINE INC. 2021
  • Management of brain tumors presenting in pregnancy: a case series and systematic review. American journal of obstetrics & gynecology MFM Rodrigues, A. J., Waldrop, A. R., Suharwardy, S., Druzin, M. L., Iv, M., Ansari, J. R., Stone, S. A., Jaffe, R. A., Jin, M. C., Li, G., Hayden-Gephart, M. 2021; 3 (1): 100256


    Patients who present with brain tumors during pregnancy require unique imaging and neurosurgical, obstetrical, and anesthetic considerations. Here, we review the literature and discuss the management of patients who present with brain tumors during pregnancy. Between 2009 and 2019, 9 patients were diagnosed at our institution with brain tumors during pregnancy. Clinical information was extracted from the electronic medical records. The median age at presentation was 29 years (range, 25-38 years). The most common symptoms at presentation included headache (n=5), visual changes (n=4), hemiparesis (n=3), and seizures (n=3). The median gestational age at presentation was 20.5 weeks (range, 11-37 weeks). Of note, 8 patients (89%) delivered healthy newborns, and 1 patient terminated her pregnancy. In addition, 5 patients (56%) required neurosurgical procedures during pregnancy (gestational ages, 14-37 weeks) because of disease progression (n=2) or neurologic instability (n=3). There was 1 episode of postneurosurgery morbidity (pulmonary embolism [PE]) and no surgical maternal mortality. The median length of follow-up was 15 months (range, 6-45 months). In cases demonstrating unstable or progressive neurosurgical status past the point of fetal viability, neurosurgical intervention should be considered. The physiological and pharmacodynamic changes of pregnancy substantially affect anesthetic management. Pregnancy termination should be discussed and offered to the patient when aggressive disease necessitates immediate treatment and the fetal gestational age remains previable, although neurologically stable patients may be able to continue the pregnancy to term. Ultimately, pregnant patients with brain tumors require an individualized approach to their care under the guidance of a multidisciplinary team.

    View details for DOI 10.1016/j.ajogmf.2020.100256

    View details for PubMedID 33451609

  • How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol. Pediatric radiology Daldrup-Link, H. E., Theruvath, A. J., Rashidi, A., Iv, M., Majzner, R. G., Spunt, S. L., Goodman, S., Moseley, M. 2021


    Gadolinium chelates have been used as standard contrast agents for clinical MRI for several decades. However, several investigators recently reported that rare Earth metals such as gadolinium are deposited in the brain for months or years. This is particularly concerning for children, whose developing brain is more vulnerable to exogenous toxins compared to adults. Therefore, a search is under way for alternative MR imaging biomarkers. The United States Food and Drug Administration (FDA)-approved iron supplement ferumoxytol can solve this unmet clinical need: ferumoxytol consists of iron oxide nanoparticles that can be detected with MRI and provide significant T1- and T2-signal enhancement of vessels and soft tissues. Several investigators including our research group have started to use ferumoxytol off-label as a new contrast agent for MRI. This article reviews the existing literature on the biodistribution of ferumoxytol in children and compares the diagnostic accuracy of ferumoxytol- and gadolinium-chelate-enhanced MRI. Iron oxide nanoparticles represent a promising new class of contrast agents for pediatric MRI that can be metabolized and are not deposited in the brain.

    View details for DOI 10.1007/s00247-021-05098-5

    View details for PubMedID 34046709

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


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

    View details for DOI 10.3390/cancers13163965

    View details for PubMedID 34439118

  • MRI pulse sequence integration for deep-learning-based brain metastases segmentation. Medical physics Yi, D., Grøvik, E., Tong, E., Iv, M., Emblem, K. E., Nilsen, L. B., Saxhaug, C., Latysheva, A., Jacobsen, K. D., Helland, Å., Zaharchuk, G., Rubin, D. 2021


    Magnetic resonance (MR) imaging is an essential diagnostic tool in clinical medicine. Recently, a variety of deep-learning methods have been applied to segmentation tasks in medical images, with promising results for computer-aided diagnosis. For MR images, effectively integrating different pulse sequences is important to optimize performance. However, the best way to integrate different pulse sequences remains unclear. In addition, networks trained with a certain subset of pulse sequences as input are unable to perform when given a subset of those pulse sequences. In this study, we evaluate multiple architectural features and characterize their effects in the task of metastasis segmentation while creating a method to robustly train a network to be able to work given any strict subset of the pulse sequences available during training.We use a 2.5D DeepLabv3 segmentation network to segment metastases lesions on brain MR's with four pulse sequence inputs. To study how we can best integrate MR pulse sequences for this task, we consider (1) different pulse sequence integration schemas, combining our features at early, middle, and late points within a deep network, (2) different modes of weight sharing for parallel network branches, and (3) a novel integration level dropout layer, which will allow the networks to be robust to performing inference on input with only a subset of pulse sequences available at the training.We find that levels of integration and modes of weight sharing that favor low variance work best in our regime of small amounts of training data (n = 100). By adding an input-level dropout layer, we could preserve the overall performance of these networks while allowing for inference on inputs with missing pulse sequences. We illustrate not only the generalizability of the network but also the utility of this robustness when applying the trained model to data from a different center, which does not use the same pulse sequences. Finally, we apply network visualization methods to better understand which input features are most important for network performance.Together, these results provide a framework for building networks with enhanced robustness to missing data while maintaining comparable performance in medical imaging applications.

    View details for DOI 10.1002/mp.15136

    View details for PubMedID 34405896

  • Development and Validation of Operator Independent Measurements of Optic Nerve Sheath Cerebral Spinal Fluid Volume from MRI Wasi, M., Iv, M., Wasi, T., Moss, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Phase I study of BPM31510 and vitamin K in patients with high grade glioma recurrent after a bevacizumab-containing regimen. Nagpal, S., Thomas, R., Bertrand, S., Yerraballa, H., Iv, M., Li, G., Klotz, A., Kiebish, M. A., Narain, N. R., Sarangarajan, R., Granger, E., Recht, L. AMER SOC CLINICAL ONCOLOGY. 2020
  • Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment JOURNAL OF NEURORADIOLOGY Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2020; 47 (1): 13–19
  • Variable Refocusing Flip Angle Single-Shot Imaging for Sedation-Free Fast Brain MRI. AJNR. American journal of neuroradiology Jabarkheel, R. n., Tong, E. n., Lee, E. H., Cullen, T. M., Yousaf, U. n., Loening, A. M., Taviani, V. n., Iv, M. n., Grant, G. A., Holdsworth, S. J., Vasanawala, S. S., Yeom, K. W. 2020


    Conventional single-shot FSE commonly used for fast MRI may be suboptimal for brain evaluation due to poor image contrast, SNR, or image blurring. We investigated the clinical performance of variable refocusing flip angle single-shot FSE, a variation of single-shot FSE with lower radiofrequency energy deposition and potentially faster acquisition time, as an alternative approach to fast brain MR imaging.We retrospectively compared half-Fourier single-shot FSE with half- and full-Fourier variable refocusing flip angle single-shot FSE in 30 children. Three readers reviewed images for motion artifacts, image sharpness at the brain-fluid interface, and image sharpness/tissue contrast at gray-white differentiation on a modified 5-point Likert scale. Two readers also evaluated full-Fourier variable refocusing flip angle single-shot FSE against T2-FSE for brain lesion detectability in 38 children.Variable refocusing flip angle single-shot FSE sequences showed more motion artifacts (P < .001). Variable refocusing flip angle single-shot FSE sequences scored higher regarding image sharpness at brain-fluid interfaces (P < .001) and gray-white differentiation (P < .001). Acquisition times for half- and full-Fourier variable refocusing flip angle single-shot FSE were faster than for single-shot FSE (P < .001) with a 53% and 47% reduction, respectively. Intermodality agreement between full-Fourier variable refocusing flip angle single-shot FSE and T2-FSE findings was near-perfect (κ = 0.90, κ = 0.95), with an 8% discordance rate for ground truth lesion detection.Variable refocusing flip angle single-shot FSE achieved 2× faster scan times than single-shot FSE with improved image sharpness at brain-fluid interfaces and gray-white differentiation. Such improvements are likely attributed to a combination of improved contrast, spatial resolution, SNR, and reduced T2-decay associated with blurring. While variable refocusing flip angle single-shot FSE may be a useful alternative to single-shot FSE and, potentially, T2-FSE when faster scan times are desired, motion artifacts were more common in variable refocusing flip angle single-shot FSE, and, thus, they remain an important consideration before clinical implementation.

    View details for DOI 10.3174/ajnr.A6616

    View details for PubMedID 32586967

  • Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study. AJNR. American journal of neuroradiology Quon, J. L., Bala, W. n., Chen, L. C., Wright, J. n., Kim, L. H., Han, M. n., Shpanskaya, K. n., Lee, E. H., Tong, E. n., Iv, M. n., Seekins, J. n., Lungren, M. P., Braun, K. R., Poussaint, T. Y., Laughlin, S. n., Taylor, M. D., Lober, R. M., Vogel, H. n., Fisher, P. G., Grant, G. A., Ramaswamy, V. n., Vitanza, N. A., Ho, C. Y., Edwards, M. S., Cheshier, S. H., Yeom, K. W. 2020


    Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification.The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (n = 122), medulloblastoma (n = 272), pilocytic astrocytoma (n = 135), and ependymoma (n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists.Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F1 score were higher than those of 2 of the 4 radiologists.We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.

    View details for DOI 10.3174/ajnr.A6704

    View details for PubMedID 32816765

  • Utilization of Novel High-Resolution, MRI-Based Vascular Imaging Modality for Preoperative Stereoelectroencephalography Planning in Children: A Technical Note. Stereotactic and functional neurosurgery Feng, A. Y., Ho, A. L., Kim, L. H., Sussman, E. S., Pendharkar, A. V., Iv, M. n., Yeom, K. W., Halpern, C. H., Grant, G. A. 2020: 1–7


    Stereoelectroencephalography (SEEG) is a powerful intracranial diagnostic tool that requires accurate imaging for proper electrode trajectory planning to ensure efficacy and maximize patient safety. Computed tomography (CT) angiography and digital subtraction angiography are commonly used, but recent developments in magnetic resonance angiography allow for high-resolution vascular visualization without added risks of radiation. We report on the accuracy of electrode placement under robotic assistance planning utilizing a novel high-resolution magnetic resonance imaging (MRI)-based imaging modality.Sixteen pediatric patients between February 2014 and October 2017 underwent SEEG exploration for epileptogenic zone localization. A gadolinium-enhanced 3D T1-weighted spoiled gradient recalled echo sequence with minimum echo time and repetition time was applied for background parenchymal suppression and vascular enhancement. Electrode placement accuracy was determined by analyzing postoperative CT scans laid over preoperative virtual electrode trajectory paths. Entry point, target point, and closest vessel intersection were measured.For any intersection along the trajectory path, 57 intersected vessels were measured. The mean diameter of an intersected vessel was 1.0343 ± 0.1721 mm, and 21.05% of intersections involved superficial vessels. There were 157 overall intersection + near-miss events. The mean diameter for an involved vessel was 1.0236 ± 0.0928 mm, and superficial vessels were involved in 20.13%. Looking only at final electrode target, 3 intersection events were observed. The mean diameter of an intersected vessel was 1.0125 ± 0.2227 mm. For intersection + near-miss events, 24 were measured. An involved vessel's mean diameter was 1.1028 ± 0.2634 mm. For non-entry point intersections, 45 intersected vessels were measured. The mean diameter for intersected vessels was 0.9526 ± 0.0689 mm. For non-entry point intersections + near misses, 126 events were observed. The mean diameter for involved vessels was 0.9826 ± 0.1008 mm.We believe this novel sequence allows better identification of superficial and deeper subcortical vessels compared to conventional T1-weighted gadolinium-enhanced MRI.

    View details for DOI 10.1159/000503693

    View details for PubMedID 32062664

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


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

    View details for DOI 10.3233/JAD-200656

    View details for PubMedID 33104030

  • Simultaneous time of flight-MRA and T2* imaging for cerebrovascular MRI. Neuroradiology Lanzman, B. A., Huang, Y. n., Lee, E. H., Iv, M. n., Moseley, M. E., Holdsworth, S. J., Yeom, K. W. 2020


    3D multi-echo gradient-recalled echo (ME-GRE) can simultaneously generate time-of-flight magnetic resonance angiography (pTOF) in addition to T2*-based susceptibility-weighted images (SWI). We assessed the clinical performance of pTOF generated from a 3D ME-GRE acquisition compared with conventional TOF-MRA (cTOF).Eighty consecutive children were retrospectively identified who obtained 3D ME-GRE alongside cTOF. Two blinded readers independently assessed pTOF derived from 3D ME-GRE and compared them with cTOF. A 5-point Likert scale was used to rank lesion conspicuity and to assess for diagnostic confidence.Across 80 pediatric neurovascular pathologies, a similar number of lesions were reported on pTOF and cTOF (43-40%, respectively, p > 0.05). Rating of lesion conspicuity was higher with cTOF (4.5 ± 1.0) as compared with pTOF (4.0 ± 0.7), but this was not significantly different (p = 0.06). Diagnostic confidence was rated higher with cTOF (4.8 ± 0.5) than that of pTOF (3.7 ± 0.6; p < 0.001). Overall, the inter-rater agreement between two readers for lesion count on pTOF was classified as almost perfect (κ = 0.98, 96% CI 0.8-1.0).In this study, TOF-MRA simultaneously generated in addition to SWI from 3D MR-GRE can serve as a diagnostic adjunct, particularly for proximal vessel disease and when conventional TOF-MRA images are absent.

    View details for DOI 10.1007/s00234-020-02499-5

    View details for PubMedID 32945913

  • Critical illness-associated cerebral microbleeds in severe COVID-19 infection. Clinical imaging Gupta, N. A., Lien, C. n., Iv, M. n. 2020; 68: 239–41


    Neurologic complications of COVID-19 infection have been recently described and include dizziness, headache, loss of taste and smell, stroke, and encephalopathy. Brain MRI in these patients have revealed various findings including ischemia, hemorrhage, inflammation, and demyelination. In this article, we report a case of critical illness-associated cerebral microbleeds identified on MRI in a patient with severe COVID-19 infection and discuss the potential etiologies of these neuroimaging findings.

    View details for DOI 10.1016/j.clinimag.2020.08.029

    View details for PubMedID 32911311

  • Brain iron deposition after Ferumoxytol-enhanced MRI: A study of Porcine Brains. Nanotheranostics Theruvath, A. J., Aghighi, M. n., Iv, M. n., Nejadnik, H. n., Lavezo, J. n., Pisani, L. J., Daldrup-Link, H. E. 2020; 4 (4): 195–200


    Recent evidence of gadolinium deposition in the brain has raised safety concerns. Iron oxide nanoparticles are re-emerging as promising alternative MR contrast agents, because the iron core can be metabolized. However, long-term follow up studies of the brain after intravenous iron oxide administration have not been reported thus far. In this study, we investigated, if intravenously administered ferumoxytol nanoparticles are deposited in porcine brains. Methods: In an animal care and use committee-approved prospective case-control study, ten Göttingen minipigs received either intravenous ferumoxytol injections at a dose of 5 mg Fe/kg (n=4) or remained untreated (n=6). Nine to twelve months later, pigs were sacrificed and the brains of all pigs underwent ex vivo MRI at 7T with T2 and T2*-weighted sequences. MRI scans were evaluated by measuring R2* values (R2*=1000/T2*) of the bilateral caudate nucleus, lentiform nucleus, thalamus, dentate nucleus, and choroid plexus. Pig brains were sectioned and stained with Prussian blue and evaluated for iron deposition using a semiquantitative scoring system. Data of ferumoxytol exposed and unexposed groups were compared with an unpaired t-test and a Mann-Whitney U test. Results: T2 and T2* signal of the different brain regions was not visually different between ferumoxytol exposed and unexposed controls. There were no significant differences in R2* values of the different brain regions in the ferumoxytol exposed group compared to controls (p>0.05). Prussian blue stains of the same brain regions, scored according to a semiquantitative score, were not significantly different either between the ferumoxytol exposed group and unexposed controls (p>0.05). Conclusions: Our study shows that intravenous ferumoxytol doses of 5-10 mg Fe/kg do not lead to iron deposition in the brain of pigs. We suggest iron oxide nanoparticles as a promising alternative for gadolinium-enhanced MRI.

    View details for DOI 10.7150/ntno.46356

    View details for PubMedID 32637297

    View details for PubMedCentralID PMC7332795

  • A PHASE 1 STUDY OF BPM31510 PLUS VITAMIN K IN SUBJECTS WITH HIGH-GRADE GLIOMA THAT HAS RECURRED ON A BEVACIZUMAB-CONTAINING REGIMEN Recht, L., Thomas, R., Bertrand, S., Yerballa, P., Li, G., Iv, M., Narain, N., Sarangarajan, R., Granger, E., Nagpal, S. OXFORD UNIV PRESS INC. 2019: 27
  • Malignant optic glioma masked by suspected optic neuritis and central retinal vein occlusion. Radiology case reports Kalnins, A. n., Penta, M. n., El-Sawy, T. n., Liao, Y. J., Fischbein, N. n., Iv, M. n. 2019; 14 (2): 226–29


    Malignant optic glioma presents a clinical and diagnostic challenge, as early imaging findings overlap with other more common causes of optic nerve enhancement and enlargement, potentially leading to delay in diagnosis. This rare diagnosis carries an extremely poor prognosis, with death usually occurring within 1 year. We present a case of malignant optic glioma that was initially diagnosed as optic neuritis and central retinal vein occlusion, and we emphasize the importance of serial imaging and definitive biopsy to promote early diagnosis and treatment of this entity.

    View details for PubMedID 30450148

  • Altered cerebral perfusion in children with Langerhans cell histiocytosis after chemotherapy. Pediatric blood & cancer Han, M. n., Kim, L. H., Shpanskaya, K. n., Kim, C. n., Iv, M. n., Jeng, M. n., Yeom, K. W. 2019: e28104


    Children with Langerhans cell histiocytosis (LCH) may develop a wide array of neurological symptoms, but associated cerebral physiologic changes are poorly understood. We examined cerebral hemodynamic properties of pediatric LCH using arterial spin-labeling (ASL) perfusion magnetic resonance imaging (MRI).A retrospective study was performed in 23 children with biopsy-proven LCH. Analysis was performed on routine brain MRI obtained before or after therapy. Region of interest (ROI) methodology was used to determine ASL cerebral blood flow (CBF) (mL/100 g/min) in the following bilateral regions: angular gyrus, anterior prefrontal cortex, orbitofrontal cortex, dorsal anterior cingulate cortex, and hippocampus. Quantile (median) regression was performed for each ROI location. CBF patterns were compared between pre- and posttreatment LCH patients as well as with age-matched healthy controls.Significantly reduced CBF was seen in posttreatment children with LCH compared to age-matched controls in angular gyrus (P = .046), anterior prefrontal cortex (P = .039), and dorsal anterior cingulate cortex (P = .023). Further analysis revealed dominant perfusion abnormalities in the right hemisphere. No significant perfusion differences were observed in the hippocampus or orbitofrontal cortex.Perfusion in specific cerebral regions may be consistently reduced in children with LCH, and may represent effects of underlying disease physiology and/or sequelae of chemotherapy. Studies that combine a formal cognitive assessment and hemodynamic data may further provide insight into perfusion deficits associated with the disease and the potential neurotoxic effects in children treated by chemotherapy.

    View details for DOI 10.1002/pbc.28104

    View details for PubMedID 31802628

  • Non-Contrast T2-Weighted MR Sequences for Long Term Monitoring of Asymptomatic Convexity Meningiomas. World neurosurgery He, J. Q., Iv, M. n., Li, G. n., Zhang, M. n., Hayden-Gephart, M. n. 2019


    Gadolinium based contrast agents (GBCA) used to enhance MRs have been linked to tissue deposition, including in the brain. The management of indolent tumors such as meningiomas requires frequent MRs to monitor for interval growth. Given concern regarding GBCA deposition, we sought to determine if non-contrast MRs in patients with asymptomatic meningiomas were equivalent to GBCA-enhanced MRs in surveillance monitoring.This IRB-approved retrospective chart review included 106 MR sequences from 18 patients. Inclusion criteria were adult patients with asymptomatic meningiomas who received baseline contrast-enhanced and non-contrast axial MR imaging of the brain. Exclusion criteria included: 1) baseline or follow-up axial images were not available for review 2) baseline scan was obtained without contrast 3) diagnosis of meningioma was uncertain. Percent tumor growth was measured by comparing cross-sectional area at maximum tumor diameter from the earliest and most recent scans. For each patient, change in tumor size over time was compared using T1+contrast, T2, and T2 FLAIR sequences. These were compared to a qualitative consensus reading by a neurosurgeon and a neuroradiologist.Measured change of greater than 10% was taken to represent tumor growth. In 17 out of 18 patients, measurement of non-contrast studies (T2 and T2 FLAIR) matched consensus. For one patient, imaging on T2 suggested 11% growth while T2 FLAIR and overall consensus was stability.Our study provides evidence that non-contrasted MR images are equivalent to contrast-weighted MRs to follow change in tumor size over time in asymptomatic meningiomas.

    View details for DOI 10.1016/j.wneu.2019.11.051

    View details for PubMedID 31734418

  • Utility of a Quantitative Approach Using Diffusion Tensor Imaging for Prognostication Regarding Motor and Functional Outcomes in Patients With Surgically Resected Deep Intracranial Cavernous Malformations. Neurosurgery Abhinav, K. n., Nielsen, T. H., Singh, R. n., Weng, Y. n., Han, S. S., Iv, M. n., Steinberg, G. K. 2019


    Resection of deep intracranial cavernous malformations (CMs) is associated with a higher risk of neurological deterioration and uncertainty regarding clinical outcomes.To examine diffusion tractography imaging (DTI) data evaluating the corticospinal tract (CST) in relation to motor and functional outcomes in patients with surgically resected deep CMs.Perilesional CST was characterized as disrupted, displaced, or normal. Mean fractional anisotropy (FA) values were obtained for whole ipsilateral CST and in 3 regions: subcortical (proximal), perilesional, and distally. Mean FA values in anatomically equivalent regions in the contralateral CST were obtained. Clinical and radiological data were collected independently. Multivariable regression analysis was used for statistical analysis.A total of 18 patients [brainstem (15) and thalamus/basal ganglia (3); median follow-up: 270 d] were identified over 2 yr. The CST was identified preoperatively as disrupted (6), displaced (8), and normal (4). Five of 6 patients with disruption had weakness. Higher preoperative mean FA values for distal ipsilateral CST segment were associated with better preoperative lower (P < .001), upper limb (P = .004), postoperative lower (P = .005), and upper limb (P < .001) motor examination. Preoperative mean FA values for distal ipsilateral CST segment (P = .001) and contralateral perilesional CST segment (P < .001) were negatively associated with postoperative modified Rankin scale scores.Lower preoperative mean FA values for overall and defined CST segments corresponded to worse patient pre- and postoperative motor examination and/or functional status. FA value for the distal ipsilateral CST segment has prognostic potential with respect to clinical outcomes.

    View details for DOI 10.1093/neuros/nyz259

    View details for PubMedID 31360998

  • The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial. BMC neurology Taylor, J. L., Hambro, B. C., Strossman, N. D., Bhatt, P. n., Hernandez, B. n., Ashford, J. W., Cheng, J. J., Iv, M. n., Adamson, M. M., Lazzeroni, L. C., McNerney, M. W. 2019; 19 (1): 326


    Mild Cognitive Impairment (MCI) carries a high risk of progression to Alzheimer's disease (AD) dementia. Previous clinical trials testing whether cholinesterase inhibitors can slow the rate of progression from MCI to AD dementia have yielded disappointing results. However, recent studies of the effects of repetitive transcranial magnetic stimulation (rTMS) in AD have demonstrated improvements in cognitive function. Because few rTMS trials have been conducted in MCI, we designed a trial to test the short-term efficacy of rTMS in MCI. Yet, in both MCI and AD, we know little about what site of stimulation would be ideal for improving cognitive function. Therefore, two cortical sites will be investigated in this trial: (1) the dorsolateral prefrontal cortex (DLPFC), which has been well studied for treatment of major depressive disorder; and (2) the lateral parietal cortex (LPC), a novel site with connectivity to AD-relevant limbic regions.In this single-site trial, we plan to enroll 99 participants with single or multi-domain amnestic MCI. We will randomize participants to one of three groups: (1) Active DLPFC rTMS; (2) Active LPC rTMS; and (3) Sham rTMS (evenly split between DLPFC and LPC locations). After completing 20 bilateral rTMS treatment sessions, participants will be followed for 6 months to test short-term efficacy and track durability of effects. The primary efficacy measure is the California Verbal Learning Test-II (CVLT-II), assessed 1 week after intervention. Secondary analyses will examine effects of rTMS on other cognitive measures, symptoms of depression, and brain function with respect to the site of stimulation. Finally, selected biomarkers will be analyzed to explore predictors of response and mechanisms of action.The primary aim of this trial is to test the short-term efficacy of rTMS in MCI. Additionally, the project will provide information on the durability of cognitive effects and potentially distinct effects of stimulating DLPFC versus LPC regions. Future efforts would be directed toward better understanding therapeutic mechanisms and optimizing rTMS for treatment of MCI. Ultimately, if rTMS can be utilized to slow the rate of progression to AD dementia, this will be a significant advancement in the field.Clinical Trials NCT03331796. Registered 6 November 2017, All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.This report is based on version 1, approved by the DSMB on 30 November, 2017 and amended on 14 August, 2018 and 19 September, 2019.

    View details for DOI 10.1186/s12883-019-1552-7

    View details for PubMedID 31842821

  • Patient-specific 3-dimensionally printed models for neurosurgical planning and education. Neurosurgical focus Panesar, S. S., Magnetta, M. n., Mukherjee, D. n., Abhinav, K. n., Branstetter, B. F., Gardner, P. A., Iv, M. n., Fernandez-Miranda, J. C. 2019; 47 (6): E12


    Advances in 3-dimensional (3D) printing technology permit the rapid creation of detailed anatomical models. Integration of this technology into neurosurgical practice is still in its nascence, however. One potential application is to create models depicting neurosurgical pathology. The goal of this study was to assess the clinical value of patient-specific 3D printed models for neurosurgical planning and education.The authors created life-sized, patient-specific models for 4 preoperative cases. Three of the cases involved adults (2 patients with petroclival meningioma and 1 with trigeminal neuralgia) and the remaining case involved a pediatric patient with craniopharyngioma. Models were derived from routine clinical imaging sequences and manufactured using commercially available software and hardware.Life-sized, 3D printed models depicting bony, vascular, and neural pathology relevant to each case were successfully manufactured. A variety of commercially available software and hardware were used to create and print each model from radiological sequences. The models for the adult cases were printed in separate pieces, which had to be painted by hand, and could be disassembled for detailed study, while the model for the pediatric case was printed as a single piece in separate-colored resins and could not be disassembled for study. Two of the models were used for patient education, and all were used for presurgical planning by the surgeon.Patient-specific 3D printed models are useful to neurosurgical practice. They may be used as a visualization aid for surgeons and patients, or for education of trainees.

    View details for DOI 10.3171/2019.9.FOCUS19511

    View details for PubMedID 31786547

  • Nodular Leptomeningeal Disease - A Distinct Pattern of Recurrence After Post-Resection Stereotactic Radiosurgery for Brain Metastases: A Multi-Institutional Study of Inter-Observer Reliability. International journal of radiation oncology, biology, physics Turner, B. E., Prabhu, R. S., Burri, S. H., Brown, P. D., Pollom, E. L., Milano, M. T., Weiss, S. E., Iv, M. n., Fischbein, N. n., Soliman, H. n., Lo, S. S., Chao, S. T., Cox, B. W., Murphy, J. D., Li, G. n., Gephart, M. H., Nagpal, S. n., Atalar, B. n., Azoulay, M. n., Thomas, R. n., Tillman, G. n., Durkee, B. Y., Shah, J. L., Soltys, S. G. 2019


    For brain metastases, surgical resection with postoperative stereotactic radiosurgery (SRS) is an emerging standard of care. Postoperative cavity SRS is associated with a specific, under-recognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease (cLMD). We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve inter-rater reliability (IRR) and validity in diagnosing LMD.Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system (CNS) expertise, completed a two-phase survey that included MRI imaging and treatment information for 30 patients. In the "pre-training" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "post-training" phase and relabeled the 30 cases using the 4 following labels: LR, DR, cLMD, nLMD.Inter-rater reliability (IRR) increased 34% after training (Fleiss' Kappa K=0.41 to K=0.55, p<0.001). IRR increased most among non-CNS specialists (+58%, p<0.001). Prior to training, IRR was lowest for LMD (K=0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD.This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training.

    View details for DOI 10.1016/j.ijrobp.2019.10.002

    View details for PubMedID 31605786

  • Macrophage Exclusion after Radiation Therapy (MERT): A First in Human Phase I/II Trial using a CXCR4 Inhibitor in Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Thomas, R. P., Nagpal, S. n., Iv, M. n., Soltys, S. G., Bertrand, S. n., Pelpola, J. S., Ball, R. L., Yang, J. n., Sundaram, V. n., Lavezo, J. L., Born, D. E., Vogel, H. n., Brown, J. M., Recht, L. n. 2019


    Preclinical studies have demonstrated that post-irradiation tumor revascularization is dependent on a stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-driven process in which myeloid cells are recruited from bone marrow. Blocking this axis results in survival improvement in preclinical models of solid tumors, including glioblastoma (GBM). We conducted a phase I/II study to determine the safety and efficacy of Macrophage Exclusion after Radiation Therapy (MERT) using the reversible CXCR4 inhibitor plerixafor in newly diagnosed glioblastoma patients.We enrolled 9 patients to the phase I study and an additional 20 patients to phase II using a modified toxicity probability interval (mTPI) design. Plerixafor was continuously infused intravenously via PICC line for four consecutive weeks beginning at day 35 of conventional treatment with concurrent chemo-radiation. Blood serum samples were obtained for pharmacokinetic analysis. Additional studies included relative cerebral blood volume (rCBV) analysis using MRI and histopathology analysis of recurrent tumors.Plerixafor was well tolerated with no drug-attributable grade 3 toxicities observed. At the maximum dose of 400 µg/kg/day, biomarker analysis found suprathreshold plerixafor serum levels and an increase in plasma SDF-1 levels. Median overall survival was 21.3 months (95% Confidence Interval (CI) 15.9, NA) with a progression-free survival of 14.5 months (95% CI 11.8, NA). MRI and histopathology support the mechanism of action to inhibit post-irradiation tumor revascularization.Infusion of the CXCR4 inhibitor plerixafor was well tolerated as an adjunct to standard chemo-irradiation in newly diagnosed GBM patients and improves local control of tumor recurrences.

    View details for DOI 10.1158/1078-0432.CCR-19-1421

    View details for PubMedID 31537527

  • Ferumoxytol-enhanced MRI for surveillance of pediatric cerebral arteriovenous malformations. Journal of neurosurgery. Pediatrics Huang, Y. n., Singer, T. G., Iv, M. n., Lanzman, B. n., Nair, S. n., Stadler, J. A., Wang, J. n., Edwards, M. S., Grant, G. A., Cheshier, S. H., Yeom, K. W. 2019: 1–8


    Children with intracranial arteriovenous malformations (AVMs) undergo digital DSA for lesion surveillance following their initial diagnosis. However, DSA carries risks of radiation exposure, particularly for the growing pediatric brain and over lifetime. The authors evaluated whether MRI enhanced with a blood pool ferumoxytol (Fe) contrast agent (Fe-MRI) can be used for surveillance of residual or recurrent AVMs.A retrospective cohort was assembled of children with an established AVM diagnosis who underwent surveillance by both DSA and 3-T Fe-MRI from 2014 to 2016. Two neuroradiologists blinded to the DSA results independently assessed Fe-enhanced T1-weighted spoiled gradient recalled acquisition in steady state (Fe-SPGR) scans and, if available, arterial spin labeling (ASL) perfusion scans for residual or recurrent AVMs. Diagnostic confidence was examined using a Likert scale. Sensitivity, specificity, and intermodality reliability were determined using DSA studies as the gold standard. Radiation exposure related to DSA was calculated as total dose area product (TDAP) and effective dose.Fifteen patients were included in this study (mean age 10 years, range 3-15 years). The mean time between the first surveillance DSA and Fe-MRI studies was 17 days (SD 47). Intermodality agreement was excellent between Fe-SPGR and DSA (κ = 1.00) but poor between ASL and DSA (κ = 0.53; 95% CI 0.18-0.89). The sensitivity and specificity for detecting residual AVMs using Fe-SPGR were 100% and 100%, and using ASL they were 72% and 100%, respectively. Radiologists reported overall high diagnostic confidence using Fe-SPGR. On average, patients received two surveillance DSA studies over the study period, which on average equated to a TDAP of 117.2 Gy×cm2 (95% CI 77.2-157.4 Gy×cm2) and an effective dose of 7.8 mSv (95% CI 4.4-8.8 mSv).Fe-MRI performed similarly to DSA for the surveillance of residual AVMs. Future multicenter studies could further investigate the efficacy of Fe-MRI as a noninvasive alternative to DSA for monitoring AVMs in children.

    View details for DOI 10.3171/2019.5.PEDS1957

    View details for PubMedID 31323627

  • Physiological motion of the optic chiasm and its impact on stereotactic radiosurgery dose. The British journal of radiology Xiang, M. n., Chan, C. n., Wang, L. n., Jani, K. n., Holdsworth, S. J., Iv, M. n., Pollom, E. n., Soltys, S. n. 2019: 20190170


    Avoidance of radiation-induced optic neuropathy (RION) from stereotactic radiosurgery (SRS) requires precise anatomical localization; however, no prior studies have characterized the physiologic motion of the optic chiasm. We measured the extent of chiasm motion and its impact on SRS dose.In this cross-sectional study, serial magnetic resonance imaging was performed in multiple planes in 11 human subjects without optic pathway abnormalities to determine chiasm motion across time. Subsequently, the measured displacement was applied to the hypothetical chiasm dose received in 11 patients treated with SRS to a perichiasmatic lesion.On sagittal images, the average anteroposterior chiasm displacement was 0.51 mm (95 % confidence interval [CI] 0.27 - 0.75 mm), and the average superior-inferior displacement was 0.48 mm (95% CI 0.22 - 0.74 mm). On coronal images, the average superior-inferior displacement was 0.42 mm (95% CI 0.13 - 0.71 mm), and the average lateral displacement was 0.75 mm (95% CI 0.42 - 1.08 mm). In 11 patients who underwent SRS to a perichiasmatic lesion, the average displacements increased the maximum chiasm dose (Dmax) by a mean of 14 % (range 6 - 23 %; p < 0.001).Average motion of the optic chiasm was approximately 0.50 - 0.75 mm, which increased chiasm Dmax by a mean of 14 %. In the occasional patient with higher-than-average chiasm motion in a region of steep dose gradient, the increase in chiasm Dmax and risk of RION could be even larger. Similarly, previously reported chiasm dose constraints may underestimate the true dose received during radiosurgery.To limit the risk of RION, clinicians may consider adding a 0.50 - 0.75 mm expansion to the chiasm avoidance structure.

    View details for PubMedID 31067077

  • Pediatric Stroke Imaging PEDIATRIC NEUROLOGY Khalaf, A., Iv, M., Fullerton, H., Wintermark, M. 2018; 86: 5–18
  • Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M. n., Wintermark, M. n., Zaharchuk, G. n., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018


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

    View details for PubMedID 29555872

  • High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations. Journal of neurosurgery. Pediatrics Iv, M. n., Choudhri, O. n., Dodd, R. L., Vasanawala, S. S., Alley, M. T., Moseley, M. n., Holdsworth, S. J., Grant, G. n., Cheshier, S. n., Yeom, K. W. 2018: 1–10


    OBJECTIVE Patients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters' grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

    View details for PubMedID 29882734

  • Conus Medullaris Dural Arteriovenous Fistula Arising From the Artery of the Filum Terminale: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Lamsam, L. n., Quon, J. n., Fischbein, N. n., Iv, M. n., Dodd, R. n., Ratliff, J. n. 2018

    View details for PubMedID 29444295

  • Practical Pearl: Use of MRI to Differentiate Pseudo-subarachnoid Hemorrhage from True Subarachnoid Hemorrhage. Neurocritical care Ho, A. L., Sussman, E. S., Pendharkar, A. V., Iv, M. n., Hirsch, K. G., Fischbein, N. J., Dodd, R. L. 2018

    View details for PubMedID 29948997

  • Lobular capillary hemangioma of the mandible: A case report. Clinical imaging Chan, C. n., Iv, M. n., Fischbein, N. n., Dahmoush, H. n. 2018; 50: 246–49


    Lobular capillary hemangiomas are acquired benign vascular neoplasms which typically affect the skin and mucous membranes. While these lesions commonly involve the head and neck, particularly the oral cavity, there are no reports in the literature of lobular capillary hemangioma arising from the mandible. The diagnosis of such a rare entity can therefore be challenging, especially as it may mimic more aggressive lesions, including malignancy. We present a rare case of an 8-year-old male with a lobular capillary hemangioma of the mandible, highlighting its imaging features and discussing the differential diagnosis of primary mandibular lesions in the pediatric population.

    View details for PubMedID 29704808

  • Tumefactive demyelination associated with developmental venous anomaly: Report of two cases CLINICAL IMAGING Ma, M., Chen, J. Y., Plowey, E. D., Fischbein, N., Iv, M. 2017; 43: 194-198


    We present two cases of tumefactive demyelination (TD) occurring in close association with a developmental venous anomaly (DVA). Our purpose is to describe the association between demyelinating lesions and venous anomalies, as only one case of TD associated with a DVA has been published in the literature. Appropriate recognition of this "do not touch" lesion may avoid invasive and potentially harmful procedures such as biopsy or resection.

    View details for DOI 10.1016/j.clinimag.2017.02.012

    View details for Web of Science ID 000401298400039

    View details for PubMedID 28364723

  • Resting-State BOLD MRI for Perfusion and Ischemia. Topics in magnetic resonance imaging Kroll, H., Zaharchuk, G., Christen, T., Heit, J. J., Iv, M. 2017; 26 (2): 91-96


    Advanced imaging techniques including computed tomography (CT) angiography, CT perfusion, magnetic resonance (MR) angiography, MR with diffusion- and perfusion-weighted imaging, and, more recently, resting-state BOLD (Blood Oxygen Level Dependent) functional MRI (rs-fMRI) are increasingly used to evaluate patients with acute ischemic stroke. Advanced imaging allows for identification of patients with ischemic stroke and determination of the size of infarcted and potentially salvageable tissue, all of which yield crucial information for proper stroke management. The addition of rs-fMRI for ischemia adds information at the microvascular level, thereby improving the understanding of pathophysiologic mechanisms of impaired cerebral perfusion and tissue oxygenation beyond the known concepts at the macrovascular level. As such, it may further delineate functional and dysfunctional neuronal networks, guide stroke interventions, and improve prognosis and monitoring of patient outcomes.

    View details for DOI 10.1097/RMR.0000000000000119

    View details for PubMedID 28277456

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


    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

  • Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous Anomalies. Journal of neuroimaging : official journal of the American Society of Neuroimaging Zhang, M. n., Telischak, N. A., Fischbein, N. J., Steinberg, G. K., Marks, M. n., Zaharchuk, G. n., Heit, J. J., Iv, M. n. 2017


    Transitional venous anomalies (TVAs) are rare cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but demonstrate early arteriovenous shunting on digital subtraction angiography (DSA) without the parenchymal nidus of arteriovenous malformations (AVMs). We investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI) can distinguish brain TVAs from DVAs and guide their clinical management.We conducted a single-center retrospective review of patients with brain parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories and follow-up information were obtained. Two readers assessed ASL signal location relative to the vascular lesion on MRI and, if available, the presence of arteriovenous shunting on DSA.Thirty patients with DVA-like lesions with increased ASL signal were identified. Clinical symptoms prompted MRI evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten percent presented with acute symptoms, only one of whom presented with hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50% in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater agreement was very good (κ = .81-1.0, P < .001).A DVA-like lesion with increased ASL signal likely represents a TVA with arteriovenous shunting. Our study indicates that these lesions are usually incidentally detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful tool to identify TVAs and guide further management of patients with TVAs.

    View details for PubMedID 29205641

  • 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


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

    View details for DOI 10.1148/rg.2017160035

    View details for Web of Science ID 000397205200021

  • Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment. Neuro-oncology Liu, T. T., Achrol, A. S., Mitchell, L. A., Rodriguez, S. A., Feroze, A., Kim, C., Chaudhary, N., Gevaert, O., Stuart, J. M., Harsh, G. R., Chang, S. D., Rubin, D. L. 2016


    In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated.A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022).Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

    View details for DOI 10.1093/neuonc/now270

    View details for PubMedID 28007759

  • Central Nervous System Perfusion Patterns in Childhood Langerhans Cell Histiocytosis Yeom, K., Kim, C., Iv, M., Jeng, M. WILEY-BLACKWELL. 2016: S36
  • 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


    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

  • Intensity-Corrected Dual-Echo Echo-Planar Imaging (DE-EPI) for Improved Pediatric Brain Diffusion Imaging PLOS ONE Yeom, K. W., Straka, M., Iv, M., Moseley, M. E., Barnes, P. D., Skare, S., Holdsworth, S. J. 2015; 10 (6)


    Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two 'echo images' for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.

    View details for DOI 10.1371/journal.pone.0129325

    View details for Web of Science ID 000356327000065

    View details for PubMedID 26069959

  • Congenital Brain Malformations in the Neonatal and Early Infancy Period SEMINARS IN ULTRASOUND CT AND MRI Kim, C., Yeom, K. W., Iv, M. 2015; 36 (2): 97-119


    Congenital brain malformations are a major cause of morbidity and mortality in pediatric patients who are younger than 2 years. Optimization of patient care requires accurate diagnosis, which can be challenging as congenital brain malformations include an extensive variety of anomalies. Radiologic imaging helps to identify the malformations and to guide management. Understanding radiologic findings necessitates knowledge of central nervous system embryogenesis. This review discusses the imaging of congenital brain malformations encountered in patients who are younger than 2 years in the context of brain development.

    View details for DOI 10.1053/j.sult.2015.01.003

    View details for PubMedID 26001941

  • Imaging Neck Masses in the Neonate and Young Infant SEMINARS IN ULTRASOUND CT AND MRI Tranvinh, E., Yeom, K. W., Iv, M. 2015; 36 (2): 120-137


    Head and neck masses occurring in the neonatal period and early infancy consist of vascular tumors, vascular malformations, benign and malignant soft tissue tumors, and other developmental lesions. Although some lesions can be diagnosed on clinical grounds, others can only be diagnosed by imaging. Beyond diagnosis, imaging plays a significant role in evaluating the location and extent of a lesion for possible intervention. In this article, we review the clinical presentation and imaging appearance of common and rare masses that may be encountered in this age group. We also highlight current treatment strategies for specific lesions.

    View details for DOI 10.1053/j.sult.2015.01.004

    View details for Web of Science ID 000355575300003

    View details for PubMedID 26001942

  • Association of developmental venous anomalies with perfusion abnormalities on arterial spin labeling and bolus perfusion-weighted imaging. Journal of neuroimaging Iv, M., Fischbein, N. J., Zaharchuk, G. 2015; 25 (2): 243-250


    To investigate the frequency and characteristics of developmental venous anomaly (DVA)-associated perfusion abnormalities on arterial spin labeling (ASL) and bolus perfusion-weighted imaging (PWI) and discuss their potential causes.We reviewed brain MR reports to identify all DVAs reported on studies performed between 2009 and 2012. DVA location and findings on PWI and/or ASL imaging were assessed by visual inspection. Sizes of DVAs were categorized as small (<15 mm), medium (15-25 mm), and large (>25 mm). For ASL, signal in the DVA, surrounding parenchyma, or associated draining vein was recorded. For PWI, changes on hemodynamic maps (cerebral blood volume [CBV], cerebral blood flow [CBF], mean transit time [MTT], and normalized time-to-peak of the residue function [Tmax]) were evaluated. Coexisting vascular malformations in association with DVAs were also identified.Six hundred and fifty-two DVAs were identified in 632 subjects. Of these, 121 underwent both perfusion modalities, 15 only PWI, and 127 only ASL. ASL abnormalities were seen in 21/248 (8%), including signal in a draining vein (2/21, 10%), in the DVA (11/21, 52%), and in the parenchyma (8/21, 38%). On PWI, the majority of DVAs demonstrated abnormalities (108/136, 79%), typically increased CBF, CBV, MTT, and Tmax. There was no association between DVA size and presence of ASL signal (P = .836). Borderline statistical significance was found between DVA size and presence of PWI abnormality (P = .046). No relationship was found between the presence of a coexisting vascular malformation and presence of ASL (P = .468) or PWI abnormality (P = .745).Perfusion changes with DVAs are common on PWI but uncommon on ASL. PWI findings are expected based on the anatomy and physiology of DVAs and are accentuated by gradient echo acquisition. DVAs with intrinsic ASL signal or signal in draining veins may be associated with arteriovenous shunting (transitional lesions).

    View details for DOI 10.1111/jon.12119

    View details for PubMedID 24717021

  • Imaging Manifestations of Primary and Disseminated Coccidioidomycosis Applied Radiology Gupta, N. A., Iv, M., Pandit, R. P., Patel, M. R. 2015; 44 (2): 9-21
  • Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era. Clinical lung cancer Riess, J. W., Nagpal, S., Iv, M., Zeineh, M., Gubens, M. A., Ramchandran, K., Neal, J. W., Wakelee, H. A. 2014; 15 (3): 202-206


    Leptomeningeal carcinomatosis (LM) is a severe complication of non-small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM.Patients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3.LM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007).In this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication.

    View details for DOI 10.1016/j.cllc.2013.12.009

    View details for PubMedID 24524822

  • Imaging Spectrum of CNS Coccidioidomycosis: Prevalence and Significance of Concurrent Brain and Spinal Disease AMERICAN JOURNAL OF ROENTGENOLOGY Lammering, J. C., Iv, M., Gupta, N., Pandit, R., Patel, M. R. 2013; 200 (6): 1334-1346


    The purpose of this study was to evaluate the prevalence and significance of concurrent coccidioidal brain and intraspinal disease.We conducted a retrospective imaging review of 23 patients with proven coccidioidal CNS meningitis.All patients had intracranial abnormalities, and 86% (19/22) who underwent spinal imaging had signs of intraspinal disease, including leptomeningeal enhancement (84%), arachnoiditis (63%), and cord signal abnormalities (37%); seven of 15 patients (47%) who underwent myelography had complete spinal blocks.The high prevalence of concurrent brain and intraspinal coccidioidomycosis supports a low threshold for spinal imaging.

    View details for DOI 10.2214/AJR.12.9264

    View details for Web of Science ID 000319447700046

    View details for PubMedID 23701073

  • Comparison of Readout-Segmented Echo-Planar Imaging (EPI) and Single-Shot EPI in Clinical Application of Diffusion-Weighted Imaging of the Pediatric Brain. AJR. American journal of roentgenology Yeom, K. W., Holdsworth, S. J., Van, A. T., Iv, M., Skare, S., Lober, R. M., Bammer, R. 2013; 200 (5): W437-43

    View details for DOI 10.2214/AJR.12.9854

    View details for PubMedID 23617511

  • Informatics in Radiology Use of a Macro Scripting Editor to Facilitate Transfer of Dual-Energy X-ray Absorptiometry Reports into an Existing Departmental Voice Recognition Dictation System RADIOGRAPHICS Iv, M., Patel, M. R., Santos, A., Kang, Y. S. 2011; 31 (4): 1181-1189


    The process of verbally reporting or manually retyping numeric data generated at dual-energy x-ray absorptiometry (DXA) involves numerous pitfalls. With use of a macro scripting editor, a customized macro was created to automate the transfer of data generated by a DXA scanner into a structured voice recognition dictation system without requiring radiologists to type in a medical record number or accession number to identify the study. A preliminary report is generated with use of software for a DXA unit and a customized template that includes numeric and qualitative assessments of osteoporosis as well as data from prior studies if available. A customized macro is then invoked by the macro scripting editor, which selectively transfers the report from the draft document into the voice recognition dictation system, thereby producing a final structured diagnostic report. All of the radiologists surveyed to evaluate this automated method reported ease of software use and greater efficiency in report production. In addition, a random audit of the 800 DXA scans that have been reported with this technique demonstrated no reports generated under an incorrect accession number and no incorrect transfer of data. Automated DXA reporting is now the preferred method of dictation at the authors' institution and represents an inexpensive, accurate, and customizable means of DXA reporting.

    View details for DOI 10.1148/rg.314105741

    View details for Web of Science ID 000292867000023

    View details for PubMedID 21546554

  • Left ventricular ejection fraction using 64-slice CT coronary angiography and new evaluation software: initial experience BRITISH JOURNAL OF RADIOLOGY Krishnam, M. S., Tomasian, A., Iv, M., Ruehm, S. G., Salieh, R., Panknin, C., Goldin, J. G. 2008; 81 (966): 450-455


    The purpose of this study was to evaluate the feasibility and reliability of software-based quantification of left ventricular function using 64-slice CT coronary angiography. Data were collected from 26 subjects who underwent a 64-slice coronary CT angiography study. Two volumetric data sets at end diastole and end systole were reconstructed from each scan by means of retrospective electrocardiogram gating. Data sets were evaluated with a prototype of now commercially available software (Syngo Circulation I; Siemens Medical Solutions, Erlangen, Germany), which automatically segments the blood volume in the left ventricle after the user defines the mitral valve plane and any point within the ventricle. After segmentation of the blood pool in end systole and end diastole, the software automatically measures end systolic and end diastolic volume and calculates stroke volume and ejection fraction (EF). Two readers processed all CT data sets twice to assess for intra- and inter-observer variation. In addition, CT EF measurements were compared with those obtained by clinical echocardiography. Intra-observer variation for the calculated EF with CT were 13.6% and 15.6% for Readers 1 and 2, respectively. No significant difference in left ventricular functional parameters on CT existed between the readers (p > 0.05). A Bland-Altman plot revealed a slight mean difference between EF measurements on CT and echocardiography, with all differences falling within two standard deviations of the mean in the setting of wide limits of agreement. In conclusion, assessment of left ventricular EF from CT coronary data using the new analysis software is rapid and easy. The software is user-friendly and provides good reproducibility for EF measurements with CT.

    View details for DOI 10.1259/bjr/54748900

    View details for Web of Science ID 000257011800004

    View details for PubMedID 18347027

  • Cardiac hemangioma: Features on cardiovascular magnetic resonance JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE Tomasian, A., Iv, M., Lai, C., Jalili, M., Krishnam, M. S. 2007; 9 (6): 873-876


    We present a case of cardiac capillary hemangioma in a patient who presented with a history of recurrent episodes of syncope. Cardiovascular magnetic resonance played an important role in the diagnosis of cardiac hemangioma in our patient.

    View details for DOI 10.1080/10976640701693642

    View details for Web of Science ID 000251394000007

    View details for PubMedID 18066746

  • Pyridines in cigarette smoke inhibit hamster oviductal functioning in picomolar doses REPRODUCTIVE TOXICOLOGY Riveles, K., Iv, M., Arey, J., Talbot, P. 2003; 17 (2): 191-202


    Past studies showed that chemicals in cigarette smoke inhibit oviductal functioning in vivo and in vitro. The purposes of this study were to identify individual toxicants in cigarette smoke solutions that inhibit various aspects of oviductal functioning and to determine their effective doses using in vitro bioassays. Solid phase extraction and gas chromatography-mass spectrometry (GC-MS) were used to identify individual chemicals in mainstream (MS) and sidestream (SS) cigarette smoke solutions. Pyridines, which were the most abundant class of compounds identified, were purchased, assayed for purity, and tested in dose-response studies on hamster oviducts. The lowest observable adverse effect level was determined for each pyridine derivative using the oocyte pick-up rate, ciliary beat frequency, and infundibular muscle contraction assays. 2-Methylpyridine, 4-methylpyridine, 2-ethylpyridine, 3-ethylpyridine, and 4-vinylpyridine were inhibitory at picomolar concentrations in all assays. This work shows picomolar doses of pyridines with single methyl or ethyl substitutions significantly inhibit oviductal functioning raising questions regarding the safety of these compounds.

    View details for DOI 10.1016/S0890-6238(02)00150-8

    View details for Web of Science ID 000182233800007

    View details for PubMedID 12642152