About

Matthew K Schindler, MD, PhD, is an Assistant Professor of Neurology at the University of Pennsylvania and also serves as an Assistant Professor in the Department of Neurology at Pennsylvania Hospital. His educational background includes a BA in Philosophy, Neuroscience, and Cognitive Psychology from Washington University in 2001, and an MD/PhD in Neuroscience from Wake Forest University School of Medicine in 2010. His clinical expertise focuses on Multiple Sclerosis and neuroinflammatory diseases. His research expertise encompasses MRI techniques, including ultra high-field (7T) MRI, and neuroinflammation. Dr. Schindler's work involves investigating mechanisms and management of neurological complications, neuroinflammatory processes, and lesion development in multiple sclerosis, utilizing advanced imaging modalities to improve diagnosis and understanding of these conditions.

Research topics

• Medicine
• Radiology
• Nuclear medicine
• Psychology
• Immunology

Selected publications

• Diagnostic performance of central vein sign and paramagnetic rim lesion integration for multiple sclerosis

  Multiple Sclerosis Journal · 2026-04-20

  articleOpen access

  Background: The central vein sign (CVS) and the paramagnetic rim lesion (PRL) are neuroimaging biomarkers of multiple sclerosis (MS). Objectives: To determine the diagnostic performance of CVS and PRL integration in people presenting for initial diagnostic evaluation of MS. Methods: Adults with clinical/radiological suspicion of MS, aged 18–65, with CVS and PRL assessment from the CentrAl Vein Sign in MS (CAVS-MS) pilot were included. Diagnostic performance of CVS and PRL combinations was evaluated, with 2017 McDonald criteria as the reference standard. Results: Seventy-eight participants were included (71% female, 86% white, 37 with MS). The combination of ⩾1 CVS and ⩾1 PRL demonstrated sensitivity/specificity of 0.76 (95% CI, 0.59, 0.88) and 0.93 (95% CI, 0.80, 0.98). The combination of ⩾6 CVS and ⩾1 PRL demonstrated sensitivity/specificity of 0.57 (95% CI, 0.39, 0.73) and 1.00 (95% CI, 0.91, 1.00). In those with cerebrospinal fluid testing ( n = 46, 24 with MS), ⩾6 CVS and ⩾1 PRL diagnostic specificity was 1.00 (95% CI, 0.85, 1.00), similar to that of oligoclonal bands and dissemination in space by magnetic resonance imaging (0.82 [95% CI, 0.60, 0.95]). Discussion: Integrating CVS and PRL represents potentially advantageous MS diagnostic biomarkers, with increased specificity and without substantial reduction in sensitivity.

  PublisherOA PDFDOI

• Multisequence 3-T Image Synthesis from 64-mT Low-Field-Strength MRI Using Generative Adversarial Networks in Multiple Sclerosis

  Radiology · 2025-04-01 · 2 citations

  articleOpen access

  LowGAN, a generative model trained on paired high-resolution 3-T and lower-resolution portable 64-mT MRI data, improved low-field-strength image quality and brain morphometry and white matter lesion conspicuity in multiple sclerosis.

  PublisherOA PDFDOI

• Uncinate Fasciculus Lesion Burden and Anxiety in Multiple Sclerosis

  JAMA Network Open · 2025-04-14 · 4 citations

  articleOpen access

  Importance: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects 2.4 million people worldwide, and up to 60% experience anxiety. Objective: To investigate whether anxiety in MS is associated with white matter lesion burden in the uncinate fasciculus (UF). Design, Setting, and Participants: This was a retrospective case-control study of participants aged 18 years or older diagnosed with MS by an MS specialist and identified from the electronic medical record at a single-center academic medical specialty MS clinic in Pennsylvania. Participants received research-quality 3-Tesla magnetic resonance neuroimaging as part of MS clinical care from January 6, 2010, to February 14, 2018. After excluding participants with poor image quality, participants were stratified into 3 groups naturally balanced in age and sex: (1) MS without anxiety, (2) MS with mild anxiety, and (3) MS with severe anxiety. Analyses were performed from June 1 to September 30, 2024. Exposure: Anxiety diagnosis and anxiolytic medication. Main Outcomes and Measures: Main outcomes were whether patients with severe anxiety had greater lesion burden in the UF than those without anxiety and whether higher anxiety severity was associated with greater UF lesion burden. Generalized additive models were used, with the burden of lesions (eg, proportion of fascicle impacted) within the UF as the outcome measure and sex, spline of age, and total brain volume as covariates. Results: Among 372 patients with MS (mean [SD] age, 47.7 [11.4] years; 296 [80%] female), after anxiety phenotype stratification, 99 (27%) had no anxiety (mean [SD] age, 49.4 [11.7] years; 74 [75%] female), 249 (67%) had mild anxiety (mean [SD] age, 47.1 [11.1] years; 203 [82%] female), and 24 (6%) had severe anxiety (mean [SD] age, 47.0 [12.2] years; 19 [79%] female). UF burden was higher in patients with severe anxiety compared with no anxiety (T = 2.01 [P = .047]; Cohen f2, 0.19 [95% CI, 0.08-0.52]). Additionally, higher mean UF burden was associated with higher severity of anxiety (T = 2.09 [P = .04]; Cohen f2, 0.10 [95% CI, 0.05-0.21]). Conclusions and Relevance: In this case-control study of UF lesion burden and anxiety in MS, overall lesion burden in the UF was associated with the presence and severity of anxiety. Future studies linking white matter lesion burden in the UF with treatment prognosis are warranted.

  PublisherOA PDFDOI

• Clinical Phenotyping of Long <scp>COVID</scp> Patients Evaluated in a Specialized Neuro‐<scp>COVID</scp> Clinic

  Annals of Clinical and Translational Neurology · 2025-04-08 · 3 citations

  articleOpen accessSenior author

  OBJECTIVE: To report Long COVID characteristics and longitudinal courses of patients evaluated between 4/14/21-4/14/22 at the University of Pennsylvania Neurological COVID Clinic (PNCC), including clinical symptoms, neurological examination findings, and neurocognitive screening tests from a standardized PNCC neurological evaluation approach. METHODS: This is a retrospective cross-sectional and longitudinal study in a single-center tertiary care academic center. Participants include 240 patients with documented evidence of a positive SARS-CoV-2 PCR or antibody test who underwent initial evaluation and 182 patients with longitudinal follow-up. Main outcomes evaluated are patient demographics, duration of illness prior to self-reported improvement, and cognitive testing results-including the Montreal Cognitive Assessment (version 8.2) (MoCA) and Oral Trail Making Test-B (OTMT-B). RESULTS: The majority (73%) of patients did not require hospitalization for their acute COVID-19 symptoms. Frequent Long COVID complaints included headache (60%), dizziness/vertigo (40%), and disturbance of taste/smell (40%). Almost all (94%) patients reported cognitive symptoms, and over 30% of patients had abnormal scores on cognitive testing. Severe infection, fewer years of education level, and non-White race were found to be statistically associated with an increased likelihood of having abnormal scores on cognitive testing. Neuroimaging and clinical laboratory testing were largely not informative for patient care. Sixty-two percent of patients with follow-up visits self-reported improvement in their primary neurological complaint within 1 year of evaluation. INTERPRETATION: Performance on standardized cognitive screening tests may not be consistent with frequently reported cognitive complaints in Long COVID patients. The most common clinical trajectory was self-reported improvement in the primary neurological symptom.

  PublisherOA PDFDOI

• Frequency and Diagnostic Implications of Paramagnetic Rim Lesions in People Presenting for Diagnosis to a Multiple Sclerosis Clinic

  Neurology · 2025-09-02 · 5 citations

  article

  BACKGROUND AND OBJECTIVES: Paramagnetic rim lesions (PRLs) are a well-established imaging biomarker of chronic active multiple sclerosis (MS) lesions. PRLs have been shown to be highly specific for MS (∼90% specificity), and their prevalence has been estimated to be approximately 50% in patients with clinically established diagnoses of MS. In this study, we evaluated the frequency and diagnostic value of PRLs in patients at first clinical presentation. METHODS: Adults age 18-64 years presenting with clinical symptoms or radiologic suspicion of demyelinating disease referred to academic specialty MS centers without a definitive diagnosis were prospectively enrolled in a multicenter, cross-sectional, observational study. Phase images from high-resolution 3D echo-planar imaging were acquired on 3-tesla brain MRI and evaluated for PRLs by 3 independent raters, blinded to diagnosis, with adjudication from a fourth expert rater. Diagnostic performance of PRLs for a diagnosis of MS using the 2017 McDonald criteria as gold standard was evaluated using diagnostic thresholds based on the presence of at least 1 PRL (≥1 PRL) or at least 2 PRLs (≥2 PRLs). RESULTS: = 0.03). DISCUSSION: PRLs are highly prevalent early in patients with MS at the time of first clinical presentation and can differentiate MS from mimics with high accuracy.

  PublisherDOI

• NOE Imaging of Multiple Sclerosis Subjects at 7T Detects Diffuse Contrast Changes

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: While standard to the diagnosis of multiple sclerosis (MS), conventional structural MRI cannot provide detailed information on changes in lipid metabolism. Goal(s): To utilize NOE imaging to investigate changes between MS and healthy control subjects. Approach: NOE imaging was performed on 15 MS and 10 healthy subjects in conjunction with a multi-pool Lorentzian line fitting model to produce several contrasts including MT, APT, amine, and rNOE. Results: Statistically significant contrast decreases were observed in both the amine (15.3% in NAWM) and rNOE (11.4% in NAWM and 10.6% in NAGM) pools. Impact: This 7T NOE imaging method for patients with MS can provide complementary lipid metabolic information to standard structural imaging and can yield improved diagnostic outcomes for this patient population.

  PublisherDOI

• 31. Association Between Anxiety Severity and Uncinate Fasciculus Lesion Burden in Multiple Sclerosis

  Biological Psychiatry · 2025-04-09

  article
  PublisherDOI

• Depression as a Disease of White Matter Network Disruption: Learning From Multiple Sclerosis

  Biological Psychiatry · 2025-11-01

  articleOpen access
  PublisherOA PDFDOI

• Automated segmentation of multiple sclerosis lesions, paramagnetic rims, and central vein sign on MRI provides reliable diagnostic biomarkers

  Imaging Neuroscience · 2025-01-01 · 2 citations

  articleOpen access

  Multiple sclerosis (MS) is characterized by central nervous system lesions detectable via MRI. Existing diagnostic criteria incorporate presence of white matter lesions, but specificity can be improved using MS-specific imaging biomarkers, including paramagnetic rim lesions (PRLs) and central vein sign (CVS). However, manual segmentation of lesions, PRLs, and CVS is time-consuming and subjective. We propose a fully-automated joint segmentation method called Automated Lesion, PRL, and CVS Analysis (ALPaCA). We trained ALPaCA using subject-level cross-validation on 47 adults with MS and 50 adults with radiological MS mimics. ALPaCA uses a voxel-wise lesion segmentation method to propose a large set of lesion candidates. Lesion candidates are input into a multi-contrast, multi-label 3D convolutional neural network as 3D patches to produce lesion, PRL, and CVS predictions. When multiple lesions exist within a patch, an attention mechanism identifies which lesion candidate to classify. At the lesion level, ALPaCA achieves cross-validation areas under the receiver operating characteristic curve (AUROCs) of 0.95, 0.91, and 0.87 for lesion, PRL, and CVS classification, outperforming previous methods (all p < 0.001). Correlations between subject-level ALPaCA lesion and PRL scores with manual counts are higher than those of previous methods (p < 0.001; p = 0.03). Subject-level ALPaCA PRL and CVS scores are highly associated with MS in logistic regressions, when controlling for age and sex (p < 0.001). ALPaCA allows for fully-automated simultaneous segmentation of MS lesions, PRLs, and CVS using clinically-feasible scans. These segmentations outperform existing methods at the lesion and subject level.

  PublisherOA PDFDOI

• Reliability of Central Vein Sign Imaging With 3T FLAIR* in a Multicenter Study

  Journal of Neuroimaging · 2025-01-01 · 3 citations

  article

  ABSTRACT Background and Purpose The central vein sign (CVS) is a diagnostic imaging biomarker for multiple sclerosis (MS). FLAIR* is a combined MRI contrast that provides high conspicuity for CVS at 3 Tesla (3T), enabling its sensitive and accurate detection in clinical settings. This study evaluated whether CVS conspicuity of 3T FLAIR* is reliable across imaging sites and MRI vendors and whether gadolinium (Gd) contrast increases CVS conspicuity. Methods A cross‐sectional, multicenter study recruited adults referred for possible diagnosis of MS at 10 sites. FLAIR* contrast was generated using high‐resolution T2*‐weighted (acquired pre‐ and post‐injection of Gd) and T2‐weighted fluid‐attenuated inversion recovery (T2‐FLAIR) brain images at 3T from two MRI vendors. Lesions and veins were segmented to compute lesion‐to‐vein contrast‐to‐noise ratio (CNR lesion‐to‐vein ), a quantitative measure of CVS conspicuity. CNR lesion‐to‐vein measures for pre‐ and post‐Gd FLAIR* were compared across sites and vendors. Results Eighty‐seven participants from nine sites were included in the analysis. There was no significant difference in mean CNR lesion‐to‐vein between sites for pre‐Gd ( p ‐value = 0.07) or post‐Gd ( p ‐value = 0.27) FLAIR*. There were also no significant differences between vendors for pre‐Gd ( p ‐value = 0.10) or post‐Gd ( p ‐value = 0.31) FLAIR*. Patient‐level pairwise differences in CNR lesion‐to‐vein between pre‐Gd and post‐Gd FLAIR* revealed a significant increase for post‐Gd FLAIR* ( p ‐value &lt; 0.001). Conclusions CVS conspicuity on 3T FLAIR* is consistent across imaging sites and MRI vendors. Moreover, Gd‐based contrast agent significantly improved CVS conspicuity on 3T FLAIR*. These findings support the implementation of FLAIR* in clinical settings for MS.

  PublisherDOI

Frequent coauthors

• Daniel S. Reich

  National Institutes of Health

  127 shared

• Pascal Sati

  Cedars-Sinai Medical Center

  82 shared

• Russell T. Shinohara

  57 shared

• Amit Bar‐Or

  University of Pennsylvania

  48 shared

• Peter A. Calabresi

  National Institutes of Health

  40 shared

• Andrew Solomon

  National Institute of Neurological Disorders and Stroke

  40 shared

• Melissa L. Martin

  University of Pennsylvania

  39 shared

• Lynn Daboul

  National Institute of Mental Health

  38 shared

Education

• Fellow, Neuroimmunology/ Translational Neuroradiology Section

  NINDS/NIH

  2018

• Neurology Residency, Neurology

  University of Pennsylvania

  2014

• MD, PhD, Medical School

  Wake Forest University

  2010