About

Matthew Dylan Tisdall, PhD, is a Research Associate Professor of Radiology at the University of Pennsylvania's Perelman School of Medicine. He is the Co-Director of the Center for Advanced Magnetic Resonance Imaging and Spectroscopy within the Department of Radiology. His research focuses on advanced magnetic resonance imaging techniques, including prospective motion correction, brain morphometry, and high-resolution imaging. Dr. Tisdall has contributed to the development of methods to reduce bias and variance in brain imaging caused by subject motion, and his work includes the quantification of fetal motion and the improvement of imaging accuracy through innovative correction techniques. He holds a BA in Computer Science from the University of Waterloo and a PhD in Computer Science from Simon Fraser University, with additional certifications in research mentor training and culturally responsive mentoring from the Perelman School of Medicine.

Research topics

• Pathology
• Neuroscience
• Medicine
• Computer Science
• Artificial Intelligence
• Radiology
• Biology
• Psychology

Selected publications

• Optimizing scan efficiency of T1-weighted imaging for whole-brain intracranial vessel wall imaging

  medRxiv · 2025-06-24

  preprintOpen accessSenior authorCorresponding

  Background: Clinical intracranial vessel wall imaging (VWI) requires high spatial resolution leading to long scan times and artifacts. Purpose: To accelerate standard-of-care (SOC) 3D T1-weighted variable-flip-angle turbo-spin-echo (VFA-TSE) sequence with parallel imaging (Generalized Autocalibrating Partially Parallel Acquisitions, GRAPPA) using compressed sensing (CS) or Controlled Aliasing in Parallel Imaging Results in Higher Acceleration (CAIPIRINHA, CAIPI) with either standard or large field-of-view (FOV) configurations to reduce scan time, artifacts and accommodate head sizes. Study Type: Prospective study. Subjects: Ten healthy volunteers. Field Strength/Sequence: 3 Telsa, 20-channel head coil, T1-weighted VFA-TSE. Assessment: Accelerated sequences were compared to SOC GRAPPA (R=2), including standard FOV CAIPI (SFCAIPI, R=4), CS (SFCS7, R=7), and large FOV CS (LFCS7, R=7; LFCS10, R=10). Four neuroradiologists rated image quality (IQ) and signal-to-noise ratio (SNR) using a 4-point Likert scale. Scores of 3-4 were categorized as clinically interpretable. Lumen and wall diameters were measured. Statistical Analysis: Descriptive statistics are reported. McNemar's test compared proportions of IQ- and SNR-based clinically interpretable scans between relevant sequences of interest. Inter- and intra-rater reliabilities were calculated with Fleiss Kappa and weighted Cohen's Kappa, respectively. Lumen and wall diameters of the CS- and CAIPI-accelerated sequences were compared to SOC using paired t-tests. Results: SFCAIPI showed the lowest mean IQ and SNR scores. SFCS7 showed no significant difference in the proportion of IQ-based clinically interpretable scans compared to SFGRAPPA. When testing FOV, LFCS7 (35/40 scans; time of acquisition (TA)=3:45) showed a significantly higher proportion of IQ-based clinically interpretable scans compared to SFCS7 (27/40, p=0.03; TA=6:37). Upon increasing acceleration (R=10), there was no difference in the proportion of IQ-based clinically interpretable scans between LFCS7 and LFCS10 (36/40, p=0.65). Large FOV eliminated aliasing artifacts compared standard FOV (aliasing in 7 of 10 subjects). LFCS10 (TA=4:55) achieved a 50.6% reduction in TA relative to SFGRAPPA (TA=9:57). Conclusion: Large FOV CS VWI sequence with 10x acceleration achieved a 50.6% reduction in scan time while delivering image quality comparable to SOC standard FOV GRAPPA.

  PublisherOA PDFDOI

• A longitudinal data resource to study brain development and transdiagnostic variation in executive function

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-12

  preprintOpen access

  Abstract Executive function (EF) develops rapidly during adolescence. However, deficits in EF also emerge in adolescence, representing a transdiagnostic symptom associated with many forms of psychopathology. To promote transdiagnostic research on EF during development, we introduce a new data resource – the Penn Longitudinal Executive functioning in Adolescent Development study (Penn LEAD) – that combines longitudinal multimodal imaging data with rich clinical and cognitive phenotyping. These data include 225 imaging sessions from 132 individuals (8-16 years old at the time of enrollment) who are typically developing (27.3%), or meet criteria for attention-deficit hyperactivity disorder (20.5%) or the psychosis-spectrum (52.3%). In addition to phenotypic data from multiple cognitive tasks focused on EF, the study includes data from structural MRI, diffusion MRI, -back task fMRI, resting-state fMRI, and arterial spin-labeled MRI. Notably, all raw data, fully-processed derived data, and detailed quality control recommendations are publicly shared on OpenNeuro. We anticipate that such analysis-ready data will accelerate research on EF development in psychiatry.

  PublisherDOI

• Optimizing Accelerated Protocols for Clinical T1w Vessel Wall Imaging: A Comparison of Deep Learning, Compressed Sensing, and CAIPI Methods

  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

  articleSenior author

  Motivation: Clinical intracranial VWI requires high spatial resolution and effective blood/CSF suppression, leading to long scan times, motion artifacts, and increased patient burden. Goal(s): To evaluate optimized protocols for intracranial VWI using accelerated 3D T1w SPACE sequences. Approach: We evaluated DL, CS, and CAIPI acceleration on 20- and 64-channel coils to reduce scan times, comparing them to the clinical GRAPPA protocol. Results: The 64-channel CS protocol with 6x acceleration matched clinical image quality and SNR with reduced scan time. CS and DL sequences had similar image quality and SNR on the 64-channel coil, with DL showing better noise suppression on the 20-channel coil. Impact: This study optimizes intracranial VWI using 3D T1w SPACE with DL, CS, and CAIPI for 20- and 64-channel coils, achieving reduced scan times. The 64-channel CS (6x) matched clinical image quality, while DL provided superior noise suppression on 20-channel coils.

  PublisherDOI

• Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling

  Acta Neuropathologica Communications · 2025-05-28 · 3 citations

  articleOpen access

  Postmortem neuropathological examination, while the gold standard for diagnosing neurodegenerative diseases, often relies on limited regional sampling that may miss critical areas affected by Alzheimer's disease and related disorders. Ultra-high resolution postmortem MRI can help identify regions that fall outside the diagnostic sampling criteria for additional histopathologic evaluation. However, there are no standardized guidelines for integrating histology and MRI in a traditional brain bank. We developed a comprehensive protocol for whole hemisphere postmortem 7T MRI-guided histopathological sampling with whole-slide digital imaging and histopathological analysis, providing a reliable pipeline for high-volume brain banking in heterogeneous brain tissue. Our method uses patient-specific 3D printed molds built from postmortem MRI, allowing standardized tissue processing with a permanent spatial reference frame. To facilitate pathology-MRI association studies, we created a semi-automated MRI to histology registration pipeline and developed a quantitative pathology scoring system using weakly supervised deep learning. We validated this protocol on a cohort of 29 brains with diagnosis on the AD spectrum that revealed correlations between cortical thickness and phosphorylated tau accumulation. This pipeline has broad applicability across neuropathological research and brain banking, facilitating large-scale studies that integrate histology with neuroimaging. The innovations presented here provide a scalable and reproducible approach to studying postmortem brain pathology, with implications for advancing diagnostic and therapeutic strategies for Alzheimer's disease and related disorders.

  PublisherOA PDFDOI

• Chi-Separation Detects Focal Changes in Cortical Paramagnetism Associated with Behavioral Variant Frontotemporal Dementia

  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

  articleSenior author

  Motivation: Syndrome-specific patterns of iron-rich cortical gliosis have been demonstrated postmortem in Frontotemporal Lobal Degeneration (FTLD) but have not been reliably detected in vivo. Goal(s): Evaluate whether Chi-separation and/or Quantitative Susceptibility Mapping (QSM) can reliably detect regional changes in cortical paramagnetism in behavioral variant frontotemporal dementia (bvFTD) patients. Approach: Patients with bvFTD, Alzheimer's disease, and one age-matched control were imaged at 3T using a multi-gradient echo sequence. Both QSM and Chi-separation maps were analyzed within DKT cortical regions associated with expected pathology. Results: Chi-separation paramagnetic maps showed statistically significant increases in anterior cingulate, a region of expected pathology. Impact: We show that chi-separations maps can be used to detect syndrome-specific paramagnetic cortical changes, demonstrating its ability to quantify the distribution of iron-rich gliosis in vivo in FTLD, which has previously only been reliably visualized postmortem.

  PublisherDOI

• Automatic Segmentation of Medial Temporal Lobe Subregions in Multi‐Scanner, Multi‐Modality Magnetic Resonance Imaging of Variable Quality

  Hippocampus · 2025-10-07

  articleOpen access

  Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, poor quality MR images can lead to unreliable segmentation of MTL subregions. Considering that different MRI contrast mechanisms and field strengths (jointly referred to as "modalities" here) offer distinct advantages in imaging different parts of the MTL, we developed a multi-modality segmentation model using both 7T and 3T structural MRI to obtain robust segmentation in poor-quality images. MRI modalities including 3T T1-weighted, 3T T2-weighted, 7T T1-weighted and 7T T2-weighted (7T-T2w) of 197 participants were collected from a longitudinal aging study at the Penn Alzheimer's Disease Research Center. Among them, 7T-T2w was used as the primary modality, and all other modalities were rigidly registered to the 7T-T2w. A model derived from nnU-Net took these registered modalities as input and outputted subregion segmentation in 7T-T2w space. 7T-T2w images most of which had high quality from 25 selected training participants were manually segmented to train the multi-modality model. Modality augmentation, which randomly replaced certain modalities with Gaussian noise, was applied during training to guide the model to extract information from all modalities. The multi-modality model delivered good performance regardless of 7T-T2w quality, while the single-modality model under-segmented subregions in poor-quality images. The multi-modality model generally demonstrated stronger discrimination of A + MCI versus A-CU. Intra-class correlation and Bland-Altman plots demonstrate that the multi-modality model had higher longitudinal segmentation consistency in all subregions while the single-modality model had low consistency in poor-quality images. The multi-modality MRI segmentation model provides an improved biomarker for neurodegeneration in the MTL that is robust to image quality. It also provides a framework for other studies which may benefit from multimodal imaging.

  PublisherDOI

• Age-related Changes in Brain Metabolites in Early Infancy: A Cross-Sectional Analysis of the First HBCD Data Release

  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: Neurometabolite concentration changes in the first few months after birth have not been studied in a large cohort. Goal(s): To assess early neurochemical development in a large cohort of 0-8 month-old infants by analyzing all available data in the first MRS data release of the HEALthy Brain and Child Development study ("HBCD"). Approach: Linear combination modeling will quantify 14 neurometabolites in this cross-sectional population. Statistical analyses will test for significant relationships between metabolite levels, birth-age and gestational age. Impact: Identifying changes in neurochemical levels in the first few months after birth in a large cohort for the first time will help deepen our understanding of the various roles these chemicals play in neurodevelopment.

  PublisherDOI

• Developing an anatomically valid segmentation protocol for anterior regions of the medial temporal lobe for neurodegenerative diseases

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-13 · 4 citations

  preprintOpen access

  Background: The anterior portion of the medial temporal lobe (MTL) is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) indicating a potential for metrics from this region to serve as imaging biomarkers. Leveraging a unique post-mortem dataset of histology and magnetic resonance imaging (MRI) scans we aimed to 1) develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 for in vivo 3 tesla (T) MRI and 2) incorporate this protocol in an automated approach. Methods: We included 20 cases (61-97 years old, 50% females) with and without neurodegenerative diseases (11 vs. 9 cases) to ensure generalizability of the developed protocol. Digitized MTL Nissl-stained coronal histology sections from these cases were annotated and registered to same-subject post-mortem MRI. The protocol was developed by determining the location of histological borders of the MTL cortices in relation to anatomical landmarks. Subsequently the protocol was applied to 15 cases twice, with a 2-week interval, to assess intra-rater reliability with the Dice Similarity Index (DSI). Thereafter it was implemented in our in-house Automatic Segmentation of Hippocampal Subfields (ASHS)-T1 approach and evaluated with DSIs. Results: The anterior histological border distances of ERC, BA35 and BA36 were evaluated with respect to various anatomical landmarks and the distance relative to the beginning of the hippocampus was chosen. To formulate segmentation rules, we examined the histological sections for the location of borders in relationship to anatomical landmarks in the coronal sections. The DSI for the anterior MTL cortices for the intra-rater reliability was 0.85-0.88 and for the ASHS-T1 against the manual segmentation was 0.62-0.65. Discussion: We developed a reliable segmentation protocol and incorporated it in an automated approach. Given the vulnerability of the anterior MTL cortices to tau deposition in AD and LATE, the updated approach is expected to improve imaging biomarkers for these diseases.

  PublisherDOI

• Pushing the Limits of ASL Spatiotemporal Resolution using 3D Accelerated Stack-of-Spirals

  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: ASL provides a quantitative biomarker of regional brain function and vascular integrity. However, current ASL methods remain hampered by trade-offs in spatial and temporal resolution. Goal(s): Improve the spatiotemporal resolution of ASL through optimized acceleration. Approach: Pseudocontinuous ASL with Stack-of-Spirals 3D TSE readouts were accelerated with ESPRiT compressed-sensing and imaging reconstruction and tested in healthy subjects. Results: Image resolution and quality comparable to highly segmented acquisitions were achieved using single- or two-shot acquisitions across all brain regions, including high-susceptibility regions. Impact: Improved spatial and temporal resolution enables enhanced applications including ASL-based resting-state or task dynamics in high-susceptibility regions.

  PublisherDOI

• Developing an Anatomically Valid Segmentation Protocol for Anterior Regions of the Medial Temporal Lobe for Neurodegenerative Diseases

  Hippocampus · 2025-07-30 · 1 citations

  articleOpen access

  The anterior portion of the medial temporal lobe (MTL) is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) and limbic-predominant age-related TDP-43 encephalopathy (LATE) indicating a potential for metrics from this region to serve as imaging biomarkers. Leveraging a unique post-mortem dataset of histology and magnetic resonance imaging (MRI) scans, we aimed to (1) develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann area (BA) 35, and BA36 for in vivo 3 T MRI and (2) incorporate this protocol in an automated approach. We included 20 cases (61-97 years old, 50% females) with and without neurodegenerative diseases (11 vs. 9 cases) to ensure generalizability of the developed protocol. Digitized MTL Nissl-stained coronal histology sections from these cases were annotated and registered to same-subject post-mortem MRI. The protocol was developed by determining the location of histological borders of the MTL cortices in relation to anatomical landmarks. Subsequently, the protocol was applied to 15 cases twice, with a 2-week interval, to assess intra-rater reliability with the Dice Similarity Index (DSI). Thereafter, it was implemented in our in-house Automatic Segmentation of Hippocampal Subfields (ASHS)-T1 approach and evaluated with DSIs. The anterior histological border distances of ERC, BA35 and BA36 were evaluated with respect to various anatomical landmarks, and the distance relative to the beginning of the hippocampus was chosen. To formulate segmentation rules, we examined the histological sections for the location of borders in relationship to anatomical landmarks in the coronal sections. The DSI for the anterior MTL cortices for the intra-rater reliability was 0.85-0.88, and for the ASHS-T1 against the manual segmentation, it was 0.62-0.65. We developed a reliable segmentation protocol and incorporated it in an automated approach. Given the vulnerability of the anterior MTL cortices to tau deposition in AD and LATE, the updated approach is expected to improve imaging biomarkers for these diseases.

  PublisherOA PDFDOI

Recent grants

• High-Speed Motion-Corrected Pediatric Neuroimaging with MRI

  NIH · $706k · 2016–2019

• NIH Grant K99HD074649

  NIH · $274k · 2015

Frequent coauthors

• André van der Kouwe

  Massachusetts General Hospital

  147 shared

• Bruce Fischl

  Harvard University

  59 shared

• Bruce R. Rosen

  Athinoula A. Martinos Center for Biomedical Imaging

  46 shared

• John A. Detre

  University of Pennsylvania

  44 shared

• Martin Reuter

  University of Bonn

  44 shared

• Randy L. Buckner

  Harvard University

  43 shared

• Paul Wighton

  42 shared

• Lawrence L. Wald

  41 shared

Awards & honors

• Research Mentor Training: Effective Communication and Aligni…
• Research Mentor Training: Culturally Responsive Mentoring (2…