About

John A. Detre is a Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. He serves as the Director of the Center for Functional Neuroimaging and the Brain Science Center, as well as co-Director of the Center for Advanced Magnetic Resonance Imaging and Spectroscopy. His research expertise includes magnetic resonance, brain mapping, cerebral blood flow, and brain injury. His overall research focuses on cerebral blood flow and metabolism under normal conditions and in response to brain injury. Specific conditions under investigation include functional activation of the human brain in response to cognitive and sensorimotor tasks, epilepsy, cerebrovascular disease, traumatic brain injury, aging, and dementia. He primarily utilizes magnetic resonance imaging and spectroscopy, optical spectroscopy and imaging, often correlating these techniques with other methods, to study brain physiology and pathophysiology of functional activation.

Research topics

• Computer Science
• Artificial Intelligence
• Medicine
• Radiology
• Neuroscience
• Data Mining
• Internal medicine
• Cardiology
• Pathology
• Biology
• Psychology
• Computer vision
• Physics
• Database
• Biochemistry
• Developmental psychology
• Audiology
• Nuclear magnetic resonance
• Cognitive psychology
• Chemistry

Selected publications

• High-fidelity infant regional cerebral blood flow map with isotropic 2mm resolution acquired through segmented 3D GRASE pCASL

  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: The small infant brain sizes necessitate high-fidelity and high-resolution imaging. Infant cerebral blood flow (CBF) maps at isotropic 2mm resolution are not available. Goal(s): We aimed to develop a high-resolution infant arterial spin-labeled (ASL) MRI protocol for understanding fundamental infant brain physiology in health and disorders. Approach: We tested and optimized a cutting-edge segmented 3D GRASE pseudo-continuous-ASL (pCASL) sequence for imaging infant brains. Results: We achieved the infant CBF maps with highest resolution available to date at isotropic 2mm, capturing the finest details of heterogeneous brain perfusion across various structures including smaller structures such as cerebellum and basal ganglia. Impact: Capitalizing on an advanced segmented 3D GRASE pCASL with background suppression, we acquired the highest-resolution infant CBF maps available at isotropic 2mm, providing unprecedented details of regional CBF variations across whole infant brain structures characterized by small sizes.

  PublisherDOI

• Normative Cerebral Perfusion Across the Lifespan

  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

  preprintOpen access

  Cerebral perfusion plays a crucial role in maintaining brain function and is tightly coupled with neuronal activity. While previous studies have examined cerebral perfusion trajectories across development and aging, precise characterization of its lifespan dynamics has been limited by small sample sizes and methodological inconsistencies. In this study, we construct the first comprehensive normative model of cerebral perfusion across the human lifespan (birth to 85 years) using a large multi-site dataset of over 12,000 high-quality arterial spin labeling (ASL) MRI scans. Leveraging generalized additive models for location, scale, and shape (GAMLSS), we mapped nonlinear growth trajectories of cerebral perfusion at global, network, and regional levels. We observed a rapid postnatal increase in cerebral perfusion, peaking at approximately 7.1 years, followed by a gradual decline into adulthood. Sex differences were evident, with distinct regional maturation patterns rather than uniform differences across all brain regions. Beyond normative modeling, we quantified individual deviations from expected CBF patterns in neurodegenerative and psychiatric conditions, identifying disease-specific perfusion abnormalities across four brain disorders. Using longitudinal data, we established typical and atypical cerebral perfusion trajectories, highlighting the prognostic value of perfusion-based biomarkers for detecting disease progression. Our findings provide a robust normative framework for cerebral perfusion, facilitating precise characterization of brain health across the lifespan and enhancing the early identification of neurovascular dysfunction in clinical populations.

  PublisherOA PDFDOI

• High-resolution practical imaging of perivascular spaces

  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: Perivascular spaces are of high relevance to the pathophysiology of Alzheimer's Disease, particularly in the context of anti-amyloid therapies. Goal(s): To evaluate the feasibility of imaging PVS using ultra-long TE 3D-T2 sequence across field strengths. Approach: We implemented a high-resolution protocol using an ultra-long-TE 3D T2-weighted TSE sequence at 1.5T and 3T, and scanned a cohort of healthy volunteers and AD patients. Results: Improved definition of PVS was obtained using our ultra-long-TE protocol compared to standard methods, and shown to be feasible across field strengths. Pilot scans in AD patients show widespread increased signal. Impact: This work demonstrates that perivascular spaces can be imaged in a clinically compatible time across field-strengths. Pilot scans in AD patients show widespread increased signal, suggesting a potential interest in specifically studying PVS in AD.

  PublisherDOI

• Segmentation and Quantification of Perivascular Spaces in Early Alzheimer’s Disease using Ultra‐long TE T2‐weighted MRI

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  Abstract Background Perivascular spaces (PVS) are small fluid‐filled structures that are of major interest in both cerebral small vessel disease (cSVD) and neurodegeneration, particularly in the pathophysiology of AD and cerebral amyloid angiopathy (CAA). Current approaches to measure and quantify PVS rely on multi‐contrast combination or high‐field MRI to enhance visualization. We propose here an optimized imaging sequence for selective imaging of intracranial fluids with high resolution and clinically practical scan time capable of detecting AD‐related PVS enlargement. Method 19 patients with MCI or mild Dementia due to AD scanned prior to initiation of anti‐amyloid therapy (73±7yo) and 19 cognitively unimpaired (CU) older adults (71±7yo) were enrolled and scanned on a Siemens Prisma 3T MRI at the University of Pennsylvania. We acquired a 3D ultra‐long‐TE T2‐weighted sequence (ulTE‐T2, TR/TE=5000/876ms, FA=75deg, BW=681Hz/pix, 1mm isotropic, GRAPPA=4) in 3min 40sec. Motion‐corrupted scans (4 AD, 2 CU) were excluded. Images were co‐registered with a T1‐weighted volume and warped into MNI space. A 3D‐Frangi filter was used to automatically segment PVS within WM‐masked regions‐of‐interest (ROI). PVS volume fractions (PVS vf = V pvs /V ROI ) were computed in various lobal (parietal/occipital/frontal/temporal) and subcortical regions of interests and whole brain PVS probability maps were also produced by averaging individual PVS segmentations. A lobar/subcortical PVS vf ratio was calculated and then compared between AD and CU. Result Figure 1 shows the sensitivity towards PVS of the ulTE‐T2 sequence and automatic segmentation results. Group probability maps show high PVSvf in the basal ganglia and in posterior > anterior WM (Figure 2). PVSvf lobar/subcortical ratio was higher in AD compared to CU (Figure 3, β =0.68 [0.11,1.26], t (35)=2.42, p =0.021) after controlling for age, which was negatively associated with PVSvf ratio ( β =‐0.41 [‐0.70, ‐0.12], t (35)=‐2.84, p =0.007). Conclusion Fluid‐specific PVS imaging can be performed within clinically feasible scan times. Early results show strong visual and quantitative sensitivity towards PVS. Furthermore, individuals with AD show increased lobar to subcortical PVS volume ratio compared to CU both on visual assessment and with quantitative evaluation. Ongoing future directions include implementing variant sequences with improved motion robustness and longitudinal follow‐up to evaluate the effects of anti‐amyloid therapy on PVS.

  PublisherOA PDFDOI

• 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

• MLC-GCN: Multi-Level Connectomes Based GCN for AD Detection

  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: Alzheimer's Disease (AD) is characterized by progressive cognitive impairments that are related to alterations in brain functional connectivity (FC). Goal(s): to design a graph convolutional network (GCN) based classifier to differentiate AD from old cognitive normal controls. Approach: We assessed the FC using Pearson correlation coefficient (CC) and cross entropy (CE) measure as association analysis and proposed a multi-level generated connectome (MLC) based GCN (MLC-GCN) containing a multi-graph generation block and a GCN prediction block to classify the fMRI data. Results: Our method showed better performance than state-of-the-art GCN and rsfMRI based AD classifiers on two independent public medical datasets: ADNI and OASIS-3. Impact: The MLC-GCN classifier significantly enhances Alzheimer's disease detection by exploiting multi-level connectomes. The clinically meaningful classifier features suggest a potential of localizing disease-related nodes or regions, facilitating clinical diagnosis and future targeted interventions.

  PublisherDOI

• High‐resolution postmortem 7 tesla MRI yields localized atrophy measures that are more sensitive to tau pathology and neuronal loss in Alzheimer’s disease than corresponding measures on antemortem 3 tesla MRI

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  Abstract Background Postmortem MRI has opened‐up avenues to study brain structure at ultra high‐resolution revealing details not possible to observe with in vivo MRI. Here, we present a novel package (purple‐mri) which performs tissue segmentation, anatomical parcellation and spatial normalization of postmortem MRI. Additionally, we provide a framework to perform point‐wise surface‐based group‐level studies linking morphometry/histopathology in common coordinate system for postmortem MRI. Method We developed a joint voxel‐ and surface‐based pipeline combining deep learning with classical techniques for topology correction, cortical modeling, inflation, and registration for accurate parcellation of postmortem cerebral hemispheres (Figure 1 Khandelwal et al. 2024). Furthermore, using the GM/WM segmentations derived from postmortem hemisphere and FreeSurfer‐processed antemortem MRI, we performed deformable image registration between the ante‐ and postmortem MRI for each brain specimen. To demonstrate the utility of purple‐mri, point‐wise analysis was performed to correlate thickness (mm) with tau and neuronal loss distribution in corresponding specimens ( N = 49) of postmortem (7T at 0.3mm 3 ) and antemortem (3T at 0.8mm 3 ) MRI (Table 1) within the AD continuum diagnosis. An additional 26 postmortem 7T scans without corresponding antemortem scans were included in some analyses. The semi‐quantitative average tau and neuronal loss ratings were derived from histopathological examination across the brain. All analyses include age, sex, and postmortem (or antemortem) interval as covariates. Result Our method parcellates postmortem brain hemisphere using a variety of brain atlases even in areas with low contrast (anterior/posterior regions), profound imaging artifacts and severely atrophied brains (Figure 1). Our registration pipeline provides one‐to‐one correspondence between the two modalities. For thickness/pathology associations (Figure 2), small sparse significant clusters only in superior temporal cortex and precuneus in antemortem MRI ( N = 49) were observed. However, postmortem MRI showed much stronger associations across large clusters in temporal, entorhinal cortex, and cingulate for both the matched cases ( N = 49) and the full cohort ( N = 75), regions implicated in ADRD. Conclusion Purple‐mri paves the way for large‐scale postmortem image analysis. Stronger associations between thickness and average tau burden/neuronal loss than antemortem MRI suggests that our pipeline could inform the development of more precise and sensitive invivo biomarkers by mapping information from postmortem to antemortem MRI in a common reference coordinate system.

  PublisherOA PDFDOI

• 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

• Comparison of long-label single-delay ASL and multi-delay ASL in healthy aging

  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: Identify the most sensitive arterial spin labeling (ASL) methods for brain aging Goal(s): Compare single- and multiple-post labeling delay (PLD) ASL protocols in healthy aging Approach: Absolute cerebral blood flow (CBF), relative CBF, and arterial transit time (ATT) from long-label (LL) single-PLD and multi-PLD sequences were correlated with age and other variables in an adult lifespan cohort. Results: Age effects were more significant in ATT and ATT-corrected CBF values than in LL single-PLD CBF, though the use of putamen-normalized relative single-PLD CBF enhanced sensitivity to age and other biological parameters. Impact: Multi-PLD ASL enhances the assessment of age effects on brain perfusion.

  PublisherDOI

• The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment

  Alzheimer s & Dementia · 2025-11-01

  articleOpen access

  INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01NS037488

  NIH · $1.5M · 2005

• NIH Grant R01DA015149

  NIH · $1.1M · 2007

• NIH Grant K24NS058386

  NIH · $597k · 2014

• Perfusion fMRI for Cognitive Neuroscience

  NSF · $754k · 2002–2007

• NIH Grant T32NS054575

  NIH · $1.1M · 2013

Frequent coauthors

• Danny J.J. Wang

  148 shared

• Hengyi Rao

  University of Pennsylvania

  100 shared

• David C. Alsop

  96 shared

• David A. Wolk

  California University of Pennsylvania

  91 shared

• Murray Grossman

  78 shared

• Sandhitsu R. Das

  Alzheimer’s Disease Neuroimaging Initiative

  74 shared

• Paul A. Yushkevich

  University of Pennsylvania

  68 shared

• Arjun G. Yodh

  University of Pennsylvania

  61 shared

Education

• MD

  Yale School of Medicine

  1986