{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:48:32Z","timestamp":1790286512447,"version":"4.1.0"},"reference-count":103,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high-resolution dataset of 135 postmortem human brain tissue specimens imaged at 0.3 mm3 isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We evaluate the reliability of this pipeline via overlap metrics with manual segmentation in 6 specimens, and intra-class correlation between cortical thickness measures extracted from the automatic segmentation and expert-generated reference measures in 36 specimens. We also segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter, providing a limited evaluation of accuracy. We show generalizing capabilities across whole-brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm3 and 0.16 mm3 isotropic T2*w fast low angle shot (FLASH) sequence at 7T. We report associations between localized cortical thickness and volumetric measurements across key regions, and semi-quantitative neuropathological ratings in a subset of 82 individuals with Alzheimer\u2019s disease (AD) continuum diagnoses. Our code, Jupyter notebooks, and the containerized executables are publicly available at the project webpage (https:\/\/pulkit-khandelwal.github.io\/exvivo-brain-upenn\/).<\/jats:p>","DOI":"10.1162\/imag_a_00171","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T19:08:30Z","timestamp":1713899310000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":14,"title":["Automated deep learning segmentation of high-resolution 7 Tesla\n                    postmortem MRI for quantitative analysis of structure-pathology correlations in\n                    neurodegenerative diseases"],"prefix":"10.1162","volume":"2","author":[{"given":"Pulkit","family":"Khandelwal","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Tran","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shokufeh","family":"Sadaghiani","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Lim","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda E.","family":"Denning","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Chung","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadhana","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United 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Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit","family":"Ittyerah","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Migdal","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of 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States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Prabhakaran","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Mizsei","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Gabrielyan","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Schuck","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winifred","family":"Trotman","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"Ohm","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Q.","family":"Trojanowski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"McMillan","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Grossman","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Detre","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dylan","family":"Tisdall","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhitsu R.","family":"Das","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E. M.","family":"Wisse","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Wolk","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Yushkevich","sequence":"additional","affiliation":[{"name":"Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"281","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"2025081116474303700_b1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.neuroimage.2013.08.067","article-title":"Histology-derived 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A case\n                        study","volume":"1","author":"Boon","year":"2019","journal-title":"Brain Communications"},{"key":"2025081116474303700_b14","doi-asserted-by":"crossref","first-page":"116808","DOI":"10.1016\/j.neuroimage.2020.116808","article-title":"Quantitative MRI and laser\n                        ablation-inductively coupled plasma-mass spectrometry imaging of iron in the\n                        frontal cortex of healthy controls and Alzheimer\u2019s disease\n                        patients","volume":"215","author":"Bulk","year":"2020","journal-title":"NeuroImage"},{"key":"2025081116474303700_b15","doi-asserted-by":"crossref","first-page":"102265","DOI":"10.1016\/j.media.2021.102265","article-title":"Robust joint registration of multiple stains and MRI for\n                        multimodal 3D histology reconstruction: Application to the Allen human brain\n                        atlas","volume":"75","author":"Casamitjana","year":"2022","journal-title":"Medical 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on histological samples, the atlas of von\n                        Economo and Koskinas, and magnetic resonance imaging","volume":"14","author":"Garc\u00eda-Cabezas","year":"2020","journal-title":"Frontiers in Neuroanatomy"},{"key":"2025081116474303700_b35","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41582-022-00642-9","article-title":"Lesions without symptoms: Understanding resilience to\n                        Alzheimer disease neuropathological changes","volume":"18","author":"G\u00f3mez-Isla","year":"2022","journal-title":"Nature\n                        Reviews Neurology"},{"key":"2025081116474303700_b36","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/jnc.13656","article-title":"Advances in neuroimaging in frontotemporal\n                        dementia","volume":"138","author":"Gordon","year":"2016","journal-title":"Journal of 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Pattern\n                        Analysis and Machine Intelligence"},{"key":"2025081116474303700_b40","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/alz.12249","article-title":"Distinct effects of beta-amyloid and tau on cortical\n                        thickness in cognitively healthy older adults","volume":"17","author":"Harrison","year":"2021","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2025081116474303700_b41","doi-asserted-by":"crossref","first-page":"117012","DOI":"10.1016\/j.neuroimage.2020.117012","article-title":"FastSurfer-A fast and accurate deep\n                        learning based neuroimaging pipeline","volume":"219","author":"Henschel","year":"2020","journal-title":"NeuroImage"},{"key":"2025081116474303700_b42","doi-asserted-by":"crossref","first-page":"giy082","DOI":"10.1093\/gigascience\/giy082","article-title":"Nighres: Processing tools for high-resolution\n                        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