Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling
Abstract 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 r...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-025-02030-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849688210941149184 |
|---|---|
| author | Chinmayee Athalye Alejandra Bahena Pulkit Khandelwal Sheina Emrani Winifred Trotman Lisa M. Levorse Zahra Khodakarami Daniel T. Ohm Eric Teunissen-Bermeo Noah Capp Shokufeh Sadaghiani Sanaz Arezoumandan Sydney A. Lim Karthik Prabhakaran Ranjit Ittyerah John L. Robinson Theresa Schuck Edward B. Lee M. Dylan Tisdall Sandhitsu R. Das David A. Wolk David J. Irwin Paul A. Yushkevich |
| author_facet | Chinmayee Athalye Alejandra Bahena Pulkit Khandelwal Sheina Emrani Winifred Trotman Lisa M. Levorse Zahra Khodakarami Daniel T. Ohm Eric Teunissen-Bermeo Noah Capp Shokufeh Sadaghiani Sanaz Arezoumandan Sydney A. Lim Karthik Prabhakaran Ranjit Ittyerah John L. Robinson Theresa Schuck Edward B. Lee M. Dylan Tisdall Sandhitsu R. Das David A. Wolk David J. Irwin Paul A. Yushkevich |
| author_sort | Chinmayee Athalye |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-16685368a109432893e20e89318fdb59 |
| institution | DOAJ |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-16685368a109432893e20e89318fdb592025-08-20T03:22:04ZengBMCActa Neuropathologica Communications2051-59602025-05-0113112510.1186/s40478-025-02030-yOperationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology samplingChinmayee Athalye0Alejandra Bahena1Pulkit Khandelwal2Sheina Emrani3Winifred Trotman4Lisa M. Levorse5Zahra Khodakarami6Daniel T. Ohm7Eric Teunissen-Bermeo8Noah Capp9Shokufeh Sadaghiani10Sanaz Arezoumandan11Sydney A. Lim12Karthik Prabhakaran13Ranjit Ittyerah14John L. Robinson15Theresa Schuck16Edward B. Lee17M. Dylan Tisdall18Sandhitsu R. Das19David A. Wolk20David J. Irwin21Paul A. Yushkevich22Department of Bioengineering, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Bioengineering, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Bioengineering, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Neurology, University of PennsylvaniaDepartment of Radiology, University of PennsylvaniaAbstract 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.https://doi.org/10.1186/s40478-025-02030-yAlzheimer’s diseasePostmortem imagingHistologyQuantitative pathologyMRI-histology registration |
| spellingShingle | Chinmayee Athalye Alejandra Bahena Pulkit Khandelwal Sheina Emrani Winifred Trotman Lisa M. Levorse Zahra Khodakarami Daniel T. Ohm Eric Teunissen-Bermeo Noah Capp Shokufeh Sadaghiani Sanaz Arezoumandan Sydney A. Lim Karthik Prabhakaran Ranjit Ittyerah John L. Robinson Theresa Schuck Edward B. Lee M. Dylan Tisdall Sandhitsu R. Das David A. Wolk David J. Irwin Paul A. Yushkevich Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling Acta Neuropathologica Communications Alzheimer’s disease Postmortem imaging Histology Quantitative pathology MRI-histology registration |
| title | Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling |
| title_full | Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling |
| title_fullStr | Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling |
| title_full_unstemmed | Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling |
| title_short | Operationalizing postmortem pathology-MRI association studies in Alzheimer’s disease and related disorders with MRI-guided histology sampling |
| title_sort | operationalizing postmortem pathology mri association studies in alzheimer s disease and related disorders with mri guided histology sampling |
| topic | Alzheimer’s disease Postmortem imaging Histology Quantitative pathology MRI-histology registration |
| url | https://doi.org/10.1186/s40478-025-02030-y |
| work_keys_str_mv | AT chinmayeeathalye operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT alejandrabahena operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT pulkitkhandelwal operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT sheinaemrani operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT winifredtrotman operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT lisamlevorse operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT zahrakhodakarami operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT danieltohm operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT ericteunissenbermeo operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT noahcapp operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT shokufehsadaghiani operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT sanazarezoumandan operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT sydneyalim operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT karthikprabhakaran operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT ranjitittyerah operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT johnlrobinson operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT theresaschuck operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT edwardblee operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT mdylantisdall operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT sandhitsurdas operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT davidawolk operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT davidjirwin operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling AT paulayushkevich operationalizingpostmortempathologymriassociationstudiesinalzheimersdiseaseandrelateddisorderswithmriguidedhistologysampling |