Automated Segmentation and Tractography of Brainstem and Subcortical White Matter
Year: 2026
Type: preprint
Abstract: Diffusion MRI enables noninvasive mapping of human white matter pathways, but automated segmentation methods have largely focused on large association, projection, and commissural bundles. Brainstem and subcortical pathways supporting basal ganglia, cerebellar, limbic/reward, sensory, and homeostatic functions remain underrepresented in large-scale connectomic analyses. To address this gap, we adapted BundleParc, a recently introduced bundle-parcellation architecture, into an automated pipeline for direct segmentation and along-tract parcellation of 97 subcortical and brainstem white matter pathways. The model was trained on a curated reference dataset derived from Human Connectome Project diffusion MRI using anatomy-guided tractography, explicit inclusion and exclusion criteria, automated outlier filtering, and manual quality assurance. Operating directly on native-space fiber orientation distributions, the algorithm successfully recovers these intricate anatomical trajectories and ordered parcellations. We show the model generalizes to diverse external datasets spanning development, aging, and neurodegenerative disease cohorts, maintaining robust performance across variations in spatial resolution and angular sampling. The released container, trained model, population atlas, reference streamlines, and quality assurance outputs provide a resource for studying deep brainstem and subcortical pathways in development, aging, disease, and neuromodulation-relevant anatomy.
Authors: Kurt G Schilling, Gaurav Rudravaram, Antoine Theberge, Matthew Amandola, Michael E. Kim, Kathryn L. Humphreys, Laurie Cutting, Derek Archer, Timothy J. Hohman, Angela L. Jefferson, Lori L. Beason Held, Murat Bilgel, Alzheimer’s Disease Neuroimaging Initiative, The BIOCARD Study Team, Maxime Chamberland, Maxime Descoteaux, Laurent Petit, Francois Rheault, Bennett Landman
Institutions: Vanderbilt University, Vanderbilt University Medical Center, Université de Sherbrooke, National Institute on Aging, Eindhoven University of Technology, Centre National de la Recherche Scientifique, Université de Bordeaux, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut des Maladies Neurodégénératives
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: High-Performance Computer Cluster for Biomedical Research, Epidemiologic Study of Neural Reserve and Neurobiology of Aging, White matter and small vessel disease in older adults, Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia., Risk factors and prevention targets for abnormal cognitive aging, Genetic Drivers of Resilience to Alzheimer's Disease, Creating a Pediatric Imaging-Genomics Data Resource, Replacement and Upgrade of a 3T MR Scanner for Research, Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia., Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Vanderbilt, White matter degeneration: biomarkers in preclinical Alzheimer's Disease, Risk Factors, Pathology, and Clinical Expressions of AD, Rush Alzheimer's Disease Core Center, Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's Disease, Predicting Late-Emerging RD: Neurobiological and Cognitive Factors, Controlling Quality and Capturing Uncertainty in Advanced Diffusion Weighted MRI, Characterizing TDP-43 related hippocampal degeneration and memory loss in aging, Vanderbilt Alzheimer's Disease Research Center, Cognitive and Neural Processes in Reading Comprehension, MRI markers of brain aging and risk factors for cognitive decline in older African Americans, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Neurobiology and Treatment of Reading Disability in NF1, In-vivo MRI-based prediction of TDP43 pathology in aging, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, Early Academic Achievement and Intervention Response: Role of Executive Function, 20/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT VCU, 3/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MINNESOTA, 4/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT FIU, 7/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT YALE, Vanderbilt Memory & Aging Project, Genomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's Disease, 17/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UCLA, 15/21 ABCD-USA Consortium: Research Project Site at LIBR, 16/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UNIVERSITY OF ROCHESTER, Vanderbilt Institute for Clinical and Translational Research (VICTR), Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium, The Longitudinal Course of Imaging Biomarkers in People At Risk for Alzheimer’s Disease, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, ABCD-USA Consortium: Coordinating Center, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, Alzheimer's Disease Neuroimaging Initiative (ADNI4), 10/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT SRI, 12/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U PITTSBURGH, Microstructure and connectivity modeling from the cortex to the spinal cord in Multiple Sclerosis, 19/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UVM, Vanderbilt Alzheimer's Disease Research Center, 1/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U UTAH, Evaluating Advanced Diffusion of the Human Spinal Cord: Application to MS, Racial Differences in Late-Life Cognitive decline and risk of Alzheimer's Disease, 11/21 ABCD-USA Consortium: Research Project Site at UWM, ABCD-USA Consortium: Data Analysis, Informatics and Resource Center, 21/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT WUSTL, 13/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT MUSC, 5/21 ABCD-USA Consortium: Research Project Site at UC San Diego, 18/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT THE UNIVERSITY OF FLORIDA, 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, Parent-child proximity and emerging psychopathology, 14/21 ABCD-USA Consortium: Research Project Site at CU Boulder, Rush Alzheimer's Disease Research Center, White matter degeneration: biomarkers in preclinical Alzheimer's Disease, Ultrascale Machine Learning to Empower Discovery in Alzheimers Disease Biobanks
OpenAlex ID: W7164481108