ORIGINAL RESEARCH article
Front. Neuroimaging
Sec. Brain Imaging Methods
Volume 4 - 2025 | doi: 10.3389/fnimg.2025.1599966
This article is part of the Research TopicMethods and Applications of Diffusion MRI TractometryView all 16 articles
Leveling Up: Along-Level Diffusion Tensor Imaging in the Spinal Cord of Multiple Sclerosis Patients
Provisionally accepted
Atlee Witt1,2*
Anna J.E. Combes2,3
Grace Sweeney2Logan Prock2Delaney Houston2Seth Stubblefield4Colin McKnight4
Kristin O'Grady2,4,5
Seth Aaron Smith2,4,5
Kurt G Schilling2,5- 1School of Medicine, Vanderbilt University, Nashville, United States
- 2Vanderbilt Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United States
- 3NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
- 4Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, United States
- 5Department of Biomedical Engineering, Vanderbilt University, Nashville, United States
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Multiple sclerosis (MS) is a chronic neuroinflammatory disease marked by demyelination and axonal degeneration, processes that can be probed using diffusion tensor imaging (DTI). In the brain, white matter (WM) tractography enables anatomically specific analysis of microstructural changes. However, in the spinal cord (SC), anatomical localization is inherently defined by cervical levels, offering an alternative framework for regional analysis. This study employed an along-level approach to assess both microstructural (e.g., fractional anisotropy) and macrostructural (e.g., cross-sectional area) features of the SC in persons with relapsing-remitting MS (pwRRMS) relative to healthy controls (HCs). Compared to conventional whole-cord averaging, along-level analyses provided enhanced sensitivity to group differences. Detailed segmentation of WM tracts and gray matter (GM) subregions revealed spatially discrete alterations along the cord and within axial cross-sections. Notably, while GM atrophy was associated with clinical disability, microstructural changes did not exhibit significant correlations with disability measures. These findings underscore the utility of level-specific analysis in detecting localized pathology and suggest a refined framework for characterizing SC alterations in MS.
Keywords: Spinal Cord, Brain, Diffusion, MRI, Vertebral level, Multiple Sclerosis, Relapsing remitting MS
Received: 25 Mar 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Witt, Combes, Sweeney, Prock, Houston, Stubblefield, McKnight, O'Grady, Smith and Schilling. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Atlee Witt, School of Medicine, Vanderbilt University, Nashville, United States
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