Gray matter is more relevant than white matter (WM) atrophy in explaining clinical disability and cognitive impairment in multiple sclerosis (MS). However, WM is a complex structure whose fiber orientation should be considered when investigating its morphology. In a group of MS patients and healthy controls, we applied constrained spherical deconvolution and fixel-based morphometry to estimate the distribution of WM fiber bundles and their cross-section area as a measure of atrophy. We found that the application of this approach in MS improved when accounting for the presence of lesions and that atrophy was specific of WM fiber bundles.
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