Fiber‐specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis

Background and purpose To clarify the relationship between fiber‐specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel‐based analysis (FBA), a novel framework for diffusion‐weighted imaging analysis. Methods We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age‐ and sex‐matched healthy controls (HCs), in this study and conducted whole‐brain FBA and voxel‐based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross‐section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract‐of‐interest analysis to extract FD values across the significant regions in the whole‐brain analysis. Then, we evaluated the associations between FD values and clinical variables. Results The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p