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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 <Â 0.05, familywise error-corrected), and the comparison of FCs revealed no region that was significantly different from another. Voxel-based morphometry showed cortical volume reduction in the regions, including the primary motor area. Clinical scores showed correlations with FD values in the CSTs (UMN score: rho =Â â��0.530, p <Â 0.001; central motor conduction time CMCT in the upper limb: rho =Â â��0.474, p =Â 0.008; disease duration: rho =Â â��0.383, p =Â 0.007; ALS Functional Rating Scale-Revised: rho =Â 0.340, p =Â 0.018). In addition, patients whose CMCT was not calculated due to unevoked waves also showed FD reduction in the CSTs. Conclusions: Our findings suggest that FD values in the CST estimated via FBA can be potentially used in evaluating UMN impairments. © 2021 European Academy of Neurology
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