Results of white matter (WM) voxel-wise analysis: A) cross-sectional results of TBSS analysis comparing ALS patients with healthy controls at baseline; B) regions of significant decrease/increase of DT MRI metrics over time, as measured in terms of slopes of FA (red), MD (blue), axD (orange), or radD (violet) change; and C) regions of significant correlation between ALSFRS-r and FA decline over follow-up time. All results are superimposed on the WM skeleton of TBSS (light green) and on the Montreal Neurological Institute (MNI) template, thresholded at p < 0.05 FWE-corrected, and adjusted for age and sex. Results displayed in B) and C) are also adjusted for baseline ALSFRS-r values. Abbreviations: ALS = amyotrophic lateral sclerosis; ALSFRS-r = ALS Functional Rating Scale, revised version, axD = axial diffusivity; CST = corticospinal tract; DT = diffusion tensor; MD = mean diffusivity; radD = radial diffusivity; TBSS = Tract-based Spatial Statistics; WM = white matter. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)