Figure 3. The Digital Pathologist.

One of the key aims of the Digital Pathologist is the examination of neuropathological spread in neurological disease. The Human ALS MRI-Histology dataset (a) facilitates these investigations, combining whole-brain multimodal MRI and histology (selected brain regions) in a cohort of 12 ALS and 3 control brains. (b) Displays the reconstruction of five white matter pathways associated with different ALS stages in a single post-mortem brain (Kassubek et al., 2014). Comparisons between ALS and control brains over the corpus callosum of the cohort (c) reveals changes in fractional anisotropy (FA, normalized to Par/Temp/Occ lobe), with biggest changes associated with motor and prefrontal regions (Hofer and Frahm, 2006) (*=p<0.05; **=p<0.05 following multiple comparison correction) (full details of the corpus callosum analysis provided in Appendix 2). This reflects the anticipated changes in ALS with brain regions associated with motor function, in good agreement with a previous study (Chapman et al., 2014), which identified the greatest FA difference between ALS and controls in these regions. Accurate MRI-histology coregistrations facilitate cross-modality comparisons, and (d) displays an example of MRI-histology coregistration over the visual cortex of a single ALS brain achieved using the Tensor Image Registration Library (TIRL) (Huszar et al., 2019). V₁=principal diffusion direction, FA=fractional anisotropy, MD=mean diffusivity, D_⊥=radial diffusivity, MO=mode from diffusion tensor output, Dyad₁=principal dyad orientation, f₁=principal fiber fraction and D=diffusivity from Ball and Two-Stick output, swMRI=susceptibility-weighted MRI, χ=magnetic susceptibility. Details of stain contrasts in (b) and (d) are provided in Table 1. ALS, amyotrophic lateral sclerosis; MRI, magnetic resonance imaging.