• Rebecca J Broad, Matt C Gabel, Nicholas G Dowell, David J Schwartzman, Anil K Seth, Hui Zhang, Daniel C Alexander, Mara Cercignani, and P Nigel Leigh.
• Department of Neuroscience, Trafford Centre for Biomedical Research, Brighton and Sussex Medical School, Brighton, UK r.broad@bsms.ac.uk.
• J. Neurol. Neurosurg. Psychiatr. 2019 Apr 1; 90 (4): 404-411.

BackgroundCorticospinal tract (CST) degeneration and cortical atrophy are consistent features of amyotrophic lateral sclerosis (ALS). We hypothesised that neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, would reveal microstructural changes associated with ALS within the CST and precentral gyrus (PCG) 'in vivo'.Methods23 participants with sporadic ALS and 23 healthy controls underwent diffusion MRI. Neurite density index (NDI), orientation dispersion index (ODI) and free water fraction (isotropic compartment (ISO)) were derived. Whole brain voxel-wise analysis was performed to assess for group differences. Standard diffusion tensor imaging (DTI) parameters were computed for comparison. Subgroup analysis was performed to investigate for NODDI parameter differences relating to bulbar involvement. Correlation of NODDI parameters with clinical variables were also explored. The results were accepted as significant where p<0.05 after family-wise error correction at the cluster level, clusters formed with p<0.001.ResultsIn the ALS group NDI was reduced in the extensive regions of the CST, the corpus callosum and the right PCG. ODI was reduced in the right anterior internal capsule and the right PCG. Significant differences in NDI were detected between subgroups stratified according to the presence or absence of bulbar involvement. ODI and ISO correlated with disease duration.ConclusionsNODDI demonstrates that axonal loss within the CST is a core feature of degeneration in ALS. This is the main factor contributing to the altered diffusivity profile detected using DTI. NODDI also identified dendritic alterations within the PCG, suggesting microstructural cortical dendritic changes occur together with CST axonal damage.© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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