Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS

Abstract

Background: Corticospinal 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'.

Methods: 23 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.

Results: In 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.

Conclusions: NODDI 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.

Figure 1

Figure demonstrating the areas of significant difference between the ALS and control groups on whole brain analysis of the NODDI parameters (A) neurite density index (NDI), (B) orientation dispersion index (ODI) and (C) isotropic compartment (ISO). The results are shown using a statistical significance of p<0.05 after family-wise error correction at the cluster level, clusters formed using p<0.001. Figures Ai - Aviii demonstrate the the areas of significant difference in NDI on axial sections from the posterior limb of the internal capsule (vi) extending rostrally up into the subcortical WM of the PCG (viii).

Figure 2

Figure demonstrating the areas of significant difference between the ALS and control groups on whole brain analysisof DTI parameters (A) fractional anisotropy (FA) and (B) mean diffusivity (MD). The results are shown using a statistical significance of p<0.05 after family-wise error correction at the cluster level, clusters formed using p<0.001.

Figure 3

Figure showing the region of significant difference in NDI on whole brain analysis between the bulbar plus limb ALS group and the limb-confined ALS group. The results are shown for p<0.05 after family-wise error correction at the cluster level, clusters formed using p<0.001.

Figure 4

Figure showing the areas of correlation on whole brain analysis of NODDI parameters and measures of disease severity. (A) Areas of correlation between orientation dispersion index and disease duration. (B) Areas of correlation between isotropic compartment and disease duration. The results are shown for p<0.05 after family-wise error correction at the cluster level, clusters formed using p<0.001.