Soma and neurite density imaging detects brain microstructural impairments in amyotrophic lateral sclerosis.

Objective: To investigate whole-brain microstructural changes in amyotrophic lateral sclerosis (ALS) using soma and neurite density imaging (SANDI), a novel multicompartment model of diffusion-weighted imaging that estimates apparent soma and neurite density.

Methods: This study consists of 41 healthy controls and 43 patients with ALS, whose diffusion-weighted data were acquired. The SANDI-derived (including signal fractions of soma (f), neurite (f), and extra-cellular space (f)) and diffusion tensor imaging (DTI)-derived metrics were obtained. Voxel-based analyses were performed to evaluate intergroup differences and the correlation of SANDI and DTI metrics with clinical parameters.

Results: In ALS patients, f reduction involved both gray matter (primarily the bilateral precentral gyri, supplementary motor area, medial frontal gyrus, anterior cingulate cortex, inferior frontal gyrus, orbital gyrus, paracentral lobule, postcentral gyrus, middle cingulate cortex, hippocampus and parahippocampal gyrus, and insula, and left anterior parts of the temporal lobe) and white matter (primarily the bilateral corticospinal tract, body of corpus callosum, and brainstem) (P <0.05 after false discovery rate correction). The f increment showed a similar spatial distribution in ALS patients. Interestingly, the decreased f in ALS primarily located in gray matter; while, the increased f primarily involved white matter. The spatial distribution of f/f/f changes was larger than that detected by conventional DTI metrics, and the f/f/f were correlated with disease severity.

Conclusions: SANDI may serve as a clinically relevant model, superior to conventional DTI, for characterizing microstructural impairments such as neurite degeneration and soma alteration in ALS.