In vivo quantification of brain soma and neurite density abnormalities in multiple sclerosis

Background Soma and neurite density imaging (SANDI) is a new biophysical model that incorporates soma in addition to neurite density, thus possibly providing more specific information about the complex pathological processes of multiple sclerosis (MS). Purpose To discriminate the pathological abnormalities of MS white matter (WM) lesions, normal-appearing (NA) WM and cortex and to evaluate the associations among SANDI-derived measures, clinical disability, and conventional MRI variables. Methods Twenty healthy controls (HC) and 23 MS underwent a 3 T brain MRI. Using SANDI on diffusion-weighted sequence, the fractions of neurite (f(neurite)) and soma (f(soma)) were assessed in WM lesions, NAWM, and cortex. Results Compared to HC WM, MS NAWM showed lower f(neurite) (false discovery rate [FDR]-p = 0.011). In MS patients, WM lesions showed lower f(neurite) and f(soma) compared to both HC and MS NAWM (FDR-p < 0.001 for all). In the cortex, MS patients had lower f(neurite) and f(soma) compared to HC (FDR-p <= 0.009). Compared to both HC and RRMS, PMS patients had lower f(neurite) in NAWM (vs HC: FDR-p < 0.001; vs RRMS: FDR-p = 0.003) and cortex (vs HC: FDR-p < 0.001; vs RRMS: p = 0.031, not surviving FDR correction), and lower cortical f(soma) (vs HC: FDR-p < 0.001; vs RRMS: FDR-p = 0.009). Compared to HC, PMS also showed a higher f(soma) in NAWM (FDR-p = 0.015). F-neurite and f(soma) in the different brain compartments were correlated with age, phenotype, disease duration, disability, WM lesion volumes, normalized brain, cortical, and WM volumes (r from - 0.761 to 0.821, FDR-p <= 0.4). Conclusions SANDI may represent a clinically relevant model to discriminate different neurodegenerative phenomena that gradually accumulate through MS disease course.