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

Abstract

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.

Keywords: MRI; Multiple sclerosis; Soma and neurite density imaging (SANDI).