A novel imaging marker of cortical "cellularity" in multiple sclerosis patients.

Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model ("soma and neurite density imaging (SANDI)") to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to investigate inflammation and degeneration-related changes in the cortical tissue of pwMS. We aimed to (i) establish whether SANDI is applicable in vivo clinical data; (ii) investigate inflammatory and degenerative changes using SANDI soma fraction (f)-a marker of cellularity-in both cortical lesions and in the normal-appearing-cortex and (iii) correlate SANDI f with clinical and biological measures in pwMS. We applied a simplified version of SANDI to a clinical scanners. We then provided evidence that pwMS exhibited an overall decrease in cortical SANDI f compared to healthy subjects, suggesting global degenerative processes compatible with neuronal loss. On the other hand, we have found that progressive pwMS showed a higher SANDI f in the outer part of the cortex compared to relapsing-remitting pwMS, possibly supporting current pathological knowledge of increased innate inflammatory cells in these regions. A similar finding was obtained in subpial lesions in relapsing-remitting patients, reflecting existing pathological data in these lesion types. A significant correlation was found between SANDI f and serum neurofilament light chain-a biomarker of inflammatory axonal damage-suggesting a relationship between SANDI soma fraction and inflammatory processes in pwMS again. Overall, our data show that SANDI f is a promising biomarker to monitor changes in cellularity compatible with neurodegeneration and neuroinflammation in the cortex of MS patients.