Longitudinal changes in cortical cell body and neurite density in people with multiple sclerosis

Detecting neuroinflammation and neurodegeneration prior to cortical atrophy and subsequent clinical disability in people with multiple sclerosis (MS) has been challenging due to limited sensitivity on MRI. Our aim was to assess longitudinal changes in cortical cell body and neurite density related to lesion formation and atrophy using high-gradient diffusion MRI. In this longitudinal study, nine people with MS underwent 3 T high-gradient diffusion MRI at baseline and follow-up (median 5 years). Intra-soma, intra-neurite and extra-cellular signal fractions and apparent soma radius were estimated at multiple cortical depths from the pial surface and in normal-appearing, pre-lesional and lesional cortex. At baseline, lower deep gray matter volume was observed in MS relative to age- and sex-matched healthy controls. MS exhibited lower intra-soma fraction compared to HC, especially in deeper layers from the pial surface. At follow-up, cortical volumes decreased in MS, which correlated with lower baseline intra-neurite fraction. Superficial cortical layers showed increased soma radius at rates approximately four times higher than cortical volume loss. Microstructural changes were evident in the cortex at baseline where lesions were subsequently observed. Pre-lesional cortex showed higher intra-neurite fraction than normal-appearing cortex and existing lesions. Our findings provide in vivo evidence that early cortical microstructural changes may be detected by high-gradient diffusion MRI, prior to formation of detectable cortical lesions and cortical volume loss.