Gray Matter Microstructure Alterations in People with Multiple Sclerosis Based on Cell Body and Neurite Density Imaging
Eva Angela Krijnen1, Andrew Russo2, Elsa Salim Karam2, Menno M Schoonheim1, Susie Huang3, Eric Klawiter2
1Amsterdam UMC, 2Neurology, Massachusetts General Hospital, 3Massachusetts General Hospital, Harvard Medical School
Objective:
To evaluate a novel compartment-based model for apparent cell body and neurite density imaging (SANDI) in gray matter (GM) in people with multiple sclerosis (MS) compared to healthy controls (HC) and its correlation with brain atrophy.
Background:
MS features focal cortical lesions and microstructural changes in normal-appearing GM, which can impact clinical function and disability. High gradient diffusion MRI has potential to optimize GM tissue microstructure characterization by overcoming challenges due to the complexity of underlying components.
Design/Methods:
41 people with MS and 37 age- and sex-matched HC were scanned on a 3T Connectom MRI scanner equipped with 300mT/m gradients using a multi-shell acquisition protocol consisting of eight b-values at 19msec diffusion time. Microstructural metrics of SANDI, including a measure of soma density (fsoma) in the cortex and deep GM, were compared between MS and HC and correlated with cortical and thalamic atrophy, correcting for multiple comparisons.
Results:
Cortical cell body signal fraction (fsoma) was decreased in MS compared to HC (0.56 vs. 0.58, p=0.027, not surviving FDR-correction). In deep GM, fsoma and extra-cellular signal fraction were significantly decreased in MS compared to HC (FDR-p=0.045 in both), which was most pronounced in progressive MS. Based on spatial analysis, fsoma of caudate nucleus and thalamus were significantly decreased in MS compared to HC (FDR-p=0.003 and FDR-p=0.027, respectively). Whereas cortical atrophy in MS was poorly correlated with cortical fsoma, thalamic atrophy in MS demonstrated moderate correlation with decreased thalamic fsoma (r=0.311, p=0.054) and decreased cortical fsoma (r=0.474, p=0.008).
Conclusions:
SANDI metrics, in particular fsoma, provide detailed GM characterization beyond cortical and thalamic volumes and are able to characterize MS-related microstructural pathology. Decreased cortical cell density correlates with declining thalamic volume and may precede volumetric measures of cortical atrophy in people with MS.