Gray Matter Microstructure Alterations in People with Multiple Sclerosis Based on Cell Body and Neurite Density Imaging (P10-3.007)

Abstract

<h3>Objective:</h3> 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. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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 (f_soma) in the cortex and deep GM, were compared between MS and HC and correlated with cortical and thalamic atrophy, correcting for multiple comparisons. <h3>Results:</h3> Cortical cell body signal fraction (f_soma) was decreased in MS compared to HC (0.56 vs. 0.58, <i>p</i>=0.027, not surviving FDR-correction). In deep GM, f_soma and extra-cellular signal fraction were significantly decreased in MS compared to HC (<i>FDR-p</i>=0.045 in both), which was most pronounced in progressive MS. Based on spatial analysis, f_soma of caudate nucleus and thalamus were significantly decreased in MS compared to HC (<i>FDR-p</i>=0.003 and <i>FDR-p</i>=0.027, respectively). Whereas cortical atrophy in MS was poorly correlated with cortical f_soma, thalamic atrophy in MS demonstrated moderate correlation with decreased thalamic f_soma (r=0.311, <i>p</i>=0.054) and decreased cortical f_soma (r=0.474, <i>p</i>=0.008). <h3>Conclusions:</h3> SANDI metrics, in particular f_soma, 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. <b>Disclosure:</b> Ms. Krijnen has nothing to disclose. Andrew Russo has nothing to disclose. Dr. Salim Karam has nothing to disclose. The institution of Menno M Schoonheim has received research support from Dutch MS Research Foundation. The institution of Menno M Schoonheim has received research support from Eurostars-EUREKA. The institution of Menno M Schoonheim has received research support from ARSEP. The institution of Menno M Schoonheim has received research support from Amsterdam Neuroscience. The institution of Menno M Schoonheim has received research support from MAGNIMS. The institution of Menno M Schoonheim has received research support from ZonMW. The institution of Menno M Schoonheim has received research support from Atara Biotherapeutics. The institution of Menno M Schoonheim has received research support from Biogen. The institution of Menno M Schoonheim has received research support from Celgene/Bristol Meyers Squibb. The institution of Menno M Schoonheim has received research support from Genzyme. The institution of Menno M Schoonheim has received research support from MedDay. The institution of Menno M Schoonheim has received research support from Merck. Dr. Huang has received personal compensation in the range of $0-$499 for serving as a Consultant for Siemens Healthineers. The institution of Dr. Huang has received research support from Siemens Healthineers. The institution of Dr. Huang has received research support from Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Galen/Atlantica. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Banner Life Sciences. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Klawiter has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for OM1. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Klawiter has received research support from Biogen. The institution of Dr. Klawiter has received research support from Abbvie. The institution of Dr. Klawiter has received research support from Genentech.