CSF-In Gradient of Thalamic and Cortical Damage in Multiple Sclerosis: A 3T Magnetization Transfer Ratio Study (S27.002)

<h3>Objective:</h3> To explore the cortical and thalamic microstructural abnormalities in MS patients according to a progressive distance from the CSF and their clinical relevance. <h3>Background:</h3> A CSF-in gradient in cortical and thalamic damage has been suggested in multiple sclerosis (MS), possibly due to CSF-mediated pathological processes. However, this pattern of damage has not been explored in vivo and concurrently both in the cortex and in the thalamus yet. <h3>Design/Methods:</h3> Brain 3T-MRI sequences were acquired from 52 MS patients (33 relapsing-remitting [RR], 19 progressive [P]) and 56 healthy controls (HC). From 3DT1-weighted sequences, cortical layers sampled at 25%–50%–75% depths from white matter (WM)-cortical interface (Freesurfer) and thalamic concentric bands at 1-2-3-voxels from ventricular-thalamus interface (in-house implemented method) were derived. Between-group comparisons of magnetization transfer ratio (MTR) values, as myelination index in cortical and thalamic layers and their correlations with clinical and structural measures were evaluated using linear mixed models and Spearman correlations. <h3>Results:</h3> Compared with HC, RRMS and PMS patients showed significantly lower MTR values in the most superficial cortical layer (RRMS=−1.23%, p=0.006, PMS=−1.70%, p=0.002), without between-group differences. Compared to HC, RRMS and PMS patients showed significantly lower MTR values in the band closest to the ventricles (RRMS=−1.63%, p=0.015, PMS=−3.62%, p&lt;0.001). PMS showed also a significantly lower MTR in ventricle-closest band compared to RRMS (p=0.022) and in the second band compared to HC (−1.07%, p=0.048). Lower MTR values of CSF-closest cortical and thalamic layers were significantly correlated with longer disease duration, higher Expanded Disability Status Scale (EDSS) score, higher WM lesion volume (r from −0.45 to −0.35, p≤0.011), lower normalized brain, thalamic and cortical volumes (r from 0.42 to 0.56, p≤0.002). <h3>Conclusions:</h3> In MS, a clinically-relevant CSF-in gradient of damage can be detected at 3T in the cortex and thalamus, being more substantial in the thalamus and in PMS. <b>Disclosure:</b> Dr. Rubin has nothing to disclose. Elisabetta Pagani has nothing to disclose. Loredana Storelli has nothing to disclose. Alessandro Meani has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Monica Margoni has received research support from MAGNIMS. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).