Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects.

Abstract

Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. Longitudinal (baseline and 2-year follow-up) retrospective study. Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects. 4.7T 10-echo gradient-echo acquisition. Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P = 0.1) to regress bulk and DARE measures with the follow-up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease (r = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS (r = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS (r = 0.68; Q = 0.0005). DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age-matched controls, respectively. Specific DARE measures of MS DGM correlated with follow-up MSSS, and may reflect complex disease pathology. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.