Progressive Iron Accumulation Across Multiple Sclerosis Phenotypes Revealed by Sparse Classification of Deep Gray Matter

Purpose: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. Materials and Methods: R2*/ QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls. Sparse classification for R2*/ QS maps of segmented caudate nucleus (CN), putamen (PU), thalamus (TH), and globus pallidus (GP) structures produced localized maps of iron/ myelin in MS patients relative to controls. Paired t-tests, with age as a covariate, were used to test for statistical significance (P <= 0.05). Results: In addition to DGM structures found significantly different in patients compared to controls using whole region analysis, singular sparse analysis found significant results in RRMS PU R2* (P50.03), TH R2* (P50.04), CN QS (P50.04); in SPMS CN R2* (P50.04), GP R2* (P50.05); and in PPMS CN R2* (P50.04), TH QS (P50.04). All sparse regions were found to conform to an iron accumulation pattern of changes in R2*/ QS, while none conformed to demyelination. Intersection of sparse R2*/ QS regions also resulted in RRMS CN R2* becoming significant, while RRMS R2* TH and PPMS QS TH becoming insignificant. Common iron-associated volumes in MS patients and their effect size progressively increased with advanced phenotypes. Conclusion: A localized technique for identifying sparse regions indicative of iron or myelin in the DGM was developed. Progressive iron accumulation with advanced MS phenotypes was demonstrated, as indicated by iron-associated sparsity and effect size. Level of Evidence: 1 Technical Efficacy: Stage 1