Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter.

Abstract

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. 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). 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* (P = 0.03), TH R2* (P = 0.04), CN QS (P = 0.04); in SPMS CN R2* (P = 0.04), GP R2* (P = 0.05); and in PPMS CN R2* (P = 0.04), TH QS (P = 0.04). 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. 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. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1464-1473.