Abstract

Objective: To investigate the differences of purported iron levels in a large sample of patients with multiple sclerosis (MS) using the novel iron-sensitive MRI measure quantitative susceptibility mapping (QSM). Background: Previous research using a variety of MRI iron-detection sensitive methods has shown that MS patients tend to have increased iron levels, especially in the deep gray matter (DGM). Large scale case-control studies using the novel QSM method have, however, not been carried out to date. Methods: 985 MS patients (relapsing-remitting (RR): 709, secondary-progressive: 231, primary-progressive: 45) and 228 age- and sex-matched healthy controls (HCs) were recruited for the present study. QSM susceptibility was determined for DGM structures with higher susceptibility representing higher iron levels. Associations with clinical and MRI measures were explored using Spearman’s correlation coefficient. MS vs. HC comparisons were conducted using analysis of variance, while RR vs progressive MS were adjusted for age. Results: Susceptibility was significantly higher in MS patients in the caudate (p<.001), globus pallidus (p<.001), putamen (p=.006) and DGM (p=.022). Thalamic susceptibility, however, was lower in MS patients than in HCs (p<.001). Thalamic susceptibility was significantly lower (p<.001), while pallidus susceptibility was significantly higher (p=.026) in progressive MS patients compared to relapsing patients. In MS, higher DGM susceptibility was associated with EDSS (r=.127 - .263, p<.001), disease duration (r=.095 - .316, p<.001), T2 lesion load (r=.153 - .387, p<.001) and lower normalized whole brain (r=-.289 - -.366, p<.001) and DGM volumes (r= -.193 - -.408, p<.001). Correlations were strongest among RR MS patients. Conclusion: The present work utilized a large sample of MS patients and HC to investigate QSM susceptibility representing DGM iron levels. MS patients had elevated susceptibility levels, except in the thalamus where susceptibility levels were lower. Higher QSM susceptibility was associated with disability and other MRI inflammatory and neurodegenerative measures. Disclosure: Dr. Hagemeier has nothing to disclose. Dr. Ferdinand has nothing to disclose. Dr. Dwyer has received personal compensation for activities with Claret Medical and EMD Serono. Dr. Polak has nothing to disclose. Dr. Bergsland has nothing to disclose. Dr. Weinstock-Guttman has received personal compensation for activities with Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, Novartis, Genzyme & Sanofi, Mylan, and Acorda. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, Novartis, Claret Medical Inc., and Genzyme Corporation as a speaker and/or consultant.