Relationship between iron accumulation and white matter injury in multiple sclerosis: a case-control study

Despite the increasing development and applications of iron imaging, the pathophysiology of iron accumulation in multiple sclerosis (MS), and its role in disease progression and development of clinical disability, is poorly understood. The aims of our study were to determine the presence and extent of iron in T2 visible lesions and gray and white matter using magnetic field correlation (MFC) MRI and correlate with microscopic white matter (WM) injury as measured by diffusion tensor imaging (DTI). This is a case-control study including a series of 31 patients with clinically definite MS. The mean age was 39 years [standard deviation (SD) = 9.55], they were 11 males and 20 females, with a disease duration average of 3 years (range 0-13) and a median EDSS of 2 (0-4.5). Seventeen healthy volunteers (6 males and 11 females) with a mean age of 36 years (SD = 11.4) were recruited. All subjects underwent MR imaging on a 3T scanner using T2-weighted sequence, 3D T1 MPRAGE, MFC, single-shot DTI and post-contrast T1. T2-lesion volumes, brain volumetry, DTI parameters and iron quantification were calculated and multiple correlations were exploited. Increased MFC was found in the putamen (p = 0.061), the thalamus (p = 0.123), the centrum semiovale (p = 0.053), globus pallidus (p = 0.008) and gray matter (GM) (p = 0.004) of MS patients compared to controls. The mean lesional MFC was 121 s(-2) (SD = 67), significantly lower compared to the GM MFC (<0.0001). The GM mean diffusivity (MD) was inversely correlated with the MFC in the centrum semiovale (p < 0.001), and in the splenium of the corpus callosum (p < 0.001). Patients with MS have increased iron in the globus pallidus, putamen and centrum with a trend toward increased iron in all the brain structures. Quantitative iron evaluation of WM and GM may improve the understanding of MS pathophysiology, and might serve as a surrogate marker of disease progression.