Recent advances in susceptibility MRI have dramatically improved the visualization of deep gray matter brain regions and the quantification of their magnetic properties in vivo, providing a novel tool to study the poorly understood iron homeostasis in the human brain. In this study, we used an advanced combination of the recent quantitative susceptibility mapping technique with dedicated analysis methods to study intra-thalamic tissue alterations in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS). Thalamic pathology is one of the earliest hallmarks of MS and has been shown to correlate with cognitive dysfunction and fatigue, but the mechanisms underlying the thalamic pathology are poorly understood. We enrolled a total of 120 patients, 40 with CIS, 40 with Relapsing Remitting MS (RRMS), and 40 with Secondary Progressive MS (SPMS). For each of the three patient groups, we recruited 40 controls, group matched for age- and sex (120 total). We acquired quantitative susceptibility maps using a single-echo gradient echo MRI pulse sequence at 3 T. Group differences were studied by voxel-based analysis as well as with a custom thalamus atlas. We used threshold-free cluster enhancement (TFCE) and multiple regression analyses, respectively. We found significantly reduced magnetic susceptibility compared to controls in focal thalamic subregions of patients with RRMS (whole thalamus excluding the pulvinar nucleus) and SPMS (primarily pulvinar nucleus), but not in patients with CIS. Susceptibility reduction was significantly associated with disease duration in the pulvinar, the left lateral nuclear region, and the global thalamus. Susceptibility reduction indicates a decrease in tissue iron concentration suggesting an involvement of chronic microglia activation in the depletion of iron from oligodendrocytes in this central and integrative brain region. Not necessarily specific to MS, inflammation-mediated iron release may lead to a vicious circle that reduces the protection of axons and neuronal repair.

No abstract

To perform follow-up brain MRI in volunteer participants who had previously received multiple doses of gadobutrol and to assess for changes in signal intensities and relaxation times. Materials and Methods: This prospective study included 160 participants who received gadobutrol only between 2007 and 2017. The participants were separated into two groups, including participants with at least five contrast agent-enhanced examinations and normal kidney function (group 1) or at least one examination and impaired renal function (group 2). Control groups with normal and impaired renal function (groups 3 and 4) without history of contrast agent exposure were included for comparison. Unenhanced brain MRI was performed in 220 participants (76, 84, 25, and 35 participants in groups 1-4, respectively) with T1weighted spin-echo and T1 and T2 mapping to determine visual signal intensity changes, signal intensity ratios (globus pallidus-tothalamus and dentate nucleus-to-pons ratios), and T1 and T2 relaxation times. Results: In groups 1 and 2, neither visual signal alterations nor differences in signal intensity ratio or T2 mapping were found. T1 mapping showed no changes for dentate nucleus, pons, and thalamus. However, shorter T1 relaxation times in the globus pallidus were found in group 1 compared with group 3 (difference of 226.2 msec; P = .002), which correlated with the number of previous gadobutrol doses in this group (P = .001). Conclusion: In study participants who had previously received gadobutrol, brain MRI showed no differences relative to healthy control participants without gadobutrol exposure. However, quantitative T1 measurements might indicate gadolinium retention in the globus pallidus.