Mapping of thalamic magnetic susceptibility in multiple sclerosis indicates decreasing iron with disease duration: A proposed mechanistic relationship between inflammation and oligodendrocyte vitality

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 advan...

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Published in:	NeuroImage (Orlando, Fla.) Vol. 167; pp. 438 - 452
Main Authors:	Schweser, Ferdinand, Raffaini Duarte Martins, Ana Luiza, Hagemeier, Jesper, Lin, Fuchun, Hanspach, Jannis, Weinstock-Guttman, Bianca, Hametner, Simon, Bergsland, Niels, Dwyer, Michael G., Zivadinov, Robert
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15-02-2018 Elsevier Limited
Subjects:	Adult Aged Axons Cognitive ability Demyelinating Diseases - diagnostic imaging Demyelinating Diseases - immunology Demyelinating Diseases - metabolism Disease Fatigue Female Homeostasis Humans Inflammation - immunology Inflammation - metabolism Iron Iron - metabolism Magnetic properties Magnetic Resonance Imaging Magnetic susceptibility Male Medical imaging Memory Microglia Middle Aged Multiple sclerosis Multiple Sclerosis, Chronic Progressive - diagnostic imaging Multiple Sclerosis, Chronic Progressive - immunology Multiple Sclerosis, Chronic Progressive - metabolism Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging Multiple Sclerosis, Relapsing-Remitting - immunology Multiple Sclerosis, Relapsing-Remitting - metabolism Neurodegeneration NMR Nuclear magnetic resonance Oligodendrocytes Oligodendroglia - metabolism Pathology Pulvinar QSM Quantitative susceptibility mapping Substantia grisea Thalamus Thalamus - diagnostic imaging Thalamus - metabolism Time Factors Tomography Young Adult Thalamus Multiple sclerosis Quantitative susceptibility mapping QSM Iron
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Summary:	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. [Display omitted] •VBA reveals disease-related focal changes in magnetic susceptibility.•Thalamic magnetic susceptibility is reduced in definite MS, but not CIS.•Reduction of thalamic magnetic susceptibility is associated with disease duration.•Findings are suggestive of oligodendroglial iron depletion.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1053-8119 1095-9572
DOI:	10.1016/j.neuroimage.2017.10.063