Abstract
Dysregulation of brain iron homeostasis is a hallmark of many neurodegenerative diseases and can be associated with oxidative stress. The objective of this study was to investigate brain iron in patients with Neuromyelitis Optica (NMO) using quantitative susceptibility mapping (QSM), a quantitative iron-sensitive MRI technique. 12 clinically confirmed NMO patients (6 female and 6 male; age 35.4y±14.2y) and 12 age- and sex-matched healthy controls (7 female and 5 male; age 33.9±11.3y) underwent MRI of the brain at 3 Tesla. Quantitative maps of the effective transverse relaxation rate (R2*) and magnetic susceptibility were calculated and a blinded ROI-based group comparison analysis was performed. Normality of the data and differences between patients and controls were tested by Kolmogorov-Smirnov and t-test, respectively. Correlation with age was studied using Spearman’s rank correlation and an ANCOVA-like analysis. Magnetic susceptibility values were decreased in the red nucleus (p<0.01; d>0.95; between -15 and -22 ppb depending on reference region) with a trend toward increasing differences with age. R2* revealed significantly decreased relaxation in the optic radiations of five of the 12 patients (p<0.0001; -3.136±0.567 s-1). Decreased relaxation in the optic radiation is indicative for demyelination, which is in line with previous findings. Decreased magnetic susceptibility in the red nucleus is indicative for a lower brain iron concentration, a chemical redistribution of iron into less magnetic forms, or both. Further investigations are necessary to elucidate the pathological cause or consequence of this finding.
Highlights
Neuromyelitis optica (NMO) is a disabling autoimmune astrocytopathy characterized by typically severe and recurrent attacks of optic neuritis and longitudinally extensive myelitis [1,2]
We investigated brain iron and myelin in NMO patients using two advanced quantitative MR imaging techniques, R2Ã mapping and quantitative susceptibility mapping (QSM)
The observed decrease of magnetic susceptibility in the red nucleus may be interpreted as locally increased myelination
Summary
Neuromyelitis optica (NMO) is a disabling autoimmune astrocytopathy characterized by typically severe and recurrent attacks of optic neuritis and longitudinally extensive myelitis [1,2]. Diffusion tensor imaging [9,10] and diffusion kurtosis imaging [11] revealed significant alterations of several diffusion parameters [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity and radial diffusivity] in normal appearing white matter (WM) of patients with NMO when compared to controls, including the pyramidal tract, optic radiations and the corpus callosum (CC). These studies suggest that extensive occult damage in normal appearing white matter (WM) is related to both demyelination and Wallerian degeneration. Other advanced imaging techniques, such as MR spectroscopy [12,13] and magnetizationtransfer contrast imaging [12,14] show little success in detecting tissue changes in NMO
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