Boxplot.

<p>Boxplot of Susceptibilities (A; in ppb) and relaxations (B; in s^-1) of controls and patients with significant alterations are represented.</p

Quantitative Susceptibility Mapping Indicates a Disturbed Brain Iron Homeostasis in Neuromyelitis Optica – A Pilot Study

<div><p>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 <i>t</i>-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 (<i>p</i><0.01; <i>d</i>>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.</p></div

Magnetic susceptibilities of controls and patients in different brain regions.

<p>Magnetic susceptibilities of controls and patients in different brain regions.</p

Detailed analysis of susceptibility in the red nucleus.

<p>(a) Susceptibility of patients and controls as a function of age. The solid line indicates the fitted normal aging trajectory. The dotted lines represent the area that provided optimal separation of patients and controls. (b) ROC curve of the classification into patients and controls by shifting the aging trajectory in (a, straight line) and considering individuals with lower susceptibility as patients. (c) Diagnostic odds ratio of the separation.</p

Effective transverse relaxation rates (R₂*) of controls and patients in different brain regions.

<p>Effective transverse relaxation rates (R₂*) of controls and patients in different brain regions.</p

Scheme of the data SWI processing pipeline.

<p>Scheme of the data SWI processing pipeline.</p

Group comparison of SWI images between ALS patients and healthy controls.

<p>ALS patients showed lower SWI signal in deep white matter tracts, including corpus callosum, corticospinal and superior longitudinal fascicle most prominent in its frontal parts. The statistical parametric maps are displayed at a threshold <i>P</i> < 0.05 and corrected for multiple comparisons using FWE.</p

Patient characteristics.

<p>Patient characteristics.</p

Scatter plots of apparent diffusion coefficient (ADC), index of diffusion anisotropy (IDA) and T₁ relaxation times as a function of age for wild type (WT) and transgenic arcAβ (ArcAβ) mice.

<p><i>Cp/lgp</i> denotes caudate putamen and lateral globus pallidus.</p

Horizontal GRE magnitude images, susceptibility weighted images and quantitative susceptibility maps of a 21 month old arcAβ mouse.

<p>Suspected microbleeds are indicated by white arrows, while structures corresponding to vessel cross-sections are indicated by red arrows. The scale bar indicates 1 mm. Topography of cerebral microbleeds (CMBs) of a an arcAβ mouse with high CMB load at 13 (A), 18 (B) and 21 (C) months of age. Average projections of the registration template over an acquired slab of 2.1 mm thickness. The brain regions affected are predominantly the cortex and olfactory bulb and to a lesser extent the hippocampus. The CMB load increases with increasing age. The frequency of overlapping CMBs in 3D assessed at a single time point is indicated by the colour bar.</p