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Cerebral blood volume estimation by ferumoxytol-enhanced steady-state MRI at 9.4 T reveals microvascular impact of α(1)-adrenergic receptor antibodies

Item Type:Article
Title:Cerebral blood volume estimation by ferumoxytol-enhanced steady-state MRI at 9.4 T reveals microvascular impact of α(1)-adrenergic receptor antibodies
Creators Name:Pohlmann, A. and Karczewski, P. and Ku, M.C. and Dieringer, B. and Waiczies, H. and Wisbrun, N. and Kox, S. and Palatnik, I. and Reimann, H.M. and Eichhorn, C. and Waiczies, S. and Hempel, P. and Lemke, B. and Niendorf, T. and Bimmler, M.
Abstract:Cerebrovascular abnormality is frequently accompanied by cognitive dysfunctions, such as dementia. Antibodies against the alpha1-adrenoceptor (alpha1-AR) can be found in patients with Alzheimer's disease with cerebrovascular disease, and have been shown to affect the larger vessels of the brain in rodents. However, the impact of alpha1-AR antibodies on the cerebral vasculature remains unclear. In the present study, we established a neuroimaging method to measure the relative cerebral blood volume (rCBV) in small rodents with the ultimate goal to detect changes in blood vessel density and/or vessel size induced by alpha1-AR antibodies. For this purpose, mapping of R2 * and R2 was performed using MRI at 9.4 T, before and after the injection of intravascular iron oxide particles (ferumoxytol). The change in the transverse relaxation rates (DeltaR2 *, DeltaR2) showed a significant rCBV decrease in the cerebrum, cortex and hippocampus of rats (except hippocampal DeltaR2), which was more pronounced for DeltaR2 * than for DeltaR2. Immunohistological analyses confirmed that the alpha1-AR antibody induced blood vessel deficiencies. Our findings support the hypothesis that alpha1-AR antibodies lead to cerebral vessel damage throughout the brain, which can be monitored by MRI-derived rCBV, a non-invasive neuroimaging method. This demonstrates the value of rCBV estimation by ferumoxytol-enhanced MRI at 9.4 T, and further underlines the significance of this antibody in brain diseases involving vasculature impairments, such as dementia.
Keywords:MRI, Cerebral Blood Volume (CBV), Ferumoxytol, Ultrasmall Superparamagnetic Iron Oxide (USPIO), alpha1-Adrenergic Receptor, Antibody, Animals, Rats
Source:NMR in Biomedicine
ISSN:0952-3480
Publisher:Wiley-Blackwell
Volume:27
Number:9
Page Range:1085-1093
Date:September 2014
Official Publication:https://doi.org/10.1002/nbm.3160
PubMed:View item in PubMed

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