title: Cerebral blood volume estimation by ferumoxytol-enhanced steady-state MRI at 9.4 T reveals microvascular impact of α1 -adrenergic receptor antibodies.
abstract: Cerebrovascular abnormality is frequently accompanied by cognitive dysfunctions, such as dementia. Antibodies against the α1 -adrenoceptor (α1 -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 α1 -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 α1 -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 (ΔR2 *, ΔR2 ) showed a significant rCBV decrease in the cerebrum, cortex and hippocampus of rats (except hippocampal ΔR2 ), which was more pronounced for ΔR2 * than for ΔR2 . Immunohistological analyses confirmed that the α1 -AR antibody induced blood vessel deficiencies. Our findings support the hypothesis that α1 -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.
authors: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Andreas
authors: A
authors: Pohlmann
authors: Peter
authors: P
authors: Karczewski
authors: Min-Chi
authors: MC
authors: Ku
authors: Babette
authors: B
authors: Dieringer
authors: Helmar
authors: H
authors: Waiczies
authors: Natali
authors: N
authors: Wisbrun
authors: Stefanie
authors: S
authors: Kox
authors: Irina
authors: I
authors: Palatnik
authors: Henning Matthias
authors: HM
authors: Reimann
authors: Christina
authors: C
authors: Eichhorn
authors: Sonia
authors: S
authors: Waiczies
authors: Petra
authors: P
authors: Hempel
authors: Bernd
authors: B
authors: Lemke
authors: Thoralf
authors: T
authors: Niendorf
authors: Marion
authors: M
authors: Bimmler
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001783:Blood Flow Velocity / Q000276:immunology; D001810:Blood Volume / Q000276:immunology*; D001811:Blood Volume Determination / Q000379:methods; D002560:Cerebrovascular Circulation / Q000276:immunology*; D003287:Contrast Media; D052203:Ferrosoferric Oxide; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D055806:Microvessels / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D003287:Contrast Media; D018340:Receptors, Adrenergic, alpha-1; D052203:Ferrosoferric Oxide
keywords: MRI; cerebral blood volume (CBV); ferumoxytol; rat; ultrasmall superparamagnetic iron oxide (USPIO); α1-adrenergic receptor antibody