Cerebral blood volume estimation by ferumoxytol‐enhanced steady‐state MRI at 9.4 T reveals microvascular impact of α1‐adrenergic receptor antibodies

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. Copyright © 2014 John Wiley & Sons, Ltd.