Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI

Magnetic resonance imaging employing administration of iron oxide-based contrast agents is widely used to visualize cellular and molecular processes in vivo. In this study, we investigated the ability of R 2 ∗ and quantitative susceptibility mapping to quantitatively assess the accumulation of ultrasmall superparamagnetic iron oxide (USPIO) particles in the arcAβ mouse model of cerebral amyloidosis. Gradient-echo data of mouse brains were acquired at 9.4 T after injection of USPIO. Focal areas with increased magnetic susceptibility and R 2 ∗ values were discernible across several brain regions in 12-month-old arcAβ compared to 6-month-old arcAβ mice and to non-transgenic littermates, indicating accumulation of particles after USPIO injection. This was concomitant with higher R 2 ∗ and increased magnetic susceptibility differences relative to cerebrospinal fluid measured in USPIO-injected compared to non-USPIO-injected 12-month-old arcAβ mice. No differences in R 2 ∗ and magnetic susceptibility were detected in USPIO-injected compared to non-injected 12-month-old non-transgenic littermates. Histological analysis confirmed focal uptake of USPIO particles in perivascular macrophages adjacent to small caliber cerebral vessels with radii of 2-8 μm that showed no cerebral amyloid angiopathy. USPIO-enhanced R 2 ∗ and quantitative susceptibility mapping constitute quantitative tools to monitor such functional microvasculopathies.