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

J Cereb Blood Flow Metab. 2016 Sep;36(9):1614-24. doi: 10.1177/0271678X15621500. Epub 2015 Dec 1.

Abstract

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 [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] and quantitative susceptibility mapping constitute quantitative tools to monitor such functional microvasculopathies.

Keywords: Cerebral amyloid angiopathy; P904; effective transverse relaxation time; magnetic susceptibility; perivascular macrophages; quantitative susceptibility mapping; superparamagnetic iron oxide particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Amyloid Angiopathy / diagnostic imaging*
  • Cerebral Amyloid Angiopathy / metabolism
  • Cerebrovascular Circulation
  • Contrast Media
  • Ferric Compounds / pharmacokinetics*
  • Macrophages / metabolism
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Microvessels / pathology*

Substances

  • Contrast Media
  • Ferric Compounds
  • ferric oxide