Imaging of the inflammatory response in reperfusion injury after transient cerebral ischemia in rats: Correlation of superparamagnetic iron oxide-enhanced magnetic resonance imaging with histopathology

Background: Acute inflammatory responses have been thought to play a central role in ischemia-reperfusion injury after acute ischemic stroke. Superparamagnetic iron oxide (SPIO) particles have been known to enable in-vivo monitoring of macrophage infiltration by magnetic resonance imaging (MRI) in the experimental ischemic rat brain. Purpose: To determine whether the accumulation of macrophages could be seen in vivo in a reperfusion animal model after focal cerebral ischemia using SPIO-enhanced MRI. Material and Methods: Thirty-four adult male rats were enrolled in this study. SPIO particles were injected into the rats at different time points after 1-hour transient occlusion of the middle cerebral artery, and three-dimensional (3D) T2*-weighted magnetic resonance (MR) images with a gradient-echo sequence were performed 24 hours later. Histochemical iron staining was compared with T2* signal abnormalities. Results: At days 3 and 4 post-reperfusion, focal areas of signal loss indicating local accumulation of SPIO particles appeared in a part of the damaged brain. Areas of signal loss corresponded to local accumulation of iron-laden macrophages in histologic sections, and SPIO-induced signal loss indicated active macrophage transmigration into the reperfused brain. Conclusion: SPIO-enhanced MRI demonstrated through in-vivo monitoring that macrophages participate in reperfusion injury at early stages of injury development. SPIO-enhanced MRI could be a useful tool to examine the inflammatory mechanisms involved in reperfusion brain injury.