MRI detection of macrophage activity after experimental stroke in rats: new indicators for late appearance of vascular degradation?

Focal cerebral ischemia was induced in rats and followed with high-resolution MRI methods for a chronic period of 10 weeks. Two weeks after stroke induction and at the end of the observation period, conventional histological analysis was combined with immunohistochemical staining for macrophages and with Prussian blue staining for the detection of ferric iron. In the late chronic phase, a patchy hypointensity was observed in the ischemic caudoputamen exclusively on T2*-weighted (T2*W) images, with no change in quantitative T(1) and T(2) relaxation time maps. This characteristic MRI pattern is different from hemorrhagic transformations (HTs) at earlier time points (2 weeks post stroke induction), which became apparent on images of all three imaging sequences. The exclusive T2*-sensitive hypointensity colocalized with iron-positive macrophages in the lesion territory at this time. These iron-containing macrophages were found predominantly around blood vessels in the ischemic tissue, and interpreted as the result of a phagocytotic incorporation of red blood cells leaking from slowly degrading vessels. The present investigation demonstrates the sensitivity of heavily T2*W 3D MRI for observing the inflammatory response in the chronic phase after stroke, without prior systemic labeling of the blood-borne macrophages by iron oxide nanoparticles.