Angiogenesis Detected After Embolic Stroke in Rat Brain Using Magnetic Resonance T2*WI

Abstract

Background and Purpose-This study uses T 2 * weighted imaging (T2*WI) to measure the temporal evolution of cerebral angiogenesis in rats subjected to embolic stroke up to 6 weeks after stroke onset with or without sildenafil treatment. Method-Male Wistar rats were subjected to embolic stroke and treated with saline (nϭ10) or with sildenafil (nϭ11), with treatment initiated at 24 hours and continued daily for 7 days after onset of ischemia. T2*WI measurements were performed at 24 hours after embolization and weekly up to 6 weeks using a 7-Tesla system. Histological measurements were obtained at 6 weeks after MRI scans. Results-Using T2*WI, cerebral angiogenesis was detected starting from 4 weeks and from 2 weeks after onset of embolic stroke in saline and sildenafil treated rats, respectively. Significant differences in the temporal and spatial features of angiogenesis after embolic stroke up to 6 weeks after onset of stroke were found between saline and sildenafil treated rats and were identified with T2*WI. MRI permeability parameter, K i , complementarily detected angiogenesis after ischemia in embolic stroke rats. Sildenafil treatment of stroke rats significantly enhanced the angiogenesis, as confirmed histologically. Conclusions-T2*WI can quantitatively measure the temporal evolution of angiogenesis in rats subjected to embolic stroke. Compared to control rats, sildenafil treatment significantly increased angiogenesis in treated animals up to 6 weeks after stroke.

Monitoring Brain Repair in Stroke Using Advanced Magnetic Resonance Imaging

“…24,38 In a rat model of stroke, perilesional angiogenesis was successfully identified on T2* and susceptibility-weighted imaging maps. 36 These techniques also detected an accelerated angiogenetic profile with sildenafil, and regions exhibiting T2* shortening spatially matched with those with elevated K i .…”

“…In another study, K i elevation was detected 1 to 3 weeks after stroke in sildenafil-treated animals compared with 1 to 6 weeks in controls, suggesting that therapy accelerates angiogenesis, and this is measurable with imaging. 36 Newly developed vasculature rich in venous blood can be detected with blood oxygenation level-dependent MRI. 36 This exploits the local magnetic field disturbances induced by the relatively high magnetic susceptibility of deoxygenated hemoglobin, which provides T2 contrast on spin-echo images and a larger T2* contrast on gradient echo images.…”

“…36 Newly developed vasculature rich in venous blood can be detected with blood oxygenation level-dependent MRI. 36 This exploits the local magnetic field disturbances induced by the relatively high magnetic susceptibility of deoxygenated hemoglobin, which provides T2 contrast on spin-echo images and a larger T2* contrast on gradient echo images. 37 Susceptibility-weighted imaging, a variant of T2*-weighted MRI that includes phase information, can further enhance the contrast of the areas with increased magnetic susceptibility.…”

In Vivo Imaging of Neurovascular Remodeling After Stroke

“…Local magnetic field inhomogeneities caused by the relatively high levels of paramagnetic deoxyhemoglobin in venules and veins result in a lower signal intensity on T 2 *-weighted and susceptibility-weighted images, which have been used to identify maturing angiogenesis in sildenafil-treated rats after embolic stroke. 35 A characteristic pattern of significant T 2 * shortening in ipsilesional brain regions was associated with angiogenesis. It should be noted, however, that local tissue T 2 * is also influenced by other factors associated with cerebrovascular disease, such as parenchymal hemorrhage and iron accumulation in macrophages.…”

Angiopoietin-2 is Vasoprotective in the Acute Phase of Cerebral Ischemia

“…[3][4][5] Vascular endothelial growth factor (VEGF), the main angiogenic growth factor, 6,7 is a key regulator of this ischemia-induced vascular restructuration. Indeed, in the acute phase of stroke, VEGF is involved in vasogenic edema formation due to its permeabilizing effect.…”