Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat

Thrombolytic therapy with rtPA increases the risk of hemorrhagic transformation (HT) after cerebral ischemia. We employed contrast enhancement MRI with Gd-DTPA to detect HT in a rat model of embolic stroke treated with rtPA and a glycoprotein IIb/IIIa receptor antagonist, 7E3 F(ab')(2), at 4 h after embolic stroke. Male Wistar rats were subjected to embolic stroke and treated with the combination of rtPA and 7E3 F(ab')(2) (n=12) or with saline (n = 10) at 4 h after onset of stroke. MRI studies were performed immediately and at 24 h after embolization using a 7-T system. Histological measurements were obtained at 48 h. With Gd-DTPA, T1WI images and permeability related MRI parameters (the blood-to-brain transfer constant, K-i, and the distribution volume of mobile protons, V-p) of 15 out of 18 animals showed hyperintensity regions in gross or microscopic HT areas at 24 h, confirmed histologically at 48 h post stroke. Contrast enhancement MRI detected six of seven (86%) animals with gross HT and nine of eleven (82%) animals with microscopic HT at 24 h after ischemia. Two of eighteen animals with HT, had MRI indices of hemorrhage at 3 h post stroke. However, compared to HT data measured histologically at 48 h in embolic stroke rats, the enhanced areas by Gd-DTPA at 24 h were larger, and the patterns (time, intensity and region) did not directly correlate to the subtypes of HT, i.e., gross or microscopic hemorrhage. Contrast enhancement MRI using Gd-DTPA provides a method to detect gross and microscopic HT after stroke in rats. (c) 2006 Elsevier B.V. All rights reserved.