Prediction of Impending Hemorrhagic Transformation in Ischemic Stroke Using Magnetic Resonance Imaging in Rats

Abstract

Background and Purpose-Hemorrhagic transformation (HT) of ischemic brain tissue may occur in stroke patients either spontaneously or after thrombolysis. A method to assess the risk of HT in ischemic tissue after stroke would improve the safety of thrombolytic therapy. As a means of predicting HT, we investigated the role of contrast-enhanced MRI at acute time points in a rat middle cerebral artery occlusion model with reperfusion. Methods-Intraluminal suture occlusion of the middle cerebral artery was used to produce transient ischemia in male Wistar rats (nϭ11). Reperfusion was performed by withdrawal of the occluding filament after 2 (nϭ4), 3 (nϭ6), or 4 (nϭ1) hours. MRI studies were performed before and after reperfusion with the use of conventional T1-weighted imaging, with and without gadolinium (Gd-DTPA) contrast agent, and T2-weighted imaging. Follow-up MRI and histological studies were obtained at 24 hours. Results-Petechial hemorrhage occurred by 24 hours in 9 of 11 animals. All animals showed brain swelling and cellular death throughout the ischemic region at 24 hours. A hyperintense region in the preoptic area became visible after Gd-DTPA injection within minutes after reperfusion in animals with subsequent HT. All animals showing acute Gd-DTPA enhancement subsequently developed petechial hemorrhage (or died) by 24 hours. In these animals, statistically significant differences in signal intensity (Pϭ.0005) between the ipsilateral enhancing region and a homologous contralateral region were detected on post-Gd-DTPA T1-weighted imaging. There was also a statistically significant correlation (Pϭ.01) between the rate of Gd-DTPA uptake and the size of the enhancing area. Two animals did not enhance with Gd-DTPA and did not exhibit hemorrhage on histological examination or MRI at 24 hours. No abnormalities were seen on precontrast T1-weighted images before and shortly after reperfusion or postcontrast T1-weighted images before reperfusion. Conclusions-The primary finding of this study was the detection of early Gd-DTPA parenchymal enhancement in 82% of the animals after reperfusion. Enhancement was seen before any detectable hemorrhage, suggesting that early endothelial ischemic damage occurs before gross brain infarction and hemorrhage. Thus, we suggest that acute Gd-DTPA enhancement may provide an early prediction of petechial hemorrhage. (Stroke. 1998;29:144-151.)

Measuring Elevated Microvascular Permeability and Predicting Hemorrhagic Transformation in Acute Ischemic Stroke Using First-Pass Dynamic Perfusion CT Imaging

“…Abnormal BBB permeability can be seen qualitatively as parenchymal enhancement in conventional delayed postgadolinium enhanced MR imaging, with enhancement in the early period of AIS being predictive of HT. [32][33][34] A conventional contrast-enhanced CT is not a component of our multimodal stroke series protocol, and no contrast-enhanced CT or MR imaging was performed during the follow-up period for our cohort. Therefore, we could not assess for conventional parenchymal enhancement in a region with elevated PS.…”

Acute blood–brain barrier opening in experimentally induced focal cerebral ischemia is preferentially identified by quantitative magnetization transfer imaging

“…Reperfusion was performed approximately 3 h following MCA occlusion by withdrawing the filament until its tip was visible in the ECA and it no longer occluded the MCA or restricted flow in the ICA. This model usually produces petechial hemorrhages in the preoptic area (POA) and caudate-putamen (CPU) at 24 h after MCA occlusion (11)(12)(13).…”

Contrast-Enhanced MR Imaging in Acute Ischemic Stroke: T2* Measures of Blood-Brain Barrier Permeability and Their Relationship to T1 Estimates and Hemorrhagic Transformation

“…Techniques capable of characterizing BBB integrity may prove particularly valuable in this regard, because there is a credible association between BBB disruption and HT. 3,4 Studies performed both in rats [5][6][7] and in patients with AIS 8,9 have indicated that permeability imaging with T1-weighted DCE-MR imaging may offer a viable strategy for detecting BBB disruption in the early hours following stroke onset, with significant increases in permeability estimates corresponding to areas of subsequent HT.…”