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(Stroke. 1998;29:144-151.)
© 1998 American Heart Association, Inc.

Original Contributions

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

R. A. Knight, PhD; P. B. Barker, DPhil; S. C. Fagan, PharmD; Y. Li, MD; M. A. Jacobs, BS; K. M. A. Welch, MD

From the Departments of Neurology (R.A.K., P.B.B., Y.L., M.A.J., K.M.A.W.) and Pharmacy (S.C.F.), Henry Ford Health Sciences Center, Detroit, Mich; College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, Mich (S.C.F.); and Department of Physics, Oakland University, Rochester, Mich (R.A.K., P.B.B., M.A.J., K.M.A.W.).

Correspondence to Robert A. Knight, PhD, Department of Neurology, NMR Facility, Henry Ford Health Sciences Center, 2799 W Grand Blvd, Detroit, MI 48202. E-mail Knight{at}neurnis.neuro.hfh.edu

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 (n=11). Reperfusion was performed by withdrawal of the occluding filament after 2 (n=4), 3 (n=6), or 4 (n=1) 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 (P=.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 (P=.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.

Editorial Comment

Marc Fisher, MD, Guest Editor

University of Massachusetts, Medical School and, Memorial Health Care Worcester, Massachusetts

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