Prediction of impending hemorrhagic transformation in ischemic stroke using magnetic resonance imaging in rats.
OBJECTIVE
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.
Knight
R A
RA
Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich 48202, USA. Knight@neurnis.neuro.hfh.edu
Barker
P B
PB
Fagan
S C
SC
Li
Y
Y
Jacobs
M A
MA
Welch
K M
KM
D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D002423:Cause of Death; D016923:Cell Death; D002539:Cerebral Arterial Diseases / Q000150:complications; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003287:Contrast Media; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D005500:Follow-Up Studies; D005544:Forecasting; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011693:Purpura / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D018570:Risk Assessment; D012449:Safety; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013997:Time Factors
D003287:Contrast Media; D019786:Gadolinium DTPA