title: Prediction of impending hemorrhagic transformation in ischemic stroke using magnetic resonance imaging in rats.
abstract: 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.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich 48202, USA. Knight@neurnis.neuro.hfh.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Knight
authors.forename: P B
authors.initials: PB
authors.lastname: Barker
authors.forename: S C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: M A
authors.initials: MA
authors.lastname: Jacobs
authors.forename: K M
authors.initials: KM
authors.lastname: Welch
mesh_terms: 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
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA