Radiology
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Published online before print June 20, 2007, 10.1148/radiol.2442061316
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(Radiology 2007;244:429-438.)
© RSNA, 2007

Experimental Studies

Microplasmin and Tissue Plasminogen Activator: Comparison of Therapeutic Effects in Rat Stroke Model at Multiparametric MR Imaging1

Feng Chen, MD, Yasuhiro Suzuki, PhD, Nobuo Nagai, PhD, Xihe Sun, MD, Huaijun Wang, MD, Jie Yu, MD, Guy Marchal, MD, PhD, and Yicheng Ni, MD, PhD

1 From the Department of Radiology, University Hospitals, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium (F.C., X.S., H.W., J.Y., G.M., Y.N.); Department of Radiology, Zhong Da Hospital, Southeast University, Nanjing, Jiangsu Province, China (F.C.); Department of Molecular and Vascular Biology, Faculty of Medicine, University of Leuven, Leuven, Belgium (Y.S., N.N.); Department of Pharmacology, Hamamatsu University, Hamamatsu, Japan (Y.S.); and the Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, China (X.S.). Received July 31, 2006; revision requested October 5; revision received October 12; final version accepted December 1. Address correspondence to Y.N. (e-mail: yicheng.ni{at}med.kuleuven.be).

Purpose: To prospectively compare therapeutic and hemorrhagic effects of microplasmin and tissue plasminogen activator (tPA) in stroke therapy by using multiparametric magnetic resonance (MR) imaging in a photothrombotic rat stroke model.

Materials and Methods: The animal experiment complied with institutional regulations for laboratory animals. Stroke was induced in rats with photothrombotic occlusion of middle cerebral artery (MCA). T2-weighted, perfusion-weighted (PW), and diffusion-weighted (DW) MR imaging was performed 1 hour and 24 hours after occlusion. On the basis of PW and DW images at 1 hour, 49 rats with cortex and subcortex involvement and with perfusion-diffusion mismatch were randomly assigned into one of four groups: control group, group treated with 7.5 mg microplasmin, group treated with 10 mg/kg microplasmin, or group treated with 10 mg/kg tPA. Agents were intravenously injected 1.5 hours after occlusion. Infarct size and hemorrhagic transformation were assessed with MR imaging and histomorphologic findings. Neurologic deficit was scored. Measurements were statistically analyzed.

Results: There were 13 rats in the control group, 13 in the 7.5 mg/kg microplasmin group, nine in the 10 mg/kg microplasmin group, and 14 in the 10 mg/kg tPA group. Despite similar baseline perfusion-diffusion mismatch, histochemically defined total infarct volume was reduced from 25% ± 5 (standard deviation) in control group to 21% ± 2, 20% ± 4, and 20% ± 5 in 7.5 mg/kg microplasmin, 10 mg/kg microplasmin, and tPA groups, respectively, as similarly shown on T2-weighted, DW, and PW images at 24 hours (P < .05). Cerebral hemorrhage rate at 24 hours was higher in tPA group than in the other three groups. Bederson score of neurologic deficits was significantly reduced in treated groups compared with that in control group.

Conclusion: Perfusion-diffusion mismatch appeared useful in selecting candidates for thrombolytic therapy. Multiparametric MR imaging allowed noninvasive assessment of effects of microplasmin and tPA in rats; microplasmin had a significantly lower hemorrhagic rate.

© RSNA, 2007