Quantitative and dynamic MRI of neuroprotection in experimental stroke.
Experimental studies of stroke in animal models have traditionally relied on histological endpoints for the measurement of neuroprotection. In this study, we used in vivo and dynamic MRI to quantify the neuroprotective effects of the non-competitive NMDA antagonist MK801. Four hours of occlusion followed by 6 h of reperfusion was performed in a rabbit model of focal cerebral ischemia. Spin-echo T2-weighted (T2W) MRI was used to quantify ischemic lesion volumes. Hemispheric measurements of perfusion deficits were assessed by using dynamic susceptibility-contrast MRI to map the first-pass transit of injected GdDTPA. Histological correlates of infarction were quantified using tetrazolium staining. Animals treated with 2 mg/kg MK801 infused immediately post-occlusion (n = 6) were compared with untreated controls (n = 8). T2W MRI scans obtained after 6 h of reperfusion showed high-intensity lesions in the ischemic basal ganglia and cortex. MK801-treated animals showed significantly decreased lesion volumes compared to untreated controls (7.3 +/- 3.2% treated vs 20.7 +/- 4.8% control, p < 0.05). Lesion volumes measured with MRI were significantly correlated with tetrazolium-defined infarct volumes (r = 0.766, p = 0.004). Dynamic MRI demonstrated the phenomenon of delayed hypoperfusion in the ischemic hemisphere during the late reperfusion phase; relative cerebral blood volume (rCBV) was 45.2 +/- 10.3% in untreated animals. MK801 slightly improved these deficits although the differences did not reach statistical significance (rCBV = 77.0 +/- 9.7%, p = 0.128).(ABSTRACT TRUNCATED AT 250 WORDS)
Pan
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Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown 02129, USA.
Lo
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Matsumoto
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Hamberg
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Jiang
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D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000503:physiopathology*; D004396:Coloring Agents; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D011817:Rabbits; D013778:Tetrazolium Salts
D004396:Coloring Agents; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C009591:triphenyltetrazolium