Delayed rt-PA treatment in a rat embolic stroke model: Diagnosis and prognosis of ischemic injury and hemorrhagic transformation with magnetic resonance imaging

The authors characterized effects of late recombinant tissue plasminogen activator (rt-PA) administration in a rat embolic stroke model with magnetic resonance imaging (MRI), to assess potential MRI correlates, or predictors, or both, of rt-PA-induced hemorrhage. Diffusion-, perfusion-, and post-contrast T₁-weighted MRI were performed between 4 and 9 hours and at 24 hours after embolic stroke in spontaneously hypertensive rats. Treatment with either rt-PA or saline was started 6 hours after stroke. A spectrophotometric hemoglobin assay quantified hemorrhage severity. Before treatment, relative cerebral blood flow index (rCBF_i) and apparent diffusion coefficient (ADC) in the ischemic territory were 30% ± 23% and 60% ± 5% (of contralateral), respectively, which increased to 45% ± 39% and 68% ± 4% 2 hours after rt-PA. After 24 hours, rCBF_i and ADC were 27% ± 27% and 59 ± 5%. Hemorrhage volume after 24 hours was significantly greater in rt-PA -treated animals than in controls (8.7 ± 3.7 μL vs. 5.1 ± 2.4 μL, P < 0.05). Before rt-PA administration, clear postcontrast T₁-weighted signal intensity enhancement was evident in areas of subsequent bleeding. These areas had lower rCBF_i levels than regions without hemorrhage (23% ± 22% vs. 36% ± 29%, P < 0.05). In conclusion, late thrombolytic therapy does not necessarily lead to successful reperfusion. Hemorrhage emerged in areas with relatively low perfusion levels and early blood-brain barrier damage. Magnetic resonance imaging may be useful for quantifying effects of thrombolytic therapy and predicting risks of hemorrhagic transformation.