Can Transcranial Ultrasonication Increase Recanalization Flow Ratio with Tissue Plasminogen Activator?
Purpose: The enhancement by a newly developed method of transcranial ultrasonication (TU) of thrombolysis with tissue plasminogen activator (TPA) was investigated in acute ischemic stroke (AIS) with an in vivo rabbit femoral artery occlusion model. Method: The femoral arteries of 36 rabbits were exposed, and stenosis was produced with 5–0 silk suture to reduce the flow to 77.3±6.9%. Poststenotic flow was measured with a flow meter at proximal segments of the femoral artery. Thrombosis was achieved by injecting thrombin through the cannulated branching artery into a 1-cm segment proximal to the stenosis which was isolated for 30 minutes. After the stability of the occlusion was confirmed, TPA was infused intravenously and ultrasound was applied through a piece of cadaver temporal bone (4 mm thick) to the thrombosis. The continuous wave ultrasound frequency was 490 kHz, and the intensity through the skull was 0.13 W/cm-2. Four groups were studied in a blinded fashion: 1.2 mg TPA with TU (1.2TU) (n=9), 1.2 mg TPA alone (1.2TPA) (n=12), 3.2 mg TPA with TU (3.2TU) (n=7), 3.2 mg TPA alone (3.2TPA) (n=8). All animals were observed for the 60 minutes of treatment. In this study, recanalization flow ratio (RFR) was defined as recanalization flow divided by poststenotic flow. Results: The RFR of the 1.2TU group (46.0±40.4%) was significantly greater than that of the 1.2TPA group (8.7±24.2%) (p<0.02). There were no significant differences in RFR among the 1.2TU, 3.2TPA, and 3.2TU groups (46±40.4%, 42.1±39.6% and 56.8±30.6%) (p>0.3). Conclusions: This study demonstrates that low-frequency and low-intensity TU with low-dose TPA is as effective as high-dose TPA in vivo and suggests that TU enhances thrombolysis in AIS.