Verification of ultrasonic thrombolysis effect by in vitro experiments

The tissue plasminogen activator (t-PA) has been approved as a thrombolytic agent for treating cerebral thrombosis. It is reported that recanalization occurs earlier in a hyperacute ischemic stroke when both t-PA and transcranial ultrasonication are applied than when t-PA alone is applied. We have developed a therapy-and-diagnostics (T/D) compound transcranial ultrasonic thrombolytic system. To minimize adverse mechanical and thermal biological effects, the frequency of the therapeutic ultrasound (US) beam is selected to be 500 kHz. The diagnostic US beam at 2 MHz is used for monitoring the recanalization. We confirmed the effect of this system using two types of experiment. One determined the recanalization rate and dissolution time of the simulated thrombotic vascular occlusion at narrowed vessels and the other determined the weight decrease of the clot, and both involved exposure to t-PA solution with and without ultrasonication. As a result, the recanalization rate is higher in the US + t-PA (92.3%) than in the t-PA-only (64.1%). The decrease rate is also higher in the US + t-PA (25.4%) than in the t-PA-only (15.1%).