In vitro demonstration of focused ultrasound thrombolysis using bifrequency excitation

Focused ultrasound involving inertial cavitation has been shown to be an efficient method to induce thrombolysis without any pharmacological agent. However, further investigation of the mechanisms involved and further optimization of the process are still required. The present work aims at studying the relevance of a bifrequency excitation compared to a classical monofrequency excitation to achieve thrombolysis without any pharmacological agent. In vitro human blood clots were placed at the focus of a piezoelectric transducer. Efficiency of the thrombolysis was assessed by weighing each clot before and after sonication. The efficiencies of mono- (550 kHz) and bifrequency (535 and 565 kHz) excitations were compared for peak power ranging from 70 W to 220 W. The thrombolysis efficiency appears to be correlated to the inertial cavitation activity quantified by passive acoustic listening. In the conditions of the experiment, the power needed to achieve 80% of thrombolysis with a monofrequency excitation is reduced by the half with a bifrequency excitation. The thermal effects of bifrequency and monofrequency excitations, studied using MR thermometry measurements in turkey muscle samples where no cavitation occurred, did not show any difference between both types of excitations when using the same power level.