Effects of Ultrasound-Induced Inertial Cavitation on Enzymatic Thrombolysis

Abstract

Cavitation induced by ultrasound enhances enzymatic fibrinolysis by increasing the transport of reactants. However, the effects of cavitation need to be fully understood before sonothrombolysis can be applied clinically. In order to understand the underlying mechanisms, we examined the effects of combining ultrasound, microbubbles and thrombolytic enzymes on thrombolysis. First, we evaluated the relations between inertial cavitation and the reduction in the weight of a blood clot. Inertial cavitation was varied by changing the amplitude and duration of the transmitted acoustic wave as well as the concentration of microbubbles used to induce cavitation. Second, we studied the combined effects of streptokinase and inertial cavitation on thrombolysis. The results show that inertial cavitation increases the weight reduction of a blood clot by up to 33.9%. With linear regression fitting, the measured differential inertial cavitation dose and the weight reduction had a correlation coefficient of 0.66. Microscopically, enzymatic thrombolysis effects manifest as multiple large cavities within the clot that are uniformly distributed on the side exposed to ultrasound. This suggests that inertial cavitation plays an important role in producing cavities, while microjetting of the microbubbles induces pits on the clot surface. These observations preliminarily demonstrate the clinical potential of sonothrombolysis. The use of the differential inertial cavitation dose as an indicator of blood clot weight loss for controlled sonothrombolysis is also possible and will be further explored.