Efficacy estimation of microbubble-assisted local sonothrombolysis using a catheter with a series of miniature transducers

Abstract

Intravascular ultrasound has good prospects for clinical applications in sonothrombolysis. The catheter-based side-looking intravascular ultrasound thrombolysis (e.g., Ekosonic catheters) used in clinical studies has a high frequency (2 MHz). The lower-frequency ultrasound requires a larger-diameter transducer. In our study, we designed and manufactured a small ultrasound-based prototype catheter that can emit a lower frequency ultrasound (1.1 MHz). In order to evaluate the safety and efficacy of local low-frequency ultrasound-enhanced thrombolysis, a microbubble (MB) was introduced to augment thrombolysis effect of locally delivered low-intensity ultrasound. The results demonstrated that combination of ultrasound and MB realized higher clot lysis than urokinase-only treatment (17.0% ± 1.2% vs. 14.9% ± 2.7%) under optimal ultrasound settings of 1.1 MHz, 0.414 MPa, 4.89 W/cm2, 5% duty cycle and MB concentration of 60 µg/mL. When urokinase was added, the fibrinolysis accelerated by MB and ultrasound resulted in a further increased thrombolysis rate that was more than two times than that of urokinase alone (36.7% ± 5.5% vs. 14.9% ± 2.7%). However, a great quantity of ultrasound energy was required to achieve substantial clot lysis without MB, leading to the situation that temperature accumulated inside the clot became harmful. We suggest that MB-assisted local sonothrombolysis be considered as adjuvant therapy of thrombolytic agents.