A computational framework for the multiphysics simulation of microbubble-mediated sonothrombolysis using a forward-viewing intravascular transducer

Sonothrombolysis is a technique that utilises ultrasound waves to excite microbubbles surrounding a clot. Clot lysis is achieved through mechanical damage induced by acoustic cavitation and through local clot displacement induced by acoustic radiation force (ARF). Despite the potential of microbubble-mediated sonothrombolysis, the selection of the optimal ultrasound and microbubble parameters remains a challenge. Existing experimental studies are not able to provide a complete picture of how ultrasound and microbubble characteristics influence the outcome of sonothrombolysis. Likewise, computational studies have not been applied in detail in the context of sonothrombolysis. Hence, the effect of interaction between the bubble dynamics and acoustic propagation on the acoustic streaming and clot deformation remains unclear. In the present study, we report for the first time the computational framework that couples the bubble dynamic phenomena with the acoustic propagation in a bubbly medium to simulate microbubble-mediated sonothrom-bolysis using a forward-viewing transducer. The computational framework was used to investigate the effects of ultrasound properties (pressure and frequency) and microbubble characteristics (radius and concentration) on the outcome of sonothrombolysis. Four major findings were obtained from the simulation results: (i) ultrasound pressure plays the most dominant role over all the other parameters in affecting the bubble dynamics, acoustic attenuation, ARF, acoustic streaming, and clot displacement, (ii) smaller microbubbles could contribute to a more violent oscillation and improve the ARF simultaneously when they are stimulated at higher ultrasound pressure, (iii) higher microbubbles concentration increases the ARF, and (iv) the effect of ultrasound frequency on acoustic attenuation is dependent on the ultrasound pressure. These results may provide fundamental insight that is crucial in bringing sonothrombolysis closer to clinical implementation.

Automated summary

Sonothrombolysis is a technique that uses ultrasonic waves and microbubbles to dissolve blood clots. The optimal ultrasound and microbubble parameters for this technique remain a challenge to determine. In this study, a computational framework was developed to simulate microbubble-mediated sonothrombolysis and investigate the effects of ultrasound pressure, frequency, microbubble radius, and concentration on clot dissolution. The results revealed the dominant role of ultrasound pressure, the potential benefits of smaller microbubbles at higher pressure, the positive impact of higher microbubble concentration, and the dependence of ultrasound frequency on acoustic attenuation. These findings provide important insights for the clinical implementation of sonothrombolysis.