A two-stage pressure ramping strategy for improving the efficacy of sonothrombolysis: Insights from a microbubble dynamics study

Sonothrombolysis is a technique that utilises ultrasound waves and microbubbles to remove blood clots. When insonated with high-pressure ultrasound waves, microbubbles undergo inertial cavitation and collapse violently to form high-speed jets. If this phenomenon occurs near the clot, the shear stress resulting from the jet impact can lead to considerable mechanical erosion of the clot surface. Efforts to enhance shear stress by optimising treatment parameters are limited by the trade-off between jet velocity and the distance travelled by the microbubble. Increasing jet velocity usually shortens the distance travelled, while extending the distance travelled often reduces jet velocity. In this study, a two-stage insonation scheme via a pressure ramping strategy was proposed to address this issue. In the first stage, low-pressure insonation enables stable oscillation and translation of the microbubble towards the clot. The pressure was then increased in the following stage to trigger inertial cavitation. Numerical findings indicated that the pressure ramping strategy can produce shear stress of 702 kPa with a ramped-up pressure of only 400 kPa. This surpasses the 487 kPa achieved without pressure ramping at a pressure magnitude of 1000 kPa. The elevated shear stress resulting from pressure ramping is due to the significant movement of the microbubble towards the clot during the initial insonation phase that utilises low pressure. In addition to enhancing shear stress, pressure ramping also facilitates drug penetration as the jet penetrates the clot. Therefore, pressure ramping may serve as an effective strategy to improve the effectiveness of sonothrombolysis.