Microbubble dynamics simulation reveals the effects of microbubble distance from the clot on the outcome of sonothrombolysis.

BACKGROUND AND OBJECTIVE: Sonothrombolysis employs ultrasound waves to induce inertial cavitation of microbubbles, generating high-speed microjets that mechanically erode blood clots. While clot lysis efficacy is closely linked to the proximity of microbubbles to the clot surface, experimental quantification remains challenging due to blood opacity and small timescales. METHODS: This study utilises a computational modelling strategy to evaluate the impact of microbubble standoff distance (10-70μm) at ultrasound pressure amplitudes (600-1500 kPa) on sonothrombolysis efficacy, as quantified by flow-induced shear stress and drug penetration caused by microjet impingement. RESULTS: Results demonstrated that at long standoff distance of 50 and 70μm, sonothrombolysis efficacy deteriorated as microjets dissipated into the surrounding blood before clot impingement. Although increasing insonation pressure compensated for this loss, shear loading and drug penetration remained inferior to shorter standoff distances. A short standoff distance of 10μm produced the highest shear loading, while the maximum drug penetration was achieved at a moderate standoff distance of 30μm. CONCLUSION: These simulation results reveal that sonothrombolytic mechanisms can be selectively tuned by adjusting microbubble proximity, providing a quantitative framework for optimising sonothrombolysis protocols with either mechanical erosion or thrombolytic drug penetration.