Numerical analysis of synergistic cavitation effect of multiple bubbles in ultrasound thrombolysis

<sec>Ultrasound thrombolysis primarily relies on transient shockwaves and microjets from collapsing cavitation bubbles to mechanically disrupt thrombus structures. Although it shows clinical potential, its efficacy is still limited by low cavitation energy transfer efficiency and unpredictable tissue damage, due to incomplete understanding of single bubble dynamics and the synergistic mechanisms of multi-bubble interactions.</sec><sec>This study introduces a hyper-viscoelastic constitutive model incorporating blood clot mechanics to analyze stress accumulation under sequential microbubble impacts. A gas-liquid-solid coupling multi-physics model quantifies bubble collapse dynamics near thrombi, and integrates structural damping terms to represent energy dissipation during fluid-solid interactions. Parameter analysis shows that the intensity of jet impact is positively correlated with thrombus mass and ultrasound amplitude, but inversely related to dimensionless distance, ultrasound frequency, and initial bubble radius.</sec><sec>The proposed rate-dependent Ogden-Prony model effectively captures thrombus behaviors under transient impacts, including strain hardening, rate-dependent strengthening, and stress relaxation. Sequential jet impacts induce cumulative stress through strain hardening, with multi-bubble synergy achieving significantly higher stresses than single-bubble impact. Optimal bubble radius distribution can amplify the normal/shear stress inside thrombi—maximum normal stress generated by the double bubble impact sequences is 6.02 MPa, exceeding the tensile strength of the thrombus, while the maximum stress generated by single bubble impact is 1.45 MPa. The key quantitative relationships between bubble cluster parameters, dimensionless distance, thrombus mass, and stress accumulation provide optimization guidelines for ultrasound thrombolysis. Notably, controlled multi-bubble jet impact sequences with attenuated pressure peaks demonstrate enhanced therapeutic potential through cumulative mechanical effects rather than a single high-intensity impact.</sec>