Monitoring and simulating stable cavitation during ultrasound-enhanced thrombolysis

Abstract

The presence of stable cavitation has been shown to be highly correlated with thrombolytic efficacy for recombinant tissue plasminogen activator (rt‐PA) mediated thrombolysis. A commercial contrast agent, Definity, was used with 120 kHz pulsed ultrasound to nucleate, promote, and sustain stable cavitation. The effect of stable cavitation on increased penetration of rt‐PA into the clots is discussed. Also, the possibility of lowering the rt‐PA dose using sustained stable cavitation adjuvant to thrombolytics is presented. To understand the bubble dynamics involved, the bubble response was studied using the Keller‐Miksis model and stable and inertial cavitation thresholds were studied as a function of bubble radius. The largest mass loss (26.2%) was observed for clots treated with 120 kHz ultrasound (0.32 MPa peak‐to‐peak pressure amplitude, 80% duty cycle), rt‐PA (96 μg/ml) and stable cavitation nucleated by Definity. A comparable mass loss of 22% was observed at a much lower concentration of 11 μg/ml in the presence of stable cavitation. In addition, the simulation results provide insight into the nuclei sizes relevant for this therapeutic application and possible mechanisms involved.