Optimization of the Shear Stress Induced by Ultrasonically-Stimulated Oscillating MBs: A Theoretical Investigation

Shear stress induced by ultrasonically-stimulated MBs has been associated with sonoporation and sonothrombolysis. In this study, the dynamics of oscillating MBs is investigated numerically using the Hoff model for varying parameters (MB radius (Ro), pulse frequency and acoustic pressure) and the average shear stress was calculated using the Rooney model. The MB oscillations were maintained below a normalized radial oscillation of two to avoid inertial cavitation. The simulations demonstrated that the shear stress induced by MBs increased significantly at exposure frequencies of non-integer multiples of the resonance frequency (fr), only above a pressure threshold. The pressure threshold, located at the saddle node bifurcation point where the MB oscillation increases suddenly, depended on MB size, pulse frequency and shell properties. The shear stress induced by a 4 um oscillating MB increased by 10-fold when exposed to 8.85 MHz (2.93fr) compared to the maximum shear stress at the MB resonance frequency (3.02 MHz). This increase is concomitant with the saddle node bifurcation in normalized radial oscillations from 1.12 to 1.69 at 1.53 MPa. In conclusion, ultrasound exposure frequency and acoustic pressure can be tailored to maximize and control the shear stress induced by MBs undergoing stable oscillation for optimizing ultrasound therapeutic bioeffects.