Dependence of bubble size and peak rarefractional pressure on maximum bubble response during therapeutic ultrasound histotripsy

Medical ultrasound has shown great potential as a minimally invasive therapy technique. It can be used in areas such as histotripsy, thermal ablation, and administering medication. The success of these therapies is improved by the cavitation of microbubbles. This study evaluated the effect of varying the pressure amplitude on cavitation resonance frequency and the corresponding bubble size at therapeutic field levels. Other research indicated that the resonance size depends on pressure amplitude; however, that investigation only considered pressure amplitudes up to 1 MPa [MacDonald et al. (2004)]. Our study was conducted by simulating the response of air bubbles in water to linearly propagating sine waves using the Gilmore-Akulichev formulation to solve for the bubble response. The frequency of the sine wave varied from 0.5 to 5 MHz while the amplitude of the sine wave varied from 0.0001 to 5 MPa. The optimal seed size for a particular frequency of excitation and amplitude, which is normally only established for stable cavitation, was defined in our study as the initial bubble size that resulted in the maximum bubble expansion prior to bubble radius dropping below its initial radius. The simulations demonstrated a downshift in resonance size with increasing pressure amplitude. Therefore, at therapeutic levels, smaller bubbles can have a more dramatic response to ultrasound than larger bubbles.