Removal of residual nuclei following a cavitation event: a parametric study

The efficacy of ultrasound therapies such as shock-wave lithotripsy and histotripsy can be compromised by residual cavitation bubble nuclei that persist following the collapse of primary cavitation. In our previous work, we have developed a unique strategy for mitigating the effects of these residual bubbles using low-amplitude ultrasound pulses to stimulate their aggregation and subsequent coalescence-effectively removing them from the field. Here, we further develop this bubble removal strategy through an investigation of the effect of frequency on the consolidation process. Bubble removal pulses ranging from 0.5 to 2 MHz were used to sonicate the population of residual nuclei produced upon collapse of a histotripsy bubble cloud. For each frequency, mechanical index (MI) values ranging from 0 to approximately 1.5 were tested. Results indicated that, when evaluated as a function of bubble removal pulse MI, the efficacy of bubble removal shows markedly similar trends for all frequencies tested. This behavior divides into three distinct regimes (with provided cutoffs being approximate): 1) MI <; 0.2: Minimal effect on the population of remanent cavitation nuclei; 2) 0.2 <; MI <; 1: Aggregation and subsequent coalescence of residual bubbles, the extent of which trends toward a maximum; and 3) MI > 1: Bubble coalescence is compromised as bubble removal pulses induce high-magnitude inertial cavitation of residual bubbles. The major distinction in these trends came for bubble removal pulses applied at 2 MHz, which were observed to generate the most effective bubble coalescence of all frequencies tested. We hypothesize that this is a consequence of the secondary Bjerknes force being the major facilitator of the consolidation process, the magnitude of which increases when the bubble size distribution is far from resonance such that the phase difference of oscillation of individual bubbles is minimal.