Active removal of residual bubble nuclei following a cavitation event

Residual microscopic bubble nuclei can persist on the order of 1 second following a cavitation event. These bubbles may limit the efficiency of ultrasound therapies such as shock wave lithotripsy and histotripsy, as they attenuate pulses that arrive subsequent to their formation and seed cavitation memory. Here, we explore a strategy for the removal of residual bubble nuclei following a cavitation event, using a low amplitude ultrasound burst to stimulate bubble coalescence. All experiments were conducted in degassed water and monitored using high speed photography. The following general pulse scheme was used: (A) Cavitation Initiation Pulse: A cavitational bubble cloud was initiated by a 1 MHz therapy transducer using a very short intense pulse (P- > 30 MPa); (B) Nuclei Removal Pulse: Residual bubble nuclei were sonicated using a 2 ms pulse from a separate 350 kHz unfocused transducer to stimulate coalescence. Nuclei removal pulses with amplitudes ranging from 0 to 750 kPa were tested; (C) Interrogation Pulse: The presence of residual nuclei following the removal pulse was probed using a second lower amplitude pulse from the therapy transducer sufficient to cause residual microscopic nuclei to expand and be more easily detected via high speed imaging. The backlit area of shadow from expanded bubbles was calculated to quantify the efficacy of nuclei removal. It was found that the control case (nuclei removal pulse amplitude = 0) generated a bubble shadow area of 0.64 ± 0.08 mm². For nuclei removal pulse amplitudes of 50 to 150 kPa, minimal coalescence was observed in high speed video, and the area of bubbles excited by the interrogation pulse did not differ significantly from control (p> 0.08). Pronounced bubble coalescence was observable for nuclei removal pulses ≥250 kPa, with the extent of coalescence increasing with pulse amplitude. Bubble shadow area was significantly reduced relative to control in these cases (p≤ 0.0- ). We hypothesize that the primary and secondary Bjerknes forces act in concert to produce the bubble coalescence observed in this study.