Dependence of inertial cavitation activity on the high intensity focused ultrasound transducer F-number

Abstract

Cavitation induced in tumors by pulsed high intensity focused ultrasound (pHIFU) without ultrasound contrast agents was shown to significantly enhance chemotherapeutic drug uptake. Such de novo cavitation is commonly assumed to require very high rarefactional pressures. However, recent studies have shown that inertial cavitation threshold also correlates with formation of shocks at the focus. The shock amplitude and corresponding peak negative pressure (p-) are primarily determined by the transducer F-number with less focused transducers producing shocks at lower p-. Here, the dependence of inertial cavitation activity on F-number was investigated in gel phantoms and ex vivo tissue samples using passive cavitation detection (PCD). Exposures at 1.5 MHz consisted of 60 pulses delivered at 1 Hz PRF, with each pulse lasting 1 ms and p- from 1 to 15 MPa. Broadband noise emissions recorded by PCD were batch-processed to extract cavitation probability and persistence. At the same p-, both metrics indicate enhanced cavitation activity at higher F-numbers; in agarose phantoms, cavitation probability reached 100% when shocks formed at the focus, with p- values 5, 9, and 14.5 MPa for respective F-numbers 1.5, 1, and 0.75. These results confirm the impact of nonlinear waveform distortion on inertial cavitation. [Work supported by NIH K01EB015745, K01DK104854, and R01EB7643.]