Effect of High Intensity Focused Ultrasound Transducer F-number and Waveform Non-Linearity on Inertial Cavitation Activity

Enhanced chemotherapeutic drug delivery has been shown using pulsed high intensity focused ultrasound (pHIFU) without contrast agents. The threshold of these inertial cavitation effects has recently been correlated to the formation of shocks at the focus. The shock amplitude and corresponding peak negative pressure (p-) are primarily determined by the transducers F-number with less focused (higher F-number) transducers producing shocks at lower p-. Here, the dependence of inertial cavitation activity on F-number was investigated in gel phantoms using passive cavitation detection (PCD) and high-speed photography. HIFU transducers with the same aperture but different F-numbers (0.77, 1.02, and 1.52), operable at three driving frequencies (1 MHz, 1.5 MHz, and 1.9 MHz), were utilized with driving conditions consisting of 1 ms pulses delivered every second and p- from 1 to 15 MPa. Broadband noise emissions recorded by PCD were batch-processed to extract cavitation probability and persistence while concurrent imaging was performed in the focal pHIFU region. At the same p-, both PCD metrics and the imaging revealed enhanced cavitation activity at higher F-numbers. These results support the use of less focused, smaller-footprint transducers for achieving desired cavitation-aided drug delivery. [Work supported by NIH R01EB023910, K01DK104854, R01EB007643, and RFBR 17-54-33034.]