Effects of ultrasound pulse parameters on cavitation properties of flowing microbubbles under physiologically relevant conditions

Acoustic cavitation from ultrasound-driven microbubbles can induce diverse bioeffects that are useful in clinical therapy. However, lack of control over the cavitation activity of flowing microbubbles results in unwanted treatment regions in the targeted tissue, which influences the therapeutic efficacy and bio-safety. The aim of this study is to understand the relationship between the ultrasound pulse parameters and cavitation properties of flowing microbubbles, including the type (and transition between types), threshold, intensity and temporal distribution of cavitation. An in vitro physiological-flow phantom was fabricated, in which the microbubbles had a constant velocity, and were sonicated to a 1-MHz focused transducer at a wide range of peak negative pressures (PNPs) (0.10-1.28 MPa), pulse repetition frequencies (PRFs) (1-200 Hz) and pulse lengths (PLs) (10-400 mu s). The signals from the flowing bubbles were passively detected by another 7.5-MHz plane transducer. From detailed time- and frequency-domain analysis, we found 1). The occurrence of stable cavitation (SC) and inertial cavitation (IC) depended on PNP and PL when the PRF was below a critical value (PRF threshold) that related to the fluid velocity and PNP full width at half maximum diameter of the transducer. 2) Below the PRF threshold, the PL had no influence on the temporal distribution of SC intensity; however, above the PRF threshold, the SC properties depended on the PL because of acoustically-driven diffusion. Specifically, at shorter PLs, the SC intensity had a uniform temporal distribution and was independent of the PRF; at longer PLs, the SC intensity correlated negatively with the PRF. 3) Below the PRF threshold, the IC properties were independent of the PRF. Increasing the PRF above the PRF threshold caused the IC intensity to decrease with a non-uniform temporal distribution. These results indicate that the fluid velocity and a pulsed acoustic field influence the number and properties of the replenished bubbles into the targeted region, resulting in the change of cavitation properties. In future therapeutic applications, the physiological fluid conditions must be taken into consideration to design reasonable pulse parameters and achieve desirable cavitation properties.