Evaluation of the Lifetime and Size Distribution of Daughter Bubbles Generated by Inertial Cavitation

Abstract

Ultrasound-driven microbubbles can improve the sensitivity of imaging or promote macromolecules delivery. However, microbubble collapse during inertial cavitation (IC) is followed by the creation of smaller daughter bubbles, that could grow and be nuclei for acoustic cavitation. Daughter bubbles exposure to ultrasound may cause undesired bioeffects in targeted region, thus it is important to determine the properties of daughter bubbles generated by IC to achieve controllable cavitation dose during therapy. In this study, theoretical dissolution dynamics of sulfur hexafluoride bubbles was calculated firstly. Then, we applied a 1-MHz single pulse with different peak negative pressures (PNPs) and pulse lengths (PLs), and multiple 5-MHz pulses with fixed acoustic conditions to elicit IC of the preformed SonoVue microbubbles and scattering of daughter bubbles, respectively. After the IC and scattering signals were received by a 7.5-MHz transducer, time- and frequency-domain analysis was performed to obtain the IC dose and scattering intensity curve. The theoretical dissolution curves and measured scattering intensity curves were combined to determine the effect of the incident pulse parameters on the lifetime, mean radius and distribution range of daughter bubbles. Increasing the PNP reduced the lifetime and mean size of the daughter bubbles population and narrowed the size distribution. The proportion of small daughter bubbles (less than resonance size) increased with an increase in the PNP from 0.6 to 1.6 MPa. Moreover, increasing the PL caused a shift of the daughter bubbles population to the smaller bubbles with shorter lifetime and narrower distribution. The proportion of small bubbles increased from as the PL was increased from 5 to $\mathbf{100} \mu \mathbf{s}$ . Finally, increasing the IC dose caused a smaller mean size, shorter lifetime and narrower distribution in the daughter bubbles population. These results provide new insight into the relationship between the incident acoustic parameters and the properties of daughter bubbles.