Abstract
The vaporization of perfluorocarbon droplets into gaseous bubbles using high-intensity focus ultrasound (HIFU) was referred to as acoustic droplet vaporization (ADV). This technique provides large bubbles for the applications of gas embolotherapy. However, the rapid volume expansion during ADV reduces the density of surfactant molecules and decreases the stability of bubbles. The characteristics of bubble population might vary under different acoustic and hemodynamic conditions. This study investigated the effects of different experimental parameters on the temporal evolution of ADV bubbles with the flowing conditions of 21.4–44.1 mm/s. The effects of acoustic parameters included peak rarefaction pressure, pulse duration, and pulse repetition frequency (PRF) and other parameters such as droplet concentrations, flow velocities, fluid viscosities were also considered. The experiments were performed in an integrated acousto-optical system comprising an HIFU transmission system, a high-frequency ultrasound imaging system, and a high-speed optical microscope. A 2-MHz HIFU transducer was used to transmit acoustic pulses to vaporize the droplets in a 200-μm semipermeable tube. Simultaneous acoustic and optical observations of bubble population were performed to monitor bubble population at up to 1.2 s after the onset of ADV. The experiments were also performed in mice bearing dorsal skinfold window chambers for observing the ADV effects in vivo. The results show that the bubbles can grow to a stable equilibrium size which is almost 2-fold larger in diameter than first vaporization in 0.5–1 s. Although the growth trend did not depend on flow velocity, it was dependent on fluid viscosity and droplet concentration since they dominate the gas content of the host medium. The result was correlated with the rates of gas uptake in bubbles and gas exchange between the inside and outside of the wall in the semipermeable tube. Varying the acoustic pressure resulted in no remarkable effects on the temporal evolution of bubble population as long as the acoustic pressure exceeded the ADV threshold pressure. Increasing both the pulse duration and PRF markedly reduces the stability of bubbles by increasing the permeability of their shells to gas. Besides, lengthening the PRF provides superior performance in bubble disruption than increasing pulse duration for the same total pulse energy. The results of the intravital microscopy have shown the ability of the post-ADV growing bubbles to reduce the blood flow or cause the embolism. This study suggests that the characteristics of ADV bubble population may be regulated using different acoustic parameters. Determining optimal acoustic parameters to produce bubbles with sizes which are suitable for gas embolotherapy may be feasible. Future study is to investigate the effectiveness of the improved gas embolotherapy in the inhibition of tumor progression.