Enhancement of focused ultrasound treatment by acoustically generated microbubbles

Microbubbles, whether introduced from outside the body or ultrasonically generated in situ, are known to significantly enhance the biological effects of ultrasound, including the mechanical, thermal, and sonochemical effects. Phase-change nanodroplets, which selectively accumulate in tumor tissue and whose phase changes to microbubbles can be induced by ultrasonic stimulation, have been proposed for high-intensity focused ultrasound (HIFU) tumor treatment with enhanced selectivity and efficiency. In this paper, a purely acoustic approach to generate microbubble clouds in the tissue to be treated is proposed. Short pulses of focused ultrasound with extremely high intensity, named trigger pulses, are used for exposure. They are immediately followed by focused ultrasound for heating with an intensity similar to or less than that of normal HIFU treatment. The localized generation of microbubble clouds by the trigger pulses is observed in a polyarylamide gel by a high-speed camera, and the effectiveness of the generated clouds in accelerating ultrasonically induced thermal coagulation is confirmed in excised chicken breast tissue. The use of second-harmonic superimposed waves as the trigger pulses is also proposed. The highly reproducible initiation of cavitation by waves with the negative peak pressure emphasized and the efficient expansion of the generated microbubble clouds by waves with the positive peak pressure emphasized are also observed by a high-speed camera in partially degassed water.