Effect of low intensity CW ultrasound on acoustic responses of microbubbles generated from phase change nano droplet

Sustaining of microbubbles generated from a phase-change nano-droplet (PCND) was demonstrated by using low intensity ultrasound aiming at precisely targeted ultrasound therapy. PCND, a droplet containing superheated perfluorocarbon, dispersed in polyacrylamide gel was exposed to 1.1-MHz ultrasound pulses at 1.2 kW/cm2 with 100 cycles. The resulting microbubbles were further exposed to very low intensity continuous wave (CW) or burst ultrasound to sustain the bubbles. When CW exposure was used for the sustaining procedure, only fundamental components were observed from the PCND at acoustic intensities around 100 mW/cm2. This suggests the fundamental signal was emitted from the sustained microbubbles because further exposure of 100 W/cm2 ultrasound following the sustaining ultrasound resulted in the generation of fractional harmonics, suggesting the induction of cavitation, while no harmonic components were observed in the absence of the sustaining ultrasound. It was possible to use pulsed ultrasound for the sustaining procedure, when the interval between each pulse was within 10 ms. The time constant was about the same as the lifetime of the microbubbles induced from the PCND in the absence of the sustaining ultrasound. The obtained results are promising for controlling the sensitivity of local sites to therapeutic ultrasound by using PCND and low intensity ultrasound