Inverse effects of flowing phase-shift nanodroplets and lipid-shelled microbubbles on subsequent cavitation during focused ultrasound exposures

This paper compared the effects of flowing phase-shift nanodroplets (NDs) and lipid-shelled microbubbles (MBs) on subsequent cavitation during focused ultrasound (FUS) exposures. The cavitation activity was monitored using a passive cavitation detection method as solutions of either phase-shift NDs or lipid-shelled MBs flowed at varying velocities through a 5-mm diameter wall-less vessel in a transparent tissue-mimicking phantom when exposed to FUS. The intensity of cavitation for the phase-shift NDs showed an upward trend with time and cavitation for the lipid-shelled MBs grew to a maximum at the outset of the FUS exposure followed by a trend of decreases when they were static in the vessel. Meanwhile, the increase of cavitation for the phase-shift NDs and decrease of cavitation for the lipid-shelled MBs had slowed down when they flowed through the vessel. During two discrete identical FUS exposures, while the normalized inertial cavitation dose (ICD) value for the lipid-shelled MB solution was higher than that for the saline in the first exposure (p-value <0.05), it decreased to almost the same level in the second exposure. For the phase-shift NDs, the normalized ICD was 0.71 in the first exposure and increased to 0.97 in the second exposure. At a low acoustic power, the normalized ICD values for the lipid-shelled MBs tended to increase with increasing velocities from 5 to 30 cm/s (r > 0.95). Meanwhile, the normalized ICD value for the phase-shift NDs was 0.182 at a flow velocity of 5 cm/s and increased to 0.188 at a flow velocity of 15 cm/s. As the flow velocity increased to 20 cm/s, the normalized ICD was 0.185 and decreased to 0.178 at a flow velocity of 30 cm/s. At high acoustic power, the normalized ICD values for both the lipid-shelled MBs and the phase-shift NDs increased with increasing flow velocities from 5 to 30 cm/s (r > 0.95). The effects of the flowing phase-shift NDs vaporized into gas bubbles as cavitation nuclei on the subsequent cavitation were inverse to those of the flowing lipid-shelled MBs destroyed after focused ultrasound exposures.