Time and Frequency Characteristics of Cavitation Activity Enhanced by Flowing Phase-Shift Nanodroplets and Lipid-Shelled Microbubbles During Focused Ultrasound Exposures.

This study investigated and compared the time and frequency characteristics of cavitation activity between phase-shift nanodroplets (NDs) and lipid-shelled microbubbles (MBs) exposed to focused ultrasound (FUS) under physiologically relevant flow conditions. Root-mean-square (RMS) of broadband noise, spectrograms of the passive cavitation detection signals and inertial cavitation doses (ICDs) were calculated during FUS at varying mean flow velocities and two different peak-rarefactional pressures. At a lower pressure of 0.94 MPa, the mean values of the RMS amplitudes versus time for the NDs showed an upward trend but slowed down as the mean flow velocity increased. For flowing NDs, the rate of growth in RMS amplitudes within 2-5 MHz decreased more obviously than those within 5-8 MHz. At a higher pressure of 1.07 MPa, the increase in RMS amplitudes was accelerated as the mean flow velocity increased from 0 to 10 cm/s and slowed down as the mean flow velocity reached 15 cm/s. The general downward trends of RMS amplitudes for the MBs were retarded as the mean flow velocity increased at both acoustic pressures of 0.94 MPa and 1.07 MPa. At 0.94 MPa, the mean ICD value for the NDs decreased from 57 to 36 as the mean flow velocity increased from 0 to 20 cm/s. At 1.07 MPa, the mean ICD value initially increased from 45 to 57 as the mean flow velocity increased from 0 to 10 cm/s and subsequently decreased to 43 as the mean flow velocity reached 20 cm/s. For the MBs, the mean ICD value increased with increasing mean flow velocity at both acoustic pressures. These results could aid in future investigations of cavitation-enhanced FUS with the flowing phase-shift NDs and encapsulated, gas-filled MBs for various applications.