  Superheated perfluorocarbon nanodroplets are emerging ultrasound imaging
contrast agents boasting biocompatible components, unique phase-change
dynamics, and therapeutic loading capabilities. Upon exposure to a sufficiently
high intensity pulse of acoustic energy, the nanodroplet perfluorocarbon core
undergoes a liquid-to-gas phase change and becomes an echogenic microbubble,
providing ultrasound contrast. The controllable activation leads to
high-contrast images, while the small size of the nanodroplets promotes longer
circulation times and better in-vivo stability. One drawback, however, is that
the nanodroplets can only be vaporized a single time, limiting their
versatility. Recently, we and others have address this issue by using a
perfluorohexane core, which has a boiling point above body temperature. Thus
after vaporization, the microbubbles recondense back into their stable
nanodroplets form. Previous work with perfluorohexane nanodroplets relied on
optical activation via pulse laser absorption of an encapsulated dye. This
strategy limits the imaging depth and temporal resolution of the method. In
this study we overcome these limitations by demonstrating acoustic droplet
vaporization with 1.1-MHz high intensity focused ultrasound. A short-duration,
high-amplitude pulse of focused ultrasound provides a sufficiently strong peak
negative pressure to initiate vaporization. When using a custom imaging
sequence with a high-frequency transducer, the repeated acoustic activation of
perfluorohexane nanodroplets can be visualized in polyacrylamide
tissue-mimicking phantoms. We demonstrate detection of hundreds of vaporization
events from individual nanodroplets with activation thresholds well below the
tissue cavitation limit. Overall, this approach has the potential to result in
reliable contrast-enhanced ultrasound imaging at clinically relevant depths.
