Perfluorocarbon-cored phase-changing nanodroplet contrast agents (PNCAs) can be molecularly targeted and used for extravascular molecular ultrasound (US) imaging. To monitor the activation and dynamics of these nanodroplets, we propose an adaptive scheme for activation and imaging comprised of plane-wave B-mode imaging and nonlinear Pulse-Inversion Harmonic imaging with optimized transmit angles, frequency, and PRF. Activation and imaging of PFC nanodroplets was conducted on a Verasonics Vantage 128 US system; both dodecafluoropentane (C5) and dodecafluorohexane (C6)-cored nanodroplets were tested. High frame-rate acquisitions capture post-activation dynamics, including growth or recondensation over time. Directly post-activation, the Weber contrast of C5 and C6 nanodroplets ranges from 0.8-1.2 and 1.5-2.3, respectively. At body temperature, both exhibit growth and continued contrast enhancement for ~1-2 seconds after activation. At ~30C, C6 nanodroplets demonstrated recondensation within 100 milliseconds of activation. This novel sequence paradigm provides a strong platform for in vitro and future in vivo optimization and guidance of PNCA molecular imaging.
