Flow-Independent Microbubble Isolation by Rapid Recondensation of Phase-Change Nanodrops after Acoustic Droplet Vaporization

A critical step in super-resolution ultrasound imaging via ultrasound localization microscopy (ULM) is the isolation contrast agents from tissue. Flow-dependent movement of mi-crobubbles relative to static tissue or non-linear imaging modes are typically utilized for contrast agent separation. The objective of this study was to investigate the spatiotemporal dynamics of phase-change nanodrop recondensation as a deactivation mechanism after acoustic droplet vaporization (ADV) and how it relates to contrast agent isolation. Perfluoropentane (PFP) nanodrops with mean diameters of approximately 100 nm recondensed after ADV at physiological temperature, while ADV of PFP microdrops resulted in stable bubble formation. Classical nucleation theory predicts that PFP droplets must be above a critical radius of 288 nm to form a stable free bubble and 100 nm to form a stable lipid-coated bubble. This blinking, on-and-off contrast signal via ADV/recondensation provided separation of contrast signal at all flow conditions (i.e. low/no flow) in tissue-mimicking flow phantom experiments.