Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated Nanodroplets

We have developed a method for super-resolution ultrasound imaging, which relies on a new class of blinking nanometer-size contrast agents: laser-activated nanodroplets (LANDs). The LANDs can be repeatedly optically triggered to undergo vaporization; the resulting spatially stationary, temporally transient microbubbles provide high ultrasound contrast for several to hundreds of milliseconds before recondensing to their native liquid nanodroplet state. By capturing high frame rate ultrasound images of blinking LANDs, we demonstrate the ability to detect individual recondensation events. Then we apply a newly developed super-resolution image processing algorithm to localize the LAND positions in vivo almost an order of magnitude better than conventional ultrasound imaging. These results pave the way for high resolution molecular imaging deep in tissue.