Light, sound, nanobubbles: New approach to contrast-enhanced ultrasound and photoacoustic imaging

Abstract

To overcome the most significant deficiencies of conventional and contrast-enhanced ultrasound imaging—low contrast and large size of microbubbles, we introduced new class of contrast agents—nanometer scale particles that are capable of escaping vascular compartments, penetrating into tissue, and then, once they reach the target site, generating sufficient ultrasound and photoacoustic contrast upon user-controlled optical activation. These multimodal contrast agents—phase-change perfluorocarbon nanodroplets and plasmonic nanoparticles covered by azide compounds—are stable at physiological temperatures, biocompatible, and monodisperse in size. Given the unique properties of the particles, our approach to image these particles is drastically different and is based on ultrasound read-out of the optically induced temporal changes. Specifically, time-varying ultrasound signals exhibited by the nanoparticles versus the static background are used to reconstruct a high contrast, background-free image of the contrast agent. Furthermore, these particles allow for multiplexed molecular imaging by permitting user-controlled triggering of distinct color-coded populations of contrast agents via tuning of the incident laser irradiation to match peak optical absorption of the particles. Finally, nanoparticles may also contain therapeutic cargo and thus can be used for controlled drug delivery and release. This presentation, via examples, will discuss diagnostic imaging and image-guided therapy using the gas-generating nanoparticles.