Sono-photoacoustic theranostics using phase-changing contrast agents

Abstract

Phase-change contrast agents are low boiling point liquid perfluorocarbon droplets that can be vaporized to form larger microbubbles. Droplet vaporization can be used for both imaging and therapy. Sono-photoacoutics is a non-linear imaging method that uses simultaneous optical and acoustic pulses to activate phase-change contrast agents. By combining photothermal heating from a laser pulse and the negative pressure from an acoustic pulse, lower droplet activation thresholds are achieved than from either source alone. In this study, we demonstrate in an in vitro model that sono-photoacoutics activation of polypyrrole coated perfluorocarbon droplets can be used to disrupt 2-cm long fibrin clots to restore flow. Polypyrrole coated droplets under 200 nm in diameter were introduced upstream and allowed to diffuse into the clot. A 1.24-MHz single element transducer coaxially aligned with a 1064-nm pulsed laser was used to scan the clot, activating any agents within the clot. Agent activation was quantified using passive cavitation detection, while flow was monitored using a digital balance. Our results show that the droplets can freely diffuse into fibrin clots and SPA activation can restore approximately 25% of the flow.