Investigation of vaporized submicron perfluorocarbon droplets as an ultrasound contrast agent

Acoustically activated submicron droplets of liquid perfluorocarbon are investigated as a new class of ultrasound contrast agent. In the liquid state, intravascular droplets can extravasate within tumours. Activation is then accomplished by using bursts of ultrasound to vaporize the droplets. We use acoustical and optical techniques to assess the characteristics of vaporized droplets and the resulting microbubbles in vitro, including size, conversion threshold, echogenicity and nonlinearity. Under exposure to single 5-50 cycle bursts of ultrasound at 7.5 MHz and mechanical index <1.0, droplets with mean diameter of 400 nm convert into microbubbles with mean diameter of 1.4 μm at 1 ms after vaporization, expanding to 5.6 μm by 1 s. The growth of microbubbles produced by vaporization causes a characteristic time-dependent increase in linear and nonlinear echogenicity, enabling selective detection with conventional bubble-specific imaging. These results suggest that submicron perfluorocarbon droplets, activated in situ, may be a candidate for an extravascular ultrasound contrast agent.