Experimental determination of phase velocity of perfluorocarbons: Applications to targeted contrast agents

Targeted acoustic contrast agents are designed to enhance the sensitivity and specificity of ultrasonic diagnoses, We have previously developed a ligand targeted ultrasonic contrast system that is a lipid-encapsulated, liquid-perfluorocarbon emulsion. The emulsion particles are small (250 nm) and have inherently low echogenicity unless bound to a surface by a pretargeted ligand through avidin-biotin interactions. We have recently proposed a simple acoustic transmission line model that treats the emulsion particles as a thin layer over the targeted surface, In this model, the acoustic reflectivity of the sample increases for perfluorocarbons with smaller velocities of longitudinal sound or lower densities, In this study, we measure and report the velocity of longitudinal sound for 20 perfluorocarbons using a broadband phase spectroscopic approach for estimating phase velocities. Experimentally determined velocities ranged from 520 +/- 2 m/sec (perfluorohexane) to 705 +/- 5 m/s (perfluorodecalin), No measurable dispersion was observed over the useful bandwidth of 2 to 22 MHz. Increasing carbon backbone chain length and fluorine substitution with halogens of greater atomic weight increased the measured speed of sound. Our experimental data were consistent (R = 0.87) with a published empirical model that predicts velocity as a function of molecular structure. These data provide a rational basis for optimizing targeted perfluorocarbon-based contrast agents and offer further insight into the physical mechanisms responsible for the observed enhancement of surface acoustic reflectivity.