(678f) Voltage-Sensitive Ultrasound Enhancing Agent: In Vitro and In Vivo analysis

We have created a voltage-sensitive ultrasound enhancing agent comprised of perfluorocarbon nano-droplets coated in a monolayer of polymeric surfactant that is then nested inside a negatively charged phospholipid bilayer. The particle, termed Electrast, is responsive to an applied electric field allowing for its internal components to become acoustically activated at ultrasound intensities that are inadequate to cause activation by ultrasound alone. Electrast is novel because activation depends on the presence of an electric field rather than the intensity of ultrasound. This talk will discuss key results from the bench top and the clinic, while commenting on the role of water transport in nesting structures, lipid relocation and reorientation, and lateral phase separation. Calcein and cobalt chloride leakage studies were performed to quantify the amount of water transported across the phospholipid bilayer when exposed to high frequency ultrasound, an applied electric field or a combination of the two. A custom-built, tissue-mimicking gel phantom coupled with a function generator was used to determine the contrast-to-tissue ratio of two different nesting architectures at varying electric field strengths and imaging parameters. Electrast has shown to be selectively activated in coronary circulation in two different animal models (rat and swine) showing an increase in brightness (dB) in the myocardium while leaving the ventricles largely unchanged. This talk will show that Electrast has the potential to be used clinically for myocardial perfusion imaging, assessing heart failure, and evaluating left ventricle wall motion.