Abstract
This work is a quantitative, in vitro investigation of cell death caused by ultrasound (US) therapy with two microbubble formulations, one typical and one nested in the aqueous core of a polymer microcapsule. In the case of un-nested mircobubbles, no cell death was observed below the inertial cavitation threshold, but cell death increased with increasing microbubble concentration and with peak negative ultrasound pressure at pressures exceeding the inertial cavitation threshold. Little to no cell death was observed with nested microbubbles, irrespective of the occurrence of inertial cavitation. We attribute the increased cell viability both to an increase in the inertial cavitation threshold and to absorbance of the energy of inertial cavitation by the outer PLA shell. Nested microbubbles can thus be considered safer than traditional, un-nested contrast agents for imaging without sacrificing the quality of the image.