Methods for Rapid Characterization of Tunable Microbubble Formulations

To optimize microbubble formulations for clinical applications, the size distribution, concentration, and acoustic intensity must be rapidly measurable to allow for the successful iteration of microbubble design. In this paper, a comprehensive method was developed to compare microbubble formulations with different lipid shell compositions using optical and acoustic methods of measurement to collect the size distribution, concentration, and mean scattering intensity. An open-source ImageJ macro code was modified for the selective counting and sizing of brightfield microbubble images. A high-throughput agarose phantom was designed to collect multiple scattering reflections of microbubble samples to estimate the echogenicity of each microbubble solution. The information contained in the size distribution and concentration, combined with the instantaneous scattering power, can identify modifications needed for prototyping specific microbubble formulations.