Characterizing how size distribution and concentration affect echogenicity of ultrasound contrast agents

We investigated the effects of UCA gas bubble size distribution and concentration on the generated ultrasound echogenicity signal. Gas bubble size characterization using Coulter Counter and cryogenic-SEM revealed the hollow structure and rare presence of microbubbles >10 µm in a commercial UCA product, Lumason™. Volume-weighed size and concentration were observed to be more sensitive to changes in UCA bubble stability than number-weighted size and concentration. Size distribution measurements showed that the force (e.g., shaking/agitation energy) used to redisperse the sample did not affect the size distribution, concentration, or echogenicity of the UCA sample. The ultrasound backscattering coefficient (BSC) of size fractionated and serial diluted microbubbles showed that the echogenicity signal correlates most with UCA bubble concentration, especially volume-weighted concentration. Findings from this study may be used to support demonstrating the equivalence of a generic UCA product to the reference listed drug.