Acoustic characterization of individual monodisperse contrast agents with an optical-acoustical system

Contrast agents that are available commercially have a polydisperse size distribution. It has been hypothesized that a uniform microbubble diameter might lead to improved imaging sensitivity. Using microfluidics technology that we have developed recently, we have been able to generate contrast agents with a nearly monodisperse size distribution. Echo responses from individual microbubbles from both monodisperse and polydisperse populations were analyzed in order to establish the relationship between scattered echo, microbubble diameter, and excitation frequency. Our experimental data were in very good agreement with simulations of bubble response from a modified Rayleigh-Plesset type model. Additionally, we performed in vivo experiments for non-targeted perfusion imaging. Simulations and experiments indicate that depending on microbubble diameter, excitation frequency, and distribution uniformity, significant differences in microbubble echo amplitude can be generated and that monodisperse contrast agents can be detected with greater amplitude than polydisperse agents under optimized conditions. These findings might have a substantial impact in the formulation of contrast agents to enhance ultrasonic sensitivity.