High throughput acoustic and optical characterization of microbubbles for optimized contrast ultrasound imaging

Abstract

Echogenic particles, such as microbubbles and volatile liquid micro-/nanodroplets, have shown considerable potential in a variety of clinical diagnostic and therapeutic applications. The accurate prediction of their response to ultrasound excitation is however extremely challenging, and this has hindered the optimization of techniques such as quantitative ultrasound imaging and targeted drug delivery. Existing characterization techniques, such as ultra-high speed microscopy, provide important insights, but suffer from a number of limitations; most significantly difficulty in obtaining large data sets suitable for statistical analysis and the need to physically constrain the particles, thereby altering their dynamics. Here, a microfluidic system is presented that overcomes these challenges to enable the measurement of single echogenic particle response to ultrasound excitation with a throughput of 20 samples/second and an uncertainty below 7% in the measurements. Demonstration of optimized contrast ultrasound imaging is shown based on the characterization of over 100,000 individual SonoVue® bubbles.