Ultrasound Contrast Agent Modeling: A Review

Ultrasound is extensively used in medical imaging, being safe and inexpensive and operating in real time. Its scope of applications has been widely broadened by the use of ultrasound contrast agents (UCAs) in the form of microscopic bubbles coated by a biocompatible shell. Their increased use has motivated a large amount of research to understand and characterize their physical properties as well as their interaction with the ultrasound field and their surrounding environment. Here we review the theoretical models that have been proposed to study and predict the behavior of UCAs. We begin with a brief introduction on the development of UCAs. We then present the basics of free-gas-bubble dynamics upon which UCA modeling is based. We review extensively the linear and non-linear models for shell elasticity and viscosity and present models for non-spherical and asymmetric bubble oscillations, especially in the presence of surrounding walls or tissue. Then, higher-order effects such as microstreaming, shedding and acoustic radiation forces are considered. We conclude this review with promising directions for the modeling and development of novel agents.