A review of theoretical models for microbubble contrast agents

Abstract

Theoretical investigation of the acoustic responses of albumin-encapsulated microspheres began nearly fifteen years ago when Albunex, the first agent approved for clinical use in the U.S., was still in development. Since that time, the number of potential ultrasound contrast agents has grown considerably. These agents utilize a variety of both shell materials (e.g., proteins, synthetic polymers, surfactants, lipids) and encapsulated gases (e.g., air, sulfur hexafluoride, perfluorocarbons). The shell may be very thick or vanishingly thin. A thorough understanding of the interaction between ultrasound pulses and contrast microbubbles is essential for the successful clinical application of a particular agent. In this talk, models developed by de Jong et al., Church, Ye, Allen et al., Khismatullin et al., and others will be reviewed. The basis of these theories is a free bubble model supplemented by the effect of the encapsulating shell. The differences among these models lie primarily in their treatment of the encapsulating layer and, to some extent, the surrounding medium. The nature of various contrast agents will be discussed, and appropriate models for each will be described. Comparisons among models will include predictions of clinically significant acoustic responses (resonance frequency, scattering strength, nonlinearity, etc.).