Physical phenomena affecting quantitative imaging of ultrasound contrast agents

Microbubbles stabilized by a surfactant or polymer coating are the most effective form of contrast agent available for ultrasound imaging. They have shown great potential as a means of quantifying tissue perfusion, in particular determining physiologically significant parameters such as relative vascular volume and flow velocity. Clinical implementation of quantitative imaging procedures, however, has been hindered by poor characterisation of the complex relationship between microbubble concentration, scattering and image intensity. The aim of this paper is to describe theoretical and experimental investigations of the physical phenomena underlying these effects, such as the time, pressure and frequency dependence of microbubble behaviour, the influence of the bubble coating, size distribution and concentration; and to discuss the challenges involved in developing accurate quantitative imaging protocols.