Microbubble Surface Modes

In the past decade, microbubble contrast agents have evolved from a technical curiosity into a new clinical modality for ultrasound imaging. Among other achievements, microbubbles can be credited with the first real time images of myocardial perfusion that have been made by medical imaging. The agents themselves are now into their second generation, dominated by the use of perfluorocarbon gases and thin, flexible shells. The first synthetic shell agents using polymers designed to decouple the physical stability of the bubble from its acoustic behavior are near to clinical availability; work is now underway to associate these constructs with targeting ligands as well as drugs, genes, and other biological agents that will eventually be delivered using bubbles. The effort to image microbubbles has warded advances in imaging technology that expand beyond contrast studies; tissue harmonic imaging has become a standard method in the clinic, often used in preference to conventional linear imaging of organ structures. For microbubble detection, the challenge of detecting bubbles without disrupting them, while rejecting both the tissue echo and the echo from the propagation harmonic has stimulated significant innovation in imaging strategies. Most approaches include sequences of pulses, with periodic modulation of amplitude or phase, or both, followed by some form of Doppler detection. Their success relies on an understanding of the behavior of bubbles in an acoustic field, an area that has benefitted from the recent advent of extremely fast cameras. In particular, the mechanisms of bubble disruption are only now beginning to be understood. These are important not only because they underlie the most sensitive method to detect a bubble, but because disruption followed by reperfusion offers a unique opportunity to quantify microvascular flow and volume. These quantitative flow measurements do, however, depend on assumptions about vascular geometry and indicator concentration and are at present less well validated than they should be. Finally, the issue of the very low concentration of microbubbles (usually less than 100 per ml of tissue) and the unknown subpopulation that undergoes resonant oscillation and hence are detectable, has yet to be addressed. One approach that will be shown involves