Reverse engineering the ultrasound contrast agent.

In this review, a brief history and current state-of-the-art is given to stimulate the rational design of new microbubbles through the reverse engineering of current ultrasound contrast agents (UCAs). It is shown that an effective microbubble should be biocompatible, echogenic and stable. Physical mechanisms and engineering calculations have been provided to illustrate these properties and how they can be achieved. The reverse-engineering design paradigm is applied to study current FDA-approved and commercially available UCAs. Given the sophistication of microbubble designs reported in the literature, rapid development and adoption of ultrasound device hardware and techniques, and the growing number of revolutionary biomedical applications moving toward the clinic, the field of Microbubble Engineering is fertile for breakthroughs in next-generation UCA technology. It is up to current and future microbubble engineers and clinicians to push forward with regulatory approval and clinical adoption of advanced UCA technologies in the years to come.