Until recently, cardiac ultrasound has offered no method of evaluating myocardial perfusion other than assessment of the end result of ischemia, such as wall motion abnormalities. Recent attempts at developing an effective contrast agent to measure myocardial perfusion have resulted in the development of microbubbles, 6 to 12 micron unstable preparations of air trapped in fluid which serves as a highly echogenic media. Clinical utility of using contrast ultrasonography to measure blood flow is critically dependent upon the development of stable microbubbles that are small enough for unhindered capillary passage for intravenous injection. The goal of the phase I grant is to develop reproducible, stable, small, air trapped spheres to serve as a perfusion contrast agent. The agent will optimally consist of 4.0 micron diameter air trapped spheres which will be tested for shelf- life echogenic properties, and preliminary toxicity. When stable preparations are made, test will be performed both in vitro as well as in vivo to demonstrate contrast efficacy. Phase II of this grant will be to commercialize this product. Phase I will serve as a basis during phase II to perform full toxicity testing in dogs and monkeys. After successful completion of toxicity testing, an IND will be filed and clinical evaluation performed to obtain FDA approval. Successful development of a stable ultrasound contrast agent will have wide applicability not only in monitoring cardiac perfusion but also in the assessment of tissue perfusion in other anatomic sites.