Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts.

The concept of contrast imaging was introduced to ultrasound almost 30 years ago. The development of ultrasound contrast agents (USCAs), initially slowed by technical limitations, has become more dynamic during the past decade. The ideal USCA should be non-toxic, injectable intravenously, capable of crossing the pulmonary capillary bed after a peripheral injection, and stable enough to achieve enhancement for the duration of the examination. While satisfying cost-benefit requirements, it should provide not only Doppler but also gray-scale enhancement. Already, Doppler examinations are improved by using USCAs when studying deep and small vessels, vessels with low or slow flow, or vessels with a non-optimal insonation angle. Ultrasound contrast agents also enhance detection of flow within abnormal vessels, including tumor vascularization and stenotic vessels, and provide better delineation of ischemic areas. Research is focusing on the development of specific contrast imaging sequences that allow detection of tissue enhancement similar to that obtained with CT or MRI. These sequences take advantage of the nonlinear behavior of the microbubbles within the ultrasound field, bringing real-time perfusion imaging for liver, kidney, and the myocardium into reach. New objectives include targeted agents that could further widen USCA applications to specific delivery of active drugs such as anticoagulants or cytotoxic compounds. The combination of new generations of USCAs and new ultrasound image sequences appears to be very promising and currently represents a significant part of ultrasound research.