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

Abstract

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.

Acoustic Cluster Therapy (ACT) — pre-clinical proof of principle for local drug delivery and enhanced uptake

“…2 min, the contrast signal from the ACT compound started a slow decrease back to baseline after some 15 min. The Sonazoid™ signal was as expected from this US contrast agents [20] and the imaging signal from ACT compound was similar to observations from earlier studies [16]. TICs of the microdroplets only control showed no significant changes of contrast intensity from baseline.…”

Contrast-enhanced ultrasonography used for post-treatment responses evaluation of radiofrequency ablations for hepatocellular carcinoma: a meta-analysis

“…SH U 508A is the first agent approved by Europe and Canada for radiology application. 25 However, Levovist (SH U 508A) has been withdrawn from the market after having been used for almost 10 years, 26 and thus contrast specific modes were much less effective in Levovist times. SonoVue and Sonazoid (also NC100100) are transpulmonary vascular agents with half-life .5 min after an intravenous bolus injection.…”

Driving delivery vehicles with ultrasound

“…Similarly, the complement activation resulting from the administration of liposomes has been examined recently, with a report that the removal of the negative charge from the lipo-polymer used to sterically stabilize microbubbles prevented complement activation [60]. Although few reports of adverse reactions to microbubbles have been published [61], the United States Food and Drug Administration has recently limited the use of microbubble contrast agents in patients with acute coronary syndrome and now requires monitoring of cardiac function after contrast imaging. These limitations have been assumed to result from anaphylaxis associated with complement activation.…”