Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications

Abstract

Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs.

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“…Therefore, it is not necessary to perform laboratory tests to assess liver or kidney function prior to their administration [47].…”

Ultrasound contrast agents

“…As true blood pool agents, perfluorocarbons bubbles range from 1 to 10 μm in size, permitting passage through the pulmonary vascular system, which is essential for access to the systemic circulation. [27] Soft shell materials consist of phospholipids or other surfactants and demonstrate improved nonlinear oscillations. [28] Protein-shelled microbubbles are also available (e.g., Optison ® ) consisting of an albumin shell around perfluoropropane gas.…”

“…With increasing acoustic pressure, nonlinear vibrational patterns appear. [27] Tissue produces harmonic resonances only at higher mechanical index (MI), thus differentiation of signal origin whether tissue or UCA is possible. Using filter systems, multiples of the natural frequencies are received, allowing a certain amount of background (non-UCA) signal suppression.…”

Detection of Myocarditis With Molecular Echo Imaging

“…Because phosphatidyl serinecoated microbubbles have already been shown to be safe in clinical trials, 10 additional studies should now be performed to determine its efficacy in detecting these common clinical problems with molecular echo imaging techniques. …”