Ultrasound contrast agents

Biomedical and Biotechnology. The use of mictocapsules for a variety of biomedical and biological appHcations has been promoted for many years (50,51). Several biomedical mictocapsule appHcations ate in clinical use or have approached clinical use. One appHcation is the use of air-fiUed human albumin mictocapsules as ultrasound contrast agents. Such mictocapsules, caUed mictobubbles, ate formed by ultrasonicating 5% albumin solutions to produce 4—10-)J.m diameter air-fiUed capsules (52). When injected the capsules act as a useful transpulmonary echo contrast agent (53) that has been approved for use in humans by the U.S. FDA. 

Kleinjan WE, de Keizer A, Janssen AJH (2003) Biologically Produced Sulfur. 230 167-188 Klibanov AL (2002) Ultrasound Contrast Agents Development of the Field and Current Status. 222 73-106... 

Klibanov AL (2002) Ultrasound Contrast Agents Development of the Eield and Current Status. 222 73-106... 

Why Use Ultrasound Imaging Modality and Ultrasound Contrast Agents ... 

The ultrasound contrast agents are manufactured from nontoxic natural or synthetic biodegradable materials (e.g., lipids or proteins), and a small amount of an inert low-solubility non-reactive gas (e.g., perfluorocarbon). These components have been shown to be harmless to the patient unlike the tens of milliliters of concentrated viscous solutions of the widely used X-ray contrast agents (which may sometimes result in nephrotoxicity). 

Known or perceived disadvantages of ultrasound contrast agents are as follows. Microbubble agents with their size of several microns cannot escape from the bloodstream under normal conditions. Thus, the imaging cannot be performed in the areas outside the normal bloodstream. Essentially, microbubbles can only go where red blood cells do. Microbubble agents last only several minutes in the bloodstream. This makes their application less convenient for lengthy multi-plane examinations, and requires multiple boluses of contrast administration or a continuous infusion. 

Particulate agents (especially gas-filled microbubble materials) are currently approached with caution by physicians, regulatory agencies and industry marketing, despite the fact that by 2001, perhaps up to 100,000 patients (a rough estimate) will have received ultrasound contrast agents with very few (mostly minor) side effects manifested. 

For all the above reasons, ultrasound contrast agents have not yet entered widespread clinical use. 

Albunex was claimed to be the first ultrasound contrast agent capable of myocardial opacification after intravenous injection [16],but very large doses of the material had to be applied. 

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