Tissue-specific ultrasound contrast agents improve the image contrast resolution through differential uptake. The concentration of microbubble contrast agents within the vasculature, reticulo-endothelial, or lymphatic systems produces an effective passive targeting of these areas. Other contrast media concepts include targeted drug delivery via contrast microbubbles.
Tissue-specific ultrasound contrast agents are injected intravenously and taken up by specific tissues or they adhere to specific targets such as venous thrombosis. These effects may require minutes to several hours to reach maximum effectiveness. By enhancing the acoustic differences between normal and diseased tissues, these tissue-specific agents improve the detectability of abnormalities.
Some microbubbles accumulate in normal hepatic tissue; some are phagocytosed by Kupffer cells in the reticuloendothelial system and others may stay in the sinusoids. Liver tumors without normal Kupffer cells can be identified by the lack of the typical mosaic color pattern of the induced acoustic emission. The hepatic parenchymal phase, which may last from less than an hour to several days, depending on the specific contrast medium used, may be imaged by bubble-specific modes such as stimulated acoustic emission (color Doppler using high MI) or pulse inversion imaging.

The traveling ultrasonic wave causes a low-level ultrasound radiation force when this energy is absorbed in tissues (absorbed dose). This force produces a pressure in the direction of the beam and away from the transducer. It should not be confused with the oscillatory pressure of the ultrasound wave itself. The pressure that results and the pressure gradient across the beam are very low, even for intensities at the higher end of the range of diagnostic ultrasound. Mechanical effects like radiation forces lead to stress at tissue interfaces. The effect of the force is manifest in volumes of fluid where streaming can occur with motion within the fluid. The fluid velocities which result are low and are unlikely to cause damage.
The effects of ultrasound radiation force (also called Bjerknes Forces) were first reported in 1906 by C. A. and V. F. K. Bjerknes, when they observed the attraction and repulsion of air bubbles in a sound field.
While incompressible objects do experience radiation forces, compressible objects driven at their resonant frequency experience far larger forces and can be observably displaced by low-amplitude ultrasound waves. A microbubble driven near its resonance frequency experiences a large net radiation force in the direction of ultrasound wave propagation. Ultrasound pulses of many cycles can deflect resonant microbubbles over distances on the order of millimeters.
In addition to primary radiation force, which acts in the direction of acoustic wave propagation, a secondary radiation force for which each individual bubble is a source and receptor causes the microspheres to attract or repel each other. The result of this secondary force is that a much larger concentration of microbubbles collects along a vessel wall than might otherwise occur.

See also Acoustically Active Lipospheres.

Vascular ultrasound contrast agents are gas microbubbles with a diameter less than 10 μm (2 to 5 μm on average for most of the newer agents) to pass through the lung capillaries and enter into the systemic circulation. Air bubbles in that size persist in solution for only a short time; too short for systemic vascular use in medical ultrasound imaging. So the gas bubbles have to be stabilized to persist long enough and survive pressure changes in the heart.
Most vascular contrast media are stabilized against dissolution and coalescence by the presence of additional materials at the gas-liquid interface. In some cases, this material is an elastic solid shell that enhances stability by supporting a strain to counter the effect of surface tension. In other cases, the material is a surfactant, or a combination of two or more surfactants.
Typically the effective duration of vascular enhancement is a few minutes, after which the microbubbles dissipate. This rather short duration of vascular enhancement makes it easy to perform repeated dynamic studies. Intravenous vascular contrast agents will be used in imaging malignant tumors in the liver, kidney, ovary, pancreas, prostate, and breast. Tumor neovascularization can be a marker for angiogenesis, and Doppler signals from small tumor vessels may be detectable after contrast injection. Contrast agents are useful for evaluating vessels in a variety of organs, including those involved in renal, hepatic, and pancreatic transplants. If an area of ischemia or a stenosis is detected after contrast administration, the use of other more expensive imaging modalities, including CT and MRI, can often be avoided.

See also Acoustically Active Lipospheres.

Albunex and Infoson, used mainly in cardiac evaluations, are first generation one-pass-only contrast agents and have been replaced by the new-generation contrast media. Albunex and Infoson are the same sonicated human serum albumin microbubbles. Infoson is licensed and manufactured in Europe, while Albunex was produced in the USA.
Albunex, an air-filled microbubble with a denatured albumin shell (modified from air-filled albumin microspheres prepared from sonicated 5% human serum albumin), was the first FDA-approved contrast agent, but is no longer in production.
Cardiac shunts and valve regurgitations are often evaluated with Color Doppler Imaging (CDI), which also improved with injections of Albunex, but this agent is pressure-sensitive and does not recirculate. It is effectively a one-pass-only agent, limiting its clinical efficacy.

See also First generation USCA, Echocardiography and Contrast Enhanced Ultrasound.

California-based research and development company. Alliance Pharmaceutical Corporation. The principal activities of the Company is identifying, designing, and developing novel medical products. The Company is engaged in development of scientific discoveries into medical products and licensing these products to multinational pharmaceutical companies in exchange for fixed payments and royalty or profit sharing payments. The Company has developed three innovative products through initial clinical (human) trials. The products are Oxygent™, Liquivent and Imavist™. The Company's strategy is to identify potential new medical products though its own efforts and scientific collaborations with researchers and clinicians in universities and medical centers. In Dec 2000 the company acquired Molecular Biosystems Inc a developer of intravenous ultrasound contrast agent for the heart.

'September 20, 2001 Alliance Pharmaceutical Corp. announced that it has won a favorable Final Judgment from the United States Patent and Trademark Office's Board of Patent Appeals and Interferences regarding claims in U.S. Patent No. 5,558,854, which is owned by Nycomed Imaging, AS. The Final Judgment determined that claims made in the Nycomed patent with respect to 'microbubbles' that contain perfluorohexane filling gas are invalid and are therefore unpatentable.'
June 04, 2010, the company announced in their quartzerly report: 'We no longer have working capital to fund our operations. Because adequate funds have not been available to us in the past, we have already delayed our Oxygent development efforts and have eliminated our other product development programs.'

Ultrasound Contrast Agents: