The gas in microbubbles is highly compressible and, when subjected to the alternating compression and refraction pressures that constitute an ultrasound pulse, microbubbles oscillate at their natural frequency at which they resonate most strongly. This is determined by their size but is also influenced by the composition of the filling gas.
Air, sulfur hexafluoride, nitrogen, and perfluorochemicals are used as filling gases. Most newer ultrasound contrast agents use perfluorochemicals because of their low solubility in blood and high vapor pressure. By substituting different types of perfluorocarbon gases for air, the stability and plasma longevity of the agents have been markedly improved, usually lasting more than five minutes.

Perfluorochemicals are used as microbubble filling gases because of their low solubility in blood and high vapor pressure. Various types of perfluorochemical gases like perfluorocarbon, perfluorobutane, perfluoropropane, and perfluorohexane are used to substitute the air in microbubbles to improve the stability and plasma longevity of the agents. Perfluorocarbons are liquids at room temperature but gas at body temperature. The large molecules of perfluorocarbons have slow diffusion and solubility which increase the enhancement time of the ultrasound contrast agent as compared to air.

See also Filling Gas, and PESDA.

[This entry is marked for removal.]

From Acusphere Inc
AI-700 (trade name Imagify™) is an US contrast agent, usable for myocardial perfusion undergoing regulatory FDA approval. The synthetic polymers used in AI-700 (perflubutane polymer microspheres) do not break during the ultrasound imaging procedure. The used perfluorocarbon filling gas is less soluble in water and therefore has the propensity to stay inside the contrast agent particles. As a result, a higher concentration of gas is delivered to the myocardium over a longer period of time, thereby enabling AI-700 to target the broader application of myocardial perfusion assessment.
Imagify is a dry powder consisting of small, porous microparticles filled with perfluoropropane. These microparticles are made of a synthetic biodegradable polymer, called poly (D, L-lactide co-glycolide), or PLGA, that has been used in other drug delivery systems approved by the FDA.
The composition and structure of the phospholipid containing microparticles and the properties of the perfluorocarbon gas slow the rate at which the gas dissolves and prevent the microparticles from being quickly broken down. The powder is to suspend in sterile water and injected by a single intravenous injection prior to ultrasound imaging.

In 2009, Acusphere Inc received feedback from the Food and Drug Administration (FDA) to their New Drug Application (NDA) stating that another clinical trial would be required for U.S. approval, this one demonstrating that Imagify with ultrasound is superior to ultrasound without Imagify.
In June 2004, Acusphere entered into a Collaboration, License and Supply Agreement with Nycomed Danmark APS for the European development and marketing rights to Acusphere's lead product candidate AI-700.
Acusphere's focus will be on preparing the Marketing Authorization Application (MAA) for filing in Q4 2010, building upon the work that the previous partner, Nycomed, had done, in concert with the NDA.


In 2008 the FDA panel rejected the regulatory application for AI-700 (Imagify™) because of safety concerns.

(AALs) Acoustically active lipospheres and ultrasound are under development to deliver bioactive molecules to the vascular endothelium. The AALs are similar to both ultrasound contrast agents and drug-delivering liposomes. They can carry bioactive substances using biologically inert shells and deliver those substances when disrupted by ultrasound.
The lipospheres consist of a small gas microbubble surrounded by a thick oil shell and are enclosed by an outermost lipid layer. The gas bubble contained in these vehicles makes them acoustically active, similar to ultrasound contrast agents. Acoustically active lipospheres can be nondestructively deflected using ultrasound radiation force, and fragmented with high intensity ultrasound pulses. Their lipid-oil complex can carry bioactive substances at high concentrations. An optimized sequence of ultrasound pulses can deflect the AALs toward a vessel wall then disrupt them, painting their contents across the vascular endothelium.

See also Filling Gas, and MRX 115.

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: