(UCA / USCA) Ultrasonic contrast agents, also called ultrasound contrast agents, are encapsulated bubbles on the order of 1-10 μm in diameter. These gas bubbles are injected into the blood stream in order to increase blood/ tissue contrast during an ultrasonogram. These microbubbles are filled with air or a gas with a lower solubility in blood than air, such as perfluorochemicals. The microbubble shell consists of albumin, phospholipid, or other material and encapsulates the gas core. Due to this construction, ultrasonic contrast agents are highly compressible, and have a high echogenicity.

See also Ultrasound Contrast Agent Safety.

(UCA / USCA) Ultrasonography is the most commonly performed diagnostic imaging procedure. The introduction of sonographic contrast media into routine practice modifies the use of ultrasound in a variety of clinical applications. USCAs consist of microbubbles filled with air or gases and can be classified according to their pharmacokinetics. Among the blood pool agents, transpulmonary ultrasound contrast agents offer higher diagnostic potential compared to agents that cannot pass the pulmonary capillary bed after a peripheral intravenous injection. In addition to their vascular phase, some USCAs can exhibit a tissue- or organ-specific phase.
The sonogram image quality is improved either by decreasing the reflectivity of the undesired interfaces or by increasing the backscattered echoes from the desired regions.

Different types of ultrasound contrast agents:
Ultrasound contrast agents act as echo-enhancers, because of the high different acoustic impedance at the interface between gas and blood. The enhanced echo intensity is proportional to the change in acoustical impedance as the sound beam crosses from the blood to the gas in the bubbles.

The ideal qualities of an ultrasound contrast agent:
A typical ultrasound contrast agent consists of a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. The choice of the microbubble shell and gas has an important influence on the properties of the agent.
Current generations of microbubbles have a diameter from 1 μm to 5 μm. The success of these agents is mostly dependent on the small size and on the stability of their shell, which allows passage of the microbubbles through the pulmonary circulation. Microbubbles must be made smaller than the diameter of capillaries or they would embolize and be ineffective and perhaps even dangerous.
The reflectivity of these microbubbles is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the contrast agent particles themselves.
Ultrasound contrast agents produce unique acoustic signatures that allow to separate their signal from tissue echoes and to depict whether they are moving or stationary. This enables the detection of capillary flow and of targeted microbubbles that are retained in tissues such as normal liver.
The new generation of contrast media is characterized by prolonged persistence in the vascular bed which provides consistent enhancement of the arterial Doppler signal. Contrast agents make it also possible to perform dynamic and perfusion studies. Targeted contrast imaging agents are for example taken up by the phagocytic cell systems and thus have liver/spleen specific effects.

See also Ultrasound Contrast Agent Safety, Adverse Reaction, Tissue-Specific Ultrasound Contrast Agent, and Bubble Specific Imaging.

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'Acusphere (NASDAQ:ACUS) was a specialty pharmaceutical company that develops new drugs and improved formulations of existing drugs using its proprietary microparticle technology. Acusphere's three initial product candidates are designed to address large unmet clinical needs within cardiology, oncology and asthma. These product candidates were created using proprietary technology that enables Acusphere to control the porosity and size of nanoparticles and microparticles in a versatile manner that allows particles to be customized to address the delivery needs of a variety of drugs. Acusphere's lead product candidate, AI-700 (new trade name Imagify™), is a cardiovascular drug in Phase 3 clinical development. AI-700 is designed to enable ultrasound to compete more effectively with nuclear stress testing, the leading procedure for detecting coronary heart disease. An estimated 9.5 million procedures are done each year in the U.S. to detect coronary heart disease, the leading cause of death in the United States.'

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

[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.

Different stages of testing drugs in humans for example ultrasound contrast agents, from first application in humans through limited and broad clinical tests, to postmarketing studies. Preclinical trials are the testing in animals.

See also Drug Development and Approval Process USA, Food and Drug Administration, and European Medicines Agency.