Solid regions have internal ultrasound echoes and are classified as echo poor, hypoechoic or hypoechogenic if there are few internal echoes. Hypoechoic structures appear dark in ultrasound imaging, more homogeneous structures are darker than heterogeneous.
Soft atherosclerotic plaque, liver adenoma or FNH appear with a nodular hypoechogenicity. As metastases close the blood vessels they infiltrate, tumor tissues become hypoechogenic after injection of contrast agent. Muscle appears relatively hypoechoic to tendon fibers, also articular hyaline cartilage appears hypoechoic.

Targeted ultrasound contrast agents provide advantages compared with usual microbubble blood pool agents. The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. Tissue-specific ultrasound contrast agents improve the image contrast resolution through differential uptake. Targeted drug delivery via contrast microbubbles is another contrast media concept and provides the potential for earlier detection and characterization of disease.
Targeted contrast imaging provides a higher sensitivity and specificity than obtained with a nontargeted contrast agent.
The detection of disease-indicative molecular signatures may allow early assessment of pathology on a molecular level.
Molecular imaging should be an efficient and less invasive technique to obtain three-dimensional localization of pathology.
Ultrasound agents typically remain within the vascular space, and therefore possible targets include molecular markers on thrombus, endothelial cells, and leukocytes. Targeted contrast agents permit noninvasive detection of thrombus, cancer, inflammation, or other sites where specific integrins or other adhesion molecules are expressed. Adhesion molecules such as monoclonal antibodies, peptides, asialoglycoproteins, or polysaccharides are incorporated into the shell of the microbubble or liposome. After injection into the bloodstream, the targeted agent accumulates via adhesion receptors at the affected site, enhancing detection with an ultrasound system.

See also Acoustically Active Lipospheres, and Tissue-Specific Ultrasound Contrast Agent.

(CEUS) Contrast agents increase the reflection of ultrasonic energy, improve the signal to noise ratio and caused by that the detection of abnormal microvascular and macrovascular disorders. Contrast enhanced ultrasound is used in abdominal ultrasound (liver sonography) as well as in cerebrovascular examinations e.g., for an accurate grading of carotid stenosis. The used contrast agents are safe and well tolerated.

The quality of the enhancement depends on:
The additional use of ultrasound contrast agents (USCAs) may overcome typical limitations like poor contrast of B-mode imaging or limited sensitivity of Doppler techniques. The development of new ultrasound applications (e.g., blood flow imaging, perfusion quantification) depends also from the development of pulse sequences for bubble specific imaging. In addition, contrast enhanced ultrasound improves the monitoring of ultrasound guided interventions like RF thermal ablation.

See also Contrast Enhanced Doppler Imaging, Contrast Harmonic Imaging, Contrast Imaging Techniques and Contrast Pulse Sequencing.

(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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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.