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.

(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.

Many different contrast imaging techniques have been developed. Most are either variations, hybrids, or combinations of the following ultrasound techniques:

See also Coherent Contrast Imaging, Ultrasound Picture and Targeted Contrast Imaging.

From POINT Biomedical Corp
M1134 is a nitrogen-filled submicron ultrasound contrast agent under development with a bilayered shell composed of a biodegradable polymer and a human serum albumin outer coating. The microbubbles have initial diameters from 500 nm to 1.3 μm, with more than 50% having a diameter smaller than a micron.
M1134 can be used in targeted contrast imaging by entering the lymphatic system after injection into the interstitium and accumulation at lymph nodes.
M1134 and M1091 are two agents made of the same polymer with the same relative wall thickness, differing only in the microbubble diameter.

MRX 408 is an investigational thrombus-specific ultrasound contrast agent for clot detection and sonothrombolysis enhancement. Targeted contrast imaging with this GPIIb receptor-targeted ultrasound contrast agent demonstrated better visualization of thrombus within AV fistulae.
MRX 408 is available (ImaRx LLC) with a mean radius of 1.0 mm and a standard deviation of 0.8 mm.