(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.

The various gas microbubble contrast media are generally safe with low toxicity in humans. The tolerance of these agents is much higher than that of most x-ray agents, a reflection perhaps of the higher expectation of safety and convenience for ultrasound.
Extensive preclinical and clinical trials have demonstrated an excellent ultrasound contrast agent safety profile, the main side effect being a mild and transient local discomfort at the injection site which results from the high osmolality of these agents. Each contrast agent has its own profile of adverse effects, but all have been trivial thus far.

See also Ultrasonic Contrast Agents.

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.

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.

Submicron ultrasound contrast agents are gas-filled, double-walled microspheres with a diameter smaller than 1 μm that rupture when exposed to ultrasound energy at megahertz frequencies. These agents differ from traditional ultrasound contrast microbubbles in that the submicron bubbles may serve as extravascular agents. They are small enough to travel through the lymphatic system and to be extravasated from tumor neovasculature. The detection of these agents is limited by their hard shell, which requires high-pressure ultrasound insonation for shell rupture and excitation of the gas bubble. After shell rupture, the gas diffuses rapidly from submicron sized agents. The optimal processing of each echo is important.