(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.

Contrast agents improve the sensitivity of vascular Doppler ultrasound, for example in cerebrovascular sonography or examinations of deep abdominal vessels. They also enlarge the role of transcranial Doppler. Microbubbles can be used with various modes e.g., color and power Doppler imaging, as well as pulsed-wave Doppler to increase the signal intensity. However, the ultrasound system must be suitable for contrast enhanced technology.
Microbubbles usually stay within the vascular space; nevertheless, the contrast enhancement is limited to 2−6 minutes caused by physiologic clearance and bubble destruction.
Depended on the application, contrast agents can be administered with a different injection rate e.g., bolus injection, slow injection, or continuous infusion. Stable, homogeneous, and prolonged enhancement can be obtained with perfusion, lasting until the infusion is stopped.

See also Cerebrovascular Ultrasonography, Multiple Frame Trigger.

From Bayer Schering Pharma AG:
Available in Europe since 1996 and in Japan since 1999. Currently, the marketing situation is unclear.
Levovist® is a first generation USCA consisting of galactose (milk sugar) ground into tiny crystals whose irregular surfaces act as nidation sites on which air pockets form when it is suspended in water, much as soda water bubbles form at small irregularities on the surface of the glass. A trace of palmitic acid is added as a surfactant to stabilize the resultant microbubbles. When Levovist® dissolves in blood, air trapped inside the galactose is released as free gas bubbles. These bubbles have a weak encapsulating shell and are easily destroyed by ultrasound.
Different contrast ultrasonography methods have been developed since the introduction of Levovist®. Initially, Levovist® was an echo contrast medium for improving sensitivity in color Doppler and Power Doppler examinations, but was found to suffer from significant blooming, making it difficult to observe small blood vessels. However, Levovist® improves the accuracy of echocardiographic examinations in such indications as assessment of left ventricular function.
In addition to their vascular phase, some ultrasound contrast agents (USCAs) can exhibit a tissue- or organ-specific phase. Levovist® can accumulate within the liver and the spleen for up to 20 min once it has disappeared from the blood pool and improves the detectability of focal liver lesions and allows more reliable control of interventional tumor treatments. Varied types of information can be obtained by applying contrast imaging at different times after the injection using Levovist® in both the arterial phase and the late organ-specific phase.
1 g Levovist® granules contain 999 mg D-galactose and 1 mg palmitic acid.
Brand names in other countries: Levovist/Levograf

From Bayer Schering Pharma AG:
Echovist-200® was an effectively one-pass-only contrast medium for contrast sonography and Doppler-echocardiographic examinations for the detection, exclusion or follow-up of pathological states leading to hemodynamic changes. Because of the short intravascular life of the microparticles and microbubbles, transit through the pulmonary circulation is unusual. In cardiac evaluations Echovist-200® has been replaced by newer ultrasound contrast agents (USCA), therefore the manufacturing was discontinued.
Another range of echo contrast application is the female genital tract, in particular for the demonstration or exclusion of acquired or congenital changes of the uterine cavity and for the visualization of the Fallopian tubes and investigation of their patency.
1 g Echovist-200 granules contain 1 g D-galactose microparticles. 1 ml aqueous solution for production of the suspension contains 200 mg D-galactose.
Brand names in other countries: Ecovist.