(CCI) A major limitation of the use of ultrasound contrast agents is the problem that signals from the microbubbles are mixed with those from tissue, so that the distribution of the microbubbles is not optimally displayed either in Doppler or gray scale.
Coherent contrast imaging is a high frame rate implementation of inverting the phase of alternate sound pulses and summing the resulting echoes. The symmetrical signals from linear reflectors are cancelled leaving those from non-linear scatterers, with the advantage that the cancellation is performed without the need to transmit two pulses per image line so that bubble destruction is minimized. Coherent contrast imaging yields best results in the vascular phase of phospholipid microbubbles (such as Definity and SonoVue).

See also Coherence.

EchoGen® is a fluorocarbon-based (dodecafluoropentane) third generation USCA. EchoGen® consists of microbubbles stabilized with surfactants in a phase shift colloid emulsion (perflenapent). EchoGen® requires no preparation, reconstitution, or refrigeration.
Perflenapent emulsion would represent a significant advance in contrast echocardiography caused by effective and long lasting opacification of the left ventricle and enhanced endocardial border delineation.
The persistence of the contrast effect permits interrogation in multiple echocardiographic views, as well as the visualization and localization of myocardial perfusion deficits at rest by producing a negative contrast effect.
October 12, 2000
Sonus Pharmaceuticals, Inc. announced a strategic decision to refocus the Company on the development of its drug delivery and blood substitute products. At the same time, Sonus has withdrawn the NDA (New Drug Application) and discontinued clinical activity for its ultrasound contrast product, EchoGen®.
August 06, 2001
Sonus Pharmaceuticals, Inc. announced that it has entered into an agreement to sell its ultrasound contrast assets for $6.5 million to Amersham plc. As part of the agreement, Sonus has also assigned to Nycomed its interest in the ultrasound contrast patent license agreement entered into with Chugai Pharmaceutical Co. Ltd. and Molecular Biosystems Inc in January 2001.

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.

Harmonic B-mode imaging takes advantage of the non-linear oscillation of microbubbles. During harmonic imaging, the sound signal is transmitted at a frequency of around 1.5 to 2.0 MHz and received at twice this frequency. The microbubbles also reflect waves with wavelengths different from the transmitted one, the detectors can be set to receive only the latter ones and create only images of the contrast agent.
Using bandpass filters the transmitted frequency is separated from the received signal to get improved visualization of vessels containing ultrasound contrast agents (USCAs). The signal to noise ratio during the presence of microbubbles in tissue is four- to fivefold higher at the harmonic compared with the basic frequency.
Using harmonic B-mode imaging, harmonic frequencies produced by the ultrasound propagation through tissue have to be taken into account. The tissue reflection produces only a small amount harmonic energy compared to USCAs, but has to be removed by background subtraction for quantitative evaluation of myocardial perfusion.

See also Non-linear Propagation.

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