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

MRX 115 is a liposome based microbubble formulation and has been demonstrated as effective for cardiac blood pool imaging, Doppler enhancement and potentially myocardial perfusion imaging.
MRX 115 is based upon the demand for a stable, robust blood pool ultrasound contrast agents, also called DMP 115 or Aerosomes™ (ImaRx LLC) and now Definity®.

Standard scanners allow visualizing microbubbles on conventional gray scale imaging in large vascular spaces. In the periphery, more sensitive techniques such as Doppler or non-linear gray scale modes must be used because of the dilution of the microbubbles in the blood pool. Harmonic power Doppler (HPD) is one of the most sensitive techniques for detecting ultrasound contrast agents.
Commonly microbubbles are encapsulated or otherwise stabilized to prolong their lifetime after injection. These bubbles can be altered by exposure to ultrasound pulses. Depending on the contrast agent and the insonating pulse, the changes include deformation or breakage of the encapsulating or stabilizing material, generation of free gas bubbles, reshaping or resizing of gas volumes.
High acoustic pressure amplitudes and long pulses increase the changes. However, safety considerations limit the pressure amplitude and long pulses decrease spatial resolution. In addition, lowering the pulse frequency increases destruction of contrast bubbles. However, at low insonation power levels, contrast agent particles resist insonation without detectable changes. Newer agents are more reflective and will usually allow gray scale imaging to be used with the advantages of better spatial resolution, fewer artifacts and faster frame rates.

Feasible imaging methods with advantages in specific acoustic microbubble properties:
Resonating microbubbles emit harmonic signals at double their resonance frequency. If a scanner is modified to select only these harmonic signals, this non-linear mode produces a clear image or trace. The effect depends on the fact that it is easier to expand a bubble than to compress it so that it responds asymmetrically to a symmetrical ultrasound wave. A special array design allows to perform third or fourth harmonic imaging. This probe type is called a dual frequency phased array transducer.

See also Bubble Specific Imaging.

A microbubble shell, designed to reduce diffusion into the blood, can be stiff (e.g., denatured albumin) or more flexible (phospholipid), varying in thickness from 10-200 nm.
The shell stabilizes against dissolution and coalescence with additional materials at the gas-liquid interface. This material can be an elastic solid shell that enhances stability by supporting a strain to counter the effect of surface tension. Also a surfactant, or a combination of two or more, improves the stability by a high reduction of the surface tension at the interface. Current ultrasound contrast agents are micron-sized bubbles with a stabilizing shell.

Non-linear imaging is used to detect primary non-linear components of the received echo. Non-linear methods like harmonic imaging and pulse inversion imaging are designed to detect ultrasound contrast agents.

See also Contrast Pulse Sequencing, and Power Modulation.