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®.

(MI) The mechanical index is an estimate of the maximum amplitude of the pressure pulse in tissue. It is an indicator of the likelihood of mechanical bioeffects (streaming and cavitation). The mechanical index of the ultrasound beam is the amount of negative acoustic pressure within a ultrasonic field and is used to modulate the output signature of US contrast agents and to incite different microbubble responses.
The mechanical index is defined as the peak rarefactional pressure (negative pressure) divided by the square root of the ultrasound frequency.
The FDA ultrasound regulations allow a mechanical index of up to 1.9 to be used for all applications except ophthalmic (maximum 0.23). The used range varies from 0.05 to 1.9.
At low acoustic power, the acoustic response is considered as linear. At a low MI (less than 0.2), the microbubbles undergo oscillation with compression and rarefaction that are equal in amplitude and no special contrast enhanced signal is created. Microbubbles act as strong scattering objects due to the difference in impedance between air and liquid, and the acoustic response is optimized at the resonant frequency of a microbubble.
At higher acoustic power (MI between 0.2-0.5), nonlinear oscillation occurs preferentially with the bubbles undergoing rarefaction that is greater than compression. Ultrasound waves are created at harmonics of the delivered frequency. The harmonic response frequencies are different from that of the incident wave (fundamental frequency) with subharmonics (half of the fundamental frequency), harmonics (including the second harmonic response at twice the fundamental frequency), and ultra-harmonics obtained at 1.5 or 2.5 times the fundamental frequency. These contrast enhanced ultrasound signals are microbubble-specific.
At high acoustic power (MI greater than 0.5), microbubble destruction begins with emission of high intensity transient signals very rich in nonlinear components. Intermittent imaging becomes needed to allow the capillaries to be refilled with fresh microbubbles. Microbubble destruction occurs to some degree at all mechanical indices. A mechanical index from 0.8 to 1.9 creates high microbubble destruction. The output signal is unique to the contrast agent.

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.

Microbubbles filled with air or inert gases are used as contrast agents in ultrasound imaging. Compression and rarefaction created by an ultrasound wave insonating a gas-filled microbubble along with the mechanical index of the ultrasonic beam lead to volume pulsations of the bubbles, and it is this change that results in the signal enhancement.
Microbubbles have diameters from 1 μm to 10 μm and a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. These microbubbles can cross the pulmonary capillaries and have a serum half-life of a few minutes. Microbubbles in the 1-10 μm range have their resonance at the frequencies used in diagnostic ultrasound (1−15MHz). Smaller bubbles resonate at higher frequencies. Caused by this coincidence, they are such effective reflectors.
The intrinsic compressibility of microbubbles is approximately 17,000 times more than water, and they are very strong scatterers of ultrasound. Under acoustic pressure the vibrating bubble radius may have a conventional linear response or a harmonic non-linear response. Microbubbles usually increase the Doppler signal amplitude by up to 30 dB.