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.

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.

Selective detection of the microbubble contrast medium can be enhanced by Doppler processing that removes signals with zero Doppler frequency shifts. This will remove tissue harmonics. By detecting overlong bursts of inverted pulses and using Doppler detection methods, very high sensitivity to microbubbles can be achieved. The bubbles can be detected at sufficiently low incident power levels to avoid destroying them. Pulse inversion Doppler has demonstrated the first real-time images of myocardial perfusion using perfluorocarbon gas agents.

See also Pulse Inversion Imaging, Myocardial Contrast Echocardiography, and Perfluorochemicals.

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.

From GE Healthcare.;
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