(UCA / USCA) Ultrasonic contrast agents, also called ultrasound contrast agents, are encapsulated bubbles on the order of 1-10 μm in diameter. These gas bubbles are injected into the blood stream in order to increase blood/ tissue contrast during an ultrasonogram. These microbubbles are filled with air or a gas with a lower solubility in blood than air, such as perfluorochemicals. The microbubble shell consists of albumin, phospholipid, or other material and encapsulates the gas core. Due to this construction, ultrasonic contrast agents are highly compressible, and have a high echogenicity.

See also Ultrasound Contrast Agent Safety.

Any abnormal reaction of a patient to an examination or procedure, like for example side effects of contrast agents or claustrophobia. Claustrophobic attacks as can happen with MRI are unknown with ultrasound examinations. Adverse reactions with ultrasonic contrast agents are very infrequent. In general, adverse reactions increase with the quantity of contrast media and also with the osmolarity of the compound.
Most frequently encountered adverse reactions are: Heat sensation, dizziness, nausea, hypotension due to vasodilatation, which can progress to hypotensive shock and anaphylactic reactions.

The various gas microbubble contrast media are generally safe with low toxicity in humans. The tolerance of these agents is much higher than that of most x-ray agents, a reflection perhaps of the higher expectation of safety and convenience for ultrasound.
Extensive preclinical and clinical trials have demonstrated an excellent ultrasound contrast agent safety profile, the main side effect being a mild and transient local discomfort at the injection site which results from the high osmolality of these agents. Each contrast agent has its own profile of adverse effects, but all have been trivial thus far.

See also Ultrasonic Contrast Agents.

(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.

(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.