Contrast-enhanced ultrasound

Contrast-enhanced ultrasound (CEUS) involves the administration of intravenous contrast agents consisting of microbubbles/nanobubbles of gas.

First-generation ultrasound contrast agents contained microbubbles of air that were dissolved in blood when exposed to acoustic pressure in the ultrasound field. First-generation contrast agents were therefore present in the bloodstream for a limited time ¹.

Second-generation contrast agents include microbubbles of perfluorocarbon, nitrogen gas, or sulfur hexafluoride stabilized in a phospholipid membrane. The bubbles oscillate when exposed to the ultrasound beam (they are being compressed by the effect of positive pressure created by the ultrasound waves and they expand in the negative pressure phase). The compression of the gas is greater than expansion which creates a non-linear response (echo). This greatly affects ultrasound backscatter and increases vascular contrast in a similar manner to intravenous contrast agents used in CT and MRI ². Examples of ultrasound contrast agents available commercially include SonoVue^® (Bracco).

Contrast-enhanced ultrasound has the advantage over contrast-enhanced MRI and CT in patients with contraindications such as renal failure or iodinated contrast allergy. CEUS also allows for dynamic and repeat examinations.

An individual microbubble is estimated to measure approximately 6 micrometres, compared to a human erythrocyte measuring approximately 9 micrometres. Microbubbles are therefore not filtered in the lungs since they are equivalent in size to red blood cells. Microbubbles are different from the agitated saline used in echocardiographic "bubble studies".

The microbubbles used for CEUS are sensitive to insonation, and as a consequence can easily be depleted by overscanning during the arterial and portal phase, potentially jeopardizing the detection of e.g. late phase wash-out. This feature can be however also exploited by deliberately destructing them using a single ultrasound pulse with very high mechanical index, commonly termed as "flash" flash⁸. Such an option is nowadays available in most CEUS-capable ultrasound scanners, and allows for the evaluation of slower, e.g. venous phase, contrast refill / reperfusion of a lesion or tissue (termed flash-replenishment technique ⁹),  it can also be used to clear residual contrast signal from the area of interest before a contrast reinjection.

Non-targeted contrast-enhanced ultrasound

The more common method

• dynamic evaluation of the vascularity of a target lesion, most commonly in the liver or kidney, may be useful in diagnosis
• used to measure organ perfusion, which can be useful in diagnosing diffuse processes (e.g. cirrhosis)

Targeted contrast-enhanced ultrasound

Contrast agents designed to bind to specific molecules, which are then targeted at tissues expressing that substance.

CEUS artefacts

In very rare cases CEUS contrast agents may accumulate in the liver and cause inhomogeneous, often confluent hyperechoic regions, or acoustic shadowing without associated clinical symptoms. This is termed prolonged heterogeneous liver enhancement and is a benign, self-limiting complication.