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Page 2 of 10 Vezeridis et al. Hepatoma Res 2020;6:53 I http://dx.doi.org/10.20517/2394-5079.2020.36

bloodstream for minutes, allowing ultrasound imaging machines with specialized contrast-specific modes
[6]
to visualize differences in the vascularity of tissues of interest . The microbubbles resonate and exhibit
harmonic signals under very weak ultrasound exposure while the background tissues exhibit only a linear
[7]
response to ultrasound signals . Contrast-specific imaging utilizes this unique property of microbubble
contrast agents, and cancels the linear tissue signal, resulting in a contrast-enhanced microbubble-only
[7]
image . CEUS is highly sensitive owing to the intrinsically high contrast of microbubbles .
[8]
Microbubble contrast agents demonstrate multiple contrast phases in the liver after they are injected
intravenously, progressing from arterial phase (~10-20 s to 30-45 s after injection) to portal venous phase
(~30-45 s to 2 min after injection) to late phase (~2 min to 4-6 min after injection) . Most malignancies
[4,9]
within the liver derive their blood supply from the hepatic arteries and not the portal vein. As a result,
malignancy typically manifests on CEUS as hyperenhancing compared to the surrounding liver on the
arterial phase and as hypoenhancing in the portal venous and late phases. This temporal reduction in the
[9]
enhancement of a lesion from earlier to later phases is also known as washout . It is important to note
that the washout of CEUS is different from that of CT or MRI, as microbubble contrast agents of CEUS
are purely intravascular, whereas CT and MR contrast agents are both intravascular as well as interstitial.
As a result, fibrous lesions such as intrahepatic cholangiocarcinoma (ICC) will appear to have delayed
enhancement by CT or MRI, while they will demonstrate washout on CEUS .
[10]

ADVANTAGES AND LIMITATIONS OF CEUS
CEUS has a number of advantages as an imaging modality. CEUS is a real-time imaging technique with
much higher temporal resolution than CT or MRI, and therefore it does not suffer from mistiming or
acquiring contrast phases that are too early or too late, as can be seen with CT or MRI . CEUS is highly
[10]
[7]
sensitive to the microbubble contrast agents . Therefore, CEUS is a good modality to confirm subtle
enhancement when it cannot be seen on CT/MRI [5,11] .

[12]
CEUS does not use ionizing radiation as does CT. CEUS is also less costly than CT or MRI . The
microbubble contrast agent for CEUS is safe in patients with severe renal impairment, unlike those used in
CT or MRI [13,14] . CEUS is approved for the pediatric population and is a very safe alternative that does not
[15]
require sedation or anesthesia .

CEUS has some potential limitations that the practitioner must recognize to tailor its use appropriately.
CEUS is usually not suitable for staging of hepatocellular carcinoma, as it is difficult to survey the entire
[16]
liver effectively with CEUS . In general, a few lesions can be characterized in one session of CEUS.
CEUS may require more planning and time on the part of the interpreting physician as lesions of interest
must be identified on the precontrast portion of the examination and correlated to the prior imaging [5,17] .
As a result, the interpreting physician is often involved in the acquisition of CEUS. As CEUS is acquired
by a sonographer and/or interpreting physician, it is typically more operator-dependent than CT or MRI.
The microbubble imaging agent Lumason® (Bracco Diagnostics, Monroe Township, NJ) became the
first agent approved by the US Food and Drug Administration (FDA) for contrast-enhanced abdominal
ultrasound imaging in adults and children in April 2016. While this agent has been used worldwide under
the name SonoVue® for well over a decade before this , given the relatively short history of FDA-approved
[13]
microbubble contrast agents, practitioner knowledge of CEUS acquisition techniques and interpretation is
generally less than conventional ultrasound, CT, and MRI.

HISTORY AND BACKGROUND OF CEUS LI-RADS
The American College of Radiology (ACR) Liver Reporting and Data System (LI-RADS®) was created as a
standardized reporting system to facilitate consistent and high-quality technique, interpretation, reporting,