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Page 4 of 11 Wilson et al. Hepatoma Res 2020;6:57 I http://dx.doi.org/10.20517/2394-5079.2020.48

(3) Direction of vascular filling (centrifugal or centripetal)

Portal venous phase (PVP) (45 s - 2 min) and Late phase (LP) (from 2 min to 5 or 6 min) observations
include:
Washout (yes or no)
(1) Timing (rapid, < 1 min; or late, > 1 min)
(2) Intensity (weak, with some bubbles remaining in a nodule which is less enhanced than the liver; or
marked, whereby the nodule appears black or punched out by 2 min)

Importance of the clinical scenario
Additionally, for all contrast-enhanced liver imaging, interpretations must be made with knowledge of
demographic and clinical information. Age and sex are helpful as are relevant health events with the
greatest importance given to a history of cancer and also risk factors for development of HCC. The clinical
indication for a scan, whether it be for surveillance for metastatic tumor or HCC or related to symptoms
may also be directive. The algorithmic interpretation of CEUS should always be guided by what is a
reasonable answer for the patient under study.

FUNDAMENTALS FOR INTERPRETATION OF CEUS OF FOCAL LIVER DISEASE
Principle 1. The intensity in a CEUS image reflects the number of microbubbles in the field of
view
As these are exclusively in blood vessels, echo-enhancement is therefore indicative of the volume of blood
and its change with time indicative of the rate of perfusion in the region of interest. All interpretations
compare nodule enhancement levels with the adjacent and enhancing liver parenchyma.

Principle 2. Determination of malignancy: importance of washout
Most malignant masses are identified by washout of the mass in the portal venous or late phase [14,15] .
Washout refers to the decline in the enhancement of a mass relative to that of the adjacent liver
parenchyma, following initial AP enhancement. Therefore, if washout is present, malignancy should be
considered likely [Figures 1 and 2]. Conversely, if washout is not present and if the mass shows sustained
[16]
enhancement, there is a high likelihood that it is benign . These rules are guidelines and there are, of
course, exceptions. These exceptions to this important rule are very important, since occasionally, benign
tumors, focal nodular hyperplasia (FNH), hemangioma, and most often adenoma, may show washout, and
some malignant tumors, especially precursor nodules for HCC and well-differentiated HCC, may show no
washout. Nonetheless, the fundamental rule is invaluable.

Principle 3. Differentiation of malignancy: importance of timing and intensity of washout
Although CT and MR scan also determine the presence of washout, CEUS additionally evaluates
the intensity and timing of washout, further differentiating hepatocellular from nonhepatocellular
[17]
malignancy . HCC tends to show late (later than 1 min) and weak washout (so that some bubbles
remain in the washout zone) [Figure 1, Video 1], whereas all nonhepatocellular malignancies, including
intrahepatic cholangiocarcinoma (ICC), lymphoma and metastasis are characterized by rapid (earlier than
1 min) and marked washout, so that all bubbles are absent from the nodule, making it appear as a black,
punched out hole [Figure 2, Video 2] [18,19] . This rapid washout may even occur so early as to be within the
traditionally defined AP, prior to 30 s.

Principle 4. Detection of malignancy
A natural consequence of the two previous principles is that the portal venous phase is the optimal
time to detect metastases, when their conspicuity will be increased relative to the enhanced background
parenchyma . This increased conspicuity makes sweeping of the entire liver at this time the ideal
[20]