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Wilson et al. Hepatoma Res 2020;6:57 I http://dx.doi.org/10.20517/2394-5079.2020.48 Page 3 of 11

Therefore, CEUS has superior temporal resolution compared to CT and MR scan, and it has, consequently,
the ability to show enhancement changes regardless of their timing or intensity.

Subtraction technique
CEUS uses a subtraction technique which effectively removes all of the background echogenicity such that
all imaging reflects microbubbles only. This microbubble only image provides exceptional sensitivity for
CEUS to show enhancement even in very small nodules and thin septations.

Purely intravascular contrast agent
CEUS is performed with purely intravascular contrast agents which will therefore always reflect the
presence of contrast agent in a tumor or the liver vasculature. Contrast agents for CT and MR, by
comparison, have a well-recognized interstitial phase whereby contrast may leak out of the vasculature into
the interstitium of a tumor. The resultant discordant imaging between CEUS and CT/MRI scan makes a
[11]
very positive contribution to the diagnosis of focal liver masses .

These unique features of CEUS imaging require that CEUS have its own algorithms.

CEUS IMAGING OF FOCAL LIVER MASSES
CEUS of a focal liver mass is based on the enhancement changes that occur over time in a nodule, which
is preidentified on greyscale US and maintained within the field of view for the entire scan. These changes
are described for the nodule relative to the adjacent liver parenchyma. Initial imaging of the pre-identified
nodule should be performed continuously, from contrast injection until peak arterial phase enhancement.
Subsequent imaging is intermittent (5-10 s every 30-60 s) to detect any washout and assess its degree, until
the end of useful enhancement, generally around 5 to 6 min.

This described technique, with only a brief initial acquisition of multiframe continuous images, audio video
interleave (avi), will minimize microbubble destruction. This improves the ability to detect late washout
and assess its degree.

Additional valuable scanning techniques include sweeping the entire liver in the portal/late phase
with suspended inspiration to identify additional areas of abnormal enhancement, especially washout.
Furthermore, injections can be repeated as needed including “on top” of a prior injection to assess
vascularity of an identified area of washout.

ALGORITHMS FOR DIAGNOSIS OF FOCAL LIVER MASSES ON CEUS
Experience with the use of microbubble contrast agents for liver mass characterization has led to the
recognition that multiple constant features lead to reliable differentiation of benign and malignant masses
and also to their specific accurate diagnoses. Resultant algorithms for diagnosis of focal liver tumors
on contrast imaging are all based on interpretation of enhancement features of an identified nodule
relative to the adjacent liver from the injection of the contrast agent to the end of useful enhancement,
[12]
generally around 5 or 6 min following injection . Time zero corresponds to the beginning of the saline
[13]
flush following the contrast injection . On CEUS, all timing is given in seconds and minutes rather
than in phases. Nonetheless, we include both specific timing and phases for completeness and modality
comparisons.

[13]
Arterial phase (AP) (from 10 to 20 - 30 to 45 s) observations include:
Enhancement (yes or no)
(1) Intensity (hyper, iso, hypo, or nonenhancing)
(2) Pattern of AP hyperenhancement (APHE) (Diffuse, nodule-in-nodule, rim, peripheral discontinuous
globular, or stellate)