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Page 8 of 11 Minami et al. Hepatoma Res 2020;6:46 I http://dx.doi.org/10.20517/2394-5079.2020.32

Inflammatory pseudotumor (IPT) of the liver is a rare benign nodule and can display various enhancement
patterns on CEUS due to pathological change during the course of disease progression. When the nodules
are abundant in inflammatory cells and granulation tissues, they often appear as an area of diffuse
homogeneous hyperenhancement. As more necrosis and fibrosis develop within the nodules, IPT may show
[31]
heterogeneous or peripheral rim-like enhancement .

Meta-analytic studies reported the ability of CEUS to accurately differentiate between benign and malignant
FLLs at a sensitivity of 93% and specificity of 90%, and also demonstrated its similar diagnostic performance
to dynamic CECT and MRI [32,33] . Furthermore, the diagnostic accuracy of CEUS for lesions that were
inconclusive on CECT increased from 42%-44% to 89%-92%, and a higher diagnostic confidence level was
confirmed [34,35] .

CEUS guidance of biopsy/ablation therapy
The correct placement of the needle into the target tumor for percutaneous biopsy/ablation therapy increases
its technical success rate. B-mode US does not accurately detect HCC in the presence of local tumor
progression after treatment or true HCC surrounded by large regenerative nodules in cirrhotic livers. The
rates of HCC with poor conspicuity on planning B-mode US for ablation therapy ranged from 5.2 to 38.8 in
previous reports [36-39] . CEUS with Sonazoid facilitates needle placement in HCC that is poorly depicted on
B-mode US because the defect lesion functions as a target for insertion.

If imaging studies fail to reveal an accurate diagnosis of FLLs, biopsy may be required. The limitations of
percutaneous liver biopsy guided with B-mode US incldue its high rates of false-negative results. However,
correct targeting and guiding steps benefit from the use of CEUS with Sonazoid [40,41] . The diagnosis of benign
FLLs may be improved with the utility of CEUS during liver biopsy without surgical intervention.

A previous study reported that the technical success rate of a single radiofrequency ablation (RFA) session
[42]
was significantly higher with CEUS than with B-mode US (94.7% vs. 65.0%, P = 0.043) . Furthermore, the
number of RFA sessions conducted in a historical cohort was smaller with Sonazoid CEUS guidance than
with B-mode US guidance [43,44] . Another study showed that the sustained local control rate was markedly
[45]
higher for CEUS-guided RFA than for B-mode US-guided RFA (85.3% vs. 66.4% at 2 years) . In addition,
inconspicuity on B-mode US and CEUS represents one of the most difficult conditions for percutaneous
RFA. The combination of fusion imaging and CEUS is an effective guidance in ablation therapy for poorly
[46]
defined HCCs on B-mode US and CEUS/fusion imaging .

CEUS may also help to identify complications immediately after ablation therapy such as active bleeding or
[47]
segmental infarction of the liver . Active hemorrhage should be visualized on CEUS as extravasation of
microbubbles and infarcted areas can show no enhancement.

Assessment of HCC treatment responses
The complete lack of enhancement in all phases on CEUS was previously demonstrated in patients with
complete treatment responses following arterial chemoembolization for HCC; while intratumoral residual
or nodular peripheral enhancement was detected in patients with residual or recurrent HCC. CEUS allows
for the reliable prediction of the risk of recurrence in patients with HCC within a short period of time
(approximately 1 week) after TACE [48,49] .

Important issues to consider in treatment response assessments of RFA are evaluations of the absence of the
vascular enhancement of HCC and the ablative margin. Residual HCC shows a focal defect in the Kupffer
phase, representing hypervascular enhancement, with reinjections of Sonazoid. However, consistent and
accurate assessments of the ablative margin by CEUS is not always be possible because the tumor boundary
[50]
may not be clearly identified on US after RFA .