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Loria et al. Hepatoma Res 2018;4:59 I http://dx.doi.org/10.20517/2394-5079.2018.75 Page 3 of 12

Therefore, thanks to the use of specific software, the linear signals are deleted from the tissues and the images
are formed only thanks to the non-linear signals coming from the microbubbles. The use of these more power-
ful acoustic waves, however, causes the breaking of part of the micro-bubbles. To minimize this phenomenon,
we have chosen to work at low mechanical indices. This study technique allows to cancel the signal coming
from the tissues and to have pure images coming exclusively from the microbubbles [25-29] .

Although the correct setting of the US scanner and the scanning techniques are important for avoiding ar-
[30]
tifacts , MI and inadequate gain are the two main causes of error in the visualization of the signals coming
from the tissues.

PROTOCOL OF SUIRVELLANCE OF HCC
In our institute, we use a HCC surveillance protocol in patients with cirrhosis, based on the six-monthly
dosing of alpha-fetus protein serum levels and on the execution of a six-monthly hepatic US examination in
patients in the Child Pugh class A and B. In patients in the Child Pugh class C, the US can be also performed
every three months.

DIAGNOSIS OF HCC
Baseline us
HCC typically appear as hypoechoic compared to the surrounding hepatic parenchyma. It can also appear as
isoechoic, hyperechoic or with mixed echogenicity, with a typical characteristic of nodule in nodule. About
[22]
50% of HCC can appear as a nodule with peripheral hypoechoic halo . Both the conventional Color-Doppler
and the Power-Doppler US have a limited ability to describe intralesional vascularization, because they are in-
sensitive to slow and deep blood flows [31,32] . Generally the Doppler HCC pattern is characterized by an arterial
vascularization with a basket pattern due to thin blood vessels that surrounds the nodule [11,22,33] .

CEUS procedures
Before starting the CEUS evaluation, it is mandatory to perform an evaluation in B-mode; in particular it is
necessary to analyze the site, the size, dimensions, echogenicity of the lesion and its relationship with the other
structures. An evaluation of the vascular pattern of the lesion in Color-Doppler is useful to define the eventual
presence of central or peripheral vascular vessels. Once the target lesion has been identified, the specific mode
of imaging must be selected for the contrast with a low MI. SonoVue is injected into the antecubital vein with
a bolus, followed by a bolus flash of a solution of 10 mL of sodium chloride. To avoid destroying the micro-
[22]
bubbles during the injection, the calibre of the needle must not be less than 20 gauge . The target lesion and
the surrounding parenchyma are observed for 5-10 min in real time and registered in a video clip. The arte-
rial phase is defined as 0-30 s from the injection, the portal phase 31-75 and the late phase from 75-180 s up to
[31]
10 min .

CEUS
The most common appearance in cirrhotic liver of HCC is an hyper-arterial enhancement compared to the
surrounding hepatic tissue [Figure 1], which is found in 93.5%-97% of cases [31,33-38] and generally appear ho-
mogeneous and intense. In the nodules that have diameters larger than 2 cm, hyper-enhancement can also be
non-homogenous because of the area of necrosis within the lesion [Figure 2]. A slight peripheral enhancement
is found in 5 (34.6%) of cases of HCC; it can represent the tumor capsule [Figure 3] or blood vessel around the
lesion [31,33-39] . In the majority of cases HCC shows a precocious enhancement compared to the surrounding tis-
sue, in particular, the rates of detection of the hyper-enhancement in lesions < 1.0 cm, 1.0-2.0 cm and 2.0-3.0
cm are respectively 67%, 83%-88% and 92%-100% [3,31,36-40] [Table 1]. Furthermore other lesions like dysplastic
[41]
nodules and hyper-vascularized hemangioma can have the same contrast enhancement pattern .