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Tamai. Hepatoma Res 2018;4:75 I http://dx.doi.org/10.20517/2394-5079.2018.98 Page 7 of 11

which could interpret the correlation between imaging features and probability of MVI is that HCC has a
strong tendency of invasive growth along with de-differentiation from well to poorly differentiated HCC.
Therefore, the accurate diagnosis of histologic differentiation and macroscopic type is essential for accurate
prediction of MVI.

US including CEUS is the most non-invasive among imaging modalities. Although most of the previous
reports cited in “US” section were about the diagnosis of HCC with poor differentiation or non-SN type,
which suggested that direct connection between US and diagnosis of MVI was a few, useful US parameters
for predicting poorly differentiated HCC or MVI are irregular intra-tumoral artery, fast washout of tumor
enhancement, and irregular tumor margin. MFI should be used to assess the intra-tumoral angioarchitec-
ture, with the deadwood pattern being a highly specific finding for predicting MVI. Although the optimal
cut off time is yet unknown, shorter washout time of tumor enhancement is also a specific finding. Based
on previous reports on assessing tumor shape by imaging, post-vascular phase (Kupffer phase) of CEUS is
considered more accurate than B-mode US or contrast CT, and the diagnostic ability of CEUS for predict-
ing HCC macroscopic type would be equal to that of the hepatobiliary phase of EOB-MRI. However, US has
several disadvantages, such as poor visualization due to dead space, artifacts, and deep lesion, and difficulty
of whole scan in larger tumors. Therefore, when the whole tumor cannot be scanned by US, another imaging
assessment using EOB-MRI or contrast CT is necessary.

Factors to consider in predicting poorly differentiated HCC or MVI on contrast CT are heterogenous en-
hancement including hypovascular components, fast washout of tumor enhancement, complete or partial
absence of peritumoral capsule (halo), the presence of intra-tumoral vessels and aneurysms on venous phase,
and irregular tumor margin. Although complete or partial absence of peritumoral capsule, the presence of
intra-tumoral vessels and aneurysms, and irregular tumor margin can be easily evaluated in large HCC,
these parameters are difficult to assess in small HCCs. The heterogenous enhancement and fast tumor en-
hancement washout are useful findings in predicting poor histologic differentiation of small HCCs.

Tumor tissue characterization such as water, fat, and metal content, or diffusion of water molecules can be
easily obtained by plain MRI. As non-hypointense HCC on T1-weighted image reflects well differentiation
of HCC, the MVI risk would be low. Since intra-tumoral fat is also often seen in well differentiated HCCs,
HCCs containing fat components would be at low risk of MVI. Accordingly, T1-weighted image including
chemical shift is important in predicting low risk of MVI. Previous reports also demonstrated that low ADC
value reflects poor differentiation. However, there is no adequate cut-off value to distinguish poorly and non-
poorly differentiated HCC on meta-analysis. This may be because the absolute ADC value depends on the
[64]
MRI equipment coil systems, imagers, vendors, and field strengths . Since the contrast between tumor and
adjacent liver tissue, measured by CNR, and the RCR on DWI, are superior in predicting poor differentiation
compared to the ADC values, the assessment of tumor contrast to adjacent liver tissue on DWI or ADC map
should be more appropriate and universal in clinical practice than quantification of ADC values. As such,
care should be taken when evaluating a very high intense HCC on DWI or low intense HCC on ADC map.
When directly predicting MVI using EOB-MRI, the important parameters include irregular margin, arte-
rial peritumoral enhancement (relative hypovascularity), and peritumoral hypointensity on hepatobiliary
phase. Although the specificities of these findings for predicting MVI were very high, the sensitivities were
low. Therefore, attention should be paid for the false negativity of these findings. To improve the sensitivity
for predicting MVI, the combined evaluation with plain MRI including DWI and EOB-MRI may be useful,
because the evaluation of diffusion parameters is highly sensitive for predicting poor differentiation or MVI.
Among common imaging modalities, the most information for predicting MVI can be obtained from MRI,
Furthermore, there are some reports that the combination of EOB-MRI with CECT or CEUS improved the
accuracy in predicting non-SN type. As mentioned above, combination of MRI with other imaging modali-
ties may provide a more accurate assessment of malignant potential of HCC.