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El-Gazzar et al. Gadobenate dimeglumine dynamic MRI for early HCC detection

Most guidelines on the management of HCC surveillance ultrasound suggest that the newly proposed
recommend four-phase multi-detector CT and/ criteria for nodules fitting the American Association for the
or contrast-enhanced MRI as standard imaging Study of Liver Diseases practice guidelines or having
modalities for diagnosis of HCC, based on the typical 3 or more findings in gadobenate dimeglumine MRI
dynamic pattern of arterial enhancement and washout can be a useful alternative providing a significant
on the portal/delayed phases. [16] Some HCC lesions, improvement in sensitivity while maintaining high
especially those less than 2-3 cm in diameter, lack specificity for diagnosis of HCC. [21] In two other studies
typical hemodynamic criteria, making diagnosis of using gadobenate dimeglumine-enhanced MR, small
HCC a big challenge. Atypical enhancement patterns nodules that show enhancement on arterial phase and
were seen in around 30% of HCC patients in many occult on the portal and equilibrium phase images as
studies and hypovascular HCC lesions have led to well as on the T1 and T2-weighted images are more
around 35% of false negative results in tumors 1-2 cm likely to be HCC in patients with hepatitis B-induced
in diameter. [9] cirrhosis [22,23] which are in accordance with our results.

HCC is a highly vascular tumor characterized by Triphasic CT and gadolinium MRI are not ideal tools
neoangiogenesis, which contributes to the high rate for diagnosis of atypical HCC as they depend only
of metastasis and dismal prognosis. On microscopic on extracellular contrast. However, gadobenate
examination, HCC displays marked vascular dimeglumine is a dual extra- and intracellular contrast
abnormalities, and aberrant microvasculature which can assess not only vascular changes in
in the form of arteriogenesis and capillarization. atypical nodules but also enzymatic activity within
Arteriogenesis is defined as the growth of functional hepatocytes that can develop earlier than vascular
collateral arteries covered with smooth muscle cells changes.
from pre-existing arteries. HCC is mainly supplied by
hepatic arteries, while in normal liver parenchyma, The cost of gadobenate dimeglumine contrast is about
regenerative and dysplastic nodules are mainly 30 euros per case, while that of gadolinium (routinely
supplied by the portal vein. [4,17] used in dynamic MRI) is around 15 euros per case,
and the average cost of triphasic CT contrast,
MR imaging with hepatobiliary contrasts such as ultravist, is about 10 euros. Unlike triaphasic CT and
multihance (gadobenate dimeglumine) and primovist gadolinium-enhanced MRI which are unreliable tools
(gadolinium ethoxybenzyl diethylenetriamine for diagnosis of small atypical HCC (almost one third
pentaacetic acid, Gd-EOB-DTPA, or gadoxetic acid) of HCC cases), gadobenate dimeglumine-enhanced
was found to be highly sensitive in HCC diagnosis. MRI was found to have higher sensitivity (87.5%)
[18] In one study, all HCC lesions were identified with and specificity (82.8%) with an accurate diagnosis of
gadoxetic acid, whereas three of 56 HCCs were not more than 80% of atypical HCC in our study. Atypical
identified on dual-contrast MRI. In 59 patients imaged HCC are usually well differentiated lesions with a
with gadoxetic acid, 10.7% of detected HCCs were better response to treatment, therefore, gadobenate
detected only on hepatocellular phase images. [19] dimeglumine MRI is likely to be more cost effective
compared to other imaging modalities which warrants
In one study evaluating 86 nodules, the diagnostic further studies.
ability of gadoxetic acid was significantly higher
than that of multi-detector triphasic CT for tumors In conclusion, gadobenate dimeglumen is a promising
less than 2 cm in diameter. There was no significant hepatobiliary contrast, which can potentially improve
difference in the detection of hypervascular HCCs the non-invasive diagnosis of early atypical small
between hepatobiliary phase images of gadoxetic HCC. The encouraging results from our pilot study
acid-enhanced MRI (43/45: 96%) and dynamic CT warrants further confirmation by larger multi-
(40/45: 89%), whereas the detection sensitivity of center studies, as well as cost effective analysis of
hypovascular tumors by gadoxetic acid-enhanced multihance MRI.
MRI was significantly higher than that by dynamic CT
(39/41: 95% vs. 25/41: 61%, P = 0.001). Gadoxetic Authors’ contributions
acid enhancement ratios were decreased in parallel Study design: M.F. El-Gazzar, M.A.S. Kohla
with the degree of differentiation in dysplastic nodules Data analysis and manuscript preparation: M.F. El-
and HCCs. [20] Gazzar, M.A.S. Kohla, M.M. El-Sakhawy, M.M.
Husseiny, R.R.H. Yousef, S.H. El-Shorbagy
In another study, imaging findings of a prospective and Critical review of manuscript: M.F. El-Gazzar, M.A.S.
consecutive sample of 1-2 cm nodules detected at Kohla, M.M. El-Sakhawy
Hepatoma Research ¦ Volume 3 ¦ June 26, 2017 127