Skip to main content
SpringerLink
Log in

Hepatocellular carcinoma: clinical significance of signal heterogeneity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging

  • Gastrointestinal
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To clarify the relationship between the biological behaviour of hepatocellular carcinomas (HCCs) and their signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging with a special focus on the signal heterogeneity.

Methods

A total of 68 patients with 70 pathologically proven HCCs were enrolled. On the basis of the signal intensity in the hepatobiliary phase, the lesions were classified into three groups: group 1, homogeneous hypointensity (n = 44); group 2, heterogeneous hyperintensity (n = 20); and group 3, homogeneous hyperintensity (n = 6). The clinicopathological findings were compared among the three groups.

Results

The tumour size and the serum level of protein induced by vitamin K absence or antagonist-II (PIVKA-II) were significantly higher in group 2 compared to group 1 (p = 0.0155, p = 0.0215, respectively) and compared to group 3 (p = 0.0330, p = 0.0220, respectively). The organic anion transporting polypeptide 8 (OATP8) expression in group 2 and group 3 was significantly higher than in group 1 (p < 0.0001, p < 0.0001, respectively). Group 2 showed a significantly lower disease-free survival rate compared to group 1 (p = 0.0125), and group 2 was an independent prognostic factor for disease-free survival (p = 0.0308).

Conclusions

HCCs in the hepatobiliary phase that are heterogeneously hyperintense on gadoxetic acid-enhanced MR imaging have more malignant potential than other types of HCCs.

Key Points

• Heterogeneous uptake of gadoxetic acid suggests more malignant potential in HCC

• Uptake of gadoxetic acid does not suggest less malignancy in HCC

• Evaluation of signal heterogeneity on gadoxetic acid-enhanced MR imaging is useful

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

AFP:

alpha-fetoprotein

HBP:

hepatobiliary phase

HCC:

hepatocellular carcinoma

MR:

magnetic resonance

OATP:

organic anion transporting polypeptide

PIVKA-II:

protein induced by vitamin K absence or antagonist-II

ROI:

region of interest

References

  1. Okuda K (1997) Hepatocellular carcinoma: clinicopathological aspects. J Gastroenterol Hepatol 12:314–318

    Article  Google Scholar 

  2. Bosch FX, Ribes J, Díaz M, Cléries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:5–16

    Article  Google Scholar 

  3. Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917

    Article  PubMed  Google Scholar 

  4. Vogl TJ, Kümmel S, Hammerstingl R et al (1996) Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology 200:59–67

    Article  CAS  PubMed  Google Scholar 

  5. Huppertz A, Balzer T, Blakeborough A, European EOB Study Group et al (2004) Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings. Radiology 230:266–275

    Article  PubMed  Google Scholar 

  6. Ahn SS, Kim MJ, Lim JS, Hong HS, Chung YE, Choi JY (2010) Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology 255:459–466

    Article  PubMed  Google Scholar 

  7. Ichikawa T, Saito K, Yoshioka N et al (2010) Detection and characterization of focal liver lesions: a Japanese phase III, multicenter comparison between gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced computed tomography predominantly in patients with hepatocellular carcinoma and chronic liver disease. Invest Radiol 45:133–141

    Article  PubMed  Google Scholar 

  8. Golfieri R, Renzulli M, Lucidi V, Corcioni B, Trevisani F, Bolondi L (2011) Contribution of the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to dynamic MRI in the detection of hypovascular small (≤2 cm) HCC in cirrhosis. Eur Radiol 21:1233–1242

    Article  PubMed  Google Scholar 

  9. Asayama Y, Tajima T, Nishie A et al (2011) Uptake of Gd-EOB-DTPA by hepatocellular carcinoma: radiologic-pathologic correlation with special reference to bile production. Eur J Radiol 80:e243–e248

    Article  PubMed  Google Scholar 

  10. Kitao A, Zen Y, Matsui O et al (2010) Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR imaging–correlation with molecular transporters and histopathologic features. Radiology 256:817–826

    Article  PubMed  Google Scholar 

  11. Narita M, Hatano E, Arizono S et al (2009) Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol 44:793–798

    Article  CAS  PubMed  Google Scholar 

  12. Kitao A, Matsui O, Yoneda N et al (2012) Hypervascular hepatocellular carcinoma: correlation between biologic features and signal intensity on gadoxetic acid-enhanced MR images. Radiology 265:780–789

    Article  PubMed  Google Scholar 

  13. Choi JW, Lee JM, Kim SJ et al (2013) Hepatocellular carcinoma: imaging patterns on gadoxetic acid-enhanced MR images and their value as an imaging biomarker. Radiology 267:776–786

    Article  PubMed  Google Scholar 

  14. Choi JY, Kim MJ, Park YN et al (2011) Gadoxetate disodium-enhanced hepatobiliary phase MRI of hepatocellular carcinoma: correlation with histological characteristics. AJR Am J Roentgenol 197:399–405

    Article  PubMed  Google Scholar 

  15. Kim JY, Kim MJ, Kim KA, Jeong HT, Park YN (2012) Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI: correlation with clinical and pathological features. Eur J Radiol 81:3877–3882

    Article  PubMed  Google Scholar 

  16. Kitao A, Matsui O, Yoneda N et al (2011) The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol 21:2056–2066

    Article  PubMed  Google Scholar 

  17. Nishie A, Asayama Y, Ishigami K et al (2014) Clinicopathological significance of the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid in hepatocellular carcinoma. J Gastroenterol Hepatol 29:561–567

    Article  CAS  PubMed  Google Scholar 

  18. Takayama Y, Nishie A, Nakayama T et al (2012) Hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with chronic liver disease: prediction of malignant transformation. Eur J Radiol 81:3072–3078

    Article  PubMed  Google Scholar 

  19. Shinozaki K, Yoshimitsu K, Irie H et al (2004) Comparison of test-injection method and fixed-time method for depiction of hepatocellular carcinoma using dynamic steady-state free precession magnetic resonance imaging. J Comput Assist Tomogr 28:628–634

    Article  PubMed  Google Scholar 

  20. Theise ND, Ishak KG, Kojiro M et al (2010) Hepatocelluilar carinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) World Health Organization classification of the digestive system. IARC, Lyon, pp 205–216

    Google Scholar 

  21. International Consensus Group for Hepatocellular Neoplasia (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the International Consensus Group for Hepatocellular Neoplasia. Hepatology 49:658–664

    Article  Google Scholar 

  22. Miyaaki H, Nakashima O, Kurogi M, Eguchi K, Kojiro M (2007) Lens culinaris agglutinin-reactive alpha-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma. J Gastroenterol 42:962–968

    Article  CAS  PubMed  Google Scholar 

  23. Nanashima A, Abo T, Tobinaga S et al (2010) Relationship between period of survival and clinicopathological characteristics in patients with hepatocellular carcinoma who underwent hepatectomy. Hepatogastroenterology 57:540–546

    PubMed  Google Scholar 

  24. Jung D, Kullak-Ublick GA (2003) Hepatocyte nuclear factor 1 alpha: a key mediator of the effect of bile acids on gene expression. Hepatology 37:622–631

    Article  CAS  PubMed  Google Scholar 

  25. Vavricka SR, Jung D, Fried M, Grützner U, Meier PJ, Kullak-Ublick GA (2004) The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3beta in hepatocellular carcinoma. J Hepatol 40:212–218

    Article  CAS  PubMed  Google Scholar 

  26. Jung D, Podvinec M, Meyer UA et al (2002) Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology 122:1954–1966

    Article  CAS  PubMed  Google Scholar 

  27. Verloh N, Haimerl M, Zeman F et al (2014) Assessing liver function by liver enhancement during the hepatobiliary phase with Gd-EOB-DTPA-enhanced MRI at 3 Tesla. Eur Radiol 24:1013–1019

    Article  CAS  PubMed  Google Scholar 

  28. Yoneyama T, Fukukura Y, Kamimura K et al (2014) Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function. Eur Radiol 24:857–865

    Article  PubMed  Google Scholar 

  29. Nishie A, Ushijima Y, Tajima T et al (2012) Quantitative analysis of liver function using superparamagnetic iron oxide- and Gd-EOB-DTPA-enhanced MRI: comparison with technetium-99m galactosyl serum albumin scintigraphy. Eur J Radiol 81:1100–1104

    Article  PubMed  Google Scholar 

  30. Verloh N, Haimerl M, Rennert J et al (2013) Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla. Eur J Radiol 82:1710–1715

    Article  CAS  PubMed  Google Scholar 

  31. Nishie A, Asayama Y, Ishigami K et al (2012) MR prediction of liver fibrosis using a liver-specific contrast agent: superparamagnetic iron oxide versus Gd-EOB-DTPA. J Magn Reson Imaging 36:664–671

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Yoshihiko Maehara, Department of Surgery and Science, Kyushu University, for providing the clinical information for this manuscript. We also thank Dr. Yoshinao Oda, Department of Anatomic Pathology, Kyushu University, for providing the pathological information for this manuscript. This work was supported by a Grant-in-Aid for Scientific Research (C) (24591814) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. The scientific guarantor of this publication is Professor Hiroshi Honda. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. No complex statistical methods were necessary for this paper. Institutional review board approval was obtained. Written informed consent was waived by the institutional review board. Approval from the institutional animal care committee was not required because the study is not on animals. Some study subjects or cohorts have not been previously reported. Methodology: retrospective, diagnostic or prognostic study/observational, performed at one institution.

Author information

Authors and Affiliations

  1. Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Yasuhiro Ushijima, Koichiro Moirta & Hiroshi Honda

  2. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yuichiro Kubo & Shinichi Aishima

  3. Department of Molecular Imaging & Diagnosis, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yukihisa Takayama

  4. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Ken Shirabe

Authors
  1. Nobuhiro Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihiro Nishie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuichiro Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshiki Asayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuhiro Ushijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yukihisa Takayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koichiro Moirta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ken Shirabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shinichi Aishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hiroshi Honda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akihiro Nishie.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujita, N., Nishie, A., Kubo, Y. et al. Hepatocellular carcinoma: clinical significance of signal heterogeneity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging. Eur Radiol 25, 211–220 (2015). https://doi.org/10.1007/s00330-014-3349-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-014-3349-9

Keywords

Search

Navigation