European Radiology

, Volume 25, Issue 11, pp 3272–3281 | Cite as

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma

  • Tomoki Kobayashi
  • Hiroshi AikataEmail author
  • Masahiro Hatooka
  • Kei Morio
  • Reona Morio
  • Hiromi Kan
  • Hatsue Fujino
  • Takayuki Fukuhara
  • Keiichi Masaki
  • Atsushi Ohno
  • Noriaki Naeshiro
  • Takashi Nakahara
  • Yohji Honda
  • Eisuke Murakami
  • Tomokazu Kawaoka
  • Masataka Tsuge
  • Akira Hiramatsu
  • Michio Imamura
  • Yoshiiku Kawakami
  • Hideyuki Hyogo
  • Shoichi Takahashi
  • Kazuaki Chayama



Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs.


A total of 85 surgically resected nodules (≤30 mm) were analyzed.

HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared.


Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95 % confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682–0.890): CEUS, 0.784 (0.679–0.889), in combination, 0.876 (0.792–0.959). The sensitivity, specificity, and accuracy were 64.1 %, 95.7 %, and 81.2 % in EOB-MRI, 56.4 %, 97.8 %, and 78.8 % in CEUS, and 84.6 %, 95.7 %, and 90.6 % in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS.


Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs.

Key Points

Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN.

Macroscopic classification is useful to choose the treatment strategy for small HCCs.

Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal.

The diagnosis of macroscopic findings by individual modality has limitations.

Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.


Hepatocellular carcinoma Macroscopic findings Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging Contrast-enhanced ultrasound Combined diagnosis 







Area under the receiver operating characteristic curve


Contrast-enhanced computed tomography


Contrast-enhanced ultrasound


Confluent multinodular type




Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging


Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid


Hepatobiliary phase


Hepatitis B virus


Hepatocellular carcinoma


Hepatitis C virus


Indocyanine green retention rate at 15 minutes


Infiltrative type


Microvascular invasion


Patients negative for both HBs antigen and HCV antibody


Negative predictive value


Positive predictive value


Portal venous-phase


Receiver operating characteristic


Simple nodular


Simple nodular type with distinct margin


Simple nodular type with extranodular growth


Small nodular type with indistinct margin





The scientific guarantor of this publication is Kazuaki Chayama, M.D., Ph.D. 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: the MRI and CEUS contrast agents used in the present study were not provided/sponsored by the industry. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional review board approval and written informed consent were not required because this study is a retrospective analysis of EOB-MRI and CEUS, obtained for clinical purposes. Methodology: retrospective, diagnostic or prognostic study / observational, performed at one institution#.


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Copyright information

© European Society of Radiology 2015

Authors and Affiliations

  • Tomoki Kobayashi
    • 1
  • Hiroshi Aikata
    • 1
    Email author
  • Masahiro Hatooka
    • 1
  • Kei Morio
    • 1
  • Reona Morio
    • 1
  • Hiromi Kan
    • 1
  • Hatsue Fujino
    • 1
  • Takayuki Fukuhara
    • 1
  • Keiichi Masaki
    • 1
  • Atsushi Ohno
    • 1
  • Noriaki Naeshiro
    • 1
  • Takashi Nakahara
    • 1
  • Yohji Honda
    • 1
  • Eisuke Murakami
    • 1
  • Tomokazu Kawaoka
    • 1
  • Masataka Tsuge
    • 1
  • Akira Hiramatsu
    • 1
  • Michio Imamura
    • 1
  • Yoshiiku Kawakami
    • 1
  • Hideyuki Hyogo
    • 1
  • Shoichi Takahashi
    • 1
  • Kazuaki Chayama
    • 1
    • 2
  1. 1.Department of Gastroenterology and MetabolismHiroshima University HospitalHiroshimaJapan
  2. 2.Liver Research Project CenterHiroshima UniversityHiroshimaJapan

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