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Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma

  • Ultrasound
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Abstract

Objectives

To evaluate the diagnostic accuracy of perfluorobutane contrast-enhanced ultrasonography (CEUS) for hepatocellular carcinoma (HCC) and to explore how accuracy can be improved compared to conventional diagnostic criteria in at-risk patients.

Methods

A total of 123 hepatic nodules (≥ 1 cm) from 123 at-risk patients who underwent perfluorobutane CEUS between 2013 and 2020 at three institutions were retrospectively analyzed. Ninety-three percent of subjects had pathological results, except benign lesions stable in follow-up images. We evaluated presence of arterial phase hyperenhancement (APHE), washout time and degree, and Kupffer phase (KP) defects. KP defects are defined as hypoenhancing lesions relative to the liver in KP. HCC was diagnosed in two ways: (1) Liver Imaging Reporting and Data System (LI-RADS) criteria defined as APHE and late (≥ 60 s)/mild washout, and (2) APHE and Kupffer (AK) criteria defined as APHE and KP defect. We explored grayscale features that cause misdiagnosis of HCC and reflected in the adjustment. Diagnostic performance was compared using McNemar’s test.

Results

There were 77 HCCs, 15 non-HCC malignancies, and 31 benign lesions. An ill-defined margin without hypoechoic halo on grayscale applied as a finding that did not suggest HCC. Regarding diagnosis of HCC, sensitivity of AK criteria (83.1%; 95% confidence interval [CI]: 72.9–90.7%) was higher than that of LI-RADS criteria (75.3%; 95% CI: 64.2–84.4%; p = 0.041). Specificity was 91.3% (95% CI: 79.2–97.6%) in both groups.

Conclusion

On perfluorobutane CEUS, diagnostic criteria for HCC using KP defect with adjustment by grayscale findings had higher diagnostic performance than conventional criteria without losing specificity.

Key Points

• Applying Kupffer phase defect instead of late/mild washout and adjusting with grayscale findings can improve the diagnostic performance of perfluorobutane-enhanced US for HCC.

• Adjustment with ill-defined margins without a hypoechoic halo for features unlikely to be HCC decreases false positives for HCC diagnosis using the perfluorobutane-enhanced US.

• After adjustment with grayscale findings, the sensitivity and accuracy of the APHE and Kupffer criteria were higher than those of the LI-RADS criteria; specificity was 91.3% for both.

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Abbreviations

AP:

Arterial phase

APHE:

Arterial phase hyperenhancement

CEUS:

Contrast-enhanced ultrasonography

CI:

Confidence interval

combined HCC-CC:

Combined hepatocellular-cholangiocarcinoma

DN:

Dysplastic nodule

HCC:

Hepatocellular carcinoma

IHCC:

Intrahepatic cholangiocarcinomas

KP:

Kupffer phase

LI-RADS:

Liver Imaging Reporting and Data System

LP:

Late phase

PVP:

Portal venous phase

SD:

Standard deviation

SPIO:

Superparamagnetic iron oxide

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Funding

The authors state that this work has not received any funding.

Author information

Author notes

  1. Woo Kyoung Jeong and Jeong Min Lee have contributed equally to this work as co-corresponding authors.

Authors and Affiliations

  1. Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Jeong Ah Hwang & Woo Kyoung Jeong

  2. Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul, 03080, Republic of Korea

    Hyo-Jin Kang & Jeong Min Lee

  3. Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea

    Eun Sun Lee & Hyun Jeong Park

Authors
  1. Jeong Ah Hwang
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Corresponding authors

Correspondence to Woo Kyoung Jeong or Jeong Min Lee.

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Guarantor

The scientific guarantors of this publication are Woo Kyoung Jeong and Jeong Min Lee.

Conflict of interest

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.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

A total of 62 study subjects have been previously reported. However, the purpose of the previous research was different from this study.

Thirty-six subjects were reported in a previous paper (Kang et al Contrast-enhanced US with sulfur hexafluoride and perfluorobutane for the diagnosis of hepatocellular carcinoma in individuals with high risk. Radiology 2020; 297:108–116). That study investigated contrast-enhanced US Liver Imaging Reporting and Data System (LI-RADS) v2017 HCC categorization by comparing perfluorobutane-enhanced US and sulfur hexafluoride–enhanced US in participants at high risk for HCC.

Twenty-six subjects were reported in a previous paper (Hwang et al Sonazoid-enhanced ultrasonography: comparison with CT/MRI Liver Imaging Reporting and Data System in patients with suspected hepatocellular carcinoma. Ultrasonography 2021;40:486-498). The aim of that study was to evaluate the association of CEUS features using Sonazoid for liver nodules with LI-RADS categories and to identify the usefulness of Kupffer phase images.

Methodology

• retrospective

• diagnostic or prognostic study

• multicenter study

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Hwang, J.A., Jeong, W.K., Kang, HJ. et al. Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma. Eur Radiol 32, 8507–8517 (2022). https://doi.org/10.1007/s00330-022-08900-6

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  • DOI: https://doi.org/10.1007/s00330-022-08900-6

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