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Multicenter Study
. 2024 Aug;49(8):2639-2649.
doi: 10.1007/s00261-024-04305-9. Epub 2024 Jun 11.

Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC

Yuko Kono  1 , F Piscaglia  2   3 , S R Wilson  4 , A Medellin  4 , S K Rodgers  5   6 , V Planz  7 , A Kamaya  8 , D T Fetzer  9 , A Berzigotti  10 , P S Sidhu  11   12 , C E Wessner  5 , K Bradigan  5 , Cristina M Kuon Yeng Escalante  5 , T Siu Xiao  5 , J R Eisenbrey  5 , F Forsberg  5 , A Lyshchik  5 ; CEUS LI-RADS Trial Group
Collaborators, Affiliations
Multicenter Study

Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC

Yuko Kono et al. Abdom Radiol (NY). 2024 Aug.

Abstract

Background: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive.

Methods: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3).

Results: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct.

Conclusion: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging.

Clinicaltrials: gov number, NCT03318380.

Keywords: CEUS; Diagnosis; Hepatocellular carcinoma; LI-RADS.

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Conflict of interest statement

YK received Research support—Bracco Diagnostics and Canon Medical Systems Inc. FP has served on advisory boards for Astrazeneca, EISAI, Exact Sciences, MSD, Roche, and Siemens Healthineers; Speeches at symposia for Astrazeneca, Bayer, Bracco, ESAOTE, EISAI, GE, IPSEN, MSD, Roche, and Samsung; and is a Consultant for Bracco and Nerviano. SRW is a member of Advisory Board of Lantheus Medical Imaging; Speakers Bureau—Philips. Equipment Support: Philips, Siemens, and Samsung. AM: None. SKR received book royalties from Elsevier. VP: None. AK: None. DF has served on the advisor board for GE HealthCare and Philips Healthcare, has lectured for Siemens Healthineers, and has active research agreements with GE HealthCare, Philips Healthcare, and Siemens Healthineers. AB is a consultant for Boehringer-Ingelheim and has received speakers’ fee from GE Healthcare and Hologic. PSS received lecture fees from Bracco SpA Milan; GE Healthcare, Samsung, and Philips—lecture fees; Itreas Inc. consulting and lecture fees; Editor-in-Chief Ultrasound in Medicine and Biology and Associate Editor Radiology. CEW is a clinical consultant for Bracco Diagnostics, a member of Speaking Bureau for Canon Medical Systems USA, and consultant for SonoSim. KB: None. KYECM: None. SXT: None. JRE received Grant, equipment and drug support from GE Healthcare; Drug support from Bracco; Equipment support from Siemens; Drug support and member of scientific advisory board of Lantheus Medical Imaging. Royalties from Elsevier; Consultant for SonoSim. FF received Equipment loan and/or grant support from The Butterfly Network, Canon Medical Systems USA, GE HealthCare, and Siemens Healthineers; Contrast agent from Bracco Diagnostics, GE HealthCare and Lantheus Medical Imaging; Advisory Board/Consultant/Lecturer for Exact Therapeutics AS, GE HealthCare, Lantheus Medical Imaging, Longeviti, and SonoThera. AL is GE Healthcare—Advisory Board Member; has a Consulting agreement and Research support; Bracco Diagnostic—Advisory Board Member, Consulting agreement, and Research support, and received royalties from Elsevier. AGS has served as a consultant or on advisory boards for Genentech, AztraZeneca, Eisai, Bayer, Exelixis, Merck, Elevar, Boston Scientific, Sirtex, HistoSonics, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, Abbott, Ascelia, Freenome, and GRAIL.

Figures

Fig. 1
Fig. 1
Hemangioma with MRI LR-3 categorization. A Pre-contrast MR image demonstrating small hypo-intense observation in the right hepatic dome (arrow). Arterial phase image which is degraded by motion artifact (B) demonstrated questionable arterial hypo enhancement in the parts of the observation, with hypoenhancement on late phase image (C), resulting in LR-3 categorization. D Grayscale ultrasound image showing hyperechoic liver nodule measuring 1.6 cm marked by calipers with peripheral interrupted APHE (E). CEUS representative image at 1 min (F) persistent hyperenhancement—typical appearance of hemangioma (LR-1)
Fig. 2
Fig. 2
HCC with CT LR-3 categorization. A Arterial phase CT image demonstrating small nodule with no APHE (arrows). Later phase images (B, C) demonstrated barely perceptible washout. D Grayscale ultrasound image demonstrating hypoechoic nodule in a fatty liver measuring 2.5 cm with clear APHE (E). CEUS representative image at 1 min (F) showing no early washout. G CEUS representative image at 3 min demonstrating late and mild washout—typical appearance of HCC (LR-5), confirmed on biopsy
Fig. 3
Fig. 3
HCC with MRI LR-3 categorization. A Pre-contrast MR image demonstrating small iso-intense observation (arrow). Arterial phase image (B) demonstrated APHE without washout on late phase image (C). D Grayscale ultrasound image showing a small exophytic nodule measuring 1.5 cm with clear APHE (E). CEUS representative image at 1 min (F) showing no early washout. G CEUS representative image at 3 min demonstrating late and mild washout—typical appearance of HCC (LR-5), confirmed on explant histology
Fig. 4
Fig. 4
CEUS LI-RADS Results in Patients with LR-3 on CT/MRI
Fig. 5
Fig. 5
CEUS LI-RADS results in patients with LR-NC on CT/MRI
Fig. 6
Fig. 6
HCC with MRI LR-NC categorization. A Pre-contrast MR image demonstrating small hypo-intense observation (arrow). Arterial phase image (B) demonstrated no enhancement, likely due to mistiming of arterial phase, with persistent hypointensity on late phase image (C). D Grayscale ultrasound image showing small nodule measuring 1.1 cm with clear APHE (E). CEUS representative image at 1 min (F) showing no early washout. G CEUS representative image at 3 min demonstrating late and mild washout—typical appearance of HCC (LR-5), confirmed on follow-up MRI
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