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Clinical Trial
. 2025 Jan;314(1):e240916.
doi: 10.1148/radiol.240916.

Contrast-enhanced US of High-Risk Indeterminate Focal Liver Observations Categorized as LR-4 or LR-M at CT/MRI

Andrej Lyshchik  1 , Cristina Kuon Yeng Escalante  1 , Tania Siu Xiao  1 , Fabio Piscaglia  1 , Yuko Kono  1 , Alexandra Medellin-Kowalewski  1 , Shuchi K Rodgers  1 , Virginia Planz  1 , Aya Kamaya  1 , David T Fetzer  1 , Annalisa Berzigotti  1 , Iuliana-Pompilia Radu  1 , Paul S Sidhu  1 , Corinne E Wessner  1 , Kristen Bradigan  1 , John R Eisenbrey  1 , Flemming Forsberg  1 , Stephanie R Wilson  1 ; CEUS LI-RADS Trial Group  1 ; CEUS LI-RADS Trial Group Members
Collaborators, Affiliations
Clinical Trial

Contrast-enhanced US of High-Risk Indeterminate Focal Liver Observations Categorized as LR-4 or LR-M at CT/MRI

Andrej Lyshchik et al. Radiology. 2025 Jan.

Abstract

Background Indeterminate focal liver observations in patients at risk for hepatocellular carcinoma (HCC) may require invasive biopsy or follow-up, which could lead to delays in definitive categorization and to postponement of treatment. Purpose To examine clinical effect of contrast-enhanced US (CEUS) in participants with high-risk indeterminate liver observations categorized as Liver Imaging Reporting and Data System (LI-RADS) category LR-4 (probably HCC) or LI-RADS category LR-M (probably or definitely malignant but not HCC specific) at CT or MRI. Materials and Methods This was a secondary analysis of a prospective international multicenter validation study for CEUS LI-RADS (January 2018 to August 2021). CEUS was performed within 4 weeks of CT or MRI. Tissue histologic and CT or MRI follow-up data were used as reference standards. Clinical effect of CEUS for HCC was evaluated in observations 10 mm or larger categorized as CT/MRI LR-4 and LR-M. Results Included were 109 participants (mean age, 64.3 years ± 8.3 [SD]; 68.8% [75 of 109] male participants) with 113 observations (≥10 mm) categorized as CT/MRI LR-4 (53.1%; 60 of 113) or LR-M (46.9%; 53 of 113). CEUS resulted in management recommendation changes in 33.6% (95% CI: 25, 43; 38 of 113) of observations; among these, 95% (95% CI: 82, 99; 36 of 38) were correct. A total of 30.1% (34 of 113) of CT/MRI LR-4 and LR-M observations were categorized at CEUS as LI-RADS category LR-5 (definite HCC), making biopsy unnecessary; 94% (32 of 34) of these categorizations were correct. Of CT/MRI LR-4 observations, 7% (four of 60) were categorized as CEUS LR-M; subsequent biopsy confirmed non-HCC malignancy in all participants. Clinical impact of CEUS was more substantial for observations 20 mm or larger (n = 68); CEUS helped appropriately categorize both LR-5 and LR-M lesions as HCC and non-HCC malignancies, respectively, and resulted in management recommendation changes in 40% (27 of 68) of observations with 100% accuracy. Conclusion CEUS resolved some high-risk indeterminate liver observations (categorized as LR-4 and LR-M at CT or MRI), with particularly high clinical impact for observations measuring at least 20 mm. Clinical trial registration no. NCT03318380 © RSNA, 2025 Supplemental material is available for this article.

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Conflict of interest statement

Disclosures of conflicts of interest: A.L. Support for study from Bracco Diagnostics; grants from GE HealthCare; royalties from Elsevier; consulting fees from GE HealthCare; payment or honoraria for lectures from GE HealthCare, ICUS; support for meetings and/or travel from ICUS; participation on a DataSafety Monitoring Board or Advisory Board from GE HealthCare, Bracco Diagnostics, ICUS; Board of Directors leadership role for ICUS. C.K.Y.E. No relevant relationships. T.S.X. No relevant relationships. F.P. Consulting fees from Signant Health; honoraria from AstraZeneca, Bracco, ESAOTE, EISAI, GE HealthCare, Gilead, IPSEN, MSD, Roche, Samsung, Siemens Healthineers; participation on a DataSafety Monitoring Board or Advisory Board for AstraZeneca, BMS, Bracco, EISAI, MSD, Nervaiano, Roche, Siemens Healthineers, Signant Health; member of the governing board of the International Contrast Ultrasound Society, president-elect of the Italian Society for Ultrasound in Medicine and Biology. Y.K. Leadership role for the International Contrast Ultrasound Society; receipt of equipment from Canon Medical, Bracco Medical Imaging. A.M.K. No relevant relationships. S.K.R. Book royalties from Elsevier. V.P. No relevant relationships. A.K. No relevant relationships. D.T.F. University research agreements with GE HealthCare, Philips Healthcare, Siemens Healthineers; consulting fees from GE HealthCare, Philips Healthcare, Siemens Healthineers, Bracco Diagnostics; speaker fees from Siemens Healthineers; equipment receipt from GE HealthCare, Philips Healthcare, Siemens Healthineers. A.B. Consulting fees from Boehringer-Ingelheim; payment for lectures from GE HealthCare, Hologic; participation on a DataSafety Monitoring Board or Advisory Board from Boehringer-Ingelheim, Bracco; leadership roles for United European Gastroenterology, Baveno Co-operation (an EASL Consortium), SASL, EASL. I.P.R. No relevant relationships. P.S.S. Research contract for Samsung, US machine loan from Philips and Samsung; book royalties from Hodder, Springer, Thieme, Elsevier; consulting fees from Itreas, Philips, Samsung, Bracco; payment for lectures from Bracco, Samsung, Philips, Siemens, Mindray; travel support from Samsung, Philips, Siemens Healthineers; participation on a DataSafety Monitoring Board or Advisory Board from Samsung, ITREAS; editor-in-chief of Ultrasound in Medicine and Biology; US machine support from Samsung, Philips; associate editor for Radiology. C.E.W. Consulting fees from Bracco Diagnostics, SonoSim, Canon Medical Systems USA; payment for lectures from Bracco Diagnostics, SonoSim, Canon Medical Systems USA; royalties from Elsevier; advisory editorial board for JUM. K.B. No relevant relationships. J.R.E. Equipment support for study from GE HealthCare, contrast agent support from Bracco; royalties from Elsevier; consulting fees from SonoSim; speaker honoraria from GE HealthCare, ICUS, Lantheus; travel support for ICUS meeting provided by ICUS, AIUM registration provided by the AIUM; member of Thomas Jefferson University Data and Safety Monitoring Board; other equipment support from GE HealthCare, Siemens Healthineers; contrast agent support from Lantheus Medical, Bracco. F.F. Grants from Canon Medical Systems USA, PA Department of Health; consultant for Exact Therapeutics, Longeviti Neuro Solutions, SonoThera; honoraria from NTNU (Trondheim, Norway), Lantheus Medical Imaging, GE HealthCare; support for meeting attendance for International Contrast Ultrasound Meeting provided by ICUS; three patents issued and one pending; deputy editor for AIUM, associate editor for Ultrasonic Imaging; stock options in SonoThera; equipment, materials support from Siemens Healthineers, GE HealthCare, Lantheus, Butterfly Network, Philips Healthcare, Bracco. S.R.W. No relevant relationships.

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