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

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.

Graphical abstract

Figure 1:

Images in a 49-year-old female participant with cryptogenic cirrhosis who presented with a 3.2-cm liver lesion. This biopsy-confirmed hepatocellular carcinoma (HCC) with an initial categorization of Liver Imaging Reporting and Data System (LI-RADS) category LR-4 (probably HCC) at CT was upgraded to LR-5 (definitely HCC) at contrast-enhanced US (CEUS). (A) Precontrast CT images in the liver with vague hypoattenuation in the medial left hepatic lobe (arrows), (B) arterial phase images demonstrate no definite arterial phase hyperenhancement (arrows), and (C) washout and an enhancing capsule (arrows) on a late-phase image resulted in a LR-4 categorization. (D) B-mode US image shows a round hypoechoic nodule (arrows) and (E) early-phase CEUS image with clear arterial-phase hyperenhancement (arrows); (F) no washout at 1 minute (arrows), and (G) late, mild washout at 4 minutes (arrows), resulting in a CEUS LR-5 categorization.

Figure 2:

Images in a 48-year-old female participant with hepatitis B virus show a nonmalignant Liver Imaging Reporting and Data System (LI-RADS) category LR-4 (probably hepatocellular carcinoma) observation at MRI that was downgraded to LI-RADS category LR-3 (intermediate probability of malignancy) at contrast-enhanced US (CEUS). (A) Precontrast T1-weighted MRI scan in the liver with vague hypointense findings in the right hepatic lobe (arrows) and (B) definite arterial phase hyperenhancement (arrows). (C) No definite washout was observed on the late-phase image (arrows), resulting in LR-4 categorization. (D) B-mode US image shows a 29-mm hypoechoic mass (arrows) with (E) arterial phase isoenhancement (arrows) and (F) no washout at 1 minute (arrows) or at (G) 4 minutes (arrows), resulting in the CEUS categorization of LR-3. Biopsy performed shortly after CEUS showed chronic hepatitis with mild activity and cirrhosis, and no tumors were evident. (H–J) One-year follow-up MRI scans also show (H) vague findings in the right hepatic lobe (arrows on H–J) on a contrast-unenhanced T1-weighted MRI scan, with (I) isoenhancement at the arterial phase and (J) no washout on the late-phase image, resulting in LR-3 categorization.

Figure 3:

Images in a 75-year-old female participant with metabolic dysfunction–associated steatohepatitis cirrhosis showed a Liver Imaging Reporting and Data System (LI-RADS) category LR-M (probably or definitely malignant but not hepatocellular carcinoma [HCC] specific) observation at MRI that was recategorized to LI-RADS category LR-5 (definitely HCC) at contrast-enhanced US (CEUS). MRI scans in the (A) early arterial and (B) late arterial phases show peripheral, targetoid arterial phase hyperenhancement (arrows on A, B). (C) Late-phase MRI scan shows peripheral washout, capsule appearance, and delayed central enhancement (arrows), resulting in LR-M categorization. (D) US image with a 1.6-cm heterogeneous echogenic nodule in the right hepatic lobe (arrows). (E) Arterial phase CEUS images show hyperenhancement (arrows), with (F) isoenhancement at 1 minute (arrows) and (G) late, mild washout at 3 minutes (arrows) resulting in CEUS LR-5 categorization.