Contrast-enhanced Ultrasound Liver Imaging Reporting And Data System Research Articles

Differences between CEUS LI-RADS and CECT LI-RADS in the diagnosis of focal liver lesions in patients at risk for HCC

ObjectivesTo compare the inter-modality consistency and diagnostic performances of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and contrast-enhanced computed tomography (CECT) LI-RADS in patients at risk for hepatocellular carcinoma (HCC), so as to help clinicians to select a more appropriate modality to follow the focal liver lesions (FLLs).MethodsThis retrospective study included untreated 277 FLLs from 247 patients who underwent both CEUS and CECT within 1 month. The ultrasound contrast medium used was SonoVue. FLL categories were independently assigned by two ultrasound physicians and two radiologists using CEUS LI-RADS v2017 and CECT LI-RADS v2018, respectively. The diagnostic performances of CEUS and CECT LI-RADS were evaluated using sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Cohen’s Kappa was employed to evaluate the concordance of the LI-RADS category.ResultsThe inter-modality consistency for CEUS and CECT LI-RADS was 0.31 (p < 0.001). HCC was more frequently observed in CECT LR-3 and LR-4 hepatic lesions than in CEUS (7.3% vs. 19.5%, p < 0.001). The specificity and PPV of CEUS and CECT LR-5 for the diagnosis of HCC were 89.5%, 95.0%, and 82.5%, 94.4%, respectively. The sensitivity of CEUS LR-5 + LR-M for the diagnosis of hepatic malignancies was higher than that of CECT (93.7% vs. 82.7%, p < 0.001). The specificity and PPV of CEUS LR-M for the diagnosis of non-HCC malignancies were lower than those of CECT (59.7% vs. 95.5%, p < 0.001; 23.4% vs. 70.3%, p < 0.001).ConclusionsThe inter-modality consistency between the CEUS and CECT LI-RADS categories is fair. CEUS LI-RADS was more sensitive than CECT LI-RADS in terms of identifying hepatic malignancies, but weaker in terms of separating HCC from non-HCC malignancies.

Compared with CT/MRI LI-RADS, whether CEUS LI-RADS is worth popularizing in diagnosis of hepatocellular carcinoma?-a direct head-to-head meta-analysis.

Until now, there has been no systematic review or meta-analysis of direct head-to-head studies that compare two liver imaging reporting and data system (LI-RADS) algorithms, contrast-enhanced ultrasound (CEUS) LI-RADS and contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) LI-RADS, for the diagnostic efficacy of hepatocellular carcinoma. The purpose of this study was to identify and head-to-head compare the diagnostic performance of both LI-RADS algorithms for hepatocellular carcinoma. We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases from the inception of each database to April 26, 2022, to find the comparative study of both LI-RADS algorithms for hepatocellular carcinoma at risk of patients who underwent both LI-RADS algorithms. Eligibility criteria included only studies published in English, full reports published, both retrospective and prospective studies. Liver histology or imaging follow-up results served as the reference standard. We analyzed the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve to determine summary estimates. The Quality Assessment of Diagnostic Accuracy Studies was utilized to assess the methodological quality. In 5 included studies (831 patients, 877 lesions), the pooled sensitivity and pooled specificity of CEUS LR-5 were 0.79, 0.81, and 0.78, 0.79 in CT/MRI LR-5, respectively. The pooled sensitivity and pooled specificity of CEUS LR-4/5 were 0.86, 0.70, and 0.93, 0.59 in CT/MRI LR-4/5, respectively. There was no obvious difference between the two LI-RADS algorithms for hepatocellular carcinoma, and there was no significant statistical difference between two LR-M algorithms for non-hepatocellular carcinoma malignancies. The results of our analysis demonstrated that CEUS LI-RADS has satisfactory diagnostic performance similar to that of CT/MRI LI-RADS, which provides a theoretical basis for the popularization of CEUS LI-RADS for diagnosing HCC. This work was supported by Sichuan Science and Technology Program (No. 2020YFS0211). We registered this study on the international prospective register of systematic reviews (PROSPERO, CRD42022328107) before the search step.

Head-to-head comparison of Sonazoid and SonoVue in the diagnosis of hepatocellular carcinoma for patients at high risk.

To compare the diagnostic efficacy of SonoVue-enhanced and Sonazoid-enhanced ultrasound (US) for hepatocellular carcinoma (HCC) in patients at high risk. Between August 2021 and February 2022, participants at high risk for HCC with focal liver lesions were enrolled and underwent both SonoVue- and Sonazoid-enhanced US. Vascular-phase and Kupffer phase (KP) imaging features of contrast-enhanced US (CEUS) were analyzed. The diagnostic performance of both contrast agent-enhanced US according to the CEUS liver imaging reporting and data system (LI-RADS) and the modified criteria (using KP defect instead of late and mild washout) were compared. Histopathology and contrast-enhanced MRI/CT were used as reference standards. In total, 62 nodules, namely, 55 HCCs, 3 non-HCC malignancies and 4 hemangiomas, from 59 participants were included. SonoVue-enhanced US had comparable sensitivity to Sonazoid-enhanced US for diagnosing HCC [80% (95% confidential interval (CI): 67%, 89.6%) versus 74.6% (95% CI: 61%, 85.3%), p = 0.25]. Both SonoVue and Sonazoid-enhanced US achieved a specificity of 100%. Compared with CEUS LI-RADS, the modified criteria with Sonazoid did not improve sensitivity for HCC diagnosis [74.6% (95% CI: 61%, 85.3%) versus 76.4% (95% CI: 63%, 86.8%), p = 0.99]. Sonazoid-enhanced US had comparable diagnostic performance to SonoVue-enhanced US for patients with HCC risk. KP did not considerably improve the diagnostic efficacy, whereas KP defects in atypical hemangioma may be pitfalls in diagnosing HCC. Further studies with larger sample sizes are needed to further validate the conclusions in the present study.

Application of DCE-US using the LI-RADS for patients with liver nodules at high risk for hepatocellular carcinoma: A preliminary study and comparison with visual interpretation

ObjectiveTo explore the value of dynamic contrast-enhanced ultrasound (DCE-US) for the Liver Imaging Reporting and Data System (LI-RADS). MethodsWe included 220 liver nodules at high risk for hepatocellular carcinoma (HCC) from January 2019 to October 2021. Visual interpretation and DCE-US-based quantitative categories using VueBox® software were compared for consistency, nodule enhancement intensity, and washout onset following the contrast-enhanced ultrasound LI-RADS. Taking the cut-off value of the ROC curve on washout onset as the time criterion of early washout of LR-M nodules, analyzed the diagnostic performance of LR-5 for HCC and compared it to that of washout onset within 60 s. ResultsThe LI-RADS visual and DCE-US interpretation results showed good consistency (Kappa = 0.730), but differed significantly in determining the LR-5 washout onset (91.2 ± 30.2 vs. 82.0 ± 32.8 s, P = 0.020) and detecting early washout (<60 s) in 196 nodules (P = 0.047). Distinguishing HCC from non-HCC malignancies had: area under the ROC curve, 0.85 (95 % confidence interval, 0.8–0.9); Youden index, 0.69; cut-off value, 48 s; sensitivity, 74.4 %; specificity, 95.0 %. When LR-M diagnosis used washout onset within 48 s, LR-5 diagnosis had sensitivity, 72.8 %; specificity, 95.0 %; positive predictive value, 98.5 %; showing a higher sensitivity than with washout onset in 60 s (62.2 %; P = 0.033). ConclusionDCE-US and visual interpretations showed high consistency in LI-RADS categories but differed in assessing the washout time. According to the DCE-US interpretation, the diagnostic performance of LR-5 could be improved using washout onset of 48 s for LR-M.

Inter-reader reliability of contrast-enhanced ultrasound Liver Imaging Reporting and Data System: a meta-analysis.

To systematically determine the inter-reader reliability of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS), with emphasis on its major features for hepatocellular carcinoma (HCC) and LR-M (LI-RADS category M) features for non-HCC malignancy. MEDLINE, EMBASE, and Cochrane databases were searched from January 2016 to March 2021 to identify original articles reporting the inter-reader reliability of CEUS LI-RADS. Meta-analytic pooled kappa values (κ) were calculated for major features [nonrim arterial-phase hyperenhancement (APHE), mild and late washout], LR-M features (rim APHE, early washout), and LI-RADS categorization using the DerSimonian-Laird random-effects model. Meta-regression analysis was performed to explore any causes of study heterogeneity. Twelve studies with a total of 2862 lesions were included. The meta-analytic pooled κ of nonrim APHE, mild and late washout, rim APHE, early washout, and LI-RADS categorization were 0.73 [95% confidence interval (CI), 0.67 - 0.79], 0.69 (95% CI, 0.54-0.84), 0.54 (95% CI, 0.37-0.71), 0.62 (95% CI, 0.45-0.79), and 0.75 (95% CI, 0.64-0.87), respectively. Compared with the major features, LR-M features had a lower meta-analytic pooled κ. Substantial study heterogeneity was noted in the LI-RADS categorization, and lesion size (p = 0.03) and the homogeneity in reader experience (p = 0.03) were significantly associated with study heterogeneity. CEUS LI-RADS showed substantial inter-reader reliability for major features and LI-RADS categorization, but relatively lower reliability was found for LR-M features. In our opinion, the definitions of imaging features require further refinement to improve the inter-reader reliability of CEUS LI-RADS.

Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

BACKGROUNDHepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) was set up for lesions that are malignant but not specific to HCC. However, a substantial number of HCC cases in this category elevated the diagnostic challenge.AIMTo investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.METHODSPatients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC (HCC classified in the CEUS LI-RADS LR-M category) between January 2015 and October 2018 were included in this retrospective study. Each ICC was assigned a category as per the CEUS LI-RADS. The enhancement pattern, washout timing, and washout degree between the ICC and LR-M HCC were compared using the χ2 test. Logistic regression analysis was used for prediction of ICC. Receiver operating characteristic (ROC) curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.RESULTSA total of 228 nodules (99 ICCs and 129 LR-M HCCs) in 228 patients were included. The mean sizes of ICC and LR-M HCC were 6.3 ± 2.8 cm and 5.5 ± 3.5 cm, respectively (P = 0.03). Peripheral rim-like arterial phase hyperenhancement (APHE) was detected in 50.5% (50/99) of ICCs vs 16.3% (21/129) of LR-M HCCs (P < 0.001). Early washout was found in 93.4% (93/99) of ICCs vs 96.1% (124/129) of LR-M HCCs (P > 0.05). Marked washout was observed in 23.2% (23/99) of ICCs and 7.8% (10/129) of LR-M HCCs (P = 0.002), while this feature did not show up alone either in ICC or LR-M HCC. Homogeneous hyperenhancement was detected in 15.2% (15/99) of ICCs and 37.2% (48/129) of LR-M HCCs (P < 0.001). The logistic regression showed that rim APHE, carbohydrate antigen 19-9 (CA 19-9), and alpha fetoprotein (AFP) had significant correlations with ICC (r = 1.251, 3.074, and -2.767, respectively; P < 0.01). Rim APHE presented the best enhancement pattern for diagnosing ICC, with an area under the ROC curve (AUC) of 0.70, sensitivity of 70.4%, and specificity of 68.8%. When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP, the AUC and sensitivity improved to 0.82 and 100%, respectively, with specificity decreasing to 63.9%.CONCLUSIONRim APHE is a key predictor for differentiating ICC from LR-M HCC. Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Hepatocellular Carcinoma: Diagnostic Performance and Interobserver Agreement.

To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). In cirrhotic patients, the specificity of LR-5 (range: 92.7-100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6-64.3 %). However, the sensitivity (range: 38.6-63.6 %) and accuracy (range: 53.4-70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6-100.0 %; accuracy range: 77.6-86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.

The predictive value of Liver Imaging Reporting and Data System with contrast-enhanced ultrasound (v2017) in the risk of hepatocellular carcinoma in high-risk population

Objective To explore the clinical value of Liver Imaging Reporting and Data System (LI-RADS) version 2017 with contrast-enhanced ultrasound (CEUS) for the risk prediction of hepatocellular carcinoma (HCC). Methods Five hundred and seventy-one patients with HCC risk factors had received CEUS examination in Tianjin Third Central Hospital, 270 patients with 295 nodules were enrolled in this study according to the inclusion criteria. The final diagnostic reference standard was decided by surgical pathology or ultrasound-guided biopsy pathology. Each nodule was classified according to CEUS LI-RADS v2017. The diagnostic accuracy of CEUS LI-RADS v2017 for the prediction of HCC was analyzed retrospectively. Results Of all 295 nodules, 95 nodules were diagnosed by surgical pathology and 200 nodules by ultrasoud-guided biopsy pathology, among which with 245 HCC, 13 intrahepatic cholangiocarcinoma (ICC), 8 combined hepatocellular cholangiocarcinoma(CHC), 2 metastatic neoplasm of other cellular origin and 27 benign nodules.The numbers of LR-3, LR-4, LR-5 and LR-M categories were 16(5.4%), 28(9.5%), 183(62.0%), 68(23.1%) and the positive predictive value (PPV) of LR-3, LR-4 and LR-5 were 43.8%, 60.7%, 98.4% for HCC, respectively. The sensitivity, specificity and positive predictive value of LR-5 category for HCC were 73.5%, 94.0%, 98.4%, respectively. 60.3%(41/68) LR-M category nodules were pathologically confirmed to be HCC. Conclusions CEUS LI-RADS v2017 classification standard has reliable risk prediction value for patients with high risk factors of HCC, of which the LR-5 category has higher PPV for HCC. However, the differential diagnosis between HCC and other non-HCC malignancies still remains to be further studied for LR-M observations. Key words: Contrast-enhanced ultrasound; Hepatocellular carcinoma; Liver Imaging Reporting and Data System