Intra-individual comparison of two-dimensional shear wave elastography techniques using plane wave imaging and the multi-beam technique: are they interchangeable in measuring liver fibrosis?

Purpose@#This study compared two different two-dimensional shear wave elastography techniques—plane wave imaging (PWI) and multi-beam (MB) imaging—from the same vendor to evaluate liver fibrosis. @*Methods@#In this prospective study, 42 patients with chronic liver disease who had recently undergone magnetic resonance elastography (<3 months) were enrolled, and their liver stiffness (LS) values were measured using PWI or MB. The LS values (kPa) were compared using the Wilcoxon rank-sum test. Inter-technique reproducibility and intra-observer repeatability were assessed using Bland-Altman analysis with 95% limits of agreement (LOA) and coefficients of variation (CVs). The cutoff values for predicting severe fibrosis (≥F3) were estimated using receiver operating characteristic curve (ROC) analysis, with magnetic resonance elastography as the reference standard. @*Results@#PWI exhibited technical failure in four patients. Therefore, 38 patients underwent both examinations. The LS values showed moderate agreement between PWI and MB (CV, 22.5%) and 95% LOA of -3.71 to 7.44 kPa. The MB technique showed good intra-observer agreement (CV, 8.1%), while PWI showed moderate agreement (CV, 11.0%). The cutoff values of PWI and MB for diagnosing ≥F3 were 12.3 kPa and 13.8 kPa, respectively, with areas under the ROC curve of 0.89 and 0.95 (sensitivity, 100% and 100%; specificity, 65.6% and 85.7%). @*Conclusion@#The LS values significantly differed between PWI and MB, hindering their interchangeable use in longitudinal follow-up. Considering its low technical failure rate and better repeatability, the MB technique may be preferable for evaluating liver fibrosis in chronic liver disease patients.

Prognostic role of computed tomography analysis using deep learning algorithm in patients with chronic hepatitis B viral infection

The prediction of clinical outcomes in patients with chronic hepatitis B (CHB) is paramount for effective management. This study aimed to evaluate the prognostic value of computed tomography (CT) analysis using deep learning algorithms in patients with CHB. Methods: This retrospective study included 2,169 patients with CHB without hepatic decompensation who underwent contrast-enhanced abdominal CT for hepatocellular carcinoma (HCC) surveillance between January 2005 and June 2016. Liver and spleen volumes and body composition measurements including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle indices were acquired from CT images using deep learning-based fully automated organ segmentation algorithms. We assessed the significant predictors of HCC, hepatic decompensation, diabetes mellitus (DM), and overall survival (OS) using Cox proportional hazard analyses. Results: During a median follow-up period of 103.0 months, HCC (n=134, 6.2%), hepatic decompensation (n=103, 4.7%), DM (n=432, 19.9%), and death (n=120, 5.5%) occurred. According to the multivariate analysis, standardized spleen volume significantly predicted HCC development (hazard ratio [HR]=1.01, P=0.025), along with age, sex, albumin and platelet count. Standardized spleen volume (HR=1.01, PP=0.004) were significantly associated with hepatic decompensation along with age and albumin. Furthermore, VAT index (HR=1.01, P=0.001) and standardized spleen volume (HR=1.01, P=0.001) were significant predictors for DM, along with sex, age, and albumin. SAT index (HR=0.99, P=0.004) was significantly associated with OS, along with age, albumin, and MELD. Conclusions: Deep learning-based automatically measured spleen volume, VAT, and SAT indices may provide various prognostic information in patients with CHB.

Quantitative Evaluation of Hepatic Steatosis Using Advanced Imaging Techniques: Focusing on New Quantitative Ultrasound Techniques

Nonalcoholic fatty liver disease, characterized by excessive accumulation of fat in the liver, is the most common chronic liver disease worldwide. The current standard for the detection of hepatic steatosis is liver biopsy; however, it is limited by invasiveness and sampling errors. Accordingly, MR spectroscopy and proton density fat fraction obtained with MRI have been accepted as non-invasive modalities for quantifying hepatic steatosis. Recently, various quantitative ultrasonography techniques have been developed and validated for the quantification of hepatic steatosis. These techniques measure various acoustic parameters, including attenuation coefficient, backscatter coefficient and speckle statistics, speed of sound, and shear wave elastography metrics. In this article, we introduce several representative quantitative ultrasonography techniques and their diagnostic value for the detection of hepatic steatosis.

Diagnostic Performance of Spin-Echo Echo-Planar Imaging Magnetic Resonance Elastography in 3T System for Noninvasive Assessment of Hepatic Fibrosis

Objective@#To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard. @*Materials and Methods@#This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0–F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal–Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. @*Results@#Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97–0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0–F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97–0.98 (sensitivity 91.2%–95.9%, specificity 90.7%–99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0–F3 stages. @*Conclusion@#The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.

Deep learning-based automated quantification of the hepatorenal index for evaluation of fatty liver by ultrasonography

Purpose@#The aim of this study was to develop and validate a fully-automatic quantification of the hepatorenal index (HRI) calculated by a deep convolutional neural network (DCNN) comparable to the interpretations of radiologists experienced in ultrasound (US) imaging. @*Methods@#In this retrospective analysis, DCNN-based organ segmentation with Gaussian mixture modeling for automated quantification of the HRI was developed using abdominal US images from a previous study. For validation, 294 patients who underwent abdominal US examination before living-donor liver transplantation were selected. Interobserver agreement for the measured brightness of the liver and kidney and the calculated HRI were analyzed between two board-certified radiologists and DCNN using intraclass correlation coefficients (ICCs). @*Results@#Most patients had normal (n=95) or mild (n=198) fatty liver. The ICCs of hepatic and renal brightness measurements and the calculated HRI between the two radiologists were 0.892 (95% confidence interval [CI], 0.866 to 0.913), 0.898 (95% CI, 0.873 to 0.918), and 0.681 (95% CI, 0.615 to 0.738) for the first session and 0.920 (95% CI, 0.901 to 0.936), 0.874 (95% CI, 0.844 to 0.898), and 0.579 (95% CI, 0.497 to 0.650) for the second session, respectively; the results ranged from moderate to excellent agreement. Using the same task, the ICCs of the hepatic and renal measurements and the calculated HRI between the average values of the two radiologists and DCNN were 0.919 (95% CI, 0.899 to 0.935), 0.916 (95% CI, 0.895 to 0.932), and 0.734 (95% CI, 0.676 to 0.782), respectively, showing high to excellent agreement. @*Conclusion@#Automated quantification of HRI using DCNN can yield HRI measurements similar to those obtained by experienced radiologists in patients with normal or mild fatty liver.

Quantitative ultrasound radiofrequency data analysis for the assessment of hepatic steatosis using the controlled attenuation parameter as a reference standard

Purpose@#This study was aimed to investigate the value of quantitative ultrasound (US) parameters from radiofrequency (RF) data analysis for assessing hepatic steatosis, using controlled attenuation parameter (CAP)-based steatosis grades as the reference standard. @*Methods@#We analyzed 243 participants with both B-mode liver US with RF data acquisition and CAP measurements. On B-mode US images, hepatic steatosis was visually scored (0/1/2/3, none/mild/moderate/severe), and the hepatorenal index (HRI) was calculated. From the RF data analysis, the tissue scatter-distribution imaging parameter (TSI-p) and tissue attenuation imaging parameter (TAI-p) of the liver parenchyma were measured. US parameters were correlated with CAP-based steatosis grades (S0/1/2/3, none/mild/moderate/severe) and their diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Multivariate linear regression analysis was performed to identify determinants of TSI-p and TAI-p. @*Results@#Participants were classified as having S0 (n=152), S1 (n=54), S2 (n=14), and S3 (n=23) on CAP measurements. TSI-p and TAI-p were significantly correlated with steatosis grades (ρ =0.593 and ρ=-0.617, P<0.001 for both). For predicting ≥S1, ≥S2, and S3, the areas under the ROC curves (AUCs) of TSI-p were 0.827/0.914/0.917; TAI-p, 0.844/0.914/0.909; visual scores, 0.659/0.778/0.794; and HRI, 0.629/0.751/0.759, respectively. TSI-p and TAI-p had significantly higher AUCs than did visual scores or HRI for ≥S1 or ≥S2 (P≤0.003). In the multivariate analysis, the transient elastography-based fibrosis grade (P=0.034) and steatosis grade (P<0.001) were independent determinants of TSI-p, while steatosis grade (P<0.001) was an independent determinant of TAI-p. @*Conclusion@#TSI-p and TAI-p derived from US RF data may be useful for detecting hepatic steatosis and assessing its severity.

Volumetric CT Texture Analysis of Intrahepatic Mass-Forming Cholangiocarcinoma for the Prediction of Postoperative Outcomes: Fully Automatic Tumor Segmentation Versus Semi-Automatic Segmentation

Objective@#To determine whether volumetric CT texture analysis (CTTA) using fully automatic tumor segmentation can help predict recurrence-free survival (RFS) in patients with intrahepatic mass-forming cholangiocarcinomas (IMCCs) after surgical resection. @*Materials and Methods@#This retrospective study analyzed the preoperative CT scans of 89 patients with IMCCs (64 male; 25 female; mean age, 62.1 years; range, 38–78 years) who underwent surgical resection between January 2005 and December 2016. Volumetric CTTA of IMCCs was performed in late arterial phase images using both fully automatic and semi-automatic liver tumor segmentation techniques. The time spent on segmentation and texture analysis was compared, and the first-order and second-order texture parameters and shape features were extracted. The reliability of CTTA parameters between the techniques was evaluated using intraclass correlation coefficients (ICCs). Intra- and interobserver reproducibility of volumetric CTTAs were also obtained using ICCs. Cox proportional hazard regression were used to predict RFS using CTTA parameters and clinicopathological parameters. @*Results@#The time spent on fully automatic tumor segmentation and CTTA was significantly shorter than that for semiautomatic segmentation: mean ± standard deviation of 1 minutes 37 seconds ± 50 seconds vs. 10 minutes 48 seconds ± 13 minutes 44 seconds (p < 0.001). ICCs of the texture features between the two techniques ranged from 0.215 to 0.980. ICCs for the intraobserver and interobserver reproducibility using fully automatic segmentation were 0.601–0.997 and 0.177– 0.984, respectively. Multivariable analysis identified lower first-order mean (hazard ratio [HR], 0.982; p = 0.010), larger pathologic tumor size (HR, 1.171; p < 0.001), and positive lymph node involvement (HR, 2.193; p = 0.014) as significant parameters for shorter RFS using fully automatic segmentation. @*Conclusion@#Volumetric CTTA parameters obtained using fully automatic segmentation could be utilized as prognostic markers in patients with IMCC, with comparable reproducibility in significantly less time compared with semi-automatic segmentation.

Additional Value of Integrated 18 F-FDG PET/MRI for Evaluating Biliary Tract Cancer: Comparison with Contrast-Enhanced CT

Objective@#To evaluate the value of 18 F-fluorodeoxyglucose PET/MRI added to contrast-enhanced CT (CECT) in initial staging, assessment of resectability, and postoperative follow-up of biliary tract cancer. @*Materials and Methods@#This retrospective study included 100 patients (initial workup [n = 65] and postoperative follow-up [n = 35]) who had undergone PET/MRI and CECT for bile duct or gallbladder lesions between January 2013 and March 2020.Two radiologists independently reviewed the CECT imaging set and CECT plus PET/MRI set to determine the likelihood of malignancy, local and overall resectability, and distant metastasis in the initial workup group, and local recurrence and distant metastasis in the follow-up group. Diagnostic performances of the two imaging sets were compared using clinical-surgicalpathologic findings as standards of reference. @*Results@#The diagnostic performance of CECT significantly improved after the addition of PET/MRI for liver metastasis (area under the receiver operating characteristic curve [A z]: 0.77 vs. 0.91 [p = 0.027] for reviewer 1; 0.76 vs. 0.92 [p = 0.021] for reviewer 2), lymph node metastasis (0.73 vs. 0.92 [p = 0.004]; 0.81 vs. 0.92 [p = 0.023]), and overall resectability (0.79 vs.0.92 [p = 0.007]; 0.82 vs. 0.94 [p = 0.021]) in the initial workup group. In the follow-up group, the diagnostic performance of CECT plus PET/MRI was significantly higher than that of CECT imaging for local recurrence (0.81 vs. 1.00 [p = 0.029]; 0.82 vs. 0.94 [p = 0.045]). @*Conclusion@#PET/MRI may add value to CECT in patients with biliary tract cancer both in the initial workup for staging and determination of overall resectability and in follow-up for local recurrence.

Quantitative Ultrasound Radiofrequency Data Analysis for the Assessment of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Using Magnetic Resonance Imaging Proton Density Fat Fraction as the Reference Standard

Objective@#To investigate the diagnostic performance of quantitative ultrasound (US) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. @*Materials and Methods@#In this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. The participants underwent US examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, the attenuation coefficient (AC) based on tissue attenuation imaging (TAI) (AC-TAI) and scatter-distribution coefficient (SC) based on tissue scatterdistribution imaging (TSI) (SC-TSI) were measured. The correlations between the quantitative US parameters (AC and SC) and MRI-PDFF were evaluated using Pearson correlation coefficients. The diagnostic performance of AC-TAI and SC-TSI for detecting hepatic fat contents of ≥ 5% (MRI-PDFF ≥ 5%) and ≥ 10% (MRI-PDFF ≥ 10%) were assessed using receiver operating characteristic (ROC) analysis. The significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis. @*Results@#The participants were classified based on MRI-PDFF: < 5% (n = 38), 5–10% (n = 23), and ≥ 10% (n = 59). AC-TAI and SC-TSI were significantly correlated with MRI-PDFF (r = 0.659 and 0.727, p < 0.001 for both). For detecting hepatic fat contents of ≥ 5% and ≥ 10%, the areas under the ROC curves of AC-TAI were 0.861 (95% confidence interval [CI]: 0.786– 0.918) and 0.835 (95% CI: 0.757–0.897), and those of SC-TSI were 0.964 (95% CI: 0.913–0.989) and 0.935 (95% CI: 0.875–0.972), respectively. Multivariable linear regression analysis showed that MRI-PDFF was an independent determinant of AC-TAI and SC-TSI. @*Conclusion@#AC-TAI and SC-TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.

Additional Value of Integrated 18 F-FDG PET/MRI for Evaluating Biliary Tract Cancer: Comparison with Contrast-Enhanced CT

Objective@#To evaluate the value of 18 F-fluorodeoxyglucose PET/MRI added to contrast-enhanced CT (CECT) in initial staging, assessment of resectability, and postoperative follow-up of biliary tract cancer. @*Materials and Methods@#This retrospective study included 100 patients (initial workup [n = 65] and postoperative follow-up [n = 35]) who had undergone PET/MRI and CECT for bile duct or gallbladder lesions between January 2013 and March 2020.Two radiologists independently reviewed the CECT imaging set and CECT plus PET/MRI set to determine the likelihood of malignancy, local and overall resectability, and distant metastasis in the initial workup group, and local recurrence and distant metastasis in the follow-up group. Diagnostic performances of the two imaging sets were compared using clinical-surgicalpathologic findings as standards of reference. @*Results@#The diagnostic performance of CECT significantly improved after the addition of PET/MRI for liver metastasis (area under the receiver operating characteristic curve [A z]: 0.77 vs. 0.91 [p = 0.027] for reviewer 1; 0.76 vs. 0.92 [p = 0.021] for reviewer 2), lymph node metastasis (0.73 vs. 0.92 [p = 0.004]; 0.81 vs. 0.92 [p = 0.023]), and overall resectability (0.79 vs.0.92 [p = 0.007]; 0.82 vs. 0.94 [p = 0.021]) in the initial workup group. In the follow-up group, the diagnostic performance of CECT plus PET/MRI was significantly higher than that of CECT imaging for local recurrence (0.81 vs. 1.00 [p = 0.029]; 0.82 vs. 0.94 [p = 0.045]). @*Conclusion@#PET/MRI may add value to CECT in patients with biliary tract cancer both in the initial workup for staging and determination of overall resectability and in follow-up for local recurrence.

Quantitative Ultrasound Radiofrequency Data Analysis for the Assessment of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Using Magnetic Resonance Imaging Proton Density Fat Fraction as the Reference Standard

Objective@#To investigate the diagnostic performance of quantitative ultrasound (US) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. @*Materials and Methods@#In this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. The participants underwent US examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, the attenuation coefficient (AC) based on tissue attenuation imaging (TAI) (AC-TAI) and scatter-distribution coefficient (SC) based on tissue scatterdistribution imaging (TSI) (SC-TSI) were measured. The correlations between the quantitative US parameters (AC and SC) and MRI-PDFF were evaluated using Pearson correlation coefficients. The diagnostic performance of AC-TAI and SC-TSI for detecting hepatic fat contents of ≥ 5% (MRI-PDFF ≥ 5%) and ≥ 10% (MRI-PDFF ≥ 10%) were assessed using receiver operating characteristic (ROC) analysis. The significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis. @*Results@#The participants were classified based on MRI-PDFF: < 5% (n = 38), 5–10% (n = 23), and ≥ 10% (n = 59). AC-TAI and SC-TSI were significantly correlated with MRI-PDFF (r = 0.659 and 0.727, p < 0.001 for both). For detecting hepatic fat contents of ≥ 5% and ≥ 10%, the areas under the ROC curves of AC-TAI were 0.861 (95% confidence interval [CI]: 0.786– 0.918) and 0.835 (95% CI: 0.757–0.897), and those of SC-TSI were 0.964 (95% CI: 0.913–0.989) and 0.935 (95% CI: 0.875–0.972), respectively. Multivariable linear regression analysis showed that MRI-PDFF was an independent determinant of AC-TAI and SC-TSI. @*Conclusion@#AC-TAI and SC-TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.

Assessment of liver fibrosis using 2-dimensional shear wave elastography: a prospective study of intra- and inter-observer repeatability and comparison with point shear wave elastography

Purpose@#The purpose of this study was to prospectively investigate the intra- and interobserver repeatability of a new 2-dimensional (2D) shear wave elastography (SWE) technique (S-Shearwave Imaging) for assessing liver fibrosis in chronic liver disease patients, and to compare liver stiffness measurements (LSMs) made using 2D-SWE with those made using point SWE (pSWE). @*Methods@#This prospective study received institutional review board approval and informed consent was obtained from all patients. Fifty-three chronic liver disease patients were randomly allocated to group 1 (for intra-observer repeatability [n=33]) or group 2 (for inter-observer repeatability [n=20]). In group 1, two 2D-SWE sessions and one pSWE sessions were performed by one radiologist. In group 2, one 2D-SWE session and one pSWE session were performed by the aforementioned radiologist, and a second 2D-SWE session was performed by another radiologist. The intraclass correlation coefficient (ICC) was used to assess intra- and interobserver reliability. LSMs obtained using 2D-SWE and pSWE were compared and correlated using the paired t test and Pearson correlation coefficient, respectively. @*Results@#LSMs made using 2D-SWE demonstrated excellent intra- and inter-observer repeatability (ICC, 0.997 [95% confidence interval, 0.994 to 0.999]) and 0.995 [0.988 to 0.998], respectively). LSMs made using 2D-SWE were significantly different from those made using pSWE (2.1±0.6 m/sec vs. 1.9±0.6 m/sec, P<0.001), although a significant correlation existed between the 2D-SWE and pSWE LSMs (rho=0.836, P<0.001). @*Conclusion@#S-Shearwave Imaging demonstrated excellent intra- and inter-observer repeatability, and a strong correlation with pSWE measurements of liver stiffness. However, because of the significant difference between LSMs obtained using 2D-SWE and pSWE, these methods should not be used interchangeably.

Reproducibility of ultrasound attenuation imaging for the noninvasive evaluation of hepatic steatosis

Purpose@#The purpose of this study was to evaluate the intra-observer reproducibility of ultrasound attenuation imaging (ATI) for the noninvasive assessment of hepatic steatosis in patients with suspected hepatic steatosis and the inter-observer reproducibility in asymptomatic volunteers. @*Methods@#This prospective study was approved by our institutional review board and informed consent was obtained from all patients. In group 1, composed of patients with suspected hepatic steatosis (n=143), one abdominal radiologist performed gray-scale ultrasonography and two sessions of ATI. In group 2, composed of healthy volunteers (n=18), three independent sessions of ATI were performed by three abdominal radiologists. The visual degree of hepatic steatosis in all study subjects was graded on a 4-point scale by two independent reviewers using gray-scale ultrasonography. Thereafter, the attenuation coefficient (AC) was correlated with the degree of hepatic steatosis using Spearman rank correlation analysis. Intra-class correlation coefficients (ICCs) were used to assess the intra-observer (group 1) and inter-observer reproducibility (group 2) of ATI measurements. @*Results@#For the intra-observer reproducibility of ATI, the ICC was 0.929 (95% confidence interval [CI], 0.901 to 0.949), and the coefficient of variation was 7.1%. Inter-observer reproducibility of ATI measurements showed an ICC of 0.792 (95% CI, 0.549 to 0.916). The AC showed a significant correlation with the visual grade of hepatic steatosis for both reviewers (rho, 0.780 and 0.695; P<0.001, respectively). @*Conclusion@#ATI showed high intra- and inter-observer reproducibility in the assessment of hepatic steatosis.

Combined Hepatocellular-Cholangiocarcinoma: Changes in the 2019 World Health Organization Histological Classification System and Potential Impact on Imaging-Based Diagnosis

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver cancer (PLC) with both hepatocytic and cholangiocytic phenotypes. Recently, the World Health Organization (WHO) updated its histological classification system for cHCC-CCA.Compared to the previous WHO histological classification system, the new version no longer recognizes subtypes of cHCC-CCA with stem cell features. Furthermore, some of these cHCC-CCA subtypes with stem cell features have been recategorized as either hepatocellular carcinomas (HCCs) or intrahepatic cholangiocarcinomas (ICCs). Additionally, distinctive diagnostic terms for intermediate cell carcinomas and cholangiolocarcinomas (previous cholangiolocellular carcinoma subtype) are now recommended. It is important for radiologists to understand these changes because of its potential impact on the imagingbased diagnosis of HCC, particularly because cHCC-CCAs frequently manifest as HCC mimickers, ICC mimickers, or as indeterminate on imaging studies. Therefore, in this review, we introduce the 2019 WHO classification system for cHCC-CCA, illustrate important imaging features characteristic of its subtypes, discuss the impact on imaging-based diagnosis of HCC, and address other important considerations.

Systematic Review with Meta-Analysis: Low-Level Alcohol Consumption and the Risk of Liver Cancer

Background/Aims@#Multiple meta-analyses and observational studies have reported that alcohol is a risk factor for liver cancer. However, whether there is a safe level of alcohol consumption remains unclear. We performed a systematic review and meta-analysis of the correlation between low-level alcohol consumption and the risk of liver cancer. @*Methods@#Nested case-control studies and cohort studies involving the general population published prior to July 2019 were searched. In total, 28 publications (31 cohorts) with 4,899 incident cases and 10,859 liver cancer-related deaths were included. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. @*Results@#Compared with those with low levels of alcohol consumption, moderate and heavy drinkers (≥1 drink/day for females and ≥2 drinks/day for males) had pooled ORs of 1.418 (95% CI, 1.192 to 1.687; p<0.001) for liver cancer incidence and 1.167 (95% CI, 1.056to 1.290; p=0.003) for liver cancer mortality. The pooled OR for liver disease-related mortality for those with more than low levels of alcohol consumption was 3.220 (95% CI, 2.116 to 4.898; p<0.001) and that for all-cause mortality was 1.166 (95% CI, 1.065 to 1.278; p=0.001). The sensitivity analysis showed that none of the studies had a strong effect on the pooled OR. The Egger test, Begg rank correlation test, and the funnel plot showed no overt indication of publication bias. @*Conclusions@#Continuous consumption of more than a low-level of alcohol (≥1 drink/day for females and ≥2 drinks/ day for males) is related to a higher risk of liver cancer.

Atypical Appearance of Hepatocellular Carcinoma and Its Mimickers: How to Solve Challenging Cases Using Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging

Hepatocellular carcinoma (HCC) can be diagnosed noninvasively with contrast-enhanced dynamic computed tomography, magnetic resonance imaging, or ultrasonography on the basis of its hallmark imaging features of arterial phase hyperenhancement and washout on portal or delayed phase images. However, approximately 40% of HCCs show atypical imaging features, posing a significant diagnostic challenge for radiologists. Another challenge for radiologists in clinical practice is the presentation of many HCC mimickers such as intrahepatic cholangiocarcinoma, combined HCC-cholangiocarcinoma, arterioportal shunt, and hemangioma in the cirrhotic liver. The differentiation of HCCs from these mimickers on preoperative imaging studies is of critical importance. Hence, we will review the typical and atypical imaging features of HCCs and the imaging features of its common mimickers. In addition, we will discuss how to solve these challenges in practice.

Validation of a New Point Shear-Wave Elastography Method for Noninvasive Assessment of Liver Fibrosis: A Prospective Multicenter Study

OBJECTIVE: To validate the diagnostic value of a new point shear-wave elastography method, S-shearwave elastography (S-SWE; Samsung Medison Co., Ltd.), in noninvasive assessment of liver fibrosis. MATERIALS AND METHODS: In this prospective multicenter study, liver stiffness (LS) measurements for 600 participants were obtained with both S-SWE and transient elastography (TE). The rates of unsuccessful LS measurements in S-SWE and TE were compared, and correlations between S-SWE and TE measurements were assessed. In 107 patients with histologic reference data, the optimal LS cut-off values for predicting severe fibrosis and cirrhosis on S-SWE were determined using receiver operating characteristic (ROC) curve analysis. The LS cut-off values in S-SWE were then validated in 463 patients without histologic reference data by using TE values as the reference standard, and the sensitivity and specificity of the cut-off values for predicting severe fibrosis and cirrhosis were calculated. RESULTS: The frequency of unsuccessful LS measurements on TE (4.5%, 27/600) was significantly higher than that (0.7%, 4/600) on S-SWE (p < 0.001). LS measurements on S-SWE showed a significant correlation with TE values (r = 0.880, p < 0.001). In 107 patients with histological reference data, the areas under the ROC curves on S-SWE were 0.845 and 0.850, with optimal cut-offs of 7.0 kilopascals (kPa) and 9.7 kPa, for the diagnosis of severe fibrosis and cirrhosis, respectively. Using these cut-off values, S-SWE showed sensitivities of 92.9% and 97.4% and specificities of 89.5% and 83.1% in TE-based evaluations of severe fibrosis and cirrhosis, respectively. CONCLUSION: LS measurements on S-SWE were well correlated with those on TE. In addition, S-SWE provided good diagnostic performance for staging of hepatic fibrosis, with a lower rate of unsuccessful LS measurements compared with TE.

Dynamic Contrast-Enhanced Ultrasound of Gastric Cancer: Correlation with Perfusion CT and Histopathology

OBJECTIVE: To assess the relationship between contrast-enhanced ultrasound (CEUS) parameters and perfusion CT (PCT) parameters of gastric cancers and their correlation with histologic features. MATERIALS AND METHODS: This prospective study was approved by our Institutional Review Board. We included 43 patients with pathologically-proven gastric cancers undergoing CEUS using SonoVue® (Bracco) and PCT on the same day. Correlation between the CEUS parameters (peak intensity [PI], area under the curve [AUC], rise time [RT] from 10% to 90% of PI, time to peak [TTPUS], and mean transit time [MTTUS]) and PCT parameters (blood flow, blood volume, TTPCT, MTTCT, and permeability surface product) of gastric cancers were analyzed using Spearman's rank correlation test. In cases of surgical resection, the CEUS and PCT parameters were compared according to histologic features using Mann-Whitney test. RESULTS: CEUS studies were of diagnostic quality in 88.4% (38/43) of patients. Among the CEUS parameters of gastric cancers, RT and TTPUS showed significant positive correlations with TTPCT (rho = 0.327 and 0.374, p = 0.045 and 0.021, respectively); PI and AUC were significantly higher in well-differentiated or moderately-differentiated tumors (n = 4) than poorly-differentiated tumors (n = 18) (p = 0.026 and 0.033, respectively), whereas MTTCT showed significant differences according to histologic types (poorly cohesive carcinoma [PCC] vs. non-PCC), T-staging (≤ T2 vs. ≥ T3), N-staging (N0 vs. N-positive), and epidermal growth factor receptor expression (≤ faint vs. ≥ moderate staining) (p values < 0.05). CONCLUSION: In patients with gastric cancers, CEUS is technically feasible for the quantification of tumor perfusion and may provide correlative and complementary information to that of PCT, which may allow prediction of histologic features.

Evaluation of the Impact of Iterative Reconstruction Algorithms on Computed Tomography Texture Features of the Liver Parenchyma Using the Filtration-Histogram Method

OBJECTIVE: To evaluate whether computed tomography (CT) reconstruction algorithms affect the CT texture features of the liver parenchyma. MATERIALS AND METHODS: This retrospective study comprised 58 patients (normal liver, n = 34; chronic liver disease [CLD], n = 24) who underwent liver CT scans using a single CT scanner. All CT images were reconstructed using filtered back projection (FBP), hybrid iterative reconstruction (IR) (iDOSE4), and model-based IR (IMR). On arterial phase (AP) and portal venous phase (PVP) CT imaging, quantitative texture analysis of the liver parenchyma using a single-slice region of interest was performed at the level of the hepatic hilum using a filtration-histogram statistic-based method with different filter values. Texture features were compared among the three reconstruction methods and between normal livers and those from CLD patients. Additionally, we evaluated the inter- and intra-observer reliability of the CT texture analysis by calculating intraclass correlation coefficients (ICCs). RESULTS: IR techniques affect various CT texture features of the liver parenchyma. In particular, model-based IR frequently showed significant differences compared to FBP or hybrid IR on both AP and PVP CT imaging. Significant variation in entropy was observed between the three reconstruction algorithms on PVP imaging (p 0.75) for CT imaging without filtration. CONCLUSION: CT texture features of the liver parenchyma evaluated using the filtration-histogram method were significantly affected by the CT reconstruction algorithm used.