MRI for Hepatitis B-Associated Intrahepatic Cholangiocarcinoma: A Multicenter Comparative Study.

BACKGROUND: The diagnosis of intrahepatic cholangiocarcinoma (iCCA) is challenging in hepatitis B virus (HBV)-infected patients, due to the overlapping clinical manifestations and atypical imaging patterns compared to patients without HBV. PURPOSE: To investigate the preoperative imaging characteristics of iCCA in patients with HBV in comparison to those without HBV. STUDY TYPE: Retrospective. SUBJECTS: 431 patients with histopathologically confirmed iCCA (143 HBV-positive and 288 HBV-negative patients) were retrospectively enrolled from three institutes, and patients were allocated to the training (n = 302) and validation (n = 129) cohorts from different institutes or time period; 100 matching HBV-positive hepatocellular carcinoma (HCC) patients were also enrolled. FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T, including T1- and T2-weighted, diffusion-weighted and dynamic gadopentetate dimeglumine-enhanced imaging. ASSESSMENT: Clinical and MRI features were analyzed and compared between HBV-positive and HBV-negative patients with iCCA, and between HBV-positive patients with iCCA and HCC. STATISTICAL TESTS: Univariate and multivariate logistic regression analyses with odds ratio (OR) to identify independent features for discriminating HBV-associated iCCA. Diagnostic model generation by incorporating independent features, and the performance for discrimination was evaluated by receiver operating characteristics with the area under the curve (AUC) and 95% confidence interval (CI). AUCs were compared by the DeLong's method. A P-value <0.05 was considered statistically significant. RESULTS: Compared to patients without HBV, washout or degressive enhancement pattern (OR = 51.837), well-defined tumor margin (OR = 8.758) and no peritumoral bile duct dilation (OR = 4.651) were independent significant features for discriminating HBV-associated iCCAs. All these features were also the predominant MRI manifestations for HBV-associated HCC. The combined index showed an AUC of 0.798 (95% CI 0.748-0.842) in the training cohort and an AUC of 0.789 (95% CI 0.708-0.856) in the validation cohort for discrimination. The sensitivity, specificity, and accuracy were all >70%, which was superior to each single feature alone in both cohorts. [Correction added after first online publication on 29 June 2023. The Field Strength/Sequence has been updated from 5-T to 1.5-T.] DATA CONCLUSION: Preoperative MRI may help to discriminate HBV-associated iCCA. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY STAGE: 2.

A multi-center diagnostic system for intrahepatic mass-forming cholangiocarcinoma based on preoperative MRI and clinical features.

OBJECTIVES: To establish a non-invasive diagnostic system for intrahepatic mass-forming cholangiocarcinoma (IMCC) via decision tree analysis. METHODS: Totally 1008 patients with 504 pathologically confirmed IMCCs and proportional hepatocellular carcinomas (HCC) and combined hepatocellular cholangiocarcinomas (cHCC-CC) from multi-centers were retrospectively included (internal cohort n = 700, external cohort n = 308). Univariate and multivariate logistic regression analyses were applied to evaluate the independent clinical and MRI predictors for IMCC, and the selected features were used to develop a decision tree-based diagnostic system. Diagnostic efficacy of the established system was calculated by the receiver operating characteristic curve analysis in the internal training-testing and external validation cohorts, and also in small lesions ≤ 3 cm. RESULTS: Multivariate analysis revealed that female, no chronic liver disease or cirrhosis, elevated carbohydrate antigen 19-9 (CA19-9) level, normal alpha-fetoprotein (AFP) level, lobulated tumor shape, progressive or persistent enhancement pattern, no enhancing tumor capsule, targetoid appearance, and liver surface retraction were independent characteristics favoring the diagnosis of IMCC over HCC or cHCC-CC (odds ratio = 3.273-25.00, p < 0.001 to p = 0.021). Among which enhancement pattern had the highest weight of 0.816. The diagnostic system incorporating significant characteristics above showed excellent performance in the internal training (area under the curve (AUC) 0.971), internal testing (AUC 0.956), and external validation (AUC 0.945) cohorts, as well as in small lesions ≤ 3 cm (AUC 0.956). CONCLUSIONS: In consideration of the great generalizability and clinical efficacy in multi-centers, the proposed diagnostic system may serve as a non-invasive, reliable, and easy-to-operate tool in IMCC diagnosis, providing an efficient approach to discriminate IMCC from other HCC-containing primary liver cancers. CLINICAL RELEVANCE STATEMENT: This study established a non-invasive, easy-to-operate, and explainable decision tree-based diagnostic system for intrahepatic mass-forming cholangiocarcinoma, which may provide essential information for clinical decision-making. KEY POINTS: • Distinguishing intrahepatic mass-forming cholangiocarcinoma (IMCC) from other primary liver cancers is important for both treatment planning and outcome prediction. • The MRI-based diagnostic system showed great performance with satisfying generalization ability in the diagnosis and discrimination of IMCC. • The diagnostic system may serve as a non-invasive, easy-to-operate, and explainable tool in the diagnosis and risk stratification for IMCC.

Apparent Diffusion Coefficient MRI Shows Association With Early Progression of Unresectable Intrahepatic Cholangiocarcinoma With Combined Targeted-Immunotherapy.

BACKGROUND: Most intrahepatic cholangiocarcinomas (ICCs) are diagnosed at advanced stage with an extremely poor prognosis. For these patients, combining targeted therapies and immunotherapy may have a promising therapeutic effect, and current Response Evaluation Criteria in Solid Tumors (RECIST) criteria have limited applicability. PURPOSE: To investigate the associations between pretreatment MRI features and the efficacy of combined targeted-immunotherapy by estimating the risk of early progression (EP) in unresectable ICC, with special emphasis on diffusion-weighted imaging. STUDY TYPE: Retrospective. SUBJECTS: A total of 43 unresectable ICC patients (24 with EP [disease progression ≤12 months after treatment] and 19 with nonearly progression [NEP, disease progression >12 months]), who received first-line systemic therapy with lenvatinib plus PD1 antibody combination. FIELD STRENGTH/SEQUENCE: The 0-T scanner, including T1- and T2-weighted imaging, diffusion-weighted imaging, and dynamic gadopentetate dimeglumine-enhanced imaging. ASSESSMENT: Clinical characteristics and MR imaging features including apparent diffusion coefficient (ADC), as well as survival analysis of EP were evaluated. STATISTICAL TESTS: Features between EP and NEP groups were compared by univariate analyses and multivariate logistic regression analysis. Diagnostic performance was analyzed by receiver operating characteristic curve. Univariate and multivariate Cox regression models were applied for survival analysis of EP. The progression-free survival (PFS) rates were estimated using the Kaplan-Meier analysis and compared by the log-rank test. The significance threshold was set at P < 0.05. RESULTS: Tumor number, tumor margin, arterial peritumoral enhancement, lymphatic metastasis, and apparent diffusion coefficient (ADC) value were significantly different between EP and NEP groups. At multivariate logistic regression analysis, ADC was the only independent variable associated with EP (odds ratio = 0.012), with an area under the curve of 0.774 (optimal cutoff value was 1.028 × 10-3  mm2 /sec). Multivariate Cox regression model proved that ADC value (hazard ratio = 0.140) and ill-defined margin (hazard ratio = 2.784) were independent risk factors. ICCs with low ADC values showed shorter PFS than those with high values (χ2  = 9.368). DATA CONCLUSION: Pretreatment MRI features were associated with EP for unresectable ICC treated with combined targeted-immunotherapy, and decreased ADC value was an independent variable. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.

Assessment of an MR Elastography-Based Nomogram as a Potential Imaging Biomarker for Predicting Microvascular Invasion of Hepatocellular Carcinoma.

BACKGROUND: Microvascular invasion (MVI) is a well-established poor prognostic factor for hepatocellular carcinoma (HCC). Preoperative prediction of MVI is important for both therapeutic and prognostic purposes, but noninvasive methods are lacking. PURPOSE: To develop an MR elastography (MRE)-based nomogram for the preoperative prediction of MVI in HCC. STUDY TYPE: Prospective. SUBJECTS: A total of 111 patients with surgically resected single HCC (52 MVI-positive and 59 MVI-negative), randomly allocated to training and validation cohorts (7:3 ratio). FIELD STRENGTH/SEQUENCE: 2D-MRE and conventional sequences (T1-weighted in-phase and opposed phase gradient echo, T2-weighted fast spin echo, diffusion-weighted single-shot spin echo echo-planar, and dynamic contrast-enhanced T1-weighted gradient echo) at 3.0 T. ASSESSMENT: MRE-stiffness and conventional qualitative and quantitative MRI features were evaluated and compared between MVI-positive and MVI-negative HCCs. STATISTICAL TESTS: Univariable and multivariable logistic regression analyses were applied to identify potential predictors for MVI, and a nomogram was constructed according to the predictive model. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. Harrell's C-index evaluated the discrimination performance of the nomogram, calibration curves analyzed its diagnostic performance and decision curve analysis determined its clinical usefulness. A P value <0.05 was considered statistically significant. RESULTS: Tumor stiffness >6.284 kPa (odds ratio [OR] = 24.38) and the presence of arterial peritumoral enhancement (OR = 6.36) were independent variables associated with MVI. The areas under the ROC curves for tumor stiffness were 0.81 (95% confidence interval [CI]: 0.70, 0.89) and 0.77 (95% CI: 0.60, 0.90) in the training and validation cohorts, respectively. When both predictive variables were integrated, the best nomogram performance was achieved with C-indices of 0.88 (95% CI: 0.78, 0.94) and 0.87 (95% CI: 0.71, 0.96) in the two cohorts, fitting well in calibration curves. The decision curve exhibited optimal net benefit with a wide range of threshold probabilities for the nomogram. DATA CONCLUSION: An MRE-based nomogram may be a potential noninvasive imaging biomarker for predicting MVI of HCC preoperatively. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Contrast-enhanced MRI could predict response of systemic therapy in advanced intrahepatic cholangiocarcinoma.

OBJECTIVE: To investigate whether pre-treatment contrast-enhanced MRI could predict the therapeutic response of systemic treatment in advanced intrahepatic cholangiocarcinoma (ICC). METHODS: This retrospective study enrolled 61 ICC participants with contrast-enhanced MRI before combined systemic therapy. Clinical characteristics and MRI features were compared between patients with and without therapeutic response by univariate and multivariate logistic regression analyses. Then, a combined MRI-based model and the nomogram were established based on the results of the multivariate analysis. The diagnostic performances of significant findings and the combined model were evaluated and compared. The progression-free survival (PFS) rates between patients with high and low combined index values were compared. RESULTS: Thirty (49.18%) patients showed overall response after therapy. In multivariate analysis, tumor margin (odds ratio (OR) = 5.004, p = 0.014), T2 homogeneity (OR = 14.93, p = 0.019), and arterial peritumoral enhancement (OR = 5.076, p = 0.042) were independent predictive factors associated with therapeutic response. The C-index with the formulated nomogram incorporating the three independent imaging features was 0.828 (95% CI 0.710-0.913). Diagnostic characteristics of the combined index were superior to any single feature alone (p = 0.0007-0.0141). ICCs with high combined index values showed higher PFS rates than those with low values (χ2 = 13.306, p < 0.0001). CONCLUSIONS: Pre-treatment contrast-enhanced MRI can be used to predict therapeutic response in advanced ICC with systemic therapy. The combination model incorporating significant MRI features achieved an improved predictive value, which may play an important role in identifying appropriate therapeutic candidates. KEY POINTS: • Contrast-enhanced MRI can predict response of systemic therapy in advanced ICC. • MRI features of tumor margin, T2 homogeneity, and arterial peritumoral enhancement are related to therapeutic response. • The combined MRI-based model may help to identify appropriate therapeutic candidates.

Histogram analyses of diffusion kurtosis indices and apparent diffusion coefficient in assessing liver regeneration after ALPPS and a comparative study with portal vein ligation.

PURPOSE: To investigate the value of diffusion kurtosis imaging (DKI) histogram analysis in assessing liver regeneration and the microstructure basis after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), in comparison with portal vein ligation (PVL). MATERIALS AND METHODS: Thirty rats were divided into the ALPPS, PVL, and control groups. Histograms of DKI using a 3T magnetic resonance imaging (MRI) scanner were performed for corrected apparent diffusion (D), kurtosis (K), and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis, and the percentiles (5th , 25th , 50th , 75th , and 95th ) were generated and compared, and radiologic-pathologic correlations were evaluated. RESULTS: There were more significant volume increases of the right median lobe after ALPPS than PVL (P = 0.0304/0.0017). The ALPPS group had larger hepatocyte size (P = 0.009/0.000), higher Ki-67 and hepatocyte growth factor expression (P = 0.001-0.036) compared with both PVL and control groups. Mean, median, 5th , 25th , 50th , 75th percentiles of D map in ALPPS were lower than the control group (P = 0.001-0.022). Skewness and 75th , 95th percentiles of K map in ALPPS were higher than the PVL group (P = 0.011-0.042). No differences existed in the ADC map between groups (P = 0.073-0.291). Mean, median, 5th , 25th , 50th percentiles of D map, and 5th percentile of K map showed significant correlations with hepatocyte size (r = -0.582 to -0.426); no significant correlations were found in ADC parameters (P = 0.460-0.934). CONCLUSION: ALPPS induced true accelerated liver hypertrophy, superior to that seen with PVL. Histogram analysis of diffusion kurtosis indices may provide added values in evaluating liver regeneration and the intrinsic microstructure basis after ALPPS in comparison with the standard monoexponential ADC. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: Stage 2 J. Magn. Reson. Imaging 2018;47:729-736.

Assessment of liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy: a comparative study with portal vein ligation.

BACKGROUND: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) in assessing liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) compared with portal vein ligation (PVL). METHODS: Thirty rats were divided into the ALPPS, PVL, and control groups. DKI and DWI were performed before and 7 days after surgery. Corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC) were calculated and compared, radiologic-pathologic correlations were evaluated. RESULTS: The volume of the right median lobe increased significantly after ALPPS. There were larger cellular diameters after ALPPS and PVL (P = 0.0003). The proliferative indexes of Ki-67 and hepatocyte growth factor were higher after ALPPS (P = 0.0024/0.0433). D, K and ADC values differed between the groups (P = 0.021/0.0015/0.0008). A significant correlation existed between D and the hepatocyte size (r = -0.523), no correlations existed in ADC and K (P = 0.159/0.111). The proliferative indexes showed moderate negative correlations with ADC (r = -0.484/-0.537) and no correlations with D and K (P = 0.100-0.877). DISCUSSION: Liver regeneration after ALPPS was effective and superior to PVL. DKI, especially the D map, may provide added value in evaluating the microstructure of liver regeneration after ALPPS, but this model alone may perform no better than the standard monoexponential model of DWI.

Prediction of therapeutic response of advanced hepatocellular carcinoma to combined targeted immunotherapy by MRI.

PURPOSE: To assess the value of pre-treatment MRI in predicting treatment response to combined targeted immunotherapy in advanced hepatocellular carcinoma (HCC). METHODS: Totally 35 HCC participants who underwent pre-treatment contrast-enhanced MRI and received combined tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody treatment were enrolled. Univariable and multivariable logistic regression analyses were carried out for comparing clinical and MRI characteristics between patients with therapeutic response and those without. A predictive model based on MRI data and the corresponding nomogram were developed using data generated by multivariate analysis, and the diagnostic performance was evaluated. A cutoff for the combined index was measured by receiver operating characteristic curve analysis, and progression-free survival (PFS) rates were compared between cases with high and low combined index values. RESULTS: Fifteen (42.86%) cases achieved overall response during treatment. Multivariable analysis revealed that homogeneous signal (odds ratio [OR] = 13.51, P = 0.010) and no arterial peritumoral enhancement (APE; OR = 10.29, P = 0.024) independently predicted treatment response. The combined model including both significant MRI parameters showed a satisfactory predictive performance with the largest area under the curve of 0.837 (95%CI 0.673-0.939), and both sensitivity and specificity of 80.0%. HCCs with high-combined index had higher PFS rate compared with those showing a low value (P = 0.034). CONCLUSION: The combination of pre-treatment MRI features of homogeneous signal and no APE could be used for predicting treatment response to combined targeted immunotherapy in advanced HCC.

Correlation analysis of MR elastography and Ki-67 expression in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver cancer with dismal outcome, high Ki-67 expression is associated with active progression and poor prognosis of iCCA, the application of MRE in the prediction of iCCA Ki-67 expression has not yet been investigated until now. We aimed to evaluate the value of magnetic resonance elastography (MRE) in assessing Ki-67 expression for iCCA. RESULTS: In the whole cohort, 97 patients (57 high Ki-67 and 40 low Ki-67; 58 males, 39 females; mean age, 58.89 years, ranges 36-70 years) were included. At the multivariate analysis, tumor stiffness (odds ratio (OR) = 1.669 [95% CI: 1.307-2.131], p < 0.001) and tumor apparent diffusion coefficient (ADC) (OR = 0.030 [95% CI: 0.002, 0.476], p = 0.013) were independent significant variables associated with Ki-67. Areas under the curve of tumor stiffness for the identification of high Ki-67 were 0.796 (95% CI 0.702, 0.871). Tumor stiffness was moderately correlated with Ki-67 level (r = 0.593, p < 0.001). When both predictive variables of tumor stiffness and ADC were integrated, the best performance was achieved with area under the curve values of 0.864 (95% CI 0.780-0.926). CONCLUSION: MRE-based tumor stiffness correlated with Ki-67 in iCCA and could be investigated as a potential prognostic biomarker. The combined model incorporating both tumor stiffness and ADC increased the predictive performance. CRITICAL RELEVANCE STATEMENT: MRE-based tumor stiffness might be a surrogate imaging biomarker to predict Ki-67 expression in intrahepatic cholangiocarcinoma patients, reflecting tumor cellular proliferation. The combined model incorporating both tumor stiffness and apparent diffusion coefficient increased the predictive performance. KEY POINTS: • MRE-based tumor stiffness shows a significant correlation with Ki-67. • The combined model incorporating tumor stiffness and apparent diffusion coefficient demonstrated an optimized predictive performance for Ki-67 expression. • MRE-based tumor stiffness could be investigated as a potential prognostic biomarker for intrahepatic cholangiocarcinoma.

Combined arterial and delayed enhancement patterns of MRI assist in prognostic prediction for intrahepatic mass-forming cholangiocarcinoma (IMCC).

OBJECTIVES: This study valued MR delayed enhancement pattern in predicting postoperative prognosis of intrahepatic mass-forming cholangiocarcinoma (IMCC). METHODS: From 2011 to 2015, 231 patients of IMCC underwent DCE-MRI preoperatively. Enhancement patterns and MRI characteristics were evaluated. Recurrence and mortality data were compared among IMCCs with different enhancement patterns. Prognostic factor analysis was performed using preoperative and postoperative clinical-pathologic factors, as well as imaging findings. RESULTS: Fifty-six (24.2%), 142 (61.5%) and 33 (14.3%) tumors showed hypo, peripheral rim and diffuse hyper enhancement in AP. Fifty-six (24.2%), 81 (35.1%) and 94 (40.7%) tumors showed hypo, heterogeneous and uniform enhancement in DP. Patients with arterial diffuse hyper enhancement or delayed uniform enhancement IMCCs had lower preoperative CA19-9 levels, smaller tumor sizes and minor operations than the rest patients (p < 0.05) and they were less associated with lymph nodes metastasis, vascular invasion, necrosis or poor tumor differentiation (p < 0.05), therefore with higher overall and disease-free survival rates (p < 0.05). The combination of AP and DP increased the detection rate of patients with good prognosis in the arterial rim enhancement group. Multivariate analysis revealed the delayed enhancement pattern (hypo HR = 6.304/10.028 for DFS/OS; heterogenous HR = 4.579/4.972 for DFS/OS), multitude of lesions (HR = 1.6/1.5 for DFS/OS) and tumor sizes (HR = 1.6 for DFS) were independent prognostic factors. CONCLUSIONS: The uniform enhancement pattern in delayed MRI was an independent optimal prognostic factor for IMCCs and increased the detection rate of patients with good prognosis compared to the arterial diffuse hyper enhancement pattern.

MRI-based Nomogram Predicts the Risk of Progression of Unresectable Hepatocellular Carcinoma After Combined Lenvatinib and anti-PD-1 Antibody Therapy.

RATIONALE AND OBJECTIVES: Combined immune and anti-angiogenic treatment has shown promising results for unresectable hepatocellular carcinoma (HCC), but with a high risk of early progression. In this study, we aimed to investigate whether pre-treatment magnetic resonance imaging (MRI) features and MRI-based nomogram could predict the risk of disease progression of unresectable HCC after first-line lenvatinib/anti-PD-1 antibody therapy. MATERIALS AND METHODS: Thirty-seven HCC participants with qualified pre-treatment contrast-enhanced MRI were enrolled. All patients received combined lenvatinib and anti-PD-1 antibody treatment. Progression free survival rate was analyzed using the Kaplan-Meier method. Potential clinical-radiological risk factors for progression were analyzed using the log-rank tests and Cox regression model. The performance of MRI-based nomogram was evaluated based on C-index, calibration, and decision curve analyses. RESULTS: The 6-month and 12-month cumulative progression free survival rates were 59.5% (95% confidence interval (CI), 43.6%-75.4%) and 48.0% (95% CI, 31.7%-64.3%). On multivariate analysis, no or incomplete tumor capsule (hazard ratio (HR) = 15.215 [95% CI 2.707-85.529], p = 0.002), heterogeneous signal on T2-weighted imaging (HR = 28.179 [95% CI 2.437-325.838]; p = 0.008) and arterial contrast-to-noise ratio ≤95.45 (HR = 5.113 [95% CI 1.538-17.00]; p = 0.008) were independent risk factors for disease progression. Satisfactory predictive performance of the nomogram incorporating the three independent imaging features was obtained with a C-index value of 0.880 (95% CI 0.824-0.937), and the combined nomogram had more favorable clinical prediction performance than any single feature. CONCLUSION: MRI features can be considered effective predictors of disease progression for unresectable HCC with first-line lenvatinib plus anti-PD-1 antibody therapy, and the combined MRI-based nomogram achieved a superior prognostic model, which may help to identify appropriate candidates for the therapy.

A Semi-Automatic Step-by-Step Expert-Guided LI-RADS Grading System Based on Gadoxetic Acid-Enhanced MRI.

PURPOSE: Liver imaging reporting and data system (LI-RADS) classification, especially the identification of LR-3 to 5 lesions with hepatocellular carcinoma (HCC) probability, is of great significance to treatment strategy determination. We aimed to develop a semi-automatic LI-RADS grading system on multiphase gadoxetic acid-enhanced MRI using deep convolutional neural networks (CNN). PATIENTS AND METHODS: An internal data set of 439 patients and external data set of 71 patients with suspected HCC were included and underwent gadoxetic acid-enhanced MRI. The expert-guided LI-RADS grading system consisted of four deep 3D CNN models including a tumor segmentation model for automatic diameter estimation and three classification models of LI-RADS major features including arterial phase hyper-enhancement (APHE), washout and enhancing capsule. An end-to-end learning system comprising single deep CNN model that directly classified the LI-RADS grade was developed for comparison. RESULTS: On internal testing set, the segmentation model reached a mean dice of 0.84, with the accuracy of mapped diameter intervals as 82.7% (95% CI: 74.4%, 91.7%). The area under the curves (AUCs) were 0.941 (95% CI: 0.914, 0.961), 0.859 (95% CI: 0.823, 0.890) and 0.712 (95% CI: 0.668, 0.754) for APHE, washout and capsule, respectively. The expert-guided system significantly outperformed the end-to-end system with a LI-RADS grading accuracy of 68.3% (95% CI: 60.8%, 76.5%) vs 55.6% (95% CI: 48.8%, 63.0%) (P<0.0001). On external testing set, the accuracy of mapped diameter intervals was 91.5% (95% CI: 81.9%, 100.0%). The AUCs were 0.792 (95% CI: 0.745, 0.833), 0.654 (95% CI: 0.602, 0.703) and 0.658 (95% CI: 0.606, 0.707) for APHE, washout and capsule, respectively. The expert-guided system achieved an overall grading accuracy of 66.2% (95% CI: 58.0%, 75.2%), significantly higher than the end-to-end system of 50.1% (95% CI: 43.1%, 58.1%) (P<0.0001). CONCLUSION: We developed a semi-automatic step-by-step expert-guided LI-RADS grading system (LR-3 to 5), superior to the conventional end-to-end learning system. This deep learning-based system may improve workflow efficiency for HCC diagnosis in clinical practice.

Single-breath-hold T2WI liver MRI with deep learning-based reconstruction: A clinical feasibility study in comparison to conventional multi-breath-hold T2WI liver MRI.

OBJECTIVE: To investigate the clinical feasibility of single-breath-hold (SBH) T2-weighted (T2WI) liver MRI with deep learning-based reconstruction in the evaluation of image quality and lesion delineation, compared with conventional multi-breath-hold (MBH) T2WI. METHODS: One hundred and fifty-two adult patients with suspected liver disease were prospectively enrolled. Two independent readers reviewed images acquired with conventional MBH-T2WI and SBH-T2WI at 3.0 T MR scanner. For image quality analyses, motion artifacts scores and boundary sharpness scores were compared using nonparametric Wilcoxon matched pairs tests between MBH-T2WI and SBH-T2WI. With the reference standard, 89 patients with 376 index lesions were included for lesion analyses. The lesion detection rates were compared by chi-square test, the lesion conspicuity scores and lesion-liver contrast ratio (CR) were compared using nonparametric Wilcoxon matched pairs tests between the two sequences. RESULTS: For both readers, motion artifacts scores of SBH-T2WI were significantly lower than MBH-T2WI (P < 0.001). Boundary sharpness scores of SBH-T2WI were significantly higher than MBH-T2WI (P < 0.001). The lesion detection rates for SBH-T2WI were significantly higher than MBH-T2WI (P < 0.001); the differences of lesion detection rates between the two sequences were statistically significant for small (≤ 10 mm) liver lesions (P < 0.001), while not significant for larger (> 10 mm) lesions (P > 0.05). Lesion conspicuity scores were significantly higher on SBH-T2WI than MBH-T2WI in the entire cohort as well as in both stratified subgroups of lesions ≤10 mm and > 10 mm (P < 0.001 for all). CRs for focal liver lesions were also significantly higher with SBH-T2WI (P < 0.001). CONCLUSION: The SBH-T2WI sequence with deep-learning based reconstruction showed promising performance as it provided significantly better image quality, lesion detectability, lesion conspicuity and contrast within a single breath-hold, compared with the conventional MBH-T2WI.

Skewness of apparent diffusion coefficient (ADC) histogram helps predict the invasive potential of intraductal papillary neoplasms of the bile ducts (IPNBs).

OBJECTIVE: This retrospective study was to explore the value of whole lesion apparent diffusion coefficient (ADC) histogram in distinguishing invasive and noninvasive intraductal papillary neoplasms of the bile ducts (IPNBs). METHOD AND MATERIALS: Fifty-two patients of IPNB underwent MRI at 1.5T with diffusion-weighted imaging (DWI, b = 500 s/mm2) before surgical resections. ADC histogram metrics were generated by using the software MR OncoTreat. The mean, standard deviation, median, skewness, kurtosis as well as the 10th, 25th, 75th, and 90th percentiles were compared between pathologically defined invasive (n = 35) and noninvasive (n = 17) IPNBs. Such conventional imaging characters as lesion location, bile duct wall dilation, and mural nodularity were also assessed. Multivariate regression analysis as well as receiver operating characteristics (ROC) analysis were then conducted to determine the predictive factors and to evaluate potential diagnostic performances. RESULTS: The inter-operator reliability was good to excellent (ICC: 0.693-979). Mean median, kurtosis, and the 10th, 25th, 75th, 90th percentiles were all greater in noninvasive group than invasive ones (P: 0.00-002). Skewness was lower in noninvasive group than invasive ones (- 1.0 ± 0.6 vs. - 0.3 ± 0.6, P = 0.00). After multivariate regression, skewness (AUC = 0.822, 95%CI 0.70-0.91) and mural nodularity (accuracy = 0.808) were the only two independent factors in predicting invasive IPNBs. The diagnostic performance improved (AUC = 0.867, 95%CI 0.742-0.946) when combining skewness and mural nodularity, however, the difference did not reach statistical significance (P = 0.16). CONCLUSION: The ADC histogram has capability of distinguishing invasive and noninvasive IPNBs, in which skewness was an independent predictive factor.

A comparative study of MR extracellular volume fraction measurement and two-dimensional shear-wave elastography in assessment of liver fibrosis with chronic hepatitis B.

OBJECTIVE: To evaluate the value of MR liver extracellular volume (ECVliver) in assessment of liver fibrosis with chronic hepatitis B (CHB), and to compare its performance with two-dimensional (2D) shear-wave elastography (SWE). MATERIALS AND METHODS: A total of 68 CHB patients who were histologically diagnosed as fibrosis stages F0 to F4 were retrospectively analyzed. All patients underwent gadopentetate dimeglumine-enhanced T1-mapping and 2D SWE. ECVliver and liver stiffness were measured and compared between fibrosis subgroups; their correlations with histologic findings were evaluated using Spearman correlation test and multiple regression analysis. Diagnostic performance in evaluating liver fibrosis stages was assessed and compared using receiver-operating characteristic analysis. RESULTS: Both ECVliver and liver stiffness increased as the fibrosis score increased (F = 17.08 to 10.99, P < 0.001). ECVliver displayed a strong correlation with fibrosis stage (r = 0.740, P < 0.001), and liver stiffness displayed a moderate correlation (r = 0.651, P < 0.001); multivariate analysis revealed that only ECVliver was independently correlated with fibrosis stage (P < 0.001). Univariate analyses showed significant correlations of ECVliver with fibrosis stage, inflammatory activity, and platelet count; among all, the fibrosis stage had the highest correlation coefficient and was the only independent factor (P < 0.001). Overall, ECVliver had no significant different performance compared with 2D SWE for the identification of both fibrosis stage s ≥ F2 and F4 (P = 0.868 and 0.171). CONCLUSION: MR ECVliver plays a promising role in the prediction of liver fibrosis for patients with CHB, comparable to 2D SWE.

Assessing liver fibrosis in chronic hepatitis B using MR extracellular volume measurements: Comparison with serum fibrosis indices.

OBJECTIVES: To evaluate the diagnostic value of liver extracellular volume (ECVliver) measurement by equilibrium MR in staging liver fibrosis in chronic hepatitis B (CHB) patients, and to compare its performance with serum fibrosis indices. MATERIALS AND METHODS: 91 CHB patients were included and underwent gadopentetate dimeglumine-enhanced MRI with T1 mapping sequence before and 15-min after contrast. ECVliver, aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated and compared between fibrosis subgroups, and the correlations between the three indices and fibrosis stage or inflammatory activity were measured by Spearman correlation analysis and stepwise multiple regression analysis. Diagnostic performance in evaluating liver fibrosis stage was assessed and compared using receiver operating characteristic analysis. RESULTS: Interobserver agreement showed an excellent interclass correlation coefficient of 0.895 for ECVliver. ECVliver, APRI and FIB-4 were different between fibrosis stages as a whole (F/H = 18.44-24.36, P ≤ 0.001). ECVliver had the strongest correlation with fibrosis stage (r = 0.727, P < 0.001), while APRI and FIB-4 had weak correlations (r = 0.466 and 0.440, P < 0.001). Multivariate analysis showed that only ECVliver was independently correlated with fibrosis stage (P < 0.001). The fibrosis stage was the only independent factor correlated with ECVliver comparing to inflammatory activity (P < 0.001). AUCs of ECVliver were larger than both APRI and FIB-4 in fibrosis staging, with significant differences in the diagnosis of advanced fibrosis (≥F3) and cirrhosis (F4) (P = 0.0024 to 0.0049). CONCLUSION: MR ECVliver provides a promising noninvasive tool in staging liver fibrosis for CHB patients, superior to the fibrosis indices of APRI and FIB-4.

Histogram Analysis of Diffusion Kurtosis Magnetic Resonance Imaging for Diagnosis of Hepatic Fibrosis.

Objective: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) histogram analysis in hepatic fibrosis staging. Materials and Methods: Thirty-six rats were divided into carbon tetrachloride-induced fibrosis groups (6 rats per group for 2, 4, 6, and 8 weeks) and a control group (n = 12). MRI was performed using a 3T scanner. Histograms of DKI were obtained for corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis and 25th and 75th percentiles were generated and compared according to the fibrosis stage and inflammatory activity. Results: A total of 35 rats were included, and 12, 5, 5, 6, and 7 rats were diagnosed as F0-F4. The mean, median, 25th and 75th percentiles, kurtosis of D map, median, 25th percentile, skewness of K map, and 75th percentile of ADC map demonstrated significant correlation with fibrosis stage (r = -0.767 to 0.339, p < 0.001 to p = 0.039). The fibrosis score was the independent variable associated with histogram parameters compared with inflammatory activity grade (p < 0.001 to p = 0.041), except the median of K map (p = 0.185). Areas under the receiver operating characteristic curve of D were larger than K and ADC maps in fibrosis staging, although no significant differences existed in pairwise comparisons (p = 0.0512 to p = 0.847). Conclusion: Corrected apparent diffusion of DKI histogram analysis provides added value and better diagnostic performance to detect various liver fibrosis stages compared with ADC.