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.

Characterization of Microvascular Invasion in Hepatocellular Carcinoma Using Computational Modeling of Interstitial Fluid Pressure and Velocity.

BACKGROUND: Most solid tumors show increased interstitial fluid pressure (IFP), and this increased IFP is an obstacle to treatment. A noninvasive model for measuring IFP in hepatocellular carcinoma (HCC) is an unresolved issue. PURPOSE: To develop a noninvasive model to measure IFP and interstitial fluid velocity (IFV) in HCC and to characterize the microvascular invasion (MVI) status by using this model. STUDY TYPE: Retrospective. POPULATION: A total of 97 HCC patients (mean age 57.6 ± 10.9 years, 77.3% males), 53 of them with MVI and 44 of them without MVI. FIELD STRENGTH/SEQUENCE: A 3-T, three-dimensional spoiled gradient-recalled echo. ASSESSMENT: MVI was defined as microscopic vascular invasion of small vessels within the peritumoral liver tissue. The volumes of interest (VOIs) were manually delineated and enclosed the tumor lesion and healthy liver parenchyma, respectively. The extended Tofts model (ETM) was used to estimate permeability parameters from all the VOIs. Subsequently, the continuity partial differential equation (PDE) was implemented and IFP and IFV were acquired. STATISTICAL TESTS: Wilcoxon signed-ranks tests, histogram analysis, Mann-Whitney U test, Fisher's exact test, least absolute shrinkage and selection operator (LASSO) logistic regression, receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC), Youden index, DeLong test, and Benjamini-Hochberg correction. A P value <0.05 was considered statistically significant. RESULTS: The HCC lesions exhibited elevated IFP and reduced IFV. There were no significant differences in any measured demographic and clinical features between the MVI-positive and MVI-negative groups, except for tumor size. Nine IFP histogram analysis-derived parameters and seven IFV histogram analysis-derived parameters could be used to characterize the MVI status. LASSO regression selected five features: IFP maximum, IFP 10th percentile, IFP 90th percentile, IFV SD, and IFV 10th percentile. The combination of these features showed the highest AUC (0.781) and specificity (77.3%). DATA CONCLUSION: A noninvasive IFP and IFV measurement model for HCC was developed. Specific IFP- and IFV-derived parameters exhibited significant association with the MVI status. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

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.

Predicting the recurrence of hepatocellular carcinoma (≤ 5 cm) after resection surgery with promising risk factors: habitat fraction of tumor and its peritumoral micro-environment.

PURPOSE: Characterizing the composition of hepatocellular carcinoma (HCC) and peritumoral micro-environment may provide sensitive biomarkers. We aimed to predict the recurrence-free survival (RFS) of HCC (≤ 5 cm) with habitat imaging of HCC and its peritumoral micro-environment. MATERIAL AND METHODS: A total of 264 patients with HCC were included. Taking advantage of the enhancement ratio at the arterial and hepatobiliary phase of contrast-enhanced MRI, all HCCs and their peritumoral tissue of 3 mm and 4 mm were encoded with different habitats. Besides, the quantitative fraction of each habitat of HCC and peritumoral tissue were calculated. Univariable and multivariable Cox regression analysis was performed to select the prognostic factors. The nomogram-based predictor was established. Kaplan-Meier analysis was conducted to stratify the recurrence risk. Fivefold cross-validation was performed to determine the predictive performance with the concordance index (C-Index). Decision curve analysis was used to evaluate the net benefit. RESULTS: Qualitatively, the spatial distribution of the habitats varied for different survival outcomes. Quantitatively, the fraction of habitat 3 in peritumoral tissue of 4 mm (f3-P4) was selected as independent risk factors (OR = 89.2, 95% CI = 14.5-549.2, p < 0.001) together with other two clinical variables. Integrating both clinical variables and f3-P4, a nomogram was constructed and showed high predictive efficacy (C-Index: 0.735, 95% CI 0.617-0.854) and extra net benefit according to the decision curve. Furthermore, patients with low f3-P4 or risk score given by nomogram have far longer RFS than those with high f3-P4 or risk score (stratification by f3-P4: 131.9 vs 55.0 months and stratification by risk score:131.9 vs 34.1 months). CONCLUSION: Habitat imaging of HCC and peritumoral microenvironment can be used for effectively and non-invasively estimating the RFS, which holds potential in guiding clinical management and decision making.

The significance of the predominant component in combined hepatocellular-cholangiocarcinoma: MRI manifestation and prognostic value.

PURPOSE: To investigate the significance of the predominant component of combined hepatocellular-cholangiocarcinoma (cHCC-CC) in terms of MRI manifestation and its potential prognostic value compared to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: A total of 300 patients with chronic liver disease from two centers were retrospectively enrolled, including 100 surgically proven cases of cHCC-CC, HCC, and ICC each. Univariate and multivariate regression analyses were performed to identify independent predictors for distinguishing HCC-predominant cHCC-CC and ICC-predominant cHCC-CC from HCC and ICC, respectively. Diagnostic models were constructed based on the independent features. Recurrence-free survival (RFS) was estimated and compared between groups. RESULTS: The predominant component was an independent predictor for RFS in cHCC-CC (hazard ratio = 1.957, P = 0.044). The presence of targetoid appearance (odds ratio(OR) = 10.907, P = 0.001), lack of enhancing capsule (OR = 0.072, P = 0.001) and arterial peritumoral enhancement (OR = 0.091, P = 0.003) were independent predictors suggestive of HCC-predominant cHCC-CC over HCC; their combination yielded an area under the curve of 0.756. No significant differences were observed in RFS between HCC-predominant cHCC-CC and HCC (P = 0.864). Male gender (OR = 4.049, P = 0.015), higher alpha fetoprotein (OR = 16.789, P < 0.001) and normal carbohydrate antigen 19-9 (OR = 0.343, P = 0.036) levels, presence of enhancing capsule (OR = 7.819, P < 0.001) and hemorrhage (OR = 23.526, P = 0.004), and lack of targetoid appearance (OR = 0.129, P = 0.005) and liver surface retraction (OR = 0.190, P = 0.021) were independent predictors suggestive of ICC-predominant cHCC-CC over ICC; their combination yielded an area under the curve value of 0.898. ICC-predominant cHCC-CC exhibited poorer survival with shorter RFS than ICC (P = 0.009). CONCLUSION: The predominant histopathological component is closely related to the imaging manifestation of cHCC-CC; and more importantly, it plays a significant prognostic role, which may alter the RFS prognosis of cHCC-CC.

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.

Multi-scale and multi-parametric radiomics of gadoxetate disodium-enhanced MRI predicts microvascular invasion and outcome in patients with solitary hepatocellular carcinoma ≤ 5 cm.

OBJECTIVES: To develop radiomics-based nomograms for preoperative microvascular invasion (MVI) and recurrence-free survival (RFS) prediction in patients with solitary hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS: Between March 2012 and September 2019, 356 patients with pathologically confirmed solitary HCC ≤ 5 cm who underwent preoperative gadoxetate disodium-enhanced MRI were retrospectively enrolled. MVI was graded as M0, M1, or M2 according to the number and distribution of invaded vessels. Radiomics features were extracted from DWI, arterial, portal venous, and hepatobiliary phase images in regions of the entire tumor, peritumoral area ≤ 10 mm, and randomly selected liver tissue. Multivariate analysis identified the independent predictors for MVI and RFS, with nomogram visualized the ultimately predictive models. RESULTS: Elevated alpha-fetoprotein, total bilirubin and radiomics values, peritumoral enhancement, and incomplete or absent capsule enhancement were independent risk factors for MVI. The AUCs of MVI nomogram reached 0.920 (95% CI: 0.861-0.979) using random forest and 0.879 (95% CI: 0.820-0.938) using logistic regression analysis in validation cohort (n = 106). With the 5-year RFS rate of 68.4%, the median RFS of MVI-positive (M2 and M1) and MVI-negative (M0) patients were 30.5 (11.9 and 40.9) and > 96.9 months (p < 0.001), respectively. Age, histologic MVI, alkaline phosphatase, and alanine aminotransferase independently predicted recurrence, yielding AUC of 0.654 (95% CI: 0.538-0.769, n = 99) in RFS validation cohort. Instead of histologic MVI, the preoperatively predicted MVI by MVI nomogram using random forest achieved comparable accuracy in MVI stratification and RFS prediction. CONCLUSIONS: Preoperative radiomics-based nomogram using random forest is a potential biomarker of MVI and RFS prediction for solitary HCC ≤ 5 cm. KEY POINTS: • The radiomics score was the predominant independent predictor of MVI which was the primary independent risk factor for postoperative recurrence. • The radiomics-based nomogram using either random forest or logistic regression analysis has obtained the best preoperative prediction of MVI in HCC patients so far. • As an excellent substitute for the invasive histologic MVI, the preoperatively predicted MVI by MVI nomogram using random forest (MVI-RF) achieved comparable accuracy in MVI stratification and outcome, reinforcing the radiologic understanding of HCC angioinvasion and progression.

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.

Value of MRI morphologic features with pT1-2 rectal cancer in determining lymph node metastasis.

BACKGROUND AND OBJECTIVES: To investigate the different features between metastatic lymph node and nonmetastatic lymph node on magnetic resonance imaging (MRI) and the relationship between the rectal lesion and lymph node metastasis (LNM). METHODS: Eighty-two patients with retrospectively consecutive pT1-2 stage rectal cancer in 2016 were divided into lymph node metastasis (LNM+) and lymph node nonmetastasis (LNM-) group based on their histopathologic examinations. We evaluated the following features of lymph nodes: number, shape, signal heterogeneity, border, and diameter of the largest lymph node on T2-weight images. We also calculated tumor apparent diffusion coefficient ratio and tumor percent enhancement. Fisher's exact test was applied for inspecting lymph node numbers on MRI and logistic regression analysis in examining risk factors for LNM. RESULTS: The MR-LN number was significantly different between the LNM+ and LNM- group (median: 4 vs 1, P = 0.001). Multivariate logistic regression analysis exhibited that the diameter of the largest lymph node and the tumor percent enhancement of the arterial phase were independent risk factors of LNM (P = 0.005 vs 0.021, respectively). CONCLUSIONS: The largest lymph node's diameter and the tumor percent enhancement of arterial phase on MRI were helpful in determining LNM in pT1-2 rectal cancer.

Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Delineation of Focal Nodular Hyperplasia: Superiority of High-Flip-Angle Imaging.

OBJECTIVE: The aim of this study was to investigate whether hepatobiliary-phase (HBP) flip-angle (FA) increase to 25° improves conspicuity of focal nodular hyperplasia (FNH) and enables HBP delay reduction. METHODS: This was a retrospective study of 23 patients with 46 FNHs. In each patient, HBP was performed with reduced-delay high FA (early/high), standard-delay high FA (late/high), and standard-delay standard FA (standard). Relative enhancement of liver and FNH periphery, FNH periphery-to-liver contrast ratio, and FNH periphery-to-central scar contrast ratio were compared between each HBP. RESULTS: Early/high, late/high, and standard HBPs were performed after 13.00 ± 2.12, 19.12 ± 3.10, and 19.68 ± 3.22 minutes, respectively. Liver and FNH periphery relative enhancement, FNH periphery-to-liver contrast ratio, and FNH periphery-to-central scar contrast ratio were higher for early/high and late/high than for standard HBP (P < 0.001 to P = 0.0048). CONCLUSIONS: Increasing FA to 25° improves delineation of FNHs in HBP. Combining FA increase with delay reduction is superior to standard HBP and is sufficient for FNH characterization.

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.

Staging liver fibrosis in chronic hepatitis B with T1 relaxation time index on gadoxetic acid-enhanced MRI: Comparison with aspartate aminotransferase-to-platelet ratio index and FIB-4.

PURPOSE: To assess the accuracy of the T1 relaxation time index on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B (CHB), in comparison and combination with the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4). MATERIALS AND METHODS: A retrospective study of gadoxetic acid-enhanced T1 mapping and serum biochemical tests was performed on 126 CHB patients who underwent gadoxetic acid-enhanced 1.5T MRI, and the histological score used as the gold standard. The reduction rate of T1 relaxation time before and 20 minutes after gadoxetic acid injection (ΔT1 , ΔR1%), the contrast uptake rate (KHep ), APRI, and FIB-4 were calculated. The diagnostic efficacy of ΔT1 , ΔR1%, KHep , APRI, and FIB-4 for predicting stage 2 or greater (≥S2), stage 3 or greater (≥S3), and stage 4 (S4) was compared. RESULTS: ΔT1 (r = -0.513, P < 0.001), ΔR1% (r = -0.626, P < 0.001), KHep (r = -0.527, P < 0.001), APRI (r = 0.519, P < 0.001), and FIB-4 (r = 0.476, P < 0.001) correlated significantly with fibrosis stages. Areas under the curves (AUCs) of ΔR1% for detecting ≥S2, ≥S3, and S4 were 0.849, 0.827, and 0.809, which were greater than that of APRI (0.763, 0.745, 0.787) and FIB-4 (0.727, 0.738, 0.772), but significant difference was found only in discriminating ≥S2 between ΔR1% and FIB-4 (P = 0.027). The combination of all five indices performed best, with AUC, sensitivity, and specificity of 0.860, 87.21%, and 72.50% for diagnosing ≥S2, 0.878, 82.81%, and 85.48% for ≥S3, and 0.867, 80.00%, and 83.95% for S4. CONCLUSION: The gadoxetic acid-enhanced T1 relaxation time index appears to be superior to APRI and FIB-4 for predicting hepatic fibrosis. The combined use of gadoxetic acid-enhanced T1 mapping, APRI, and FIB-4 may be more reliable for staging liver fibrosis in CHB. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:1186-1194.

Role of MR in the differentiation of IgG4-related from non-IgG4-related hepatic inflammatory pseudotumor.

BACKGROUND: Hepatic inflammatory pseudotumor (IPT) is classified into 2 types based on IgG4 stain: IgG4-related and non-IgG4-related; the two types differ not only in their pathological characteristics, but also in the clinical features. This study aimed to investigate the MR character of hepatic IPT, and differentiate the IgG4-related IPT from the non-IgG4-related IPT. METHODS: Twenty-five patients with 27 histologically proven hepatic IPTs were retrospectively analyzed. Ten lesions were diagnosed as IgG4-related IPT, and the other 17 as non-IgG4-related IPT. The MR signal features on T1, T2-weighted, dynamic-enhanced, and diffusion-weighted imaging were evaluated and compared. RESULTS: The dominant lesions were subcapsularly distributed (n=17, 63.0%) with clear boundary (n=20, 74.1%), and showed progressive enhancement pattern (n=21, 77.8%) with diffuse homogeneous (n=12, 44.4%) or heterogeneous (n=8, 29.6%) hyperintensity, accompanied by delayed capsule-like enhancement (n=17, 63.0%) and central nonenhanced areas (n=18, 66.7%). Morphological features (P>0.05) were not sufficient to differentiate IgG4-related IPT from non-IgG4-related IPT; the wash-out pattern was only found in 2 IgG4-related IPT, while the progressive enhancement pattern was more common in the non-IgG4-related lesions (n=16) (P=0.022). During portal and delayed phases, iso-/hypoenhanced lesions were only seen in 3 IgG4-related IPT, and circular-enhanced lesions (n=5) existed exceptionally in the non-IgG4-related group with significant differences (P=0.029 and 0.027). Most IgG4-related IPTs had lower apparent diffusion coefficient compared with the liver parenchyma (n=6), while most non-IgG4-related IPTs had higher apparent diffusion coefficient value (n=13) (P=0.046). CONCLUSIONS: Although MR images of hepatic IPT have certain characteristics, they are not enough to differentiate IgG4-related IPT from non-IgG4-related IPT. The enhancement pattern, signal features on portal and delayed phases, and the apparent diffusion coefficient value of the lesion may be helpful for the diagnosis.

Intrahepatic distant recurrence following complete radiofrequency ablation of small hepatocellular carcinoma: risk factors and early MRI evaluation.

BACKGROUND: Radiofrequency ablation (RFA) is related to a high intrahepatic distant recurrence (IDR) rate, and the associations between IDR and relevant imaging features have not yet been fully investigated. This study aimed to determine both clinical and imaging risk factors of IDR after complete RFA for HBV-related small hepatocellular carcinoma (HCC) (≤ 3 cm). METHODS: Thirty-five patients (29 men and 6 women; mean age 60.7 years) with 40 HBV-related small HCCs who underwent complete RFA were included in our study. The incidence and potential clinical and MR imaging risk factors for IDR after RFA were assessed using the Kaplan-Meier method, the log-rank test and a stepwise Cox hazard model. RESULTS: The median follow-up period was 25 (4-45) months, and IDR was observed in 20 (57.1%) patients. The 12- and 24-month cumulative IDR-free survival rates were 76.7% and 61.3%, respectively. Univariate analysis revealed that pretreatment albumin < 3.5 g/dL (P = 0.026), multinodular tumor (P = 0.032), ablative margin < 3 mm (P = 0.007), no or disrupted periablational enhancement within 24 hours (P = 0.001) and at 1 month (P = 0.043) after RFA, and hyperintensity of the central ablative zone on T1-weighted images (T1WI) at 1 month after RFA (P = 0.004) were related to IDR. Multivariate analysis showed that pretreatment albumin < 3.5 g/dL (P = 0.032), multinodular tumor (P = 0.012), no or disrupted periablational enhancement within 24 hours after RFA (P = 0.001), and hyperintensity of the central ablative zone on T1WI at 1 month after RFA (P = 0.003) were independent risk factors for IDR. During the 1-month follow-up, the apparent diffusion coefficient exhibited an up-and-down evolution without significant value in the prediction of IDR following RFA. CONCLUSIONS: Patients with HBV-related small HCC had a high IDR rate after RFA. The risk factors included low serum albumin, multiple nodules, lesions with no or disrupted periablational enhancement and persistent hyperintensity in the central ablative zone on T1WI within 1 month after RFA.

MR imaging of primary hepatic neuroendocrine neoplasm and metastatic hepatic neuroendocrine neoplasm: a comparative study.

PURPOSE: To investigate MR characteristics in differentiating primary hepatic neuroendocrine neoplasm (PHNEN) from metastatic hepatic neuroendocrine neoplasm (MHNEN). MATERIALS AND METHODS: Thirty-nine patients with histopathologically proven liver neuroendocrine neoplasm were retrospectively analyzed. The morphological and MR signal features on T1, T2-weighted, dynamic-enhanced, and diffusion-weighted imaging were evaluated and compared between the PHNEN group (n = 12) and the MHNEN group (n = 27). RESULTS: The tumor size (P = 0.0084), number (P = 0.017), distribution (P = 0.000), contour (P = 0.041), the presence of capsule-like enhancement (P = 0.034), tumor homogeneity (P = 0.018) and the apparent diffusion coefficient (ADC) values (P = 0.024) were different between PHNENs and MHNENs. Large, solitary or massive-growing nodules with lobulated or irregular contour, capsule-like enhancement, heterogeneous signals or lower ADC values supported the diagnosis of PHNEN compared with MHNEN. ROC analysis demonstrated an area under the curve of 0.746, when the optimal cutoff value of 1.049 × 10(-3) mm(2)/s was used, a sensitivity of 63.0 % (95 % CI, 44.2-79.4 %), a specitivity of 80.0 % (95 % CI, 50.1-96.4 %), a positive predictive value of 89.5 % (95 % CI, 70.9-98.2 %), and a negative predictive value of 44.4 % (95 % CI, 23.4-67.0 %) can be achieved. CONCLUSIONS: MRI may provide valuable information for the diagnosis and differential diagnosis of PHNENs and MHNENs.

[Correlation analysis of magnetic resonance imaging characteristics and intrahepatic recurrence of small hepatocellular carcinoma after radiofrequency ablation].

OBJECTIVE: To investigate the correlation between magnetic resonance imaging (MRI) characteristics and intrahepatic recurrence of small hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). METHODS: A total of 34 patients with 39 small HCC who underwent RFA were included in our study.MRI characteristics were compared between the recurrence group and the non-recurrence group; and a subgroup comparison was also made between the solitary recurrence group and the multiple recurrence group.Kaplan-Meier test,t-test/Mann-Whitney U test,Fisher's exact test and F-test were used for statistical analyses. RESULTS: The median follow-up period was 25 (4-45) months and recurrence was observed in 19 (55.9%) of the patients.The 12-and 24-month cumulative recurrence-free survival rates were 71.3% and 51.8%,respectively.The recurrence group had a higher prevalence of lack of tumour capsule before RFA (P =0.017),no or disrupted periablational enhancement within 24 hours after RFA (P =0.012),and a smaller ablative margin (P=0.037).Meanwhile,the average apparent diffusion coefficient value within 24 hours after RFA was higher in the multiple recurrence group (1.57 * 10-3mm2/s) than in the solitary recurrence group (1.34 * 10(-3) mm2/s) (P =0.04). CONCLUSION: MRI can provide early noninvasive findings useful for advanced warning ofintrahepatic recurrence after RFA.

Detecting microvascular invasion in hepatocellular carcinoma using the impeded diffusion fraction technique to sense macromolecular coordinated water.

OBJECTIVES: Impeded diffusion fraction (IDF) is a novel and promising diffusion-weighted imaging (DWI) technique that allows for the detection of various diffusion compartments, including macromolecular coordinated water, free diffusion, perfusion, and cellular free water. This study aims to investigate the clinical potential of IDF-DWI in detecting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: 66 patients were prospectively included. Metrics derived from IDF-DWI and the apparent diffusion coefficient (ADC) were calculated. Multivariate logistic regression was employed to identify clinical risk factors. Diagnostic performance was evaluated using the area under the receiver operating characteristics curve (AUC-ROC), the area under the precision-recall curve (AUC-PR), and the calibration error (cal-error). Additionally, a power analysis was conducted to determine the required sample size. RESULTS: The results suggested a significantly higher fraction of impeded diffusion (FID) originating from IDF-DWI in MVI-positive HCCs (p < 0.001). Moreover, the ADC was found to be significantly lower in MVI-positive HCCs (p = 0.019). Independent risk factors of MVI included larger tumor size and elevated alpha-fetoprotein (AFP) levels. The nomogram model incorporating ADC, FID, tumor size, and AFP level yielded the highest diagnostic accuracy for MVI (AUC-PR = 0.804, AUC-ROC = 0.783, cal-error = 0.044), followed by FID (AUC-PR = 0.693, AUC-ROC = 0.760, cal-error = 0.060) and ADC (AUC-PR = 0.570, AUC-ROC = 0.651, cal-error = 0.164). CONCLUSION: IDF-DWI shows great potential in noninvasively, accurately, and preoperatively detecting MVI in HCC and may offer clinical benefits for prognostic prediction and determination of treatment strategy.

The value of varying diffusion curvature MRI for assessing the microvascular invasion of hepatocellular carcinoma.

PURPOSE: Varying diffusion curvature (VDC) MRI is an emerging diffusion-weighted imaging (DWI) technique that can capture non-Gaussian diffusion behavior and reflect tissue heterogeneity. However, its clinical utility has hardly been evaluated. We aimed to investigate the value of the VDC technique in noninvasively assessing microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: 74 patients with HCCs, including 39 MVI-positive and 35 MVI-negative HCCs were included into this prospective study. Quantitative metrics between subgroups, clinical risk factors, as well as diagnostic performance were evaluated. The power analysis was also carried out to determine the statistical power. RESULTS: MVI-positive HCCs exhibited significantly higher VDC-derived structural heterogeneity measure, D1 (0.680 ± 0.100 × 10-3 vs 0.572 ± 0.148 × 10-3 mm2/s, p = 0.001) and lower apparent diffusion coefficient (ADC) (1.350 ± 0.166 × 10-3 vs 1.471 ± 0.322 × 10-3 mm2/s, p = 0.0495) compared to MVI-negative HCCs. No statistical significance was observed for VDC-derived diffusion coefficient, D0 between the subgroups (p = 0.562). Tumor size (odds ratio (OR) = 1.242) and alpha-fetoprotein (AFP) (OR = 2.527) were identified as risk factors for MVI. A predictive nomogram was constructed based on D1, ADC, tumor size, and AFP, which exhibited the highest diagnostic accuracy (AUC = 0.817), followed by D1 (AUC = 0.753) and ADC (AUC = 0.647). The diagnostic performance of the nomogram-based model was also validated by the calibration curve and decision curve. CONCLUSION: VDC can aid in the noninvasive and preoperative diagnosis of HCC with MVI, which may result in the clinical benefit in terms of prognostic prediction and clinical decision-making.