Preoperative Gadoxetic Acid-Enhanced MRI Features for Evaluation of Vessels Encapsulating Tumor Clusters and Microvascular Invasion in Hepatocellular Carcinoma: Creating Nomograms for Risk Assessment.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) and microvascular invasion (MVI) have a synergistic effect on prognosis assessment and treatment selection of hepatocellular carcinoma (HCC). Preoperative noninvasive evaluation of VETC and MVI is important. PURPOSE: To explore the diagnosis value of preoperative gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) features for MVI, VETC, and recurrence-free survival (RFS) in HCC. STUDY TYPE: Retrospective. POPULATION: 240 post-surgery patients with 274 pathologically confirmed HCC (allocated to training and validation cohorts with a 7:3 ratio) and available tumor marker data from August 2014 to December 2021. FIELD STRENGTH/SEQUENCE: 3-T, T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT: Three radiologists subjectively reviewed preoperative MRI, evaluated clinical and conventional imaging features associated with MVI+, VETC+, and MVI+/VETC+ HCC. Regression-based nomograms were developed for HCC in the training cohort. Based on the nomograms, the RFS prognostic stratification system was further. Follow-up occurred every 3-6 months. STATISTICAL TESTS: Chi-squared test or Fisher's exact test, Mann-Whitney U-test or t-test, least absolute shrinkage and selection operator-penalized, multivariable logistic regression analyses, receiver operating characteristic analysis, Harrell's concordance index (C-index), Kaplan-Meier plots. Significance level: P < 0.05. RESULTS: In the training group, 44 patients with MVI+ and 74 patients with VETC+ were histologically confirmed. Three nomograms showed good performance in the training (C-indices: MVI+ vs. VETC+ vs. MVI+/VETC+, 0.892 vs. 0.848 vs. 0.910) and validation (C-indices: MVI+ vs. VETC+ vs. MVI+/VETC+, 0.839 vs. 0.810 vs. 0.855) cohorts. The median follow-up duration for the training cohort was 43.6 (95% CI, 35.0-52.2) months and 25.8 (95% CI, 16.1-35.6) months for the validation cohort. Patients with either pathologically confirmed or nomogram-estimated MVI, VETC, and MVI+/VETC+ suffered higher risk of recurrence. DATA CONCLUSION: GA-enhanced MRI and clinical variables might assist in preoperative estimation of MVI, VETC, and MVI+/VETC+ in HCC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Diagnostic Model for Proliferative HCC Using LI-RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI-ICI Combination.

BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). FIELD STRENGTH/SEQUENCE: 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. ASSESSMENT: LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). DATA CONCLUSION: The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. TECHNICAL EFFICACY: Stage 2.

A multivariate model based on gadoxetic acid-enhanced MRI using Li-RADS v2018 and other imaging features for preoperative prediction of dual­phenotype hepatocellular carcinoma.

OBJECTIVE: To investigate the diagnostic value of liver imaging reporting and data system (LI-RADS) v2018 and other imaging features in dual-phenotype hepatocellular carcinoma (DPHCC), establish a prediagnostic model based on gadoxetic acid-enhanced MRI, and explore the prognostic significance after surgery of the DPHCC. MATERIALS AND METHODS: Preoperative enhanced MRI findings and the clinical and pathological data of patients with surgically confirmed HCC were analysed retrospectively. Image analysis was based on LI-RADS v2018 and other image features. Univariate analysis was used to screen for predictive factors of DPHCC, and multivariate logistic regression analysis was used to determine the predictive factors. A regression diagnostic model was established. Receiver operating characteristic (ROC) curve analysis was used to determine the critical value, area under curve (AUC), and the corresponding 95% confidence interval (95% CI). The diagnostic performance was verified by fivefold cross-validation. Cox regression analysis was used to determine the prognostic factors associated with early recurrence after surgical resection. RESULTS: In total, 158 patients were included, of whom 79 had DPHCC and 79 had non-DPHCC. Multivariate analysis showed that rim arterial phase hyperenhancement (Rim APHE) and targetoid restriction were independent risk factors for DPHCC (P < 0.05). The AUC (95% CI) of the model was 0.862 (0.807-0.918), sensitivity was 81.01%, and specificity was 89.874%. Cox regression analysis showed that DPHCC, microvascular invasion, tumour diameter, and an increase of alpha-fetoprotein were independent factors for recurrence. CONCLUSION: Rim APHE and targetoid restriction were sensitive imaging features of DPHCC before surgery, and the identification of DPHCC has important prognostic significance for early recurrence.

Patient Controlled Subcutaneous Analgesia of Hydromorphone Versus Morphine to Treat Moderate and Severe Cancer Pain: A Randomized Double-Blind Controlled Trial.

CONTEXT: Hydromorphone and morphine are the common drugs used for the treatment of moderate to severe cancer pain. Patient controlled subcutaneous analgesia (PCSA) is an effective technique to manage cancer pain. However, few studies have been conducted to show the efficacy and safety of PCSA of hydromorphone for the relief of cancer pain. OBJECTIVES: To explore the short-term efficacy and safety of PCSA elicited by hydromorphone for moderate to severe cancer pain. METHODS: This was a single-center, randomized, active-controlled, double-blind trial (from April 2019 to August 2021). Sixty patients with moderate to severe cancer pain were randomized (1:1) to hydromorphone or morphine groups according to drug delivery by PCSA. The primary outcome was the pain intensity measured by a numerical rating scale (NRS) at 72 hours. Secondary outcomes included pain intensity measured by NRS at baseline, 15 minutes, 30 minutes, two hours, eight hours, 24 hours and 48 hours. The daily occurrence of breakthrough pain (BTP), impact of pain on quality of life measured by the brief pain inventory (BPI), the daily additional consumption of opioids and the incidence of adverse events were also recorded. Adverse events included nausea, vomiting, dizziness, constipation and respiratory depression. RESULTS: A total of 57 patients (28 patients in the hydromorphone group and 29 patients in the morphine group) in the West China Hospital of Sichuan University were investigated. The mean (standard deviation [SD]) NRS in the two groups at baseline was 7.8 (1.7) in the hydromorphone group and 7.6 (1.7) in the morphine group, and at 72 hours were 3.4 (1.8) and 3.2 (1.5), respectively. The postoperative NRS in both groups was decreased significantly compared to baseline. The mean (SD) NRS at 30 minutes in the hydromorphone group was significantly lower than in the morphine group (3.9 [2.6] vs. 5.3 [2.1], P = 0.035). The daily occurrence of BTP in both groups at 48 hours and 72 hours decreased significantly compared to the corresponding baseline (P < 0.05), and there was no significant difference between the two groups. The total scores and sub-item scores of BPI at 24 hours and 72 hours after PCSA in both groups decreased significantly from baseline. A comparison of daily additional consumption of opioids between the two groups revealed no statistically significant difference. There were no significant differences in the incidences of nausea, vomiting, dizziness or constipation between the two groups (P > 0.05). CONCLUSION: This study found that the PCSA of both hydromorphone and morphine could effectively and safely relieve short-term moderate to severe cancer pain. Of note, the PCSA of hydromorphone took effect more quickly than that of morphine.

Gadoxetic Acid-Enhanced MRI-Based Radiomic Models for Preoperative Risk Prediction and Prognostic Assessment of Proliferative HCC.

RATIONALE AND OBJECTIVES: Proliferative hepatocellular carcinoma (HCC) is associated with high invasiveness and poor prognosis. This study aimed to investigate the preoperative risk prediction and prognostic value of different radiomics models and a nomogram for proliferative HCC. MATERIALS AND METHODS: Patients were randomly divided into a training cohort (n = 156) and a validation cohort (n = 66) in a 7:3 ratio. Original and delta (the different value between imaging features extracted from two different phases) radiomics features were extracted from T1-weighted imaging (T1WI), arterial, and hepatobiliary phases to construct models using different machine learning algorithms. Logistic regression was used to select clinical independent risk factors. A nomogram was constructed by integrating the optimal radiomics model score with independent risk factors. The diagnostic efficacy and clinical utility of the models were assessed. Subsequently, patients were stratified into high-risk and low-risk subgroups based on radiomics model scores and nomogram scores, and both recurrence-free survival (RFS) and overall survival (OS) were evaluated. RESULTS: Multivariate logistic regression analysis showed that BCLC stage and combined radscore were independent predictors of proliferative HCC. The area under the curve (AUC) of the nomogram incorporating these factors was 0.838 and 0.801 in the training and validation cohorts, respectively, with good predictive performance. Multivariate Cox regression analysis shows that the delta radiomics model (DR)-predicted proliferative HCC can independently predict RFS and OS, with scores from the delta radiomics model performing best in prognostic risk stratification. CONCLUSION: The nomogram can effectively predict proliferative HCC, while different radiomics models and the nomogram can offer varying prognostic stratification values.

Radiomics analysis of gadoxetic acid-enhanced MRI for evaluating vessels encapsulating tumour clusters in hepatocellular carcinoma.

Purpose: The aim of this study was to develop an integrated model that combines clinical-radiologic and radiomics features based on gadoxetic acid-enhanced MRI for preoperative evaluating of vessels encapsulating tumour clusters (VETC) patterns in hepatocellular carcinoma (HCC). Methods: This retrospective study encompassed 234 patients who underwent surgical resection. Among them, 101 patients exhibited VETC-positive HCC, while 133 patients displayed VETC-negative HCC. Volumes of interest were manually delineated for entire tumour regions in the arterial phase (AP), portal phase (PP), and hepatobiliary phase (HBP) images. Independent predictors for VETC were identified through least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis, utilising radiomics-AP, PP, HBP, along with 24 imaging features and 19 clinical characteristics. Subsequently, the clinico-radiologic model, radiomics model, and integrated model were established, with a nomogram visualising the integrated model. The performance for VETC prediction was evaluated using a receiver operating characteristic curve. Results: The integrated model, composed of 3 selected traditional imaging features (necrosis or severe ischemia [OR=2.457], peripheral washout [OR=1.678], LLR_AP (Lesion to liver ratio_AP) [OR=0.433] and radiomics-AP [OR=2.870], radiomics-HBP [OR=2.023], radiomics-PP [OR=1.546]), showcased good accuracy in predicting VETC patterns in both the training (AUC=0.873, 95% confidence interval [CI]: 0.821-0.925)) and validation (AUC=0.869, 95% CI:0.789-0.950) cohorts. Conclusion: This study established an integrated model that combines traditional imaging features and radiomic features from gadoxetic acid-enhanced MRI, demonstrating good performance in predicting VETC patterns.

Prediction for Aggressiveness and Postoperative Recurrence of Hepatocellular Carcinoma Using Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To investigate the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) features on the pathologic grade, microvascular invasion (MVI), and cytokeratin-19 (CK19) expression in hepatocellular carcinomas (HCC), and to evaluate their association with postoperative recurrence of HCC. MATERIALS AND METHODS: This retrospective study included 147 patients with surgically confirmed HCCs who underwent gadoxetic-enhanced MRI. The lesions were evaluated quantitatively in terms of the relative enhancement ratio (RER), and qualitatively based on imaging features and clinical parameters. Logistic regression analyses were performed to investigate the value of these parameters in predicting the pathologic grade, MVI, and CK19 in HCC. Predictive factors for postoperative recurrence were determined using a Cox proportional hazards model. RESULTS: Peritumoral enhancement (odds ratio [OR], 3.396; p = 0.025) was an independent predictor of high pathologic grades. Serum protein induced by vitamin K absence or antagonist (PIVKA) level > 40 mAU/mL (OR, 3.763; p = 0.018) and peritumoral hypointensity (OR, 4.343; p = 0.003) were independent predictors of MVI. Predictors of CK19 included serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 4.576; p = 0.005), rim enhancement (OR, 5.493; p = 0.024), and lower RER (OR, 0.013; p = 0.011). Peritumoral hypointensity (hazard ratio [HR], 1.957; p = 0.027) and poor pathologic grades (HR, 2.339; p = 0.043) were independent predictors of recurrence. CONCLUSION: We demonstrated the value of preoperative gadoxetic-enhanced MRI in predicting aggressive pathological features of HCC. Poor pathologic grades and peritumoral hypointensity may independently predict the recurrence of HCC.

A model incorporating histopathology and preoperative gadoxetic acid-enhanced MRI to predict early recurrence of hepatocellular carcinoma without microvascular invasion after curative hepatectomy.

OBJECTIVES: To assess the predictive value of preoperative gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) features and postoperative histopathological grading for early recurrence of hepatocellular carcinoma (HCC) without microvascular invasion (MVI) after curative hepatectomy. METHODS: A total of 85 MVI-negative HCC cases were retrospectively analyzed. Cox analyses were used to identify the independent predictors of early recurrence (within a 24 months span). The clinical prediction Model-1 or Model-2 was established without or with postoperative pathological factor, respectively. Nomogram models were constructed and receiver operating characteristic (ROC) curve analysis was used to assess the models' predictive ability. Internal validation of the prediction models for early HCC recurrence was performed using a bootstrap re-sampling approach. RESULTS: In the multivariate cox regression analysis, Edmondson-Steiner grade, peritumoral hypointensity on hepatobiliary phase (HBP), and relative intensity ratio (RIR) in HBP were identified as independent variables associated with early recurrence. The C-index of the nomogram models and internal validation were both between 0.7 and 0.8, showing good model fitting and calibration effects. The area under the ROC curve (AUC) was 0.781 for Model-1 based on the two preoperative MRI factors. When a third factor, the Edmondson-Steiner grade, was included (Model-2), the AUC increased to 0.834, and the sensitivity increased from 71.4 to 96.4%. CONCLUSIONS: Edmondson-Steiner grade, peritumoral hypointensity on HBP, and RIR on HBP can help predict early recurrence of MVI-negative HCC. In comparison with Model-1 (only imaging features), Model-2 (imaging features + histopathological grades) increases the sensitivity in predicting early recurrence of HCC without MVI. ADVANCES IN KNOWLEDGE: Preoperative GA-enhanced MRI signs are of great value in predicting early postoperative recurrence of HCC without MVI, and a combined pathological model was established to evaluate the feasibility and effectiveness of this technique.

Quantitative assessment of liver function with hepatocyte fraction: Comparison with T1 relaxation-based indices.

PURPOSE: This study aimed to assess the use of hepatocyte fraction in gadoxetic acid-enhanced magnetic resonance imaging (MRI) for quantitatively evaluating the liver function in comparison with T1 relaxation-based indices. METHODS: This retrospective study included 79 patients with chronic liver disease, who were divided into 2 groups based on the results of the indocyanine green retention test (ICG). All patients underwent a gadoxetic acid-enhanced MRI of the liver. Pre- and post-contrast Look-Locker sequences were used 20 min after gadoxetic acid administration to acquire T1 mapping. Two readers independently identified and measured the MRI parameters [five T1 relaxation-based indices (T1pre, T1post, rrT1, R1post/R1pre and ΔR1) and two hepatocyte fraction indices (HeF and KHep)]. An Independent-samples t test was used to compare each parameter for the two groups. Pearson correlation analysis was used to analyze the correction in each parameter and 15-minute ICG retention rate (ICG-R15). Receiver operating characteristic analyses were performed to differentiate the diagnostic performance of each parameter in ICG-R15 ≤ 20 % and ICG-R15 > 20 % groups. RESULTS: T1pre and T1post were significantly lower in the ICG-R15 ≤ 20 % group than in the ICG-R15 > 20 % group (P < 0.05). rrT1, R1post/R1pre, ΔR1, HeF, and KHep were significantly higher in the ICG-R15 ≤ 20 % group than in the ICG-R15 > 20 % group (P < 0.05). The correction coefficients between T1pre, T1post, rrT1, R1post/R1pre, ΔR1, HeF, KHep, and ICG-R15 were 0.343, 0.783, -0.833, -0.781, -0.803, -0.819, and -0.832, respectively. The area under the curves (AUCs) of T1pre, T1post, rrT1, R1post/R1pre, ΔR1, HeF, and KHep in assessing the ICG-R15＞20 % groups were 0.761, 0.945, 0.912, 0.912, 0.948, 0.945, and 0.950, respectively. KHep had the highest AUC, sensitivity, and specificity. CONCLUSION: Hepatocyte fraction based on gadoxetic acid-enhanced T1-mapping MRI is an efficient diagnostic tool for the quantitative evaluation of liver function.

Evaluation of liver function using the hepatocyte enhancement fraction based on gadoxetic acid-enhanced MRI in patients with chronic hepatitis B.

OBJECTIVES: This study aimed to evaluate the feasibility of using the hepatocyte enhancement fraction (HEF) based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for assessing the liver function in patients with chronic hepatitis B. METHODS: Sixty patients with Child-Pugh grade A (CP-A), 18 with Child-Pugh grade B (CP-B), 2 with Child-Pugh grade C (CP-C), and 20 with normal liver function (NLF) were enrolled. Gadolinium ethoxybenzyldiethy-lenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was conducted. T1 mapping imaging was performed before and 20 min after Gd-EOB-DTPA administration. The pre- and post-contrast T1 values of the liver (T1pre and T1post), increase in the T1 relaxation rate (ΔR1), rate of decrease in the T1 relaxation time (ΔT1), HEF, and uptake coefficient (K) parameters in the NLF, CP-A, and CP-B + CP-C groups were compared using one-way analysis of variance. The effectiveness of each parameter in differentiating the NLF + CP-A group from the CP-B + CP-C group was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: The HEF, K, ΔT1, and ΔR1 values decreased, while the T1post and T1pre values increased, with the increase in liver function damage. Significant differences in T1post, ΔT1, ΔR1, and HEF were found between different groups, except for the CP-A and NLF groups. However, no significant difference was observed in the T1pre among the three groups. HEF exhibited the largest area under the ROC curve. CONCLUSION: The HEF is an effective method for evaluating liver function in patients with hepatitis B.