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.

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.

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.

Higher field reduced FOV diffusion-weighted imaging for abdominal imaging at 5.0 Tesla: image quality evaluation compared with 3.0 Tesla.

OBJECTIVE: To evaluate the image quality of reduced field-of-view (rFOV) DWI for abdominal imaging at 5.0 Tesla (T) compared with 3.0 T. METHODS: Fifteen volunteers were included into this prospective study. All the subjects underwent the 3.0 T and 5.0 T MR examinations (time interval: 2 ± 1.9 days). Free-breathing (FB), respiratory-triggered (RT), and navigator-triggered (NT) spin-echo echo-planner imaging-based rFOV-DWI examinations were conducted at 3.0 T and 5.0 T (FB3.0 T, NT3.0 T, RT3.0 T, FB5.0 T, NT5.0 T, and RT5.0 T) with two b values (b = 0 and 800 s/mm2), respectively. The signal-to-noise ratio (SNR) of different acquisition approaches were determined and statistically compared. The image quality was assessed and statistically compared with a 5-point scoring system. RESULTS: The SNRs of any 5.0 T DWI images were significantly higher than those of any 3.0 T DWI images for same anatomic locations. Moreover, 5.0 T rFOV-DWIs had the significantly higher sharpness scores than 3.0 T rFOV-DWIs. Similar distortion scores were observed at both 3.0 T and 5.0 T. Finally, RT5.0 T displayed the best overall image quality followed by NT5.0 T, FB5.0 T, RT3.0 T, NT3.0 T and FB3.0 T (RT5.0 T = 3.9 ± 0.3, NT5.0 T = 3.8 ± 0.3, FB5.0 T = 3.4 ± 0.3, RT3.0 T = 3.2 ± 0.4, NT3.0 T = 3.1 ± 0.4, and FB3.0 T = 2.7 ± 0.4, p < 0.001). CONCLUSION: The 5.0 T rFOV-DWI showed better overall image quality and improved SNR compared to 3.0 T rFOV-DWI, which holds clinical potential for identifying the abdominal abnormalities in routine practice. CRITICAL RELEVANCE STATEMENT: This study provided evidence that abdominal 5.0 Tesla reduced field of view diffusion-weighted imaging (5.0 T rFOV-DWI) exhibited enhanced image quality and higher SNR compared to its 3.0 Tesla counterparts, holding clinical promise for accurately visualizing abdominal abnormalities. KEY POINTS: • rFOV-DWI was firstly integrated with high-field-MRI for visualizing various abdominal organs. • This study indicated the feasibility of abdominal 5.0 T-rFOV-DWI. • Better image quality was identified for 5.0 T rFOV-DWI.

The Feasibility of Using Tri-Exponential Intra-Voxel Incoherent Motion DWI for Identifying the Microvascular Invasion in Hepatocellular Carcinoma.

Purpose: To assess the effectiveness of tri-exponential Intra-Voxel Incoherent Motion (tri-IVIM) MRI in preoperatively identifying microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Patients and Methods: In this prospective study, 67 patients with HCC were included. Metrics from bi-exponential IVIM (bi-IVIM) and tri-IVIM were calculated. Subgroup comparisons were analyzed using the independent Student's t-test or Mann-Whitney U-test. Logistic regression was performed to explore clinical risk factors. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis. Results: MVI-positive HCCs exhibited significantly lower true diffusion coefficient (Dt) from bi-IVIM, as well as fast-diffusion coefficients (Df) and slow-diffusion coefficients (Ds) from tri-IVIM, compared to MVI-negative HCCs (p < 0.05). Tumor size and alpha-fetoprotein (AFP) were identified as risk factors. The combination of tri-IVIM-derived metrics (Ds and Df) yielded higher diagnostic accuracy (AUC = 0.808) compared to bi-IVIM (AUC = 0.741). A predictive model based on a nomogram was constructed using Ds, Df, tumor size, and AFP, resulting in the highest diagnostic accuracy (AUC = 0.859). Decision curve analysis indicated that the constructed model, provided the highest net benefit by accurately stratifying the risk of MVI, followed by tri-IVIM and bi-IVIM. Conclusion: Tri-IVIM can provide information on perfusion and diffusion for evaluating MVI in HCC. Additionally, tri-IVIM outperformed bi-IVIM in identifying MVI-positive HCC. By integrating clinical risk factors and metrics from tri-IVIM, a predictive nomogram exhibited the highest diagnostic accuracy, potentially aiding in the noninvasive and preoperative assessment of MVI.

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.

Preoperatively Identify the Microvascular Invasion of Hepatocellular Carcinoma with the Restricted Spectrum Imaging.

RATIONALE AND OBJECTIVES: To noninvasively and preoperatively identify the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) with the restricted spectrum imaging (RSI). MATERIALS AND METHODS: 62 patients were included into this prospective study and underwent the RSI examination with a 3.0-T scanner. Mono-exponential diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) and RSI-derived metrics including f1 (fraction of restricted diffusion), f2 (fraction of hindered diffusion), f3 (fraction of free diffusion), and f1f2 (the multiply of f1 and f2) were calculated. Univariate and multivariate logistic regression were used to select the independent risk factors. Nomogram-based model was constructed with the selected indexes. Receiver operative characteristics analysis and calibration curve were used to evaluate the diagnostic accuracy. RESULTS: MVI-positive HCC showed significantly higher f1 and lower ADC values (ADC: 1.549 ± 0.228 ×10-3 vs 1.365 ± 0.239 ×10-3 mm2/s, P = .003; f1: 0.1633 ± 0.0341 vs 0.2221 ± 0.0491, P < .001). Tumor size and f1 were selected as independent risk factors for MVI. The nomogram-based model was then constructed with tumor size and f1. Nomogram-based model (area under ROC curve [AUC]= 0.856) yielded the best diagnostic accuracy followed by f1 (AUC=0.842) and ADC (AUC=0.708). The AUC of both the f1 and nomogram model were significantly higher than that of ADC. CONCLUSION: RSI-derived metrics can be utilized to noninvasively and efficiently identify the MVI of HCC. Considering the importance of MVI as a significant prognostic factor for HCC, the utilization of RSI has the potential to assist in prognostic prediction and clinical management.

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.

Preliminary radiogenomic study of hepatitis B virus-related hepatocellular carcinoma: associations between MRI features and mutations.

Aim: To investigate associations between MRI features and high-frequency mutations of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: This study included 58 HCC patients who underwent contrast-enhanced MRI prior to surgical resection and genome sequencing. MRI features and mutation information were evaluated. Results: The top five most frequently mutated genes in HCC were TP53 (53.45%), TAF1 (24.14%), PDE4DIP (22.41%), ABCA13 (18.97%) and LRP1B (17.24%). Mutations in TP53 and LRP1B were associated with tumor necrosis (p = 0.035) and mosaic architecture (p = 0.015), respectively. Mutations in ABCA13 were associated with mosaic architecture (p = 0.025) and necrosis (p = 0.010). Conclusion: This preliminary radiogenomics analysis showed associations between MRI features and high-frequency mutations in HBV-related HCCs.

Radiogenomics has been helpful for disease prevention, diagnosis, treatment, prognosis and drug development, and has shown good prospects in gene function analysis and gene therapy research. Some studies have explored the relationship between the underlying genotype and MRI features. However, few studies have indicated the relationship between the underlying genotype and MRI features of hepatocellular carcinoma (HCC) so far. In this study, the top five most frequently mutated genes in hepatitis B virus-related HCCs were TP53, TAF1, PDE4DIP, ABCA13 and LRP1B and certain associations existed between MRI features and high-frequency mutations. These results demonstrated the potential clinical value of imaging traits as surrogate markers of molecular portraits in HCC. The potential correlations between MRI features and high-frequency mutations may provide effective clinical information for hepatitis B virus-related HCCs.

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.

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.

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.

Radiomics on Gadoxetate Disodium-enhanced MRI: Non-invasively Identifying Glypican 3-Positive Hepatocellular Carcinoma and Postoperative Recurrence.

RATIONALE AND OBJECTIVES: To investigate the impact of preoperative gadoxetate disodium (EOB) MRI-based radiomics on predicting glypican 3 (GPC3)-positive expression and the relevant recurrence-free survival (RFS) of HCC ≤ 5 cm. MATERIALS AND METHODS: Between January 2014 and October 2018, 259 patients with solitary HCC ≤ 5 cm who underwent hepatectomy and preoperative EOB-MRI were retrieved. Multivariate logistic regression was implemented to identify independent predictors for GPC3. By combining five feature selection strategies and three classifiers, 15 GPC3-oriented radiomics models could be constructed, the best of which with independent clinicoradiologic predictors was integrated into the comprehensive nomogram. RESULTS: GPC3 was an independent risk factor of postoperative recrudescence for HCC. Alpha-fetoprotein >20 ng/mL, homogenous T2 signal and hypointensity on hepatobiliary phase were independently related to GPC3-positive expression in the clinicoradiologic model. With 10 features selected by support vector machines-recursive feature elimination, logistic regression-based classifier achieved the best performance among 15 radiomics models. After five-fold cross-validation, our comprehensive nomogram acquired better average area under receiver operating characteristic curves (training and validation cohorts: 0.931 vs. 0.943) than the clinicoradiologic algorithm (0.738 vs. 0.739) and the optimal radiomics model (0.943 vs. 0.931). Net reclassification indexes further demonstrated the superiority of GPC3 nomogram over clinicoradiologic and radiomics algorithms (46.54%, p < 0.001; 7.84%, p = 0.207). Meanwhile, higher radiomics score significantly shortened the median RFS (from >77.9 to 48.2 months, p = 0.044), which was analogue to that of the histological GPC3-positive phenotype (from >73.9 to 43.2 months, p < 0.001). CONCLUSIONS: Preoperative EOB-MRI radiomics-based nomogram satisfactorily distinguished GPC3 status and outcomes of solitary HCC ≤ 5 cm.

Renal imaging at 5 T versus 3 T: a comparison study.

BACKGROUND: Recently, a whole-body 5 T MRI scanner was developed to open the door of abdominal imaging at high-field strength. This prospective study aimed to evaluate the feasibility of renal imaging at 5 T and compare the image quality, potential artifacts, and contrast ratios with 3 T. METHODS: Forty healthy volunteers underwent MRI examination both at 3 T and 5 T. MRI sequences included T1-weighted gradient-echo (GRE), T2-weighted fast spin echo, diffusion-weighted imaging, and multi-echo GRE T2* mapping. Image quality and presence of artifacts were assessed for all sequences using four-point scales. For anatomical imaging, the signal-to-noise ratio (SNR) and contrast ratio (CR) of abdomen organ tissues were calculated. Besides, for functional imaging, the contrast-to-noise ratio of cortex/medulla was calculated. Wilcoxon signed rank-sum test was used to compare the visual evaluation scores and quantitative measurements between 3 and 5 T images. RESULTS: Compared to 3 T examination, T1-weighted sequence at 5 T showed significantly better image quality with higher conspicuity of the renal veins and arteries, and comparable artifacts. Image quality was comparable between both field strengths on T2-weighted images, whereas a significantly higher level of artifacts was observed at 5 T. Besides, 5 T MRI contributed to higher SNR and CR for abdomen organ tissues. For functional imaging, 5 T MRI showed improved corticomedullar discrimination. There was no significant difference between apparent diffusion coefficient of renal at 3 T and 5 T, while 5 T MRI resulted in significantly shorter T2* values in both cortex and medulla. CONCLUSIONS: 5 T MRI provides anatomical and functional images of the kidney with sufficient image quality.

Free-Breathing Liver Magnetic Resonance Imaging With Respiratory Frequency-Modulated Continuous-Wave Radar-Trigger Technique: A Preliminary Study.

Purpose: The aim of this study is to evaluate the performance of free-breathing liver MRI with a novel respiratory frequency-modulated continuous-wave radar-trigger (FT) technique on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) for both healthy volunteers and patients in comparison to navigator-trigger (NT) and belt-trigger (BT) techniques. Methods: In this prospective study, 17 healthy volunteers and 23 patients with known or suspected liver diseases were enrolled. Six sequences (T2WI and DWI with FT, NT, and BT techniques) were performed in each subject. Quantitative evaluation and qualitative assessment were analyzed by two radiologists. Overall image quality, blurring, motion artifacts, and liver edge delineations were rated on a 4-point Likert scale. The liver and lesion signal-to-noise ratio (SNR), the lesion-to-liver contrast-to-noise ratio (CNR), as well as the apparent diffusion coefficient (ADC) value were quantitatively calculated. Results: For volunteers, there were no significant differences in the image quality Likert scores and quantitative parameters on T2WI and DWI with three respiratory-trigger techniques. For patients, NT was superior to other techniques for image quality on T2WI; conversely, little difference was found on DWI in qualitative assessment. The mean SNR of the liver on T2WI and DWI with BT, NT, and FT techniques was similar in patients, which is in line with volunteers. FT performed better in terms of higher SNR (705.13 ± 434.80) and higher CNR (504.41 ± 400.69) on DWI at b50 compared with BT (SNR: 651.83 ± 401.16; CNR:429.24 ± 404.11) and NT (SNR: 639.41 ± 407.98; CNR: 420.64 ± 416.61) (p < 0.05). The mean ADC values of the liver and lesion with different techniques in both volunteers and patients showed non-significant difference. Conclusion: For volunteers, the performance of T2WI as well as DWI with three respiratory-trigger techniques was similarly good. As for patients, FT-DWI is superior to BT and NT techniques in terms of higher lesion SNR and CNR at b50.

Gadoxetate-Enhanced MRI as a Diagnostic Tool in the Management of Hepatocellular Carcinoma: Report from a 2020 Asia-Pacific Multidisciplinary Expert Meeting.

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

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.