Association Between MRI-Based Radiomics Features and Regional Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma and Its Clinical Outcome.

BACKGROUND: Regional lymph node metastasis (LNM) assessment is crucial for predicting intrahepatic cholangiocarcinoma (iCCA) prognosis. However, imaging assessment has limitations for identifying LNM. PURPOSE: To investigate the association between MRI radiomics features, regional LNM status, and prognosis in iCCA. STUDY TYPE: Retrospective. SUBJECTS: Two hundred ninety-six patients (male = 197) with surgically confirmed iCCA. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T. DWI, T2WI, and contrast-enhanced T1WI. ASSESSMENT: Clinical information, radiologic, and MRI-based radiomics features associated with LNM status were collected to establish models. Performance of MRI, PET/CT, and the combined LNM models were compared in training (N = 207) and test (N = 89) datasets. Overall survival (OS) was compared based on LNM status. STATISTICAL TESTS: The independent features were selected by 5-fold cross-validation. The performance of MRI, PET/CT, and the models was evaluated using the area under receiver operating characteristic curve (AUC). Univariable and multivariable Cox regression were used to identify independent variables for OS. Kaplan-Meier curves were compared with the log-rank test between LNM positive and negative groups. P < 0.05 was considered statistically significant. RESULTS: Intrahepatic duct dilatation, enhancement pattern, and CA19-9 were independent clinicoradiologic features. The radiomics model was constructed by the independent radiomics features extracted from T2WI and delay phase T1WI. The combined LNM model showed AUC of 0.888, 0.884, and 0.811 in training, validation, and test cohorts with a positive net benefit. PET/CT exhibited similar sensitivity to the combined LNM model (0.750 vs. 0.733, P > 0.999) while the combined LNM model showed higher specificity (0.703 vs. 0.630, P = 0.039) in the test cohort. High risk of regional LNM was significantly associated with worse OS (median: 24 months) than low risk (median: 30 months, P < 0.0001). DATA CONCLUSIONS: The combined LNM model has the strongest correlation with LNM status for mass-forming iCCA patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Diagnostic algorithm for subcentimeter hepatocellular carcinoma using alpha-fetoprotein and imaging features on gadoxetic acid-enhanced MRI.

OBJECTIVE: To investigate the role of serum alpha-fetoprotein (AFP) in diagnosing subcentimeter hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI (EOB-MRI). METHODS: This study retrospectively enrolled treatment-naïve patients with chronic hepatitis B who had a solitary subcentimeter observation on EOB-MRI from January 2017 to March 2023. Final diagnosis was confirmed by pathology for HCC and pathology or follow-up for benign controls. The AFP cutoff value for HCC was determined using Youden's index. Diagnostic criteria were developed according to significant findings in logistic regression analyses based on AFP and imaging features. The diagnostic performance of possible criteria was compared to the diagnostic hallmarks of HCC (arterial-phase hyperintensity and portal-phase hypointensity). RESULTS: A total of 305 patients (mean age, 51.5 ± 10.7 years; 153 men) were divided into derivation and temporal validation cohorts. Four findings, namely AFP >13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity, were predictors of HCC. A new criterion (at least three of the four findings) showed higher sensitivity than the diagnostic hallmarks (derivation cohort, 71.6% vs. 52.3%, p < 0.001; validation cohort, 75.0% vs. 47.5%, p = 0.003) without decreasing specificity (derivation cohort, 92.5% vs. 92.5%, p > 0.999; validation cohort, 92.0% vs. 92.0%, p > 0.999). Another criterion (all four findings) achieved a slightly higher specificity than the diagnostic hallmark (derivation cohort, 99.1% vs. 92.5%, p = 0.023; validation cohort, 100.0% vs. 92.0%, p = 0.134). Subgroup analysis for hepatobiliary hypointense observations yielded similar results. CONCLUSION: Including AFP in the diagnostic algorithm may improve the diagnostic performance for subcentimeter HCC. CLINICAL RELEVANCE STATEMENT: Combining imaging features on gadoxetic acid-enhanced MRI with alpha-fetoprotein may enhance the diagnostic performance for subcentimeter HCC in treatment-naïve patients with chronic hepatitis B. KEY POINTS: • The traditional diagnostic hallmark of HCC (arterial-phase hyperintensity and portal-phase hypointensity) shows modest diagnostic performance for subcentimeter HCC on EOB-MRI. • Serum alpha-fetoprotein > 13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity were independent predictors for subcentimeter HCC. • A criterion of at least three of the four above findings achieved a higher sensitivity without decreasing specificity.

Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis.

BACKGROUND AND AIMS: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. METHODS: Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. RESULTS: Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. CONCLUSION: This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

An MRI-Based Prognostic Stratification System for Medical Decision-Making of Multinodular Hepatocellular Carcinoma Patients Beyond the Milan Criteria.

BACKGROUND: The suitability of hepatectomy among patients with multinodular hepatocellular carcinoma (MHCC) beyond the Milan criteria remains controversial. There is a need for a reliable risk stratification tool among these patients for the selection of ideal candidates of curative resection. PURPOSE: To determine the clinicoradiological prognostic factors for patients with MHCC beyond the Milan criteria to further develop a stratification system. STUDY TYPE: Retrospective. SUBJECTS: 176 patients with pathologically confirmed MHCC beyond the Milan criteria. FIELD STRENGTH/SEQUENCE: The 1.5 T scanner, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT: Conventional MRI features and preoperative laboratory data including aspartate aminotransferase (AST) and α-fetoprotein (AFP) were collected and analyzed. Two nomograms incorporating clinicoradiological variables were independently constructed to predict recurrence-free survival (RFS) and overall survival (OS) with Cox regression analyses and verified with 5-fold cross validation. Based on the nomograms, two prognostic stratification systems for RFS and OS were further developed. STATISTICAL TESTS: The Cohen's kappa/intraclass correlation coefficient, C-index, calibration curve, Kaplan-Meier curve, log-rank test. A P value <0.05 was considered statistically significant. RESULTS: AST > 40 U/L, increased tumor burden score, radiological liver cirrhosis and nonsmooth tumor margin were independent predictors for poor RFS, while AST > 40 U/L, AFP > 400 ng/mL and radiological liver cirrhosis were independent predictors for poor OS. The two nomograms demonstrated good discrimination performance with C-index of 0.653 (95% confidence interval [CI], 0.602-0.794) and 0.685 (95% CI, 0.623-0.747) for RFS and OS, respectively. The 5-fold cross validation further validated the discrimination capability of the nomograms. Based on the nomogram models, MHCC patients beyond the Milan criteria were stratified into low-/medium-/high-risk groups with significantly different RFS and OS. DATA CONCLUSION: The proposed MRI-based prognostic stratification system facilitates the refinement and further subclassification of patients with MHCC beyond the Milan criteria. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: 2.

An improved diagnostic algorithm for subcentimeter hepatocellular carcinoma on gadoxetic acid-enhanced MRI.

OBJECTIVES: Accurate diagnosis of subcentimeter hepatocellular carcinoma (HCC) is a challenge also with gadoxetic acid-enhanced MRI (EOB-MRI). This study aimed to assess the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for subcentimeter HCC and to determine whether new diagnostic criteria (washout either on portal venous phase (PVP) or transitional phase (TP)) would improve the diagnostic performance. METHODS: We evaluated 240 subcentimeter observations in 225 consecutive treatment-naïve patients at risk of HCC. Final diagnoses were 132 HCCs (all by pathology) and 108 non-HCC (41 by pathology and 67 by follow-up). Two radiologists assessed MR imaging features and assigned LI-RADS categories. A variety of diagnostic criteria were developed by combining significant MRI features based on washout on PVP or TP. Diagnostic performance was compared. RESULTS: Non-rim arterial phase hyperenhancement (non-rim APHE), washout on PVP or TP, and hepatobiliary-phase hypointensity were significant predictors for subcentimeter HCC diagnosis according to multivariable analysis. One criterion (non-rim APHE and washout on PVP or TP) yielded higher sensitivity (68.2% vs. 56.8%, p = 0.011) with comparable specificity (91.7% vs. 92.6%, p > 0.999) compared to the LR-4 category. This criterion had improved sensitivity (68.2% vs. 49.2%, p < 0.001) and slightly decreased specificity (91.7% vs. 94.4%, p = 0.250) compared to non-rim APHE with washout on PVP. CONCLUSIONS: LI-RADS exhibits modest diagnostic performance for subcentimeter HCC. Our new criterion (non-rim APHE and non-peripheral washout on PVP or TP) may increase the diagnostic sensitivity without compromised specificity compared to the LR-4 category. KEY POINTS: • The LR-4 category shows modest diagnostic performance for the diagnosis of subcentimeter HCC on EOB-MRI with a sensitivity and specificity of 56.8% and 92.6%, respectively. • Non-rim APHE, non-peripheral washout on PVP or TP, and HBP hypointensity were independent predictors for the diagnosis of subcentimeter HCC. • The combination of non-rim APHE and non-peripheral washout on PVP or TP improves the sensitivity from 56.8 to 68.2% (p = 0.011) with comparable specificity (91.7 vs. 92.6%, p > 0.999).

Prognostic factors for long-term outcome in bifocal hepatocellular carcinoma after resection.

OBJECTIVES: This study aimed to evaluate whether the radiological similarity and clinicopathological factors determine the prognosis in bifocal hepatocellular carcinoma (bHCC) stratified by the Milan criteria. METHODS: Consecutive patients with pathologically confirmed bHCC examined between January 2016 and December 2018 were retrospectively enrolled and grouped based on the Milan criteria. Two radiologists independently evaluated whether the imaging features of both tumors were consistent or not, which was defined as the radiological similarity. The clinicopathological data were also collected. The multivariable Cox regression was applied to separately identify the independent factors for recurrence-free survival (RFS) and overall survival (OS) in bHCC within and beyond the Milan criteria. RESULTS: A total of 193 patients were evaluated and divided into the within the Milan criteria group (n = 72) and the beyond the Milan criteria group (n = 121). bHCC within the Milan criteria showed a significantly better prognosis than those beyond the criteria. In the within the Milan criteria group, HBV-DNA load >104 IU/mL, microvascular invasion (MVI), and different enhancement patterns were independently associated with poor RFS. MVI was an independent prognostic factor for poor OS. In the beyond the Milan criteria group, HBV infection, MVI, increased ratio of the larger to the smaller tumor diameter (RLSD) value, and low comprehensive similarity were associated with shorter RFS, whereas MVI and increased RLSD value were independent predictors for poor OS. CONCLUSIONS: Our study revealed that in addition to MVI- and HBV-related factors, similarity in imaging features between lesions of bHCC is associated with the long-term prognosis. KEY POINTS: • The prognosis of bifocal HCC patients within the Milan criteria is significantly better than those beyond the criteria. • The similarity in imaging features between lesions of bHCC was an independent prognostic factor. • The more similar the bifocal lesions are in imaging features, the better the prognosis is.

Combined hepatocellular carcinoma-cholangiocarcinoma with a predominant HCC component: better survival and MRI-based prediction.

OBJECTIVES: To determine the optimal cutoff value of HCC% for predicting the outcome of patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) and to investigate how preoperative MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) are related to the HCC% in cHCC-CCA. METHODS: The study enrolled 107 patients pathologically confirmed to have single cHCC-CCA according to the 2019 WHO classification. A receiver operating characteristic (ROC) curve was used to find the optimal cutoff value of HCC% based on overall survival (OS). The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the high HCC% and low HCC% groups. RESULTS: In total, 107 patients (mean age, males vs. females: 56.6 ± 10.7 years vs. 54.2 ± 12.8 years) were evaluated. Analysis of the relationship between HCC% and OS by ROC curve suggested that the optimal cutoff value was 65%, by which 51 (47.7%) patients were assigned to the high HCC% group. LI-RADS categorization (OR = 3.657, p = 0.006 vs. OR = 4.075, p = 0.004) and serum carcinoembryonic antigen (CEA) >5 ng/mL (OR = 0.348, p = 0.089 vs. OR = 0.298, p = 0.040) were significant predictors for HCC% in cHCC-CCA in both univariate and multivariate analysis. CONCLUSIONS: cHCC-CCA patients with HCC components higher than 65% tend to exhibit better overall survival, and MRI-based LI-RADS categorization and serum CEA level are valuable for identifying HCC% in cHCC-CCA preoperatively. KEY POINTS: • cHCC-CCA patients with HCC components higher than 65% tend to exhibit better overall survival. • MRI-based LI-RADS categorization and serum CEA level were significant predictors for HCC% in cHCC-CCA in both univariate and multivariate analyses and valuable for identifying HCC% in cHCC-CCA preoperatively.

Development and validation of combined Ki67 status prediction model for intrahepatic cholangiocarcinoma based on clinicoradiological features and MRI radiomics.

PURPOSE: Incidence and mortality of intrahepatic cholangiocarcinoma (ICC) have been increasing over the past few decades, and Ki67 is an adverse prognostic predictor and an attractive therapeutic target for ICC patients. Thus, we aim to develop and validate a combined Ki67 prediction model for ICC patients. MATERIALS AND METHODS: Preoperative contrast-enhanced MR images were collected from 178 patients with postoperative pathologically confirmed ICC, and randomly divided into training and validation cohorts in a ratio of 7:3 (124:54). A time-independent test cohort of 49 ICC patients was used for validation. Independent clinicoradiological features of Ki67 status were determined by multivariate analysis. Optimal radiomics features were selected by least absolute shrinkage and selection operator logistic regression and linear discriminant analysis was used to construct combined models. The prediction efficacy of combined model was assessed by receiver operating characteristics curve, and verified by its calibration, decision and clinical impact curves. RESULTS: HBV (p = 0.022), arterial rim enhancement (p = 0.006) and enhancement pattern (p = 0.012) are independent clinicoradiological features. The radiomics model achieves good prediction efficacy in the training cohort (AUC = 0.860) and validation cohort (AUC = 0.843). The combined Ki67 prediction model incorporates clinicoradiological and radiomics features, and it yields desirable predictive efficiency in test cohort (AUC = 0.815). Decision curves and clinical impact curves further validate that the combined Ki67 prediction model can achieve net benefits in clinical work. CONCLUSION: The combined Ki67 model incorporating HBV, arterial rim enhancement, enhancement pattern and radiomics features is a potential biomarker in Ki67 prediction and stratification.

Comprehensive analysis of tumor immune microenvironment and prognosis of m6A-related lncRNAs in gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal roles in gastric cancer (GC) progression. The emergence of immunotherapy in GC has created a paradigm shift in the approaches of treatment, whereas there is significant heterogeneity with regard to degree of treatment responses, which results from the variability of tumor immune microenvironment (TIME). How the interplay between m6A and lncRNAs enrolling in the shaping of TIME remains unclear. METHODS: The RNA sequencing and clinical data of GC patients were collected from TCGA database. Pearson correlation test and univariate Cox analysis were used to screen out m6A-related lncRNAs. Consensus clustering method was implemented to classify GC patients into two clusters. Survival analysis, the infiltration level of immune cells, Gene set enrichment analysis (GSEA) and the mutation profiles were analyzed and compared between two clusters. A competing endogenous RNA (ceRNA) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied for the identification of pathways in which m6A-related lncRNAs enriched. Then least absolute shrinkage and selection operator (LASSO) COX regression was implemented to select pivotal lncRNAs, and risk model was constructed accordingly. The prognosis value of the risk model was explored. In addition, the response to immune checkpoint inhibitors (ICIs) therapy were compared between different risk groups. Finally, we performed qRT-PCR to detect expression patterns of the selected lncRNAs in the 35 tumor tissues and their paired adjacent normal tissues, and validated the prognostic value of risk model in our cohort (N = 35). RESULTS: The expression profiles of 15 lncRNAs were included to cluster patients into 2 subtypes. Cluster1 with worse prognosis harbored higher immune score, stromal score, ESTIMATE score and lower mutation rates of the genes. Different immune cell infiltration patterns were also displayed between the two clusters. GSEA showed that cluster1 preferentially enriched in tumor hallmarks and tumor-related biological pathways. KEGG pathway analysis found that the target mRNAs which m6A-related lncRNAs regulated by sponging miRNAs mainly enriched in vascular smooth muscle contraction, cAMP signaling pathway and cGMP-PKG signaling pathway. Next, eight lncRNAs were selected by LASSO regression algorithm to construct risk model. Patients in the high-risk group had poor prognoses, which were consistent in our cohort. As for predicting responses to ICIs therapy, patients from high-risk group were found to have lower tumor mutation burden (TMB) scores and account for large proportion in the Microsatellite Instability-Low (MSI-L) subtype. Moreover, patients had distinct immunophenoscores in different risk groups. CONCLUSION: Our study revealed that the interplay between m6A modification and lncRNAs might have critical role in predicting GC prognosis, sculpting TIME landscape and predicting the responses to ICIs therapy.

Histopathological components correlated with MRI features and prognosis in combined hepatocellular carcinoma-cholangiocarcinoma.

OBJECTIVES: To distinguish MR features according to different proportions of the histopathological hepatocellular carcinoma (HCC) component and to investigate whether the proportion of the HCC component can predict the prognosis of patients with cHCC-CCA. METHODS: The study enrolled 106 cHCC-CCA patients confirmed by histopathology. The MR imaging features and clinicopathological findings were retrospectively evaluated and compared between two subgroups with different proportions of the HCC component. The recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, whether the proportion of the HCC component was a predictor of RFS and OS was investigated using Cox regression analyses. RESULTS: The Liver Imaging Reporting and Data System (LI-RADS) category 4/5 was more prevalent in cHCC-CCAs with an HCC component > 50% (odds ratio (OR) = 5.559, p = 0.018), 70% (OR = 4.031, p = 0.008), and 90% (OR = 6.282, p = 0.012) than in those with an HCC component ≤ 50%, 70%, and 90%, respectively. In addition, cHCC-CCAs with an HCC component > 70% (HR: 0.241, p = 0.023) had a better OS prognosis than those with an HCC component ≤ 70%. CONCLUSIONS: cHCC-CCAs categorized as LR-4/5 are mainly composed of HCC component, and cHCC-CCAs with an HCC component > 70% are associated with better OS than those with an HCC component ≤ 70%. These findings suggest that the proportion of HCC or CCA component can predict the prognosis of cHCC-CCA patients. KEY POINTS: • cHCC-CCAs categorized as LR-4/5 are mainly composed of HCC component. • cHCC-CCAs with an HCC component > 70% are associated with better OS than those with an HCC component ≤ 70%.

Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis.

OBJECTIVES: To determine how MRI features are correlated to biomarkers, and to the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients. METHODS: The study enrolled 160 cHCC-CCA patients pathologically confirmed according to the 2019 WHO classification. The preoperative MRI features and clinical data were retrospectively evaluated and compared between patients grouped by AFP or CA19-9 level and with pathological findings. The RFS and OS of cHCC-CCA patients were estimated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, predictors of RFS and OS were investigated using Cox regression analyses. RESULTS: One hundred and sixty patients (mean age, males vs. females: 55.7 ± 10.2 years vs. 54.9 ± 14.0 years) were evaluated. The incidence of nodule-in-nodule architecture, mosaic architecture, intratumoral hemorrhage, hepatic capsule retraction, arterial phase peritumoral enhancement, and portal vein thrombus was significantly higher in patients with AFP > 20 ng/ml (all p < 0.05). Multivariate Cox regression analysis indicated that age (HR 1.031, p = 0.03), CA19-9 > 37 U/ml (HR 1.880, p = 0.04), arterial phase peritumoral enhancement (HR 2.287, p = 0.01), and delayed enhancement (HR 0.377, p = 0.02) were independent predictors of poor RFS, while arterial phase peripheral enhancement (HR 2.391, p = 0.04) was an independent predictor of poor OS. CONCLUSIONS: cHCC-CCA imaging features are complex and not correlated with AFP or CA19-9. Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor RFS. Arterial phase peripheral enhancement is an independent predictor of poor OS. KEY POINTS: • The imaging features of combined hepatocellular carcinoma-cholangiocarcinoma are complex and are not correlated with the alpha fetoprotein or CA19-9 levels. • Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor recurrence-free survival in combined hepatocellular carcinoma-cholangiocarcinoma patients. • Arterial phase peripheral enhancement is an independent predictor of poor overall survival in patients with combined hepatocellular carcinoma-cholangiocarcinoma.

Risk stratification of LI-RADS M and LI-RADS 4/5 combined hepatocellular cholangiocarcinoma: prognostic values of MR imaging features and clinicopathological factors.

OBJECTIVES: To investigate the role of clinicopathological factors and MR imaging factors in risk stratification of combined hepatocellular cholangiocarcinoma (cHCC-CCA) patients who were classified as LR-M and LR-4/5. METHODS: We retrospectively identified consecutive patients who were confirmed as cHCC-CCA after surgical surgery in our institution from June 2015 to November 2020. Two radiologists evaluated the preoperative MR imaging features independently, and each lesion was assigned with a LI-RADS category. Preoperative clinical data were also collected. Multivariate Cox proportional hazards model was applied to separately identify the independent factors correlated with the recurrence of cHCC-CCAs in LR-M and LR-4/5. Risk stratifications were conducted separately in LR-M and LR-4/5. Recurrence-free survival (RFS) rates and overall survival (OS) rates were analyzed by using the Kaplan-Meier survival curves and log-rank test. RESULTS: A total of 131 patients with single primary lesion which met the 2019 WHO classification criteria were finally included. Corona enhancement, delayed central enhancement, and microvascular invasion (MVI) were identified as predictors of RFS in LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in LR-4/5. Based on the number of these independent predictors, patients were stratified into favorable-outcome groups (LR-ML subgroup and LR-4/5L subgroup) and dismal-outcome groups (LR-MH subgroup and LR-4/5H subgroup). The corresponding median RFS for LR-ML, LR-MH, LR-5L, and LR-5H were 25.6 months, 8.2 months, 51.7 months, and 18.1 months. CONCLUSION: Our study explored the prognostic values of imaging and clinicopathological factors for LR-M and LR-4/5 cHCC-CCA patients, and different survival outcomes were observed among four subgroups after conducting risk stratifications. KEY POINTS: • Corona enhancement, delayed central enhancement, and MVI were identified as predictors of RFS in cHCC-CCAs which were classified into LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in cHCC-CCAs which were classified into LR-4/5. • Based on the identified risk factors, LR-M and LR-4/5 cHCC-CCA patients could be stratified into two subgroups respectively, with significantly different RFS and OS. • cHCC-CCA patients from LR-M did not always have worse RFS and OS than those from LR-4/5 in some cases.

Association Between Incomplete Circle of Willis and Carotid Vulnerable Atherosclerotic Plaques.

Objective- Carotid high-risk plaque, characterized by intraplaque hemorrhage, fibrous cap rupture, and large lipid-rich necrotic core, is associated with cerebrovascular events. This study sought to investigate the relationship between high-risk carotid plaque and an incomplete circle of Willis (COW). Approach and Results- Patients were recruited from a multicenter study, Chinese Atherosclerosis Risk Evaluation (CARE-II) and underwent 3-dimensional time-of-flight magnetic resonance angiography for intracranial arteries and 2-dimensional multicontrast magnetic resonance vessel wall imaging for carotid arteries on a 3.0T magnetic resonance scanner. The integrity of the COW in anterior and posterior portions was evaluated. Characteristics of carotid plaques were assessed. Correlation between incomplete COW and carotid plaque features was determined. Of 482 eligible patients, patients with carotid intraplaque hemorrhage showed significantly higher prevalence of an incomplete anterior COW (52.7% versus 38.5%; P=0.022) compared with those without. An incomplete anterior COW was associated with intraplaque hemorrhage before (odds ratio, 1.781; 95% CI, 1.083-2.931; P=0.023) and after adjusted for clinical risk factors (odds ratio, 1.945; 95% CI, 1.139-3.321; P=0.015). The unilateral carotid artery stenosis showed no correlation with incomplete anterior COW and posterior COW (all P>0.025). No significant associations were found between other plaque features and any type of incomplete COW (all P>0.025). Conclusions- An incomplete COW is independently associated with intraplaque hemorrhage of carotid atherosclerotic plaques. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017756.

How to differentiate between combined hepatocellular carcinoma-cholangiocarcinoma and intrahepatic cholangiocarcinoma with rim arterial phase hyperenhancement?

PURPOSE: To analyze and compare the differences in MRI features between combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) and intrahepatic cholangiocarcinoma (iCCA) with arterial phase peripheral enhancement, so as to provide valuable references for preoperative differential diagnosis. METHODS: Seventy cHCC-CCA patients and 74 iCCA patients confirmed by pathology were included in this study. Their contrast-enhanced MRI showed rim arterial phase hyperenhancement (Rim APHE). The differences of clinicopathological data and MRI features between cHCC-CCA and iCCA were compared. Then, the sensitivity, specificity, and area under curve (AUC) were also analyzed and compared. RESULTS: Seventy cHCC-CCA patients (mean age, 55.7 ± 10.6 years) and 74 iCCA patients (mean age, 61.1 ± 10.5 years) were evaluated. In this study, univariable and multivariable regression analysis showed that AFP > 20 ng/ml (OR = 5.824, p = 0.006), enhancing capsule (OR = 7.252, p = 0.001), and mosaic architecture (OR = 32.732, p < 0.001) were independent risk factors of cHCC-CCA with Rim APHE. However, only hepatic capsule retraction (OR = 0.091, p < 0.001) was an independent predictor of iCCA. In addition, combining AFP > 20 ng/ml with enhancing capsule (96.7% vs. 79.2%, p < 0.001) and/or mosaic architecture (96.4% vs. 94.7%, p < 0.001) can improve the sensitivity of differentiating cHCC-CCA (vs. iCCA) with Rim APHE. CONCLUSION: The combination of elevated AFP and MRI features, such as enhancing capsule and mosaic architecture, will help in preoperative differential diagnosis of cHCC-CCA and iCCA with Rim APHE.

MR radiomics to predict microvascular invasion status and biological process in combined hepatocellular carcinoma-cholangiocarcinoma.

OBJECTIVES: To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. METHODS: The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan-Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. RESULTS: One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. CONCLUSION: A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. CRITICAL RELEVANCE STATEMENT: MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. KEY POINTS: MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA.

Value of magnetic resonance imaging for diagnosis of LR­3 and LR-4 lesions coexisting with hepatocellular carcinoma.

PURPOSE: To explore which preoperative clinical data and conventional magnetic resonance imaging (MRI) features may indicate the presence of hepatocellular carcinoma (HCC) in HCC patients coexisting with LR-3 and LR-4 lesions. METHODS: HCC Patients coexisting with LR-3 and LR-4 lesions who participated in a prospective clinical trial (XX) were included in this study. Two radiologists independently assessed the preoperative MRI features and each lesion was assigned according to the liver imaging reporting and data system (LI-RADS). The preoperative clinical data were also evaluated. The relative values of these parameters were assessed as potential predictors of HCC for coexisting LR-3 and LR-4 lesions. RESULTS: We enrolled 102 HCC patients (58.1 ± 11.5 years; 84.3% males) coexisting with 110 LR-3 and LR-4 lesions (HCCs group [n = 66]; non-HCCs group [n = 44]). The presence of restricted diffusion (OR: 18.590, p < 0.001), delayed enhancement (OR: 0.113, p < 0.001), and mild-moderate T2 hyperintensity (OR: 3.084, p = 0.048) were found to be independent predictors of HCC diagnosis. The sensitivity and specificity of the above independent variables for the diagnosis of HCC ranged from 66.7 to 80.3% and 56.8 to 88.6%, respectively. ROC analysis showed that, in discriminating HCC, the AUCs of the above factors were 0.777, 0.686, and 0.670, respectively. Combining these three findings for the prediction of HCC resulted in a specificity greater than 97%, and the AUC further increased to 0.874. CONCLUSION: The presence of restricted diffusion, delayed enhancement, and mild-moderate T2 hyperintensity can be useful features for risk stratification of coexisting LR-3 and LR-4 lesions in HCC patients. Trial registration a prospective clinical trial (ChiCTR2000036201).

Component prediction in combined hepatocellular carcinoma-cholangiocarcinoma: habitat imaging and its biologic underpinnings.

PURPOSE: To construct an MRI-based habitat imaging model to help predict component percentage in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) preoperatively, and investigate the biologic underpinnings of habitat imaging in cHCC-CCA. METHODS: The study consisted of one retrospective model-building dataset and one prospective validation dataset from two hospitals. All voxels were assigned into different clusters according to the similarity of enhancement pattern by using K-means clustering method, and each habitat's volume fraction in each lesion was calculated. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select optimal predictors, and then to establish an MRI-based habitat imaging model. R-squared was calculated to evaluate performance of the prediction models. Model performance was also verified in the prospective dataset with RNA sequencing data, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then applied to investigate the biologic underpinnings of habitat imaging. RESULTS: A total of 129 patients were enrolled (mean age, 56.1 ± 10.4, 102 man), among which 104 patients were in the retrospective model-building set, while 25 patients in the prospective validation set. Three habitats, habitat1 (HCC-alike habitat), habitat2 (iCCA-alike habitat), and habitat3 (in-between habitat), were identified. Habitat 1's volume fraction, habitat 3's volume fraction, nonrim APHE, nonperipheral washout, and LI-RADS categorization were selected to develop an HCC percentage prediction model with R-squared of 0.611 in the model-building set and 0.541 in the validation set. Habitat 1's volume fraction was correlated with genes involved in regulation of actin cytoskeleton and Rap1 signaling pathway, which regulate cell migration and tumor metastasis. CONCLUSION: Preoperative prediction of HCC percentage in patients with cHCC-CCA was achieved using an MRI-based habitat imaging model, which may correlate with signaling pathways regulating cell migration and tumor metastasis.

Subcentimeter Nodules with Diagnostic Hallmarks of Hepatocellular Carcinoma: Comparison of Pathological Features and Survival Outcomes with Nodules Measuring 1-2 cm.

Objective: To compare the pathologic diagnosis and survival of patients with subcentimeter and 1-2 cm nodules that present with diagnostic hallmarks of hepatocellular carcinoma (HCC). Methods: Diagnostic hallmarks of HCC were defined as hyperintensity on T2 weighted imaging, restricted diffusion, arterial phase hyperenhancement, washout on portal venous phase, and hypointensity on hepatobiliary phase. We retrospectively included 139 patients undergoing curative resection with single nodules ≤2 cm that present imaging features described above on gadoxetic acid-enhanced MRI. The final diagnosis was confirmed by histopathological assessment. Recurrence-free survival (RFS) was compared using Kaplan-Meier analysis with the Log-rank test. Factors associated with overall and early recurrence were identified using Cox regression analysis. Results: Among 139 nodules (49 nodules <1 cm), there was no significant difference in the percentage of HCC between subcentimeter and 1-2 cm nodules (94.0% vs 94.4%, P > 0.999). Microvascular invasion (MVI) was less common in subcentimeter HCC (4.3% vs 17.6%, P = 0.032). There were 27 recurrences during a median follow-up time of 46.7 months. Patients with subcentimeter HCC achieved less recurrence, with a 5-year RFS rate of 87.3%. The MVI-positive patients had more early and overall recurrence. A tumor size <1 cm was associated with lower overall recurrence (HR, 0.336; P = 0.047). No factors were independently associated with early recurrence. Conclusion: Subcentimeter nodules with diagnostic hallmarks of HCC are highly associated with HCC diagnosis and achieve less tumor recurrence after resection. Early diagnosis and treatment of subcentimeter HCC may be more appropriate.

Preoperative subcategorization based on magnetic resonance imaging in intrahepatic cholangiocarcinoma.

BACKGROUND: Appropriate preoperative identification of iCCA subtype is essential for personalized management, so the aim of this study is to investigate the role of MR imaging features in preoperatively differentiating the iCCA subtype. METHODS: Ninety-three patients with mass-forming intrahepatic cholangiocarcinoma (iCCA, 63 small duct type and 30 large duct type) were retrospectively enrolled according to the latest 5th WHO classification (mean age, males vs. females: 60.66 ± 10.53 vs. 61.88 ± 12.82, 50 men). Significant imaging features for differentiating large duct iCCA and small duct iCCA were identified using univariate and multivariate logistic regression analyses, and a regression-based predictive model was then generated. Furthermore, diagnostic performance parameters of single significant imaging features and the predictive model were obtained, and corresponding receiver operating characteristic (ROC) curves were subsequently presented. RESULTS: The univariate analysis showed that tumor in vein, arterial phase hypoenhancement, intrahepatic duct dilatation, lack of targetoid restriction and lack of targetoid appearance in T2 were predictors of large duct type iCCA. Arterial phase hypoenhancement, intrahepatic duct dilatation and lack of targetoid restriction were independent predictors for large duct type iCCA in multivariate analysis. The regression-based predictive model has achieved the best preoperative prediction performance in iCCA subcategorization so far. The area under the ROC curve of the regression-based predictive model was up to 0.91 (95% CI: 0.85, 0.98), and it was significantly higher than every single significant imaging feature. CONCLUSIONS: Arterial phase hypoenhancement, intrahepatic duct dilatation and lack of targetoid restriction could be considered reliable MR imaging indicators of large duct type iCCA. MR imaging features can facilitate noninvasive prediction of iCCA subtype with satisfactory predictive performance.

Prognosis of Primary Liver Cancer Based on LI-RADS Classification with Extracellular Agent-Enhanced MRI.

Objective: The prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) 2018 in differentiating hepatocellular carcinoma (HCC) from other primary liver cancers (PLC) with cirrhosis is unclear. We aim to evaluate the value of LI-RADS 2018 with agent-enhanced MRI in the postoperative prognosis of PLC patients with cirrhosis. Methods: Between 2016 and 2021, 432 patients with cirrhosis and surgically proven single primary liver cancer were retrospectively evaluated. Two radiologists evaluated the preoperative MRI features independently and assigned each lesion a LI-RADS category. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, Log rank test, and Cox proportional hazards model. Results: The mean age of 432 patients (239 HCCs, 93 ICCs, and 100 cHCC-CCAs) was 57.27±10.92 years. The LR-M category showed poorer OS and RFS than the LR-4 or LR-5 category did for all primary liver cancers (P <0.001 for both), and so did HCCs with tumor size less than 30mm (P =0.003 and P =0.04, respectively). In the multivariable analysis, the LI-RADS category and tumor size > 30 mm had independent correlations with OS and RFS (all P < 0.05). Multivariable Cox analysis identified rim arterial phase hyperenhancement (APHE) as independent determinants of poor OS and RFS in primary liver cancers (all P < 0.05). Conclusion: The LI-RADS categories can predict the postsurgical prognosis of primary liver cancers independently.