Arterial Phase Hyperenhancement Research Articles

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

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. 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. Seventy cHCC-CCA patients (mean age, 55.7 ± 10.6years) and 74 iCCA patients (mean age, 61.1 ± 10.5years) were evaluated. In this study, univariable and multivariable regression analysis showed that AFP > 20ng/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 > 20ng/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. 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.

Contrast-Enhanced Ultrasound With Perfluorobutane for Hepatocellular Carcinoma Diagnosis: Comparison of Imaging Phases and Diagnostic Criteria.

BACKGROUND. Contrast-enhanced ultrasound (CEUS) with perfluorobutane has used varying protocols and diagnostic criteria for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to assess diagnostic performance for HCC of CEUS with perfluorobutane in high-risk patients using various criteria. METHODS. This retrospective post hoc study evaluating individual patient data from three earlier prospective studies from one hospital included 204 patients (136 men, 68 women; mean age, 63 ± 11 [SD] years) at high risk of HCC with 213 liver observations. Patients underwent CEUS using perfluorobutane from March 2019 to June 2022. Three radiologists (the examination's operator and two subsequent reviewers) independently interpreted examinations, assessing arterial, portal venous (arterial phase completion through 2 minutes), transitional (2-5 minutes after injection), and Kupffer (≥ 10 minutes after injection) phase findings. Six criteria for HCC were tested: 1, any arterial phase hyperenhancement (APHE) with Kupffer phase hypoenhancement; 2, nonrim APHE with Kupffer phase hypoenhancement; 3, nonrim APHE with portal venous washout; 4, nonrim APHE with portal venous washout and/or Kupffer phase hypoenhancement; 5, nonrim APHE with portal venous and/or transitional washout; 6, nonrim APHE with any of portal venous washout, transitional washout, or Kupffer phase hypoenhancement. Depending on the criteria, observations were instead deemed to be a non-HCC malignancy if showing rim APHE, early washout (at < 1 minute), or marked washout (at 2 minutes). Reference was pathology for malignant observations and pathology or imaging follow-up for benign observations. Diagnostic performance was assessed, pooling readers' data. RESULTS. Criterion 1 (no recognized features of non-HCC malignancy) had highest sensitivity (86.9%) but lowest specificity (43.2%) for HCC. Compared with nonrim APHE and portal venous washout (criterion 3), the addition of Kupffer phase hypoenhancement (criterion 4), transitional washout (criterion 5), or either feature (criterion 6) significantly increased sensitivity (34.4% vs 62.6-64.2%) and accuracy (61.8% vs 75.1-76.5%), but significantly decreased specificity (98.5% vs 91.9-94.1%). Criteria 2, 4, 5, and 6 (all incorporating transitional washout and/or Kupffer phase hypoenhancement) showed no significant differences in sensitivity (62.6-64.2%), specificity (91.9-94.1%), or accuracy (75.1-76.5%). CONCLUSION. Recognition of features of non-HCC malignancy improved specificity for HCC. Incorporation of the findings of transitional washout and/or Kupffer phase hypoenhancement improved sensitivity and accuracy, albeit lowered specificity, versus arterial and portal venous findings alone, without further performance variation among criteria incorporating those two findings. CLINICAL IMPACT. Kupffer phase acquisition may be optional for observations classified as HCC or non-HCC malignancy by arterial, portal venous, and transitional phases.

Comparison contrast-enhanced CT with contrast-enhanced US in diagnosing combined hepatocellular-cholangiocarcinoma: a propensity score-matched study

ObjectivesTo develop and compare noninvasive models for differentiating between combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and HCC based on serum tumor markers, contrast-enhanced ultrasound (CEUS), and computed tomography (CECT).MethodsFrom January 2010 to December 2021, patients with pathologically confirmed cHCC-CCA or HCC who underwent both preoperative CEUS and CECT were retrospectively enrolled. Propensity scores were calculated to match cHCC-CCA and HCC patients with a near-neighbor ratio of 1:2. Two predicted models, a CEUS-predominant (CEUS features plus tumor markers) and a CECT-predominant model (CECT features plus tumor markers), were constructed using logistic regression analyses. Model performance was evaluated by the area under the curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 135 patients (mean age, 51.3 years ± 10.9; 122 men) with 135 tumors (45 cHCC-CCA and 90 HCC) were included. By logistic regression analysis, unclear boundary in the intratumoral nonenhanced area, partial washout on CEUS, CA 19-9 > 100 U/mL, lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT were independent factors for a diagnosis of cHCC-CCA. The CECT-predominant model showed almost perfect sensitivity for cHCC-CCA, unlike the CEUS-predominant model (93.3% vs. 55.6%, p < 0.001). The CEUS-predominant model showed higher diagnostic specificity than the CECT-predominant model (80.0% vs. 63.3%; p = 0.020), especially in the ≤ 5 cm subgroup (92.0% vs. 70.0%; p = 0.013).ConclusionsThe CECT-predominant model provides higher diagnostic sensitivity than the CEUS-predominant model for CHCC-CCA. Combining CECT features with serum CA 19-9 > 100 U/mL shows excellent sensitivity.Critical relevance statementCombining lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT with serum CA 19-9 > 100 U/mL shows excellent sensitivity in differentiating cHCC-CCA from HCC.Key points1. Accurate differentiation between cHCC-CCA and HCC is essential for treatment decisions.2. The CECT-predominant model provides higher accuracy than the CEUS-predominant model for CHCC-CCA.3. Combining CECT features and CA 19-9 levels shows a sensitivity of 93.3% in diagnosing cHCC-CCA.Graphical

Are dilution, slow injection and care bolus technique the causal solution to mitigating arterial-phase artifacts on gadoxetic acid–enhanced MRI? A large-cohort study

ObjectiveArterial-phase artifacts are gadoxetic acid (GA)–enhanced MRI’s major drawback, ranging from 5 to 39%. We evaluate the effect of dilution and slow injection of GA using automated fluoroscopic triggering on liver MRI arterial-phase (AP) acquisition timing, artifact frequency, and lesion visibility.Methods and materialsSaline-diluted 1:1 GA was injected at 1 ml/s into 1413 patients for 3 T liver MRI. Initially, one senior abdominal radiologist, i.e., principal investigator (PI), assessed all MR exams and compared them to previous and follow-up images, as well as the radiology report on record, determining the standard of reference for lesion detection and characterization. Then, three other readers independently evaluated the AP images for artifact type (truncation (TA), transient severe motion (TSM) or mixed), artifact severity (on a 5-point scale), acquisition timing (on a 4-point scale) and visibility (on a 5-point scale) of hypervascular lesions ≥ 5 mm, selected by the PI. Artifact score ≥ 4 and artifact score ≤ 3 were considered significant and non-significant artifacts, respectively.ResultsOf the 1413 exams, diagnostic-quality arterial-phase images included 1100 (77.8%) without artifacts, 220 (15.6%) with minimal, and 77 (5.4%) with moderate artifacts. Only 16 exams (1.1%) had significant artifacts, 13 (0.9%) with severe artifacts (score 4), and three (0.2%) non-diagnostic artifacts (score 5). AP acquisition timing was optimal in 1369 (96.8%) exams. Of the 449 AP hypervascular lesions, 432 (96.2%) were detected.ConclusionCombined dilution and slow injection of GA with MR results in well-timed arterial-phase images in 96.8% and a reduction of exams with significant artifacts to 1.1%.Clinical relevance statementHypervascular lesions, in particular HCC detection, hinge on arterial-phase hyperenhancement, making well-timed, artifact-free arterial-phase images a prerequisite for accurate diagnosis. Saline dilution 1:1, slow injection (1 ml/s), and automated bolus triggering reduce artifacts and optimize acquisition timing.Key Points• There was substantial agreement among the three readers regarding the presence and type of arterial-phase (AP) artifacts, acquisition timing, and lesion visibility.• Impaired AP hypervascular lesion visibility occurred in 17 (3.8%) cases; in eight lesions due to mistiming and in nine lesions due to significant artifacts.• When AP timing was suboptimal, it was too late in 40 exams (3%) and too early in 4 exams (0.2%) of exams.

FI-CEUS: a solution to improve the diagnostic accuracy in MRI LI-RADS-indeterminate (LR-3/4) FLLs at risk for HCC.

To evaluate the diagnostic accuracy of fusion imaging contrast-enhanced ultrasound (FI-CEUS) of magnetic resonance imaging (MRI) LI-RADS-indeterminate (LR-3/4) and conventional ultrasound undetected focal liver lesions (FLLs) in patients at risk for hepatocellular carcinoma (HCC). Between February 2020 and July 2021, 71 FLLs in 63 patients were registered for diagnostic performance evaluation respectively for ultrasound-guided thermal ablation evaluation in this retrospective study. Diagnostic performance regarding FLLs was compared between FI-CEUS and contrast-enhanced MRI (CE-MRI). For diagnostic performance evaluation, among 71 lesions in 63 patients, the diagnostic efficacy of FI-CEUS with LI-RADS was significantly higher than that of CE-MRI (P < 0.05) in both overall and hierarchical comparison (except for the group with lesion diameter ≥2 cm). For malignant lesions, the proportion of arterial phase hyperenhancement (APHE) and washout on FI-CEUS was higher than that on CE-MRI (P < 0.05). FI-CEUS has a high value in the precise qualitative diagnosis of small FLLs (<2 cm) of MRI LI-RADS-indeterminate diagnosis (LR-3/4) that are undetected by conventional ultrasound in patients at risk for HCC and can be a good supplementary CE-MRI diagnostic method for thermal ablation evaluation.

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

The timing phase affected the inconsistency of APHE subtypes of liver observations in patients at risk for HCC on the multi-hepatic arterial phase imaging.

To investigate whether liver observations in patients at risk for hepatocellular carcinoma (HCC) display inconsistent arterial phase hyperenhancement (APHE) subtypes on the multi-hepatic arterial phase imaging (mHAP) and to further investigate factors affecting inconsistent APHE subtype of observations on mHAP imaging. From April 2018 to June 2021, a total of 141 patients at high risk of HCC with 238 liver observations who underwent mHAP MRI acquisitions were consecutively included in this retrospective study. Two experienced radiologists reviewed individual arterial phase imaging independently and assessed the enhancement pattern of each liver observation according to LI-RADS. Another two experienced radiologists identified and recorded the genuine timing phase of each phase independently. When a disagreement appeared between the two radiologists, another expert participated in the discussion to get a final decision. A separate descriptive analysis was used for all observations scored APHE by the radiologists. The Kappa coefficient was used to determine the agreement between the two radiologists. Univariate analysis was performed to investigate the factors affecting inconsistent APHE subtype of liver observations on mHAP imaging. The interobserver agreement was substantial to almost perfect agreement on the assessment of timing phase (κ=0.712-0.887) and evaluation of APHE subtype (κ=0.795-0.901). A total of 87.8% (209/238) of the observations showed consistent nonrim APHE and 10.2% (24/238) of the observations showed consistent rim APHE on mHAP imaging. A total of 2.1% (5/238) of the liver observations were considered inconsistent APHE subtypes, and all progressed nonrim to rim on mHAP imaging. 87.9% (124/141) of the mHAP acquisitions were all arterial phases and 12.1% (17/141) of the mHAP acquisitions obtained both the arterial phase and portal venous phase. Univariate analysis was performed and found that the timing phase of mHAP imaging affected the consistency of APHE subtype of liver observations. When considering the timing phase and excluding the portal venous phase acquired by mHAP imaging, none of the liver observations showed inconsistent APHE subtypes on mHAP imaging. The timing phase which mHAP acquisition contained portal venous phase affected the inconsistency of APHE subtype of liver observations on mHAP imaging. When evaluating the APHE subtype of liver observations, it's necessary to assess the timing of each phase acquired by the mHAP technique at first.

Hepatobiliary-Phase Hypointense Nodules Without Arterial-Phase Hyperenhancement: Developing a Risk Stratification for Hypervascular Transformation Based on a Real-World Observational Cohort Study.

To develop a risk stratification based on MRI features to predict hypervascular transformation for hepatobiliary-phase (HBP) hypointense nodules without arterial-phase hyperenhancement (APHE). This retrospective observational cohort study included 55 HBP hypointense nodules without APHE in 35 patients with chronic liver disease, cirrhosis, or current hepatocellular carcinoma (HCC) who underwent gadoxetic acid-enhanced MRI. The hypervascular transformation during the follow-up MRI(s) was the primary endpoint analyzed for the nodules. Univariable and multivariable Cox proportional hazard regression analyses were performed to identify risk features predicting transformation and assess their predictive value. Among the 55 nodules, 27 developed hypervascular transformation, while 28 did not. Diffusion-weighted imaging (DWI) hyperintensity (hazard ratio [HR], 4.98; 95% confidence interval [CI]: 1.60, 15.54; p = 0.006) and portal venous phase (PVP) hypointensity (HR, 4.08; 95% CI: 1.43, 11.64; p = 0.009) were associated with hypervascular transformation. DWI hyperintensity and PVP hypointensity had 44.4% (95% CI: 26.0%, 64.4%) and 81.9% (95% CI: 61.3%, 93.0%) sensitivity, while their specificity was 78.2% (95% CI: 64.6%, 87.8%) and 67.9 (95% CI: 47.6%, 83.4%), respectively. The specificity of the combination of two features was 100% (95% CI: 85.0%, 100%). The hypervascular transformation rates for nodules with both, either and neither of the risk MRI findings were 100% (10/10), 60.9% (14/23), and 13.6% (3/22), respectively; the median intervals for transformation were 312 (range: 73-838), 409 (range: 50-1643) and 555 (range: 423-968) days, respectively. The combination of DWI hyperintensity and PVP hypointensity may be used as a high-risk indicator for the hypervascular transformation of HBP hypointense nodules without APHE; nodules without either feature may be treated as low-risk nodules and could adopt an extended interval follow-up schedule.

Based on Gadolinium Ethoxybenzyl DTPA-Enhanced MRI: Diagnostic Performance of the Category-Modified LR-5 Criteria in Patients At Risk for Hepatocellular Carcinoma.

Introduction: We aimed to modify the LR-5 strategy to improve the diagnostic sensitivity for hepatocellular carcinoma (HCC) in high-risk patients while maintaining specificity. Methods: This study retrospectively analyzed 412 patients with 445 liver observations who underwent preoperative gadolinium ethoxybenzyl DTPA (GD-EOB-DTPA)-enhanced MRI followed by surgical procedures or biopsies. All observations were classified according to LI-RADS v2018, and the classifications were adjusted by modifying major features (MF)(substituting threshold growth with a more HCC-specific ancillary features (AF): presence of blood products within the mass, arterial phase hyperenhancement (APHE) was interpreted with hypointensity on precontrast imaging- isointensity in arterial phase (AP) and extending washout to transitional phase (TP)(2 min)). The specificity, sensitivity, and positive predictive value (PPV) were assessed to compare LR-5 (definitely HCC) diagnostic efficacy between LI-RADS version 2018 and modified LI-RADS. Results: Apart from nonenhancing "capsule", the interreader agreement of MFs and HCC-specific AFs between the two readers reached substantial or excellent ranges (κ values ranging from 0.631 to 0.911). According to LI-5 v2018, the specificity, sensitivity and PPV of HCC were 90.74%, 82.35%, and 98.17%, respectively. Based on a more HCC-specific AF, signal intensity in AP and TP (2 min), the sensitivity of the three modified strategies were 86.19%, 93.09%, 96.67% (P < .05)), while maintaining high specificity and PPV rates at 88.89% and 98.25% (P > .05) Conclusion: Further investigation into the efficacy of threshold growth as a MF is warranted. By utilizing GD-EOB-DTPA-enhanced MRI, enhancing the sensitivity of the modified LR-5 category may be achieved without compromising specificity and PPV in diagnosing HCC among high-risk patients.

Primary hepatic neuroendocrine neoplasms: imaging characteristics and misdiagnosis analysis.

To analyze the CT and MR features of Primary hepatic neuroendocrine neoplasms (PHNENs) in order to enhance the diagnostic accuracy of this disease. A retrospective analysis was conducted on patients diagnosed with hepatic neuroendocrine neoplasms, excluding other sites of origin through general examination and postoperative follow-up. The CT and MR signs were analyzed according to the 2018 version of Liver Imaging Reporting and Data System (LI-RADS), along with causes of misdiagnosis. Twelve patients, including 6 males and 6 females, were enrolled in this study. There was no significant increase in liver tumor markers among all cases. Most masses were multiple (9/12), exhibiting low attenuation on pre-contrast CT scans, T1-hypointense signal, T2-hyperintense signal, and restricted diffusion. The majority of these masses (7/10) demonstrated similar rim arterial phase hyper-enhancement as well as peripheral "washout" during venous portal phase and delayed phase imaging. Three cases had incomplete capsules while one case had a complete capsule. Cyst/necrosis was observed in 7 out of all cases following administration of contrast agent, with 5 mainly distributed in the periphery. All masses lacked fat, calcification, vascular or bile duct tumor thrombus formation. The imaging findings associated with PHNENs possess certain specificity, often presenting as multiple masses within the liver accompanied by peripheral cyst/necrosis, similar rim arterial phase hyper-enhancement during venous portal phase and delayed phase imaging.

Predicting glypican-3 expression in hepatocellular carcinoma: A comprehensive analysis using combined contrast-enhanced ultrasound and clinical factors.

Glypican-3 (GPC3) has emerged as a significant marker for the diagnosis and prognosis of hepatocellular carcinoma (HCC) and has garnered considerable attention as an immunotherapeutic target. In this study, we propose a combination of preoperative contrast-enhanced ultrasound (CEUS) imaging features and clinical factors to predict the positive expression of GPC3 in HCC patients. We retrospectively included 30 cases of GPC3-negative HCC and 115 cases of GPC3-positive HCC patients who underwent conventional ultrasound and CEUS evaluation. We assessed and compared the clinical characteristics, conventional ultrasound features, and CEUS features between the two groups of HCC patients. Based on the clinical and ultrasound features between the two groups, we developed a binary logistic regression model for predicting GPC3-positive HCC. A total of 145 HCC patients were included in this study. Binary logistic regression analysis showed that AFP > 20 ng/mL (OR = 4.047; 95% CI: 1.467-11.16; p = 0.007), arterial phase hyperenhancement (APHE) (OR = 12.557; 95% CI: 3.608-43.706; p < 0.001), and asynchronous perfusion (OR = 4.209; 95% CI: 1.206-14.691; p = 0.024) were predictive factors for GPC3-positive HCC. Receiver operating characteristic (ROC) analysis was conducted to predict GPC3-positive expression. The model combining the three independent predictive factors showed good predictive performance (AUC 0.817, 95% CI: 0.731-0.902, sensitivity: 91.3%, specificity: 60.0%). This combined model demonstrated excellent discriminatory ability to predict GPC3-positive HCC. Preoperative integration of CEUS features and clinical factors can non-invasively and effectively identify GPC3-positive HCC patients, providing valuable assistance in making personalized treatment decisions.

Intrahepatic splenosis: Contrast enhanced ultrasound and magnetic resonance imaging findings.

To evaluate the contrast enhanced ultrasound (CEUS) and contrast enhanced magnetic resonance imaging (CEMRI) features of intrahepatic splenosis (IHS). Five patients (three males and two females, median age, 44 years; range,32-73 years) with seven IHSs were retrieved from the database of our hospital from March 2012 to October 2021. All IHSs were confirmed histologically by surgery. The CEUS and CEMRI characteristics of individual lesion were fully analyzed. All IHS patients were asymptomatic and four out of five patients had history of splenectomy. On CEUS, all IHSs were hyperenhancement in arterial phase. 71.4% (5/7) of IHSs manifested overall filling within few seconds, the other two lesions showed centripetal filling. Subcapsular vascular hyperenhancement and feeding artery was seen in 28.6% (2/7) and 42.9% (3/7) of IHSs, respectively. During portal venous phase, IHSs presented hyperenhancement (2/7) or isoenhancement (5/7). Moreover, rim-like hypoenhanced area was uniquely observed surrounding 85.7% (6/7) of IHSs. In late phase, seven IHSs remained continuous hyper- or isoenhancement. On CEMRI, five IHSs showed mosaic hyperintense in early arterial phase, the other two lesions showed homogeneous hyperintense. In portal venous phase, all IHSs revealed continuous hyper- (71.4%, 5/7) or iso-intense (28.6%, 2/7). During late phase, one IHS (14.3%, 1/7) became hypointense, the other lesions remained hyper- or isointense. Diagnosis of IHS can be based on typical CEUS and CEMRI features in patients with history of splenectomy.

Prediction of macrotrabecular-massive hepatocellular carcinoma by using MR-based models and their prognostic implications.

To evaluate the efficacy of MRI-based radiomics and clinical models in predicting MTM-HCC. Additionally, to investigate the ability of the radiomics model designed for MTM-HCC identification in predicting disease-free survival (DFS) in patients with HCC. A total of 336 patients who underwent oncological resection for HCC between June 2007 and March 2021 were included. 127 patients in Cohort1 were used for MTM-HCC identification, and 209 patients in Cohort2 for prognostic analyses. Radiomics analysis was performed using volumes of interest of HCC delineated on pre-operative MRI images. Radiomics and clinical models were developed using Random Forest algorithm in Cohort1 and a radiomics probability (RP) of MTM-HCC was obtained from the radiomics model. Based on the RP, patients in Cohort2 were divided into a RAD-MTM-HCC (RAD-M) group and a RAD-non-MTM-HCC (RAD-nM) group. Univariate and multivariate Cox regression analyses were employed to identify the independent predictors for DFS of patients in Cohort2. Kaplan-Meier curves were used to compare the DFS between different groups pf patients based on the predictors. The radiomics model for identifying MTM-HCC showed AUCs of 0.916 (95% CI: 0.858-0.960) and 0.833 (95% CI: 0.675-0.935), and the clinical model showed AUCs of 0.760 (95% CI: 0.669-0.836) and 0.704 (95% CI: 0.532-0.843) in the respective training and validation sets. Furthermore, the radiomics biomarker RP, portal or hepatic vein tumor thrombus, irregular rim-like arterial phase hyperenhancement (IRE) and AFP were independent predictors of DFS in patients with HCC. The DFS of RAD-nM group was significantly higher than that of the RAD-M group (p < .001). MR-based clinical and radiomic models have the potential to accurately diagnose MTM-HCC. Moreover, the radiomics signature designed to identify MTM-HCC also can be used to predict prognosis in patients with HCC, realizing the diagnostic and prognostic aims at the same time.

Liver Lesions at Risk of Transformation into Hepatocellular Carcinoma in Cirrhotic Patients: Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement.

Recent technical advances in liver imaging and surveillance for patients at high risk for developing hepatocellular carcinoma (HCC) have led to an increase in the detection of borderline hepatic nodules in the gray area of multistep carcinogenesis, particularly in those that are hypointense at the hepatobiliary phase (HBP) and do not show arterial phase hyperenhancement. Given their potential to transform and advance into hypervascular HCC, these nodules have progressively attracted the interest of the scientific community. To date, however, no shared guidelines have been established for the decision management of these borderline hepatic nodules. It is therefore extremely important to identify features that indicate the malignant potential of these nodules and the likelihood of vascularization. In fact, a more complete knowledge of their history and evolution would allow outlining shared guidelines for their clinical-surgical management, to implement early treatment programs and decide between a preventive curative treatment or a watchful follow-up. This review aims to summarize the current knowledge on hepatic borderline nodules, particularly focusing on those imaging features which are hypothetically correlated with their malignant evolution, and to discuss current guidelines and ongoing management in clinical practice.

Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma-a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®.

The recognition of arterial phase hyperenhancement (APHE) and washout during the late phase is key for correct diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). This meta-analysis was conducted to compare SonoVue®-enhanced and Sonazoid®-enhanced ultrasound in the assessment of HCC enhancement and diagnosis. Studies were included in the analysis if they reported data for HCC enhancement in the arterial phase and late phase for SonoVue® or in the arterial phase and Kupffer phase (KP) for Sonazoid®. Forty-two studies (7502 patients) with use of SonoVue® and 30 studies (2391 patients) with use of Sonazoid® were identified. In a pooled analysis, the comparison between SonoVue® and Sonazoid® CEUS was performed using chi-square test. An inverse variance weighted random-effect model was used to estimate proportion, sensitivity, and specificity along with 95% confidence interval (CI). In the meta-analysis, the proportion of HCC showing APHE with SonoVue®, 93% (95% CI 91-95%), was significantly higher than the proportion of HCC showing APHE with Sonazoid®, 77% (71-83%) (p < 0.0001); similarly, the proportion of HCC showing washout at late phase/KP was significantly higher with SonoVue®, 86% (83-89%), than with Sonazoid®, 76% (70-82%) (p < 0.0001). The sensitivity and specificity for the detection of APHE plus late-phase/KP washout detection in HCC were also higher with SonoVue® than with Sonazoid® (sensitivity 80% vs 52%; specificity 80% vs 73% in studies within unselected patient populations). APHE and late washout in HCC are more frequently observed with SonoVue® than with Sonazoid®. This may affect the diagnostic performance of CEUS in the diagnosis of HCCs. Meta-analysis data show the presence of key enhancement features for diagnosis of hepatocellular carcinoma is different between ultrasound contrast agents, and arterial hyperenhancement and late washout are more frequently observed at contrast-enhanced ultrasound with SonoVue® than with Sonazoid®. • Dynamic enhancement features are key for imaging-based diagnosis of HCC. • Arterial hyperenhancement and late washout are more often observed in HCCs using SonoVue®-enhanced US than with Sonazoid®. • The existing evidence for contrast-enhanced US may need to be considered being specific to the individual contrast agent.

Preoperative prediction of cholangiocyte phenotype hepatocellular carcinoma on contrast-enhanced MRI and the prognostic implication after hepatectomy

BackgroundHepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy.MethodsBetween January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan–Meier and log-rank methods were used to evaluate survival outcomes.ResultsIn total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including “rim arterial phase hyperenhancement” (OR = 5.9, 95% confidence interval [CI]: 2.9–12.0, 10 points), “nodule in nodule architecture” (OR = 3.5, 95% CI: 2.1–5.9, 7 points), “non-smooth tumor margin” (OR = 1.6, 95% CI: 0.8–2.9, 3 points), and “non-peripheral washout” (OR = 0.6, 95% CI: 0.3–1.0, − 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively.ConclusionsContrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy.Critical relevance statementFour contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making.Key points• Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC.• A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features.• Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection.Graphical

Assessment of LI-RADS efficacy in classification of hepatocellular carcinoma and benign liver nodules using DCE-MRI features and machine learning

PurposeThe current study aimed to evaluate the efficiency of dynamic contrast-enhanced (DCE) MRI visual features in classifying benign liver nodules and hepatocellular carcinoma (HCC) using a machine learning model. Methods115 LI-RADS3, 137 LI-RADS4, and 140 LI-RADS5 nodules were included (392 nodules from 245 patients), which were evaluated by follow-up imaging for LR-3 and pathology results for LR-4 and LR-5 nodules. Data was collected retrospectively from 3 T and 1.5 T MRI scanners. All the lesions were categorized into 124 benign and 268 HCC lesions. Visual features included tumor size, arterial-phase hyper-enhancement (APHE), washout, lesion segment, mass/mass-like, and capsule presence. Gini-importance method extracted the most important features to prevent over-fitting. Final dataset was split into training(70%), validation(10%), and test dataset(20%). The SVM model was used to train the classifying algorithm. For model validation, 5-fold cross-validation was utilized, and the test data set was used to assess the final accuracy. The area under the curve and receiver operating characteristic curves were used to assess the performance of the classifier model. ResultsFor test dataset, the accuracy, sensitivity, and specificity values for classifying benign and HCC lesions were 82%,84%, and 81%, respectively. APHE, washout, tumor size, and mass/mass-like features significantly differentiated benign and HCC lesions with p-value < .001. ConclusionsThe developed classification model employing DCE-MRI features showed significant performance of visual features in classifying benign and HCC lesions. Our study also highlighted the significance of mass and mass-like features in addition to LI-RADS categorization. For future work, this study suggests developing a deep-learning algorithm for automatic lesion segmentation and feature assessment to reduce lesion categorization errors.

A nomogram based on ultrasonographic features and clinical indicators for differentiating mass-forming intrahepatic cholangiocarcinoma and liver metastatic colorectal adenocarcinoma.

This study aimed to develop and validate a nomogram based on ultrasonographic features and clinical indicators to differentiate mass-forming intrahepatic cholangiocarcinoma (MF-ICC) from hepatic metastatic colorectal adenocarcinoma. A total of 343 patients with pathologically confirmed MF-ICC or metastatic colorectal adenocarcinoma were enrolled between October 2018 and July 2022. Patients were randomly assigned to training and validation sets at a ratio of 7:3. Preoperative ultrasound features and clinical indicators were retrieved. Univariate logistic regression analysis was employed to select relevant features. Multivariate logistic regression analysis was used to establish a predictive model, which was presented as a nomogram in training sets. The model's performance was assessed in terms of discrimination, calibration, and clinical usefulness. The study included 169 patients with MF-ICC and 174 with liver metastatic colorectal adenocarcinoma, assigned to training (n=238) and validation (n=105) cohorts. The nomogram incorporated ultrasound features (tumor size, lesion number, echogenicity, tumor necrosis, and rim arterial phase hyperenhancement) and clinical information (serum levels of CEA, CA19-9, CA125). The nomogram demonstrated promising performance in differentiating these two entities in both training and validation sets, with an AUC value of 0.937 (95%CI: 0.907,0.969) and 0.916 (95%CI: 0.863,0.968), respectively. The Hosmer-Lemeshow test and calibration curves confirmed good consistency between predictions and observations. Additionally, decision curve analysis confirmed the nomogram's high clinical practicability. The nomogram based on ultrasound features and clinical indicators demonstrated good discrimination performance in differentiating MF-ICC from metastatic colorectal adenocarcinoma, which may enhance clinical decision-making process in managing these challenging diagnostic scenarios.

Prognostic MRI features to predict postresection survivals for very early to intermediate stage hepatocellular carcinoma

ObjectivesContrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS).Materials and methodsConsecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS.ResultsThis study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p = .02). Nonperipheral washout (p = .006), markedly low apparent diffusion coefficient value (p = .02), intratumoral arteries (p = .01), and width of the main portal vein (p = .03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p = .02). Multiple tumors (p = .048) and radiologically-evident cirrhosis (p < .001) were the only predictors for L-RFS.ConclusionTwelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs.Clinical relevance statementThe prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models.Key Points• Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival.• Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival.• Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years.Graphical

Fat-containing hepatocellular carcinoma in patients with cirrhosis: proposal of a diagnostic modification regarding enhancement characteristics.

The aim of this study was to develop and validate an algorithm for the non-invasive diagnosis of these fat-containing HCCs. Eighty-four cirrhotic patients with 77 fat-containing HCCs and 11 non-HCC fat-containing nodules were retrospectively included. All MRIs were reviewed; nodule characteristics, European Association for the Study of the Liver (EASL) and LI-RADS classifications, and survival were collected. One of the major features of LI-RADS v2018 (non-rim-like arterial phase hyperenhancement [APHE]) was changed to include different enhancing patterns at arterial phase and a new fat-LI-RADS algorithm was created for fat-containing nodules in cirrhosis. Its diagnostic performance was evaluated in both a derivation and external validation cohort (external cohort including 58 fat-containing HCCs and 10 non-HCC fat nodules). Reproducibility of this new algorithm was assessed. In the derivation cohort, 54/77 (70.1%) fat-containing HCCs had APHE, 62/77 (80.5%) had enhancement compared to the nodule itself at arterial phase (APE), 43/77 (55.8%) had washout, and 20/77 (26.0%) had an enhancing capsule. EASL and LI-RADS had a sensitivity of 37.7% (29/77) and 36.4% (28/77), respectively, for the diagnosis of fat-containing HCC and both had a specificity of 100% (11/11). The new fat-LI-RADS algorithm increased sensitivity to 50.6% (39/77) without decreasing the specificity of 100% (11/11). The validation cohort confirmed the increased sensitivity, with a slight decrease in specificity. The concordance for the diagnosis of HCC for fat-LR5 was 85.3% (58/68). The new fat-LI-RADS algorithm proposed here significantly improves the performance of the non-invasive diagnosis of fat-containing HCC and thus could reduce the number of biopsies conducted for fat-containing HCCs. The European Association for the Study of the Liver and LI-RADS guidelines are poorly sensitive for the diagnosis of fat-containing HCC, mainly because of the low rate of arterial phase hyperenhancement (APHE) displayed by fat-containing HCC. Using all types of enhancement instead of APHE improves sensitivity of LI-RADS. • Fat-containing HCCs on MRI account for 7.5% of HCCs and have different imaging characteristics from non-fatty HCCs. • The European Association for the Study of the Liver and LI-RADS algorithms for the non-invasive diagnosis of HCC have low sensitivity for the diagnosis of fat-containing HCC with MRI (37.7% and 36.4%, respectively). • The new fat-LI-RADS, which includes a slight modification of the "arterial enhancement" criterion, improves the sensitivity for the diagnosis of fat-containing HCC using MRI, without degrading the specificity.