Gadoxetic Acid-enhanced Magnetic Resonance Imaging Research Articles

Differentiation of Hepatic Sclerosed Hemangiomas From Cavernous Hemangiomas Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging Features.

The objective of this study was to evaluate the imaging features of a hepatic sclerosed hemangioma by comparing them with those of a cavernous hemangioma using magnetic resonance imaging with gadoxetic acid enhancement. Nine patients with hepatic sclerosed hemangiomas and 36 patients with cavernous hemangiomas (control group) who underwent gadoxetic acid-enhanced magnetic resonance imaging were included. Qualitative values (imaging findings and enhancement pattern [typical vs atypical enhancement]) and quantitative values (apparent diffusion coefficient) were evaluated. Patients with sclerosed hemangiomas showed significantly more irregular tumor margin on hepatobiliary phase images, peritumoral arterial enhancement, and a lower proportion of hyperintensity on heavily T2-weighted images compared with controls (all P values <0.05). In addition, the sclerosed hemangioma group had significantly more frequent atypical enhancement patterns than did the control group (88.9% vs 33.3%; P = 0.006). However, the mean apparent diffusion coefficient value of hemangiomas was not significantly different between the 2 groups (P = 0.639). Gadoxetic acid-enhanced magnetic resonance images can help in differentiating between hepatic sclerosed hemangiomas and cavernous hemangiomas.

Whole-body MRI added to gadoxetic acid-enhanced liver MRI for detection of extrahepatic disease in patients considered eligible for hepatic resection and/or local ablation of colorectal cancer liver metastases.

Background Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can detect extrahepatic disease before local treatment of colorectal liver metastases. Purpose To investigate if whole-body magnetic resonance imaging (MRI) added to gadoxetic acid liver MRI could replace FDG-PET/CT for detection of extrahepatic disease in patients with colorectal liver metastases eligible for hepatic local treatment. Material and Methods This health-research-ethics-committee-approved prospective consecutive diagnostic accuracy study with written informed consent analyzed 79 cases included between 29 June 2015 and 7 February 2017. Whole-body MRI covering the thorax, abdomen, and pelvis and FDG-PET/CT including contrast-enhanced CT was performed 0–3 days before local treatment of liver metastases. Whole-body MR images were read independently by two readers. FDG-PET/CT images were read independently by two pairs of readers. Histopathology and follow-up imaging were used as reference standard. Sensitivities and specificities were calculated and compared including noninferiority analysis. Results Seventy-five malignant lesions and 419 benign lesions were confirmed. Sensitivities of both PET/CT reader pairs 1 and 2 (56.7 and 67.9%) and MRI reader 2 (63.0%) were significantly higher than that of MRI reader 1 (42.7) (P&lt;0.04). Specificities of both PET/CT reader pairs 1 and 2 (92.5 and 92.4%) and MRI reader 1 (91.1%) were significantly higher than that of MRI reader 2 (86.3%) ( P &lt; 0.02). Sensitivity of MRI reader 2 was non-inferior compared to PET/CT reader pair 1. Specificities of both MRI readers were non-inferior to both PET/CT reader pairs. Conclusion For detection of extrahepatic disease in patients with colorectal liver metastases, whole-body MRI was non-inferior to FDG-PET/CT for some reader combinations. However, reader-independent non-inferiority could not be demonstrated.

Gadoxetic acid-enhanced magnetic resonance imaging can predict the pathologic stage of solitary hepatocellular carcinoma.

BACKGROUNDAlthough important for determining long-term outcome, pathologic stage of hepatocellular carcinoma (HCC) is difficult to predict before surgery. Current state-of-the-art magnetic resonance imaging (MRI) using gadoxetic acid provides many imaging features that could potentially be used to classify single HCC as pT1 or pT2.AIMTo determine which gadoxetic acid-enhanced MRI (EOB-MRI) findings predict pathologic stage T2 in patients with solitary HCC (cT1).METHODSPre-operative EOB-MRI findings were reviewed in a retrospective cohort of patients with solitary HCC. The following imaging features were examined: Hyperintensity in unenhanced T2-weighted images, hypointensity in unenhanced T1-weighted images, arterial enhancement, corona enhancement, washout appearance, capsular appearance, hypointensity in the tumor tissue during the hepatobiliary (HB) phase, peritumoral hypointensity in the HB phase, hypointense rim in the HB phase, intratumoral fat, hyperintensity on diffusion-weighted imaging, hypointensity on apparent diffusion coefficient map, mosaic appearance, nodule-in-nodule appearance, and the margin (smooth or irregular). Surgical pathology was used as the reference method for tumor staging. Univariate and multivariate analyses were performed to identify predictors of microvascular invasion or satellite nodules.RESULTSThere were 39 (34.2%; 39 of 114) and 75 (65.8%; 75 of 114) pathological stage T2 and T1 HCCs, respectively. Large tumor size (≥ 2.3 cm) and two MRI findings, i.e., corona enhancement [odds ratio = 2.67; 95% confidence interval: 1.101-6.480] and peritumoral hypointensity in HB phase images (odds ratio = 2.203; 95% confidence interval: 0.961-5.049) were associated with high risk of pT2 HCC. The positive likelihood ratio was 6.25 (95% confidence interval: 1.788-21.845), and sensitivity of EOB-MRI for detecting pT2 HCC was 86.2% when two or three of these MRI features were present. Small tumor size and hypointense rim in the HB phase were regarded as benign features. Small HCCs with hypointense rim but not associated with aggressive features were mostly pT1 lesions (specificity, 100%).CONCLUSIONImaging features on EOB-MRI could potentially be used to predict the pathologic stage of solitary HCC (cT1) as pT1 or pT2.

Optimal lexicon of gadoxetic acid-enhanced magnetic resonance imaging for the diagnosis of hepatocellular carcinoma modified from LI-RADS.

To define the optimal lexicon of major imaging findings on gadoxetic acid-enhanced MRIs to diagnose HCC to improve diagnostic performance of the LI-RADS. Two hundred forty-one hepatic lesions (149 HCC, six other malignancies, 86 benign lesions) in 177 treatment-naïve patients at risk of HCC who underwent gadoxetic acid-MRIs from January 2013 to December 2015 were retrospectively reviewed using either histopathological or follow-up imaging findings as a standard reference. Two board-certified radiologists independently evaluated the imaging features and categorized the nodules based on the original and the following modified definitions in LI-RADS: (1) washout appearance in the portal venous phase (PVP) only versus that in the PVP or transitional phase, and (2) enhancing capsule only versus enhancing or non-enhancing capsule. Diagnostic performance and inter-observer agreement of LR-5 were assessed and compared between the algorithms using generalized estimation equation. The sensitivity [79.2% (95% confidence interval 71.9, 85.0)] and accuracy [84.6% (79.5, 88.7)] of LR-5 were significantly higher for modified lexicon compared with original LI-RADS [60.4% (52.3, 67.9) and 73.9% (67.9, 79.0); P < 0.001 in all cases]. There was no significant difference in specificity [93.5% (86.2, 97.0) and 95.7% (89.0, 98.4); P = 0.153]. Subgroups of lesions < or ≥ 2cm showed similar tendencies. Inter-observer agreement for capsule appearance was fair to moderate, whereas that for other imaging findings was good to excellent. Compared to original LI-RADS, LI-RADS with modified lexicon showed higher sensitivity for the diagnosis of HCC using gadoxetic acid-MRI, with similar specificity.

Differentiation of hypervascular primary hepatic tumors showing hepatobiliary hypointensity on gadoxetic acid-enhanced magnetic resonance imaging.

To determine the imaging features that help differentiate hypervascular primary hepatic tumors showing hepatobiliary hypointensity on gadoxetic acid MRI. This study comprised 148 patients with pathologically proven hypervascular hepatic tumors who underwent gadoxetic acid MRI. Tumors included 23 atypical focal nodular hyperplasias (FNHs), 11 hepatocellular adenomas (HCAs), 15 neuroendocrine tumors (NETs), 25 intrahepatic cholangiocarcinomas (ICCs), and 74 hepatocellular carcinomas (HCCs). MRIs were analyzed for morphologic features, signal intensity, and enhancement pattern of the tumors to determine the differential features using multivariate logistic regression analysis. We evaluated the diagnostic performance of the MRI features for differentiating the five tumor types upon review by two observers. Multivariate analysis revealed that reverse target sign on hepatobiliary phase in FNHs (p = 0.009), iso or hyperintensity on ADC map in FNHs and HCAs (p = 0.009, < 0.001, respectively), central hypointensity on arterial phase in NETs (p = 0.001), hepatobiliary target sign in ICCs (p = 0.002), the presence of septum and capsule in HCCs (all p < 0.001) were significant independent features of each tumor group over other tumor groups. Diagnostic accuracy for both observers was 98-98.6% for FNHs, 96.6-98% for HCAs, 97.3-98.6% for NETs, 90.5-94.6% for ICCs, and 85.8-93.2% for HCCs. Ancillary MRI features established in our study can be helpful in the differentiation of hypervascular and hepatobiliary hypointense primary hepatic tumors on gadoxetic acid MRI.

Hepatocellular carcinoma: radiomics nomogram on gadoxetic acid-enhanced MR imaging for early postoperative recurrence prediction

BackgroundThis study was performed to prospectively develop and validate a radiomics nomogram for predicting postoperative early recurrence (≤1 year) of hepatocellular carcinoma (HCC) using whole-lesion radiomics features on preoperative gadoxetic acid-enhanced magnetic resonance (MR) images.MethodsIn total, 155 patients (training cohort: n = 108; validation cohort: n = 47) with surgically confirmed HCC were enrolled in this IRB-approved prospective study. Three-dimensional whole-lesion regions of interest were manually delineated along the tumour margins on multi-sequence MR images. Radiomics features were generated and selected to build a radiomics score using the least absolute shrinkage and selection operator (LASSO) method. Clinical characteristics and qualitative imaging features were identified by two independent radiologists and combined to establish a clinical-radiological nomogram. A radiomics nomogram comprising the radiomics score and clinical-radiological risk factors was constructed based on multivariable logistic regression analysis. Diagnostic performance and clinical usefulness were measured by receiver operation characteristic (ROC) and decision curves.ResultsIn total, 14 radiomics features were selected to construct the radiomics score. For the clinical-radiological nomogram, the alpha-fetoprotein (AFP) level, gross vascular invasion and non-smooth tumour margin were included. The radiomics nomogram integrating the radiomics score with clinical-radiological risk factors showed better discriminative performance (AUC = 0.844, 95%CI, 0.769 to 0.919) than the clinical-radiological nomogram (AUC = 0.796, 95%CI, 0.712 to 0.881; P = 0.045), with increased clinical usefulness confirmed using a decision curve analysis.ConclusionsIncorporating multiple predictive factors, the radiomics nomogram demonstrated great potential in the preoperative prediction of early HCC recurrence after surgery.

Consistency of hepatocellular gadoxetic acid uptake in serial MRI examinations for evaluation of liver function.

To assess the consistency of liver enhancement in gadoxetic acid-enhanced magnetic resonance imaging (MRI) over serial examinations. This retrospective study included 554 patients who underwent at least 2 serial gadoxetic acid-enhanced MRI scans at either 1.5 or 3.0 Tesla at our institution between 2014 and 2018. Signal intensities (SI) were measured on T1-weighted images before and approx. 20min after intravenous injection of gadoxetic acid. Relative enhancement (RE) of the liver, liver-to-spleen SI ratio (LSR), and liver-to-muscle SI ratio (LMR) were calculated. Means were compared with the paired t test, Greenhouse-Geisser test, and linear mixed model analysis, accordingly. Multiple linear regression analysis was used to elucidate possible predictors of RE and bivariate correlation analysis of patient age with RE was performed. No statistically significant difference in RE, LSR, and LMR between two consecutive MRI scans was found when tested with paired t test or Greenhouse-Geisser test (n = 554, 519, and 554, respectively), while the latter revealed a statistically significant difference between the first and fourth MRI scan which was not confirmed in the linear mixed model. Patient age correlated negatively with RE of the liver (p = 0.002), LSR (p < 0.001), and LMR (p = 0.006). Relative enhancement of the liver in the hepatobiliary phase of gadoxetic acid-enhanced MRI is consistent over successive examinations, different scanner types, and field strengths while correlating negatively with age, which further underscores the validity of gadoxetic acid-enhanced MRI as an imaging-based liver function test.

Imaging biomarkers for well and moderate hepatocellular carcinoma: preoperative magnetic resonance image and histopathological correlation

BackgroundOur aim of the study is to investigate the feasibility of preoperative prediction for hepatocellular carcinoma (HCC) histological grading using gadoxetic acid-enhanced magnetic resonance imaging (MRI).MethodsThis study included one hundred and fifty-six patients with solitary HCC. Preoperative gadoxetic acid-enhanced MRI findings were retrospectively analyzed. MRI qualitative features such as tumor size, margin, capsule status, signal homogeneity, intratumoral vessels, peritumoral enhancement during mid-arterial phase, peritumoral hypointensity during the hepatobiliary phase (HBP) were investigated. Apparent diffusion coefficients (ADCs), T1 reduction ratio of pre- and post-contrast enhanced images of the tumors were calculated. HCC histological grading in surgical specimens were confirmed by Edmonson’s criteria. Correlations between these MRI features and HCC histological grading were analyzed using multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the model.ResultsUnivariate analysis showed that maximum tumor diameter (p = 0.004), tumor margin (p = 0.006), intratumoral vessels (p = 0.001) and peritumoral hypointensity during HBP (p = 0.000), were significantly correlated with HCC histological grading. There was no relationship between capsule, tumor signal, venous thrombosis, peritumoral enhancement during mid-arterial phase, ADC value, T1 reduction ratio, and HCC histological grading. Multivariate logistic regression analysis demonstrated that the maximum tumor diameter (p = 0.012, odds ratio = 1.002, 95% confidence interval: 1.007–1.046)) was an independent risk factor for high grade HCC.ConclusionsGreater tumor size, a more irregular margin, presence of intratumoral vessels, and peritumoral hypointensity during HBP were indicators for high grade HCC. The maximum tumor diameter was an independent risk factor for high grade HCC.

Nomogram Development and Validation to Predict Hepatocellular Carcinoma Tumor Behavior by Preoperative Gadoxetic Acid-Enhanced MRI

Background: Pretreatment evaluation of tumor biology and microenvironment of hepatocellular carcinoma (HCC) are important to predict prognosis and plan treatment. We aimed to develop nomograms based on Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) to predict microvascular invasion (MVI), tumor differentiation, and immunoscore. Methods: This retrospective study included 273 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI. Patients were assigned to two groups: training (N = 191) and validation (N = 82). Univariable and multivariable logistic regression analyses were performed to investigate clinical variables and MRI features' associations with MVI, tumor differentiation and immunoscore. Nomograms were developed based on features associated with these histopathological features in the same training cohort, then validated, and evaluated. Findings: Predictors of MVI included tumor size (P = 0.002), rim enhancement (P = 0.017), percent reduction in T1 images (T1D%; P = 0.043), and standard deviation of apparent diffusion coefficient (P = 0.028), while capsule (P = 0.007), mean relaxation time on the hepatocellular phase (T1E; P < 0.001), and alpha-fetoprotein levels (P = 0.003) predicted tumor differentiation. Predictors of immunoscore included the radiologic score (P = 0.001) constructed by tumor number, intratumoral vessel, margin, capsule, rim enhancement, T1D%, relaxation time on plain scan (T1P) and T1E, and serum alpha-fetoprotein (P = 0.027) and alanine aminotransferase levels (P = 0.028). Three nomograms achieved high C-index in predicting MVI (0.754, 0.746), tumor differentiation (0.758, 0.699) and immunoscore (0.737, 0.726) in the training and validation cohorts, respectively. Interpretation:MRI-based nomograms effectively predict tumor behaviors in HCC and may assist clinicians in prognosis prediction. Funding: This work was funded by the National Natural Science Foundation of China (No. 81771908, 81571750, 81801703), the National Science Fund for Distinguished Young Scholars (No. 81825013) and the Guangdong Natural Science Foundation of Guangdong Province (No. 2018A030310282). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The Institutional Ethic Review Board has approved our study, and informed consent was waived due to the retrospective nature of the study.

Predicting liver failure after extended right hepatectomy following right portal vein embolization with gadoxetic acid-enhanced MRI.

Predicting post-hepatectomy liver failure (PHLF) after extended right hepatectomy following portal vein embolization (PVE) from serial gadoxetic acid-enhanced magnetic resonance imaging (MRI). Thirty-six patients who underwent hepatectomy following PVE were evaluated prospectively with gadoxetic acid-enhanced MRI examinations at predefined intervals during the course of their treatment, i.e., before and 14days and 28days after PVE as well as 10days after hepatectomy. Relative enhancement (RE) and volume of the left and right liver lobes were determined. The study population was divided into two groups with respect to signs of PHLF. Differences between the two groups were assessed using the Mann-Whitney U test, and predictive parameters for group membership were investigated using ROC and logistic regression analysis. RE of the left lobe prior to PVE versus 14days after PVE was significantly lower in patients with PHLF than in those without PHLF (Mann-Whitney U test p < 0.001) and proved to be the best predictor of PHLF in ROC analysis with an AUC of 0.854 (p < 0.001) and a cutoff value of - 0.044 with 75.0% sensitivity and 92.6% specificity. Consistent with this result, logistic linear regression analysis adjusted for age identified the same parameter to be a significant predictor of PHLF (p = 0.040). Gadoxetic acid-enhanced MRI performed as an imaging-based liver function test before and after PVE can help to predict PHLF. The risk of PHLF can be predicted as early as 14days after PVE. • To predict the likelihood of post-hepatectomy liver failure, it is important to estimate not only future liver remnant volume prior to extended liver resection but also future liver remnant function. • Future liver remnant function can be predicted by performing gadoxetic acid-enhanced MRI as an imaging-based liver function test before and after portal vein embolization. • A reduction of relative enhancement of the liver in gadoxetic acid-enhanced MRI after portal vein embolization of 0.044 predicts post-hepatectomy liver failure with 75.0% sensitivity and 92.6% specificity.

A Radiomics-Based Biomarker for Cytokeratin 19 Status of Hepatocellular Carcinoma with Gadoxetic Acid-Enhanced MRI

Background: We aimed to develop and validate a radiomics-based model derived from gadoxetic acid-enhanced MR images to preoperatively identify cytokeratin (CK) 19 status of hepatocellular carcinoma (HCC). Methods: A cohort of 227 patients with single HCC was classified into a training set (n=159) and a time-independent validated set (n=68). A total of 647 radiomic features were extracted from multi-sequence MR images separately. The least absolute shrinkage and selection operator regression and decision tree methods were utilized for feature selection and radiomics signature construction. A further multivariable-based model was built for predicting CK19 status of HCC. Findings: By combining 11 and 6 radiomics features extracted in arterial phase and hepatobiliary phase images, respectively, a fusion radiomics signature achieved a satisfying performance for CK19 stratification. The final combined model integrated serum a-fetoprotein levels, arterial rim enhancement pattern, irregular tumor margin and the fusion radiomics signature, with a sensitivity of 0.818 and specificity of 0.974 in the training cohort and that of 0.769 and 0.818 in the validated cohort. The nomogram based on the combined model showed satisfactory prediction performance in training (C-index: 0.959) and validation (C-index: 0.846) dataset. Interpretations: The combined model based on a fusion radiomics signature derived from arterial phase and hepatobiliary phase images of gadoxetic acid-enhanced MRI can be a reliable biomarker for identifying CK19 status of HCC. Funding: This paper is supported by National Natural Science Foundation of China; Ministry of Science and Technology of China; Chinese Academy of Sciences; the Strategic Priority Research Program of Chinese Academy of Science; the Shanghai Sailing Program. Declaration of Interest: All authors declare no potential conflict of interest. Ethical Approval: The retrospective study was approved by our Institutional Review Board (approval number B2018-236) and the requirement for informed consent was waived.

Personalized 3D-Printed Transparent Liver Model Using the Hepatobiliary Phase MRI: Usefulness in the Lesion-by-Lesion Imaging-Pathologic Matching of Focal Liver Lesions-Preliminary Results.

The aim of this study was to investigate the usefulness of a personalized, 3-dimensional (3D)-printed, transparent liver model with focal liver lesions (FLLs) for lesion-by-lesion imaging-pathologic matching. This preliminary, prospective study was approved by our institutional review board, and written informed consent was obtained. Twenty patients (male-to-female ratio, 13:7; mean age, 56 years) with multiple FLLs, including at least one presumed malignant, or an indeterminate lesion 10 mm or less on the preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI), were included. After digital segmentation of hepatobiliary phase MRI, a transparent, 3D-printed liver model with colored anatomical structures and FLLs was produced. During the gross examination of the liver specimen, the per-lesion detection rates were compared between those without (routine protocol) and those with the aid of the 3D-printed liver model. Among 98 MRI-detected FLLs (11.5 ± 12.5 mm), the per-lesion detection rate on gross examination using the 3D-printed liver model was 99.0% (97/98), which was significantly higher than that obtained on routine examination (82.7% [81/98]; P < 0.001). In the subgroup analysis, according to the tumor size, 23.9% (16/67) of FLLs 10 mm or less were additionally detected using the liver model, whereas none were additionally detected in greater than 10 mm. The additionally detected 16 FLLs in 12 patients included histologic diagnoses of viable metastases, pathologic complete response of metastases, hepatocellular carcinomas, focal nodular hyperplasia-like nodules, and hemangiomas. A personalized, 3D-printed liver model with FLLs may improve the lesion-by-lesion imaging-pathologic matching for small FLLs, thus leading to accurate pathologic tumor staging and obtaining a reliable reference for imaging-detected FLLs.

Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Pyrrolizidine Alkaloid-Induced Hepatic Sinusoidal Obstruction Syndrome and Association with Liver Function

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. In this study, the aim of our study was to investigate the imaging features of PAs-induced HSOS on gadoxetic acid-enhanced magnetic resonance imaging (MRI), susceptibility-weighted imaging(SWI) and T2* weighted imaging (T2* WI). We analyzed medical records and MR images of 28 PAs-induced HSOS patients enrolled from Feb, 2013, to Apr, 2017. Abnormal liver function was observed in most of the PAs-induced HSOS patients. Heterogeneity of liver parenchyma in hepatobillary phase (HBP) of gadoxetic acid-enhanced MR scan was observed in 100% of the PAs-induced HSOS patients. Distributional patterns of heterogeneous hypointensity were multifocal distribution (mild) in 4 patients (14.29%), multifocal distribution (severe) in 15 cases (53.57%), and diffuse distribution in 9 patients (32.14%). Hypointense in SWI and T2*WI was observed in the patients of PAs-induced HSOS, and the distribution of hypointense in SWI and T2*WI was similar to that of portal-venous phase of MR scan. The severity of heterogeneous hypointensity scored by volume fraction in hepatobillary phase of gadoxetic acid-enhanced MRI was positively correlated with PT and INR, the severity of hypointensity in HBP was a risk factor of death events. In conclusion: Heterogenous hypointensity of liver parenchyma was an imaging sign of hepatobillary phase in gadoxetic acid-enhanced MRI; thus, it will provide evidences for the diagnosis of PA-induced HSOS.

Gadoxetic acid-enhanced magnetic resonance imaging: Hepatocellular carcinoma and mimickers.

Gadoxetic acid, a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent, has emerged as an important tool for hepatocellular carcinoma (HCC) diagnosis. Gadoxetic acid-enhanced MRI is useful for the evaluation of early-stage HCC, diagnosis of HCC precursor lesions, and highly sensitive diagnosis of HCC. Furthermore, functional information provided by gadoxetic acid-enhanced MRI can aid in the characterization of focal liver lesions. For example, whereas lesions lack functioning hepatocytes appear hypointense in the hepatobiliary phase, preserved or enhanced expression of organic anion transporting polypeptides in some HCCs as well as focal nodular hyperplasia lead to hyperintensity in the hepatobiliary phase; and a targetoid appearance on transitional phase or hepatobiliary phase imaging can be helpful for identifying the histopathological composition of tumors. While gadoxetic acid-enhanced MRI may improve the sensitivity of HCC diagnosis and provide new insights into the characterization of focal liver lesions, there are many challenges associated with its use. This article reviews the pros and cons of HCC diagnosis with gadoxetic acid-enhanced MRI and discuss some clues in the radiological differentiation of HCC from HCC mimickers.

Value of Texture Analysis on Gadoxetic Acid-enhanced MR for Detecting Liver Fibrosis in a Rat Model.

Objective To explore the ability of texture analysis of gadoxetic acid-enhanced magnetic resonance imaging (MRI) T1 mapping images, as well as T1-weighted (T1W), T2-weighted (T2W) and apparent diffusion coefficient (ADC) maps for distinguishing between varying degrees of hepatic fibrosis in an experimental rat model.Methods Liver fibrosis in rats was induced by carbon tetrachloride intraperitoneal injection for 4-12 weeks (n=30). In the control group (n=10) normal saline was applied. The MRI protocol contained T2W, diffusion weighted imaging, pre-and post-contrast image series of T1W and T1 mapping images. METAVIR score was used to grade liver fibrosis as normal (F0), mild fibrosis (F1-2), and advanced fibrosis (F3-4). Texture parameters including mean gray-level intensity (Mean), standard deviation (SD), Entropy, mean of positive pixels (MPP), Skewness, and Kurtosis were obtained. Nonparametric Mann-Whitney U test was used to compare the average value of each texture parameter in each sequence for assessing the difference between F0 and F≥1 as well as F0-2 and F3-4. Receiver operating characteristic (ROC) curves were obtained to assess the diagnosing accuracy of the parameters for differentiating no liver fibrosis from liver fibrosis and rats with liver fibrosis grading F0-2 from those with grading F3-4. The area under ROC curve (AUC) was calculated to evaluate the diagnostic efficiency of texture parameters.Results Finally, 20 rats completed MR T1 mapping image scan. The pathologic staging of these 20 rats was no fibrosis (F0, n=6), mild fibrosis (F1-2, n=5) and advanced fibrosis (F3-4, n=9). On pre-contrast T1 mapping image, Entropy was seen to be statistically significant higher in the F≥1 group than that in the F0 group at each spatial scaling factor (SSF) setting (P=0.015, 0.015, 0.015, 0.013, 0.015 and 0.018 respectively to SSF=0, 2, 3, 4, 5, 6), and Mean of the F≥1 rats was statistically significant higher than that of the F0 rats at SSF 4, 5, 6 (P=0.004, 0.006, and 0.013, respectively). Entropy and Mean showed a moderate diagnostic performance in most SSF settings of T1 mapping pre-contrast images for differentiation of normal liver from liver fibrosis.Conclusions Certain texture features of gadoxetic acid-enhanced MR images, especially the Entropy of non-contrast T1 mapping image, was found to be a useful biomarker for the diagnosis of liver fibrosis.

Atypical Appearance of Hepatocellular Carcinoma and Its Mimickers: How to Solve Challenging Cases Using Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging.

Hepatocellular carcinoma (HCC) can be diagnosed noninvasively with contrast-enhanced dynamic computed tomography, magnetic resonance imaging, or ultrasonography on the basis of its hallmark imaging features of arterial phase hyperenhancement and washout on portal or delayed phase images. However, approximately 40% of HCCs show atypical imaging features, posing a significant diagnostic challenge for radiologists. Another challenge for radiologists in clinical practice is the presentation of many HCC mimickers such as intrahepatic cholangiocarcinoma, combined HCC-cholangiocarcinoma, arterioportal shunt, and hemangioma in the cirrhotic liver. The differentiation of HCCs from these mimickers on preoperative imaging studies is of critical importance. Hence, we will review the typical and atypical imaging features of HCCs and the imaging features of its common mimickers. In addition, we will discuss how to solve these challenges in practice.

Combining the Arterial Phase of Contrast-Enhanced Ultrasonography, Gadoxetic Acid-Enhanced Magnetic Resonance Imaging and Diffusion-Weighted Imaging in the Diagnosis of Hepatic Nodules ≤20 mm in Patients with Cirrhosis

Contrast-enhanced ultrasonography (CEUS) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) were compared with respect to diagnostic efficacy in the detection of small hepatocellular carcinoma. A new diagnostic strategy that combines the arterial phase of CEUS, the hepatobiliary phase of EOB-MRI and diffusion-weighted MR imaging (DWI) is described. One hundred sixteen nodules were enrolled to validate the performance of the strategy. For lesions ≤20 mm in size, the areas under the receiver operating characteristic curves (Az) of CEUS and EOB-MRI were 0.930 (95% confidence interval [CI]: 0.867–0.969) and 0.920 (95% CI: 0.855–0.962) (p = 0.796), respectively. The Az value of the new diagnostic strategy was 0.985 (95% CI: 0.942–0.999) (vs. CEUS, p = 0.026; vs. EOB-MRI, p = 0.014). The sensitivity, specificity and diagnostic accuracy of the new strategy were 95.5% (95% CI: 88.9%–98.8%), 96.3% (95% CI: 81.0%–99.9%) and 95.7% (95% CI: 91.9%–99.4%), respectively. The new diagnostic strategy based on the arterial phase of CEUS, hepatobiliary phase of EOB-MRI and DWI represents an appealing solution for distinguishing small hepatocellular carcinomas from benign lesions, especially when the nodules present atypical enhancement patterns.

Value of Texture Analysis on Gadoxetic Acid-Enhanced MRI for Differentiating Hepatocellular Adenoma From Focal Nodular Hyperplasia.

The objective of our study was to assess the diagnostic performance of texture analysis (TA) on gadoxetic acid-enhanced MR images for differentiation of hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH). This study included 40 patients (39 women and one man) with 51 HCAs and 28 patients (27 women and one man) with 32 FNH lesions. All lesions were histologically proven with preoperative MRI performed with gadoxetic acid. Two readers reviewed all the imaging sequences to assess the qualitative MRI characteristics. The T2-weighted fast spin-echo, hepatic arterial phase (HAP), and hepatobiliary phase (HBP) sequences were used for TA. Textural features were extracted using commercially available software (TexRAD). The differences in distributions of TA parameters of FNHs and HCAs were assessed using the Mann-Whitney U test. Area under the ROC curve (AUROC) values were calculated for statistically significant features. A logistic regression analysis was conducted to explore the added value of TA. A p value < 0.002 was considered statistically significant after Bonferroni correction for multiple comparisons. Multiple TA parameters showed a statistically different distribution in HCA and FNH including skewness on T2-weighted imaging, skewness on HAP imaging, skewness on HBP imaging, and entropy on HBP imaging (p < 0.001). Skewness on HBP imaging showed the largest AUROC (0.869; 95% CI, 0.777-0.933). A skewness value on HBP imaging of greater than -0.06 had a sensitivity of 72.5% and a specificity of 90.6% for the diagnosis of HCA. Six of 51 (11.8%) HCAs lacked hypointensity on HBP imaging. A binary logistic regression analysis including hypointensity on HBP imaging and the statistically significant TA parameters yielded an AUROC of 0.979 for the diagnosis of HCA and correctly predicted 96.4% of the lesions. TA may be of added value for the diagnosis of atypical HCA presenting without hypointensity on HBP imaging.

Management of sub-centimeter recurrent hepatocellular carcinoma after curative treatment: Current status and future

Hepatocellular carcinomas (HCCs) frequently recur despite initial successful surgical resection or local ablation therapy. Diagnostic methods for small HCCs have improved with the introduction of gadoxetic acid-enhanced liver magnetic resonance imaging and diffusion-weighted imaging (DWI). Currently, sub-centimeter recurrent nodules showing typical hallmark imaging findings of HCC are frequently detected in patients with a treatment history for HCC. With five typical magnetic resonance findings, including arterial enhancement, washout on portal or transitional phase, high signal intensity on both T2-weighted image and DWI, and low signal intensity on hepatobiliary phase, sub-centimeter recurrent HCC can be diagnosed with high accuracy. Although more information is needed to determine the treatment of choice, local ablation therapy under fusion imaging and/or contrast-enhanced ultrasound guidance or cone-beam computed tomography-guided chemoembolization seem to be promising as they are effective and safe for the management of sub-centimeter recurrent HCCs.

Prediction of sorafenib treatment-related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation.

To investigate the feasibility of prediction for targeted therapy-related gene expression in hepatocellular carcinoma (HCC) using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI). Ninety-one patients (81 men, mean age 53.9 ± 12years) with solitary HCC who underwent preoperative enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, intratumoral vessels, peritumor enhancement, peritumor hypointensity, signal intensity ratio on DWI, T1 relaxation times, and the reduction rate between pre- and post-contrast enhancement images were assessed. The operation and histopathological evaluation were performed within 2weeks after MRI examination (mean time 7days). The expression levels of BRAF, RAF1, VEGFR2, and VEGFR3 were evaluated. The associations between these imaging features and gene expression levels were investigated. Tumor incomplete capsules or non-capsules (p = 0.001) and intratumoral vessels (p = 0.002) were significantly associated with BRAF expression, and tumor incomplete capsules or non-capsules (p = 0.001) and intratumoral vessels (p = 0.013) with RAF1 expression. There was no significant association between the expression of VEGFR2, VEGFR3, and all examined MRI features. Multivariate logistic regression showed that incomplete tumor capsule (p = 0.002) and non-capsule (p = 0.004) were independent risk factors of HCC with high BRAF expression; incomplete tumor capsule (p < 0.001) and non-capsule (p = 0.040) were independent risk factors of HCC with high RAF1 expression. The presence of incomplete capsule or intratumoral vessels and the absence of capsule are potential indicators of high BRAF and RAF1 expression. Gadoxetic acid-enhanced MRI may facilitate the choice of gene therapy for patients with HCC. • Incomplete tumor capsule and non-capsule were independent risk factors of HCC with high BRAF and RAF1 expression. • The presence of intratumoral vessels was a potential indicator of high BRAF and RAF1 expression. • Gadoxetic acid-enhanced MRI may be a predictor of efficacy of treatment with sorafenib.