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

Objective To identify the preoperative MRI findings for predicting microvascular invasion (MVI) using texture analysis (TA) on multiple MRI sequences. Methods Two hundred and fifty patients with HCC pathologically confirmed by surgery in Zhongshan Hospital from October 2015 to October 2016 were analyzed retrospectively. All patients underwent conventional MRI plain scan and dynamic contrast?enhanced examination within 2 weeks before operation. According to the ratio of 1∶1, the patients were divided into a training set (125 cases) and a test set (125 cases).The training set was used to establish a classifier to predict MVI of HCCs via the TA, and the test set was used to evaluate the performance of the classifier. An image analysis was performed using an in?house software contained a set of 2 415 features which were generated from all conventional axial sequences, including the T2WI, DWI, ADC map, and dynamic enhancement images.. A four?fold cross validation (FFCV) and sequential forward floating feature selection strategy (SFFS) were employed to select an optimal subset of features and a linear discriminant analysis (LDA) was employed to establish a classifier. The clinical laboratory examination, morphologic characteristics and quantitative analysis of conventional MR were used to compare the performance of predicting MVI with the classifier. A Chi?squared test or Fisher exact probablities test were used for categorical variables, and independent t test or Mann?Whitney U test were used for used for continuous variables. Factors with a P value less than 0.05 at univariate analyses were entered into the multivariate model to identify independent predictors. The Hosmer?Lemeshow test was performed to explain the goodness of fit of the multivariate logistic model. A receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance. Results The classifier set up by the training set consists of 13 texture features. When conventional MRI texture features of test set were used to judge whether there was MVI or not, the AUC of all texture features of arterial phase (AP) was the highest (0.506 3). Univariate regression analysis showed that there were significant differences in pathological grade (P=0.026), AFP level (P=0.033), lesion edge shape (P=0.038), AP enhancement (P=0.038), and AP peritumoral enhancement (P=0.008). Multivariate binary logistic regression analysis showed that peritumoral enhancement and texture classifier assessed MVI with P values of 0.005 and 0.001,which were independent risk factors for MVI. The significance level of Hosmer Lemeshow test was 0.796, indicating the goodness of fit of acceptable models. The AUCs of single variable, combined variable (including of AFP level, irregular tumor margin, enhancement intensity in AP and peritumoral enhancement in AP) and texture classifier for MVI were 0.588 to 0.627, 0.798 and 0.733, respectively. When compared the AUC of the combination features (including of AFP level, irregular tumor margin, enhancement intensity in AP and peritumoral enhancement in AP) with the classifier to identify MVI of HCC in the test set, no significant difference was found(P=0.108 6). However, although the sensitivity of them were same as 70.73%, the specificity of the combination features was mildly higher than that of classifier (82.14% vs. 78.57%). Conclusions Combination features of AFP level, tumor margin, enhancement intensity in AP and peritumoral enhancement in AP can be used to predict MVI of HCCs. It is a new method of noninvasive evaluation of MVI before operation. The performance of the classifier made by TA was not superior to that of combination features based on clinic and conventional MR sequences.

Objective To investigate the risk factors of intrahepatic recurrence after resection for Barcelona Clinic Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC).Methods 58 patients with pathologically confirmed BCLC stage 0 HCC treated with liver resection at the Zhongshan Hospital,Fudan University from January to December 2011 were included in this study.The male/female ratio was 50/8.The age ranged from 31 to 72 years.The clinical,pathological and MR imaging features of these patients were analyzed.The recurrence-free survival rates between patients with HCC ≤ 1.5 cm (n=27) and ＞ 1.5 cm (n=31) were compared.The risk factors of intrahepatic recurrence for HCCs were compared using the Cox regression analysis.Results Intrahepatic recurrence was identified in 25 patients,and the median recurrence time was 33 months.The 3-and 5-year cumulative recurrence-free survival rates were 73.0％ (95％CI:60.7％～85.3％) and 52.3％ (95％CI:37.2％～67.4％).No significant differences were found in the recurrence-free survival rates between tumors ≤ 1.5 cm and ＞ 1.5 cm (P＞0.05).Multivariate analyses demonstrated that serum alpha-fetoprotein level ＞20 g/L (HR 3.773,95％CI:1.628～8.745;P＜0.05) and irregular tumor shape (HR 4.584,95％CI:1.485～ 14.155;P＜0.05) were independent risk factors of intrahepatic recurrence.Conclusions Elevated serum alpha-fetoprotein level and irregular tumor shape were associated with an increased risk of intrahepatic recurrence for BCLC stage 0 HCC patients after resection.They could be used as early prognostic indicators in clinical practice.

Objective To compare the MRI features of focal nodular hyperplasia (FNH) and inflammatory hepatocellular adenoma (Ⅰ-HCA),with an aim to improve the diagnostic accuracy in the two lesions.Methods Patients who underwent dynamic-enhanced MRI with histopathologically confirmed FNHs (21 patients with 21 tumors) and Ⅰ-HCAs (10 patients with 12 tumors) were included in this retrospective study.The clinical and the imaging features,including the T2-and T1-weighted,diffusion weighted images,and the dynamic enhanced imagings were analyzed.Results No significant difference was observed in the clinical data between the 2 groups of patients,except in the serum levels of C-reactive protein.The serum C-reactive protein levels were significantly elevated in Ⅰ-HCA than in FNH.Significant differences between patients with FNHs and Ⅰ-HCAs were also found in the morphologic findings and the signal intensities (including shape,centre scar,necrosis,signal intensity of T2WI and DWI,and lesion signal intensity compared to those of the liver in the portal venous phase and delayed phase).The differences in lesion to liver signal in FNH were significantly lower than those in Ⅰ-HCA in the T2WI and the delayed phases.The area under the curve (AUC) for the 2 groups of patients were 0.843 and 0.743,respectively,with no significant difference between them.Conclusions The MRI appearances of atypical FNHs overlapped with Ⅰ-HCA.MRI features of isointensity on T2 Wl and DWI,and isointensity to the liver in the delayed phase were valuable to differentiate FNHs from Ⅰ-HCAs.Most Ⅰ-HCAs showed moderate and marked high signal intensity on T2WI and DWI.These features,when combined with an elevated serum C-reaction protein,necrosis in the lesion and hyperintensity in the delayed phase,were valuable in differentiating Ⅰ-HCAs from FNH.

Objective: To investigate the diagnostic value of extracellular volume (ECV) imaging by magnetic resonance imaging for liver fibrosis of hepatitis B. Methods: A retrospective analysis was recruited in patients with chronic hepatitis B, who underwent liver surgery from April to October 2017 for pathological evaluation of liver tissues, and all patients underwent Gd-EOB-DTPA-enhanced T1 mapping to calculate the liver ECV score. The correlation between ECV and staging of hepatic fibrosis and inflammatory activity were compared to clarify the diagnostic value of staging of fibrosis. Results: 66 patients were enrolled in this study. Concerning the staging of liver fibrosis, there were 13, 4, 13, 10, and 26 cases with F0, F1, F2, F3 and F4 stages, respectively. ECV values had high interobserver consistency (correlation coefficient 0.860). The ECV difference between different stages of liver fibrosis was statistically significant (F = 15.02, P < 0.001). There was a significant positive correlation between ECV and fibrosis stage (r = 0.622, P < 0.001), and weak correlation with inflammatory activity (r = 0.332, P = 0.007). Fibrosis staging was an independent factor influencing ECV (P < 0.001). The area under the receiver operator characteristic curve for the diagnosis of liver fibrosis staging F≥1, F≥3 and F4 were 0.760, 0.846 and 0.873, respectively. The diagnostic sensitivity and specificity were 64.15%, 92.31%, 77.78%, 80.00% and 88.46, 72.50%, respectively. Conclusion MRI-ECV imaging has great value for staging hepatic fibrosis of hepatitis B, and it can provide an effective method for diagnosis, staging, and evaluating the curative effect of fibrosis.

Objective To investigate the diagnostic value of diffusion kurtosis imaging(DKI)in the classification of hepatic fibrosis. Methods Thirty-five male SD rats were randomly divided into two groups:the hepatic fibrosis group(n=28)and the control group(n=7). The rats in hepatic fibrosis group were randomly divided into 4 subgroups and seven rats per group, the rats were administrated 50％ CCl4 intraperitoneally twice a week to establish hepatic fibrosis , and the four subgroups were injected 2, 4, 6, and 8 weeks, respectively. The rats in the control group were administrated same dose of olive oil for 8 weeks. One rat in hepatic fibrosis group was died of liver failure in the 7th week, and a total of 27 fibrosis experimental rats and 7 control rats were finally included in this study. DKI was performed at the end of the injection period for all rats, the apparent diffusion(D)and kurtosis(K)values were evaluated. Rats were sacrificed immediately after MRI scan and liver specimens were collected. The liver tissues were examined by pathology, liver fibrosis degree, which was graded from S0 to S4, and inflammatory activity, which was graded from G0 to G3 were graded. The difference of D value and K value between different liver fibrosis and inflammatory activity scores was compared by one-way ANOVA(normal distribution)or Kruskal-Wallis test(skewed distribution). Spearman correlation analysis and multiple regression analysis were used to reveal the correlation between DKI parameters and fibrosis staging/necroinflammatory activity grade. To confirm the efficiency of using the ROC curve of DKI parameters to qualify the liver fibrosis grade, which grade was≥3. Results Seven, 6, 6, 7, 8 rats were diagnosed as S0 to S4, respectively. The difference of D value and K value among different fibrosis grades was statistically significant(P<0.05). D value and the degree of fibrosis was negatively correlated(r=-0.650, P<0.01);K value and liver fibrosis grade no correlation(r=0.336, P=0.080). Thirteen, 6, 8, 7 rats were diagnosed as G0 to G3, respectively. D value was negatively correlated with inflammatory activity(r=-0.590, P=0.001);K value was no correlation with inflammatory activity(r=0.169, P=0.389). Compared with inflammatory activity, fibrosis classification was an independent factor in determining D values(P=0.001). ROC analyses demonstrated an area under the curve(AUC)of D value, K value, D value combined with K value in the diagnosis of liver fibrosis grading ≥ 3 level were 0.781, 0.672 and 0.833, respectlively. The sensitivity and specificity of D value combined with K value were 83.3％ and 75.0％, respectively. Conclusion DKI imaging is of great value in the classification of hepatic fibrosis and can be used as an effective method for the diagnosis of fibrosis.

Objective To investigate the MRI findings of combined hepatocellular cholangio-carcinoma(cHCC-CC)and their correlation with pathologic types. Methods Twenty-nine patients with surgical pathology-confirmed cHCC-CC(20 patients with 24 cHCC-CCs were categorized as classical, and 9 patients with 10 cHCC-CCs as subtypes with stem cell features)were retrospectively analyzed. The clinical features, morphological and MRI signal characteristics on T1WI, T2WI, dynamic enhancement patterns and diffusion-weighted imaging were evaluated in detail and compared these imaging findings with pathologic types. The ADC values of 17 patients with 24 cHCC-CCs were measured. The imaging features were compared by using t test and Fisher test. Results The average maximum diameter of classical type and stem cell feature type were (3.8 ± 2.5) cm and (4.5 ± 1.8) cm, respectively, there was no significant difference(t=0.749,P=0.462). Seven cHCC-CCs showed heterogeneously high signal and twenty-seven cHCC-CCs showed low signal on T1WI. Seventeen cHCC-CCs showed hypointense in the central with mixed high and low signal on T2WI. Twenty-one cHCC-CCs showed peripheral enhancement and 13 lesions showed heterogeneously enhancement during arterial phase. The enhancement pattern of quickly wash-in and quickly wash-out were seen in 17 lesions, the other 17 lesions showed reversal enhancement. Twenty-five lesions presented with pseucapsule. There was no significant difference in clinical features and MRI findings between the two pathologic tumor types(classical type versus stem cell feature type)except for the enhancement pattern in arterial phase and peri-tumoral bile duct dilatation(P<0.05).The mean ADC value of the tumors with stem cell feature type(1.41 ± 0.52) × 10-3mm2/s was mildly lower than that of classical type (1.60 ± 0.39) × 10-3mm2/s, and no statistical differences were found(t=-1.005,P=0.326). Conclusions The MRI findings of cHCC-CCs has specificity. However, it is not easy to distinguish the classical type and stem cell feature type of cHCC-CC only by MRI findings.

Objective To value the capability of MRI in assessing invasiveness of intraductal papillary neoplasms of the bile duct(IPNB). Methods Thirty-nine patients with pathologically confirmed IPNB, who had upper abdominal MR examination within 6 weeks before complete resection of the tumor, were included in the retrospective study. Patients were divided into noninvasive and invasive groups pathologically. Eighteen cases were noninvasive and 21 were invasive. All had undergone MRI plain scans, MR cholangiopancreatography as well as contrast enhanced scans including arterial, portal and delayed phases. Tumor size, location, biliary dilation, thread signs, lesion morphology, lobe atrophy, cholelithiasis, biliary hemorrhage, vascular invasion and intraperitoneal lymphadenopathy were observed on MRI. ADC values and enhancement level of lesions were also measured. Between invasive and noninvasive groups, laboratory results, enhancement levels and ADC values were compared by t test or Mann-Whitney U test, and categorical variables like location and lesion morphology were compared by χ2 test. The diagnostic accuracy was calculated using receiver operating characteristic(ROC)curve analysis. Results No difference was found between invasive and noninvasive groups on gender, age, lesion morphology, bile duct diameter, location, existence of thread signs or cholelithiasis(P>0.05). While the differences on serum CA19-9 level, lesion size, ADC value, and lymph nodes/vascular invasion between groups reached statistical significance (P<0.05). Other than on plain scan(P>0.05), CNR and enhancement levels were also statistically different on arterial, portal and delayed phases between both groups(P<0.05). CA199, enhancement level and CNR of portal phase, as well as ADC value exhibited areas under the ROC curve(AUC)of 0.790, 0.891, 0.817 and 0.882 respectively in invasiveness judgment. Conclusion MR demonstrated relatively high value in assessing invasiveness of IPNB.

Objective To investigate the MRI findings of combined hepatocellular cholangio-carcinoma(cHCC-CC)and their correlation with pathologic types. Methods Twenty-nine patients with surgical pathology-confirmed cHCC-CC(20 patients with 24 cHCC-CCs were categorized as classical, and 9 patients with 10 cHCC-CCs as subtypes with stem cell features)were retrospectively analyzed. The clinical features, morphological and MRI signal characteristics on T1WI, T2WI, dynamic enhancement patterns and diffusion-weighted imaging were evaluated in detail and compared these imaging findings with pathologic types. The ADC values of 17 patients with 24 cHCC-CCs were measured. The imaging features were compared by using t test and Fisher test. Results The average maximum diameter of classical type and stem cell feature type were (3.8 ± 2.5) cm and (4.5 ± 1.8) cm, respectively, there was no significant difference(t=0.749,P=0.462). Seven cHCC-CCs showed heterogeneously high signal and twenty-seven cHCC-CCs showed low signal on T1WI. Seventeen cHCC-CCs showed hypointense in the central with mixed high and low signal on T2WI. Twenty-one cHCC-CCs showed peripheral enhancement and 13 lesions showed heterogeneously enhancement during arterial phase. The enhancement pattern of quickly wash-in and quickly wash-out were seen in 17 lesions, the other 17 lesions showed reversal enhancement. Twenty-five lesions presented with pseucapsule. There was no significant difference in clinical features and MRI findings between the two pathologic tumor types(classical type versus stem cell feature type)except for the enhancement pattern in arterial phase and peri-tumoral bile duct dilatation(P<0.05).The mean ADC value of the tumors with stem cell feature type(1.41 ± 0.52) × 10-3mm2/s was mildly lower than that of classical type (1.60 ± 0.39) × 10-3mm2/s, and no statistical differences were found(t=-1.005,P=0.326). Conclusions The MRI findings of cHCC-CCs has specificity. However, it is not easy to distinguish the classical type and stem cell feature type of cHCC-CC only by MRI findings.

Objective To investigate the MRI features of hepatic IgG4?related inflammatory pseudotumor (IPT). Methods Nine patients with 11 histopathologically proven IgG4?related hepatic IPTs were retrospectively analyzed. The clinical, morphological and MRI signal features on T1WI, T2WI, dynamic?enhanced, and diffusion?weighted imaging were assessed in detail and correlated with pathological findings. The paired t test was used to compare the ADC values of the tumors and the hepatic tissue. Results Hepatic IgG4?related IPT displayed certain MRI features. The dominant lesions were subcapsularly distributed (n=7) with a clear boundary (n=8), which typically showed hypointensity on T1WI (n=11), mild hyperintensity on T2WI (n=8), progressive (n=5) or persistent (n=4) enhancement pattern. Accompanied signs included delayed capsule?like enhancement (n=6) and central nonenhanced areas (n=7). Two lesions showed atypical wash?out pattern with iso or hypointensity on portal and delayed phases. In diffusion weighted imaging, all lesions were hyperintense, and the mean ADC value of the lesions [(1.42 ± 0.36) × 10?3mm2/s] was mildly lower than that of surrounding liver [(1.55±0.31)×10?3mm2/s], although no statistical differences were found(t=0.78, P=0.46). Conclusions Hepatic IgG4?related IPTs display various MRI manifestations. The lesions normally show progressive enhancement pattern with diffuse homogeneous or heterogeneous hyperintensity, accompanied by delayed capsule?like enhancement and central nonenhanced areas.