Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid Research Articles

The diagnostic performance of version 2018 LI-RADS for hepatocellular carcinoma on Gd-EOB-DTPA enhanced MRI

Objective To explore the diagnostic performance of the most recent 2018 version of liver reporting and data system (LI-RADS) on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI to diagnose hepatocellular carcinoma (HCC) in high-risk patients. Methods From July 2015 to September 2018, 130 consecutive high-risk patients with 134 focal liver lesions were retrospectively enrolled in our center and underwent Gd-EOB-DTPA-enhanced MRI and subsequent hepatectomy within 1 month. Two independent radiologists blindly reviewed the preoperative MR images of all patients, and determined the presence of major features, ancillary features and the LI-RADS categories according to the version 2018 LI-RADS of each liver observation. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index and accuracy of the 2018 version of LI-RADS were evaluated with postoperative histopathological results as references. The inter-observer agreement between the two radiologists was tested by Kappa analysis. Results The Kappa value of the LI-RADS categories between two radiologists was 0.628 (95%CI: 0.565 to 0.691). The sensitivity, specificity, Youden index values and accuracy of LR-5 by the two reviewers were 80.4% (78/97), 87.6% (85/97); 75.7% (28/37), 73.0% (27/37); 0.560 8, 0.605 9; 79.1% (106/134), 83.6% (112/136), respectively. These measures of LR-4+LR-5 were 91.8% (85/97), 96.9% (94/97); 67.6% (25/37), 67.6% (25/37); 0.605 9, 0.644 6; 82.1% (110/134), 88.8% (119/134), respectively. Conclusion Version 2018 LI-RADS demonstrated high sensitivity and accuracy to diagnosis HCC in high-risk patients on Gd-EOB-DTPA enhanced MRI. Key words: Liver neoplasms; Magnetic resonance imaging; Media contrast; Liver imaging reporting and data system

Gadoxetic acid enhanced T1ρ and intravoxel incoherent motion MRI in quantitatively assessing the stages of nonalcoholic steatohepatitis

Objective To explore the values of metrics on intravoxel incoherent motion (IVIM) and gadoxetic acid enhanced T1ρ imaging for staging of non-alcoholic fatty liver disease activity scores (NAS) and inflammation in nonalcoholic steatohepatitis (NASH) rabbits model. Methods NASH rabbits model was established by feeding with a varied duration (4, 8, 12 weeks) of high-fat, high-cholesterol diet. IVIM and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced T1ρ images were performed by a 3.0 T MR scanner. The inter-class correlation coefficients (ICC) and Bland-Altman analysis were applied to evaluate the reproducibility of the IVIM and Gd-EOB-DTPA enhanced T1ρ mapping measurers. Spearman correlation analysis were used to assess the correlation between MR metrics, including ADC, D, D*, f, T1ρ, T1ρ (hepatobiliary phase, HBP), and NAS score and inflammation grades respectively with reference to histopathology. ROC curve analysis was used to evaluate the diagnostic performance of T1ρ and IVIM parameters for NASH, inflammation grade, and hepatic fibrosis. Multiple linear regression equations were used to analyze the independent influence factors of T1ρ (HBP). Results The f value was negatively correlated with the NAS score (r=-0.530, P<0.01). The f value of the fibrosis S1-2 was significantly lower than that of the S0 (P<0.01). There was no statistical difference in D, D*, ADC among NASH score, inflammation, and fibrosis stage. T1ρ and T1ρ (HBP) values were positively correlated with NAS scores and inflammation grades. The area under curve (AUC) for the diagnosis of NASH for T1ρ, T1ρ(HBP), ADC, D, D*, and f values were 0.849, 0.949, 0.728, 0.596, 0.522, and 0.871, respectively. The AUCs of T1ρ (HBP)+f in the diagnosis of NASH, G2-3 inflammation, and F1-2 fibrosis were 0.971, 0.935, and 0.903, respectively. Fibrosis (R2=0.624, P=0.002) and inflammation (R2=0.746, P=0.002) were major independent factors of T1ρ (HBP). Conclusion Gd-EOB-DTPA enhanced T1ρ imaging can reflect the severity of NASH and degree of inflammation. IVIM measurements are not accurate enough to stage liver inflammatory activity of NASH. T1ρ (HBP)+f might be a superior noninvasive imaging biomarker than either non-enhanced T1ρ or IVIM for NASH activity and inflammation assessments. Key words: Magnetic resonance imaging; Nonalcoholic steatohepatitis; Intravoxel incoherent motion; Gadoxetate acid disodium

Diagnostic Value of Gd-EOB-DTPA-Enhanced MRI for the Expression of Ki67 and Microvascular Density in Hepatocellular Carcinoma.

National Natural Science Foundation of China; Contract grant number: 81260214. Recent studies have highlighted the diagnostic value of Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in small hepatocellular carcinoma (HCC). Ki67 and CD34 are histologic markers that reflect the proliferation of tumor cells and the microvascular density (MVD). To explore the diagnostic value of Gd-EOB-DTPA-enhanced MRI for Ki67 expression and MVD in HCC. Retrospective. In all, 180 patients with HCC. 3.0T, Gd-EOB-DTPA-enhanced T1 WI volumetric interpolated breath-hold examination (VIBE) axial fat suppression plain, and enhanced scanning. The T1 relaxation time (T1 rt) and signal intensity (SI) of the lesion were measured. The Ki67 expressions and MVD were evaluated by immunohistochemistry. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic efficacy of T1 rt for high Ki67 expression (≥50%) and high MVD (≥100). The T1 rt-20min, rrT1 rt-20min, and SI-hepatobiliary phase (SI-HBP) were strongly correlated with Ki67, the r values were 0.846, -0.765, and -0.760 (P < 0.05), respectively. There were moderate correlations with CD34, with r values -0.444, 0.336, and -0.463 (P < 0.05), respectively. The T1 rt-Pre, T1 rt-20min, SI-Pre, and SI-HBP were significantly different both between the high and low ki67 expression groups (P < 0.05) and between the high MVD and low MVD groups (P < 0.05). In the two groups the T1 rt-20min and SI-HBP was 800.06 ± 128.91 vs. 530.06 ± 139.29 (P < 0.05) and 122.29 ± 39.39 vs. 173.49 ± 46.15 (P < 0.05); T1 rt-20min was found to have high diagnostic efficiency for high ki67 expression (area under the curve [AUC], 0.937; P < 0.05) T1 rt-20min had moderate diagnostic value for high MVD (AUC, 0.716; P < 0.05). The T1 rt and SI of Gd-EOB-DTPA-enhanced MRI were correlated with Ki67 expression and MVD. T1 rt-20min has a high diagnostic value for high ki67 expression and high MVD in HCC tissues. 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1755-1763.

Pathobiological and Radiological Approach For Hepatocellular Carcinoma Subclassification

Many advances have been made in the imaging diagnosis and in the histopathological evaluation of HCC. However, the classic imaging and histopathological features of HCC are still inadequate to define patient’s prognosis. We aimed to find the link between new proposed morphovascular patterns of hepatocellular carcinoma (HCC) and magnetic resonance imaging (MRI) features to identify pre-operatory markers of biologically aggressive HCC. Thirty-nine liver nodules in 22 patients were consecutively identified. Histopathological analysis and immunohistochemistry for CD34 and Nestin were performed to identify the four different HCC morphovascular patterns. MRI was performed using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. Three out of four morphovascular HCC patterns showed peculiar MRI features: in particular Pattern D (solid aggressive HCCs with CD34+/Nestin+ new-formed arteries) were isointense on T1-WI in 83% of cases and hyperintense on T2-WI in 50%. Five histologically-diagnosed HCC were diagnosed as non-malignant nodules on MRI due to their early vascularization and low aggressiveness (Pattern A). The comparison between histology and MRI confirms that a subclassification of HCC is possible in a pre-operatory setting. MRI seems to reinforce once more the identity of the different morphovascular HCC patterns and the possibility to pre-operatively identify HCCs with features of biological aggressiveness.

Prediction of Hepatic Parenchymal Change in Gd-EOB-DTPA MR Images after Stereotactic Body Radiation Therapy by Cycle GAN Deep Neural Network

Stereotactic body radiation therapy (SBRT) is known to be an excellent ablative treatment option for small hepatocellular carcinoma (HCC), while possibly deteriorating hepatic function due to inevitable irradiation to surrounding non-tumorous liver parenchyma. A previous work attempted to reveal the threshold dose of parenchymal change after SBRT to be around 20 Gy by analyzing hypo-signal intensity on the hepatobiliary phase (HBP) of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images. However, it found that estimating the parenchymal change is hard as the threshold dose can be patient-specific, ranging from 18 to 33 Gy. Thus, this work proposes to construct a prediction model for the hepatic parenchymal change after SBRT in Gd-EOB-DTPA enhanced MR images by using an image-based deep neural network. The deep learning with convolutional neural network encouraged numerous applications to the image-based prediction. This study aims to build an image-based deep-neural network that predicts the hepatic parenchymal change on HBP in follow-up enhanced MR images by correlating 3-channel input images of pre-treatment enhanced MR, CT and dose images to the output of the follow-up enhanced MR images. The recent advance in deep learning enabled for translating different types of medical imaging modalities by so-called generative adversarial network (GAN). The prediction accuracy could be further enhanced by placing additional generator in reverse direction to be robust to the image misalignment across different imaging modalities, which is named cycle-consistent GAN (cGAN). In this work, the proposed network based on cGAN was trained and tested with 36 and 7 patient cases, respectively. The prediction accuracy was assessed by comparing the predicted and enhanced follow-up MR images in root-mean-squared error (RMSE) and structural similarity (SSIM). For the seven testing cases, the image similarity was measured only inside the manually drawn liver contours, and 5 Gy iso-dose line. Inside the liver contours, the RMSE and SSIM between the reference follow-up MR and predicted MR images from cGAN were 591.21, and 0.9242, which outperformed the results from GAN. For the 5 Gy iso-dose lines, the structural similarity (SSIM) was reduced to 0.6511, which is mainly due to smoothed intensity transition in the predicted MR images. When visually checked, the locations with the signal intensity transition in predicted images correspond to the reference images. The image-based deep neural network with cGAN could possibly predict the hepatic parenchymal change in the follow-up enhanced MR images after SBRT for HCC.Abstract 2305; Table 1Comparison in prediction accuracy of GAN and cGAN deep neural networkLiver Contour>5Gy iso-dose lineRMSESSIMRMSESSIMGAN514.620.6217854.10.9127cGAN350.40.6511623.90.9242 Open table in a new tab

Visibility of B1 and Right/Left Dissociation Using Gd-EOB-DTPA-enhanced T1-weighted Magnetic Resonance Cholangiography in Live Liver Transplant Donors

PurposeWe aimed to determine the visibility of bile ducts of the caudate lobe (B1s) and right/left (R/L) dissociation on contrast-enhanced T1-magentic resonance cholangiography after gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid administration (CE-T1-MRC) in live liver donors. Materials and MethodsIn 300 live liver donors who underwent CE-T1-MRC, the visibility and R/L dissociation of B1 were evaluated. Confidence level of B1 visibility and depiction of the presence of R/L dissociation on axial and coronal reconstruction images were compared. Strength of agreement between R/L dissociation on MRC and that on intraoperative cholangiography was evaluated. ResultsAt least 1 B1 was visible on CE-T1-MRC in 142 of 300 subjects (47.3%; a total of 195 B1s; 0.64 [SD, 0.80], 0-4 branches per person). Of 195 subjects with visible B1, 55 ducts showed R/L dissociation (28.2%; right-to-left crossover, n = 28; left-to-right crossover, n = 27). The confidence level of B1 visibility on axial images of MRC was significantly higher than that on coronal images of MRC (P < .001). Of 55 B1s with R/L dissociation, axial images were superior to coronal images in depicting B1 crossover in 31 and vice versa in 2 (equal between axial and coronal images in 22). The agreement for R/L dissociation between CE-T1-MRC and intraoperative cholangiography was excellent (κ = 0.819; 95% CI, 0.722-0.917). ConclusionBile ducts of the caudate lobe with R/L dissociation can be occasionally identified on CE-T1-MRC. Axial reconstruction is superior to coronal counterpart.

The diagnostic performance of gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced multi-detector computed tomography in detecting hepatocellular carcinoma: a meta-analysis of eight prospective studies.

The purpose of this study was to determine the relative diagnostic benefit of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) over contrast-enhanced multi-detector computed tomography (CEMDCT) for the detection of hepatocellular carcinoma (HCC). Two investigators searched multiple databases from inception to January 8, 2019, for studies comparing Gd-EOB-DTPA-enhanced MRI with CEMDCT in adults suspected of HCC. Two reviewers independently selected studies and extracted data. Eight studies were included enrolling 498 patients. MRI showed significantly higher sensitivity than CT (0.85 vs. 0.68). There was no significant difference in the specificity of MRI and CT (0.94 vs. 0.93). The negative likelihood ratio and positive likelihood ratio of MRI and CT were not significantly different (0.16 vs. 0.15 and 14.7 vs. 11.2, respectively). The summary receiver operating characteristics (SROC) of MRI was higher than that of CT at 0.96 vs. 0.91. In the subgroup analysis with a lesion diameter below 2cm, the sensitivity of MRI was significantly higher than that of CT (0.79 vs. 0.46). Gd-EOB-DTPA-enhanced MRI showed higher sensitivity and overall diagnostic accuracy than CEMDCT especially for hepatocellular carcinoma lesions smaller than 2cm. • Gd-EOB-DTPA-enhanced MRI can detect small lesions of hepatocellular carcinoma. • Gd-EOB-DTPA-enhanced MRI showed higher sensitivity and overall diagnostic accuracy than CEMDCT in patients with hepatocellular carcinoma. • Eight prospective studies showed that Gd-EOB-DTPA-enhanced MRI provides greater diagnostic confidence.

Establishment and Characterization of a New Cell Line Permissive for Hepatitis C Virus Infection

Hepatitis C virus (HCV) cell culture systems have facilitated the development of efficient direct-acting antivirals against HCV. Huh-7.5, a subline of the human hepatoma cell line Huh-7, has been used widely to amplify HCV because HCV can efficiently replicate in these cells due to a defect in innate antiviral signalling. Recently, we established a novel cell line, KH, derived from human hepatocellular carcinoma, which showed atypical uptake of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in a Gd-EOB-DTPA-enhanced magnetic resonance imaging study. KH cells expressed hepatocyte markers including microRNA-122 (miR-122) at a lower level than Huh-7.5 cells. We demonstrated that KH cells could support the entire life cycle of HCV; however, HCV replicated at a lower rate in KH cells compared to Huh-7.5 cells, and virus particles produced from KH cells seemed to have some disadvantages in viral assembly compared with those produced from Huh-7.5 cells. KH cells had more robust interferon-stimulated gene expression and induction upon HCV RNA transfection, interferon-α2b addition, and HCV infection than Huh-7.5 cells. Interestingly, both miR-122 supplementation and IRF3 knockout in KH cells boosted HCV replication to a similar level as in Huh-7.5 cells, suggesting that intact innate antiviral signalling and lower miR-122 expression limit HCV replication in KH cells. KH cells will enable a deeper understanding of the role of the innate immune response in persistent HCV infection.

Potential of Gd-EOB-DTPA as an imaging biomarker for liver injury estimation after radiation therapy

BackgroundHepatic radiation injury severely restricts irradiation treatment for liver carcinoma. The purpose of this study was to investigate the clinical application of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB-MRI) in the assessment of liver function after external radiation therapy and to determine the relationship between focal liver reaction (FLR) and liver function. MethodsA total of 47 patients with liver malignancies who underwent external beam radiation therapy were enrolled. EOB-MRI was performed on each patient at approximately one month post-radiotherapy. The hepatobiliary (HPB) phase images from EOB-MRI were fused with the planning CT images, and the isodose lines from the patients’ treatment plans were overlaid onto the fused images. The correlation of the EOB-MR image intensity distribution with the isodose lines was studied. We also compared liver function in patients between pre-treatment and post-treatment. ResultsDecreased uptake of Gd-EOB-DTPA, which was manifested by well-demarcated focal hypointensity of the liver parenchyma or FLR to high-dose radiation, was observed in the irradiated areas of 38 patients. The radiotherapy isodose line of decreased uptake area of Gd-EOB-DTPA was 30–46 Gy. The median corresponding dose curve of FLR was 34.4 Gy. Nine patients showed the absence of decreased uptake area of Gd-EOB-DTPA in the irradiated areas. Compared to the 38 patients with the presence of decreased uptake area of Gd-EOB-DTPA, 9 patients with the absence of decreased uptake area of Gd-EOB-DTPA showed significant higher levels of total bile acid, total bilirubin, direct bilirubin and alpha-fetoprotein (P < 0.05). There were no significant differences in alanine transaminase, aspartate aminotransferase, gamma-glutamyl transpeptidase or albumin levels between the two groups (P > 0.05). ConclusionsVisible uptake of Gd-EOB-DTPA by the liver parenchyma was significantly associated with liver function parameters. EOB-MRI can be a valuable imaging biomarker for the assessment of liver parenchyma function outside of radiation area.

Longitudinal Visualization of Viable Cancer Cell Intratumoral Distribution in Mouse Models Using Oatp1a1-Enhanced Magnetic Resonance Imaging.

Multimodality reporter gene imaging provides valuable, noninvasive information on the fate of engineered cell populations. To complement magnetic resonance imaging (MRI) measures of tumor volume and 2-dimensional reporter-based optical measures of cell viability, reporter-based MRI may offer 3-dimensional information on the distribution of viable cancer cells in deep tissues. Here, we engineered human and murine triple-negative breast cancer cells with lentivirus encoding tdTomato and firefly luciferase for fluorescence imaging and bioluminescence imaging (BLI). A subset of these cells was additionally engineered with lentivirus encoding organic anion transporting polypeptide 1a1 (Oatp1a1) for MRI. Oatp1a1 operates by transporting gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) into cells, and it concomitantly improves BLI substrate uptake. After orthotopic implantation of engineered cells expressing or not expressing Oatp1a1, longitudinal fluorescence imaging, BLI, and 3-Tesla MRI were performed. Oatp1a1-expressing tumors displayed significantly increased BLI signals relative to control tumors at all time points (P < 0.05). On MRI, post-Gd-EOB-DTPA T1-weighted images of Oatp1a1-expressing tumors exhibited significantly increased contrast-to-noise ratios compared with control tumors and precontrast images (P < 0.05). At endpoint, tumors expressing Oatp1a1 displayed intratumoral MR signal heterogeneity not present at earlier time points. Pixel-based analysis of matched in vivo MR and ex vivo fluorescence microscopy images revealed a strong, positive correlation between MR intensity and tdTomato intensity for Oatp1a1-expressing tumors (P < 0.05), but not control tumors. These results characterize Oatp1a1 as a sensitive, quantitative, positive contrast MRI reporter gene for 3-dimensional assessment of viable cancer cell intratumoral distribution and concomitant BLI enhancement. This multimodality reporter gene system can provide new insights into the influence of viable cancer cell intratumoral distribution on tumor progression and metastasis, as well as improved assessments of anticancer therapies.

Four-dimensional fully convolutional residual network-based liver segmentation in Gd-EOB-DTPA-enhanced MRI.

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) tends to show higher diagnostic accuracy than other modalities. There is a demand for computer-assisted detection (CAD) software for Gd-EOB-DTPA-enhanced MRI. Segmentation with high accuracy is important for CAD software. We propose a liver segmentation method for Gd-EOB-DTPA-enhanced MRI that is based on a four-dimensional (4D) fully convolutional residual network (FC-ResNet). The aims of this study are to determine the best combination of an input image and output image in our proposed method and to compare our proposed method with the previous rule-based segmentation method. We prepared a five-phase image set and a hepatobiliary phase image set as the input image sets to determine the best input image set. We also prepared a labeled liver image and labeled liver and labeled body trunk images as the output image sets to determine the best output image set. In addition, we optimized the hyperparameters of our proposed model. We used 30 cases to train our model, 10 cases to determine the hyperparameters of our model, and 20 cases to evaluate our model. Our network with the five-phase image set and the output image set of labeled liver and labeled body trunk images showed the highest accuracy. Our proposed method showed higher accuracy than the previous rule-based segmentation method. The Dice coefficient of the liver region was 0.944 ± 0.018. Our proposed 4D FC-ResNet showed satisfactory performance for liver segmentation as preprocessing in CAD software.

Transarterial Chemoembolization of Hepatocellular Carcinoma Using Radiopaque Drug-Eluting Embolics: How to Pursue Periprocedural Cross-Sectional Imaging?

PurposeTo compare different imaging techniques (volume perfusion CT, cone-beam CT, and dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid–enhanced dynamic contrast–enhanced MR imaging with golden-angle radial sparse parallel MR imaging) in evaluation of transarterial chemoembolization of hepatocellular carcinoma (HCC) using radiopaque drug-eluting embolics (DEE). Materials and MethodsMR imaging and CT phantom investigation of radiopaque DEE was performed. In the clinical portion of the study, 13 patients (22 HCCs) were prospectively enrolled. All patients underwent cross-sectional imaging before and after transarterial chemoembolization using 100–300 μm radiopaque DEE. Qualitative assessment of images using a Likert scale was performed. ResultsIn the phantom study, CT-related beam-hardening artifacts were markedly visible at a concentration of 12% (v/v) radiopaque DEE; MR imaging demonstrated no significant detectable signal intensity changes. Imaging obtained before transarterial chemoembolization showed no significant difference regarding tumor depiction. Visualization of tumor feeding arteries was significantly improved with volume perfusion CT (P < .001) and cone-beam CT (P = .002) compared with MR imaging. Radiopaque DEE led to significant decrease in tumor depiction (P = .001) and significant increase of beam-hardening artifacts (P = .012) using volume perfusion CT before versus after transarterial chemoembolization. Greater residual arterial tumor enhancement was detected with MR imaging (10 HCCs) compared with volume perfusion CT (8 HCCs) and cone-beam CT (6 HCCs). ConclusionsUsing radiopaque DEE, the imaging modalities provided comparable early treatment assessment. In HCCs with dense accumulation of radiopaque DEE, treatment assessment using volume perfusion CT or cone-beam CT may be impaired owing to resulting beam-hardening artifacts and contrast stasis. Dynamic contrast–enhanced MR imaging may add value in detection of residual arterial tumor enhancement.

Liver assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging in primary biliary cholangitis patients.

To evaluate the feasibility of utilizing gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the assessment of Child-Pugh class and for differentiating between patients with primary biliary cholangitis (PBC) and posthepatitic cirrhosis. 45 PBC patients and 45 posthepatitic cirrhosis patients were enrolled and Gd-EOB-DTPA-enhanced MRI was applied. The average relative signal enhancement (RE) of the liver and average contrast to noise ratio (CNR) of common bile duct at 4, 20, and 50 min between different Child-Pugh classes of PBC patients were compared. The RE and CNR in all timepoints in patients with the same Child-Pugh class were compared between PBC patients and posthepatitic cirrhosis patients. The RE of liver and CNR of common bile duct at 4, 20, and 50min was significantly different between all Child-Pugh classes of PBC patients. There were also no significant differences in the RE of liver and CNR of common bile duct in all timepoints between patients with PBC and posthepatitic cirrhosis in the same Child-Pugh class. Gd-EOB-DTPA-enhanced MRI is feasible for liver function assessment in PBC patients. However, the ability of this modality in differentiating liver cirrhosis of different etiologies requires further investigation.

A Clinical Scoring System for Predicting Microvascular Invasion in Patients with Hepatocellular Carcinoma Within the Milan Criteria

BackgroundMicrovascular invasion (MVI) is recognized as a risk factor for early recurrence of hepatocellular carcinoma (HCC) within the Milan criteria after curative treatment. MethodsOne hundred eleven consecutive patients with HCC within the Milan criteria who underwent hepatic resection were retrospectively reviewed. Independent preoperative predictors of MVI were identified, and a scoring system was developed using significant predictors. ResultsMVI was identified in 51 of 111 patients (46%). Multivariate analysis identified the following independent predictors of MVI: alpha-fetoprotein (AFP) of > 95 ng/mL (odds ratio [OR], 9.87; 95% confidence interval [95% CI], 2.24–56.8; P = 0.002), des-γ-carboxy prothrombin (DCP) of > 55 mAU/mL (OR, 5.50; 95% CI, 2.09–15.4; P < 0.001), tumor size of > 2.8 cm (OR, 6.10; 95% CI, 2.07–20.0; P < 0.001), and non-smooth tumor margin in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) (OR, 5.34; 95% CI, 1.84–16.9; P = 0.002). A clinical scoring system was developed using these four variables. Within a total possible score of 0 to 4, the prevalence of MVI with a score of 0, 1, 2, 3, and 4 was 4.5%, 24.0%, 45.5%, 91.7%, and 100%, respectively (P < 0.001). The area under the curve of the scoring system was 0.865 based on the receiver operating characteristic curve analysis of the prediction score. ConclusionsOur clinical scoring system, consisting of AFP, DCP, tumor size, and tumor margin in Gd-EOB-DTPA-enhanced MRI, can be valuable for predicting MVI in HCC within the Milan criteria before curative treatment.

Assessing Liver Function by T1 Maps on Gd-EOB-DTPA-Enhanced MRI for up to 50 Min in Rat Models of Liver Fibrosis: A Longer Hepatobiliary Time Period may Help

Objectives To investigate whether a longer time period of gadolinium ethoxybenzyl diethylenetriaminepen-taacetic acid (Gd-EOB-DTPA)-enhanced T1 mapping scanning, as well as dynamic contrast-enhanced (DCE) and multiple hepatobiliary phase magnetic resonance imaging (MRI) have the potential to provide information about liver function in rats with liver fibrosis. Methods Forty rats were divided into the carbon tetrachloride-induced hepatic injury groups [carbon tetrachloride for four (n=14), eight (n=8), or twelve (n=8) weeks] and the control group (n=10). Gd-EOB-DTPA-enhanced MRI was performed including T1-mapping (delayed to 50 min), DCE, and multiple hepatobiliary phases. Indocyanine green retention rate at 15 min (ICG-R15) was determined. Parameters such as T1 reduction rate (ΔT1), elimination half-life of ΔT1 (TΔT1 1/2), relative enhancement (RE), time to maximum RE (Tmax), and perfusion parameters were calculated. Pearson correlation analysis was used for correlation analysis between ICG-R15 and each MRI indices. Results ΔT1 at 30, 40, and 50 min showed significant positive correlations with ICG-R15 ( r=0.784, 0.653, 0.757, P=0.007, 0.041, 0.030). TΔT1 1/2 showed a significant positive correlation with ICG-R15 (r=0.685, P=0.029). Tmaxshowed a significant positive correlation with ICG-R15 (r=0.532, P=0.019). Conclusions ΔT1 in the late hepatobiliary phase and T ΔT1 1/2 exhibited moderate correlations with liver function. The longer time period of Gd-EOB-DTPA-enhanced T1 mapping scanning, as well as DCE and multiple hepatobiliary phases, may be of some value for estimating liver function in rats with liver fibrosis.

Usefulness of Gd-EOB-DTPA-enhanced MRI for evaluating the potential for early development of hepatocellular carcinoma after HCV eradication by direct-acting antiviral treatment.

Objective: The development of hepatocellular carcinoma (HCC) is not uncommon in patients who achieve eradication of the hepatitis C virus through direct-acting antiviral (DAA) treatment. The aim of this study was to identify the patients at high risk for novel HCC development after a sustained virologic response (SVR) by DAA treatment.Patients and Methods: A total of 518 patients with no history of HCC treatment and who achieved SVR by DAA treatment were evaluated retrospectively. The correlations between HCC development and the patients’ characteristics were evaluated. For patients who underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) or dynamic contrast-enhanced computed tomography, the relationship between the imaging findings and subsequent HCC development was also assessed.Results: HCC developed newly in 22 patients, and the 1-year and 3-year cumulative HCC rates were 2.0% and 8.5%, respectively. In multivariate analysis, a FIB-4 index >4.0 and a post-treatment α-fetoprotein >4.0 ng/ml were significant risk factors for HCC. In 26 of 118 patients who underwent an MRI before DAA treatment, a non-hypervascular hypo-intense nodule was seen in the hepatobiliary phase, and in 6 of 182 patients who underwent a CT, a non-hypervascular hypo-enhanced nodule was seen in the delayed phase. The sensitivity and specificity of the MRI-positive findings for the subsequent development of HCC were 0.92 and 0.87, respectively, and those of the CT were 0.40 and 0.99, respectively. In multivariate analysis of patients who underwent an MRI, a non-hypervascular hypo-intense nodule was the only factor that was significantly related to HCC development (HR 32.4, p = 0.001).Conclusion: Gd-EOB-DTPA-enhanced MRI was found to be reliable for risk evaluation of subsequent HCC development in patients after SVR by DAA treatment. Patients with a non-hypervascular hypo-intense nodule need more careful observation for incident HCC.

Advances in Assessing Preoperative Liver Function with Gd-EOB-DTPA Dynamic Contrast Enhanced MRI

Liver cancer is the common malignant tumor in China and current treatment is based on surgery. However, liver function of many liver cancer patients is impaired before surgery, so there’s a high possibility of occurrence of liver failure after the tumor resection. Therefore, it’s necessary to accurately evaluate liver function before surgery. Currently, clinical methods are mostly limited to assess the function of overall liver. But the application of hepatocyte-specific contrast agent—gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) makes it possible to assess the function of local liver segment accurately. This paper reviewed the progress of using Gd-EOB-DTPA dynamic contrast enhanced magnetic resonance imaging (MRI) to assess liver function preoperatively, such as parameters selection for liver function assessment, clinical factors affecting Gd-EOB-DTPA enhanced MRI and so on.

Gadolinium Ethoxybenzyl Diethylene-triamine-pentaacetic-acid-enhanced Magnetic Resonance Imaging Perfusion and Multiple Hepatobiliary-phase Imaging for Quantitative Assessment of Liver Fibrosis in Rat Models

Objective To investigate the value of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting different stages of liver fibrosis in rats.Methods Rat models of liver fibrosis were induced by carbon tetrachloride intraperitoneal injection for 4 - 12 weeks (n=45). The control group was applied with 0.9% saline (n=15). The MRI protocol contained both dynamic contrast-enhanced sequence (60 continuous scans within 3 minutes,including three pre-contrast measurements) and multiple hepatobiliary-phase acquisitions (every 5 minutes after contrast injection,60 minutes in total). METAVIR score was used to grade liver fibrosis:normal (F0),mild fibrosis (F1 - F2),and advanced fibrosis (F3 - F4). Liver perfusion parameters [transfer constant (K trans),extravascular extracellular volume fraction (Ve),initial area under curve (iAUC),maximum relative enhancement (REmax),and time of maximum RE (Tmax)] as well as hepatobiliary-phase parameters [RE at different time point,the decrease of RE (REchange=RE3 min - RE60 min),and elimination half-life of RE (TRE1/2)] were measured and compared with ANOVA analysis and Spearman rank correlation.Results Thirty-one rats completed MRI exams and were then divided into normal (n=10),mild fibrosis (n=10),and advanced fibrosis (n=11) groups. K trans,Ve and iAUC decreased as liver fibrosis progressed (r=-0.631,P=0.002;r=-0.503,P=0.017;r=-0.446,P=0.037). K trans and Ve showed significant differences among three groups(F=7.011,P=0.005;F=4.656,P=0.023). K trans and Ve were significantly lower in advanced fibrosis group than in normal group (P=0.001,P=0.009). There were statistical significant differences of Tmax,TRE1/2 and REchange among groups(F=6.633,P=0.005;F=5.493,P=0.010;F=5.343,P=0.014). Compared to normal and mild fibrosis groups,advanced fibrosis group had significantly longer Tmax and TRE1/2 (P=0.005,P=0.004;P=0.008,P=0.008)and significantly lower REchange(P=0.007,P=0.012).Conclusion Perfusion and multi-hepatobiliary-phase parameters such as K trans,Ve,Tmax, TREI/2 and REchange obtained from Gd-EOB-DTPA-enhanced MRI,may be valuable for detecting and staging liver fibrosis.

Gd-EOB-DTPA dynamic contrast-enhanced magnetic resonance imaging is more effective than enhanced 64-slice CT for the detection of small lesions in patients with hepatocellular carcinoma.

This study aimed to compare the sensitivity and accuracy for the detection of small lesions in patients with hepatocellular carcinoma (HCC) using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 64-slice computed tomography (CT) enhanced scanning, and to evaluate the necessity to perform MRI in patients diagnosed with HCC by CT.The clinical data from 209 patients with HCC diagnosed prior to surgery in the Affiliated Hospital of Guilin Medical University, China were retrospectively analyzed. The 64-slice dynamic contrast-enhanced multi-detector CT (MDCT) and 3.0 T Gd-EOB-DTPA DCE MRI procedures were successively carried out on all patients who were enrolled in a self-controlled study including detection and diagnosis of HCC lesions by MRI and CT, respectively.A total of 243 lesions were detected and both imaging methods could accurately detect lesions of diameter >2 cm. For lesions <2 cm, MRI detected 47, while CT detected 25 lesions indicating that the detection rate of MRI was 88% higher than that of CT. In addition, MRI detected lesions in 15 cases (7.81% in the total of 209 cases) that were not diagnosed by CT. Among these cases, 2 patients were diagnosed to have no lesion by CT.Gd-EOB-DTPA DCE-MRI performed as a routine check prior to surgery in HCC patients can improve the detection of small HCC lesions.

Diagnostic performance of Gd-EOB-DTPA-enhanced MRI for evaluation of liver dysfunction: a multivariable analysis of 3T MRI sequences.

ObjectiveThe aim of this study was to evaluate the diagnostic performance of a multiparametric gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI examination for the estimation of liver dysfunction classified by the Model for End-Stage Liver Disease (MELD) score.ResultsLiver dysfunction can be assessed by different methods. In a logistic regression analysis, T1- and T2-weighted images were affected by impaired liver function. In the assessment of liver dysfunction, the reduction rate in T1 mapping sequences showed a significant correlation in simple and multiple logistic regression.ConclusionChanges in Gd-EOB-DTPA-enhanced MRI between plain images and images obtained during the hepatobiliary phase allowed good prediction of liver dysfunction, especially when using T1 mapping sequences.Materials and MethodsA total of 199 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. In the multivariable analysis, the full range of available MRI sequences was used to estimate the liver dysfunction of patients with various MELD scores.