Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid Research Articles

Hepatology highlights

Hepatology highlights

Abstract 4688: Novel prognostic subtype of hepatocellular carcinoma reflecting stem/maturational status of the tumor defined by Gd-EOB-DTPA-enhanced MRI and serum AFP

Abstract Survival of patients with hepatocellular carcinoma (HCC) varies on an individually basis, even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI) has recently been introduced to evaluate hepatic lesions with regard to the activity of the organic anion transporter OATP1B3 as well as vascularity. Here we report that Gd-EOB-DTPA-Enhanced MRI and serum alpha-fetoprotein (AFP) status reflects the stem/maturation status of HCC with distinct biology and prognostic information. Atypical uptake of Gd-EOB-DTPA in the hepatobiliary phase was observed in ∼ 15% of HCCs. This uptake correlated with the low serum alpha-fetoprotein (AFP) levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A, and good prognosis. In contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP presented poor prognosis with the activation of an oncogene FOXM1. Knockdown of HNF4A in cancer cells, obtained from a surgically resected HCC showing atypical uptake of Gd-EOB-DTPA, resulted in the increase of AFP and FOXM1 and the loss of OATP1B3 expression accompanied with the mesenchymal morphological changes, enhanced cell proliferation and tumorigenesis in vivo. HCC classification based on EOB-MRI and serum AFP level (EOB-AFP classification) predicted overall survival in a retrospective cohort (n = 70), and its prognostic utility was validated in a multi-institution cohort of early-stage HCCs (n = 109). This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging to improve management algorithms, especially in early stage. Citation Format: Taro Yamashita, Masao Honda, Shuichi Kaneko. Novel prognostic subtype of hepatocellular carcinoma reflecting stem/maturational status of the tumor defined by Gd-EOB-DTPA-enhanced MRI and serum AFP. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4688. doi:10.1158/1538-7445.AM2014-4688

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n=70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n=109). This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease.

Quantitative evaluation of liver function by liver enhancement in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI

Objective To investigate the utilization of liver enhancement in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for liver function evaluation.Methods Fifty-five patients who received enhanced MRI with Gd-EOB-DTPA were retrospectively analyzed.Images were obtained before injection and in hepatobiliary phase (5,10,and 20 minutes after Gd-EOB-DTPA injection).The patients were assigned into two subgroups according to individual liver function (n =35 in Group 1:normal liver and Child-Pugh class A; n =20 in Group 2:Child-Pugh class B and C).The relative liver enhancement (RE) was calculated at different time point.The general data (age,sex) and relevant laboratory results were recorded.Independent sample t-test was conducted to compare the RE between two groups at different time point.ROC curve was used to determine the best time point and RE threshold that can reflect the differences between two groups.Univariate analyses was performed to analyze the relationship between RE at the best time point and laboratory results.Multivariate analyses was performed to screen the independent influencing factor for RE at the best time point.Results The differences of RE between two groups were statistically significant at all time points (P ＜ 0.0001).10 minutes was the best time point for detecting the differences of liver function between two groups.When an RE cutoff value (＞ 1.52) was applied,normal or Child-Pugh class A could be predicted with sensitivity of 74.3％ and specificity of 90％.RE at the best time point was significantly related with total serum bilirubin level (TBil),serum albumin level (Alb) and prothrombin time (PT).And TBil was an independent influencing factor.Conclusion RE can be used to evaluate the liver function,and 10 minutes is the best time point that can be used to differentiate patients with normal or mild liver damage from those with moderate or severe liver damage. Key words: Liver function; Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) ; Magnetic resonance imaging (MRI)

Relationship between liver enhancement in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI and liver function

Objective To evaluate the effect of liver function on liver enhancement in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)-enhanced MRI.Methods Sixty-seven patients who suffered from cirrhosis and received enhanced MRI with Gd-EOB-DTPA were retrospectively analyzed,and divided into three subgroups according to ChildPugh score(45 patients in group A,20 in group B,5 in group C).All the individuals of both groups had MRI before injection,and hepatobiliary phase images were obtained at 5,10,and 20 minutes after bolus administration of Gd-EOB-DTPA.The relative enhancement(RE) was calculated by dividing the signal intensity of liver(SI) at t min after injection(SIt) by precontrast SI(SI0).The total serum bilirubin level(TB),serum albumin level(Alb) and prothrombin time(PT) were recorded.The one-way ANOVA was used to compare the RE among three groups at 5,10 and 20 minutes.SNK was used for further pairwise comparison.The effect of liver function on RE was assessed with the generalized linear model.Pearson correlation coefficients were measured between each biochemical test result(TB,Alb,PT) and RE at different time points.Results The RE at 5,10 and 20 minutes were 1.59±0.20,1.65±0.22,1.69±0.25 of group A; 1.47± 0.14,1.48±0.18,1.50±0.22 of group B,1.35±0.07,1.27±0.06,1.26±0.06 of group C.There were statistically significant differences of RE among groups at 5,10 and 20 minutes(F=5.854,11.207,9.666,P＜0.01).Statistically pairwise comparison differences of RE were found between group A and C at 5,10 and 20 minutes(P＜0.01),between B and C at 10 and 20 minutes(P＜0.05),between A and B at 10 minutes(P＜ 0.05).There were statistically significant differences of TB,Alb and PT among groups(P＜0.01).RE at 10 and 20 minutes had moderate negative correlation with TB(r=-0.483,-0.500; P＜0.01),low negative correlation with PT(r=-0.326,-0.351;P＜0.01) and weak positive correlation with Alb(r=0.290,0.292;P＜0.05).Conclusions There are differences of RE among patients with different liver function,and the RE is associated with TB,Alb and PT.Thus,it may allow us to estimate the liver function. Key words: Liver function; Contrast media; Magnetic resonance imaging

Non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of outcomes for early-stage HCC.

In patients with hepatocellular carcinoma (HCC), gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often identifies non-hypervascular hypointense hepatic nodules during the hepatobiliary phase, but their prognostic significance is unclear. We conducted a prospective observational study to investigate the impact of non-hypervascular hypointense hepatic nodules detected by Gd-EOB-DTPA-enhanced MRI on the outcome of patients with early-stage HCC. Post-treatment recurrence and survival rates were analyzed in 138 patients with non-recurrent, early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0 or A] and Child-Pugh A liver function according to the presence of non-hypervascular hypointense nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Non-hypervascular hypointense hepatic nodules were detected in 51 (37.0%) patients with early-stage HCC on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrence rates were significantly higher in patients with non-hypervascular hypointense nodules (p < 0.0001). Based on a multivariate analysis, the presence of non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI was independently associated with an increased recurrence rate, independent of tumor progression or treatment (p = 0.0005). The survival rate was significantly lower in patients with non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI (p = 0.0108). In patients with early-stage typical HCC (BCLC 0 or A), the presence of concurrent non-hypervascular hypointense hepatic nodules in the hepatobiliary phase of pretreatment Gd-EOB-DTPA-enhanced MRI is an indicator of higher likelihood of recurrence after treatment and may be a marker for unfavorable outcome.

Clinical utility of imaging for evaluation of hepatocellular carcinoma.

The hemodynamics of a hepatocellular nodule is the most important imaging parameter used to characterize various hepatocellular nodules in liver cirrhosis, because sequential changes occur in the feeding vessels and hemodynamic status during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular carcinoma (HCC) are also usually based on vascular findings, eg, early arterial uptake followed by washout in the portal venous and equilibrium phases. Contrast-enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT), and dynamic magnetic resonance (MR) imaging with gadopentetate dimeglumine (Gd-DTPA) are useful for detecting hypervascular HCC on the basis of vascular criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), a hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC. Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically differentiated HCC as hypointense relative to the liver parenchyma. 18F-fluorodeoxyglucose positron emission tomography imaging might not be suitable for the screening and detection of HCC, given its lower diagnostic performance. However, this technique plays an important role in determining whether HCC has spread beyond the liver.

Impaired hepatic Gd-EOB-DTPA enhancement after radioembolisation of liver malignancies.

To evaluate the uptake of the liver-specific magnetic resonance imaging (MRI) contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by functional liver parenchyma after radioembolisation (RE) of hepatic malignancies. Uptake of Gd-EOB-DTPA prior to RE versus 60+/-24d and 126+/-32d after RE was compared in a group of 33 patients with primary or secondary hepatic malignancies. In patients who underwent single-lobe treatment, left and right lobes were compared 59+/-24 days after RE. Gd-EOB-DTPA uptake was determined as follows: ratio of mean signal intensity in liver parenchyma to muscle in Gd-EOB-DTPA-enhanced T1-weighted MRI was subtracted from ratio of mean intensity in liver parenchyma to muscle in unenhanced T1-weighted MRI. Gd-EOB-DTPA uptake in liver parenchyma was 0.845+/-0.29 before RE, 0.615+/-0.38 (P = 0.0022) at day 60+/-24, and 0.739+/-0.30 at day 126+/-32 after RE. In cases of single-lobe treatment, Gd-EOB-DTPA uptake was 0.581+/-0.256 for treated and 0.828+/-0.32 (P = 0.0164) for untreated hepatic lobes. Uptake of Gd-EOB-DTPA by liver parenchyma is impaired after RE, indicating dysfunction of the local hepatic system. These findings suggest that Gd-EOB-DTPA-enhanced MRI has the potential to be used for monitoring liver damage after RE.

Quantitative evaluation of enhancement patterns in focal solid liver lesions with Gd-EOB-DTPA-enhanced MRI.

PurposeThe objective was to investigate the dynamic enhancement patterns in focal solid liver lesions after the administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of dynamic magnetic resonance imaging (MRI) including hepatobiliary phase (HP) images 20 min after Gd-EOB-DTPA administration.Materials and MethodsNon-enhanced T1/T2-weighted as well as dynamic magnetic resonance (MR) images during the arterial phase (AP), the portal venous phase (PVP), the late phase (LP), and the HP (20 min) were obtained from 83 patients (54 male, 29 female, mean age 62.01 years) with focal solid liver lesions. MRI was conducted by means of a 1.5-T system for 63 patients with malignant liver lesions (HCCs: n = 34, metastases: n = 29) and for 20 patients with benign liver lesions (FNH lesions: n = 14, hemangiomas: n = 3, adenomas: n = 3). For quantitative analysis, signal-to-noise ratios (SNR), contrast enhancement ratios (CER), lesion-to-liver contrast ratios (LLC), and signal intensity (SI) ratios were measured.ResultsThe SNR of liver parenchyma significantly increased in each dynamic phase after Gd-EOB-DTPA administration compared to the SNR of non-enhanced images (p<0.001). The CER of HCCs and metastases significantly decreased between LP and HP images (p = 0.0011, p<0.0001). However, FNH lesions did not show any significant difference, whereas an increased CER was found in hemangiomas. The mean LLCs of FNH lesions were significantly higher than those of HCCs and metastases. The LLC values of hemangiomas remained negative during the entire time course, whereas the LLC of adenomas indicated hyperintensity from the AP to the LP. Furthermore, adenomas showed hypointensity in HP images.ConclusionGd-EOB-DTPA-enhanced MRI may help diagnose focal solid liver lesions by evaluating their enhancement patterns.

Effect of Gd-EOB-DTPA on hepatic fat quantification using high-speed T2-corrected multi-echo acquisition in 1H MR spectroscopy

PurposeTo determine whether gadolinium ethoxybenzyldiethylenetriaminepentaacetic acid (Gd-EOB-DTPA) administration affects hepatic fat quantification by magnetic resonance spectroscopy (MRS) using the fast breath-hold high-speed T2-corrected multiecho (HISTO) technique. Materials and MethodsSeventy-six patients underwent Gd-EOB-DTPA-enhanced liver MR and 15sec breath-hold HISTO MRS (4 times), twice before and twice after Gd-EOB-DTPA administration. Two consecutive MRSs were performed immediately before the dynamic study. Post-contrast MRS was performed twice continuously, approximately 15min after contrast injection, prior to obtaining 20-min hepatobiliary phase images. We used paired t-test and intraclass correlation coefficient (ICC) to evaluate the variability of the mean fat fraction (FF) on pre-contrast MRS and post-contrast MRS and the effect of the contrast agent on the mean FF. ResultsThe mean FFs were not significantly different between pre-contrast MRS and post-contrast MRS (6.50%±6.54 versus 6.70%±6.61, P=0.15). The ICC of FF calculation between pre- and post-contrast MRS was 0.984. The ICCs for the FF magnitude between pre- and post-contrast MRS were 0.452, 0.771, and 0.995 for FF <5%, FF 5–10%, and FF ≥10%, respectively. ConclusionGd-EOB-DTPA does not appear to influence hepatic fat quantification, especially for patients with hepatic steatosis.

Diagnostic accuracy for macroscopic classification of nodular hepatocellular carcinoma: comparison of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and angiography-assisted computed tomography

The macroscopic type of hepatocellular carcinoma (HCC) is a predictor of prognosis. We clarified the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in the macroscopic classification of nodular hepatocellular carcinoma (HCC) as compared to angiography-assisted computed tomography (CT). A total of 71 surgically resected nodular HCCs with a maximum diameter of ≤5 cm were investigated. HCCs were evaluated preoperatively using Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT. HCCs were pathologically classified as simple nodular (SN), SN with extranodular growth (SN-EG), or confluent multinodular (CMN). SN-EG and CMN were grouped as non-SN. Five readers independently reviewed the images using a five-point scale. We examined the accuracy of both imaging modalities in differentiating between SN and non-SN HCC. Overall, the area under the receiver operating characteristic curve (A z ) for the diagnosis of non-SN did not differ between Gd-EOB-DTPA-enhanced MRI and angiography-assisted CT [0.879 (95% confidence interval (CI), 0.779-0.937) and 0.845 (95% CI, 0.723-0.919), respectively]. For HCCs >2 cm, the A z for Gd-EOB-DTPA-enhanced MRI was greater than 0.9. The sensitivity, specificity, and accuracy of Gd-EOB-DTPA-enhanced MRI for identifying non-SN were equal to or higher than values with angiography-assisted CT in all three categories (all tumors, ≤2 cm, and >2 cm), but the differences were not statistically significant. Using Gd-EOB-DTPA-enhanced MRI to assess the macroscopic findings in nodular HCC was equal or superior to using angiography-assisted CT.

Clinicopathological significance of the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid in hepatocellular carcinoma

A faint hypointensity in the noncancerous tissue around hepatocellular carcinoma (HCC) in the hepatobiliary phase of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) is encountered. The goal is to elucidate the significance of this type of pseudolesion designated as the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) (PDUAE). This study group consisted of 61 patients with 61 surgically resected HCCs who underwent preoperative Gd-EOB-DTPA-enhanced MRI. The presence of a faint and hypointense area around the tumor in the hepatobiliary phase was defined as PDUAE. The frequency with which PDUAE was seen was compared between pairs of groups determined by clinical and pathological parameters using a Fisher's exact probability test. The parameters showing significant differences in this test were further tested by multiple logistic regression analysis. PDUAE was observed in 25 cases. In univariate analysis, the values of alpha-fetoprotein and protein-induced by vitamin K absence or antagonist-II, maximal diameter, the presence of a capsule, and vascular invasion were significantly correlated with the frequency with which PDUAE was seen. In multivariate analysis, only maximal diameter and vascular invasion were significantly correlated. When the presence of PDUAE was used as an indicator of vascular invasion, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 72%, 80.6%, 77%, 72%, and 80.6%, respectively. By using this indicator, "microscopic" vascular invasion of HCC can be easily predicted with Gd-EOB-DTPA-enhanced MRI.

Radial MRI during free breathing in contrast-enhanced hepatobiliary phase imaging

Use of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for diagnosis of hepatic tumors has been previously reported. Fat-saturated 3D T1-weighted gradient echo sequence (TIGRE) imaging using a breath-hold technique is usually used for dynamic studies and hepatobiliary phase Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). In cases where the patient has difficulty holding their breath, this scanning method can be difficult. To investigate the usefulness of a fat-saturated T1-weighted spin-echo (SE) sequence using a radial read-out (radial acquisition regime-SE, RADAR-SE) during free breathing for hepatobiliary phase Gd-EOB-DTPA-enhanced MRI. Images were acquired at 1.5 T. First, a phantom with diluted Gd-EOB-DTPA was scanned using the TIGRE sequence and the RADAR-SE sequence. Contrast ratios of the sequences were compared. Next, the hepatobiliary phase was imaged in 62 patients using the TIGRE sequence with breath-hold and the RADAR-SE during free breathing. Qualitative and quantitative evaluations were compared. In the phantom study, RADAR-SE had a higher contrast ratio than TIGRE. In the clinical study, artifacts were more conspicuous in RADAR-SE compared to TIGRE images in the qualitative evaluation. However, RADAR-SE images were equal to or better than TIGRE images in patients who had difficulty holding their breath. The signal intensity ratio of the liver was statistically higher using RADAR-SE than TIGRE. RADAR-SE can be useful for hepatobiliary phase Gd-EOB-DTPA-enhanced MRI in patients who have difficulty holding their breath.

Functional magnetic resonance cholangiography with Gd-EOB-DTPA: A study in healthy volunteers

PurposeTo describe the patterns of bile distribution in the biliary tree, duodenum, jejunum, and stomach, and to determine the gallbladder ejection fraction (GBEF) by using functional magnetic resonance cholangiography (MRC) with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in healthy volunteers. Materials and MethodsForty subjects were included in this study. After conventional MRC, pre-fatty meal MRC (PRFM) was obtained at 30, 40, 50, and 60min after contrast agent injection. Then, post-fatty meal MRC (POFM) was obtained every 10min for 1h. We assessed the PRFM and POFM for opacification of contrast agent in the first- and second-order intrahepatic ducts (IHDs) and the common bile duct (CBD). Contrast agent opacification in the cystic duct was assessed, and the percentage volume of contrast agent filling in the gallbladder (GB) was calculated on PRFM. We calculated the GBEF and assessed the presence of contrast agent in the GB, duodenum, jejunum, and stomach. ResultsThirty-six (90%) subjects showed grade 3 CBD opacification (visible contrast and well-defined bile duct border) on 60-min PRFM. Thirty-four (85%) subjects showed grade 3 first-order IHD opacification on 60-min PRFM. All (100%) subjects showed cystic duct opacification of contrast agent, and the average percentage volume of contrast agent filling in the GB was 68.81%±16.84% on 60-min PRFM. The GBEF at 30-min POFM was 35.00%±18.26%. Ten (25%) subjects had no contrast agent in the stomach and small bowel on all PRFMs. Twelve (30%) subjects had contrast medium in the stomach on PRFM and/or POFM. ConclusionsFunctional MRC with Gd-EOB-DTPA can allow determining the distribution of bile in the biliary tree and small intestine, as well as the GBEF.

Accumulation of Bile in the Gallbladder: Evaluation by means of Serial Dynamic Contrast-Enhanced Magnetic Resonance Cholangiography with Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid.

The aim of this study was to evaluate the process of biliary excretion of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) into the biliary tract and to assess the accumulation patterns in the gallbladder using MR cholangiography obtained with Gd-EOB-DTPA which is a liver-specific hepatobiliary contrast agent. Seventy-five patients underwent Gd-EOB-DTPA enhanced MR imaging. Serial multiphasic hepatobiliary phase imaging was qualitatively reviewed to evaluate the process of the biliary excretion of contrast agent into the bile duct and the gallbladder. The accumulation pattern of contrast agent into gallbladder was classified into two groups (group 1 = orthodromic type and group 2 = delayed type). Furthermore, the results in differences of the presence of T1 hyperintense bile or sludge of gallbladder, gall stones, wall thickening of gallbladder, chronic liver disease, and liver cirrhosis between two groups were compared. Forty-eight of 75 patients (64%) were included in group 1, and remaining 27 (36%) were in group 2. The frequency of the presence of T1 hyperintense bile or sludge of gallbladder was significantly higher in patients with group 2 than that in patients with group 1 (P = 0.041). MR cholangiography obtained with Gd-EOB-DTPA showed that there may be an association between the biliary accumulation pattern in the gallbladder and the pathological condition.

Detection and Localization of Bile Duct Leaks After Cholecystectomy Using Gd-EOB-DTPA—Enhanced MR Cholangiography

To determine if gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) cholangiography can detect and localize bile duct leaks in postcholecystectomy patients. Four blinded independent radiologists performed a retrospective review of 16 consecutive patients who underwent MR cholangiography with intravenous Gd-EOB-DTPA for the evaluation of possible biliary leak. Image quality, ductal opacification, and presence and location of any bile leak were evaluated. An independent observer determined the criterion standard using a consensus of all chart, clinical, and imaging findings. All 6 bile leaks confirmed at endoscopic retrograde cholangiopancreatography were diagnosed by all reviewers (sensitivity, 100%). Of the 10 patients with no leak, only one reader incorrectly diagnosed a bile leak in a single case (specificity, 98%). The accuracy for detection of the site of leak with Gd-EOB-DTPA-enhanced MR cholangiography was 80%. Gadolinium-EOB-DTPA-enhanced MR can detect bile leaks with a high sensitivity and specificity.

Evaluation of Neuroendocrine Liver Metastases

The objective of this study was to evaluate the correlation between dynamic gadoxetic acid-enhanced magnetic resonance imaging parameters and specific uptake values (SUVs) derived from ¹⁸fluorodeoxyglucose (¹⁸F-FDG) and ⁶⁸Ga-DOTA-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with liver metastases of neuroendocrine neoplasms. A total of 42 patients with hepatic metastases of neuroendocrine neoplasms were prospectively enrolled and underwent both dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and PET/CT, using either ¹⁸F-FDG or ⁶⁸Ga-DOTATATE as tracer. The DCE-MRI was performed at 3 T with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid acquiring 48 slices every 2.2 seconds for 5 minutes. Three regions of interest (ROIs) representing the liver background and up to 3 ROIs representing metastatic liver tissue were coregistered in the PET/CT and in the DCE-MRI data sets. For each patient, a dedicated dual-inlet, 2-compartment uptake model was fitted to the enhancement curves of DCE-MRI ROIs and perfusion parameters were calculated. Lesion-to-background ratios of SUVs were correlated with corresponding lesion-to-background ratios of the perfusion parameters arterial plasma flow, venous plasma flow, total plasma flow, extracellular mean transit time, extracellular volume, arterial flow fraction, intracellular uptake rate, and hepatic uptake fraction using the Spearman coefficient. Whereas the lesion-to-background ratios of arterial plasma flow and arterial flow fraction of liver metastases correlated negatively with the lesion-to-background ratios of SUV(mean) derived from ⁶⁸Ga-DOTATATE PET/CT (r = -0.54, P < 0.001; r = -0.39, P < 0.001, respectively), they correlated positively with the lesion-to-background ratios of SUV(mean) derived from ¹⁸F-FDG-PET/CT (r = 0.51, P < 0.05; r = 0.68, P < 0.01, respectively). The lesion-to-background ratios of the DCE-MRI parameters extracellular mean transit time and extracellular volume correlated very weakly with the lesion-to-background ratios of SUV(mean) from ⁶⁸Ga-DOTATATE PET/CT, whereas venous plasma flow, total plasma flow, hepatic uptake fraction, and intracellular uptake rate showed no correlation between DCE-MRI and PET/CT. Both ⁶⁸Ga-DOTATATE and ¹⁸fluorodeoxyglucose PET/CT partially correlate with MRI perfusion parameters from the dual-inlet, 2-compartment uptake model. The results indicate that the paired imaging methods deliver complementary functional information.

Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function

We aimed to develop and assess the efficacy of a liver function index that combines liver enhancement and liver volume to standard liver volume (LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. In all, 111 patients underwent a Gd-EOB-DTPA-enhanced MRI, including T1 mapping, before and 20min after Gd-EOB-DTPA administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver function indices: relative enhancement of the liver, corrected enhancement of the liver-to-spleen ratio, LSC_N20, increase rate of the liver-to-muscle ratio, reduction rate of T1 relaxation time of the liver, ΔR1 of the liver and K Hep; the indices were multiplied by the LV/SLV ratio. We calculated the correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by using Pearson correlation analysis. There were significant correlations between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P < 0.001) were more strongly correlated with the ICG clearance than those without multiplication by the LV/SLV ratio. Gd-EOB-DTPA-enhanced MRI-based liver function indices that combine liver enhancement and the LV/SLV ratio may more reliably estimate liver function. • Gd-EOB-DTPA-enhanced MRI is useful for assessing liver function. • Liver enhancement on Gd-EOB-DTPA-enhanced MRI correlates with indocyanine green (ICG) clearance. • Liver volume to standard liver volume (LV/SLV) ratio correlates with ICG clearance. • Liver enhancement and LV/SLV ratio help to estimate liver function.

Comparison between T1 relaxation time of Gd‐EOB‐DTPA‐enhanced MRI and liver stiffness measurement of ultrasound elastography in the evaluation of cirrhotic liver

To compare four imaging approaches in cirrhotic estimation; pre-enhancement T1 relaxation time (T1RT), reduction rate (RR) of T1RT, signal-based liver-to-muscle ratio (L/M ratio) on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), and liver stiffness measurement (LSM) of US elastography. Consecutive 58 patients with chronic liver diseases who underwent both Gd-EOB-DTPA-enhanced MRI and FibroScan were analyzed. Four imaging approaches were evaluated by fibrosis score from liver biopsy and receiver operating characteristic (ROC) analysis. RR was found to be inversely correlated with LSM (r = -0.65). RR decreased with degree of fibrosis (F0-F1, 58.5 ± 6.2%, versus F2-F3-F4, 48.8 ± 11.7%, P = 0.010, F0-F1-F2, 58.2 ± 6.2% versus F3-F4, 45.5 ± 12.3%, P = 0.010 and F0-F1, 58.5 ± 6.2%, versus F2-F3, 52.1 ± 12.0%, P = 0.0038). LSM increased with degree of fibrosis (F0-F1, 5.4 ± 2.2 kPa versus F2-F3-F3, 19.3 ± 15.5 kPa, P = 0.0011 and F0-F1-F2, 6.8 ± 3.6 kPa versus F3-F4, 23.8 ± 17.1 kPa, P = 0.0029 and F0-F1, 5.4 ± 2.2 kPa, versus F2-F3, 11.4 ± 7.2 kPa, P = 0.0098). Area under ROC curves were 0.83 (F3-F4), 0.72 (F2-F3-F4), 0.68 (F2-F3) for RR and 0.83 (F3-F4), 0.88 (F2-F3-F4), 0.81 (F2-F3) for LSM in discriminating between patients with fibrosis. The capability by LSM was better than those by RR of T1RT, pre-enhancement T1RT, and L/M ratio to differentiate F ≥ 2, but LSM and RR of T1RT showed the same value to differentiate F ≥ 3.

Co‐registered positron emission tomography/computed tomography and gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid magnetic resonance imaging features of multiple angiosarcoma of the liver

Hepatic angiosarcoma is a very rare disease, accounting for only 2% of primary liver malignancy. An 82-year-old man was admitted to our hospital because of jaundice and weight loss. Computed tomography (CT) and magnetic resonance imaging (MRI) showed diffuse and multiple space-occupying lesions. On gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, the tumor was not enhanced intensely in the arterial phase following contrast injection, and was then gradually enhanced homogeneously. In the delayed phase and hepatobiliary phase, the tumor was completely washed out. Whole-body (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT fusion scanning confirmed metabolic activity with maximum uptake value of 3.64 in the lesions. A liver biopsy showed spindle-shaped tumor cells proliferating along sinusoids, with elongated and hyperchromatic nuclei. Immunohistochemical studies showed tumor cells positive for von Willebrand factor and CD34. These findings were consistent with angiosarcoma of the liver. This case report is the first description of co-registered FDG-PET/CT images and Gd-EOB-DTPA-enhanced MRI of primary hepatic angiosarcoma.