Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid Research Articles

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.

Quantitative evaluation of liver function with T1 relaxation time index on Gd‐EOB‐DTPA‐enhanced MRI: Comparison with signal intensity‐based indices

To evaluate whether the reduction rate of T1 relaxation time of the liver (T1 relaxation time index) before and 20 minutes after gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) injection has the potential to serve as an magnetic resonance imaging (MRI)-based liver function test in comparison with signal intensity-based indices. Ninety-nine patients with suspected liver lesions underwent Gd-EOB-DTPA-enhanced MRI. T1 maps using 3D T1-weighted gradient-echo volumetric interpolated examination with two different flip angles were also performed before and 20 minutes after Gd-EOB-DTPA administration. T1 relaxation time index was compared with four signal intensity-based indices in terms of the ability to discriminate Child-Pugh A (CPA) and Child-Pugh B (CPB) from normal liver function (NLF), and in terms of its correlation with indocyanine green (ICG) clearance. Twenty-four patients were classified as NLF, 64 patients were classified as CPA, and 11 were classified as CPB group. The T1 relaxation time index was significantly lower for CPA (0.62 ± 0.08 vs. 0.68 ± 0.07, P = 0.021) and CPB (0.55 ± 0.15 vs. 0.68 ± 0.07, P < 0.001) than for NLF. All signal intensity-based indices showed significant differences only when comparing NLF and CPB. The correlation coefficient with ICG clearance was the highest for T1 relaxation time index (r = -0.605, P < 0.001). The T1 relaxation time index has the potential to serve as an MRI-based liver function test, and is most strongly correlated with ICG clearance among the Gd-EOB-DTPA MRI-based indices investigated.

Hypovascular Hepatic Nodules Showing Hypointense on the Hepatobiliary-Phase Image of Gd-EOB-DTPA-Enhanced MRI to Develop a Hypervascular Hepatocellular Carcinoma: A Nationwide Retrospective Study on Their Natural Course and Risk Factors

Objective: We aimed to investigate the natural outcome of nonhypervascular lesions detected in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI by performing a longitudinal study retrospectively enrolled in a nationwide manner. Methods: Between February 2008 and March 2011, 224 patients with 504 nodules that were diagnosed as nonhypervascular by imaging were recruited from institutions that participated in the present study. We examined the natural outcome of nonhypervascular lesions and evaluated the risk factors. Results: Of the 504 nodules, 173 (34.3%) showed hypervascular transformation. The overall cumulative incidence of hypervascular transformation was 14.9% at 12 months and 45.8% at 24 months. Multivariate analysis using the Cox regression model revealed previous treatment history for hepatocellular carcinoma (HCC; relative risk = 1.498; p = 0.036, 95% CI 1.03-2.19) and hyperintensity on T2-weighted images (relative risk = 1.724; p = 0.015, 95% CI 1.11-2.67) were identified as independent factors for hypervascular transformation. Conclusions: Patients who have a previous treatment history for HCC and with hypointense nodules showing hyperintensity on T2-weighted images need careful follow-up because of the high incidence of hypervascular transformation.

Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging for the detection of hepatocellular carcinoma: A meta-analysis

To evaluate the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for hepatocellular carcinoma (HCC).A systematic, comprehensive literature search was conducted in PubMed (2004 [Gd-EOB-DTPA was first approved in Europe in 2004] to April 2013), Embase (2004 to April 2013), Web of Science (2004 to April 2013), and the Cochrane Library (2004 to April 2013). The Quality Assessment of Diagnostic Studies (QUADAS) items was used to evaluate the quality of the included studies. Stata 12.0 was used to analyze the data. Pooled sensitivity (SEN), pooled specificity (SPE), pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), pooled diagnostic odds ratio (dOR), and summary receiver operating characteristic (SROC) curves were calculated to assess the diagnostic value of the individual diagnostic tests.A total of 11 articles were included, involving 1578 nodules from four countries. The results of the meta-analysis showed that the pooled SEN, SPE, and SROC curve values were 0.92 (95% confidence interval [CI]: 0.89-0.94) 0.95 (95% CI: 0.93-0.97), and 0.98 (95% CI: 0.95-0.99), respectively, and subgroup analyses were performed.Gd-EOB-DTPA-enhanced MRI has value for the detection of HCC; in particular, it has high sensitivity for the detection of lesions larger than 10 mm.

Can biliary–cyst communication be predicted by Gd-EOB-DTPA-enhanced MR cholangiography before treatment for hepatic hydatid disease?

To evaluate the role of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (MRC) in the evaluation of biliary-cyst communication (BCC) before treatment for hepatic hydatid disease (HHD). Thirty-one patients with clinical and laboratory follow-up for HHD with suspected diagnosis of BCC underwent three-dimensional (3D) T2-weighted MRC and T1-weighted contrast-enhanced MRC, dynamic 3D gradient echo (GRE) sequences, using Gd-EOB-DTPA to identify the presence or absence of BCC. A total of 45 hepatic hydatid cysts in the 31 patients were evaluated for cyst diameter, BCC, and the time to contrast-enhancement of the hydatid cyst after Gd-EOB-DTPA injection. The surgical and interventional radiological procedures and imaging findings were compared. The sensitivity, specificity, and accuracy of both techniques in identification of BCC were calculated. The accuracy of contrast-enhanced MRC for identifying BCC was superior with a sensitivity of 87.4% and accuracy of 90.5% (p < 0.05). A diameter of ≥10 cm was associated with significantly increased risk of BCC on contrast-enhanced MRC images (p < 0.05). The use of Gd-EOB-DTPA-enhanced MRC yields information that complements T2-weighted MRC findings and improves identification of BCC. The use of T2-weighted MRC, in addition to contrast-enhanced MRC, is recommended to increase preoperative accuracy of identifying BCC.

Infantile hemangioma of the liver in an adult: A case report and review of the literature

Infantile hemangioma (IH), a representative vascular liver tumor, usually occurs in infancy or early childhood but rarely in adults. In this study, we describe a case of IH in a 47-year-old female and we also review the literature. A plain computed tomography (CT) image revealed five hypoattenuating masses in the liver. A dynamic study revealed the masses appeared to be well-enhanced in the arterial phase, and were considered to be high-flow hemangiomas. The tumors appeared as hypointense tumors on the T1-weighted images and as hyperintensities on fat-suppression T2-weighted images. Following the administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), tumors appeared to be well-enhanced in the arterial phase. In the portal phase, tumors demonstrated isointensity compared with the surrounding liver parenchyma, and hypointensity in the equilibrium and hepatobiliary phases. The apparent diffusion coefficient (ADC) values ranged from 2.0 to 2.4x10(-3) mm2/sec. Microscopically, the tumors were composed of numerous capillary-like small vessels lined with plump endothelial cells, arranged in a single layer without mitoses, and small bile ducts were trapped and scattered within the tumor. These findings were considered to be characteristic of IH. To the best of our knowledge, this case is the third report on IH in adults.

Contrast-enhanced ultrasonography findings using a perflubutane-based contrast agent in patients with early hepatocellular carcinoma

ObjectiveWe evaluated the contrast-enhanced ultrasonography (US) imaging features of early hepatocellular carcinomas (HCCs) and compared these findings with those obtained using contrast-enhanced computed tomography (CT). Subjects and methodsForty-three patients with 52 early HCCs with a mean maximal diameter of 15.6mm were enrolled in this retrospective study. After confirming the location of the target lesion using fusion imaging combining conventional US and hepatobiliary phase of contrast-enhanced magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid, we evaluated findings of contrast-enhanced US using a perflubutane-based contrast agent. The contrast-enhanced US detection rates for hyper-vascularity in early HCCs were compared with those obtained for contrast-enhanced CT. ResultsTransient hypo-vascularity subsequent to iso-vascularity during arterial phase and iso-vascularity during portal and post-vascular phases were the predominant contrast-enhanced US findings seen for 25 (48.1%) of the 52 early HCCs. Nine (17.3%) showed iso-vascularity during all three phases, while 1 (1.9%) showed hypo-vascularity during all three phases. The remaining 17 (32.7%) showed partial or whole hyper-vascularity during arterial phase, iso-vascularity during portal phase, and iso- or hypo-vascularity during post-vascular phase. The detection rate for the hyper-vascularity of early HCCs using contrast-enhanced US (32.7%, 17/52) was significantly higher than that obtained using contrast-enhanced CT (21.2%, 11/52) (P<0.05 by McNemar test). ConclusionHypo-vascularity, iso-vascularity, and hyper-vascularity were observed during the arterial phase of contrast-enhanced US in 50.0%, 17.3%, and 32.7% of the early HCCs, respectively. Contrast-enhanced US was more sensitive than contrast-enhanced CT for the detection of hyper-vascularity in early HCCs. Of note, early HCCs might not exhibit the early arterial enhancement that is generally considered to be a typical finding for HCCs.

A simple and inexpensive system for controlling body temperature in small animal experiments using MRI and the effect of body temperature on the hepatic kinetics of Gd-EOB-DTPA

The purpose of this study was to develop a simple and inexpensive system for controlling body temperature in small animal experiments using magnetic resonance imaging (MRI) and to investigate the effect of body temperature on the kinetic behavior of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in the liver.In our temperature-control system, body temperature was controlled using a feedback-regulated heated or cooled air flow generated by two Futon dryers. The switches of the two Futon dryers were controlled using a digital temperature controller, in which the rectal temperature of a mouse measured by an optical fiber thermometer was used as the input.In experimental studies, male ICR mice aged 8weeks old were used and allocated into 5 groups (39-, 36-, 33-, 30-, and 27-degree groups, n=10), in which the body temperature was maintained at 39 °C, 36 °C, 33 °C, 30 °C, and 27 °C, respectively, using our system. The dynamic contrast-enhanced MRI (DCE-MRI) data were acquired with an MRI system for animal experiments equipped with a 1.5-Tesla permanent magnet, for approximately 43min, after the injection of Gd-EOB-DTPA into the tail vein. After correction of the image shift due to the temperature-dependent drift of the Larmor frequency using the gradient-based image registration method with robust estimation of displacement parameters, the kinetic behavior of Gd-EOB-DTPA was analyzed using an empirical mathematical model. With the use of this approach, the upper limit of the relative enhancement (A), the rates of contrast uptake (α) and washout (β), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum relative enhancement (REmax), the time to REmax (Tmax), and the elimination half-life of the contrast agent (T1/2) were calculated.The body temperature of mice could be controlled well by use of our system. Although there were no significant differences in α, AUC, and q among groups, there were significant differences in A, REmax, β, Tmax, and T1/2, indicating that body temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the liver.In conclusion, our system will be useful for controlling body temperature in small animal experiments using MRI. Because body temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the liver, the control of body temperature is essential and should be carefully considered when performing DCE-MRI studies in small animal experiments.

Liver function test by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging with consideration of intrahepatic regional differences.

To accurately quantify liver function using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR imaging. A total of 105 patients with suspicion of a hepatic tumor (Child–Pugh scores: 5 in 56, 6 in 26, 7 in 20, and 8 in 3) who underwent Gd-EOB-DTPA-enhanced MR imaging and an indocyanine green retention rate at 15 min (ICG-R15) evaluation were retrospectively analyzed. The hepatobiliary images were taken at 20 min after Gd-EOB-DTPA injection. The quantitative liver–spleen contrast ratio (Q-LSC) was measured by calculating the signal intensity of the spleen and 12 intrahepatic points consisting of each central zone (near the porta hepatis) and peripheral zone (near the subcapsular zone) in the two main liver lobes. Each averaged Q-LSC of six points in the central zone or right lobe was significantly higher than that in the peripheral zone or left lobe regardless of hepatic function. The mean Q-LSC of the 12 points was significantly correlated with the ICG-R15 and significantly decreased with elevation of the Child–Pugh score. The hepatic enhancement by Gd-EOB-DTPA is influenced by zonal and lobar differences. This method with consideration of regional differences is valid for estimation of liver function by Gd-EOB-DTPA-enhanced MR imaging.

Functional magnetic resonance cholangiography enhanced with Gd-EOB-DTPA: Effect of liver function on biliary system visualization

To evaluate effect of liver function on biliary system visualization using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (CE-MRC). In all, 39 patients were divided into three groups according to their Child-Pugh classification: group A, Child-Pugh class A (23); group B, class B (11); and group C, class C (5). They underwent Gd-EOB-DTPA CE-MRC. Biliary system visualization was qualitatively rated on a 5-point scale. Relative signal intensity (RSI) of common bile duct (CBD) and liver was quantitatively measured. Laboratory findings and the Model of Endstage Liver Disease (MELD) score were recorded. Visualization ratings of CBD, left hepatic duct, right hepatic duct, segmental branches of intrahepatic ducts, cystic duct, and gallbladder of group A were: 3.61 ± 0.58, 2.87 ± 0.97, 2.96 ± 0.77, 1.17 ± 0.58, 3.04 ± 0.83, 3.00 ± 0.95, respectively; group B: 2.00 ± 0.61, 1.09 ± 0.64, 0.91 ± 0.54, 0.27 ± 0.13, 1.36 ± 0.62, 1.45 ± 0.54, respectively; group C: 1.40 ± 0.73, 1.00 ± 0.51, 1.00 ± 0.51, 0.00 ± 0.00, 0.60 ± 0.39, 0.60 ± 0.39, respectively. RSI of CBD of groups A to C were 17.12 ± 0.41, 3.95 ± 0.63, 3.33 ± 0.30, respectively. RSI of liver of groups A to C were 6.73 ± 0.72, 2.53 ± 1.02, 2.05 ± 0.11, respectively. CE-MRC images of group A were significantly better than those of group B and C in terms of both visualization ratings and RSI of CBD. CBD RSI positively correlated with liver RSI (r = 0.99, P < 0.001). The total serum bilirubin level and MELD score were significant predictors of RSI of CBD. Different liver function according to Child-Pugh classification significantly affects biliary system visualization of Gd-EOB-DTPA CE-MRC.

Surgical value of contrast‐enhanced ultrasonography in laparoscopic hepatectomy using energy devices

Recent technological innovations and advances in surgical techniques have improved the feasibility and safety of laparoscopic hepatectomy (LH) [1]. However, intraoperative techniques for tumor detection during LH are limited as compared to those available for open hepatectomy (OH). Here, we report a case of LH conducted under the guidance of contrast-enhanced intraoperative ultrasonography (CE-IOUS). A 73-year-old male who had undergone left hemicolectomy for colon cancer presented with a liver metastasis in segment VIII. Magnetic resonance imaging using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid revealed a tumor measuring 12 mm in diameter (Fig. 1, left), which was visualized as a hypointensity in the hepatobiliary phase, although the tumor could not be clearly identified on computed tomography (Fig. 1, right). Due to the ill-defined margin of the tumor, we planned to perform laparoscopic limited liver resection of segment VIII under the guidance of CE-IOUS with perfluorobutane microbubbles (Sonazoid; GE Healthcare, Oslo, Norway) [2]. The patient was placed in the left lateral decubitus position. A 12-mm trocar was placed on the right side of the umbilicus. In addition to the two trocars placed in the right upper quadrant of the abdomen, a balloon-tipped trocar was placed in the ninth intercostal space. Following mobilization of the right liver, intraoperative ultrasonography (IOUS) and also CE-IOUS were performed with the ultrasound system Prosound α7 and the laparoscopic probe UST-5418 (Hitachi-Aloka Medical, Tokyo, Japan). Although the tumor was visualized by IOUS, its border was still unclear (Fig. 2, Video S1). Therefore, we applied CE-IOUS 15 min after intravenous injection of Sonazoid (0.12 μl microbubbles/kg), which enabled clear demarcation between the tumor and the liver parenchyma (Fig. 2, Video S1). Based on this information, the resection line was marked with electrocautery. During transection, CE-IOUS was performed again to confirm the relation between the resection line and the tumor (Fig. 3, Video S1), after which limited resection was performed. The postoperative course was uneventful, and the patient was discharged on postoperative day 4. One of the limitations during LH is the lack of satisfactory tumor detection techniques. Compared with the case for OH, the palpation is impossible, the rotation of the liver is inadequate, and IOUS is inflexible during LH. Also, energy devices, which are very frequently used during LH, tend to influence the liver parenchyma through thermal metamorphism, making it hard to identify tumors by ultrasonography Y. Kawaguchi · N. Kokudo (*) Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: kokudo-2su@h.u-tokyo.ac.jp

Ethoxybenzyl diethylenetriamine pentaacetic acid Relationship between liver function and relative signal intensity of MR cholangiography using gadolinium

Objective To evaluate the effect of liver function on the biliary visualization of MR cholangiography (CE-MRC) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). Methods Thirty-nine patients were divided into three groups based on Child-Pugh score (23 patients in group A,11 in B,and 5 in C).CE-MRC was scanned 50 minutes after Gd-EOBDTPA injection.Biliary visualization of CE-MRC at that time was qualitatively assessed by 5-point scale.The relative signal intensity (RSI) of the common bile duct (CBD) was quantitatively measured.The serum bilirubin level and the model of end-stage liver disease (MELD) score were recorded.Kruskal-Wallis test was used to compare the rating scores among three groups.Bonferroni method was used to further pairwise comparison.The one-way ANOVA was used to compare the RSI of CBD among three groups.And regression analysis was used to evaluate the relationship between RSI and the influenced factors. Results Visualization rating scores of the CBD,left hepatic duct (LHD),right hepatic duct (RHD),subbranches of intrahepatic bile ducts (SIBD),cystic duct (CD) and gallbladder (GB) were 4 (3,4),3 (2,4),3 (2,4),1 (1,2),3 (2,4),3 (2,4) of group A;3 (0,3),1 (0,2),1 (0,2),0 (0,1),2 (0,2),2 (0,2) of group B; and 1 (1,2),1 (1,1),1 (1,1),0 (0,0),0 (0,1),0 (0,1) of group C.Statistically significant differences were found in visualization rating scores of the CBD,LHD,RHD,SIBD,CD and GB among the 3 groups (χ2=17.881,18.707,23.328,13.016,20.170,19.938,P<0.01).Statistically pairwise comparison differences were found between group A and B,either between group A and C.The RSI of the CBD of these three groups was 17.12±0.41,3.95±0.63 and 3.33±0.30 respectively.There were statistically significant difference between 3 groups. (F=235.843,P<0.01).Statistically significant differences of the RSI were shown between group A and B,also between group A and C.The total serum bilirubin level and the MELD score predicted the RSI of the CBD (β=-0.834,-1.042,P<0.01). Conclusion Liver function could affect CE-MRC with Gd-EOB-DTPA and RSI of the CBD.The RSI may reflect liver cell function. Key words: Liver diseases; Contrast media; Magnetic resonance imaging

Dynamic Contrast-Enhanced MRI of the Liver in Mrp2-Deficient Rats Using the Hepatobiliary Contrast Agent Gd-EOB-DTPA

The objective of this study was to compare the hepatic uptake and biliary excretion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in control and multidrug resistance-associated protein 2 (Mrp2)-deficient rats by noninvasive dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the impact of Mrp2 deficiency on organic anion-transporting polypeptide 1 (Oatp1) transporters and liver vascularization by immunohistochemistry. Twenty rats were used in the normal control (n = 10) and Mrp2-deficient rat groups (n = 10). Dynamic contrast-enhanced magnetic resonance imaging studies were performed using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg body weight) as the contrast agent. The percentages of relative enhancement were calculated at each time point after Gd-EOB-DTPA injection. In addition, relative enhancement maps were generated through pixel-by-pixel calculations before the injection and at 5, 10, 20, 30, and 40 minutes after the injection. After the DCE-MRI study, blood was sampled from all rats and 6 blood sample parameters, serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids, were measured. Rat livers were processed for histologic diagnosis to clarify contrast agent uptake/efflux by examining Oatp1, Mrp2, and platelet endothelial cell adhesion molecule immunohistochemical staining. The relative enhancement of the Mrp2-deficient, Eisai hyperbilirubinuria rats (EHBRs) (48.6% [3.4%]) was significantly lower than that of the control rats (64.0% [3.2%]; P < 0.001) 5 minutes after the Gd-EOB-DTPA injection. Thereafter, the relative enhancement observed in the EHBRs (10 minutes, 59.6% [5.4%]; 20 minutes, 67.8% [4.1%]; 30 minutes, 69.1% [4.2%]; 40 minutes, 71.0% [4.2%]; P < 0.0001) was significantly higher than that in the control rats at the same time points after the Gd-EOB-DTPA injection. The aspartate aminotransferase and alanine aminotransferase values were not significantly different between the 2 groups. However, total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids levels in EHBRs were significantly higher than those in the control rats. The percentages of the Mrp2-positive cells in the control rats were higher compared with the EHBRs (control, 0.3% [0.1%]; EHBR, 14.1% [3.6%]; P < 0.01). However, the percentages of the Oatp1-positive cells were not different between the 2 groups. Moreover, the percentages of the platelet endothelial cell adhesion molecule-positive cells in the blood vessels of the control rat livers were higher compared with the EHBRs (control, 17.5% [3.3%]; EHBR, 9.5% [3.9%]; P < 0.01). The utility of noninvasive DCE-MRI with Gd-EOB-DTPA as a tool for the assessment of Mrp2-deficient hyperbilirubinuria rats was demonstrated. We also clarified that the lower vascular density in the EHBRs may cause delayed uptake of the contrast agent compared with the control rats. In addition, the lower Mrp2 transporter expression may cause the lower efflux of the contrast agent from the Mrp2-deficient rats compared with the control rats.

Magnetic Resonance–Guided Freehand Radiofrequency Ablation of Malignant Liver Lesions

The aims of this study were to develop magnetic resonance (MR)-guided freehand radiofrequency ablation (RFA) using a near-real-time interactive MR platform in an open 1.0-T MR scanner and to determine the feasibility and safety of this new approach in the clinical setting. The study was performed using an open 1.0-T MR system and a low-pass filter to prevent interaction between the RFA generator and the scanner. Artifact size of the radiofrequency needle was measured in 2 perpendicular views (transversal [tra] and coronal [cor]) in vitro and in the tra orientation in vivo for diagnostic (T1 high resolution isotropic volume excitation [THRIVE]/T2 turbo spin-echo [TSE]) and near-real-time (T1 fast-field-echo [FFE]) imaging. A liver-specific contrast medium (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) was administered 20 minutes before the intervention to enhance lesion visibility. Visibility was rated and compared for both interventional and diagnostic imaging sequences using a 10-point grading scale. Intervention time and complications were recorded. The mean diameter of needle artifact size for interventional T1 FFE was 17.4 ± 0.7 mm (tra) and 17.1 ± 1.1 mm (cor) in vitro and 15.2 ± 1.5 mm (tra) in vivo. Artifact size for diagnostic imaging was 12.5 ± 1.8 mm (tra) and 11.2 ± 1.4 mm (cor) in vitro and 10.5 ± 1.7 mm in vivo using THRIVE and 8.1 ± 2.4 mm (tra) and 10.8 ± 1.8 mm (cor) in vitro and 9.7 ± 2.0 mm (tra) in vivo using T2 TSE. A total of 57 patients with liver malignancies (mean tumor size, 17 ± 7 mm) underwent freehand MR-guided RFA. In all patients, the ablative procedure was technically successful. Lesion visibility of the diagnostic T2 TSE sequence (4 ± 2) was significantly decreased compared with both the diagnostic (THRIVE, 7 ± 2) and interventional (T1 FFE, 8 ± 1) T1-weighted sequences. Mean time to position the applicator was 7.5 ± 2 minutes. Procedure times ranged from 30 to 60 minutes. The mean in-room time was 57 ± 22 minutes. No major complications were recorded. Magnetic resonance-guided freehand RFA using a near-real-time interactive MR platform in an open 1.0-T MR scanner is feasible, safe, and applicable in clinical routine. The administration of a hepatocyte-specific contrast agent enhances lesion visualization and therefore improves targeting. Without the need for additional sophisticated devices, this new approach simplifies and shortens the RFA procedure compared with previously published methods.

Non-invasive detection of biliary leaks using Gd-EOB-DTPA-enhanced MR cholangiography: comparison with T2-weighted MR cholangiography

ObjectiveTo evaluate the added role of T1-weighted (T1w) gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (MRC) compared with T2-weighted MRC (T2w-MRC) in the detection of biliary leaks.MethodsNinety-nine patients with suspected biliary complications underwent routine T2w-MRC and T1w contrast-enhanced (CE) MRC using Gd-EOB-DTPA to identify biliary leaks. Two observers reviewed the image sets separately and together. MRC findings were compared with those of surgery and percutaneous transhepatic cholangiopancreatography. The sensitivity, specificity and accuracy of the techniques in identifying biliary leaks were calculated.ResultsAccuracy of locating biliary leaks was superior with the combination of Gd-EOB-DTPA-enhanced MRC and T2w-MRC (P < 0.05).The mean sensitivities were 79 % vs 59 %, and the mean accuracy rates were 84 % vs 58 % for combined CE-MRC and T2w-MRC vs sole T2w-MRC. Nineteen out of 21 patients with biliary-cyst communication, 90.4 %, and 12/15 patients with post-traumatic biliary extravasations, 80 %, were detected by the combination of Gd-EOB-DTPA-enhanced MRC and T2w-MRC images, P < 0.05.ConclusionsGd-EOB-DTPA-enhanced MRC yields information that complements T2w-MRC findings and improves the identification and localisation of the bile extravasations (84 % accuracy, 100 % specificity, P < 0.05). We recommend Gd-EOB-DTPA-enhanced MRC in addition to T2w-MRC to increase the preoperative accuracy of identifying and locating extravasations of bile.Key Points• Magnetic resonance cholangiography (MRC) does not always detect bile leakage and cysto-biliary communications.• Gd-EOB-DTPA-enhanced MRC helps by demonstrating extravasation of contrast material into fluid collections.• Gd-EOB-DTPA-enhanced MRC also demonstrates the leakage site and bile duct injury type.• Combined Gd-EOB-DTPA-enhanced and T2w-MRC can provide comprehensive information about biliary system.• Gd-EOB-DTPA-enhanced MRC is non-invasive and does not use ionising radiation.

Serum amyloid A-positive hepatocellular neoplasms in the resected livers from 3 patients with alcoholic cirrhosis.

Twelve hepatocellular nodules were characterized in the resected livers from 3 patients (2 men and a woman) with alcoholic cirrhosis. Imaging techniques suggested that the nodules were hypervascular and may be hepatocellular carcinoma. Five nodules (4-31 mm in diameter) were serum amyloid A-positive hepatocellular neoplasm, which shares features with inflammatory hepatocellular adenoma. The remaining 7 nodules (5-8 mm) were focal nodular hyperplasia-like nodules showing focal or no immunostaining for serum amyloid A. The serum amyloid A-positive hepatocellular neoplasms showed increased cellular density, inflammatory infiltrate, sinusoidal dilatation, and ductular reaction to various degrees. These histologic features tended to be less extensive in focal nodular hyperplasia-like nodules. Three of 4 serum amyloid A-positive hepatocellular neoplasms showed slight hypointensity in the hepatobiliary phase on the magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) enhancement. In contrast, 3 focal nodular hyperplasia-like nodules showed iso-intensity in the hepatobiliary phase. This study further confirms characteristics of serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis that share features with inflammatory hepatocellular adenomas. Serum amyloid A-positive hepatocellular neoplasms sometimes co-exist with focal nodular hyperplasia-like nodules and may show different findings on Gd-EOB-enhanced MR imaging.

Coexpression of organic anion-transporting polypeptides 1B3 and multidrug-resistant proteins 2 increases the enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid on hepatocellular carcinoma in magnetic resonance imaging

We aimed to elucidate the relationship between the contrast enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on magnetic resonance imaging (MRI) of hepatocellular carcinomas (HCC) and the expressions of hepatocyte transporters (i.e. organic anion-transporting polypeptide [OATP]1B3, multidrug-resistant protein [MRP]2 and MRP3) and to clarify the characteristics of HCC with an MRI high-contrast enhancement effect. We retrospectively examined the relationship between the relative enhancement ratio (RER) of HCC, absolute and relative immunohistochemical staining scores of hepatocyte transporters, and histological differentiation of 22 HCC from 21 patients who had undergone preoperative Gd-EOB-DTPA-enhanced MRI. RER had a significant correlation with OATP1B3 expression according to the absolute and relative scores (P = 0.016 vs 0.0006). The RER of HCC with high OATP1B3 and MRP2 expression levels was higher than that of HCC with low OATP1B3 or MRP2 expression levels (P = 0.0003). The RER of HCC with higher OATP1B3 rates was greater than that of HCC with lower OATP1B3 rates (P = 0.0005). HCC histological differentiation showed a significant correlation with OATP1B3 expression and RER (P = 0.023 vs 0.0095). We found that coexpression of OATP1B3 and MRP2 influenced the high contrast enhancement of HCC on MRI.

Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis

The aims of this study were to use dynamic hepatocyte-specific contrast-enhanced MRI to evaluate liver volume and function in liver cirrhosis, correlate the results with standard scoring models and explore the inhomogeneous distribution of liver function in cirrhotic livers. 10 patients with liver cirrhosis and 20 healthy volunteers, serving as controls, were included. Hepatic extraction fraction (HEF), input relative blood flow and mean transit time were calculated on a voxel-by-voxel basis using deconvolutional analysis. Segmental and total liver volumes as well as segmental and total hepatic extraction capacity, expressed in HEFml, were calculated. An incongruence score (IS) was constructed to reflect the uneven distribution of liver function. The Mann-Whitney U-test was used for group comparison of the quantitative liver function parameters, liver volumes and ISs. Correlations between liver function parameters and clinical scores were assessed using Spearman rank correlation. Patients had larger parenchymal liver volume, lower hepatocyte function and more inhomogeneous distribution of function compared with healthy controls. The study demonstrates the non-homogeneous nature of liver cirrhosis and underlines the necessity of a liver function test able to compensate for the heterogeneous distribution of liver function in patients with diseased liver parenchyma. The study describes a new way to quantitatively assess the hepatic uptake of gadoxetate or gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid in the liver as a whole as well as on a segmental level.

Selection for hepatic resection of colorectal liver metastases: expert consensus statement

Hepatic resection offers a chance of a cure in selected patients with colorectal liver metastases (CLM). To achieve adequate patient selection and curative surgery, (i) precise assessment of the extent of disease, (ii) sensitive criteria for chemotherapy effect, (iii) adequate decision making in surgical indication and (iv) an optimal surgical approach for pre‐treated tumours are required. For assessment of the extent of the disease, contrast‐enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA) is recommended depending on the local expertise and availability. Positron emission tomography (PET) and PET/CT may offer additive information in detecting extrahepatic disease. The RECIST criteria are a reasonable method to evaluate the effect of chemotherapy. However, they are imperfect in predicting a pathological response in the era of modern systemic therapy with biological agents. The assessment of radiographical morphological changes is a better surrogate of the pathological response and survival especially in the patients treated with bevacizumab. Resectability of CLM is dependent on both anatomic and oncological factors. To decrease the surgical risk, a sufficient volume of liver remnant with adequate blood perfusion and biliary drainage is required according to the degree of histopathological injury of the underlying liver. Portal vein embolization is sometimes required to decrease the surgical risk in a patient with small future liver remnant volume. As a complete radiological response does not signify a complete pathological response, liver resection should include all the site of a tumour detected prior to systemic treatment.

Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy

The gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often depicts non-hypervascular hypointense hepatic nodules during the hepatobiliary phase in patients with hepatocellular carcinoma (HCC). It is unclear whether the presence of these nodules is associated with HCC recurrence after hepatectomy. We conducted a prospective observational study to investigate the impact of the presence of non-hypervascular hypointense hepatic nodules on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI on the recurrence of HCC after hepatectomy. A total of 77 patients who underwent hepatectomy for primary, non-recurrent, hypervascular HCC were prospectively followed up after hepatectomy. Post-operative recurrence rates were compared according to the presence of non-hypervascular hypointense nodules on preoperative Gd-EOB-DTPA-enhanced MRI. Recurrence rates after hepatectomy were higher in patients with non-hypervascular hypointense nodules (risk ratio 1.9396 [1.3615-2.7222]) and the presence of non-hypervascular hypointense nodules was an independent factor associated with postoperative recurrence (risk ratio 2.1767 [1.5089-3.1105]) along with HCC differentiation and portal vein invasion. While no differences were found in the rate of intrahepatic metastasis recurrence based on the preoperative presence of non-hypervascular hypointense hepatic nodules, the rate of multicentric recurrence was significantly higher in patients with preoperative non-hypervascular hypointense hepatic nodules. Patients with preoperative non-hypervascular hypointense hepatic nodules detected during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI are at higher risk of HCC recurrence after hepatectomy, mainly due to multicentric recurrence.