gadoxetic-acid-disodium and Bile-Duct-Diseases

The advent of gadolinium-based "hepatobiliary" contrast agents offers new opportunities for diagnostic magnetic resonance imaging (MRI) and has triggered great interest for innovative imaging approaches to the liver and bile ducts. In this review article we discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the U.S., gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared toward optimizing workflow and imaging quality are also discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents and will stimulate the reader's pursuit of new applications for future benefit.

Topics: Bile Duct Diseases; Contrast Media; Gadolinium DTPA; Humans; Liver Diseases; Magnetic Resonance Imaging; Meglumine; Organometallic Compounds

Gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA, Primovist in Europe and Eovist in the USA) is a liver-specific magnetic resonance imaging contrast agent that has up to 50% hepatobiliary excretion in the normal liver. After intravenous injection, Gd-EOB-DTPA distributes into the vascular and extravascular spaces during the arterial, portal venous and late dynamic phases, and progressively into the hepatocytes and bile ducts during the hepatobiliary phase. The hepatocyte uptake of Gd-EOB-DTPA mainly occurs via the organic anion transporter polypeptides OATP1B1 and B3 located at the sinusoidal membrane and biliary excretion via the multidrug resistance-associated proteins MRP2 at the canalicular membrane. Because of these characteristics, Gd-EOB-DTPA behaves similarly to non-specific gadolinium chelates during the dynamic phases, and adds substantial information during the hepatobiliary phase, improving the detection and characterization of focal liver lesions and diffuse liver disease. This information is particularly relevant for the detection of metastases, and for the detection and characterization of nodular lesions in liver cirrhosis, including early hepatocellular carcinomas. Finally, GD-EOB-DTPA-enhanced magnetic resonance imaging may provide quantitative assessment regarding liver perfusion and hepatocyte function in diffuse liver diseases. The full potential of GD-EOB-DTPA-enhanced magnetic resonance imaging has to be established further. It is already clear that GD-EOB-DTPA-enhanced magnetic resonance imaging provides anatomic and functional information in the setting of focal and diffuse liver disease that is unattainable with magnetic resonance imaging enhanced with non-specific contrast agents.

Topics: Bile Duct Diseases; Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Humans; Image Enhancement; Liver Function Tests; Liver Neoplasms; Magnetic Resonance Imaging

Gadoxate disodium [gadolinium EOB DTPA, Gd-EOB-DTPA, gadoxetic acid, Eovist injection, Primovist] is a hydrophilic paramagnetic contrast agent being developed by Schering AG for hepatobiliary magnetic resonance imaging. In April 2004, gadoxate disodium (Primovist) was approved in Sweden, the reference member state for the EU registration. Following the Swedish approval, Schering will initiate a mutual recognition procedure for the EU with approvals expected in most countries during 2004. Gadoxate disodium is in phase III clinical trials in the US and has completed phase III studies in Japan. Submissions for approval in Japan and other Asian countries are planned for 2004. Schering AG plans to launch Eovist in Japan in 2005. Schering AG acquired a worldwide, royalty-bearing licence to EPIX Medical's patents covering liver-enhancing agents such as Eovist injection. These included a European patent (222886) and the US patents (4,899,755 and 4,888,008) that EPIX Medical exclusively licensed from the Massachusetts General Hospital (MGH). The MGH patents, a part of EPIX's extensive intellectual property, also covered albumin-targeted agents such as MS 325 (AngioMARK). Schering AG formally withdrew from the opposition proceedings against EPIX's EU patent 222886 following its acquisition of EPIX's intellectual property. These EU and US patents were also non-exclusively licensed by EPIX Medical to Bracco in September 2001. Apart from covering Eovist (Schering AG), the EU patent also covered gadobenate dimeglumine (MultiHance Bracco). Following the licensing agreement, Bracco withdrew its opposition to the patents in Europe and Japan, and both EPIX Medical and Bracco settled their European patent dispute. In its 2002 Annual Report, Schering predicted that Eovist has the potential to reach peak sales of euro50 million, three years after launch--at the time, launch in Europe was anticipated in 2004, followed by launch in Japan in 2005. This is down from earlier predictions, made at an analyst presentation in Berlin in March 2002, when the company forecast the product to reach peak sales of euro100 million.

Topics: Animals; Bile Duct Diseases; Clinical Trials, Phase III as Topic; Contrast Media; Gadolinium DTPA; Humans; Liver; Liver Diseases; Randomized Controlled Trials as Topic

We assessed the added efficacy of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (gadolinium-EOB) in depicting biliary structures compared with T2-weighted MR cholangiopancreatography (T2-MRCP) and measured reviewer preference and willingness-to-pay for the added value of biliary contrast.. Ten patients prospectively underwent T2-MRCP and gadolinium-EOB-enhanced MR cholangiography (EOB-MRC). Three radiologists reviewed the unpaired, then the paired, examinations, rating biliary visualization using a 5-point scale. The common bile, right and left hepatic ducts, and second-order branches were evaluated. Improved biliary visualization using paired over unpaired tests indicated the added value of contrast media. Kappa values measured interobserver reliability. A regression model controlling for fixed effects due to reviewer and subject correlation quantified improvement in ratings attributable to paired review.. Average visualization ratings for unpaired review of EOB-MRC were the following: common bile duct, 3.3; right hepatic duct, 2.7; left hepatic duct, 2.5; second-order branches, 1.4. Average visualization ratings for unpaired review of T2-MCRP were the following: common bile duct, 3.4; right hepatic duct, 1.8; left hepatic duct, 2.2; second-order branches, 0.9. Ratings improved using paired tests over EOB-MRC and T2-MRCP for all structures (p < 0.001) except for T2-MRCP common bile duct ratings (p > 0.05). Agreement was moderate to good except for EOB-MRC common bile duct ratings. Paired review improved ratings (chi(2) < 0.0001) over T2-MRCP alone by 1.05 and over EOB-MRC alone by 0.68. Despite significant improvement, reviewers preferred unpaired T2-MRCP (53%) over unpaired EOB-MRC (17%) or paired tests (30%). Reviewers were willing to pay $25 (median) for gadolinium-EOB.. Combining T2-MRCP and EOB-MRC significantly improved biliary visualization over each test alone. However, improvement was small, and the perceived added value of gadolinium-EOB was modest.

Topics: Adult; Aged; Bile Duct Diseases; Cholangiography; Consumer Behavior; Contrast Media; Female; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity

Topics: Anastomotic Leak; Bile Duct Diseases; Bile Ducts; Biliary Atresia; Biliary Tract; Contrast Media; Extravasation of Diagnostic and Therapeutic Materials; Female; Gadolinium DTPA; Humans; Imino Acids; Infant; Ligaments; Liver; Magnetic Resonance Imaging; Portoenterostomy, Hepatic; Tissue Distribution

To investigate the feasibility of gadoxetate disodium-enhanced magnetic resonance (MR) cholangiography in chronic obstructive cholestatic biliary disease in the clinical setting.. Twenty-three patients with dilated bile duct trees and ten volunteers underwent gadoxetate disodium-enhanced liver MR cholangiography and were enrolled in the present retrospective study. Gadoxetate disodium was given in a standardized manner as a bolus injection at a dose of 0.25 mmol/kg of body weight (0.1 ml/kg). Region of interest-based measurement of mean enhancement of the dilated bile ducts was performed in series before gadoxetate disodium administration and during hepatobiliary phases.. Direct comparison of mean bile duct enhancement during hepatobiliary phases in the clinical imaging window between healthy volunteers [4.7 ± 2.2 arbitrary units (au)] and patients with dilated bile ducts (0.1 ± 0.3 au) revealed significantly lower or absent enhancement in dilated bile ducts (p = 0.001).. Standard clinical gadoxetate disodium-enhanced MR cholangiography is not a reliable technique for the evaluation of the biliary trees, because of altered biliary gadoxetate disodium elimination in patients with chronic obstructive biliary diseases.

Topics: Adult; Bile Duct Diseases; Bile Ducts; Cholangiography; Cholestasis; Chronic Disease; Contrast Media; Feasibility Studies; Female; Gadolinium DTPA; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Retrospective Studies

The cholangiopathies are a diverse group of biliary tract disorders, many of which lack effective treatment. Murine models are an important tool for studying their pathogenesis, but existing noninvasive methods for assessing biliary disease in vivo are not optimal. Here we report our experience with using micro-computed tomography (microCT) and nuclear magnetic resonance (MR) imaging to develop a technique for live-mouse cholangiography. Using mdr2 knockout (mdr2KO, a model for primary sclerosing cholangitis (PSC)), bile duct-ligated (BDL), and normal mice, we performed in vivo: (1) microCT on a Siemens Inveon PET/CT scanner and (2) MR on a Bruker Avance 16.4 T spectrometer, using Turbo Rapid Acquisition with Relaxation Enhancement, IntraGate Fast Low Angle Shot, and Half-Fourier Acquisition Single-shot Turbo Spin Echo methods. Anesthesia was with 1.5-2.5% isoflurane. Scans were performed with and without contrast agents (iodipamide meglumine (microCT), gadoxetate disodium (MR)). Dissection and liver histology were performed for validation. With microCT, only the gallbladder and extrahepatic bile ducts were visualized despite attempts to optimize timing, route, and dose of contrast. With MR, the gallbladder, extra-, and intrahepatic bile ducts were well-visualized in mdr2KO mice; the cholangiographic appearance was similar to that of PSC (eg, multifocal strictures) and could be improved with contrast administration. In BDL mice, MR revealed cholangiographically distinct progressive dilation of the biliary tree without ductal irregularity. In normal mice, MR allowed visualization of the gallbladder and extrahepatic ducts, but only marginal visualization of the diminutive intrahepatic ducts. One mouse died during microCT and MR imaging, respectively. Both microCT and MR scans could be obtained in ≤20 min. We, therefore, demonstrate that MR cholangiography can be a useful tool for longitudinal studies of the biliary tree in live mice, whereas microCT yields suboptimal duct visualization despite requiring contrast administration. These findings support further development and application of MR cholangiography to the study of mouse models of PSC and other cholangiopathies.

Topics: Animals; Bile Duct Diseases; Cholangiography; Contrast Media; Disease Models, Animal; Female; Gadolinium DTPA; Magnetic Resonance Imaging; Male; Mice; X-Ray Microtomography

To determine the need for precontrast T1-weighted imaging in determining cystic duct patency using hepatobiliary phase imaging with gadoxetate disodium-enhanced magnetic resonance imaging (MRI).. MRI exams using gadoxetate disodium from October 4, 2008 to April 14, 2010 were reviewed in a retrospective fashion. Two reviewers independently reviewed only the 20-minute T1-weighted delayed postcontrast images to determine the presence of excreted contrast in the gallbladder lumen. Contrast was deemed present if hyperintense signal material was seen in the antidependent portion of the gallbladder lumen. The actual presence of contrast in the gallbladder was determined by directly comparing the pre- and postcontrast T1-weighted images using consensus review.. In all, 187 cases were included. Three (1.6%) were deemed indeterminate due to complete homogeneous opacification of the gallbladder. All three cases were identified as indeterminate by both reviewers. Of the remaining 184 cases, 136 filled (74%) and 48 did not fill (26%). Both reviewers correctly identified 136/136 cases of gallbladder filling. Reviewer A identified 47/48 cases of nonfilling and reviewer B identified 46/48 cases of nonfilling. Sensitivity and specificity were 100% and 98% for reviewer A and 100% and 96% for reviewer B, respectively.. The presence of excreted contrast in the gallbladder lumen can be determined using gadoxetate disodium-enhanced MRI without precontrast T1-weighted imaging.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bile Duct Diseases; Contrast Media; Cystic Duct; Female; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity

To assess the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MR cholangiography for the detection of bile leaks after hepatobiliary surgery.. Twenty-three patients with symptoms suggestive of bile leak underwent conventional fat-suppressed T1- and T2-weighted MR cholangiography followed by Gd-EOB-DTPA-enhanced MR cholangiography using gradient-echo (GRE) T2-weighted sequences and fat-suppressed T1-weighted 3D gradient-echo sequences 20 min after an intravenous bolus of Gd-EOB-DTPA. The results of Gd-EOB-DTPA-enhanced MR cholangiography correlated with clinical findings, surgical repair, and the results of endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography.. The results of Gd-EOB-DTPA-enhanced MR cholangiography were negative in 13 patients (cholecystectomy 5, liver transplantation 2, liver resection for focal lesions 2, cholangiocarcinoma 1, and partial hepatectomy after liver injury 1). In 10 patients in whom bile leaks were detected, this complication occurred after liver resection for focal lesions in 3, cholecystectomy in 4, liver transplantation in 2, and liver resection for intrahepatic cholangiocarcinoma in 1. The diagnostic accuracy of Gd-EOB-DTPA-enhanced MR for the detection or exclusion of bile leaks was 100%.. Gd-EOB-DTPA-enhanced MR cholangiography is a highly reliable technique for the detection of bile leaks after hepatobiliary surgery and may avoid the use of other, potentially risky invasive diagnostic techniques.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Diseases; Bile Ducts; Cholangiopancreatography, Endoscopic Retrograde; Cholangiopancreatography, Magnetic Resonance; Contrast Media; Female; Gadolinium DTPA; Humans; Liver Diseases; Male; Middle Aged; Postoperative Complications

The hepatocyte-specific contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) was developed to improve the detection and characterization of focal liver lesions at magnetic resonance (MR) imaging. Approximately 50% of the injected dose is taken up into the functional hepatocyte and is excreted via the biliary system. Because of this property, Gd-EOB-DTPA has the potential to be a biliary contrast agent. When combined with T2-weighted MR cholangiography, Gd-EOB-DTPA-enhanced MR imaging can allow morphologic and functional assessment of the biliary system. Gd-EOB-DTPA-enhanced MR cholangiography could be effective in evaluation of biliary anatomy, differentiation of biliary from extrabiliary lesions, diagnosis of cholecystitis, assessment of bile duct obstruction, detection of bile duct injury including leakage and stricture, evaluation of biliary-enteric anastomoses, postprocedure evaluation, differentiation of biloma from other pathologic conditions, and evaluation of sphincter of Oddi dysfunction. However, the clinical applications of this imaging technique have not yet been fully explored, and further investigations are needed to determine the utility of Gd-EOB-DTPA-enhanced MR cholangiography in a clinical setting.

Topics: Bile Duct Diseases; Bile Ducts; Contrast Media; Gadolinium DTPA; Humans; Image Enhancement; Magnetic Resonance Imaging