Enhancement of liver parenchyma after injection of hepatocyte‐specific MRI contrast media: A comparison of gadoxetic acid and gadobenate dimeglumine

Purpose:

To compare enhancement of liver parenchyma in MR imaging after injection of hepatocyte‐specific contrast media.

Materials and Methods:

Patients (n = 295) with known/suspected focal liver lesions randomly received 0.025 mmol gadoxetic acid/kg body weight or 0.05 mmol gadobenate dimeglumine/kg body weight by means of bolus injection. MR imaging was performed before and immediately after injection, and in the delayed phase at approved time points (20 min after injection of gadoxetic acid and 40 min after injection of gadobenate dimeglumine). The relative liver enhancement for the overall population and a cirrhotic subgroup was compared in T1‐weighted GRE sequences. An independent radiologist performed signal intensity measurements. Enhancement ratios were compared using confidence intervals (CIs).

Results:

The relative liver enhancement in the overall population was superior with gadoxetic acid (57.24%) versus gadobenate dimeglumine (32.77%) in the delayed‐imaging phase. The enhancement ratio between the contrast media was statistically significant at 1.75 (95% CI: 1.46–2.13). In the delayed phase, the enhancement of cirrhotic liver with gadoxetic acid (57.00%) was comparable to that in the overall population. Enhancement with gadobenate dimeglumine was inferior in cirrhotic liver parenchyma (26.85%).

Conclusion:

In the delayed, hepatocyte‐specific phase, liver enhancement after injection of gadoxetic acid was superior to that obtained with gadobenate dimeglumine. J. Magn. Reson. Imaging 2010; 31: 356–364. © 2010 Wiley‐Liss, Inc.

     

Hepatic hemangiomas: difference in enhancement pattern on 3T MR imaging with gadobenate dimeglumine versus gadoxetate disodium

Purpose

To compare intraindividual differences in enhancement pattern of hepatic hemangiomas between gadobenate dimeglumine (Gd-BOPTA) and gadoxetate disodium (Gd-EOB-DTPA)-enhanced 3T MR imaging.

Materials and methods

This is a HIPAA-compliant, IRB-approved retrospective study with waiver for informed consent granted. From 10/07 to 5/09, 10 patients (2 males, 8 females; mean age, 57.3 years) with 15 hepatic hemangiomas (mean diameter, 4.4 ± 5.6 cm) underwent both Gd-BOPTA- and Gd-EOB-DTPA-enhanced 3T MR imaging (mean interval, 266 days; range, 38–462 days). Diagnosis of hemangioma was based on strict imaging criteria. MR imaging was obtained during three arterial, portal venous, and up to four delayed phases. During each phase, hemangioma-to-liver contrast-to-noise ratio (CNR) was measured for each lesion on both examinations. Statistical analysis was performed using paired Student's t-test.

Results

Hemangioma-to-liver CNR peaked during the portal venous phase (Gd-BOPTA: 48.9 ± 65.8, Gd-EOB-DTPA: 0.7 ± 3.8). During all imaging phases except the first arterial phase, hemangioma-to-liver CNR was significantly lower on Gd-EOB-DTPA-enhanced compared to Gd-BOPTA-enhanced MR images (p < 0.05). Notably, Gd-EOB-DTPA yielded negative hemangioma-to-liver CNR (−2.5 ± 2.4) compared to Gd-BOPTA (40.7 ± 56.4) during the first delayed phase (7–8 min after contrast administration), remaining negative for the rest of the delayed phases (up to 26 min after contrast administration).

Conclusion

The enhancement patterns of hepatic hemangiomas differs significantly between Gd-BOPTA and Gd-EOB-DTPA-enhanced 3T MR imaging. The smaller dose, shorter plasma half-life, and increased hepatobiliary uptake of Gd-EOB-DTPA leads to a negative CNR of hemangioma-to-liver on delayed phases and could create an imaging pitfall with this agent.     

Optimized high-resolution contrast-enhanced hepatobiliary imaging at 3 tesla: a cross-over comparison of gadobenate dimeglumine and gadoxetic acid

Purpose:

To evaluate the signal to noise ratio (SNR) and contrast to noise ratio (CNR) performance of 0.05 mmol/kg gadoxetic acid and 0.1 mmol/kg gadobenate dimeglumine for dynamic and hepatobiliary phase imaging. In addition, flip angles (FA) that maximize relative contrast‐to‐noise performance for hepatobiliary phase imaging were determined.

Materials and Methods:

A cross‐over study in 10 volunteers was performed using each agent. Imaging was performed at 3 Tesla (T) with a 32‐channel phased‐array coil using breathheld 3D spoiled gradient echo sequences for SNR and CNR analysis, and for FA optimization of hepatobiliary phase imaging.

Results:

Gadobenate dimeglumine (0.1 mmol/kg) had superior SNR performance during the dynamic phase, statistically significant for portal vein and hepatic vein in the portal venous and venous phase (for all, P < 0.05) despite twice the approved dose of gadoxetic acid (0.05 mmol/kg), while gadoxetic acid had superior SNR performance during the hepatobiliary phase. Optimal FAs for hepatobiliary phase imaging using gadoxetic acid and gadobenate dimeglumine were 25–30° and 20–30° for relative contrast liver versus muscle (surrogate for nonhepatocellular tissues), and 45° and 20° (relative contrast liver versus biliary structures), respectively.

Conclusion:

Gadobenate dimeglumine may be preferable for applications that require dynamic phase imaging only, while gadoxetic acid may be preferable when the hepatobiliary phase is clinically important. Hepatobiliary phase imaging with both agents benefits from flip angle optimization. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents

The relaxivities r₁ and r₂ of magnetic resonance contrast agents and the T₁ relaxation time values of tissues are strongly field dependent. We present quantitative data and simulations of different gadolinium-based extracellular fluid contrast agents and the modulation of their contrast enhancement by the magnetic field to be able to answer the following questions: How are the dose and field dependences of their contrast enhancement? Is there an interrelationship between dose and field dependence? Should one increase or decrease doses at specific fields? Nuclear magnetic relaxation dispersion data were acquired for the following contrast agents: gadopentetate dimeglumine, gadoterate meglumine, gadodiamide injection, and gadoteridol injection, as well as for several normal and pathological human tissue samples. The magnetic field range stretched from 0.0002 to 4.7 T, including the entire clinical imaging range. The data acquired were then fitted with the appropriate theoretical models. The combination of the diamagnetic relaxation rates (R₁ = 1/T₁ and R₂ = 1/T₂) of tissues with the respective paramagnetic contributions of the contrast agents allowed the prediction of image contrast at any magnetic field. The results revealed a nearly identical field and dose-dependent increase of contrast enhancement induced by these contrast agents within a certain dose range. The target tissue concentration (TTC) was an important though nonlinear factor for enhancement. The currently recommended dose of 0.1 mmol/kg body weight seems to be a compromise close to the lower limits of diagnostically sufficient contrast enhancement for clinical imaging at all field strengths. At low field contrast enhancement might be insufficient. Adjustment of dose or concentration, or a new class of contrast agents with optimized relaxivity, would be a valuable contribution to a better diagnostic yield of contrast enhancement at all fields. Received: 20 March 1998; Revision received: 25 June 1998; Accepted: 22 July 1998     

Enhancing lesions of the brain: intraindividual crossover comparison of contrast enhancement after gadobenate dimeglumine versus established gadolinium comparators

RATIONALE AND OBJECTIVES: Gadobenate dimeglumine (Gd-BOPTA) possesses a two-fold higher T1 relaxivity compared to other available gadolinium contrast agents. The study was conducted to evaluate the benefits of this increased relaxivity for MR imaging of intracranial enhancing brain lesions. MATERIALS AND METHODS: Forty-five patients (31 males, 14 females) with suspected glioma or cerebral metastases were evaluated. Patients received Gd-BOPTA and either Gd-DTPA (n = 23) or Gd-DOTA (n = 22) in fully randomized order at 0.1 mmol/kg body weight and at a flow rate of 2 ml/s. The second agent was administered 1-14 days after the first agent. Images were acquired precontrast (T1wSE, T2wFSE sequences) and at sequential postcontrast time-points (T1wSE sequences at 0, 2, 4, 6, and 8 and 15 min and a T1wSE-MT sequence at 12 min) at 1.0 or 1.5 T using a head coil. Determination of contrast enhancement was performed quantitatively (lesion-to-brain ratio, contrast-to-noise ratio, and percent enhancement) and qualitatively (border delineation, internal morphology, contrast enhancement, and diagnostic preference) by two independent, fully blinded readers. RESULTS: Images from 43/45 patients were available for quantitative assessment. After correction for precontrast values, significantly greater lesion-to-brain ratio (P < .003), contrast-to-noise ratio (P < .03), and percent enhancement (P < .0001) was noted by both readers for Gd-BOPTA-enhanced images at all time-points from 2 min postcontrast. Qualitative assessment of all patients similarly revealed significant preference for Gd-BOPTA for lesion border delineation (P < .004), lesion internal morphology (P < .008), contrast enhancement (P < .0001), and diagnostic preference (P < .0005). CONCLUSIONS: The greater T1 relaxivity of Gd-BOPTA permits improved visualization of intracranial enhancing lesions compared to conventional gadolinium agents.     

Transient increased segmental hepatic enhancement distal to portal vein obstruction on dynamic gadolinium-enhanced gradient echo MR images

The purpose of the present study was to demonstrate the frequency of occurrence of transient increased segmental hepatic enhancement distal to portal veto obstruction in patients with a lobar (main branch) portal vein obstruction. MR images of all patients with main and lobar branch portal vein obstruction examined by dynamic gadolinium enhanced gradient echo MR images between December 1990 and July 1994 were reviewed retrospectively. All studies included T2-weighted imaging, Tl-weighted spoiled gradient echo‘fast low angle shot ([FLASH])’ and postgadolinium enhanced PLASH imaging at 1, 45, and 90 sec and 10 min. Fourteen patients were identified with portal vein obstruction which Included: six with main portal and right and left branch occlusion, six with right lobar, and two with left lobar. In the six patients with main portal vein obstruction, enhancement on 1-sec postgadolinium FLASH images was homogenous (three patients), diffusely heterogeneous (two patients), or peripherally hyperintense (one patient). In eight of eight patients with isolated obstruction of the right or left lobar portal vein, transient-increased segmental enhancement distal to portal vein occlusion was observed on immediate postcontrast images. Relatively high signal intensity of the involved segments was present on 1-sec images and liver parenchymal enhancement became more homogeneous by 45 to 90 sec in all cases. In conclusion, transient-increased segmental enhancement occurred in eight of eight patients with isolated right or left portal vein occlusion. We postulate that this effect occurs due to increased hepatic arterial blood flow in the presence of portal vein obstruction.     

MR imaging contrast agents — what's in a name?

The purpose of this brief review is to reduce the confusion surrounding the nomenclature of MRI contrast agents. There are several different categories of contrast agents for potential use in human diagnosis and several alternative names for each contrast agent, an array of choices that actually changes over time. This review describes the general process by which these various agents are named, presents one general categorization by which these agents can be considered, and provides a concise table to which readers can refer to identify the proper name to use for each of the agents that has thus far been administered to humans.     

Contrast-enhanced MR angiography of the run-off vasculature: intraindividual comparison of gadobenate dimeglumine with gadopentetate dimeglumine

PURPOSE: To compare intraindividually gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for multi-station MR Angiography of the run-off vessels. MATERIALS AND METHODS: Twenty-one randomized healthy volunteers received either Gd-BOPTA or Gd-DTPA as a first injection and then the other agent as a second injection after a minimum interval of 6 days. Each agent was administered at a dose of 0.1 mmol/kg bodyweight followed by a 25-mL saline flush at a single constant flow rate of 0.8 mL/second. Images were acquired sequentially at the level of the pelvis, thigh, and calf using a fast three-dimensional (3D) gradient echo sequence. Source, subtracted source, maximum intensity projection (MIP), and subtracted MIP image sets from each examination were evaluated quantitatively and qualitatively on a segmental basis involving nine vascular segments. RESULTS: Significantly (P < 0.05) higher signal-to-noise and contrast-to-noise ratios were noted for Gd-BOPTA compared to Gd-DTPA, with the more pronounced differences evident in the more distal vessels. Qualitative assessmentrevealed no differences in the abdominal vasculature, a preference for Gd-BOPTA in the pelvic vasculature, and markedly better performance for Gd-BOPTA in the femoral and tibial vasculature. Summation of individual diagnostic quality scores for each segment revealed a significantly (P = 0.0001) better performance for Gd-BOPTA compared to Gd-DTPA. CONCLUSION: Greater vascular enhancement of the run-off vasculature is obtained after Gd-BOPTA, particularly in the smaller more distal vessels. Enhancement differences are not merely dose dependent, but may be due to different vascular enhancement characteristics of the agents.     

Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

Although the diagnostic application of echoplanar imaging (EPI) has until now been limited, recent technical advances provide anatomic resolution and signal-to-noise ratios comparable to that of conventional MR imaging. The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flash images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. Approved aqueous gastrointestinal contrast media or flavored saline with long relaxation times may serve as safe, simple, and effective gastrointestinal contrast agents in abdominal EPI. Correspondence to: P. Reimer     

Safety characteristics of gadobenate dimeglumine: clinical experience from intra- and interindividual comparison studies with gadopentetate dimeglumine

PURPOSE: To evaluate the safety and tolerability of gadobenate dimeglumine (Gd-BOPTA) relative to that of gadopentetate dimeglumine (Gd-DTPA) in patients and volunteers undergoing MRI for various clinical conditions. MATERIALS AND METHODS: A total of 924 subjects were enrolled in 10 clinical trials in which Gd-BOPTA was compared with Gd-DTPA. Of these subjects, 893 were patients with known or suspected disease and 31 were healthy adult volunteers. Of the 893 patients, 174 were pediatric subjects (aged two days to 17 years) referred for MRI of the brain or spine. Safety evaluations included monitoring vital signs, laboratory values, and adverse events (AE). RESULTS: The rate of AE in adults was similar between the two agents (Gd-BOPTA: 51/561, 9.1%; Gd-DTPA: 33/472, 7.0%; P = 0.22). In parallel-group studies in which subjects were randomized to either agent, the rate of AE was 10.9% for Gd-BOPTA and 7.9% for Gd-DTPA (P = 0.21). In the subset of subjects receiving both agents in intraindividual crossover trials, the rate of AE was 8.0% for Gd-BOPTA and 8.5% for Gd-DTPA (P = 0.84). Results of other safety assessments (laboratory tests, vital signs) were similar for the two agents. CONCLUSION: The safety profile of Gd-BOPTA is similar to Gd-DTPA in patients and volunteers. Both compounds are equally well-tolerated in patients with various disease states undergoing MRI.     

Enhancement of the liver and pancreas in the hepatic arterial dominant phase: Comparison of hepatocyte‐specific MRI contrast agents,gadoxetic acid and gadobenate dimeglumine,on 3 and 1.5 tesla MRI in the same patient

Purpose:

To evaluate the relative enhancement of liver, pancreas, focal nodular hyperplasia (FNH), pancreas‐to‐liver index, and FNH‐to‐liver index in the hepatic arterial dominant phase (HADP) after injection of hepatocyte‐specific MRI contrast agents, gadoxetic acid and gadobenate dimeglumine, on 3 and 1.5 Tesla (T) MRI in the same patient.

Materials and Methods:

The MRI database was retrospectively searched to identify consecutive patients who underwent abdominal MRI at 3T and 1.5T systems, using both 0.025 mmol/kg gadoxetic acid‐enhanced and 0.05 mmol/kg gadobenate dimeglumine‐enhanced MRI at the same magnetic strength field system. 22 patients were identified, 10 were scanned at 3T system and 12 at 1.5T system. The enhancement of liver, pancreas, and FNH was evaluated quantitatively on MR images.

Results:

The relative enhancement of liver in HADP in the gadobenate dimeglumine‐enhanced group in all subjects was significantly higher than that in gadoxetic acid‐enhanced group (P = 0.023). The gadobenate dimeglumine‐enhanced group in HADP had better relative enhancement of pancreas and FNH, pancreas‐to‐liver index, and FNH‐to‐liver index than gadoxetic acid‐enhanced group, but the difference was not statistically significant.

Conclusion:

The 0.05 mmol/kg gadobenate dimeglumine‐enhanced abdominal MRI studies at 3T and 1.5T MR systems are superior in relative enhancement of the liver in HADP to 0.025 mmol/kg gadoxetic acid‐enhanced MRI. This type of assessment may provide comparative effectiveness data. J. Magn. Reson. Imaging 2013;37:903–908. © 2012 Wiley Periodicals, Inc.     

Time course of contrast enhancement patterns after Gd-BOPTA in correlation to myocardial infarction and viability: a feasibility study.

Our objective was to analyze contrast enhancement patterns (CEP) and their time course after myocardial infarction (MI) following injection of Gd-BOPTA in correlation with recovery of regional function. Seven patients with subacute MI (18 +/- nine days) were examined before, as well as three and six (n = six) months after, revascularization of the infarct-related artery. Regional wall motion abnormalities were assessed by cine-MRI, and repetitive images of one representative slice were acquired up to 45 minutes after 0.05 mmol/kg Gd-BOPTA using a T1-w TSE-sequence. Two patients showed mid-wall/subendocardial, one patient subendocardial enhancement of MI associated with mechanical improvement after revascularization. Three patients without improvement revealed a mid-wall hypoenhanced zone within the first five minutes after injection, which was unchanged at follow-up. One patient with partial functional improvement showed transmural enhancement and a mid-wall hypoenhanced zone in adjacent areas. With this feasibility study, we concluded that mid-wall and/or subendocardial enhancement after Gd-BOPTA was associated with viable myocardium, whereas detection of microvascular obstruction correlating with scar formation is suggested by mid-wall hypoenhancement within the first five minutes after injection.     

Contrast agents for MR imaging of the liver

The evolution of contrast agents for MR imaging of the liver has proceeded along several different paths with the common goal of improving liver-lesion contrast. These contrast agents are used to accentuate the inherent differences in liver-lesion signal intensity through differential enhancement of proton relaxation within adjacent tissues. Contrast agents used for hepatic MR imaging can be broadly categorized into those that target the extracellular space, the hepatobiliary system, and the reticuloendothelial system. Although only a small number of liver contrast agents are currently available, others are rapidly proceeding through clinical trials and may soon be added to our clinical armamentarium. This article will briefly review the current clinical experience with these agents, discussing their mechanism of contrast enhancement, pharmacokinetics, and efficacy in the evaluation of focal liver lesions.     

Comparison of different contrast agents and doses for quantitative MR myocardial perfusion imaging

PURPOSE: To investigate three different contrast agents at different injection volumes for repetitive quantitative multislice myocardial perfusion imaging using the prebolus technique. MATERIALS AND METHODS: Two consecutive prebolus perfusion measurements were performed on a 1.5 T scanner using identical injection volumes for the first and second examination to test the reproducibility for possible rest and stress examination in normal volunteers. Either 1-8 mL, 1-12 mL Gd-DTPA, 1-4 mL, 1-6 mL, 1-9 mL Gd-BOPTA, or 1-4 mL, 1-6 mL gadobutrol were applied. RESULTS: In cases where injection volumes were sufficiently small, there was no indication of significant differences in quantitative perfusion values with respect to the different contrast agents. Increasing the bolus volume improved the contrast-to-noise ratio (CNR) but led to saturation effects and underestimation of the true perfusion. The highest CNR was measured for gadobutrol (6 mL, p < 0.0005 compared to 8 mL Gd-DTPA). The smallest difference of perfusion values between the first and the second prebolus examination was found for Gd-BOPTA (p < or = 0.006 compared Gd-DTPA). CONCLUSION: Prebolus examinations for quantitative myocardial perfusion imaging are possible with all three contrast agents for sufficient small injection volumes. Gd-BOPTA was found to be advantageous for a combined quantitative rest and stress examination.     

Gadobenate dimeglumine (BOPTA) enhanced MR imaging: Patterns of enhancement in normal liver and cirrhosis

To determine whether gadobenate dimeglumine (BOPTA) will adequately enhance cirrhotic liver parenchyma, and to document the enhancement patterns in cirrhosis, 14 cirrhotic and 20 non-cirrhotic patients were evaluated before and 60–120 minutes after gadolinium-BOPTA. Proof of liver cirrhosis was biopsy (6), surgical resection (3), and clinical follow-up (5). Enhancement effects were compared quantitatively by determining the liver signal-to-noise ratio (SNR) and signal enhancement in both populations. Qualitatively assessment of the liver enhancement was performed and classified as homogeneous or heterogeneous. Quantitative analysis: cirrhotic liver parenchyma presented a higher increase in SNR values, relative to noncirrhotic liver parenchyma, on postcontrast images. Likewise the signal enhancement of cirrhotic liver parenchyma was superior to non-cirrhotic liver on T1-weighted SE images (P = .02) and in-phase GRE images (P < .001). There was no statistical difference on out-of-phase GRE images. Qualitative analysis: on T1-weighted SE postcontrast images, cirrhotic liver parenchyma showed a homogeneous enhancement in 7 patients and heterogeneous in 7. Whereas on GRE images, cirrhotic parenchyma showed heterogeneous enhancement in 9 patients and homogeneous in 5 patients. The heterogeneous enhancement was due to the presence of hypointense nodules in 7 patients and hyperintense nodules in 2 patients. In conclusion, our study has shown that the hepatobiliary contrast agent Gd-BOPTA is effective in the cirrhotic liver, demonstrating an increased liver enhancement compared with non-cirrhotic patients.     

Focal liver lesions: comparison of dual-phase CT and multisequence multiplanar MR imaging including dynamic gadolinium enhancement

The purpose of this study was to compare dual-phase spiral computed tomography (CT) and magnetic resonance imaging (MRI) using dynamic gadolinium enhancement for liver lesion detection and characterization. Twenty-two consecutive patients underwent dual-phase spiral CT and MRI for the evaluation of focal liver disease within a 1-month period. Spiral CT and MR images were interpreted prospectively, in a blinded fashion by separate, individual, experienced investigators, to determine lesion detection and characterization. Liver lesions were confirmed by surgery and pathology in 6 patients, and by clinical and imaging follow-up in the other 16 patients. Pathological correlation of a primary extrahepatic malignancy was available in 5 of the 16 patients who had metastatic liver disease. Spiral CT and MRI detected 53 and 63 lesions, and characterized 39 and 62 true positive lesions, respectively. A kappa statistic test was applied to assess agreement between MR and CT results. MR versus CT for lesion detection resulted in a kappa statistic of 0.54 (95% confidence interval), indicating moderate agreement, and 0.32 (95% confidence interval) for lesion characterization, indicating only slight agreement. More lesions were detected on MR images than CT images in 6 (27%) patients, with lesions detected only on MR images in 4 (18%) patients. More lesions were characterized on MR images in 9 (41%) patients. In 9 patients with a discrepancy between MR and CT findings, the MR images added information considered significant to patient management in all 9 cases. MRI was moderately superior to dual-phase spiral CT for lesion detection, and was markedly superior for lesion characterization, with these differences having clinical significance.     

Safety assessment of gadobenate dimeglumine (MultiHance): extended clinical experience from phase I studies to post-marketing surveillance

Clinical trials completed by September 2000 on gadobenate dimeglumine (Gd-BOPTA; MultiHance) included 2540 adult and pediatric subjects that were administered this agent. For adult patient volunteers, the overall incidence of adverse events (AEs) was 19.8%, although marked study- and indication-related differences were apparent. Events potentially related to Gd-BOPTA administration were reported for 15.1% of adult patients. The vast majority of AEs were non-serious, mild, transient, and self-resolving. Headache, injection site reaction, nausea, taste perversion, and vasodilation were the most common AEs, reported with a frequency of between 1.0% and 2.6%. Serious AEs potentially related to Gd-BOPTA were reported for five (0.2%) patients overall. Controlled studies revealed no differences between Gd-BOPTA and other gadolinium chelates or placebo in the incidence and type of AEs. Similarly, no differences with respect to adult patients and/or comparator were noted in studies on pediatric subjects and subjects with renal or liver insufficiency. Post-marketing surveillance of approximately 100000 doses revealed an overall AE incidence of < 0.03% with serious AEs reported for < 0.005% of patients.     

Optimal dose of hepatobiliary contrast agent for MR cholangiography: Experimental study in rats

The purpose of this study is to clarify the optimal dose of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) for cholangiography in conventional T1-weighted imaging. We divided 30 rats into three dose groups (3, 10, and 30 μmol/kg). For the in vitro study, we collected bile and measured the concentration of gadolinium in bile after Gd-EOB-DTPA injection. T1-weighted images of the collected bile were obtained for measurement of signal intensity. For the in vivo study, we obtained T1-weighted images before and after injection and evaluated bile duct/liver contrast by the signal intensity ratio and visual assessment of the images. The gadolinium concentration had an early peak; however, the signal intensity of the bile had a later peak because of the high gadolinium concentration during the early phase, which induced a T2-shortening effect. Optimal bile duct/liver contrast was obtained in the 10-μmol/kg groups at all time points. We conclude that the optimal dose of Gd-EOB-DTPA for MR cholangiography in rats is 10 μmol/kg, one-third of the dose used in liver imaging.     

Pharmacokinetics and enhancement patterns of macromolecular MR contrast agents with various sizes of polyamidoamine dendrimer cores.

Four macromolecular contrast agents are synthesized to visualize small vessels by MRI using generation-3 (G3D), -4 (G4D), -5 (G5D), and -6 (G6D) polyamidoamine dendrimers conjugated to chelated gadolinium (Gd). The pharmacokinetics, enhancement patterns, and the ability of these constructs to visualize fine vessels is evaluated by dynamic MRI in relationship to their size. Gd-G6D and -G5D exhibit a prolonged high vascular (ventricular) signal intensity (SI) with high ventricle-to-organ SI ratios. The initial high vascular SI with Gd-G4D decreases to a value as low as that obtained with Gd-G3D and Gd-dimeglumine-diethylenetriaminepentaacetic acid (Gd-DTPA). Gd-G5D, -G4D, and -G3D show high renal SIs, and Gd-DTPA prominently enhances the skin. Gd-G6D and -G5D present fine vasculature significantly more clearly than Gd-G3D and -DTPA (P < 0.005). As the molecular size increases, the excretion of the 153Gd-conjugates is retarded. In conclusion, Gd-G6D and -G5D are retained in the blood and present fine vessels with high quality and detail, and should be adequate for visualizing small tumor vasculature.