Comparison of contrast agents with high molarity and with weak protein binding in cerebral perfusion imaging at 3 T

PURPOSE: To examine and compare properties of high-molarity contrast agent gadobutrol (Gadovist) and weakly protein-binding agent gadobenate-dimeglumine (MultiHance in dynamic susceptibility contrast (DSC) perfusion imaging at 3 T. MATERIALS AND METHODS: Sixteen healthy volunteers underwent three separate examinations with contrast agent doses of 0.1 and 0.2 mmol/kg body weight (bw) gadobutrol and 0.1 mmol/kg bw gadobenate-dimeglumine. Maps of relative regional cerebral blood volume (rCBV) and blood flow (rCBF) were calculated using deconvolution based on singular value decomposition. Signal and concentration time curves, the concentration-to-noise ratio (SNR(c)), and gray matter (GM)-to-white matter (WM) rCBV and rCBF contrast and ratios were evaluated in a region of interest (ROI)-based analysis. Image quality of calculated parametric maps was assessed in direct visual comparison and with respect to suitability for diagnostic purposes. RESULTS: The contrast agents displayed very similar results in the 0.1 mmol/kg examinations, both with respect to the quantitative evaluation parameters and in the qualitative assessment of the calculated parametric maps. Maps from 0.2 mmol/kg examinations were rated as being superior in quality, but with respect to diagnostic suitability all contrast agents and doses yielded images of sufficient quality. CONCLUSION: At 3 T, a gadobutrol or gadobenate-dimeglumine dose of 0.1 mmol/kg is sufficient for DSC magnetic resonance imaging (MRI) perfusion assessment. At the used small injection volumes, the tissue concentration curve was determined only by the gadolinium (Gd) dosage in mmol/kg, and the T2* relaxation effects of the two agents can be considered to be nearly identical in the applied gradient-echo (GRE) sequence.     

Comparison of MultiHance and Gadovist for cerebral MR perfusion imaging in healthy volunteers

To evaluate the weakly protein interacting MR contrast agent MultiHance((R)) and the one-molar agent Gadovist((R)) for cerebral perfusion MR imaging, a randomized intraindividual study was conducted in 12 healthy male volunteers. Perfusion-MRI was performed with single and double dose of each contrast agent on a 1.5T MR system using a gradient-echo EPI sequence. The imaging parameters, slice positioning and contrast media application were standardized. For the quantitative assessment rCBV and rCBF measurements of gray and white matter were performed. Additionally, the percentage of signal drop and the full width half maximum (FWHM) of ROI signal time curves were quantified. In a qualitative analysis the image quality of the rCBV and rCBF maps were assessed. Single dosage of the used new contrast agents was sufficient to achieve high quality perfusion maps. The susceptibility effect, described by percentage of signal loss (Gadovist((R)): 29.4% vs. MultiHance((R)): 28.3%) and the FWHM (Gadovist((R)): 6.4 s vs. Multihance((R)): 7.0 s) were not different between the agents for single dose. The one molar MR contrast agent Gadovist((R)) has no advantages over MultiHance((R)), a MR contrast agent with a higher relaxivity in perfusion MRI. Both agents allow the calculation of high quality perfusion maps at a dosage of 0.1 mmol/kg bw with physiologic absolute values for regional CBV and CBF. The susceptibility effect is comparable for both agents and stronger than with conventional MR contrast media.     

Multiphasic MR angiography as an intra-individual comparison between the contrast agents Gd-DTPA,Gd-BOPTA,and Gd-BT-DO3A

QUESTION: The availability of new MR contrast agents having either a protein binding effect or higher concentration leads to the question if they differ from standard compounds in their vascular contrasting properties. METHODS: By intraindividual comparison five volunteers were examined (1.5 T MR system) with a multi-phasic MRA of the abdomen each receiving three different contrast agents (gadopentetate dimeglumine 0.5 M; gadobenate dimeglumine 0.5 M, and gadobutrol 1.0 M).The dose (0.15 mmol/kg body weight) and flow rate (3.0 ml/s) were kept identical. All images were quantitatively and qualitatively evaluated by blinded assessment. RESULTS: Significantly higher maximum signal intensity was found in the arteries for the protein interacting gadobenate dimeglumine (p = 0.05). No significant difference in vascular enhancement was demonstrated in the comparison of gadobutrol to gadopentetate dimeglumine. CONCLUSION: Gadobenate dimeglumine was shown to be a favorable contrast agent for multi-phasic MRA. A higher concentrated Gd-chelate does not automatically lead to improved vascular contrast if standard imaging protocols are used.     

Diffusion-perfusion in intra-axial brain tumors with high relaxivity contrast agents

A high relaxivity contrast agent is indicated for use in MRI of the central nervous system to visualize lesions with an abnormal blood-brain barrier (BBB) or abnormal vascularity of the brain. We evaluated MultiHance (gadobenate dimeglumine, Gd-BOPTA) on T2*-weighted perfusion imaging in 33 histologically proven intra-axial brain tumors. The higher T1 relaxivity, and therefore better contrast-enhanced T1 imaging led to significantly better tumor delineation. The higher T2 relaxivity allowed high quality T2* perfusion MRI and post processed rCBV maps, with a dose of 0.1 mmol/kg MultiHance.     

Perfusion MRI in CNS disease: current concepts

Today there are several indications for cerebral perfusion MRI. The major indications routinely used in increasing numbers of imaging centers include cerebrovascular disease, tumor imaging and recently psychiatric disorders. Perfusion MRI is based on the injection of a gadolinium chelate and the rapid acquisition of images as the bolus of contrast agent passes through the blood vessels in the brain. The contrast agent causes a signal change; this signal change over time can be analysed to measure cerebral hemodynamics. The quality of brain perfusion studies is very dependent on the contrast agent used: a robust and strong signal decrease with a compact bolus is needed. MultiHance (gadobenate dimeglumine, Gd-BOPTA) is the first of a new class of paramagnetic MR contrast agents with a weak affinity for serum proteins. Due to the interaction of Gd-BOPTA with serum albumin, MultiHance presents with significantly higher T1- and T2-relaxivities enabling a sharper bolus profile. This article reviews the indications of perfusion MRI and the performance of MultiHance in MR perfusion of different diseases. Previous studies using perfusion MRI for a variety of purposes required the use of double dose of contrast agent to achieve a sufficiently large signal drop to enable the acquisition of a clear input function and the calculation of perfusion rCBV and rCBF maps of adequate quality. Recent studies with Multi-Hance suggest that only a single dose of this agent is needed to cause a signal drop of about 30% which is sufficient to allow the calculation of high quality rCBV and rCBF maps.     

Three-dimensional contrast-enhanced magnetic-resonance angiography of the renal arteries: Interindividual comparison of 0.2 mmol/kg gadobutrol at 1.5 T and 0.1 mmol/kg gadobenate dimeglumine at 3.0 T

The purpose was to evaluate the image quality of high-spatial resolution MRA of the renal arteries at 1.5 T after contrast-agent injection of 0.2 mmol/kg body weight (BW) in an interindividual comparison to 3.0 T after contrast-agent injection of 0.1 mmol/kg BW contrast agent (CA). After IRB approval and informed consent, 40 consecutive patients (25 men, 15 women; mean age 53.9 years) underwent MRA of the renal arteries either at a 1.5-T MR system with 0.2 mmol/kg BW gadobutrol or at a 3.0-T MR scanner with 0.1 mmol/kg BW gadobenate dimeglumine used as CA in a randomized order. A constant volume of 15 ml of these contrast agents was applied. The spatial resolution of the MRA sequences was 1.0 × 0.8 × 1.0 mm³ at 1.5 T and 0.9 × 0.8 × 0.9 mm³ at 3.0 T, which was achieved by using parallel imaging acceleration factors of 2 at 1.5 T and 3 at 3.0 T, respectively. Two radiologists blinded to the administered CA and the field strength assessed the image quality and the venous overlay for the aorta, the proximal and distal renal arteries independently on a four-point Likert-type scale. Phantom measurements were performed for a standardized comparison of SNR at 1.5 T and 3.0 T. There was no significant difference (p > 0.05) between the image quality at 3.0 T with 0.1 mmol/kg BW gadobenate dimeglumine compared to the exams at 1.5 T with 0.2 mmol/kg BW gadobutrol. The median scores were between 3 and 4 (good to excellent vessel visualization) for the aorta (3 at 1.5 T/4 at 3.0 T for reader 1 and 2). For the proximal renal arteries, median scores were 3 for the left and right renal artery at 1.5 T for both readers. At 3.0 T, median scores were 3 (left proximal renal artery) and 4 (right proximal renal artery) for reader 1 and 3 (left/right) for reader 2 at 3.0 T. For the distal renal arteries, median scores were between 2 and 3 at both field strengths (moderate and good) for both readers. The κ values for both field strengths were comparable and ranged between 0.571 (moderate) for the distal renal arteries and 0.905 (almost perfect) for the proximal renal arteries. In the phantom measurements, a 40% higher SNR was found for the measurements at 3 T with gadobenate dimeglumine. High-spatial resolution renal MRA at 3.0 T with 0.1 mmol/kg BW gadobenate dimeglumine yields at least equal image quality compared with renal MRA at 1.5 T with 0.2 mmol/kg BW gadobutrol. Ulrike I. Attenberger and Henrik J. Michaely contributed equally.     

Does a higher concentration of gadolinium chelates improve first-pass cardiac signal changes?

The purpose of this study was to evaluate first-pass cardiac signal changes with a higher concentrated gadolinium-chelate (gadobutrol) and its influence on bolus geometry. Phantom studies and in vivo first-pass cardiac studies were performed in rabbits (n = 8 experiments) under general anesthesia at 1.0 T using an ultrafast T1-weighted Turbo-fast low-angle shot (FLASH) sequence (TR/TE 4.7/1. 6 msec, alpha = 90 degrees ) with a time resolution of 870 msec. Gadobutrol was injected as an intravenous bolus at two concentrations (0.5 and 1.0 mol Gd/L) and five doses (0.3, 0.15, 0.1, 0.055, and 0.03 mmol Gd/kg bw). The blood-pool gadolinium compound gadopentetate dimeglumine-polylysine (0.15, 0.075, 0.05, and 0.015 mmol Gd/kg bw, 0.5 mol Gd/L) and the standard extracellular gadopentetate dimeglumine (0.1 and 0.05 mmol Gd/kg bw, 0.5 mol Gd/L) served as reference agents. Cardiac signal changes were calculated from serial signal intensity measurements. Maximum signal intensity changes and best peak profiles during first pass of the right and left ventricle were observed with a dose of 0.03 mmol Gd/kg bw gadobutrol using T1-weighted Turbo-FLASH. At the low application volumes used, the higher concentration of 1.0 mol Gd/L gadobutrol did not increase the degree of signal intensity changes or sharpen the bolus profile. First-pass cardiac signal changes using T1-weighted Turbo-FLASH with the new extracellular contrast agent gadobutrol are best observed at a dose of 0.03 mmol Gd/kg bw. There is no advantage to the concentrated formulation (1 mol Gd/L gadobutrol) when using small injection volumes. J. Magn. Reson. Imaging 1999;10:806-812.     

Renal time-resolved MR angiography: quantitative comparison of gadobenate dimeglumine and gadopentetate dimeglumine with different doses

PURPOSE: Results with different doses of gadobenate dimeglumine and gadopentetate dimeglumine were compared at magnetic resonance (MR) angiography of the renal arteries. The signal-to-noise ratio (SNR) was evaluated as a quantitative measure of image quality. MATERIALS AND METHODS: Sixty consecutive patients (age range, 24-81 years; mean age, 65 years) underwent intraarterial digital subtraction angiography (DSA) and contrast material-enhanced time-resolved MR angiography. DSA was the standard of reference. Fifteen patients received gadopentetate dimeglumine at doses of 0.2 or 0.1 mmol per kilogram of body weight. Fifteen patients received gadobenate dimeglumine at doses of 0.05 or 0.1 mmol/kg. The SNR was calculated in the aorta and both main renal arteries. The number and degree of stenoses of the renal arteries and accessory vessels were evaluated by four observers. RESULTS: SNRs with gadobenate dimeglumine at a dose of 0.1 mmol/kg were significantly superior to those with gadopentetate dimeglumine at a dose of 0.1 mmol/kg. Differences were not statistically significant between the SNRs in the other groups. Eleven (85%) of 13 hemodynamically significant renal artery stenoses were detected correctly with MR angiography as were 22 (85%) of 26 accessory renal arteries. CONCLUSION: SNRs with gadobenate dimeglumine were higher than those with gadopentetate dimeglumine, but in most cases the differences in SNRs were not statistically significant.     

Gadobenate dimeglumine--a new contrast agent for MR imaging: preliminary evaluation in healthy volunteers.

Gadobenate dimeglumine (formerly known as Gd-BOPTA) is a recently developed paramagnetic contrast agent that undergoes biliary as well as renal excretion. It may, therefore, be useful in MR imaging of the liver. Its safety, tolerance, and usefulness in visualizing hepatobiliary structures were studied in eight healthy subjects. Axial abdominal images were obtained with T1-weighted spin-echo and gradient-echo sequences at 1.5 T before and after IV administration of gadobenate dimeglumine in doses of 0.005, 0.05, 0.1, and 0.2 mmol/kg body weight. Two subjects received each dose. Administration of 0.1 mmol/kg resulted in a maximum liver enhancement of 149% on the gradient-echo sequence and of 90% on the T1-weighted spin-echo sequence 60 min after injection. The contrast enhancement of the liver remained virtually constant for 2 hr. The signal-to-noise ratio of the biliary tract increased from 38 to 121 after 2 hr on gradient-echo images. In addition, there was significant contrast enhancement of the kidneys. Optimal visualization of the liver parenchyma was achieved with doses of 0.05 and 0.1 mmol gadobenate dimeglumine/kg. Mild to moderate side effects such as nausea and retching, a sense of warmth at the infusion site, and transient pruritus lasting 1 min were reported by three (38%) of the subjects. The initial results of the first application of gadobenate dimeglumine in humans are encouraging because the contrast agent appears to be reasonably well tolerated at the doses appropriate for hepatobiliary imaging. Further clinical studies of this contrast agent are warranted to assess its effect on liver lesion conspicuity and the frequency with which side effects occur.     

Double-blind, efficacy evaluation of gadobenate dimeglumine, a gadolinium chelate with enhanced relaxivity, in malignant lesions of the brain

BACKGROUND AND PURPOSE: The diagnostic efficacy of gadobenate dimeglumine (Gd BOPTA) was compared with that of gadodiamide (Gd DTPA-BMA) in patients with primary malignant tumors or metastases of the brain. METHODS: A subset of patients was evaluated from the 410 enrolled in the United States in phase III central nervous system clinical trials with gadobenate dimeglumine. From these trials, there were 82 patients with intraaxial malignant neoplasms of the brain, the focus of the current study. Patients were randomized to one of three incremental dosing regimens. Imaging with gadodiamide at doses of 0.1 and 0.3 mmol/kg was compared with gadobenate dimeglumine at doses of 0.05 and 0.15 mmol/kg and at doses of 0.1 and 0.2 mmol/kg. The on-site physician, patient, and all off-site reviewers were blinded to the agent injected and the administered dose. Scans were obtained before contrast administration and within 5 minutes after administration of each dose. The two contrast injections in any one patient were separated by 15 minutes. An independent laboratory performed signal intensity measurements. The magnetic resonance (MR) films were evaluated for level of diagnostic information, number of lesions detected, and confidence in MR imaging diagnosis by two independent board-certified neuroradiologists unaffiliated with any study site. RESULTS: The lesion-to-brain signal intensity ratio after a dose of 0.1 mmol/kg gadobenate dimeglumine was higher than that after a dose of 0.1 mmol/kg gadodiamide, with this result statistically significant (P = 0.02). After the second dose of contrast, results were comparable in all three groups. The level of diagnostic information contained on the MR films increased significantly for all three groups from pre- to postcontrast for both the first and second administered doses. In between-group comparisons, the level of diagnostic information was similar after the first contrast dose for all three dosing regimens. This was also true after the second contrast dose. For all three groups, the number of lesions detected increased significantly postdose (whether first or second). Confidence in MR diagnosis increased from predose to postdose for all three groups, with no statistically significant difference between groups. CONCLUSION: Gadobenate dimeglumine, used at slightly lower doses, is comparable to gadodiamide in terms of efficacy in imaging of malignant intraaxial brain lesions. As with other gadolinium chelates, higher doses (0.15 and 0.2 mmol/kg) of gadobenate dimeglumine offer greater diagnostic information.     

Time-resolved contrast-enhanced three-dimensional pulmonary MR-angiography: 1.0 M gadobutrol vs. 0.5 M gadopentetate dimeglumine

PURPOSE: To compare contrast characteristics and image quality of 1.0 M gadobutrol with 0.5 M Gd-DTPA for time-resolved three-dimensional pulmonary magnetic resonance angiography (MRA). MATERIALS AND METHODS: Thirty-one patients and five healthy volunteers were examined with a contrast-enhanced time-resolved pulmonary MRA protocol (fast low-angle shot [FLASH] three-dimensional, TR/TE = 2.2/1.0 msec, flip angle: 25 degrees, scan time per three-dimensional data set = 5.6 seconds). Patients were randomized to receive either 0.1 mmol/kg body weight (bw) or 0.2 mmol/kg bw gadobutrol, or 0.2 mmol/kg bw Gd-DTPA. Volunteers were examined three times, twice with 0.2 mmol/kg bw gadobutrol using two different flip angles and once with 0.2 mmol/kg bw Gd-DTPA. All contrast injections were performed at a rate of 5 mL/second. Image analysis included signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements in lung arteries and veins, as well as a subjective analysis of image quality. RESULTS: In patients, significantly higher SNR and CNR were observed with Gd-DTPA compared to both doses of gadobutrol (SNR: 35-42 vs.17-25; CNR 33-39 vs. 16-23; P < or = 0.05). No relevant differences were observed between 0.1 mmol/kg bw and 0.2 mmol/kg bw gadobutrol. In volunteers, gadobutrol and Gd-DTPA achieved similar SNR and CNR. A significantly higher SNR and CNR was observed for gadobutrol-enhanced MRA with an increased flip angle of 40 degrees. Image quality was rated equal for both contrast agents. CONCLUSION: No relevant advantages of 1.0 M gadobutrol over 0.5 M Gd-DTPA were observed for time-resolved pulmonary MRA in this study. Potential explanations are T2/T2*-effects caused by the high intravascular concentration when using high injection rates.     

Contrast-enhanced, high-resolution, susceptibility-weighted magnetic resonance imaging of the brain: dose-dependent optimization at 3 tesla and 1.5 tesla in healthy volunteers

OBJECTIVES: We sought to determine the optimal dose of a contrast agent with known high relaxivity on 1.5 and 3 Tesla scanners that would achieve the best compromise between image quality and scan time for the clinical application of contrast-enhanced susceptibility-weighted imaging (CE-SWI). METHODS: Pre- and postcontrast SWI was performed with different contrast agent doses (0.05, 0.1, and 0.2 mmol/kg gadobenate dimeglumine) at both 1.5 and 3 T in 6 healthy volunteers, resulting in 72 examinations. Venograms were created from minimum intensity projection reconstructions over specified deep white matter volumes to enhance the visual appearance of connected venous structures. Three independent radiologists blindly rated the visibility of the veins on a continuous scale of 1 to 10. A general linear model was used for statistical evaluation, with fixed effects of the contrast agent dose, the field strength, the rater and the patients as a random effect. RESULTS: With CE-SWI, we found significant differences in the visibility of the deep veins dependent on the contrast media dose (P=0.02). At 3 T, the visibility of deep venous vessels, with regard to susceptibility effect, image quality, and scan time reduction after a standard contrast agent dose 0.1 mmol/kg was significantly better than that achieved with 0.05 mmol/kg. The visibility was considered equal with 0.1 mmol/kg of the contrast agent to the precontrast images and a dose of 0.2 mmol/kg. At 1.5 T, no significant difference was found between the 4 contrast agent doses. We found no difference in the visibility of the veins with the shorter sequences at 3 T compared with the sequences at 1.5 T. CONCLUSIONS: Only a standard dose (0.1 mmol/kg) of gadobenate dimeglumine is required to achieve the optimum susceptibility effect and image quality at 3 T, together with a reduced scan time. This result can be attributed to the higher relaxivity of gadobenate dimeglumine, compared with conventional gadolinium chelates.     

A clinical comparison of the safety and efficacy of MultiHance (gadobenate dimeglumine) and Omniscan (Gadodiamide) in magnetic resonance imaging in patients with central nervous system pathology

RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.     

Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for MR imaging of acute hepatitis in a rat model

This work was conducted to test the hypothesis that contrast-enhanced MRI with hepatocyte-specific contrast agents facilitates quantitation and mapping of diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine (Gd-BOPTA/Dimeg, Bracco SpA, Milano, Italy) is a new paramagnetic hepatocytespecific contrast agent currently undergoing clinical trials. We have assessed the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver diseases in a rat model of chemically induced hepatitis. The study was based on the measurements of in vivo liver relaxation times as well as on the acquisition of standard SE images. Acute hepatitis considerably reduced the degree of T1 shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images was inferior, in terms of both strength and duration, to that recorded in control rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our results show that gadobenate dimeglumine enhanced MR imaging has the potential for visualization of hepatitis and for assessment of liver function. Our conclusions differ from those previously published on this subject by other authors. The reasons that led to differing conclusions are discussed.     

Gadobenate dimeglumine-enhanced MRI of the breast: analysis of dose response and comparison with gadopentetate dimeglumine

OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy and dose response relationship of three doses of gadobenate dimeglumine for MRI of the breast and to compare the results with those obtained after a dose of 0.1 mmol/kg of body weight of gadopentetate dimeglumine. SUBJECTS AND METHODS. Gadobenate dimeglumine at 0.05, 0.1, or 0.2 mmol/kg of body weight or gadopentetate dimeglumine at 0.1 mmol/kg of body weight was administered by IV bolus injection to 189 patients with known or suspected breast cancer. Coronal three-dimensional T1-weighted gradient-echo images were acquired before and at 0, 2, 4, 6, and 8 min after the administration of the dose. Images were evaluated for lesion presence, location, size, morphology, enhancement pattern, conspicuity, and type. Lesion signal intensity-time curves were acquired, and lesion matching with on-site final diagnosis was performed. A determination of global lesion detection from unenhanced to contrast-enhanced and combined images was performed, and evaluations were made of the diagnostic accuracy for lesion detection and characterization. A full safety evaluation was conducted. RESULTS: Significant dose-related increases in global lesion detection were noted for patients who received gadobenate dimeglumine (p < 0.04, all evaluations). The sensitivity for detection was comparable for 0.1 and 0.2 mmol/kg of gadobenate dimeglumine, and specificity was highest with the 0.1 mmol/kg dose. Higher detection scores and higher sensitivity values for lesion characterization were found for 0.1 mmol/kg of gadobenate dimeglumine compared with 0.1 mmol/kg of gadopentetate dimeglumine, although more variable specificity values were obtained. No differences in safety were observed, and no serious adverse events were reported. CONCLUSION: Gadobenate dimeglumine is a capable diagnostic agent for MRI of the breast. Although preliminary, our results suggest that 0.1 mmol/kg of gadobenate dimeglumine may offer advantages over doses of 0.05 and 0.2 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadopentetate dimeglumine for breast lesion detection and characterization.     

Intra-individual randomised comparison of gadobutrol 1.0?M versus gadobenate dimeglumine 0.5?M in patients scheduled for preoperative breast MRI

Objective

To demonstrate non-inferiority of gadobutrol versus gadobenate dimeglumine by intra-individually comparing 0.1?mmol/kg body weight doses for contrast-enhanced breast magnetic resonance imaging (MRI) and prospectively evaluating lesion detection and characterisation in a multicentre trial.

Methods

Two identical breast MRI examinations were performed in 72 patients with biopsy-proven breast cancer, separated by 1?C7?days. Gadobutrol 1.0?M or gadobenate 0.5?M were administered in a randomised order. Lesion detection and characterisation were performed by two independent blinded readers. Lesion tracking, which compared on-site readings and histology from surgery or biopsy, was performed by a third reader. Differences in lesion detection and characterisation were compared between the two contrast agents.

Results

Among 103 lesions, 96 were malignant and 7 were benign. No difference in lesion detection was identified between the contrast agents (82.33?% for gadobutrol, 81.60?% for gadobenate). Assessment of sensitivity in lesion characterisation and Breast Imaging Reporting and Data Systems showed no difference between gadobutrol (92.63?%) and gadobenate (90.53?%). Regarding morphology, there was more non-focal enhancement for gadobutrol than for gadobenate (P?=?0.0057).

Conclusion

Non-inferiority of gadobutrol compared with gadobenate was demonstrated for breast lesion detection and sensitivity in lesion characterisation in breast MRI.

Key Points

? Contrast-enhanced magnetic resonance imaging is now widely used for breast problems. ? Lesion detection in breast MRI differs according to the contrast agent. ? Thus we compared gadobutrol 1?M with gadobenate dimeglumine 0.5?M. ? Gadobutrol was non-inferior to gadobenate dimeglumine for detecting and characterising malignant lesions.     

Gadobenate dimeglumine-enhanced MR imaging breast vascular maps: association between invasive cancer and ipsilateral increased vascularity

PURPOSE: To retrospectively compare three different doses of gadobenate dimeglumine with a standard dose of gadopentetate dimeglumine for magnetic resonance (MR) imaging evaluation of breast vessels and to evaluate the accuracy of one-sided increased vascularity seen on gadobenate dimeglumine-enhanced MR images as an indicator of ipsilateral breast cancer. MATERIALS AND METHODS: The original study had local ethics committee approval; informed consent was obtained from all enrolled patients. Ninety-five patients known to have or suspected of having breast cancer were randomly assigned to four groups to receive gadobenate dimeglumine at a dose of 0.05, 0.10, or 0.20 mmol per kilogram of body weight or gadopentetate dimeglumine at a dose of 0.10 mmol/kg. T1-weighted gradient-echo MR images were acquired before and 2 minutes after intravenous contrast material injection. Subtracted images were used to obtain maximum intensity projections (MIPs). Two readers blinded to the type and dose of contrast agent administered scored the MIPs obtained in the dose groups for vessel number, length, and conspicuity from 0, which indicated absent or low breast vascularity, to 3, which indicated high breast vascularity. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of one-sided increased vascularity in association with ipsilateral malignancy for 69 histopathologically confirmed lesions (reference standard) were determined after gadobenate dimeglumine-enhanced MR imaging. RESULTS: The mean MIP scores assigned to the gadobenate dimeglumine groups were significantly higher than those assigned to the gadopentetate dimeglumine group (P < or = .044). Histopathologic analysis revealed malignant lesions in 52 of 69 patients examined with gadobenate dimeglumine MR imaging: invasive ductal carcinoma in 45, invasive lobular carcinoma in four, and invasive mixed ductal-lobular carcinoma in three patients. Seventeen patients had benign lesions. Two cases of bilateral invasive cancer with symmetric breast vascular maps were excluded. Thus, the overall sensitivity, specificity, accuracy, PPV, and NPV of one-sided increased vascularity as a finding associated with ipsilateral malignancy were 88% (44 of 50 patients), 82% (14 of 17 patients), 87% (58 of 67 patients), 94% (44 of 47 patients), and 70% (14 of 20 patients), respectively. CONCLUSION: Gadobenate dimeglumine is effective for MR imaging evaluation of breast vessels at doses as low as 0.05 mmol/kg. One-sided increased vascularity is an MR imaging finding frequently associated with ipsilateral invasive breast cancer.     

Primary and secondary brain tumors at MR imaging: bicentric intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine

PURPOSE: To evaluate the safety of and compare the enhancement characteristics of gadobenate dimeglumine (MultiHance; Bracco Imaging, Milan, Italy) with those of a standard gadolinium chelate (gadopentetate dimeglumine, Magnevist; Schering, Berlin, Germany) in primary and secondary brain tumors on the basis of qualitative and quantitative parameters, on an intraindiviual basis. MATERIALS AND METHODS: Twenty-seven patients with either high-grade glioma or metastases were enrolled in a bicentric intraindividual crossover study to compare lesion enhancement with doses of 0.1 mmol per kilogram of body weight of 0.5 mol/L gadopentetate dimeglumine and 0.5 mol/L gadobenate dimeglumine. MR imaging was performed before injection (T1-weighted spin-echo [SE] and T2-weighted fast SE acquisitions) and at 1, 3, 5, 7, 9, and 16 minutes after injection (T1-weighted SE acquisitions). Qualitative assessment was performed by blinded off-site readers (for 22 patients) and on-site investigators (for 24 patients) in terms of global contrast enhancement, lesion-to-brain contrast, lesion delineation, internal lesion morphology and structure, tumor vascularization, and global image preference. Additional quantitative assessment with region-of-interest analysis was performed by off-site readers alone. Statistical analysis of qualitative data was performed with the Wilcoxon signed rank test, whereas a nonparametric approach was adopted for analysis of quantitative data. RESULTS: Significant (P <.05) preference for gadobenate dimeglumine over gadopentetate dimeglumine was noted both off-site and on-site for the global assessment of contrast enhancement. For off-site readers 1 and 2 and the on-site investigators, respectively, gadobenate dimeglumine was preferred in 13, 17, and 16 patients; gadopentetate dimeglumine was preferred in four, four, and four patients; and equality was found in five, one, and four patients). Similar preference for gadobenate dimeglumine was noted by off-site readers and on-site investigators for lesion-to-brain contrast and all other qualitative parameters. Off-site quantitative evaluation revealed significantly (P <.05) superior enhancement for gadobenate dimeglumine compared with that for gadopentetate dimeglumine at all time points from 3 minutes after injection. CONCLUSION: Significantly superior contrast enhancement of intraaxial enhancing brain tumors was achieved with 0.1 mmol/kg gadobenate dimeglumine compared with that with 0.1 mmol/kg gadopentetate dimeglumine.     

Gadobenate dimeglumine in MRI of acute myocardial infarction: results of a phase III study comparing dynamic and delayed contrast enhanced magnetic resonance imaging with EKG, (201)Tl SPECT, and echocardiography

RATIONALE AND OBJECTIVES: To evaluate the safety and utility of gadobenate dimeglumine as a magnetic resonance (MR) contrast agent in patients with acute myocardial infarction (MI). METHODS: One hundred three patients with acute MI received intravenous bolus gadobenate dimeglumine (0.05 mmol/kg) during MR examination. Dynamic and delayed T1-weighted spin-echo postcontrast images were compared with precontrast images, EKG, resting (201)Tl SPECT and echocardiography. RESULTS: Gadobenate dimeglumine was well tolerated. Dynamic imaging with gadobenate dimeglumine was more sensitive (72% vs 56%) than delayed spin echo imaging (P < 0.001). No difference in specificity was seen (98% vs 99%). (201)Tl SPECT was a sensitive (96%) test, but was not specific (63%). Echocardiography was not sensitive (32%), but was specific (92%). CONCLUSION: The intravenous use of gadobenate dimeglumine, at a bolus dose of 0.05 mmol/kg, is safe in patients with an acute MI. Dynamic contrast enhanced MR imaging has moderate sensitivity and high specificity for demonstrating infarct.     

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.