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.     

Contrast-enhanced MR Angiography of the renal arteries: blinded multicenter crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine

PURPOSE: To prospectively and intraindividually compare 0.1 mmol/kg gadobenate dimeglumine with 0.2 mmol/kg gadopentetate dimeglumine for contrast material-enhanced magnetic resonance (MR) angiography of the renal arteries. MATERIALS AND METHODS: Institutional review board approval was granted by each of three participating centers. The study accorded with international standards for good clinical practice and Declaration of Helsinki and subsequent amendments. Patients gave written informed consent before enrollment. Patients (n = 34) underwent two MR angiographic examinations more than 48 hours but less than 12 days apart. Gadobenate dimeglumine followed by gadopentetate dimeglumine was administered in 18 patients; the order of administration was reversed in 16 patients. A 1.5-T MR imager was used with a phase-encoded three-dimensional spoiled breath-hold pulse sequence. Two blinded independent readers qualitatively assessed randomized subtracted maximum intensity projection images. A three-point scale for diagnostic quality (0, poor; 1a or 1p, moderate; and 2a or 2p, adequate [a and p refer, respectively, to absence and presence of vascular lesions]) was used to score each of nine segments of the abdominal aorta and both renal arteries (possible overall score, 18). Quantitative assessment (vessel signal-to-noise ratio [SNR], vessel-muscle contrast-to-noise ratio [CNR]) of source images was performed for regions of interest in supra-, juxta-, and infrarenal aorta segments and psoas muscle. Data were tested with analysis of variance for two-period crossover design. Interreader agreement was evaluated with Cohen kappa statistics. RESULTS: No difference in mean image quality between the two contrast agents was observed; scores for gadobenate dimeglumine and gadopentetate dimeglumine were 15.15 and 15.23 for reader 1 and 16.77 and 17.01 for reader 2. The order of contrast material administration likewise produced no quality differences: readers 1 and 2 reported scores of 14.4 +/- 4.2 (standard deviation) and 16.7 +/- 2.3, respectively, when gadobenate dimeglumine was given first, and 15.2 +/- 1.8 and 16.6 +/- 1.6, respectively, when gadopentetate dimeglumine was given first. Results of quantitative evaluation showed increasing SNR and CNR with gadobenate dimeglumine in segments at progressively lower levels of the aorta, but increases in SNR and CNR at the infrarenal aorta (48.3 vs 40.6 and 44.2 vs 36.4, respectively) were not significant (P = .05 for both). CONCLUSION: Gadobenate dimeglumine at a dose of 0.1 mmol/kg is comparable to gadopentetate dimeglumine at 0.2 mmol/kg for contrast-enhanced renal MR angiography.     

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.     

Breast lesion detection and characterization at contrast-enhanced MR mammography: gadobenate dimeglumine versus gadopentetate dimeglumine

PURPOSE: To prospectively and intraindividually compare equivalent (0.1 mmol per kilogram of body weight) doses of gadobenate dimeglumine and gadopentetate dimeglumine for accuracy of detection and characterization of breast lesions at contrast material-enhanced magnetic resonance (MR) mammography. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Twenty-six consecutive women (mean age, 47.8 years) suspected of having a breast tumor at mammography and sonography underwent two identical MR examinations at 1.5 T; examinations were separated by more than 48 hours but less than 72 hours. A T1-weighted three-dimensional gradient-echo sequence was used, and images were acquired before and at 0, 2, 4, 6, and 8 minutes after randomized injection of gadopentetate dimeglumine or gadobenate dimeglumine at an identical flow rate of 2 mL/sec. Separate and combined assessment of unenhanced, contrast-enhanced, and subtracted images was performed blindly by two readers in consensus. Accuracy for lesion detection was determined against a final diagnosis based on findings at conventional mammography, sonography, and surgery. Sensitivity, specificity, positive and negative predictive values, and overall accuracy for malignant lesion identification were determined against histologic results. Data were analyzed with the McNemar test, proportional odds models, and analysis of variance. RESULTS: MR mammography with gadobenate dimeglumine depicted significantly (P = .003) more lesions (45 of 46) than did that with gadopentetate dimeglumine (36 of 46), and detected lesions were significantly (P < .001) more conspicuous with gadobenate dimeglumine. Confidence for characterization was significantly (P = .031) greater with gadobenate dimeglumine. Comparison of the contrast agents for their ability to help identify malignant lesions revealed significant (P = .02) superiority for gadobenate dimeglumine: Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for malignant lesion identification were, respectively, 94.7%, 100%, 100%, 80.0%, and 95.6% with gadobenate dimeglumine and 76.3%, 100%, 100%, 47.1%, and 80.4% with gadopentetate dimeglumine. Quantitative evaluation of signal intensity-time curves revealed significantly (P < .001) greater lesion enhancement with gadobenate dimeglumine. CONCLUSION: Detection of breast lesions and accurate identification of malignant lesions at MR imaging are significantly superior with gadobenate dimeglumine in comparison with gadopentetate dimeglumine.     

Gadobenate dimeglumine-enhanced MR angiography of the abdominal aorta and renal arteries

OBJECTIVE: This study was conducted to determine the efficacy and safety of four different doses of gadobenate dimeglumine for contrast-enhanced three-dimensional MR angiography of the abdominal aorta and renal arteries. SUBJECTS AND METHODS: Ninety-four patients with suspected abnormality of the abdominal aorta or renal arteries underwent unenhanced three-dimensional gradient-recalled echo time-of-flight MR angiography and contrast-enhanced MR angiography after the IV injection of one of four doses of gadobenate dimeglumine (0.025, 0.05, 0.1, and 0.2 mmol/kg of body weight). Efficacy was assessed on-site and by two blinded off-site reviewers in terms of change in total diagnostic quality score and diagnostic quality score per vessel segment from baseline unenhanced time-of-flight MR angiography to contrast-enhanced MR angiography. Secondary efficacy end points included lesion count and level of confidence in lesion characterization. Safety assessments comprised adverse event monitoring, physical evaluation, vital signs, ECG, and laboratory investigations. RESULTS: A significant change in the total diagnostic quality score from unenhanced to contrast-enhanced MR angiography was observed at all doses. The change increased with increased dose, plateauing at the 0.1 mmol/kg dose level. More patients with lesions detected and increased reviewer confidence for lesion characterization were noted on contrast-enhanced MR angiography compared with unenhanced MR angiography, although no dose-related trends were observed. All doses were well tolerated, and no significant changes in safety parameters were observed. CONCLUSION: Gadobenate dimeglumine is an effective and safe agent for contrast-enhanced MR angiography of the abdominal aorta and renal arteries. A dose of 0.1 mmol/kg of body weight appears to be the most suitable.     

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.     

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.     

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.     

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.     

Phase II double-blind, dose-ranging clinical evaluation of gadobenate dimeglumine in focal liver lesions: with analysis of liver and kidney signal change on early and delayed imaging

To evaluate the effect of contrast dose using gadobenate dimeglumine, 30 patients with focal liver lesions documented by computed tomography or ultrasound were studied by magnetic resonance imaging at 1.5 T. Patients received one of four doses of gadobenate dimeglumine (0.025, 0.05, 0.1, or 0.2 mmol/kg) or saline. The order of dosage was randomized, with both the physician and patient blinded to the administered dose. Scans were obtained before, immediately following injection, and after 80 minutes of delay. Enhancement effects were quantified by region of interest measurements. Films were also reviewed in a randomized prospective fashion by an abdominal radiologist blinded to contrast dose and diagnosis. Higher doses led to a statistically significant improvement in enhancement of normal liver, both on immediate (P = 0.01 for the comparison of 0.1 and 0.2 mmol/kg immediately post-contrast) and delayed scans (P = 0.003 for the same comparison). Liver-lesion contrast-to-noise ratio also increased with dose, although results for most comparisons by dose were not statistically significant. Scans following gadobenate dimeglumine injection were judged to provide additional diagnostic confidence sufficient to affect patient management in 10 of 24 cases. In seven cases this information was provided by dynamic scans, in one case by delayed scans, and in two cases by both dynamic and delayed scans. In 2 of the 10 cases the dose was 0.025 mmol/kg, in 2 cases 0.05 mmol/kg, in 3 cases 0.1 mmol/kg, and in 3 cases 0.2 mmol/kg. Gadobenate dimeglumine is effective for imaging of focal liver lesions at a range of doses, with trends toward improved diagnostic information at higher doses.     

Contrast enhancement of central nervous system lesions: multicenter intraindividual crossover comparative study of two MR contrast agents

PURPOSE: To prospectively compare gadobenate dimeglumine with gadopentetate dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance (MR) imaging of central nervous system (CNS) lesions. MATERIALS AND METHODS: This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test. RESULTS: Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P < .0001). Significant (P < .0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P < .001) in patients with intraaxial and extraaxial lesions. CONCLUSION: Gadobenate compared with gadopentetate at an equivalent dose provides significantly better enhancement and diagnostic information for CNS MR imaging.     

Gadobenate dimeglumine-enhanced magnetic resonance angiography of the pelvic arteries

RATIONALE AND OBJECTIVES: To evaluate 4 doses of gadobenate dimeglumine (Gd-BOPTA) for contrast-enhanced magnetic resonance angiography (CE-MRA) of the pelvic arteries and to compare CE-MRA with unenhanced time-of-flight MRA (2D-TOF-MRA). METHODS: A multicenter Phase II dose-finding study was performed in 136 patients with Gd-BOPTA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg bodyweight. Evaluation of CE-MRA images and comparison with 2D-TOF-MRA images was performed onsite and by 2 blinded offsite reviewers in terms of subjective image quality, number of lesions detected, and confidence in lesion characterization. RESULTS: Significant (P < 0.05) improvements over unenhanced findings were observed for CE-MRA at all dose levels. For reviewer 1 and the onsite investigators, the overall image quality increased up to a dose of 0.1 mmol/kg and then plateaued. For reviewer 2, increased image quality was noted up to a dose of 0.2 mmol/kg. Significant (P < 0.005) increases in diagnostic confidence on CE-MRA versus unenhanced MRA was observed for all dose groups by reviewer 1 and the onsite investigators and for the 0.1 and 0.2 mmol/kg dose groups by reviewer 2. No serious adverse events were recorded that were attributable to the study drug and no trends in laboratory parameters, vital signs, or electrocardiogram recordings were observed. CONCLUSIONS: Gadobenate dimeglumine-enhanced MRA is safe and significantly more effective than unenhanced 2D-TOF-MRA for imaging the pelvic arteries. A dose of 0.1 mmol/kg appears the most appropriate dose for subsequent Phase III clinical evaluation.     

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.     

Dynamic gadolinium-enhanced echo-planar MR imaging of the liver: Effect of pulse sequence and dose on enhancement

To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine—enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1, 0.2, and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine—enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine—enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization.     

Multicenter,double‐blind,randomized, intra‐individual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine in MRI of brain tumors at 3 tesla

Purpose

To prospectively compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast‐enhanced MRI of brain lesions at 3 Tesla (T).

Materials and Methods

Forty‐six randomized patients underwent a first examination with gadobenate dimeglumine (n = 23) or gadopentetate dimeglumine (n = 23) and then, after 2–7 days, a second examination with the other agent. Contrast administration (volume, rate), sequence parameters (T1wSE; T1wGRE), and interval between injection and image acquisition were identical for examinations in each patient. Three blinded neuroradiologists evaluated images qualitatively (lesion delineation, lesion enhancement, global preference) and quantitatively (lesion‐to‐brain ratio [LBR], contrast‐to‐noise ratio [CNR], % lesion enhancement). Differences were assessed using Wilcoxon's signed‐rank test. Reader agreement was determined using kappa (κ) statistics.

Results

There were no demographic differences between groups. The three readers preferred gadobenate dimeglumine globally in 22 (53.7%), 21 (51.2%), and 27 (65.9%) patients, respectively, compared with 0, 1, and 0 patients for gadopentetate dimeglumine. Similar significant (P < 0.001) preference was expressed for lesion border delineation and enhancement. Reader agreement was consistently good (κ = 0.48–0.64). Significantly (P < 0.05) higher LBR (+43.5– 61.2%), CNR (+51.3–147.6%), and % lesion enhancement (+45.9–49.5%) was noted with gadobenate dimeglumine.

Conclusion

Brain lesion depiction at 3T is significantly improved with 0.1 mmol/kg gadobenate dimeglumine. J. Magn. Reson. Imaging 2009;29:760–767. © 2009 Wiley‐Liss, Inc.     

Gadobenate dimeglumine-enhanced MR angiography: Diagnostic performance of four doses for detection and grading of carotid, renal, and aorto-iliac stenoses compared to digital subtraction angiography

PURPOSE: To determine the diagnostic performance of contrast-enhanced MR angiography (CE-MRA) with four doses of gadobenate dimeglumine for detection of significant steno-occlusive disease of the carotid, renal, and pelvic vasculature. MATERIALS AND METHODS: Eighty-four patients with suspected disease of the renal (n = 16), pelvic (n = 41), or carotid (n = 27) arteries underwent CE-MRA (3D-spoiled gradient-echo sequences) at 1.5T. CE-MRA was performed with gadobenate dimeglumine at 0.025, 0.05, 0.1, or 0.2 mmol/kg (23, 24, 19, and 18 patients, respectively) administered at 2 mL/sec. Accuracy, sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) for detection of significant disease (>50% stenosis or occlusion for renal/pelvic arteries; >70% stenosis or occlusion for carotid arteries) was determined by three fully blinded, independent radiologists using conventional digital subtraction angiography (DSA) as reference standard. All comparisons were tested statistically (ANOVA, chi-square, and Mantel-Haenszel tests as appropriate) and reader agreement (kappa) was assessed. RESULTS: Values for accuracy, sensitivity, specificity, PPV, and NPV on CE-MRA were consistently higher for 0.1 mmol/kg gadobenate dimeglumine (accuracy = 95.2-97.3%, sensitivity = 84.2% (all readers), specificity = 96.9-99.2%, PPV = 80.0-94.1%, NPV = 97.6-97.7%). The greater accuracy of the 0.1 mmol/kg dose was significant (P < 0.01, all readers) compared to all other dose groups. Agreement between the three readers was good for all dose groups (kappa >/=0.58), with the highest percent agreement (85.7%) noted for the 0.1 mmol/kg dose. CONCLUSION: Significantly better diagnostic performance on CE-MRA of the renal, pelvic, and carotid arteries is achieved with a gadobenate dimeglumine dose of 0.1 mmol/kg bodyweight.     

MR evaluation of CNS tumors: dose comparison study with gadopentetate dimeglumine and gadoteridol

In phase II and III trials of gadoteridol (Gd-HP-D03A), a new nonionic, low-osmolar contrast agent, 40 patients with intracranial neoplasms underwent magnetic resonance (MR) imaging with experimental doses of 0.05-0.3 mmol/kg. Fifteen patients also underwent contrast studies with the standard dose (0.1 mmol/kg) of gadopentetate dimeglumine. Both gadopentetate dimeglumine and gadoteridol appear to have a similar effect when given in equal doses (0.1 mmol/kg, n = 5). Lesion enhancement and delineation were better at higher experimental doses (0.2 or 0.3 mmol/kg, n = 7) and worse at a lower experimental dose (0.05 mmol/kg, n = 3). Quantitative analysis of 10 lesions examined with identical imaging protocols revealed a directly proportional relationship (r = .975) between lesion contrast ratio and dose over a range of 0.05-0.3 mmol/kg. Phantom experiments support the clinical results. Improved enhancement, detection, and delineation of central nervous system (CNS) neoplasms resulting from increased injected doses of gadoteridol have the potential to be clinically significant and may justify the possibly higher cost of increased contrast material dosage. Lower doses may not be adequate for the evaluation of most CNS tumors.     

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 (Gd-DTPA) vs gadopentetate dimeglumine (Gd-BOPTA) for contrast-enhanced magnetic resonance angiography (MRA): improvement in intravascular signal intensity and contrast to noise ratio

PURPOSE: The purpose of this study was to compare contrast enhanced MR angiography (MRA) with gadopentetate dimeglumine (Gd-DTPA) to MRA with gadobenate dimeglumine (Gd-BOPTA), a high relaxivity paramagnetic contrast agent. MATERIALS AND METHODS: Twelve patients referred for carotid artery stenosis were examined with MR angiography using a fast spoiled gradient echo sequence. Gd-DTPA and Gd-BOPTA enhanced MR angiography were performed within 48-72 hours using a dose of 0.1 mmol/kg for Gd-BOPTA and 0.2 mmol/kg for Gd-DTPA, at a flow rate of 2 ml/s. Images were evaluated by two blinded radiologists. Qualitative and quantitative evaluations were performed comparing the sets of images from the two examinations. RESULTS: Qualitative evaluation demonstrated superior arterial contrast enhancement and vessel conspicuity with Gd-BOPTA compared with Gd-DTPA. Quantita-tive evaluation showed an improvement in both signal intensity and contrast to noise ratio with Gd-BOPTA. CONCLUSION: The greater relaxivity of Gd-BOPTA, at lower doses, compared with Gd-DTPA, provides higher intravascular signal and signal to noise ratio. Gd-BOPTA appears to be an optimal contrast agent for contrast enhanced MRA.