Intraindividual comparison of gadopentetate dimeglumine,gadobenate dimeglumine,and gadobutrol for pelvic 3D magnetic resonance angiography

RATIONALE AND OBJECTIVES: To compare the effect on image quality of a 1.0 mol/L gadolinium chelate with that of two 0.5 mol/L gadolinium compounds. MATERIALS AND METHODS: Five healthy volunteers underwent a mono-station 3D MRA exam (Siemens SONATA, Erlangen, Germany) four times using four separate gadolinium preparations. All subjects first received a fixed volume of undiluted gadobutrol (1 mol/L), which corresponded to a dose between 0.1 and 0.15 mmol/kg body weight. This gadobutrol dosage was then diluted with saline into twice the volume and administered as a bolus at twice the injection rate. For Gd-DTPA and Gd BOPTA, because these contrast agents are 0.5 mol/L preparations, the volume and flow rate were doubled to match diluted gadobutrol volume and concentration. Quantitative and qualitative analysis of the angiographic data sets was performed on nine arterial segments. RESULTS: Image quality was rated diagnostic for all image data sets without statistically significant differences between any of the compounds (P > 0.3). Quantitative measurements of Gd BOPTA (SNR: 81.15; CNR: 68.91) and both standard and diluted forms of gadobutrol (SNR: 84.33; CNR: 71.62; SNR(diluted): 79,23; CNR(diluted): 66.26) yielded significantly higher results (P < 0.02) in comparison with Gd-DTPA (SNR: 49.55; CNR: 38.24). The difference between either form of gadobutrol and Gd BOPTA was not shown to be statistically significant (P > 0.3), whereas both the SNR and CNR of standard gadobutrol were significantly higher than diluted gadobutrol. CONCLUSION: Gadobutrol- and Gd BOPTA-MRA exams lead to improved delineation of the pelvic arterial morphology compared with MRA exams performed with Gd-DTPA.     

Comparison of gadobenate dimeglumine with gadopentetate dimeglumine for magnetic resonance imaging of liver tumors

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for magnetic resonance imaging of the liver. METHODS: The contrast agent Gd-BOPTA or Gd-DTPA was administered at a dose of 0.1 mmol/kg to 257 patients suspected of having malignant liver tumors. Dynamic phase images, spin-echo images obtained within 10 minutes of injection, and delayed images obtained 40 to 120 minutes after injection were acquired. All postcontrast images were compared with unenhanced T1-weighted and T2-weighted images obtained immediately before injection. A full safety assessment was performed. RESULTS: The contrast efficacy for dynamic phase imaging was moderately or markedly improved in 90.9% (110/121) and 87.9% (109/124) of patients for Gd-BOPTA and Gd-DTPA, respectively. At 40 to 120 minutes after injection, the cor- responding improvements were 21.7% (26/120) and 11.6% (14/121) for spin-echo sequences and 44.5% (53/119) and 19.0% (23/121) for breath-hold gradient-echo sequences, respectively. The differences at 40 to 120 minutes after injection were statistically significant (P < 0.02). Increased information at 40 to 120 minutes after injection compared with information acquired within 10 minutes of injection was available for 24.0% (29/121) of patients with Gd-BOPTA and for 14.5% (18/124) of patients with Gd-DTPA (P < 0.03). Adverse events were seen in 4.7% (6/128) and 1.6% (2/127) of patients receiving Gd-BOPTA and Gd-DTPA, respectively. The difference was not statistically significant. CONCLUSIONS: The efficacy of Gd-BOPTA is equivalent to that of Gd-DTPA for liver imaging during the dynamic phase and superior during the delayed (40-120 minutes) phase of contrast enhancement. Both agents are safe for use in magnetic resonance imaging of the liver.     

Low-dose gadobenate dimeglumine versus standard-dose gadopentate dimeglumine for delayed contrast-enhanced cardiac magnetic resonance imaging

RATIONALE AND OBJECTIVES: The purpose of our study was to compare gadopentate dimeglumine (Gd-DTPA) and gadobenate dimeglumine (Gd-BOPTA) for the evaluation of myocardial infarction (MI) and in the grading transmural extent on late-contrast enhanced cardiac magnetic resonance imaging. MATERIALS AND METHODS: Twenty-three patients with clinically proven MI were examined with the use of 0.2 mmol/kg Gd-DTPA and 0.1 mmol/kg Gd-BOPTA in 2 days interval. All patients were examined with the use of segmented two-dimensional inversion-recovery turbo fast-field echo pulse sequence with an inversion time 210-300 milliseconds. Fifteen minutes time delay was used on both examinations after the injection of contrast agent. Contrast-to-noise ratio between normal myocardium and infarcted myocardium and signal intensity ratio (SIR) of the enhanced myocardium to blood pool was derived and compared for each contrast agent. RESULTS: A total of 61 infarcted segments were analyzed. All of the infarcted segments were visualized on both Gd-BOPTA and Gd-DTPA enhanced images. There was statistically no significant difference between 0.2 mmol/kg Gd-DTPA and 0.1 mmol/kg Gd-BOPTA in the mean contrast-to-noise ratio (10.19 versus 10.22; P = .96), SNR (14.29 versus 14.25; P = .96), and SIR (4.34 versus 4.21; P = .38) of the infarcted segments. Intraobserver agreement (kappa) between Gd-DTPA and Gd-BOPTA were R1 = 91% and R2 = 86%. Interobserver agreements between the readers were Gd-DTPA = 85% and Gd-BOPTA = 88%. CONCLUSION: According to our data, the diagnostic efficacy of 0.1 mmol/kg dose Gd-BOPTA is equivalent to that of 0.2 mmol/kg Gd-DTPA for the assessment of MI on delayed enhanced magnetic resonance images.     

Low-dose gadobenate dimeglumine versus standard dose gadopentetate dimeglumine for contrast-enhanced magnetic resonance imaging of the liver: an intra-individual crossover comparison

RATIONALE AND OBJECTIVES: Gadobenate dimeglumine (Gd-BOPTA) has a two-fold higher T1 relaxivity compared with gadopentetate dimeglumine (Gd-DTPA) and can be used for both dynamic and delayed liver MRI. This intraindividual, crossover study was conducted to compare 0.05 mmol/kg Gd-BOPTA with 0.1 mmol/kg Gd-DTPA for liver MRI. MATERIALS AND METHODS: Forty-one patients underwent two identical MR examinations separated by >or= 72 hours. Precontrast T1-FLASH-2D and T2-TSE sequences and postcontrast T1-FLASH-2D sequences were acquired during the dynamic and delayed (1-2 hours) phases after each contrast injection. Images were evaluated on-site by two independent, blinded off-site readers in terms of confidence for lesion detection, lesion number, character and diagnosis, enhancement pattern, lesion-to-liver contrast, and benefit of dynamic and delayed scans. Additional on-site evaluation was performed of the overall diagnostic value of each agent. RESULTS: Superior diagnostic confidence was noted by on-site investigators and off-site assessors 1 and 2 for 6, 4 and 2 patients with Gd-BOPTA, and for 3, 1 and 2 patients with Gd-DTPA, respectively. No consistent differences were noted for other parameters on dynamic phase images whereas greater lesion-to-liver contrast was noted for more patients on delayed images after Gd-BOPTA. More correct diagnoses of histologically confirmed lesions (n = 26) were made with the complete Gd-BOPTA image set than with the complete Gd-DTPA set (reader 1: 68% vs. 59%; reader 2: 78% vs. 68%). The overall diagnostic value was considered superior after Gd-BOPTA in seven patients and after Gd-DTPA in one patient. CONCLUSION: The additional diagnostic information on delayed imaging, combined with the possibility to use a lower overall dose to obtain similar diagnostic information on dynamic imaging, offers a distinct clinical advantage for Gd-BOPTA for liver MRI.     

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.     

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.     

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.     

Intraindividual comparison of gadobenate dimeglumine and gadobutrol for cerebral magnetic resonance perfusion imaging at 1.5 T

RATIONALE AND OBJECTIVE: The objective of this study was to compare 0.1 and 0.2 mmol/kg body weight (bw) doses gadobenate dimeglumine (Gd-BOPTA; MultiHance) and gadobutrol (Gd-BT-DO3A; Gadovist) for cerebral perfusion magnetic resonance (MR) imaging at 1.5 T. METHODS: Twelve healthy male volunteers enrolled into a randomized intraindividual comparative study underwent 4 perfusion MR imaging examinations with 0.1 and 0.2 mmol/kg bw doses of each contrast agent. The imaging parameters, slice positioning, and contrast agent application were highly standardized. Quantitative determinations based on signal intensity/time (SI/T) curves at regions of interest (ROI) on the gray and white matter were made of the regional cerebral blood volume and flow (rCBV and rCBF, respectively), the percentage signal drop, and the full width half maximum (FWHM) of the SI/T curve. Qualitative evaluation of the quality of the rCBV and rCBF maps was assessed by an independent offsite blinded reader. RESULTS: A single dose of both agents was sufficient to achieve high-quality, diagnostically valid perfusion maps at 1.5 T, and no significant benefit for one agent over the other was noted for quantitative or qualitative determinations. The susceptibility effect, described by percentage of signal loss (gadobutrol: 29.4% vs gadobenate dimeglumine: 28.3%) and the FWHM (gadobutrol: 6.4 seconds vs gadobenate dimeglumine: 7.0 seconds) were similar for 0.1 mmol/kg bw doses of the 2 agents. Double doses of the 2 agents produced better overall image quality but no clinical benefit over the single-dose examinations. CONCLUSION: Both the 1 molar MR contrast agent gadobutrol and the weak protein-interacting agent gadobenate dimeglumine permit the acquisition of high-quality perfusion maps at doses of 0.1 mmol/kg bw. The susceptibility effect is comparable for both agents and stronger than for conventional MR contrast agents.     

Gadobenate dimeglumine (MultiHance) for magnetic resonance angiography: review of the literature

Although limited in number, reports describing the use of Gd-BOPTA for 3D CE-MRA reveal that this agent is safe, well tolerated and effective for CE-MRA at doses up to 0.3 mmol/kg bodyweight. The use of Gd-BOPTA leads to additional diagnostically relevant information comparable to that attainable with conventional DSA and superior to that on non-enhanced MRA in most arterial territories. In studies in which Gd-BOPTA is compared at equal dose with other gadolinium-based MR contrast agents, Gd-BOPTA has consistently shown significantly better quantitative and qualitative performance. Thus, Gd-BOPTA can be considered to have a very favorable risk/benefit ratio for MRA. In summary, it is likely the documented superiority of Gd-BOPTA for MR angiography will lead to its broad usage for this indication wherever the agent becomes available.     

Evaluation of a novel time-efficient protocol for gadobenate dimeglumine (Gd-BOPTA)-enhanced liver magnetic resonance imaging

OBJECTIVE: We sought to evaluate gadobenate dimeglumine for the detection and characterization of focal liver lesions in the unenhanced and already pre-enhanced liver. MATERIALS AND METHODS: Sixty patients were evaluated prospectively. Unenhanced T1-weighted gradient echo (T1wGRE) and T2-weighted turbo spin echo (T2wTSE) images were acquired followed by contrast-enhanced T1wGRE images during the dynamic, equilibrium, and delayed phases after the bolus injection of 0.05 mmol/kg gadobenate dimeglumine. An identical series of dynamic images was then acquired after the delayed scan following a second 0.05 mmol/kg bolus of gadobenate dimeglumine. Images were evaluated randomly in 2 sessions by 3 independent blinded readers. Evaluated images in the first session comprised the unenhanced images, the first or second set of dynamic images, and the delayed images. The second session included the unenhanced images, the dynamic images not yet evaluated in the first session, and the delayed images. The 2 reading sessions were compared for lesion characterization and diagnosis, and kappa (kappa) values for interobserver agreement were determined. Quantitative evaluation of lesion contrast enhancement was also performed. RESULTS: The enhancement behavior in the second dynamic series was similar to that in the first series, although pre-enhancement of the normal liver resulted in reduced lesion-liver contrast-to-noise ratios and the visualization of some lesions only on arterial phase images. Typical imaging features for the lesions included in the study were visualized clearly in both series. Strong agreement (kappa=0.56-0.89; all evaluations) between the 2 images sets was noted by all readers for differentiation of benign from malignant lesions and for definition of specific diagnosis, and between readers for diagnoses established based on images acquired in the unenhanced and pre-enhanced liver. CONCLUSION: Dynamic imaging in the hepatobiliary phase gives similar information as dynamic imaging of the unenhanced liver. This might prove advantageous for screening protocols involving same session imaging of primary extrahepatic tumors and liver.     

Optimization of contrast dosage for gadobenate dimeglumine-enhanced high-resolution whole-body 3D magnetic resonance angiography

RATIONALE AND OBJECTIVES: To determine the optimal dose of gadobenate dimeglumine for diagnostic high-resolution whole-body 3D-MR angiography. METHODS: Ten healthy volunteers were examined three times with an ascending dose of Gd-BOPTA (0.1/0.2/0.3 mmol/kg BW). Three-dimensional data sets were collected with a rolling table platform (AngioSURF; MR-Innovation GmbH, Essen, Germany) which integrates the torso surface coil, using a 3D FLASH sequence at five stations from carotid arteries to the trifurcation vessels in 72 seconds. SNR- and contrast-to-noise-values were calculated for 30 segments per patient. For qualitative evaluation a 4-point-visualization scale was used. RESULTS: Overall, significantly (P < 0.05) higher signal-to-noise values and CNR values were determined for Gd-BOPTA at a dose of 0.2 and 0.3 mmol/kg compared with 0.1 mmol/kg. Similarly, the qualitative analysis demonstrated image quality to be superior with 0.2 and 0.3 mmol/kg compared with 0.1 mmol/kg (P < 0.05). Qualitative and quantitative assessment failed to demonstrate a statistically significant difference between 0.2 and 0.3 mmol/kg BW (P > 0.05). CONCLUSION: A dose of 0.2 mmol/kg BW Gd-BOPTA rendered diagnostic image quality in all vascular segments of all volunteers.     

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.     

Magnetic resonance imaging of metastatic disease to the brain with gadobenate dimeglumine

Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.