Injection Of Gadobutrol Research Articles

Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5years.

To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (0.15mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. • Gadobutrol does not lead to neuronal signal alterations after 5years. • Neuronal deposition of macrocyclic contrast agent could not be confirmed. • Macrocyclic contrast agents in a proven dosage are safe.

Effect of steatosis on liver signal and enhancement on multiphasic contrast-enhanced magnetic resonance imaging

To investigate the effect of steatosis on liver signal and enhancement in multiphasic contrast-enhanced (MCE) MRI. In this IRB-approved, HIPAA-compliant, retrospective, observational study, 1217 MCE abdominal MRIs performed during 2014 at a single institution were reviewed. Of these, 1085 were excluded, due to potential factors other than steatosis that may affect liver signal intensity and/or enhancement. In the remaining 132, liver fat fraction (FF) was calculated from the in- and opposed-phase 2D T1-weighted images. Liver signal intensity, absolute enhancement, and relative enhancement on fat-suppressed (Dixon method) 3D T1-weighted images before and after injection of gadobutrol (arterial, portal venous, and equilibrium phases) were plotted against co-localized FF values and the linear trend was evaluated by Pearson correlation coefficient (r). P values <0.05 were considered statistically significant. Liver signal intensity negatively correlated with FF for all phases (r=-0.388 to -0.544, p<0.001). Absolute enhancement negatively correlated with FF for the portal venous and equilibrium phases (r=-0.286 and -0.289, respectively, p<0.001), but not for the arterial phase (r=-0.042, p=0.632). Relative enhancement did not significantly correlate with FF for any phase (p≥0.125). Steatosis reduces liver signal intensity in MCE MRI. This effect of steatosis was reduced in calculated absolute enhancement and eliminated in calculated relative enhancement.

Safety of gadobutrol in over 23,000 patients: the GARDIAN study, a global multicentre, prospective, non-interventional study

ObjectivesTo investigate the safety and tolerability of gadobutrol at the recommended dose in patients requiring contrast-enhanced magnetic resonance imaging/angiography (MRI/MRA) in the routine setting.MethodsGARDIAN prospectively enrolled 23,708 patients undergoing routine gadobutrol-enhanced MRI/MRA for approved indications at 272 study centres in Europe, Asia, North America, and Africa and monitored for adverse events.ResultsMedian gadobutrol dose was 0.11 mmol/kg body weight. The overall incidence of adverse drug reactions (ADRs) was 0.7 % (n = 170 patients), with similar incidences in patients with renal impairment or cardiac disease, from different geographic regions and in different gadobutrol dose groups. Patients at risk for contrast media reaction had an ADR incidence of 2.5 %. Five patients (0.02 %) experienced serious adverse events, four were drug-related. One patient experienced a fatal anaphylactoid shock, assessed to be related to injection of gadobutrol. The contrast quality of gadobutrol-enhanced images was rated by treating physicians as good or excellent in 97 % cases, with similar ratings in all patient subgroups and indications.ConclusionsThe GARDIAN study shows that gadobutrol at the recommended dose is well tolerated across a large, diverse patient population.Key points• Gadobutrol at recommended dose shows low rates of adverse drug reactions• Gadobutrol demonstrates a uniform safety profile across diverse patient groups• Gadobutrol provides excellent contrast quality in routine practice

The Efficacy of One Molar Contrast Material in the Evaluation of Breast Lesions with MR Imaging.

SummaryBackgroundTo investigate the efficacy of 1 molar (containing 1 mol/mL gadobutrol) contrast material in the differentiation of malignant and benign breast lesions with MRI.Material/MethodsThirty-seven women (age range: 22–77 years, mean: 43.7 years) with 76 breast lesions were included in this study. Dynamic post-contrast images with 0.2 mL/kg gadobutrol (Gadovist) injection were obtained in all patients. Contrast-to-noise-ratio (CNR) of the lesions, as well as their contrast enhancement patterns (ring, heterogeneous, homogenous), and perilesional increased vascularity were studied.ResultsFifty-six benign and 20 malignant lesions were examined histopathologically. In malignant cases, heterogeneous and peripheral enhancements were most commonly determined, whereas homogeneous enhancement was most commonly determined in benign cases. CNR was 450% in malignant lesions, and 60% in benign lesions.ConclusionsType II/III contrast-time curves, ring/heterogeneous enhancement, prominent increase in CNR, and perilesional vascularity increase are important findings determining malignancy, whereas Type I curves, homogenous enhancement, a slight increase in CNR, and absence of perilesional vascularity increase support findings of benign breast lesions. By increasing CNR and providing increased perilesional vascularity, Gadovist can help in the determination of malignant breast lesions.

Integrated 18F-FDG PET/MR imaging in the assessment of cardiac masses: a pilot study.

The objective of the present study was to evaluate whether integrated (18)F-FDG PET/MR imaging could improve the diagnostic workup in patients with cardiac masses. Twenty patients were prospectively assessed using integrated cardiac (18)F-FDG PET/MR imaging: 16 patients with cardiac masses of unknown identity and 4 patients with cardiac sarcoma after surgical therapy. All scans were obtained on an integrated 3-T PET/MR device. The MR protocol consisted of half Fourier acquisition single-shot turbo spin-echo sequence, cine, and T2-weighted images as well as T1-weighted images before and after injection of gadobutrol. PET data were acquired simultaneously with the MR scan after injection of 199 ± 58 MBq of (18)F-FDG. Patients were prepared with a high-fat, low-carbohydrate diet in a period of 24 h before the examination, and 50 IU/kg of unfractionated heparin were administered intravenously 15 min before (18)F-FDG injection. Cardiac masses were diagnosed as follows: metastases, 3; direct tumor infiltration via pulmonary vein, 1; local relapse of primary sarcoma after surgery, 2; Burkitt lymphoma, 1; scar/patch tissue after surgery of primary sarcoma, 2; myxoma, 4; fibroelastoma, 1; caseous calcification of mitral annulus, 3; and thrombus, 3. The maximum standardized uptake value (SUVmax) in malignant lesions was significantly higher than in nonmalignant cases (13.2 ± 6.2 vs. 2.3 ± 1.2, P = 0.0004). When a threshold of 5.2 or greater was used, SUVmax was found to yield 100% sensitivity and 92% specificity for the differentiation between malignant and nonmalignant cases. T2-weighted hyperintensity and contrast enhancement both yielded 100% sensitivity but a weak specificity of 54% and 46%, respectively. Morphologic tumor features as assessed by cine MR imaging yielded 86% sensitivity and 92% specificity. Consent interpretation using all available MR features yielded 100% sensitivity and 92% specificity. A Boolean 'AND' combination of an SUVmax of 5.2 or greater with consent MR image interpretation improved sensitivity and specificity to 100%. In selected patients, (18)F-FDG PET/MR imaging can improve the noninvasive diagnosis and follow-up of cardiac masses.

Evaluation of plaque detection and optimum time of enhancement in acute attack multiple sclerosis after contrast injection

Magnetic resonance imaging (MRI) is important in the early diagnosis of novel or relapsing multiple sclerosis (MS). In addition, the optimal MRI protocol plays an important role in detecting MS plaques. To find the best time to detect MS plaques on MRI after Gadobutrol injection. Sixty-two relapsing-remitting type MS patients, (56 women, 6 men) with the mean age of 31 ± 7 years were enrolled into this study. The patients underwent T1-weighted MRI scan without contrast agents. Subsequently, Gadobutrol was injected (0.1 mmol/kg) and MRI scanning was repeated after 30 s, 5, 10, 15, and 30 min of Gadobutrol injection. The size, signal intensity, and enhancement pattern were determined for each plaque by contrast-enhanced T1-weighted images. Enhancing plaques were seen in 42 out of 62 patients. The mean number of enhancing plaques was 4 ± 8 plaques after 30 s of contrast injection. This figure increased to 7 ± 13 plaques after 15 min and 6 ± 10 plaques after 30 min. The signal intensity and size of plaques increased progressively, and the maximum signal intensity and plaque size were seen after 30 min (P < 0.001). The maximum number of enhancing plaques in MS patients was detected 15 min after contrast agent administration and the size and signal intensity of the lesions also increased remarkably at this time.

Effect of Imaging Time in the Magnetic Resonance Detection of Intracerebral Metastases Using Single Dose Gadobutrol

ObjectiveTo compare the effect of imaging time delay on the MR detection of intracerebral metastases using single dose gadobutrol.Materials and MethodsTwenty-one patients with intracerebral metastases underwent contrast-enhanced MR with three-dimensional T1-weighted sequence at 1 minute, 5 minutes and 10 minutes after a single dose injection of gadobutrol. One hundred index metastatic lesions (1 to 30 mm; median, 7 mm) were chosen for the analysis. For the qualitative analysis, lesion conspicuity were assessed on a 1 (worst) to 5 (best) scale of the index lesions by an expert reader. For the quantitative analysis, signal intensity (SI) of enhancing lesions and normal parenchyma was measured to determine the contrast rate (CR, %) ([postcontrast SI lesion - postcontrast SI white matter] × 100 / postcontrast SI white matter) and the enhancement rate (ER, %) ([postcontrast SI lesion - baseline SI gray matter] × 100 / baseline SI gray matter). Statistical comparisons were made between three different time delays.ResultsLesion conspicuity did not differ significantly among the three time delays (p = 0.097). Although the SI, CR and ER of lesions did not reveal any significant difference between 1 minute and 5 minutes delayed images, both the 1 minute and 5 minutes delayed images showed significantly higher CRs of lesions compared with the 10 minutes delayed images (p = 0.004 and p = 0.001, respectively).ConclusionWith single dose gadobutrol, imaging time delay did not have an effect on lesion conspicuity. Both 1-minute and 5-minute-delayed imaging after gadobutrol injection appears to be effective for the detection of intracerebral metastases.

Self-navigated free-breathing isotropic 3D whole heart MRI for the characterization of complex cardiac anatomy in patients with congenital heart malformations

Introduction: Cardiac anatomy of patients with congenital heart disease (CHD) is often complex and accurate evaluation mandates MR image acquisition in several non-standardized planes requiring considerable operator involvement and multiple breath-holds. The utility of self-navigated isotropic 3D-free-breathing whole-heart MRI (SN-3D) was assessed for the visualization of the heart, coronary arteries (CA) and great vessels (GV) in CHD patients. Methods: Data acquisition was performed during free breathing on a 1.5T-MRI scanner with a 3D-radial trajectory modified for respiratory self-navigation after gadobutrol injection; it was ECG-triggered, with a T2-preparation pulse and fat-saturated SSFP readout. The isotropic image data were reformatted offline. Image quality was graded and GV diameters were measured at several levels in all patients. 3D MR-angiography (MRA) was performed in a subset of patients and the GV diameters were also measured for comparison. Results: 38 patients (66% male, age 23±10y) were included. Heart rate was 71±13 bpm, scan duration 9.1±4.2 min, isotropic resolution 1.1×1.1×1.1 mm3. Image quality was good in 23, moderate in 10, mediocre in 2, and poor in 3. 3D datasets allowed the assessment of the arrangement of heart chambers and great vessels, the venous return anatomy after atrial switch for transposition of the great arteries (TGA), the morphology of cavo-pulmonary connections after Fontan operation, the morphology of the pulmonary arteries in tetralogy of Fallot or morphology of the great vessels after arterial switch for TGA. GV diameters with SN-3D were accurate using conventional MRA as the gold standard (n=25, r2=0.91, bias 0.1±2.2 mm), with a low intra- and inter-observer variability (3.7% and 5.4%). Moreover, the proximal 3 cm of the CA could be well visualized and its 3D course followed in most of the patients with moderate or good image quality (n=33: LAD 97%, LCx 73%, RCA 91%), making SN-3D useful to detect anomalous CA. Conclusion: The SN-3D methodology enables time-efficient whole-heart coverage during free breathing. The high isotropic resolution supports multi-planar offline reformatting in any plane orientation, which is particularly useful in CHD patients with complex anatomy. Self-navigation and the absence of fold-over artifacts enhance the ease of use and favor a fast acquisition planning. Reformatted images allow accurate measurement of the GV, and even small anatomical structures could be precisely identified illustrating the potential of this methodology to assess the anatomy of the proximal course of CA.

MRI assessment of experimental gliomas using 17.6 T

Using ultra-high-field contrast-enhanced magnetic resonance imaging (MRI), an increase of field strength is associated with a decrease of T 1 relaxivity. Yet, the impact of this effect on signal characteristics and contrast-enhanced pathology remains unclear. Hence, we evaluated the potential of a 17.6-T MRI to assess contrast-enhancing parts of experimentally induced rat gliomas compared to 3 T. A total of eight tumor-bearing rats were used for MRI assessments either at 17.6 T (four rats) or at 3 T (four rats) at 11 days after stereotactic implantation of F98 glioma cells into the right frontal lobe. T 1-weighted sequences were used to investigate signal-to-noise-ratios, contrast-to-noise-ratios, and relative contrast enhancement up to 16 min after double-dose contrast application. In addition, tumor volumes were calculated and compared to histology. The 17.6-T-derived contrast-enhancing volumes were 31.5 ± 15.4 mm(3) at 4 min, 38.8 ± 12.7 mm(3) at 8 min, 51.1 ± 12.6 mm(3) at 12 min, and 61.5 ± 10.8 mm(3) at 16 min after gadobutrol injection. Corresponding histology-derived volumes were clearly higher (138.8 ± 8.4 mm(3); P < 0.01). At 3 T, contrast-enhancing volumes were 85.2 ± 11.7 mm(3) at 4 min, 107.3 ± 11.0 mm(3) at 8 min, 117.0 ± 10.5 mm(3) at 12 min, and 129.1 ± 10.0 mm(3) at 16 min after contrast agent application. Averaged histology-derived volumes (139.1 ± 13.4 mm(3)) in this group were comparable to the 16-min volume (P ↔16 min = 0.38). Compared to ultra-high-field MRI, all 3-T-derived volumes were significantly higher (P < 0.02). Compared to 3-T-derived images and histology, tumor volumes were underestimated by approximately 50 % at 17.6 T. Hence, contrast-enhanced 17.6-T MRI provided no further benefits in tumor measurement compared to 3 T.

Safety and efficacy of gadobutrol-enhanced MRI in patients aged under 2 years-a single-center, observational study.

Gadobutrol is a 1-molar gadolinium-based contrast agent with well-characterized safety and efficacy for magnetic resonance imaging (MRI) in adults and children ≥ 2 years old. This observational study assessed gadobutrol-enhanced MRI in children < 2 years of age. Sixty infants (mean age 11.1 months) underwent MRI using gadobutrol at standard dose of 0.1 mL/kg (0.1 mmol/kg) body weight. MRI examinations included brain, spine, and neck (n = 24), subcutaneous soft tissues (n = 14), chest, abdomen, and pelvis (n = 12), musculoskeletal system (n = 7) and vascular system (n = 3). No patients experienced adverse events related to gadobutrol injection. In 57 patients with confirmed diagnoses, gadobutrol-enhanced MRI provided findings consistent with confirmed pathologies. This study indicates that gadobutrol at a standard dose for MRI is safe in patients aged < 2 years and provides diagnostic information for multiple pathologies.

Contrast enhancement kinetics of normal breast parenchyma in dynamic MR mammography: effects of menopausal status, oral contraceptives, and postmenopausal hormone therapy

To investigate effects of menopausal status, oral contraceptives (OC), and postmenopausal hormone therapy (HT) on normal breast parenchymal contrast enhancement (CE) and non-mass-like enhancing areas in magnetic resonance mammography (MRM). A total of 459 female volunteers (mean age 49.1 ± 12.5 years) underwent T1-weighted 3D MRM 1-5 min after bolus injection of gadobutrol. Quantitative analysis was performed in normal breast parenchyma by manually tracing regions of interest and calculating percentage CE. Semiquantitative analysis was performed in non-mass-like enhancing areas, and signal intensity changes were characterised by five predefined kinetic curve types. The influence of OC (n = 69) and HT (n = 24) on CE was studied using random effects models. Breast parenchymal enhancement was significantly higher in premenopausal than in postmenopausal women (P < 0.001). CE decreased significantly with the use of OC (P = 0.01), while HT had negligible effects (P = 0.52). Prevalence of kinetic curve types of non-mass-like enhancement differed strongly between pre- and postmenopausal women (P < 0.0001), but was similar in OC users and non-OC users (P = 0.61) as well as HT users and non-HT users (P = 0.77). Normal breast parenchymal enhancement and non-mass-like enhancing areas were strongly affected by menopausal status, while they were not affected by HT use and only moderately by OC use. Breast parenchymal enhancement at MR mammography is stronger in premenopausal than postmenopausal women. The prevalence of strong enhancing non-mass-like areas is greater before menopause. Such enhancing non-mass-like areas may impair lesion detection in premenopausal women. Breast parenchymal enhancement is only marginally affected by hormone use. Discontinuation of hormone use before MR mammography may be unnecessary.

Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease

ObjectivesTo prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. MethodsPatients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of gadobutrol, single shot fast spin echo sequence and 3D T1-weighted spoiled gradient echo sequence, a dynamic coronal 3D T1-weighted fast spoiled gradient were performed before and after gadobutrol. Maximum enhancement (ME) and initial slope of increase (ISI) were calculated for four colon segments (ascending colon+coecum, transverse colon, descending colon+sigmoid, rectum) and (neo)terminal ileum. C-reactive protein (CRP), Crohn's disease activity index (CDAI), per patient and per segment Crohn's disease endoscopic index of severity (CDEIS) and disease duration were determined. Mean values of the (DCE-)MRI parameters in each segment from each patient were compared between four disease activity groups (normal mucosa, non-ulcerative lesions, mild ulcerative and severe ulcerative disease) with Mann–Whitney test with Bonferroni adjustment. Spearman correlation coefficients were calculated for continuous variables. ResultsThirty-three patients were included (mean age 37 years; 23 females, median CDEIS 4.4). ME and ISI correlated weakly with segmental CDEIS (r=0.485 and r=0.206) and ME per patient correlated moderately with CDEIS (r=0.551). ME was significantly higher in segments with mild (0.378) or severe (0.388) ulcerative disease compared to normal mucosa (0.304) (p<0.001). No ulcerations were identified at conventional sequences. ME correlated with disease duration in diseased segments (r=0.492), not with CDAI and CRP. ConclusionsDCE-MRI can be used as a method for detecting Crohn's disease ulcerative lesions.

Intraindividual Comparison of Gadobutrol and Gadopentetate Dimeglumine for Detection of Myocardial Late Enhancement in Cardiac MRI

Gadobutrol is an extracellular macrocyclic gadolinium chelate recently introduced in MRI, and it has already been used for cardiac late enhancement imaging; however, until now it has never been compared with gadopentetate dimeglumine. The purpose of our study was to compare 0.1 mmol/kg gadobutrol to 0.2 mmol/kg gadopentetate dimeglumine for the detection of myocardial late enhancement in the same group of patients. This was an exploratory single-blind parallel group study comparing gadobutrol (0.1 mmol/kg) to gadopentetate dimeglumine (0.2 mmol/kg) in 20 adult patients scheduled for cardiac late enhancement MRI with gadopentetate dimeglumine and whose MR images showed late enhancement. MR images were acquired at 10, 15, and 20 minutes after peripheral injection of gadobutrol by using a 3D turbo field echo inversion recovery T1-weighted sequence. Volume and percentage of late enhancement, number of involved segments, late enhancement localization and pattern, and late enhancement signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between contrast agents. Late enhancement was not significantly different with gadobutrol and gadopentetate dimeglumine both in terms of total volume of myocardium (mean ± SD, 37.8 ± 56.1 and 35.1 ± 46.7 cm(3), respectively; p = 0.33) and percentage of myocardial wall involvement (22.5% ± 19.1% and 22.0% ± 17.2%, respectively; p = 0.67). The number of segments involved was not different (138 with gadobutrol vs 134 with gadopentetate dimeglumine). Furthermore, SNR and CNR were not different (gadopentetate dimeglumine, 123.8 ± 82.9 and gadobutrol, 117.2 ± 88.6, p = 0.58 and gadopentetate dimeglumine, 96.2 ± 68.9 and gadobutrol, 88.4 ± 72.9, p = 0.53, respectively). A single dose of gadobutrol seems to be as effective as a double dose of gadopentetate dimeglumine for the detection of late enhancement.

Measurement of glomerular filtration rate using dynamic magnetic resonance imaging in patients with chronic kidney disease

Determination of glomerular filtration rate (GFR) using plasma disappearance curves requires the injection of a filtration marker and repeated timed blood collections. Gadolinium-containing contrast media are excreted exclusively by glomerular filtration and could provide a novel approach to quantifying GFR using magnetic resonance (MR) imaging. The aim of this study was to demonstrate the feasibility of measuring GFR by the clearance of gadolinium-containing contrast medium in patients with chronic kidney disease (CKD). Informed consent was obtained from stable CKD patients in stages 1, 2 or 3 (n=16; 5 women, 11 men; median age 54 years). GFR was measured after a bolus injection of gadobutrol (4 mL, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. The obtained MR-GFR was compared with simultaneously measured plasma clearance of inulin and gadobutrol. Technical failure occurred in 2 patients. The mean obtained MR-GFR was 71 ± 25 (SD) mL/min per 1.73 m² and agreed well with the mean inulin-GFR (70 ± 24 mL/min per 1.73 m²). Pearson's correlation coefficient was r=0.91. The mean of the paired differences was 1 ± 10 mL/min per 1.73 m² and not significantly different from zero. GFR obtained from gadobutrol plasma clearance also agreed well with inulin-GFR and MR-GFR (r=0.92 and r=0.75, respectively). We describe a novel method of determining GFR from MR imaging using a low dose of gadobutrol in patients with reduced GFR that enables the absolute quantification of GFR after routine contrast-enhanced MR imaging.

Comments on the case report reported by Elmholdt et al.

Comments on the case report reported by Elmholdt et al.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging

Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

Pharmacokinetics and Safety of Gadobutrol-Enhanced Magnetic Resonance Imaging in Pediatric Patients

This clinical study investigated the pharmacokinetics and safety of gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in pediatric patients aged 2 to 17 years. In this open-label, multicenter study, patients scheduled for routine contrast-enhanced MR imaging of the brain, spine, liver or kidney, or MR angiography received a single intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were stratified by age groups (2-6, 7-11, and 12-17 years). Blood and urine samples were collected at prespecified time points and analyzed for gadolinium concentrations. Plasma data were evaluated by means of a nonlinear mixed effects model, and urine data were analyzed using descriptive statistics. In addition, the safety of gadobutrol was evaluated. A total of 130 patients (2-6 years, n = 45; 7-11 years, n = 39; 12-17 years, n = 46) were included in the final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in children aged 2 to 17 years were adequately described by an open 2-compartment model with elimination from the central compartment. The median estimates (2.5th percentile, 97.5th percentile) of body weight-normalized total body clearance (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and 0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group. Median gadolinium plasma concentrations at 20 minutes postinjection were simulated using the population pharmacokinetic model and ranged from 414 (13 kg subject) to 518 micromol/L (65 kg subject). Body weight was identified as the major covariate influencing the pharmacokinetic parameters of total body clearance and central volume of distribution. Age was not found to be an additional independent parameter. The median amount of renally excreted gadolinium was 77.0% of the administered dose within 6 hours postinjection, indicating that gadobutrol was renally excreted in this pediatric population aged 2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of mild intensity reported for 8 (5.8%) of 138 patients. Observed differences in pharmacokinetics were attributed to body weight, with no additional independent effect of age. Thus, no dose adjustment from the standard dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in the pediatric population in this study.

Dynamic Contrast Enhancement of Experimental Glioma: An Intra-individual Comparative Study to Assess the Optimal Time Delay

The aim of this study was to compare tumor signal and contrast media uptake characteristics on contrast-enhanced T1-weighted sequences at 3 Tesla over 30 minutes after double-dose administration of different contrast agents in an animal model of brain glioma. Nine rats underwent magnetic resonance imaging (MRI) after stereotactic F98 glioma cell implantation before and repetitively for 30 minutes after injection of gadobutrol, gadopentetate, and gadobenate, respectively. Signal-to-noise ratio (SNR) and tumor contrast-to-noise ratio (CNR) were evaluated and MRI-derived tumor volumes were compared to histology. Postcontrast tumor SNR and CNR peaked at 4 minutes after contrast application. While contrast-enhancement within the tumor was fading, tumor volume increased by continuous contrast-uptake of peripheral parts between 4 minutes (137 + or - 29 mm(3), 126 + or - 16 mm(3), 141 + or - 24 mm(3)) and 20 minutes (182 + or - 35 mm(3), 164 + or - 32 mm(3), 191 + or - 25 mm(3)), respectively. At 8 and 12 minutes, 84% and 91% of the tumor volume were definable, respectively. Optimal correlation between MRI-derived tumor volume and histology is achieved by imaging up to 20 minutes after contrast application. At 4 minutes (this delay is mostly used in clinical routine), only 75% of the enhancing tumor volume is assessable. A delay of 8 minutes already reveals 84% of the tumor and seems to be a practical clinical compromise.

Normal Dynamic MRI Enhancement Patterns of the Upper Abdominal Organs: Gadoxetic Acid Compared With Gadobutrol

The purpose of this study was to investigate whether, at dynamic MRI of the upper abdominal organs, contrast enhancement with gadoxetic acid, a hepatobiliary contrast agent, is comparable with that achieved with an extracellular contrast agent. Dynamic gadoxetic acid-enhanced MRI of the pancreas, spleen, kidney, liver, and abdominal aorta was performed on 50 patients; dynamic gadobutrol-enhanced MRI was performed on a control group of 50 patients; and the images were compared. Dynamic imaging with a T1-weighted volumetric interpolated breath-hold examination gradient-echo sequence (TR/TE, 3.35/1.35; flip angle, 12 degrees ) was performed before and 20 (arterial phase), 55 (portal venous phase), and 90 (hepatic venous phase) seconds after bolus injection of gadoxetic acid (0.25 mmol/mL) or gadobutrol (1.0 mmol/mL). Signal-to-noise ratios and enhancement indexes were calculated for each organ and time. All MR images in both groups were of diagnostic quality. During the early dynamic phases, significantly lower mean enhancement indexes were found in the gadoxetic acid group than in the gadobutrol group in the pancreas (portal venous phase, 0.66, 1.39, p <or= 0.001; hepatic venous phase, 0.51, 1.36, p <or= 0.001), spleen (portal venous phase, 1.54, 2.41, p <or= 0.001; hepatic venous phase, 1.19, 2.23, p <or= 0.001), renal cortex (portal venous phase, 1.76, 2.63, p <or= 0.001; hepatic venous phase, 1.60, 2.63, p <or= 0.001), and liver (portal venous phase, 0.76, 0.94, p = 0.016; hepatic venous phase, 0.76, 1.04, p <or= 0.001). In the abdominal aorta, the mean enhancement index was greater after bolus injection of gadoxetic acid (arterial phase, 3.33, 2.24, p <or= 0.005). Early dynamic MRI of the upper abdominal organs, especially the spleen, pancreas, and kidney, benefits from the higher gadolinium concentration of gadobutrol than in the organ-specific contrast agent gadoxetic acid. Higher protein binding resulting in increased relaxivity of gadoxetic acid compensates for the low gadolinium concentration in the abdominal aorta.

Prevalence of acute adverse reactions to gadobutrol—A highly concentrated macrocyclic gadolinium chelate: Review of 14,299 patients from observational trials

Objective To determine the safety and tolerability of gadobutrol in a large number of non-selected patients from routine clinical radiology practices. Materials and methods Six prospectively planned, observational surveillance studies were conducted at more than 300 institutions in Europe and Canada from 2000 to 2007. Demographic and medical status data, details of the diagnostic procedure, contrast agent administration and adverse drug reaction (ADR) data were collected using a standardized questionnaire. Results A total of 14,299 patients were enrolled. The mean age of the patients was 53.7 years; 1.3% of the patients were <18 years old and 40.8% were 60 years or older. The body regions most frequently examined were head/neck/brain (54.3%), followed by spine (7.2%), pelvis/joints/limbs (6.7%) and multiple body regions (6.4%). Gadobutrol-enhanced magnetic resonance angiography (MRA) was performed in 14.7% of patients. Overall, the mean volume of gadobutrol administered for contrast-enhanced magnetic resonance imaging was 12 mL (0.16 mmol gadolinium [Gd]/kg body weight [BW]; mean BW: 75.5 kg), whereas for contrast-enhanced MRA the mean volume was 15.7 mL (0.21 mmol Gd/kg BW). Seventy-eight of the 14,299 patients (0.55%) reported at least one ADR. Two (0.01%) serious ADRs were reported. The most frequently reported ADR was nausea, which occurred in 36 patients (0.25%). Conclusion Gadobutrol 1.0 M is very well tolerated and has a good safety profile. The occurrence of ADRs observed following the intravenous injection of gadobutrol is comparable with the published data of other Gd-based contrast agents.