Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo.

BACKGROUND: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H2 O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. PURPOSE: Validate theory describing blood behavior of R1 and R2 * in an animal model. STUDY TYPE: Prospective, animal. ANIMAL MODEL: Seven swine (54-65 kg). FIELD STRENGTH/SEQUENCE: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences. ASSESSMENT: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R1 and R2 * effects (whole-blood model) and simpler models incorporating linear R1 , with and without R2 * effects. Predicted SIs were compared to measured aortic SI. STATISTICAL TESTS: Linear correlation (coefficient of determination, R2 ) and mean errors were compared across the SI prediction models. RESULTS: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R1 and high blood R2 * (regression slopes 0.91-1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2 * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). DATA CONCLUSION: Incorporating sub-linear R1 and high first-pass R2 * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Gadoteridol-enhanced MRI of the breast: can contrast agent injection rate impact background parenchymal enhancement?

BACKGROUND: Normal background parenchymal enhancement (BPE) is a dynamic parameter affected by multiple factors. PURPOSE: To determine whether contrast agent injection rate affects the degree of BPE in women undergoing breast magnetic resonance imaging (MRI). MATERIAL AND METHODS: A total of 85 patients included in our prospective study randomly received 0.1 mmol/kg gadoteridol at a rate of 3 mL/s (group A; n = 46) or 2 mL/s (group B; n = 39). Breast MRI was performed at 3T using a standard protocol including postcontrast axial 3D GRE T1-weighted sequences. Two expert breast radiologists, blinded to clinical and radiological information, independently quantified BPE on early postcontrast subtracted images, assigning a score of 1-4. Mean comparison and regression analysis were performed to assess the influence of injection rate on BPE. RESULTS: Groups were homogeneous in terms of age and final BI-RADS score. The mean BPE score was significantly lower among patients in group A (mean of two readers: 1.36 vs. 1.90; P < 0.01) with 70%-72% of patients assigned a BPE score of 1, compared with 36%-38% of patients in group B. Lower BPE scores were noted with the higher flow rate in subgroup analyses of both pre- and postmenopausal women, although the effect was more evident in premenopausal women. Regression analysis confirmed that the likelihood of a BPE 1 score was significantly increased with a higher flow rate (P < 0.01). The inter-reader agreement was excellent (0.83). CONCLUSION: A higher contrast agent injection flow rate (3 mL/s) during breast MRI significantly reduces the degree of BPE, potentially allowing improved diagnostic accuracy by reducing false-positive and false-negative findings.

Gadolinium Clearance in the First 5 Weeks After Repeated Intravenous Administration of Gadoteridol, Gadoterate Meglumine, and Gadobutrol to rats.

BACKGROUND: Studies of gadolinium (Gd) clearance from animals in the first weeks after administration of gadolinium-based contrast agents (GBCAs) have previously looked at solitary timepoints only. However, this does not give information on differences between GBCAs and between organs in terms of Gd elimination kinetics. PURPOSE: To compare Gd levels in rat cerebellum, cerebrum, skin, and blood at 1, 2, 3, and 5 weeks after repeated administration of macrocyclic GBCAs. STUDY TYPE: Prospective. ANIMAL MODEL: One hundred eighty male Sprague-Dawley rats randomized to three groups (n = 60/group), received intravenous administrations of gadoteridol, gadoterate meglumine, or gadobutrol (0.6 mmol/kg for each) four times/week for 5 consecutive weeks. Rats were sacrificed after washout periods of 1, 2, 3, or 5 weeks. FIELD STRENGTH/SEQUENCE: Not applicable. ASSESSMENT: Cerebellum, cerebrum, skin, and blood were harvested for Gd determination by inductively coupled plasma-mass spectrometry (15 animals/group/all timepoints). STATISTICAL TESTS: Anova and Dunnett's test (data with homogeneous variances and normal distribution). Kruskal-Wallis and Wilcoxon's rank sum tests (data showing nonhomogeneous variances or a non-normal distribution, significance levels: P < 0.05, P < 0.01, and P < 0.001). RESULTS: Gd levels in cerebellum, cerebrum, and skin were significantly lower after gadoteridol than after gadoterate and gadobutrol at all timepoints. Mean cerebellum Gd concentrations after gadoteridol, gadoterate, and gadobutrol decreased from 0.693, 0.878, and 1.011 nmol Gd/g at 1 week to 0.144, 0.282, and 0.297 nmol Gd/g at 5 weeks after injection. Similar findings were noted for cerebrum and skin. Conversely, significantly higher Gd levels were noted in blood after gadoteridol compared to gadobutrol at 1, 2, and 3 weeks and compared to gadoterate at all timepoints. DATA CONCLUSION: Gadoteridol is eliminated more rapidly from rat cerebellum, cerebrum, and skin compared to gadoterate and gadobutrol in the first 5 weeks after administration, resulting in lower levels of retained Gd in these tissues. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 5.

Dose-Lowering in Contrast-Enhanced MRI of the Central Nervous System: A Retrospective, Parallel-Group Comparison Using Gadobenate Dimeglumine.

BACKGROUND: Concerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols. PURPOSE: To compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS). STUDY TYPE: Retrospective, multicenter. POPULATION: Three hundred and fifty-two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate. FIELD STRENGTH/SEQUENCES: 1.5 T and 3.0 T/precontrast and postcontrast T1-weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2-weighted FSE and T2-FLAIR. ASSESSMENT: Images of patients with extra-axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quantitative (lesion-to-brain ratio [LBR], contrast-to-noise ratio [CNR]; SI measurements at regions-of-interest on lesion and normal parenchyma) enhancement measures. Noninferiority of 0.05 mmol/kg gadobenate was determined for each qualitative endpoint if the lower limit of the 95% confidence interval (CI) for the difference in precontrast + postcontrast means was above a noninferiority margin of -0.4. STATISTICAL TESTS: Student's t-test for comparison of mean qualitative endpoint scores, Wilcoxon signed rank test for comparison of LBR and CNR values; Wilcoxon rank sum test for comparison of SI changes. Tests were significant for P < 0.05. RESULTS: The mean change from precontrast to precontrast + postcontrast was significant for all endpoints. Readers 1, 2, and 3 evaluated 304, 225, and 249 lesions for 0.05 mmol/kg gadobenate, and 382, 309, and 298 lesions for 0.1 mmol/kg gadobenate. The lower limit of the 95% CI was above -0.4 for all comparisons. Significantly, higher LBR and CNR was observed with the higher dose. DATA CONCLUSION: 0.05 mmol/kg gadobenate was noninferior to 0.1 mmol/kg gadobenate for lesion visualization. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Differences in gadolinium retention after repeated injections of macrocyclic MR contrast agents to rats.

PURPOSE: To compare the levels of gadolinium in the blood, cerebrum, cerebellum, liver, femur, kidneys, and skin after multiple exposure of rats to the macrocyclic gadolinium-based contrast agents (GBCAs) gadoterate, gadobutrol, and gadoteridol. MATERIALS AND METHODS: Fifty male Wistar Han rats were randomized to three exposure groups (n = 15 per group) and one control group (n = 5). Animals in the exposure groups received a total of 20 GBCA administrations (four administrations per week for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After a 28-day recovery period animals were sacrificed and the blood and tissues harvested for determination of gadolinium (Gd) levels. Gd determination was performed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: After 28 days' recovery no Gd was found in the blood, liver, or skin of any animal in any group. Significantly lower levels of Gd were noted with gadoteridol compared to gadoterate and gadobutrol in the cerebellum (0.150 ± 0.022 vs. 0.292 ± 0.057 and 0.287 ± 0.056 nmol/g, respectively; P < 0.001), cerebrum (0.116 ± 0.036 vs. 0.250 ± 0.032 and 0.263 ± 0.045 nmol/g, respectively; P < 0.001), and kidneys (25 ± 13 vs. 139 ± 88 [P < 0.01] and 204 ± 109 [P < 0.001], respectively). Higher levels of Gd were noted in the femur (7.48 ± 1.37 vs. 5.69 ± 1.75 and 8.60 ± 2.04 nmol/g, respectively) with significantly less Gd determined for gadoterate than for gadobutrol (P < 0.001) and gadoteridol (P < 0.05). CONCLUSION: Differences exist between macrocyclic agents in terms of their propensity to accumulate in tissues. The observed differences in Gd concentration point to differences in GBCA washout rates in this setting and in this experimental model, with gadoteridol being the GBCA that is most efficiently removed from both cerebral and renal tissues. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:746-752.

Non-clinical assessment of safety and gadolinium deposition after cumulative administration of gadobenate dimeglumine (MultiHance®) to neonatal and juvenile rats.

To determine the impact of single and cumulative doses of MultiHance on toxicity, pharmacokinetics, tissue gadolinium presence, behavior and neurological function in juvenile rats. Juvenile male and female rats received either physiological saline or MultiHance at 0.6, 1.25 or 2.5 mmol/kg bodyweight. Animals received either single or six consecutive MultiHance administrations and were sacrificed the day after the last administration or after a 60-day treatment-free period. Animals were assessed for behavior, cognitive function, grip strength, gait, pupillary reflex, and auditory reflex, as well as for physical development, sexual maturation and histopathology. Gadolinium presence in brain, femur, kidneys, liver and skin was determined using inductively coupled plasma-mass spectrometry (ICP-MS). No effects of MultiHance on behavior, cognitive function or any other parameter were noted, even for the highest administered cumulative dose (15 mmol/kg). Gadolinium presence was variable across tissues and decreased during the 60-day treatment-free period. The highest levels were noted in the femur and the lowest levels in the brain. Gadolinium presence in juvenile rat brain following single or repeated MultiHance administrations was minimal and non-impactful.

Pharmacokinetics of gadobenate dimeglumine in children 2 to 5 years of age undergoing MRI of the central nervous system.

PURPOSE: To determine the pharmacokinetic profile of gadobenate dimeglumine in children aged between 2 and 5 years. MATERIALS AND METHODS: Fifteen children scheduled to undergo contrast-enhanced MRI for suspected disease of the central nervous system received a single intravenous injection of 0.1 mmol/kg gadobenate dimeglumine. Children were stratified into three age groups: 2 to <3 years, 3 to <4 years, and 4 to 5 (i.e., <6 years). Serial blood and urine samples collected at prespecified time-points before and after contrast administration were analyzed for gadolinium concentrations. Pharmacokinetic parameters were calculated using noncompartmental and compartmental techniques. RESULTS: Mean values of 65.7 µg/mL for highest blood gadolinium concentration, 0.2 L/h/kg for blood clearance, 0.32 L/kg for steady-state volume of distribution, and 1.2 h for terminal elimination half-life were determined across all age groups combined. On average, more than 80% of the dose was eliminated in the urine during the first 24 h after administration. All pharmacokinetic parameters were similar between age groups and no effects of gender were noted. No adverse events considered related to gadobenate dimeglumine administration were reported. CONCLUSION: In terms of pharmacokinetic profile no dosage adjustment from the approved adult gadobenate dimeglumine dose of 0.1 mmol/kg bodyweight is necessary in children aged between 2 and 5 years.

Development of a New Imaging Bulk Package for Multipatient Use in MDCT.

OBJECTIVE: Multidose presentations of U.S. Food and Drug Administration (FDA)-approved radiographic contrast agents have been considered pharmacy bulk packages. However, the use of pharmacy bulk packages for multipatient dosing does not meet the U.S. Pharmacopeia definition of a pharmacy bulk package. The purpose of this study was to validate and gain FDA approval for a new multidose preparation of iopamidol for safe, compliant multipatient dosing in the CT suite. MATERIALS AND METHODS: An FDA-approved development program was undertaken to determine whether multidose presentations of iopamidol used in combination with a transfer set remain free of chemical and microbiologic contamination during the labeled maximum hold time after container closure penetration and simulated worst-case handling conditions. The program comprised antimicrobial effectiveness testing of iopamidol-300 and iopamidol-370 containers with seven microbes. Microbial growth was evaluated at five time points up to 28 days after introduction. Microbial ingress testing involved inoculation of four challenge sites with each of four microorganisms for up to 14 hours. Chemical compatibility and extractable testing was performed to ensure chemical integrity. RESULTS: No growth of microorganisms occurred. All evaluated samples remained sterile, indicating no microbial contamination through 14 hours of simulated clinical use. No effect on chemical integrity was found in any of the drawn iopamidol samples meeting the chemical specifications for iopamidol, and no leachable compounds were detected. CONCLUSION: The absence of any chemical or microbiologic contamination led the FDA to approve the iopamidol multidose container and transfer set as a combination product for multipatient use. The approval resulted in a new U.S. Pharmacopeia category of multidose presentation-the imaging bulk package.

Prospective Cohort Study of Nephrogenic Systemic Fibrosis in Patients With Stage 3-5 Chronic Kidney Disease Undergoing MRI With Injected Gadobenate Dimeglumine or Gadoteridol.

OBJECTIVE: The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderate-to-severe impairment of kidney function who had not previously been exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. SUBJECTS AND METHODS: Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in cohort 2, < 30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study A) or gadoteridol (study B). A third study (study C) determined the incidence of NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years before enrollment. Monitoring for signs and symptoms suggestive of NSF was performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring at 1 and 2 years. RESULTS: For studies A and B, the populations evaluated for NSF comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort 1 of each study, respectively, and with 45 and 12 patients in cohort 2, respectively. No signs or symptoms of NSF were reported or detected during the 2 years of patient monitoring. Likewise, no cases of NSF were reported for any of the 405 subjects enrolled in study C. CONCLUSION: To our knowledge, and consistent with reports in the literature, no association of gadobenate dimeglumine or gadoteridol with unconfounded cases of NSF has yet been established. Study data confirm that both gadoteridol and gadobenate dimeglumine properly belong to the class of GBCAs considered to be associated with the lowest risk of NSF.

Low-dose gadobenate dimeglumine-enhanced MRI of the kidney for the differential diagnosis of localized renal lesions.

OBJECTIVE: To evaluate low-dose gadobenate dimeglumine-enhanced MRI for the differential diagnosis of malignant renal tumors. METHODS: Sixty-two consecutive patients with unclear diagnosis at MDCT/ultrasound underwent dynamic CE-MRI of the kidneys with 0.05 mmol/kg gadobenate dimeglumine. Retrospective image evaluation was performed by two blinded readers. Lesion diagnosis at CE-MRI was correlated with findings from histology following tumor resection or from imaging follow-up after at least 1 year. Assessments were performed of diagnostic quality and level of diagnostic information. RESULTS: Thirty-nine (63 %) patients were correctly diagnosed with malignant lesions (36 with RCC, 2 with renal metastases, 1 with lymphoma) while 14 (22.6 %) patients were correctly diagnosed with benign (n = 12) or no (n = 2) lesions. Eight patients were considered false positive (5 with oncocytoma, 3 with atypical AML) and 1 patient false negative (atypical RCC). The sensitivity, specificity, accuracy, PPV, and NPV for the diagnosis of malignant renal lesions were 97.5 % (39/40), 63.6 % (14/22), 85.5 % (53/62), 83.0 % (39/47), and 93.3 % (14/15), respectively. Images were excellent in 60 and good in 2 patients. Minimal artifacts that did not compromise diagnosis were noted in 4/62 patients. CONCLUSION: Low-dose gadobenate dimeglumine-enhanced MRI is effective for the differential diagnosis of malignant renal tumors.

Contrast-enhanced MR angiography: does a higher relaxivity MR contrast agent permit a reduction of the dose administered for routine vascular imaging applications?

PURPOSE: The authors prospectively compared single dose (0.1 mmol/kg bodyweight) gadobenate dimeglumine with double dose (0.2 mmol/kg bodyweight) gadopentetate dimeglumine for contrast-enhanced magnetic resonance angiography (CE-MRA) in patients with suspected or known steno-occlusive disease of the carotid, renal or peripheral vasculature using an intra-individual crossover study design. MATERIALS AND METHODS: Twenty-eight patients with suspected or known steno-occlusive disease of the carotid (n = 16), renal (n = 5) or peripheral arteries (n = 7) were randomised to receive either 0.1 mmol/kg gadobenate dimeglumine or 0.2 mmol/kg gadopentetate dimeglumine for a first CE-MRA procedure. After 3-5 days all patients underwent a second identical CE-MRA procedure with the other contrast agent. Three blinded readers assessed images for vessel anatomical delineation, disease detection/exclusion, and global preference. Diagnostic performance for detection of ≥51 % stenosis was determined for 20/28 patients who also underwent digital subtraction angiography (DSA). Non-inferiority was assessed using the Wilcoxon signed rank, McNemar and Wald tests. Quantitative (signal-to-noise and contrast-to-noise ratio) enhancement based on 3D maximum intensity projection reconstructions was compared. RESULTS: No differences were noted for any qualitative parameter. Equivalence was reported for all diagnostic preference end-points. Superiority for gadobenate dimeglumine was reported by all readers for sensitivity for disease detection (80.8-86.5 vs. 75.0-82.7 %). Quantitative enhancement was similar for single dose gadobenate dimeglumine and double dose gadopentetate dimeglumine. CONCLUSIONS: Under identical examination conditions a single 0.1 mmol/kg body weight dose of gadobenate dimeglumine can fully replace a double 0.2 mmol/kg body weight dose of gadopentetate dimeglumine for routine CE-MRA procedures.

Lowering radiation exposure in CT angiography using automated tube potential selection and optimized iodine delivery rate.

OBJECTIVE: The purpose of this study was to determine the effectiveness of a radiation dose reduction strategy for CT angiography by the combination of higher iodine delivery rate and automated tube potential selection with adjusted reference values for tube current-exposure time product, as well as to measure the impact of this approach on image quality. SUBJECTS AND METHODS: One hundred consecutive patients underwent high-pitch CT angiography of the thorax and abdomen using either 90 mL of iomeprol 300 (n = 44, protocol A) or 90 mL of iomeprol 400 (n = 56, protocol B) at the same flow rate. Automated tube potential selection was used with reference tube current-time products of 330 mAs and 250 mAs for protocols A and B, respectively. Twenty vascular segments were analyzed for attenuation and image noise by two readers. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for all segments. The dose-length product (DLP) was documented to calculate effective dose and was compared between protocols both globally and for body mass index (BMI) subgroups. RESULTS: There were no differences in sex, height, weight, or BMI between both groups. Images from patients scanned with protocol B showed higher levels of image noise but also higher signal in all vascular segments. As a result, there were no differences in SNR between both groups. Conversely, CNR was significantly higher for almost all vascular segments in the group scanned using protocol B. Furthermore, DLP was significantly lower when protocol B was used, particularly in patients with a BMI of less than 30. CONCLUSION: In CT angiography, a combination of higher iodine delivery rate and automated tube potential selection with adjusted reference values for the tube current-time product allows reductions in radiation dose by approximately 30% without compromising image quality.

Safety and adverse effects during 24 hours after contrast-enhanced MRI with gadobenate dimeglumine (MultiHance) in children.

BACKGROUND: Gadolinium-based MR contrast agents have long been considered safe for routine diagnostic imaging. However, the advent of nephrogenic systemic fibrosis (NSF) among certain patients with severe renal insufficiency has brought the issue of safety into question. Nowhere is safety of greater concern than among children who frequently require multiple contrast-enhanced MRI examinations over an extended period of time. OBJECTIVE: To retrospectively evaluate the safety of gadobenate dimeglumine for contrast-enhanced (CE) MRI across a range of indications. MATERIALS AND METHODS: Two hundred pediatric inpatients (age: 4 days to 15 years) underwent CE MRI as part of clinical routine. The children received a gadobenate dimeglumine dose of either 0.05 mmol/kg body weight (liver, abdominal imaging, musculoskeletal imaging, brain and other rare indications) or 0.1 mmol/kg bodyweight (cardiovascular imaging, MR-urography). Young (< 8 years) children with congenital heart disease were intubated and underwent MRA evaluation with controlled ventilation. Monitoring for adverse events was performed for at least 24 h after each gadobenate dimeglumine injection. Depending on clinical necessity, laboratory measurements and, in some cases, vital sign and ECG determinations were made before and after contrast injection. Safety was evaluated by age group, indication and dose administered. RESULTS: No clinically adverse events were reported among children who had one MRI scan only or among children who had several examinations. There were no changes in creatinine or bilirubin levels even in very young children. CONCLUSIONS: No adverse events were recorded during the first 24 h following administration of gadobenate dimeglumine in 200 children.

Gadolinium retention in a rat model of subtotal renal failure: are there differences among macrocyclic GBCAs?

BACKGROUND: Gd levels are higher in tissues of animals with compromised renal function, but studies to compare levels after exposure to different macrocyclic gadolinium-based contrast agents (GBCAs) are lacking. We compared Gd levels in tissues of subtotally nephrectomised (SN) rats after repeated exposure to macrocyclic GBCAs. METHODS: Sprague-Dawley SN male rats (19 per group) received 16 injections of gadoteridol, gadobutrol, or gadoterate meglumine at 0.6 mmol Gd/kg 4 times/weeks over 4 weeks. A control group of healthy male rats (n = 10) received gadoteridol at the same dosage. Plasma urea and creatinine levels were monitored. Blood, cerebrum, cerebellum, liver, femur, kidney(s), skin and peripheral nerves were harvested for Gd determination by inductively coupled plasma-mass spectrometry at 28 and 56 days after the end of treatment. RESULTS: Plasma urea and creatinine levels were roughly twofold higher in SN rats than in healthy rats at all timepoints. At day 28, Gd levels in the peripheral nerves of gadobutrol- or gadoterate-treated SN animals were 5.4 or 7.2 times higher than in gadoteridol-treated animals (p < 0.001). Higher Gd levels after administration of gadobutrol or gadoterate versus gadoteridol were also determined in kidneys (p ≤ 0.002), cerebrum (p ≤ 0.001), cerebellum (p ≤ 0.003), skin (p ≥ 0.244), liver (p ≥ 0.053), and femur (p ≥ 0.271). At day 56, lower Gd levels were determined both in SN and healthy rats for all GBCAs and tissues, except the femur. CONCLUSIONS: Gd tissue levels were lower following gadoteridol exposure than following gadobutrol or gadoterate exposure.

Gadobenate dimeglumine (MultiHance) in MR angiography: an in-vitro phantom comparison with gadopentetate dimeglumine (Magnevist) at different concentrations.

BACKGROUND: Numerous clinical studies suggest that gadobenate dimeglumine is diagnostically superior to other gadolinium chelates for MR imaging applications, including contrast-enhanced MR angiography (CE-MRA). However, confirmatory in-vitro phantom studies have thus far been lacking. PURPOSE: To evaluate the difference in signal intensity achieved with the high-relaxivity MR contrast agent gadobenate dimeglumine (MultiHance) relative to that achieved with the standard-relaxivity non-specific agent gadopentetate dimeglumine (Magnevist) at different concentrations using an in-vitro phantom study design. MATERIAL AND METHODS: Test tubes with whole human blood were prepared with concentrations of gadobenate dimeglumine or gadopentetate dimeglumine ranging from 0 to 12 mM. A three-dimensional (3D) T1-weighted gradient echo sequence normally used for CE-MRA of the renal arteries was performed at flip angles of 25° and 35°. The signal-to-noise ratio (SNR) was calculated for all concentrations of both contrast agents. Furthermore a Look-Locker sequence was used and quantitative T1 mapping was performed for all the test tubes. The contrast agent concentration in the aorta was simulated using previously published data on T1 in the aorta during the first pass of a contrast agent. The differences between gadobenate dimeglumine and gadopentetate dimeglumine were compared at the simulated concentrations. RESULTS: The SNR achieved with gadobenate dimeglumine was consistently greater than that achieved with gadopentetate dimeglumine at all concentrations. An improvement of 15-25% in SNR was obtained when increasing the flip angle from 25° to 35°. The relative improvement in SNR with gadobenate dimeglumine relative to gadopentetate dimeglumine ranged from 25-72% and was markedly greater at lower concentrations with a flip angle of 35°. CONCLUSION: Our findings suggest that the relative benefit of gadobenate dimeglumine over gadopentetate dimeglumine for CE-MRA applications is greater at lower concentrations.

The TRUTH confirmed: validation of an intraindividual comparison of gadobutrol and gadoteridol for imaging of glioblastoma using quantitative enhancement analysis.

BACKGROUND: Previous intraindividual comparative studies evaluating gadobutrol and gadoteridol for contrast-enhanced magnetic resonance imaging (MRI) of brain tumours have relied on subjective image assessment, potentially leading to misleading conclusions. We used artificial intelligence algorithms to objectively compare the enhancement achieved with these contrast agents in glioblastoma patients. METHODS: Twenty-seven patients from a prior study who received identical doses of 0.1 mmol/kg gadobutrol and gadoteridol (with appropriate washout in between) were evaluated. Quantitative enhancement (QE) maps of the normalised enhancement of voxels, derived from computations based on the comparison of contrast-enhanced T1-weighted images relative to the harmonised intensity on unenhanced T1-weighted images, were compared. Bland-Altman analysis, linear regression analysis and Pearson correlation coefficient (r) determination were performed to compare net QE and per-region of interest (per-ROI) average QE (net QE divided by the number of voxels). RESULTS: No significant differences were observed for comparisons performed on net QE (mean difference -24.37 ± 620.8, p = 0.840, r = 0.989) or per-ROI average QE (0.0043 ± 0.0218, p = 0.313, r = 0.958). Bland-Altman analysis revealed better per-ROI average QE for gadoteridol-enhanced MRI in 19/27 (70.4%) patients although the mean difference (0.0043) was close to zero indicating high concordance and the absence of fixed bias. CONCLUSIONS: The enhancement of glioblastoma achieved with gadoteridol and gadobutrol at 0.1 mmol/kg bodyweight is similar indicating that these agents have similar contrast efficacy and can be used interchangeably, confirming the results of a prior double-blind, randomised, intraindividual, crossover study.

Role of breast MR imaging for predicting malignancy of histologically borderline lesions diagnosed at core needle biopsy: prospective evaluation.

PURPOSE: To prospectively determine the diagnostic performance of breast magnetic resonance (MR) imaging in predicting the malignancy of breast lesions classified as borderline at core needle biopsy (CNB). MATERIALS AND METHODS: This prospective study was approved by the local ethics committee, and all patients provided written informed consent. Between February 2007 and October 2009, 193 patients underwent ultrasonography (US)-guided CNB. Thirty-two lesions in 32 patients were classified as "borderline" ("lesions of uncertain malignant potential" according to the United Kingdom National Health Service Breast Screening program or those that are "probably benign" according to the Breast Imaging Reporting and Data System [BI-RADS] lexicon) at pathologic examination and were evaluated. All 32 patients underwent contrast agent-enhanced breast MR imaging 1-3 weeks after CNB; surgical biopsy was performed within 60 days of MR imaging. Results were compared with histologic findings. Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated. RESULTS: Findings from surgical biopsy confirmed the diagnosis of seven atypical ductal hyperplasia lesions, four atypical lobular hyperplasia (ALH) lesions, five papillary lesions, two fibroepithelial lesions, three radial scars, three lobular carcinomas in situ, three ductal carcinomas in situ (DCIS), four invasive ductal carcinomas, and one invasive lobular carcinoma. With regard to malignancy, breast MR imaging helped correctly classify 22 of the 32 lesions as negative and seven as positive. Two of the lesions confirmed to be ALH were incorrectly classified as suspicious (BI-RADS category IV; false-positive finding), whereas one small DCIS was incorrectly classified as nonsuspicious (BI-RADS category II; false-negative finding). The sensitivity, specificity, accuracy, and positive and negative predictive values for the correct demonstration of malignancy at MR imaging were 88% (seven of eight lesions), 92% (22 of 24 lesions), 91% (29 of 32 lesions), 78% (seven of nine lesions), and 96% (22 of 23 lesions), respectively. CONCLUSION: Breast MR imaging can improve the evaluation of lesions classified as borderline at CNB. In cases of nonsuspicious enhancement or no enhancement at breast MR imaging, follow-up rather than surgical biopsy might be performed.

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for MR angiography of peripheral arteries.

PURPOSE: To prospectively compare the image quality and diagnostic performance achieved with doses of gadobenate dimeglumine and gadopentetate dimeglumine of 0.1 mmol per kilogram of body weight in patients undergoing contrast material-enhanced magnetic resonance (MR) angiography of the pelvis, thigh, and lower-leg (excluding foot) for suspected or known peripheral arterial occlusive disease. MATERIALS AND METHODS: Institutional review board approval was granted from each center and informed written consent was obtained from all patients. Between November 2006 and January 2008, 96 patients (62 men, 34 women; mean age, 63.7 years +/- 10.4 [standard deviation]; range, 39-86 years) underwent two identical examinations at 1.5 T by using three-dimensional spoiled gradient-echo sequences and randomized 0.1-mmol/kg doses of each agent. Images were evaluated on-site for technical adequacy and quality of vessel visualization and offsite by three independent blinded readers for anatomic delineation and detection/exclusion of pathologic features. Comparative diagnostic performance was determined in 31 patients who underwent digital subtraction angiography. Data were analyzed by using the Wilcoxon signed-rank, McNemar, and Wald tests. Interreader agreement was determined by using generalized kappa statistics. Differences in quantitative contrast enhancement were assessed and a safety evaluation was performed. RESULTS: Ninety-two patients received both agents. Significantly better performance (P < .0001; all evaluations) with gadobenate dimeglumine was noted on-site for technical adequacy and vessel visualization quality and offsite for anatomic delineation and detection/exclusion of pathologic features. Contrast enhancement (P < or = .0001) and detection of clinically relevant disease (P < or = .0028) were significantly improved with gadobenate dimeglumine. Interreader agreement for stenosis detection and grading was good to excellent (kappa = 0.749 and 0.805, respectively). Mild adverse events were reported for four (six events) and five (eight events) patients after gadobenate dimeglumine and gadopentetate dimeglumine, respectively. CONCLUSION: Higher-quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease.

Interaction of macrocyclic gadolinium-based MR contrast agents with Type I collagen. Equilibrium and kinetic studies.

The interactions of gadoterate meglumine, gadobutrol, gadoteridol and Gd(HB-DO3A) with bovine Type I collagen were investigated by ultrafiltration and dialysis. The affinity of the four agents to collagen is similar. However, the maximum adsorbed amount of GdIII-complexes decreases in the following order: gadoterate meglumine > gadobutrol > gadoteridol > Gd(HB-DO3A). Calculations with the open three-compartment model reveal that the structural homologs gadoteridol and Gd(HB-DO3A) have a lower adsorption onto collagen, which may explain the less prolonged in vivo retention of gadoteridol observed in soft tissues of rats.