Administration Of Gadolinium-based Contrast Agents Research Articles

Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly better (n = 20, P = 0.039) motion-artifact suppression was noted in the synthesized images. The noninferiority test rejects the inferiority of the synthesized to true full-dose images for image quality (95% CI: -14-9%), artifacts suppression (95% CI: -5-20%), and contrast enhancement (95% CI: -13-6%). With the proposed deep learning method, gadolinium dose can be reduced 10-fold while preserving contrast information and avoiding significant image quality degradation. 3 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2018;48:330-340.

The Impact of Gadolinium Deposition on Radiology Practice: An International Survey of Radiologists

Brain deposition of gadolinium following the administration of gadolinium-based contrast agents (GBCAs) was initially reported in 2014. Gadolinium deposition is now recognized as a dose-dependent consequence of exposure. The potential clinical implications are not yet understood. The purpose of this study was to determine radiologists' reporting practices in response to gadolinium deposition. An electronic survey querying radiologists' practices regarding gadolinium deposition was distributed by Radiopaedia.org from November-December 2015. Our study sample included 94 total respondents (50% academic; 27% private practice; 23% hybrid) from 30 different countries (USA 18%). Fifty-seven (62%) radiologists had observed brain gadolinium deposition on MRI brain studies howerver more than half of these (30 of 57) reported detecting dentate T1 shortening only rarely (<1/month). Among respondents, 58% (52 of 89) do not or would not include the finding in the radiology report; only 12 (13%) report the finding in the impression of their reports. The most common reason for not reporting gadolinium deposition was the risk of provoking unnecessary patient anxiety (29%, 20 of 70). Recent data on gadolinium deposition has led to a reported practice change in 24 of 87 (28%) of respondents. Recognition of, and attitudes toward, brain gadolinium deposition were inconsistent in this worldwide sample. Most surveyed radiologists do not routinely report dentate T1shortening as a marker of gadolinium deposition. Fear of provoking patient/clinician anxiety and an incomplete understanding of the implications of gadolinium deposition contribute to inconsistencies in reporting.

The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

BackgroundCardiovascular magnetic resonance (CMR) imaging has been used to visualise post-ablation atrial scar (PAAS), generally employing a three-dimensional (3D) late gadolinium enhancement (LGE) technique. However the reproducibility of PAAS imaging has not been determined. This cross-over study is the first to investigate the reproducibility of the technique, crucial for both future research design and clinical implementation.MethodsForty subjects undergoing first time ablation for atrial fibrillation (AF) had detailed CMR assessment of PAAS. Following baseline pre-ablation scan, two scans (separated by 48 h) were performed at three months post-ablation. Each scan session included 3D LGE acquisition at 10, 20 and 30 min post administration of gadolinium-based contrast agent (GBCA). Subjects were allocated at second scan post-ablation to identical imaging parameters (‘Repro’, n = 10), 3 T scanner (‘3 T’, n = 10), half-slice thickness (‘Half-slice’, n = 10) or half GBCA dose (‘Half-gad’, n = 10). PAAS was compared to baseline scar and then reproducibility was assessed for two measures of thresholded scar (% left atrial (LA) occupied by PAAS (%LA PAAS) and Pulmonary Vein Encirclement (PVE)), and then four measures of non-thresholded scar (point-by-point assessment of PAAS, four normalisation methods). Thresholded measures of PAAS were evaluated against procedural outcome (AF recurrence).ResultsA total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. At 20 and 30 min, inter-scan reproducibility was good to excellent (coefficient of variation at 20 min and 30 min: %LA PAAS 0.41 and 0.20; PVE 0.13 and 0.04 respectively for ‘Repro’ group). Changes in imaging parameters, especially reduced GBCA dose, reduced inter-scan reproducibility, but for most measures remained good to excellent (ICC for %LA PAAS 0.454–0.825, PVE 0.618–0.809 at 30 min). For non-thresholded scar, highest reproducibility was observed using blood pool z-score normalisation technique: inter-scan ICC 0.759 (absolute agreement, ‘Repro’ group). There was no significant relationship between indices of PAAS and AF recurrence.ConclusionPAAS imaging is a reproducible finding. Imaging should be performed at least 20 min post-GBCA injection, and a blood pool z-score should be considered for normalisation of signal intensities. The clinical implications of these findings remain to be established in the absence of a simple correlation with arrhythmia outcome.Trial registrationUnited Kingdom National Research Ethics Service 08/H0802/68 – 30th September 2008.

Optimization of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

BackgroundCardiovascular magnetic resonance (CMR) imaging may be used to visualize post-ablation atrial scar (PAAS), and three-dimensional late gadolinium enhancement (3D LGE) is the most widely employed technique for imaging of chronic scar. Detection of PAAS provides a unique non-invasive insight into the effects of the ablation and may help guide further ablation procedures. However, there is evidence that PAAS is often not detected by CMR, implying a significant sensitivity problem, and imaging parameters vary between leading centres. Therefore, there is a need to establish the optimal imaging parameters to detect PAAS.MethodsForty subjects undergoing their first pulmonary vein isolation procedure for AF had detailed CMR assessment of atrial scar: one scan pre-ablation, and two scans post-ablation at 3 months (separated by 48 h). Each scan session included ECG- and respiratory-navigated 3D LGE acquisition at 10, 20 and 30 min post injection of a gadolinium-based contrast agent (GBCA). The first post-procedural scan was performed on a 1.5 T scanner with standard acquisition parameters, including double dose (0.2 mmol/kg) Gadovist and 4 mm slice thickness. Ten patients subsequently underwent identical scan as controls, and the other 30 underwent imaging with a reduced, single, dose GBCA (n = 10), half slice thickness (n = 10) or on a 3 T scanner (n = 10). Apparent signal-to-noise (aSNR), contrast-to-noise (aCNR) and imaging quality (Likert Scale, 3 independent observers) were assessed. PAAS location and area (%PAAS scar) were assessed following manual segmentation. Atrial shells with standardised %PAAS at each timepoint were then compared to ablation lesion locations to assess quality of scar delineation.ResultsA total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. Likert scale of imaging quality had high interobserver and intraobserver intraclass correlation coefficients (0.89 and 0.96 respectively), and showed lower overall imaging quality on 3 T and at half-slice thickness. aCNR, and quality of scar delineation increased significantly with time. aCNR was higher with reduced, single, dose of GBCA (p = 0.005).Conclusion3D LGE CMR atrial scar imaging, as assessed qualitatively and quantitatively, improves with time from GBCA administration, with some indices continuing to improve from 20 to 30 min. Imaging should be performed at least 20 min post-GBCA injection, and a single dose of contrast should be considered.Trial registrationTrial registry- United Kingdom National Research Ethics Service 08/H0802/68 – 30th September 2008.

Contrast media in urogenital radiology

BACKGROUND. Contrast media are widely used in urogenital radiology. The ideal contrast agent should be totally inert, causing no interactions with organism, and with a rapid and complete excretion. Adverse reactions could occur after using any type of contrast media. Contrast enhanced procedures are performed with increasing frequency and the patients population is progressively older and with multiple co-morbid conditions, thus contrast media toxicity is becoming a serious problem. Contrast media-induced nephropathy (CIN) is considered an important cause of hospital-acquired renal failure. The administration of gadolinium-based contrast agents has been recently associated with the development of a serious adverse reaction, potentially lethal in patients with renal insufficiency, named nephrogenic systemic fibrosis (NSF). METHODS. Literature review on contrast media in urogenital radiology, CIN, NSF. CONCLUSIONS. Since 1996, the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) has released its guidelines regarding safety about the use of contrast media. CIN, and the emerging NSF, are topics of increasing interest for urologists, radiologists, nephrologists, dermatologists and all the clinicians. Contrast media have progressively become safer in the last years. Even if rare, some adverse reactions still occurr up to now. CIN and its prevention remain an issue under debate. In the past, whenever a patient required a contrast-enhanced imaging study, the trend was to select magnetic resonance imaging with gadolinium-based contrast agents in order to avoid the well-known CIN of iodinated-based contrast agents. The awareness of NFS is changing the contrast-enhanced imaging in patients with renal failure. At present we have to investigate NSF etiopathogenesis, in order to prevent and eventually to cure it. The understanding of the risk factors for both CIN and NSF is an emerging need, the adoption of all preventive measures to reduce the risks remain a mandatory issue.

Development of High Signal Intensity within the Globus Pallidus and Dentate Nucleus following Multiple Administrations of Gadobenate Dimeglumine.

Previous studies have evaluated various gadolinium based contrast agents and their association with gadolinium retention, however, there is a discrepancy in the literature concerning the linear agent gadobenate dimeglumine. Our aim was to determine whether an association exists between the administration of gadobenate dimeglumine and the development of intrinsic T1-weighted signal in the dentate nucleus and globus pallidus. In this single-center, retrospective study, the signal intensity of the globus pallidus, dentate nucleus, thalamus, and middle cerebellar peduncle was measured on unenhanced T1-weighted images in 29 adult patients who had undergone multiple contrast MRIs using exclusively gadobenate dimeglumine (mean, 10.1 ± 3.23 doses; range, 6-18 doses). Two neuroradiologists, blinded to the number of prior gadolinium-based contrast agent administrations, separately placed ROIs within the globi pallidi, thalami, dentate nuclei, and middle cerebellar peduncles on the last MR imaging examinations. The correlations between the globus pallidus:thalamus and the dentate nucleus:middle cerebellar peduncle signal intensity ratios with the number of gadolinium-based contrast agent administrations and cumulative dose were tested with either 1-tailed Pearson or Spearman correlations. A priori, P < .05 was considered statistically significant. Both the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the number of gadolinium-based contrast agent administrations (r = 0.39, P = .017, and r = 0.58, P = .001, respectively). Additionally, the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncle ratios showed significant correlation with the cumulative dose of gadobenate dimeglumine (r = 0.48, P = .004, and r = 0.43, P = .009, respectively). Dentate nucleus hyperintensity was qualitatively present on the last MR imaging in 79.3%-86.2% of patients and in all patients who had received >10 doses. At high cumulative doses (commonly experienced by patients, for example, with neoplastic disease), gadobenate dimeglumine is associated with an increase in the globus pallidus:thalamus and dentate nucleus:middle cerebellar peduncles signal intensity ratios.

Gadolinium-Based Contrast Agents in Kidney Disease: A Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists.

Purpose of review:Use of gadolinium-based contrast agents (GBCA) in renal impairment is controversial, with physician and patient apprehension in acute kidney injury (AKI), chronic kidney disease (CKD), and dialysis because of concerns regarding nephrogenic systemic fibrosis (NSF). The position that GBCA are absolutely contraindicated in AKI, category G4 and G5 CKD (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2), and dialysis-dependent patients is outdated and may limit access to clinically necessary contrast-enhanced magnetic resonance imaging (MRI) examinations. This review and clinical practice guideline addresses the discrepancy between existing Canadian guidelines regarding use of GBCA in renal impairment and NSF.Sources of information:Published literature (including clinical trials, retrospective cohort series, review articles, and case reports), online registries, and direct manufacturer databases were searched for reported cases of NSF by class and specific GBCA and exposed patient population.Methods:A comprehensive review was conducted identifying cases of NSF and their association to class of GBCA, specific GBCA used, patient, and dose (when this information was available). Based on the available literature, consensus guidelines were developed by an expert panel of radiologists and nephrologists.Key findings:In patients with category G2 or G3 CKD (eGFR ≥ 30 and < 60 mL/min/1.73 m2), administration of standard doses of GBCA is safe and no additional precautions are necessary. In patients with AKI, with category G4 or G5 CKD (eGFR < 30 mL/min/1.73 m2) or on dialysis, administration of GBCA should be considered individually and alternative imaging modalities utilized whenever possible. If GBCA are necessary, newer GBCA may be administered with patient consent obtained by a physician (or their delegate) citing an exceedingly low risk (much less than 1%) of developing NSF. Standard GBCA dosing should be used; half or quarter dosing is not recommended and repeat injections should be avoided. Dialysis-dependent patients should receive dialysis; however, initiating dialysis or switching from peritoneal to hemodialysis to reduce the risk of NSF is unproven. Use of a macrocyclic ionic instead of macrocyclic nonionic GBCA or macrocyclic instead of newer linear GBCA to further prevent NSF is unproven. Gadopentetate dimeglumine, gadodiamide, and gadoversetamide remain absolutely contraindicated in patients with AKI, those with category G4 or G5 CKD, or those on dialysis. The panel agreed that screening for renal disease is important but less critical when using macrocyclic and newer linear GBCA. Monitoring for and reporting of potential cases of NSF in patients with AKI or CKD who have received GBCA is recommended.Limitations:Limited available literature (number of injections and use in renal impairment) regarding the use of gadoxetate disodium. Limited, but growing and generally high-quality, number of clinical trials evaluating GBCA administration in renal impairment. Limited data regarding the topic of Gadolinium deposition in the brain, particularly as it related to patients with renal impairment.Implications:In patients with AKI and category G4 and G5 CKD (eGFR < 30 mL/min/1.73 m2) and in dialysis-dependent patients who require GBCA-enhanced MRI, GBCA can be administered with exceedingly low risk of causing NSF when using macrocyclic agents and newer linear agents at routine doses.

A Radiological Encomium Depicting Pancreatic Fibrosis and Sarcopenia: A Research Perspective

Aims and Objectives: In this study we compared DW MRI findings with the results of histological examination and CT findings in patients with chronic pancreatitis and pancreatic cancer, to confirm a non-invasive diagnostic method, determining pancreatic fibrosis. Moreover, we looked for correlation between histologically determined PF and sarcopenia, since this pathology is highly suspected in patients of our research.Materials and Methods: We collected a group of 9 patients, who underwent surgical resection of the pancreas due to pancreatic cancer or chronic pancreatitis. All patients were treated at the Department of Gastroenterology and Surgery of P.B.M hospital, Bikaner, Rajasthan after being approved by the ethical committee of the assocaited Sardar Patel Medical College, Bikaner. All examinations and surgeries were performed in 2017.Conclusion: We found that ADC value in histologically determined fibrotic pancreatic tissue is significant lower. Since DW MRI can be performed relatively quickly, does not require administration of gadolinium-based contrast agents and enables qualitative and quantitative assessment of tissue diffusivity, it can be routinely implemented in clinical protocols.

Evaluation of Gadolinium Retention After Serial Administrations of a Macrocyclic Gadolinium-Based Contrast Agent (Gadobutrol): A Single-Institution Experience With 189 Patients.

There has been controversy as to whether gadobutrol, one of the widely used macrocyclic gadolinium-based contrast agents, can lead to gadolinium retention after serial injections. Our aim was to validate whether serial administrations of gadobutrol can cause signal increase in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images due to gadolinium retention. A total of 189 patients who had undergone at least 2 contrast-enhanced MR scans using only gadobutrol between August 2009 and August 2016 were retrospectively included. The DN-to-pons and GP-to-thalamus signal intensity (SI) ratio differences on unenhanced T1-weighted MR images were calculated by subtracting the SI ratios at the first MR images from those at the last MR images. One-sample t tests were used to evaluate whether the SI ratio differences differed from 0. Linear regression and Pearson correlations were performed to assess correlations between SI ratio differences and various confounding variables, including the number of MR scans, mean time interval between MR scans, age, sex, history of radiation therapy or chemotherapy, and renal and liver functions. Patients underwent a mean of 5.9 ± 6.3 contrast-enhanced MR scans with a mean interval of 42.8 ± 49.5 weeks between the scans. Sixty-three patients underwent 6 or more MR scans, whereas 126 patients underwent fewer than 6 MR scans. Neither the DN-to-pons SI nor the GP-to-thalamus SI ratio differences differed significantly from 0, with mean values of -0.012 ± 0.115 (P = 0.148) and 0.012 ± 0.111 (P = 0.126), respectively. Serial administrations of gadobutrol did not result in signal increases in the DN or GP on unenhanced T1-weighted MR images due to gadolinium retention.

The use of gadolinium-based contrast agents in Ghana with a focus on residual intracranial gadolinium deposition

IntroductionThe aim of the survey was to identify current practice of the use of gadolinium-based contrast agents (GBCAs) in the wake of recent reports on gadolinium deposition in the brain following repeated administration of GBCAs. MethodA total of 13 facilities in Ghana with magnetic resonance imaging (MRI) departments were contacted via email with a two-page questionnaire. ResultsA response rate of 69.2% (n = 9) was achieved. Gadodiamide (Omniscan) was the most commonly used GBCA. Slightly more than half of respondents were aware of residual deposition of GBCAs in the brain. Majority of the respondents were aware of GBCA deposition in individuals with abnormal renal function, but not aware of its deposition in those with normal renal function. A great majority of the respondents do not record the type and dose of GBCA after each intravenous administration, and such information is not provided in MRI reports. More than half of the respondents do not check eGFR prior to the administration of GBCA even when a high-risk agent is used. ConclusionGadodiamide (Omniscan) a high-risk agent remains the most commonly used GBCA in Ghana. Awareness of current findings of GBCA deposition in the brain following repeated doses are not encouraging as revealed in this study. The need to adopt international standard guidelines into practice cannot be overemphasized in order to reduce the potential long-term effect of this deposition.

Observed Deposition of Gadolinium in Bone Using a New Noninvasive in Vivo Biomedical Device: Results of a Small Pilot Feasibility Study.

Purpose To perform a preliminary evaluation of a noninvasive measurement system to assess gadolinium deposition in bone and to investigate the relationship between the administration of gadolinium-based contrast agents (GBCAs) and gadolinium retention in bone. Materials and Methods In vivo measurement of gadolinium retention in tibia bones was performed in 11 exposed subjects who previously received GBCAs (six exposed subjects were from a study performed 5 years previously involving injection of GBCAs in healthy volunteers; five exposed subjects had self-reported GBCA exposure), and 11 sex- and age-matched control subjects without a history of GBCA exposure. Each subject underwent one measurement of gadolinium retention in the tibia with x-ray fluorescence in a laboratory at McMaster University. A one-tailed t test was performed to compare gadolinium concentration in the exposed group with that in the control group. The relationship between the dose of GBCA administered and the gadolinium concentration measured in bone was analyzed with linear regression. Results Gadolinium concentration in bone was significantly higher in exposed subjects (mean, 1.19 μg Gd/g bone mineral ± 0.73 [standard deviation]) than in control subjects (mean, -1.06 μg Gd/g bone mineral ± 0.71) (P = .01). There was also a positive correlation between the dose of GBCA administered and the gadolinium concentration measured in bone (R2 = 0.41); gadolinium concentration in bone increased by 0.39 μg Gd/g bone mineral ± 0.14 per 1 mL of GBCA administered. Gadolinium was detected in bone up to 5 years after one GBCA administration. Conclusion This x-ray fluorescence system is capable of measuring gadolinium deposition in bone noninvasively in vivo. Gadolinium can be retained in bone after one dose of GBCA in healthy subjects. © RSNA, 2017 Online supplemental material is available for this article.

Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within the dentate nucleus following repeated gadolinium-based contrast agent administration

To determine whether repeated gadolinium-based contrast agent administration (GBCA) in children is associated with the development of increased T1-weighted signal intensity within the cerebellar dentate nucleus. With institutional review board approval for this The Health Insurance Portability and Accountability Act-compliant retrospective study, a cohort of 41 patients under the age of 18 years who underwent at least four contrast-enhanced magnetic resonance imaging (MR) examinations of the brain from 2005 to 2015 were identified. For each examination, both dentate nuclei were manually contoured, and the mean dentate nucleus-to-pons signal intensity (DN-P SI) ratio was calculated. The DN-P SI ratios from the last to first MRI examination were compared, and the correlation between DN-P SI ratio and cumulative gadolinium dose was calculated using a linear mixed effect model to control for potentially confounding variables. For the 41 patients in the cohort, there was a significant increase in the mean DN-P SI ratio from the first MRI to the last MRI examination (1.05 versus 1.11, p=0.004). After controlling for patient diagnosis, history of chemotherapy or radiation, sex, and age, there was a significant positive association between DN-P SI ratio and cumulative gadolinium dose (coefficient=0.401, p=0.032). Repeated GBCA administration in children is associated with increased T1-weighted signal intensity within the dentate nucleus.

Magnetic Resonance Myocardial Perfusion Imaging: Safety and Indications in Pediatrics and Young Adults.

The purpose of this study was to assess the safety and indications for cardiac magnetic resonance (CMR) with myocardial perfusion imaging (MPI) in a cohort of children and young adults. A retrospective review of 178 children and young adults who underwent CMR with MPI was performed. Studies were categorized based on study protocols as MPI with resting perfusion only, adenosine stress MPI, exercise-induced stress MPI, and MPI for cardiac mass diagnosis. Relevant clinical history, exam indications, and adverse reactions following gadolinium-based contrast agent and adenosine administration were recorded. Studies were reviewed for the presence of myocardial perfusion defects, wall motion abnormalities, and delayed myocardial enhancement. The most common indications from MPI were congenital heart disease (CHD), Kawasaki disease, anomalous coronary artery, or myocardial mass characterization. Of these, 51% were protocoled with adenosine stress, 23% without stress, 6% with exercise stress, and 20% for cardiac mass evaluation. Excluding patients for myocardial mass evaluation, MPI defects were present in 16% (14 with adenosine stress, 1 with exercise stress, 8 on resting studies only). For cardiac mass evaluation, a mass was confirmed in 58%. No adverse reactions occurred with intravenous administration of a gadolinium-based contrast agent. Three self-limited adverse reactions, 2 patients with chest pain, and 1 patient with bradycardia, occurred following adenosine administration. MPI is a safe modality for the evaluation of pediatric and young adults with minimal adverse events. The most common indications for MPI were for the evaluation of CHD, Kawasaki disease, anomalous coronary artery, or myocardial mass characterization.

Absence of clinical cerebellar syndrome after serial injections of more than 20 doses of gadoterate, a macrocyclic GBCA: a monocenter retrospective study

Sound evidence of gadolinium accumulation in brain has been recently provided after repeated administrations of linear gadolinium-based contrast agents (GBCAs), especially at the cerebellum level. Although data regarding brain accumulation of macrocyclic GBCAs are more reassuring, there is now a genuine concern ("gadolinium-phobia") about possible long-term consequences of gadolinium deposits, especially in terms of cerebellar sequelae. We, therefore, questioned about the clinical impact of serial administration of gadoterate meglumine, a macrocyclic GBCA. In this retrospective study (2000-2016) of medical files of patients who received more than 20 administrations of gadoterate, we searched for cerebellar symptoms and signs developing during the regular follow-up. We reviewed medical files of ten patients (mean age 34.4±20.8years; 4 males, 6 females) who received 28.2±5.3 doses of gadoterate (average total dose of GBCA 518±226ml; range 185-785ml). Patients were examined by at least two medical specialists depending on initial diagnosis, and at least once by a neurosurgeon. Mean follow-up time was 91months (range 49-168) and six out of ten patients experienced new symptoms or signs. No clinician reported the appearance of a rising cerebellar syndrome, nor newly appeared symptoms or signs suggested cerebellar toxicity. This retrospective clinical study shows no de novo clinical cerebellar syndrome following repeated administrations of gadoterate. Our results argue against a cerebellar toxicity of this macrocyclic agent. Still, confirmation in a larger number of subjects is required, as well as clinical studies concerning linear GBCAs whose structure and in vivo stability are distinct.

Signal Enhancement of the Dentate Nucleus at Unenhanced MR Imaging after Very High Cumulative Doses of the Macrocyclic Gadolinium-based Contrast Agent Gadobutrol: An Observational Study.

Purpose To test for measurable visual enhancement of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance (MR) images in a cohort of patients with a primary brain tumor who had not received linear gadolinium-based contrast agents (GBCAs) but had received many injections of macrocyclic GBCAs. Materials and Methods Seventeen patients with high-grade gliomas who had received 10-44 administrations of the macrocyclic GBCA gadobutrol (0.1 mmol/kg of body weight) were retrospectively included in this regional ethics committee-approved study. Two neuroradiologists inspected T1-weighted MR images with optimized window settings to visualize small differences in contrast at the baseline and at the last examination for the presence of visual DN signal enhancement. Signal intensity (SI) in the DN was normalized to the SI of the pons, and a one-sample t test was used to test for differences between baseline normalized SI (nSI) in the DN (nSIDN) and the average change in nSIDN of all postbaseline MR imaging sessions (ΔnSIDNavg) or the change in nSIDN from baseline to the last MR imaging session (ΔnSIDN). Linear and quadratic correlation analyses were used to examine the association between the number of macrocyclic GBCA administrations and ΔnSIDN or ΔnSIDNavg. Results The mean ± standard deviation number of macrocyclic GBCA administrations was 22.2 ± 10.6 administered throughout 706 days ± 454. Visually appreciable signal enhancement was observed in two patients who had received 37 and 44 macrocyclic GBCA injections. Mean ΔnSIDN was greater than zero (0.03 ± 0.05; P = .016), and there was a significant linear association between the number of macrocyclic GBCA injections and ΔnSIDN (r = 0.69, P = .002) and ΔnSIDNavg (r = 0.77, P < .001). Conclusion A small but statistically significant dose-dependent T1-weighted signal enhancement was observed in the DN after multiple macrocyclic GBCA injections. Visually appreciable enhancement in the DN was observed on contrast-optimized images in two patients who had received 37 and 44 standard doses of macrocyclic GBCAs. © RSNA, 2017 Online supplemental material is available for this article.

Gadolinium Retention in the Rat Brain: Assessment of the Amounts of Insoluble Gadolinium-containing Species and Intact Gadolinium Complexes after Repeated Administration of Gadolinium-based Contrast Agents.

Purpose To evaluate the speciation of gadolinium-containing species after multiple administrations of the gadolinium-based contrast agents (GBCAs) gadodiamide and gadoteridol and to quantify the amount of intact gadolinium complexes and insoluble gadolinium-containing species. Materials and Methods A total dose of 13.2 mmol per kilogram of body weight of each GBCA was administered in healthy Wistar rats over a period of 8 weeks. Three days after the final administration, rats were sacrificed, and the brains were excised and divided into three portions. Each portion of brain homogenate was divided into two parts, one for determination of the total gadolinium concentration with inductively coupled plasma mass spectrometry and one for determination of the amount of intact GBCA and gadolinium-containing insoluble species. Relaxometric measurements of gadodiamide and gadolinium trichloride in the presence of polysialic acid were also performed. Results The mean total gadolinium concentrations for gadodiamide and gadoteridol, respectively, were 0.317 μg/g ± 0.060 (standard deviation) and 0.048 μg/g ± 0.004 in the cortex, 0.418 μg/g ± 0.078 and 0.051 μg/g ± 0.009 in the subcortical brain, and 0.781 μg/g ± 0.079 and 0.061 μg/g ± 0.012 in the cerebellum. Gadoteridol comprised 100% of the gadolinium species found in rats treated with gadoteridol. In rats treated with gadodiamide, the largest part of gadolinium retained in brain tissue was insoluble species. In the cerebellum, the amount of intact gadodiamide accounts for 18.2% ± 10.6 of the total gadolinium found therein. The mass balance found for gadolinium implies the occurrence of other soluble gadolinium-containing species (approximately 30%). The relaxivity of the gadolinium polysialic acid species formed in vitro was 97.8 mM/sec at 1.5 T and 298 K. Conclusion Gadoteridol was far less retained, and the entire detected gadolinium was intact soluble GBCA, while gadodiamide yielded both soluble and insoluble gadolinium-containing species, with insoluble species dominating. © RSNA, 2017 Online supplemental material is available for this article.

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg-1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the injury induced by gadolinium-based contrast agents.

Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients.

PurposeTo determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations.Materials and methodsIn this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student’s t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy.ResultsThe mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis.ConclusionMultiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.

Immediate Allergic Reactions to Gadolinium-based Contrast Agents: A Systematic Review and Meta-Analysis.

Purpose To perform a systematic review and meta-analysis to determine if there are differences in rates of immediate allergic events between classes of gadolinium-based contrast agents (GBCAs). Materials and Methods PubMed and Google Scholar databases were searched for studies in which rates of immediate adverse events to GBCAs were reported. The American College of Radiology classification system was used to characterize allergic-like events as mild, moderate, or severe, and the total number of administrations of each GBCA was recorded. Where necessary, authors of studies were contacted to clarify data and eliminate physiologic reactions. Relative risks of GBCA types were estimated by using the Mantel-Haenszel type method. Results Nine studies in which immediate reactions to GBCA were recorded from a total of 716 978 administrations of GBCA met the criteria for inclusion and exclusion. The overall rate of patients who had immediate allergic-like reactions was 9.2 per 10 000 administrations and the overall rate of severe immediate allergic-like reactions was 0.52 per 10 000 administrations.. The nonionic linear chelate gadodiamide had the lowest rate of reactions, at 1.5 (95% confidence interval [CI]: 0.74, 2.4) per 10 000 administrations, which was significantly less than that of linear ionic GBCAs at 8.3 (95% CI: 7.5, 9.2) per 10 000 administrations (relative risk, 0.19 [95% CI: 0.099, 0.36]; P < .00001) and less than that for nonionic macrocyclic GBCAs at 16 (95% CI: 14, 19) per 10 000 administrations (relative risk, 0.12 [95% CI: 0.05, 0.31]; P < .001). GBCAs known to be associated with protein binding had a higher rate of reactions, at 17 (95% CI: 15, 20) per 10 000 administrations compared with the same chelate classification without protein binding, at 5.2 (95% CI: 4.5, 6.0) per 10 000 administrations (relative risk, 3.1 [95% CI: 2.4, 3.8]; P < .0001). Conclusion These data show the lowest rate of immediate allergic adverse events with use of the nonionic linear GBCA gadodiamide in comparison with those of ionic linear or nonionic macrocyclic GBCAs. A higher rate of immediate allergic adverse events was associated with ionicity, protein binding, and macrocyclic structure. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on August 31, 2017.

Erratum to: Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naive patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.