Gadolinium Exposure Research Articles

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS

BackgroundHypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated. Therefore, comparing the safety of different GBCAs in terms of HSRs and GDD/SAGE using the latest post-marketing safety data should yield further insights into safely using GBCAs.MethodsThe safety differences between all GBCAs to GDD and the spectrum of GBCA-related HSRs were all compared and analyzed by using the World Health Organization database VigiBase and the FDA Adverse Event Reporting System (FAERS) database in this study. A further analysis of SAGE was also conducted using FAERS data. The lower limit of the reporting odds ratio (ROR) 95% confidence interval was used for signal detection. Moreover, the frequency of HSRs was calculated by dividing the number of reports in VigiBase by the total sales volume (measured in millions) from 2008 to 2022 in the IQVIA Multinational Integrated Data Analysis System. All adverse events were standardized using the Medical Dictionary for Drug Regulatory Activities (MedDRA) 26.0.ResultsThis study shows that all GBCAs have the potential to induce HSRs, with nonionic linear GBCAs exhibiting a comparatively lower signal. According to standardized MedDRA query stratification analysis, gadobutrol had a greater ROR025 for angioedema. The ROR025 of gadobenate dimeglumine and gadoteridol is larger for anaphylactic/anaphylactoid shock conditions. Regarding severe cutaneous adverse reactions, only gadoversetamide and gadodiamide showed signals in FAERS and VigiBase. There were also differences in the frequency of HSRs between regions. Regarding GDD, gadoterate meglumine, and gadoteridol had a lower ROR025. An analysis of the 29 preferred terms linked to SAGE indicated that special consideration should be given to the risk of skin induration associated with gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoteridol. Additionally, gadodiamide and gadoteridol pose a greater risk of skin tightness compared to other GBCAs.ConclusionsThe risk differences among GBCAs using data from several sources were compared in this study. However, as a hypothesis-generating method, a clear causal relationship would require further research and validation.

The safety of magnetic resonance imaging contrast agents.

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.

Assessing teratogenic risks of gadolinium in freshwater environments: Implications for environmental health

Gadolinium (Gd) is among the rare earth elements extensively utilized in both industrial and medical applications. The latter application appears to contribute to the rise in Gd levels in aquatic ecosystems, as it is excreted via urine from patients undergoing MRI scans and often not captured by wastewater treatment systems. The potential environmental and biological hazards posed by gadolinium exposure are still under investigation. This study aimed to assess the teratogenic risk posed by a gadolinium chelate on the freshwater cnidarian Hydra vulgaris. The experimental design evaluated the impact of pure Gadodiamide (25 μg/l, 50 μg/l, 100 μg/l, 500 μg/l) and its commercial counterpart compound (Omniscan®; 100 μg/l, 500 μg/l, 782.7 mg/l) at varying concentrations using the Teratogenic Risk Index (TRI). Here we showed a moderate risk (Class III of TRI) following exposure to both tested formulations at concentrations ≥ 100 μg/l. Given the potential for similar concentrations in aquatic environments, particularly near wastewater discharge points, a teratogenic risk assessment using the Hydra regeneration assay was conducted on environmental samples collected from three rivers (Tiber, Almone, and Sacco) in Central Italy. Additionally, chemical analysis of field samples was performed using ICP-MS. Analysis of freshwater samples revealed low Gd concentrations (≤ 0.1 μg/l), despite localized increases near domestic and/or industrial wastewater discharge sites. Although teratogenic risk in environmental samples ranged from high (Class IV of TRI) to negligible (Class I of TRI), the low Gd concentrations, particularly when compared to higher levels of other contaminants like arsenic and heavy metals, preclude establishing a direct cause-effect relationship between Gd and observed teratogenic risks in environmental samples. Nevertheless, the teratogenic risks observed in laboratory tests warrant further investigation.

Gadolinium Effects on Liposome Fluidity and Size Depend on the Headgroup and Side Chain Structure of Key Mammalian Brain Lipids.

The lanthanide metal gadolinium has been used in the healthcare industry as a paramagnetic contrast agent for years. Gadolinium deposition in brain tissue and kidneys has been reported following gadolinium-based contrast agent administration to patients undergoing MRI. This study demonstrates the detrimental effects of gadolinium exposure at the level of the cell membrane. Biophysical analysis using fluorescence spectroscopy and dynamic light scattering illustrates differential interactions of gadolinium ions with key classes of brain membrane lipids, including phosphatidylcholines and sphingomyelins, as well as brain polar extracts and biomimetic brain model membranes. Electrostatic attraction to negatively charged lipids like phosphatidylserine facilitates metal complexation but zwitterionic phosphatidylcholine and sphingomyelin interaction was also significant, leading to membrane rigidification and increases in liposome size. Effects were stronger for fully saturated over monounsaturated acyl chains. The metal targets key lipid classes of brain membranes and these biophysical changes could be very detrimental in biological membranes, suggesting that the potential negative impact of gadolinium contrast agents will require more scientific attention.

Update on Gadolinium-Based Contrast Agent Safety, From the AJR Special Series on Contrast Media.

Since its introduction more than 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. Although extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include acute allergiclike reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, although rare, serious reactions can occur. NSF is a rare but serious sclerodermalike condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) group I GBCAs. Group II and III GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data show any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classifications, and describes approaches for strengthening the evidence needed for regulatory decisions.

Reducing Gadolinium Exposure in Patients Undergoing Monitoring for Meningiomas.

Background Due to the non-malignant and slow-growing nature of many meningiomas, surveillance with serial magnetic resonance imaging (MRI) serves as an acceptable management plan. However, repeated imaging with gold-standard contrast-based studies may lead to contrast-associated adverse effects. Non-gadolinium T2 sequences may serve as a suitable alternative without the risk of adverse effects of contrast. Thus, this study sought to investigate the agreement between post-contrast T1 and non-gadolinium T2 MRI sequences in the measurement of meningioma growth. Methodology The Virginia Commonwealth University School of Medicine (VCU SOM) brain tumor database was used to create a cohort of meningioma patients and determine the number of patients who had T1 post-contrast imaging accompanied by readily measurable imaging from either T2 fast spin echo (FSE) or T2 fluid-attenuated inversion recovery (FLAIR) sequences. Measurements of the largest axial and perpendicular diameters of each tumor were conducted by two independent observers using T1 post-contrast, T2 FSE, and T2 FLAIR imaging series.Lin's concordance correlation coefficient (CCC) was calculated to assess inter-rater reliability between observers and agreement between measurements of tumor diameter among the different imaging sequences. Results In total, 33 patients (average age = 72.1 ± 12.9 years, 90% female) with meningiomas were extracted from our database, with 22 (66.7%) undergoing T1 post-contrast imaging accompanied with readily measurable imaging from T2 FSE and/or T2 FLAIR sequences. The inter-rater reliability between the measurements of T1 axial and perpendicular diameters was 0.96 (95% confidence interval (CI) = 0.92-0.98) and 0.92 (95% CI = 0.83-0.97), respectively. The inter-rater reliability between the measurements of T2 axial perpendicular diameters was 0.93 (95% = CI 0.92-0.97) and 0.89 (95% CI = 0.74-0.95), respectively. The agreements between the measurement of T1 and T2 FSE axial diameter by each observer were 0.97 (95% CI = 0.93-0.98) and 0.92 (95% CI = 0.81-0.97). The agreements between the measurements of T1 and T2 FSE perpendicular diameter measurements by each observer were 0.98 (95% CI = 0.95-0.99) and 0.88 (95% CI = 0.73-0.95). Conclusions Two-thirds of our patients had meningiomas that were readily measurable on either T2 FSE or T2 FLAIR sequences. Additionally, there was excellent inter-rater reliability between the observers in our study as well as an agreement between individual measurements of T1 post-contrast and T2 FSE tumor diameters. These findings suggest that T2 FSE may serve as a safe and similarly effective surveillance method for the long-term management of meningioma patients.

The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further.

Nephrogenic Systemic Fibrosis in Patients with Chronic Kidney Disease after the Use of Gadolinium-Based Contrast Agents: A Review for the Cardiovascular Imager.

Gadolinium-enhanced cardiac magnetic resonance has revolutionized cardiac imaging in the last two decades and has emerged as an essential and powerful tool for the characterization and treatment guidance of a wide range of cardiovascular diseases. However, due to the high prevalence of chronic renal dysfunction in patients with cardiovascular conditions, the risk of nephrogenic systemic fibrosis (NSF) after gadolinium exposure has been a permanent concern. Even though the newer macrocyclic agents have proven to be much safer in patients with chronic kidney disease and end-stage renal failure, clinicians must fully understand the clinical characteristics and risk factors of this devastating pathology and maintain a high degree of suspicion to prevent and recognize it. This review aimed to summarize the existing evidence regarding the physiopathology, clinical manifestations, diagnosis, and prevention of NSF related to the use of gadolinium-based contrast agents.

Use of Real-Life Safety Data From International Pharmacovigilance Databases to Assess the Importance of Symptoms Associated With Gadolinium Exposure.

ObjectiveRecent scientific publications have reported cases of patients who complained from a variety of symptoms after they received a gadolinium-based contrast agent (GBCA). The aim of this study was to appreciate the importance of these clinical manifestations in the overall population by assessing the weight of “symptoms associated with gadolinium exposure” (SAGE) among the bulk of safety experiences reported to major health authorities.Materials and MethodsSymptoms associated with gadolinium exposure were identified from a review of the scientific literature, and the corresponding preferred terms were searched in each system organ class (SOC) category recorded in the European and North American pharmacovigilance databases EudraVigilance (EV) and FDA Adverse Event Reporting System (FAERS), respectively. The numbers of SAGE per preferred term, and cumulatively per SOC, were recorded and their weights in the overall spectrum of adverse events (AEs) were determined for each GBCA.ResultsThe analysis of the selected AEs revealed a significantly higher SAGE weight for gadobenate dimeglumine (EV: 25.83%, FAERS: 32.24%) than for gadoteridol (EV: 15.51%; FAERS: 21.13%) and significantly lower SAGE weights for gadobutrol (EV: 7.75%; FAERS: 13.31%) and gadoterate meglumine (EV: 8.66%; FAERS: 12.99%). A similar ranking was found for most of the SOCs except for “nervous system disorders,” probably owing to a limitation in the methods of data selection. Furthermore, this analysis showed a greater percentage of reports mentioning a decrease in the quality of life of the patients when they were exposed to gadobenate dimeglumine or gadoteridol than to gadobutrol or gadoterate meglumine.ConclusionThis study showed that SAGE represent a significant percentage of the bulk of AEs reported to the health authorities for each GBCA. It provided real-life arguments suggesting that SAGE may be more prevalent with linear than macrocyclic GBCAs and that gadoteridol may present a higher SAGE risk than the other macrocyclic contrast agents.

Symptoms Associated with Gadolinium Exposure (SAGE): A Suggested Term.

In this article, members of the American College of Radiology Committee on Drugs and Contrast Media propose a new term for symptoms reported after intravascular exposure to gadolinium-based contrast agents-Symptoms Associated with Gadolinium Exposure, or SAGE. This term is advocated in lieu of other proposed nomenclature that presumes a causal relationship that has not yet been scientifically verified. The purpose of this new term, SAGE, is to assist researchers and clinical providers in describing such symptoms without prematurely causally attributing them to a disease and to standardize reporting of these symptoms to allow for coherent interpretation of related studies.

Intracranial meningioma surveillance using volumetrics from T2-weighted MRI.

The gold standard for imaging of meningiomas is MRI with gadolinium-based contrast agent. Due to increased costs, time, and uncertain chronic effects of gadolinium exposure, use of noncontrast T2-weighted imaging (T2WI) in lieu of contrast-enhanced MRI has been an increasing focus of research across various diagnostic scenarios. The purpose of this study was to evaluate the diagnostic accuracy of T2WI in detecting changes in meningioma tumor volume. Imaging and clinical data were reviewed for 82 consecutive patients undergoing MR-surveillance of intracranial meningioma. Using volumetric-T2WI, two neuroradiologists independently calculated tumor volumes. Measurements were compared to a baseline study contrast-enhanced T1 tumor volume. Using contrast-enhanced sequences as the reference standard, statistical analysis was performed to determine the accuracy of T2WI in detecting changes of meningioma volume. Using only T2WI, readers detected meningioma volume change ≥ 20% in 19/82 patients and volume change <20% in 63/82 patients. Reader accuracy for detecting change in tumor volume on T2WI ≥ 20% was 0.85, sensitivity 0.65, specificity 0.93, positive predictive value (PPV) 0.79, and negative predictive value (NPV) 0.87. For meningiomas >1 ml, reader accuracy for detecting change in tumor volume on T2WI ≥20% was 0.90, sensitivity 0.78, specificity 0.95, PPV 0.88, and NPV 0.91. Change in tumor volume on T2WI ≥20% was detected with 100% accuracy for posterior fossa meningiomas. Inter-reader agreement for all meningiomas was moderate (κ = 0.45) improving to substantial agreement (κ = 0.77) with tumor volumes >1 ml. Volumetric-T2WI detects changes in meningioma volume with comparable accuracy to gold standard T1 postcontrast imaging, particularly with higher tumor volumes and posterior fossa locations.

Can Deep Learning Replace Gadolinium in Neuro-Oncology?: A Reader Study.

This monocentric retrospective study leveraged 200 multiparametric brain MRIs acquired between November 2019 and February 2020 at Gustave Roussy Cancer Campus (Villejuif, France). A total of 145 patients were included: 107 formed the training sample (55 ± 14 years, 58 women) and 38 the separate test sample (62 ± 12 years, 22 women). Patients had glioma, brain metastases, meningioma, or no enhancing lesion. T1, T2-FLAIR, diffusion-weighted imaging, low-dose, and standard-dose postcontrast T1 sequences were acquired. A deep network was trained to process the precontrast and low-dose sequences to predict "virtual" surrogate images for contrast-enhanced T1. Once trained, the deep learning method was evaluated on the test sample. The discrepancies between the predicted virtual images and the standard-dose MRIs were qualitatively and quantitatively evaluated using both automated voxel-wise metrics and a reader study, where 2 radiologists graded image qualities and marked all visible enhancing lesions. The automated analysis of the test brain MRIs computed a structural similarity index of 87.1% ± 4.8% between the predicted virtual sequences and the reference contrast-enhanced T1 MRIs, a peak signal-to-noise ratio of 31.6 ± 2.0 dB, and an area under the curve of 96.4% ± 3.1%. At Youden's operating point, the voxel-wise sensitivity (SE) and specificity were 96.4% and 94.8%, respectively. The reader study found that virtual images were preferred to standard-dose MRI in terms of image quality (P = 0.008). A total of 91 reference lesions were identified in the 38 test T1 sequences enhanced with full dose of contrast agent. On average across readers, the brain lesion SE of the virtual images was 83% for lesions larger than 10 mm (n = 42), and the associated false detection rate was 0.08 lesion/patient. The corresponding positive predictive value of detected lesions was 92%, and the F1 score was 88%. Lesion detection performance, however, dropped when smaller lesions were included: average SE was 67% for lesions larger than 5 mm (n = 74), and 56% with all lesions included regardless of their size. The false detection rate remained below 0.50 lesion/patient in all cases, and the positive predictive value remained above 73%. The composite F1 score was 63% at worst. The proposed deep learning method for virtual contrast-enhanced T1 brain MRI prediction showed very high quantitative performance when evaluated with standard voxel-wise metrics. The reader study demonstrated that, for lesions larger than 10 mm, good detection performance could be maintained despite a 4-fold division in contrast agent usage, unveiling a promising avenue for reducing the gadolinium exposure of returning patients. Small lesions proved, however, difficult to handle for the deep network, showing that full-dose injections remain essential for accurate first-line diagnosis in neuro-oncology.

Influence of aging and gadolinium exposure on T1, T2, and T2*-relaxation in healthy women with an increased risk of breast cancer with and without prior exposure to gadoterate meglumine at 3.0-T brain MR imaging

ObjectivesWe examined the effects of aging and of gadolinium-based contrast agent (GBCA) exposure on MRI measurements in brain nuclei of healthy women.MethodsThis prospective, IRB-approved single-center case-control study enrolled 100 healthy participants of our high-risk screening center for hereditary breast cancer, who had received at least six doses of macrocyclic GBCA (exposed group) or were newly entering the program (GBCA-naïve group). The cutoff “at least six doses” was chosen to be able to include a sufficient number of highly exposed participants. All participants underwent unenhanced 3.0-T brain MRI including quantitative T1, T2, and R2* mapping and T1- and T2-weighted imaging. The relaxation times/signal intensities were derived from region of interest measurements in the brain nuclei performed by a radiologist and a neuroradiologist, both board certified. Statistical analysis was based on descriptive evaluations and uni-/multivariable analyses.ResultsThe participants (exposed group: 49, control group: 51) were aged 42 ± 9 years. In a multivariable model, age had a clear impact on R2* (p < 0.001–0.012), T2 (p = 0.003–0.048), and T1 relaxation times/signal intensities (p < 0.004–0.046) for the majority of deep brain nuclei, mostly affecting the substantia nigra, globus pallidus (GP), nucleus ruber, thalamus, and dentate nucleus (DN). The effect of prior GBCA administration on T1 relaxation times was statistically significant for the DN, GP, and pons (p = 0.019–0.037).ConclusionsIn a homogeneous group of young to middle-aged healthy females aging had an effect on T2 and R2* relaxation times and former GBCA applications influenced the measured T1 relaxation times.Key PointsThe quantitative T1, T2, and R2* relaxation times measured in women at high risk of developing breast cancer showed characteristic bandwidth for all brain nuclei examined at 3.0-T MRI.The effect of participant age had a comparatively strong impact on R2*, T2, and T1 relaxation times for the majority of brain nuclei examined.The effect of prior GBCA administrations on T1 relaxation times rates was comparatively less pronounced, yielding statistically significant results for the dentate nucleus, globus pallidus, and pons.Summary statementHealthy women with and without previous GBCA-enhanced breast MRI exhibited age-related T2* and T2 relaxation alterations at 3.0 T-brain MRI. T1 relaxation alterations due to prior GBCA administration were comparatively less pronounced.

Susceptibility-Weighted Imaging of the Pediatric Brain after Repeat Doses of Gadolinium-Based Contrast Agent.

Gadolinium complexes have paramagnetic properties; thus, we aimed to determine the susceptibility changes in the globus pallidus and dentate nucleus following administration of linear or macrocyclic gadolinium-based contrast agents in children. Thirty-three patients with linear gadolinium-based contrast agent gadopentetate dimeglumine administration, 33 age- and sex-matched patients with macrocyclic gadolinium-based contrast agent gadobutrol administration, and 33 age- and sex-matched control subjects without gadolinium exposure were enrolled in this retrospective study. The signal intensity on SWI and T1WI was determined in the dentate nucleus, middle cerebellar peduncle, globus pallidus, and pulvinar of the thalamus in an ROI-based analysis to calculate dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios. A repeated measures ANOVA was performed to compare SWIminimum, SWImean, and T1WI signal intensity ratios between gadolinium-based contrast agent groups and control subjects. Pearson correlation analysis was performed to determine any correlation between signal intensity ratios and variables. Dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios for both SWImean and SWIminimum were lower for the linear gadolinium-based contrast agent group compared with macrocyclic gadolinium-based contrast agent and control groups (P < .05). No significant difference of the SWImean and SWIminimum ratios were noted between the macrocyclic gadolinium-based contrast agent group and the control group (P > .05). Both dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios on T1WI in the linear gadolinium-based contrast agent group were higher than in the control group and the macrocyclic gadolinium-based contrast agent group (P < .05). A negative correlation was identified between SWImean and SWIminimum ratios and the number of linear gadolinium-based contrast agent administrations (dentate nucleus-to-middle cerebellar peduncle ratio: SWImean, r = -0.43, P = .005; SWIminimum, r = -0.38, P = .011; globus pallidus-to-thalamus ratio: SWImean, r = -0.39, P = .009; SWIminimum, r = -0.33, P = .017). SWI analysis of the pediatric brain demonstrated a statistically significant decrease in SWIminimum and SWImean values for the dentate nucleus and globus pallidus after administration of linear gadolinium-based contrast agents but not macrocyclic gadolinium-based contrast agents.

Gadolinium-based contrast media exposure and the possible risk of subclinical kidney damage: a pilot study.

We performed a pilot study to evaluate the feasibility of future research about the presence of subclinical kidney damage after Gadolinium-based contrast media exposure. The future study aims to understand which are the behaviors of two markers of kidney damage, such as urinary NephroCheck (NC) and/or neutrophil gelatinase-associated lipocalin (NGAL). Specifically, after GBCM exposure, NC urinary detection should identify proximal tubule damage while NGAL urinary detection should be related to distal tubule damage. We performed a pilot study in patients who had Gadolinium exposure. The feasibility of future study is reached when at least 90% of candidates completed the pilot study. In each patient, we tested urinary NC and NGAL levels 24h before magnetic resonance imaging (MRI) and 12-24h after the exposure. Furthermore, we evaluated the administration of other nephrotoxic agents, the presence of comorbidity, and kidney function by S-creatinine and urine protein before the MRI. We enrolled 35 candidates of whom 33 patients completed all study procedures. Our population had a mean age of 60.7 ± 14.8years with normal kidney function with a median S-creatinine equal to 0.7mg/dl (Interquartile range [IQR] 0.6-0.91). Urinary NC levels increased from 0.21ng2/ml2 (IQR 0.11-0.4) before MRI to 0.34ng2/ml2 (IQR 0.16-0.86) (p = 0.005). Conversely, we did not appreciate any significant modification in urinary NGAL (p = 0.53). Our pilot study seems adequate in terms of feasibility and encourages us to focus our future research on renal proximal tubule, as the principal site of subclinical kidney damage after Gadolinium exposure.

Role of gadolinium-based contrast agents in neurological disorders.

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to help with the diagnostic and monitoring processes of many diseases, including neurological disorders. Initially, it was assumed that GBCAs carry minimal risk, are safe and well tolerated. But recent reports of GBCA-associated deposition in many body tissues have raised concerns about the broader health impacts of gadolinium exposure. The aim of this review was to summarise knowledge regarding gadolinium deposition, primarily in the brain structures, and of potential GBCA-associated toxicity. Moreover, we discuss the current recommendations on the use of GBCAs, as well as alternative contrast agents and imaging techniques.

The Diagnostic Accuracy of Magnetic Resonance Imaging for Maternal Acute Adnexal Torsion during Pregnancy: Single-Institution Clinical Performance Review.

Background: For acute adnexal torsion of pregnant women, appropriate treatment based on an accurate diagnosis is especially important for fertility preservation and timely treatment. The 2017 American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 723 announced its practice-changing guidelines to ensure that diagnostic magnetic resonance imaging (MRI) conducted during the first trimester and gadolinium exposure at any time during pregnancy are safe for fetal stability. Unfortunately, few studies have been performed to evaluate the usefulness of the diagnostic accuracy of MRI for acute adnexal torsion during pregnancy. Objective: We sought to determine the efficacy of diagnostic MRI modality using multiparameter for maternal adnexal torsion during pregnancy. Methods: From 1 January 2007 to 31 January 2019, 131 pregnant with MRI tests were reviewed. In this retrospective cohort study, 94 women were excluded due to conditions other than an adnexal mass, and 37 were identified through MRI analyses conducted before surgery for suspected adnexal torsion. The primary outcome was the diagnostic accuracy of sonography and MRI, and the secondary outcome was the usefulness of Apparent diffusion coefficient (ADC) values for predicting the severity of hemorrhagic infarction between the medulla and cortex of the torsed ovarian parenchyma. Results: Our study demonstrates that in the diagnosis of adnexal torsion during pregnancy, the sensitivity, specificity, positive predictive value, and negative predictive value are 62.5%, 83.3%, 90.9%, and 45.5% for sonography and 100%, 77.8%, 90.5%, and 100% for MRI. MRI results in surgical-proven adnexal torsion patients revealed unilocular ovarian cysts (36.8% (7/19)), multilocular ovarian cysts (31.6% (6/19)), and near normal-appearing ovaries (31.6% (6/19)). Pathology in adnexal torsion revealed a corpus luteal ovarian cyst (63.2% (12/19)) and underlying adnexal pathology (46.8% (7/19)). Maternal adnexal torsion during pregnancy was more likely to occur in corpus luteal ovarian cysts than in underlying adnexal masses (odds ratio, 2.14; 95% confidence interval (CI), 0.428–10.738). MRI features for adnexal torsion were as follows: tubal wall thickness, 100% (19/19); ovarian stromal (medullary) edema, 100% (19/19); symmetrical or asymmetrical ovarian cystic wall, 100%(19/19); prominent follicles in the ovarian parenchyma periphery, 57.9% (11/19); periadenxal fat stranding, 84.2% (16/19); uterine deviation to the twisted side, 21.1% (4/19); and peritoneal fluid, 42.1% (8/19). The signal intensity of the ADC values of the ovarian medulla and cortex were compared between the cystectomy and detorsion (CD) and salpingo-oophorectomy (SO) groups. The ADC values of the CD and SO groups were 1.81 ± 0.09 × 10−3 mm2/s and 1.91 ± 0.18 × 10−3 mm2/s, respectively (P = 0.209), in the ovarian medulla and 1.37 ± 0.32 × 10−3 mm2/s and 0.96 ± 0.36 × 10−3 mm2/s, respectively (P = 0.022), in the ovarian cortex. The optimal cut-off value of ADC values for predictable total necrosis in the torsed ovarian cortex was ≤ 1.31 × 10−3 mm2/s (area under the curve (AUC) = 0.81; 95% CI 0.611–1.0; P = 0.028). Conclusion: Our data showed that maternal adnexal torsion during pregnancy occurred in most corpus luteal cystic ovary cases and some normal-appearing ovary during the 1st and 2nd trimesters of gestation. Therefore, this study is the first study to elaborate on the existence or usefulness of the diagnostic MRI for acute maternal adnexal torsion during pregnancy and to provide a predictive diagnosis of the severity of hemorrhagic infarction for deciding surgical radicality.

Dentate Nucleus Signal Intensity Increases Following Repeated Gadobenate Dimeglumine Administrations: A Retrospective Analysis.

Background Increased cerebral signal intensity (SI) has been reported in patients undergoing MRI with gadolinium-based contrast agents (GBCAs). Published data on gadobenate dimeglumine have been somewhat contradictory. Purpose To evaluate the relationship between dosage of gadobenate dimeglumine and SI change at MRI following multiple gadobenate dimeglumine administrations. Materials and Methods In this retrospective study, patients referred for clinically indicated brain MRI from January 2006 through May 2016 were evaluated for inclusion. Eligible patients were between 18 and 90 years old at their baseline brain MRI and had never received a GBCA, had undergone three or more MRI examinations with gadobenate dimeglumine, and had the baseline scan and another brain MRI scan available for comparison. The primary group consisted of patients with four or fewer supratentorial lesions smaller than 3 cm who underwent axial T1-weighted MRI at 1.5 T. One patient had also undergone prior radiation therapy. The secondary group consisted of patients with a history of brain radiation therapy or craniotomy who underwent 1.5-T and 3-T same-plane T1-weighted MRI (in any order). The SI for up to eight brain MRI examinations per patient was measured, and relative SI changes from baseline to interval scans were calculated. A subgroup analysis was performed to assess the gadobenate dimeglumine washout since the last gadolinium exposure. All patients had normal renal and liver functions. Linear mixed regression analyses were performed for variables with P < .05. Results In 43 patients (14 men, 29 women; median age, 49 years; age range, 25-73 years), the dentate nucleus (DN)-to-middle cerebral peduncle (MCP) SI ratio showed a mean increase of 6.7% ± 3.9 in the primary group and 4.0% ± 2.7 in the secondary group (both P < .001) following the administration of 134 mL ± 141 gadobenate dimeglumine over 55 months ± 35.2. The DN/MCP SI ratio increased linearly with the amount of gadobenate dimeglumine, with a mean increase of 0.015% ± 0.004 per 1 mL of gadobenate dimeglumine (R2 = 0.3, P < .001). Conclusion In patients receiving multiple doses of gadobenate dimeglumine, a linear relationship existed between gadobenate dimeglumine administrations and an increase in the dentate nucleus-to-middle cerebral peduncle signal intensity ratio at MRI. © RSNA, 2020 See also the editorial by McDonald and Kallmes in this issue.

Exposure to gadolinium and neurotoxicity: current status of preclinical and clinical studies.

Gadolinium is a rare-earth lanthanide metal that is known to have a direct neurotoxic effect. The scope of the present review is to summarize the current preclinical and clinical evidence on the association between exposure to gadolinium of the central nervous system and neurotoxicity. A literature review was performed by searching for original research papers investigating on gadolinium exposure and neurotoxicity. Gadolinium is neurotoxic through multiple mechanisms, mainly involving Ca++ homeostasis and mitochondrial functions, as shown by preclinical in vitro studies. The available evidence related to the four different classes of gadolinium-based contrast agents commonly applied in clinical practice (i.e., linear and macrocyclic based on ligand structure, and ionic and non-ionic based on their net molecular charge) suggests that serial intravenous injections of gadolinium-based contrast agents and gadolinium brain depositions are not associated to histological changes, as confirmed by preclinical animal and human (MR imaging and autopsy) studies. To date, no cause-effect relationship has been demonstrated in patients between brain gadolinium exposure and clinical consequences specific to neurological toxicity.

Prospective Imaging Trial Assessing Gadoteridol Retention in the Deep Brain Nuclei of Women Undergoing Breast MRI

To assess for indirect evidence of gadoteridol retention in the deep brain nuclei of women undergoing serial screening breast MRI. This HIPAA-compliant prospective observational noninferiority imaging trial was approved by the IRB. From December 2016 to March 2018, 12 consented subjects previously exposed to 0-1 doses of gadoteridol (group 1) and 7 consented subjects previously exposed to ≥4 doses of gadoteridol (group 2) prospectively underwent research-specific unenhanced brain MRI including T1w spin echo imaging and T1 mapping. Inclusion criteria were: (1) planned breast MRI with gadoteridol, (2) no gadolinium exposure other than gadoteridol, (3) able to undergo MRI, (4) no neurological illness, (5) no metastatic disease, (6) no chemotherapy. Regions of interest were manually drawn in the globus pallidus, thalamus, dentate nucleus, and pons. Globus pallidus/thalamus and dentate nucleus/pons signal intensities and T1-time ratios were calculated using established methods and correlated with cumulative gadoteridol dose (mL). All subjects were female (mean age: 50 ± 12 years) and previously had received an average of 0.5 ± 0.5 (group 1) and 5.9 ± 2.1 (group 2) doses of gadoteridol (cumulative dose: 8 ± 8 and 82 ± 31 mL, respectively), with the last dose an average of 492 ± 299 days prior to scanning. There was no significant correlation between cumulative gadoteridol dose (mL) and deep brain nuclei signal intensity at T1w spin echo imaging (p = 0.365-0.512) or T1 mapping (p = 0.197-0.965). We observed no indirect evidence of gadolinium retention in the deep brain nuclei of women undergoing screening breast MRI with gadoteridol.