Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents

Fingerhut, Stefanie; Niehoff, Ann-Christin; Sperling, Michael; Jeibmann, Astrid; Paulus, Werner; Niederstadt, Thomas; Allkemper, Thomas; Heindel, Walter; Holling, Markus; Kärst, Uwe

doi:10.1016/j.jtemb.2017.10.004

Cited by 47 publications

(27 citation statements)

References 39 publications

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“…The hypothesis is that Gd precipitates along with calcium phosphate and forms persistent insoluble deposits with diameters of a few micrometers, triggering the circulation of fibrocytes, which subsequently initiate fibrosis [188]. With their distinct advantages and limitations, a broad range of techniques, such as scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), transmission electron microscopy (TEM), secondary ion mass spectrometry (SIMS), extended X-ray absorption fine structure (EXAFS) spectroscopy, synchrotron X-ray fluorescence (SXRF) microscopy, and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), are available to perform elemental bio-imaging (EBI) and study insoluble Gd-containing deposits [175,[189][190][191][192][193].…”

Section: Human Health Risks Of Gd Anthmentioning

confidence: 99%

Gadolinium as an Emerging Microcontaminant in Water Resources: Threats and Opportunities

Ebrahimi

Barbieri

2019

Geosciences

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As a result of high doses of paramagnetic gadolinium (Gd) chelates administered in magnetic resonance imaging (MRI) exams, their unmetabolized excretion, and insufficient removal in wastewater treatment plants (WWTPs), large amounts of anthropogenic Gd (Gdanth) are released into surface water. The upward trend of gadolinium-based contrast agent (Gd-CA) administrations is expected to continue growing and consequently higher and higher anthropogenic Gd concentrations are annually recorded in water resources, which can pose a great threat to aquatic organisms and human beings. In addition, the feasibility of Gd retention in patients administered with Gd-CAs repeatedly, and even potentially fatal diseases, including nephrogenic systemic fibrosis (NSF), due to trace amounts of Gd have recently arisen severe health concerns. Thus, there is a need to investigate probable adverse health effects of currently marketed Gd-CAs meticulously and to modify the actual approach in using Gd contrast media in daily practice in order to minimize unknown possible health risks. Furthermore, the employment of enhanced wastewater treatment processes that are capable of removing the stable contrast agents, and the evaluation of the ecotoxicity of Gd chelates and human exposure to these emerging contaminants through dermal and ingestion pathways deserve more attention. On the other hand, point source releases of anthropogenic Gd into the aquatic environment presents the opportunity to assess surface water—groundwater interactions and trace the fate of wastewater plume as a proxy for the potential presence of other microcontaminants associated with treated wastewater in freshwater and marine systems.

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Section: Human Health Risks Of Gd Anthmentioning

confidence: 99%

Gadolinium as an Emerging Microcontaminant in Water Resources: Threats and Opportunities

Ebrahimi

Barbieri

2019

Geosciences

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“…The following MS conditions were used: 1550 W rf power, 14 L min −1 cooling gas flow, 0.9 L•min −1 nebulizer gas flow, and 0.8 L•min −1 auxiliary gas flow. The isotopes 158 Gd + 16 O and 160 Gd + 16 O were monitored with dwell times of 0.08 second each to achieve optimum detection limits based on a study by Clases et al 20 and Fingerhut et al, 21,22 whereas 31 P+ 16 O, 57 Fe, 65 Cu, and 66 Zn were monitored with dwell times of 0.04 second each. For bulk analysis of the gadolinium concentration in the gelatin standards, the same ICP-MS instrument as for laser ablation analysis was used with standard liquid sample introduction fed by an ASX-560 autosampler (Teledyne CETAC Technologies).…”

Section: Laser Ablation and Icp-ms Parametersmentioning

confidence: 99%

Gadolinium Deposition in the Brain in a Large Animal Model

et al. 2019

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Objective: Recent studies reported a signal intensity increase in the deep cerebellar nuclei (DCN) on magnetic resonance images caused by gadolinium deposition after the injection of gadoliniumbased contrast agents (GBCAs). There is an ongoing debate if the propensity of a GBCAto deposit gadolinium is primarily determined by its class as either linear or macrocyclic. In the current study, we aimed to compare the amount and the distribution of retained gadolinium of linear and macrocyclic GB-CAs in the DCN after a single injection at a dose comparable to a human patient's in a large animal model. Materials and Methods: Eighteen sheep were randomly assigned in 6 groups of 3 animals, which received a single injection of 0.1 mmol/kg body weight of either the macrocyclic GBCAs gadobutrol, gadoteridol, or gadoterate meglumine; the linear GBCAs gadobenate dimeglumine or gadodiamide; or saline. Animals were euthanized 10 weeks after injection. Local distribution and concentration of gadolinium and colocalization to other metals (iron, zinc, copper) in the DCN was assessed by laser ablation-inductively coupled plasma-mass spectrometry. Results: Average gadolinium concentration for the macrocyclic GBCAs and the saline groupwas below the limit of quantification (5.7 ng/g tissue). In contrast, 14 (for gadobenate) and 27 (for gadodiamide) times more gadolinium than the limit of quantification was found for the linear GBCAs gadobenate (mean, 83 ng/g) or gadodiamide (mean, 155 ng/g brain tissue). Gadolinium distribution colocalized with other metals for linear GBCAs and a specific accumulation in the DCN was found. Discussion: The current study supports the hypothesis that the amount of gadolinium deposited in the brain is primarily determined by its class as either macrocyclic or linear. The accumulation of gadolinium in the DCN for linear GBCAs explains the hyperintensities in the DCN found in previous patient studies with linear GBCAs.

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“…More recently, increased signal intensity on unenhanced T1 W MRI and the presence of gadolinium in the brain of patients with normal renal function have been reported [ 70 , 71 ], with increased signal intensity robustly associated with linear rather than macrocyclic GBCAs such as gadobutrol [ 72 – 77 ]. Trace amounts of gadolinium have also been measured at autopsy in the brain and other body regions after both linear and macrocyclic GBCAs [ 78 – 84 ]. To date, none of the many imaging studies have shown an association between the observed increased signal intensity in the brain after repeated GBCA administrations and the occurrence of any adverse health effects [ 85 ], including in patients with normal renal function [ 70 , 71 ].…”

Section: Place Of Gadobutrol In Ce Mri and Mramentioning

confidence: 99%

Gadobutrol: A Review in Contrast-Enhanced MRI and MRA

Scott¹

2018

Clin Drug Investig

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Intravenous gadobutrol [Gadovist™ (EU); Gadavist® (USA)] is a second-generation, extracellular non-ionic macrocyclic gadolinium-based contrast agent (GBCA) that is approved for use in paediatric (including term neonates) and adult patients undergoing diagnostic contrast-enhanced (CE) MRI for visualization of pathological lesions in all body regions or for CE MRA to evaluate perfusion and flow-related abnormalities. Its unique physicochemical profile, including its high thermostability and proton relaxation times, means that gadobutrol is formulated at twice the gadolinium ion concentration of other GBCAs, resulting in a narrower bolus and consequently, improved dynamic image enhancement. Based on >  20 years of experience in the clinical trial and real-world settings (>  50 million doses) and its low risk for developing nephrogenic systemic fibrosis (NSF), gadobutrol represents an effective and safe diagnostic GBCA for use in CE MRI and MRA to visualize pathological lesions and vascular perfusion and flow-related abnormalities in all body regions in a broad spectrum of patients, including term neonates and other paediatric patients, young and elderly adult patients, and those with moderate or severe renal or hepatic impairment or cardiovascular (CV) disease.

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Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents

Cited by 47 publications

References 39 publications

Gadolinium as an Emerging Microcontaminant in Water Resources: Threats and Opportunities

Gadolinium as an Emerging Microcontaminant in Water Resources: Threats and Opportunities

Gadolinium Deposition in the Brain in a Large Animal Model

Gadobutrol: A Review in Contrast-Enhanced MRI and MRA

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