Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy

Kanda, Tomonori; Fukusato, Toshio; Matsuda, Megumi; Toyoda, Keiko; Oba, Hiroshi; Kotoku, J.; Haruyama, Takahiro; Kitajima, Kazuhiro; Furui, Shigeru

doi:10.1148/radiol.2015142690

Cited by 788 publications

(614 citation statements)

References 16 publications

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“…Gadolinium presence was originally observed in bone [5,6,30] and more recently in the brain [7][8][9][31][32][33][34][35][36][37][38][39] in patients with normal renal function.…”

Section: Gadolinium Storage Conditionmentioning

confidence: 98%

“…The authors found proportionate content of brain and bone, with bone having approximately 20 times the concentration of gadolinium compared to brain, with both linear and macrocyclic agents [9]. What is currently known, is that gadolinium is retained in body tissues, regardless of renal function or even GBCA stability [5][6][7][8][9]. Higher concentrations appear to occur in patients with renal impairment [40] or after exposure to the less stable GBCAs [41,42].…”

Section: Gadolinium Storage Conditionmentioning

confidence: 99%

“…The potential implication of this was not fully appreciated, until almost a decade later when gadolinium was found in brain tissue [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Gadolinium toxicity and treatment

Ramalho

Jay

et al. 2016

Magnetic Resonance Imaging

103

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a b s t r a c t a r t i c l e i n f oGadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known.

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“…Gadolinium presence was originally observed in bone [5,6,30] and more recently in the brain [7][8][9][31][32][33][34][35][36][37][38][39] in patients with normal renal function.…”

Section: Gadolinium Storage Conditionmentioning

confidence: 98%

Section: Gadolinium Storage Conditionmentioning

confidence: 99%

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Gadolinium toxicity and treatment

Ramalho

Jay

et al. 2016

Magnetic Resonance Imaging

103

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“…These differences in the chemical structure of the ligands explain the difference in thermodynamic and kinetic stability, whereby the non-ionic linear chelates are the least stable and the ionic macrocyclic chelates are the most stable [3]. The free gadolinium ion is mostly hydrated in biological systems, and this Gd(H 2 O) 8 3+ ion is toxic because of its chemical similarities to Ca 2+ , which is an important factor for proper functioning of many processes in the human body such as contraction of the heart muscle and smooth muscle cells, and nerve transmission. Gd 3+ can compete with Ca 2+ due to its similarity in ion radius, and could thereby disturb physiological processes.…”

Section: Introductionmentioning

confidence: 99%

Gadolinium retention after administration of contrast agents based on linear chelators and the recommendations of the European Medicines Agency

2017

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The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) earlier this year recommended to suspend some marketing authorisations for Gadolinium Containing Contrast Agents (GCCAs) based on linear chelators due to the potential risk of gadolinium retention in the human body. These recommendations have recently been re-evaluated by EMA's Committee for Medicinal Products for Human Use (CHMP), and confirmed the final opinion of the European Medicines Agency. This editorial provides an overview of the available GCCAs and summarises the recent evidence of gadolinium retention. Moreover, a critical appraisal of the strengths and limitations of the scientific evidence currently available on gadolinium retention is given. Key points • EMA recommended suspension of some EU marketing authorisations of four linear GCCAs. • Brain MRI findings indicating gadolinium retention have been confirmed by mass spectrometry.• Current scientific evidence for gadolinium retention has several methodological limitations.• No clear clinical evidence exists indicating that gadolinium retention causes neurotoxicity.• Long-term safety of GCCAs, however, remains unclear.

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“…Gadolinium deposition in brain tissue and its relation to T1 signal intensity changes was confirmed by histopathological human studies [10][11][12][13]. However, these studies found that gadolinium deposits were present in all evaluated brain tissues (with higher concentration in DN followed by GP) after the administration of either linear or macrocyclic agents, suggesting that MRI has a relative limited sensitivity to detect gadolinium deposition in brain tissue.…”

Section: Introductionmentioning

confidence: 92%

Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration

Ramalho

AlObaidy

et al. 2016

Magnetic Resonance Imaging

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Over the last 2 years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility.

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Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy

Abstract: Even in subjects without severe renal dysfunction, GBCA administration causes gadolinium accumulation in the brain, especially in the DN and GP.

Cited by 788 publications

References 16 publications

Gadolinium toxicity and treatment

Gadolinium toxicity and treatment

Gadolinium retention after administration of contrast agents based on linear chelators and the recommendations of the European Medicines Agency

Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration

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