Effect of Renal Function on Gadolinium-Related Signal Increases on Unenhanced T1-Weighted Brain Magnetic Resonance Imaging

Cao, Yan; Zhang, Yang; Shih, George; Zhang, Yan; Bohmart, Andrew; Hecht, Elizabeth M.; Prince, Martin R.

doi:10.1097/rli.0000000000000294

Cited by 45 publications

(31 citation statements)

References 41 publications

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“…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]. This entity of simple retention in tissues has been recently termed "gadolinium storage condition (GSC)" [29].…”

Section: Gadolinium Storage Conditionmentioning

confidence: 99%

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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Section: Gadolinium Storage Conditionmentioning

confidence: 99%

Gadolinium toxicity and treatment

Ramalho

Jay

et al. 2016

Magnetic Resonance Imaging

103

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“…T1-weighted hyperintensity in the dentate nucleus has been shown recently to occur at lower cumulative doses of linear agents in patients on dialysis than in prior studies of patients with normal renal function. 46 Evidence-from both clinical and preclinical studies-to date favors that patients with impaired renal function are at higher risk for gadolinium accumulation in the brain and in bone, with this conclusion applying only to the group of agents that have such gadolinium deposition, the linear chelates. 34 Both cited studies furthermore noted deposition of gadolinium in the choroid plexus (beyond what was previously established, specifically the dentate nucleus and the globus pallidus).…”

Section: Minimizing Riskmentioning

confidence: 99%

Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents

2017

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For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.

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“…One possible pathway for gadolinium entering the brain might be passage of GBCAs directly from blood into the cerebrospinal fluid (CSF). Recently, Cao et al [26] reported on the renal function effect on gadolinium-related signal increase on unenhanced T1-MRI, and found a trend toward increased choroid plexus signal intensity after GBCA exposure, which also supports this hypothesis.…”

Section: Quantitative Ratios Measurementsmentioning

confidence: 61%

“…Cao et al [26] recently demonstrated that the dentate T1 signal increase occurring in hemodialysis patients was significantly higher compared with that of control subjects matched for age, sex, and GBCA exposure; suggesting that the longer exposure to GBCAs, due to longer dwell time, leads to a greater effect on the DN in renal failure patients. Fortunately, all published studies either used abnormal kidney function as an exclusionary factor in their analysis or conducted careful controlled for kidney function to ensure that any gadolinium deposition in the brain was not caused by deficient clearance of GBCAs by the kidneys [31].…”

Section: Population Variabilitymentioning

confidence: 99%

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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Effect of Renal Function on Gadolinium-Related Signal Increases on Unenhanced T1-Weighted Brain Magnetic Resonance Imaging

Abstract: Hemodialysis patients receiving linear GBCA have greater dentate nucleus signal increases on unenhanced T1-weighted images, suggesting that renal function may affect the rate of gadolinium accumulation in the brain after linear GBCA-enhanced magnetic resonance imaging.

Cited by 45 publications

References 41 publications

Gadolinium toxicity and treatment

Gadolinium toxicity and treatment

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

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