Elsevier

The Lancet Neurology

Volume 16, Issue 7, July 2017, Pages 564-570
The Lancet Neurology

Personal View
Gadolinium deposition in the brain: summary of evidence and recommendations

https://doi.org/10.1016/S1474-4422(17)30158-8Get rights and content

Summary

Emerging evidence has linked MRI signal changes in deep nuclei of the brain with repeated administration of gadolinium-based contrast agents. Gadolinium deposits have been confirmed in brain tissue, most notably in the dentate nuclei and globus pallidus. Although some linear contrast agents appear to cause greater MRI signal changes than some macrocyclic agents, deposition of gadolinium has also been observed with macrocyclic agents. However, the extent of gadolinium deposition varies between agents. Furthermore, the clinical significance of the retained gadolinium in the brain, if any, remains unknown. No data are available in human beings or animals to show adverse clinical effects due to the gadolinium deposition in the brain. On behalf of the International Society for Magnetic Resonance in Medicine, we present recommendations for the clinical and research use of gadolinium-based contrast agents. These recommendations might evolve as new evidence becomes available.

Introduction

Gadolinium-based contrast agents (GBCAs) are widely used in research and clinical settings, for diagnosis and monitoring of many diseases. The signal intensity of an MR image is affected by T1 and T2 relaxation times, which are characteristic physical properties of each tissue related to its behaviour in a magnetic field. GBCAs shorten the T1 relaxation time of water protons near the agent, and this phenomenon produces images in which tissues with a high concentration of contrast agent are brighter than those with lower concentrations.

Over 30 million doses of GBCA are administered worldwide annually, and over 300 million doses have been administered since their introduction in 1987.1 The risks associated with the use of GBCAs include allergic and adverse reactions (which are infrequent, but can be serious),2, 3 and nephrogenic systemic fibrosis in patients with renal failure. Nephrogenic systemic fibrosis is a rare scleroderma-like illness that occurs in patients with severe renal disease and after exposure to certain GBCAs. Its incidence has been effectively eliminated by restricting the administration of the GBCAs most closely associated with nephrogenic systemic fibrosis in high-risk populations, and by lowering of GBCA dosage.

Multiple studies have shown evidence of residual brightness of tissue in the deep nuclei of the brain, particularly the globus pallidus and the dentate nucleus, in people who have received a GBCA; additional evidence shows that these regional signal changes are directly associated with the deposition of the contrast agent. These findings raise concerns about the context in which gadolinium deposits in the brain, and pose the question as to whether this deposition might cause any harm.

On behalf of the International Society for Magnetic Resonance in Medicine (ISMRM), we summarise the evidence on gadolinium deposition in the brain, contextualise this evidence according to knowledge obtained from cases of nephrogenic systemic fibrosis, and provide recommendations for future use of GBCAs in research and clinical practice.

Section snippets

Gadolinium deposition in the brain

The presence of high MRI signal intensity on unenhanced T1-weighted images of the dentate nucleus and the globus pallidus of patients who had undergone multiple GBCA-enhanced MRI examinations was first described in 2014.4 Increased relative signal intensity correlated with the number of contrast-agent administrations. A comparison of signal intensities in a subgroup of patients who had undergone at least six contrast-enhanced MRI examinations, with either gadopentetate dimeglumine or

Is there any evidence of harm?

The clinical and biological significance of retained gadolinium in the brain, if any, remains unknown. No harm from gadolinium exposure has been seen in animal models and no behavioural changes were reported in animals undergoing repeated examinations with gadolinium agents over a very short time period.21 Burke and colleagues35 have reported a list of non-specific symptoms from a survey of patients who believed that they suffered from gadolinium toxicity, though no evidence is available from

Conclusions and future directions

Convincing evidence is available for the deposition of gadolinium in the deep nuclei of the brain, particularly after repeated exposure to GBCAs. Although differences in gadolinium deposition are apparent among the agents and between agents' class, some data are contradictory. Additionally, no data are available regarding gadolinium deposition for some contrast agents. The detection of gadolinium deposition in the brain is concerning; however, there are no reliable data regarding its clinical

Search strategy and selection criteria

A literature search was done for this Personal View, consisting of PubMed, Google Scholar, and ISI Web of Science searches for the terms “gadolinium deposition”, “brain gadolinium”, “gd deposition”, and “deposition MRI” between September, 2015, and March, 2017. Because of the large number of published reports on this topic, those deemed most relevant for the aims of this Personal View were selected. Excluded from our selection were research articles that provided only anecdotal evidence. Papers

References (42)

  • J Ramalho et al.

    High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear gadolinium-based contrast agents

    Radiology

    (2015)
  • JH Miller et al.

    MRI brain signal intensity changes of a child during the course of 35 gadolinium contrast examinations

    Pediatrics

    (2015)
  • T Kanda et al.

    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

    Radiology

    (2015)
  • AP Smith et al.

    Clearance of gadolinium from the brain with no pathologic effect after repeated administration of gadodiamide in healthy rats: an analytical and histologic study

    Radiology

    (2017)
  • M Port et al.

    Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review

    Biometals

    (2008)
  • ACR manual on contrast media version v10·1

    (2015)
  • DR Roberts et al.

    Distribution map of gadolinium deposition within the cerebellum following GBCA administration

    Neurology

    (2017)
  • T Kanda et al.

    High signal intensity in dentate nucleus on unenhanced T1-weighted MR Images: association with linear versus macrocyclic gadolinium chelate administration

    Radiology

    (2015)
  • P Robert et al.

    Linear gadolinium-based contrast agents are associated with brain gadolinium retention in healthy rats

    Invest Radiol

    (2016)
  • Y Cao et al.

    Signal change in the dentate nucleus on T1-weighted MR images after multiple administrations of gadopentetate dimeglumine versus gadobutrol

    AJR Am J Roentgenol

    (2016)
  • L Schlemm et al.

    Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients

    Mult Scler

    (2016)
  • Cited by (0)

    View full text