The presence of the gadolinium-based contrast agent depositions in the brain and symptoms of gadolinium neurotoxicity - A systematic review

PLoS One. 2017 Feb 10;12(2):e0171704. doi: 10.1371/journal.pone.0171704. eCollection 2017.


Background and purpose: Gadolinium based contrast agents (GBCAs) are widely used in magnetic resonance imaging, but recently, high signal intensity in the cerebellum structures was reported after repeated administrations of contrast- enhanced magnetic resonance images. The aim of this systematic review was to investigate the association between increased signal intensity in the dentate nucleus and globus pallidus in the brain and repeated administrations of GBCAs. Additionally, we focused on possible short- and long-term consequences of gadolinium use in those patients.

Methods: Systematic review of retrospective investigations in PubMed and Medline was performed in July 2016. Primary outcomes included the presence of increased signal intensity within the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in patients following administrations of GBCAs. Two independent reviewers were responsible for search and data extraction.

Results: 25 publications satisfied inclusion criteria (19 magnetic resonance images analyses, 3 case reports; 3 autopsy studies). Magnetic resonance images of 1247 patients with increased signal intensity on unenhanced T1-weighted MR images were analyzed as well as tissue specimens from 27 patients. Signal intensity correlated positively with the exposure to GBCAs and was greater after serial administrations of linear nonionic than cyclic contrast agents. Gadolinium was detected in all tissue examinations.

Conclusions: High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance images were associated with previous administration of GBCAs. Signal intensity correlated negatively with stability of contrast agents. Clinical significance of gadolinium deposition in the brain remains unclear. There is a strong need for further research to identify type of gadolinium deposited in the brain as well as to gather knowledge about long-term consequences.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / pathology
  • Contrast Media / adverse effects*
  • Contrast Media / toxicity
  • Gadolinium / adverse effects*
  • Gadolinium / toxicity
  • Humans
  • Magnetic Resonance Imaging / adverse effects
  • Neurotoxins / adverse effects*
  • Neurotoxins / toxicity


  • Contrast Media
  • Neurotoxins
  • Gadolinium

Grant support

The authors received no specific funding for this work.