Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents

PLoS One. 2020 Feb 3;15(2):e0227649. doi: 10.1371/journal.pone.0227649. eCollection 2020.

Abstract

Objective: To determine the effect of a linear gadolinium-based contrast agent (GBCA) on the signal intensity (SI) of the deep cerebellar nuclei (DCN) in a retrospective clinical study on dogs after multiple magnetic resonance (MR) examinations with intravenous injections of gadodiamide and LA-ICP-MS analysis of a canine cerebellum after gadodiamide administration.

Animals: 15 client-owned dogs of different breeds and additionally 1 research beagle dog cadaver.

Procedures: In the retrospective study part, 15 dogs who underwent multiple consecutive MR imaging examinations with intravenous injection of linear GBCA gadodiamide were analyzed. SI ratio differences on unenhanced T1-weighted MR images before and after gadodiamide injections was calculated by subtracting SI ratios between DCN and pons of the first examination from the ratio of the last examination. Additionally, 1 research beagle dog cadaver was used for LA-ICP-MS (Laser ablation inductively coupled plasma mass spectrometry) analysis of gadolinium in the cerebellum as an add-on to another animal study. Descriptive and non-parametrical statistical analysis was performed and a p-value of < 0.05 was considered significant.

Results: No statistically significant differences of SI ratios, between DCN and pons, were detectable based on unenhanced T1-weighted MR images. LA-ICP-MS analyses showed between 1.5 to 2.5 μg gadolinium/g tissue in the cerebellum of the examined dog, 35 months after the last of 3 MRI examination with gadodiamide (two examinations at a dose of 1 x 0.1mmol/kg, last examination at a dose of 3 x 0.05mmol/kg).

Conclusion and clinical relevance: Although the retrospective MRI study did not indicate any visible effect of SI increase after multiple gadodiamide exposures, further studies based on LA-ICP-MS showed that the optical threshold was not reached for a potential visible effect. Gadolinium was detectable at a level of 1.5 to 2.5 μg gadolinium/g tissue by using LA-ICP-MS in the cerebellum 35 months after last MRI examination. The general importance of gadolinium retention of subvisible contents requires further investigation.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Cerebellar Nuclei / diagnostic imaging*
  • Contrast Media / pharmacology*
  • Dogs
  • Gadolinium / pharmacology*
  • Humans
  • Magnetic Resonance Imaging

Substances

  • Contrast Media
  • Gadolinium

Grants and funding

The author(s) received no specific funding for this work.