Gadolinium Toxicity

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MRI brain signal changes reported in a child

The November 2015 issue of Pediatrics includes a case study by Miller et al.  The article, MRI Brain Signal Intensity Changes of a Child During the Course of 35 Gadolinium Contrast Examinations, describes the quantitative signal intensity changes in the brain of a pediatric patient who had 35 MRIs with a linear gadolinium-based contrast agent (GBCA) between the ages of 8 and 20 years.  The authors report that progressive increases were the most evident in the dentate nuclei, the globus pallidus, and the thalamus.  They noted that the pattern of regional brain hyperintensity observed is consistent with findings from recent adult studies.

High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images was first reported by Kanda et al in late 2013 and has been found to be the result of gadolinium deposition in the brain.

Sharon Williams

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Miller, J. H., Hu, H. H., Pokorney, A., Cornejo, P., & Towbin, R. (2015). MRI Brain Signal Intensity Changes of a Child During the Course of 35 Gadolinium Contrast Examinations. Pediatrics, peds.2015–2222–. http://doi.org/10.1542/peds.2015-2222

Kanda, T., Ishii, K., Kawaguchi, H., Kitajima, K., & Takenaka, D. (2013). High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-based Contrast Material. Radiology, 131669. http://doi.org/10.1148/radiol.13131669

New study did not find signal increases in brain after repeat administrations of Gadovist.

A new study by Radbruch et al concerning gadobutrol has been published online ahead-of-print in Investigative Radiology.  The paper, High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol, did not find signal increases in the dentate nucleus (DN) or in the globus pallidus (GP) after serial administrations of gadobutrol (Gadovist, Bayer Healthcare).  The study included 30 patients who had received at least 5 MRI examinations with only Gadovist.

The findings are in contrast to a previously published study by Stojanov et al that we reported about.  That paper was titled, Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-bases contrast agent, gadobutrol (European Radiology, 2015). 

Radbruch and his colleagues concluded that their finding “adds further support to the hypothesis that the molecular structure of a gadolinium-based contrast agent as either macrocyclic or linear is a crucial factor for its potential to cause gadolinium deposition in the brain”.  The authors also noted that future studies are needed to assess this hypothesis.

I agree that additional research is needed.  I would be interested to find out if gadolinium from macrocyclic agents is being deposited in the brain, but perhaps in smaller quantities than from linear agents.  If so, it might be that the amount of deposited gadolinium has to reach a certain level before signal increases are detected on magnetic resonance images (MRI).  Still to be determined are the long-term effects of any amount of gadolinium deposition in the brain or elsewhere in the body.

Sharon Williams

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Radbruch, A., Weberling, L. D., Kieslich, P. J., Hepp, J., Kickingereder, P., Wick, W., … Bendszus, M. (2015). High-Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol. Investigative Radiology, 50(12). Retrieved from http://journals.lww.com/investigativeradiology/Fulltext/2015/12000/High_Signal_Intensity_in_the_Dentate_Nucleus_and.1.aspx

Stojanov, D. A., Aracki-Trenkic, A., Vojinovic, S., Benedeto-Stojanov, D., & Ljubisavljevic, S. (2015). Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast age. European Radiology. http://doi.org/10.1007/s00330-015-3879-9

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