Gadolinium Toxicity

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Gadolinium retention in brain tissue of patients with normal renal function

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On April 6, 2015, a study by Radbruch et al was published online ahead of print in Radiology.  Like other recent studies, it reports on evidence of gadolinium retention in brain tissues of patients who had multiple MRIs with a gadolinium-based contrast agent or GBCA.  The study, Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent, found that increased signal intensity (SI) in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted MR images is caused by serial administration of the linear GBCA gadopentetate dimeglumine (Magnevist), but not by the macrocyclic GBCA gadoterate meglumine (Dotarem).

The retrospective study was comprised of two groups of 50 patients who had undergone at least 6 consecutive MRIs with only the linear agent Magnevist or only the macrocyclic agent Dotarem.  All patients had an estimated glomerular filtration rate (eGFR) greater than 60 – which is a level of renal function not considered to be at risk of retaining gadolinium from the administered gadolinium-based contrast agent.  Of the 100 patients included in the study, 21 had an eGFR 60-90, and 79 patients had an eGFR greater than 90. 

Besides excluding patients that had an eGFR less than 60, other exclusion criteria included: history of brain hemorrhage, stroke, or brain ischemia; edema, tumor, or other lesions located in the cerebellum or pons; history of intracranial infection, such as meningitis or encephalitis; missing documentation of the contrast agent administered.  They also checked liver function, but they did not exclude patients with abnormal liver function since the two GBCAs in the study are eliminated by the kidneys.

The image analysis was conducted as described in previously published studies by Kanda et al, but the cerebrospinal fluid (CSF) was added as an additional validator.  In this study, the dentate nucleus signal intensity was compared with that of three structures: the pons, CSF, and cerebellum.  In all the comparisons, the difference was significantly larger in the linear GBCA group than in the macrocyclic group.

The results showed that both the number of contrast-enhanced MRI and the accumulated dose of GBCA were predictors of increased signal intensity for the linear GBCA (Magnevist) group, but not the macrocyclic (Dotarem) group.  Despite a greater cumulative dosage in the macrocyclic group, only the group that received the linear GBCA showed increased signal intensities on unenhanced T1-weighted MR images.

What do these findings mean for patients?  Radbruch and his colleagues said, “Even though no clinical implications can be drawn from the reported hyperintensities in the DN [dentate nucleus] and GP [globus pallidus], the findings are worrisome and should be taken into account when deciding whether to use gadopentetate dimeglumine”.  “Future studies should be conducted to investigate whether this difference holds true for all linear and macrocyclic GBCAs.”

All of the recent studies have involved findings of gadolinium retention in the brain.  However, Radbruch and his colleagues said, “It is still unclear whether the potential gadolinium retention is also present in other parts of the human body”.  It would seem that additional research is urgently needed to make that determination, especially since systemic internal damage caused by retained gadolinium has already been well-documented in NSF cases.

For more information about Gadolinium and Gadolinium-Based Contrast Agents see Background on Gadolinium and Background on GBCAs in the Background section of our website.

Sharon Williams

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Radbruch, A., Weberling, L. D., Kieslich, P. J., Eidel, O., Burth, S., Kickingereder, P., … Bendszus, M. (2015). Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent. Radiology, 150337. http://doi.org/10.1148/radiol.2015150337

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. doi:10.1148/radiol.13131669.  Retrieved from http://pubs.rsna.org/doi/abs/10.1148/radiol.13131669

Kanda, T., Osawa, M., Oba, H., Toyoda, K., Kotoku, J., Haruyama, T., … Furui, S. (2015). High Signal Intensity in Dentate Nucleus on Unenhanced T1-weighted MR Images: Association with Linear versus Macrocyclic Gadolinium Chelate Administration. Radiology, 140364. http://doi.org/10.1148/radiol.14140364


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