A preclinical study by Bower et al. found that gadolinium-based contrast agents (GBCAs) have a toxic effect on mitochondrial respiratory function and cell viability in human neurons.  The study, Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases with Reduced Kinetic Stability of the Agent, was published online ahead of print in Investigative Radiology.  For the study, neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is one of two brain regions that displays the greatest T1-dependent signal hyperintensity changes.  Multiple studies have shown that T1-signal intensity changes in the brain are the result of gadolinium deposition.  The authors noted that there is increasing evidence that all agents (linear and macrocyclic) remain in human brain tissue for some period of time, where they may be taken up into various cell types, including glia and neurons.

Reports of possible clinical symptoms experienced by patients after a contrast-enhanced MRI have been published. However, until this study, it was unknown whether GBCAs induce toxic effects on the cellular function of human neurons.  This study provides the first definitive evidence that GBCAs induce mitochondrial toxicity and cell death in cultured human neurons.  The authors said that the “magnitude of the measured toxicity broadly increases as the kinetic stability of the contrast agent decreases, and the lower stability agents induce toxicity at concentrations that fall within the range detected in some autopsy patients”.  “For all agents, the magnitude of the toxicity increases with concentration.”

An answered question is whether cellular dysfunction could produce clinical effects.  The authors noted that “any cellular toxicity is concerning, and any cellular toxicity may accelerate cell death due to normal aging, which could become clinically significant in older patients who have received multiple MRIs with a GBCA over the course of their life”.

My thoughts –

While more research is needed, I believe it is time to “officially” recognize the clinical symptoms of gadolinium toxicity reported by patients with normal kidney function after their MRIs with a GBCA.  Their symptoms are like those documented in the published literature for NSF patients, and many of the symptoms are included in a list of symptoms of Mitochondrial Diseases published by Cleveland Clinic in 2018.  Mitochondrial diseases can affect almost any part of the body, including cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas.  That might explain why, according to the National Organization of Rare Diseases’ (NORD) website, that the non-dermal symptoms of NSF are “highly variable depending upon the specific organ systems involved”, and “the severity and progression of the disorder can vary from one person to another”.

If NSF is caused by retained gadolinium and gadolinium has a toxic effect on mitochondrial respiratory function and cell viability in human neurons, then why couldn’t retained gadolinium be the cause of the symptoms experienced by patients with normal kidney function after their MRIs with a gadolinium-based contrast agent?  The patients’ symptoms may not all be exactly the same, but according to NORD, they were not the same in NSF patients either.

Sharon Williams
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References:
Bower, D. V, Richter, J. K., von Tengg-Kobligk, H., Heverhagen, J. T., & Runge, V. M. (9000). Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases With Reduced Kinetic Stability of the Agent. Investigative Radiology, Publish Ah. Retrieved from https://journals.lww.com/investigativeradiology/Fulltext/publishahead/Gadolinium_Based_MRI_Contrast_Agents_Induce.98911.aspx

MITOCHONDRIAL DISEASES Cleveland Clinic. (2018, October). https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases

National Organization of Rare Diseases. (2014). Nephrogenic Systemic Fibrosis. Retrieved from https://rarediseases.org/rare-diseases/nephrogenic-systemic-fibrosis/