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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.” (more…)
The National Center for Health Research (NCHR) recently published a new white paper on its website about gadolinium-based contrast agents (GBCAs). The title of the paper is “The Health Risks of Gadolinium-Based Contrast Agents used in MRIs” and the authors are Stephanie Fox-Rawlings, PhD, and Diana Zuckerman, PhD. The paper provides a detailed history of GBCAs from regulation, to gadolinium toxicity and its clinical effects, possible treatments, and environmental exposure.
While there is much that we know about gadolinium and GBCAs, the authors acknowledge that there are still uncertainties, but that “the research thus far suggests that some people with healthy kidney function have been harmed by gadolinium. This conclusion is based on the clear evidence of its accumulation and studies correlating its presence with symptoms”.
The authors pose several major questions concerning GBCAs and potential long-term harm. They also describe the difficulties involved with designing studies to answer those questions. However, they make it clear that new studies with carefully selected populations and study designs are needed.
Hopefully NCHR’s white paper about GBCAs will generate more research and interest in the potentially serious health risks associated with gadolinium retention and its long-term toxic effects.
About NCHR –
NCHR is a nonprofit, nonpartisan think tank that is focused on research that can improve the health of adults and children. They do not accept funding from companies that make medical treatments.
According to its website, NCHR focuses on the programs and policies that they believe can most benefit from the research-based information that they can provide and the attention that they can generate.
You can read the article and learn more about NCHR here –
February 24, 2019 – Researchers from Finland, led by Dr. Aida Kiviniemi, found that gadolinium deposits can be detected in both enhancing and non-enhancing gliomas, adjacent normal brain tissue, and necrosis. The authors said that to their knowledge, “this is the first study to provide quantitative data of gadolinium retention in gliomas and neighboring normal brain with respect to tumor enhancement and type of GBCA used”. “The levels of gadolinium in the tumor and normal brain correlated suggesting a possible transit of gadolinium to the surroundings of the brain lesion. The most powerful predictor of gadolinium retention was the type of GBCA administered with significantly higher gadolinium accumulation detected with linear (gadodiamide and gadopentetate dimeglumine) relative to macrocyclic (gadoterate meglumine and gadobutrol) agents.” The study, Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents, was recently published online in Neuroradiology. (more…)
A new study by Alwasiyah et al. concluded that the current reference range of 0.7 μg/24hr for 24-hour urinary gadolinium is not applicable to patients for at least 30 days following exposure to a gadolinium-based contrast agent (GBCA). In the study, the authors “calculated an estimated average of 57 days for the urinary gadolinium to creatinine ratio to reach below the current reference range following GBCA exposure and possibly much longer (i.e., 80+ days)”. The article, “Urinary Gadolinium Levels After Contrast-Enhanced MRI in Individuals with Normal Renal Function: a Pilot Study”, was published online December 12, 2018 in the Journal of Medical Toxicology.
This was a prospective, observational pilot study to determine urine gadolinium concentrations over a 30-day period after GBCA administration in patients with normal renal function. The 13 subjects were between 18 and 65 years of age and were reported to have received a gadolinium-based contrast agent for the first time. Prior to contrast administration, spot urine samples were obtained and tested for gadolinium and creatinine. All testing was performed by Mayo Medical Laboratories in Rochester, MN. Post-MRI 24-hour urine testing was performed on day 3, 10 and 30. Eight subjects received gadobutrol (Gadavist®), four received gadopentetate dimeglumine (Magnevist®), and 1 received gadoxetate disodium (Eovist®) for their MRIs with contrast. The authors reported that all 13 subjects had 24-hour gadolinium levels higher than 0.7 μg/24hr on day 3, day 10, and day 30 after contrast administration. The authors estimated that “urinary gadolinium levels will often remain above the current reference range for >50 days”. (more…)