Gadolinium Not Linked to Neurologic Harm
Large study at Mayo Clinic shows no evidence that gadolinium accumulation in the brain speeds cognitive decline.
Four years ago, a research group in Japan saw a curious thing in brain scans of people who had had multiple MRIs using gadolinium. They saw that certain parts of the brain appeared to be getting brighter, suggesting that gadolinium persisted in the body.
Gadolinium is a common contrast-enhanced magnetic resonance agent used for many different indications, including helping to image tumors in the brain, the breast and other tissues. Its deposition in the brain appeared more prevalent in people who had undergone multiple procedures with the agent. This touched off concern that its prolonged presence in the body could have toxic effects.
"We read that paper, like everyone else, and thought, 'This is fascinating,'" said Robert McDonald, a radiologist at the Mayo Clinic in Rochester, Minnesota.
For radiologists, this is a significant issue because more than 400 million doses of gadolinium have been administered to patients since its approval by the U.S. Food and Drug Administration in 1988. Experts say those agents are needed for treatment because they allow scans to be better interpreted, improving care for patients with a number of conditions, including cancer.
"If we don't have that contrast agent, there is no good alternative," said Max Wintermark, a radiologist at Stanford University in Palo Alto, California. McDonald agreed.
"The agents help millions of people a year -- they save lives," he said. Use of gadolinium has accelerated in the last 29 years, he added, and he predicts gadolinium administrations may reach a billion doses within another decade.
But some patients have claimed they suffer health consequences as a result of the gadolinium. Concerns over its effects have led the European Medicines Agency to recommend suspending some gadolinium agents and restricting the use of others. Earlier this year, the FDA recommended adding warning labels to gadolinium-based agents.
The issue looms large over the field, McDonald said, and may continue to do so until the science is fully understood. "[It's] probably the most contentious issue in radiology right now," he said.
Multiple studies have expounded on the Japanese observation by looking at the deposition of gadolinium in rodents or its presence in postmortem tissue taken from the cadavers of people who underwent procedures while alive. In McDonald's own laboratory, he and his colleagues have used mass spectrometry to quantify the amount of gadolinium in postmortem tissue samples, and they used electron microscopy to image it in those same brain sections.
But while the deposition of gadolinium in the brain has been confirmed, there has been no clear evidence of its clinical relevance. It appears to be there -- but is it harmful?
Last month at the Radiological Society of North America meeting in Chicago, McDonald presented a study that partly answered this question, showing that gadolinium is not linked to neurological harm. The study found gadolinium use caused no neurologic harm in 4,261 people.
Those people had been recruited to participate in the world's largest population-based cohort on aging, known as the Mayo Clinic Study of Aging, which is focused on understanding more about memory, aging and dementia. Its participants undergo evaluations designed to measure neurologic function.
Some 1,092 of these people had received one or more doses of gadolinium, and McDonald and his colleagues used this information to determine whether gadolinium exposure was linked to cognitive decline -- after adjusting for age, sex, education level and other factors. They found gadolinium use was not a significant predictor of cognitive decline, dementia, diminished neuropsychological performance or diminished motor performance.
McDonald's new study was the first of its kind, said Wintermark, who was not involved in the research but chaired a committee of experts who selected the study for presentation to the press. Large, prospective clinical studies like this are necessary to establish a medical consensus on the issue, he said.
"It's hard at the present time to really put all the pieces of the puzzle together," Wintermark said. "We need studies like that to understand what is the link exactly."
The bottom line, McDonald said, is that the field needs to keep investigating this, but there should be definitive evidence of harm before eliminating these products from our markets.
"The amounts received are incredibly tiny," McDonald said. "You need some of the most sophisticated instruments in the world to detect it."