麻豆传媒

Gadolinium from imaging contrast agents sticks to neural tissues even in patients who don't have intracranial abnormalities, according to a small, single-center, retrospective study.

In a postmortem study comparing tissues from the brains of five patients who had several magnetic resonance imaging (MRI) scans using gadolinium with 10 patients who had MRIs without contrast, elemental gadolinium was detected in four neuroanatomic regions of all five patients, with concentrations ranging from 0.1 to 19.4 mcg per gram of tissue, Robert McDonald, MD, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues . No gadolinium was detected in the brains of controls.

"Our results suggest that current thinking with regard to the permeability of the blood brain barrier is greatly oversimplified, as gadolinium appears to accumulate even among patients with normal brain tissue and no history of intracranial pathology," McDonald said in a statement. "It will take additional research to understand how and why this deposition is occurring."

The authors were quick to note, however, that they did not find any histologic changes that suggested toxicity. However, further investigation is needed, they said, "in light of the cytotoxic and genotoxic potential of free lanthanide rare earth metals."

Just last month, the FDA similarly concluded that there are from gadolinium retained in the brain after contrast MRI, so restricting use of the agent is not warranted. But the agency said it would have a public meeting on the issue in the future.

McDonald and colleagues said their study bolsters previous research in patients who have intracranial abnormalities -- underlying brain pathology such as a tumor or infection that was thought to be the culprit behind gadolinium buildup.

But in the McDonald et al study, the researchers assessed patients who had contrast MRI mainly for gut imaging, to test the hypothesis that gadolinium accumulation would occur in those with normal brains, too, as some recent evidence has suggested.

The team studied postmortem neuronal tissue samples from five patients who had four to 18 gadolinium-enhancing MRI scans between 2005 and 2015 and 10 patients who had MRI scans without the agent (none had neurologic symptoms, and imaging was mainly for intraabdominal or intrapelvic disease). The tissue was studied with electron microscopy, mass spectroscopy, and x-ray spectroscopy. The median age at the time of death was 68 in the contrast MRI group and 79 in the control group.

Overall, McDonald and colleagues found dose-dependent gadolinium deposits in four neuroanatomical brain regions in those who had contrast MRI, with concentrations ranging from 0.1 to 19.4 mcg of gadolinium per gram of tissue. These were highest in the globus pallidus and in the dentate nucleus.

None of the patients in the control group had detectable levels of elemental gadolinium.

Both the globus pallidus and the dentate nucleus are prone to mineralization and hemorrhage, which "may suggest that parts of the brain may have a less robust barrier and may be more susceptible to this deposition," McDonald explained. In addition, gadolinium is similar to calcium in size and charge, so the body may mistake it for the endogenous metal, which is often taken up in areas of brain as patients age.

Regarding study limitations, the researchers noted the small number of patients, so it was not possible to analyze the data with multivariate methods. In addition, the findings are not applicable to more stable macrocyclic gadolinium chelates, since gadodiamide was the only contrast agent used.

Implications for MS Patients?

Patients with multiple sclerosis (MS) have long been raising questions about frequent contrast-enhancing brain scans, but MS experts contacted by 麻豆传媒 said the new results don't have any impact on current practice -- notably because the data are from people without underlying brain pathology.

For example, John Corboy, MD, of the University of Colorado in Denver, noted that clinicians try to limit the use of gadolinium because of a lack of complete understanding of the potential risks, the cost, and the side effects, since some patients get a distinct taste in their mouth and others have a true allergy.

"In a stable [MS] patient, it does not add that much info, especially in older stable patients," Corboy said of gadolinium-enhancing scans. "So, we use them for diagnosis, for clinical changes, and to rule out other pathology as needed -- for example, a brain tumor. Otherwise, we try to avoid it. We can also use different dyes that have lesser risks of being taken up in brain or other tissues."

Fred Lublin, MD, director of the Center for Multiple Sclerosis at Mount Sinai Medical Center in New York City, agreed that the data will not change practice: "While there is currently no evidence of any harmful effects of retained gadolinium, since this issue has arisen, we now determine on each ordered scan whether gadolinium is needed," he said.

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