Gadolinium Deposits from MRI Contrast Dyes May Pass from Tumors to Normal Brain Tissue

Published on February 12, 2019 by Sandy Liebhard

Researchers have discovered gadolinium deposits in the brain tissue of patients with primary glioma, suggesting that, after an MRI, the potentially-toxic heavy metal may travel from the site of a pathological brain lesion to adjacent normal tissue.

How the Gadolinium Study Was Conducted

The study, which was published February 2^nd in Neuroradiology, appears to be the first to provide quantitative data regarding gadolinium retention in gliomas and neighboring normal brain tissue with respect to tumor enhancement, as well as the type of agent used.

The investigation involved 69 patients with newly-diagnosed primary glioma who had undergone a gadolinium-based MRI prior to surgery.

Seven patients received a linear gadolinium agent, either Ominiscan (gadodiamide) or Magnavist (gadopentetate dimeglumine). The remaining 69 received a macrocyclic agent — either Gadovist (gadobutrol) or Dotarem (gadoterate meglumine).

The study authors measured gadolinium deposition in tumor samples collected from all 69 patients, along with 13 normal brain tissue samples and necrosis samples from 14 glioblastomas.

The amount of tumor enhancement was assessed as none, minimal, or noticeable.

Highest Gadolinium Deposits with Linear Gadolinium Agents

The research team detected gadolinium deposits in:

• 39 (57%) of tumor samples
• 8 (62%) of normal brain tissue samples
• 12 of 14 necrotic tissue samples

The deposits were highest in gliomas samples with noticeable contrast enhancement and in patients who received a linear gadolinium contrast dyes as opposed to macrocylic agents. Similar retention levels and influence of gadolinium type was also observed in normal brain tissue and necrosis samples.

Although contrast enhancement is expected in brain tumors, the presence of gadolinium in adjacent normal brain tissue – where contrast uptake is less likely – was surprising. The study authors suggested that cerebrospinal fluid or the brain’s glymphatic system might provide a pathway gadolinium to travel from gliomas to nearby normal tissue.

“While further studies are needed to confirm this association, an interesting question arises whether gadolinium traverses from the region of brain lesion to neighboring sites in other brain abnormalities such as ischemia, infection, or multiple sclerosis,” they wrote.

Gadolinium Retention in Patients with Healthy Kidneys

Gadolinium contrast dyes are used to enhance the appearance of tumors and other images on an MRI scan.

The agents are contraindicated in patients with impaired kidneys, as the inability to eliminate gadolinium from their bodies can cause a life-threatening disorder called nephrogenic systemic fibrosis. Until recently, however, it was believed that gadolinium retention would not occur in patients with healthy kidneys.

In December 2018, the U.S. Food & Drug Administration (FDA) warned that this was not actually the case, as recent studies suggest gadolinium deposits can remain in the body long after an MRI, even in patients with normal kidney function. Among other things, the agency noted that linear agents appeared to be associated with higher rates of gadolinium retention compared to macrocylic agents.

So far, the FDA has not concluded that gadolinium deposits cause any health problems in patients with healthy kidneys. However, the agency has ordered gadolinium contrast dye manufacturers to conduct animal and human studies to help it better understand the safety and effectiveness of these products.

The FDA has also cautioned doctors to consider the retention characteristics of each agent when choosing an MRI contrast dye for patients who may be at higher risk for gadolinium retention, including:

• Those requiring multiple lifetime doses
• Pregnant women
• Children
• Patients with inflammatory conditions

Additionally, physicians should minimize repeated gadolinium imaging studies when possible, particularly closely-spaced MRI scans. However, the agency also cautioned doctors not to avoid or defer gadolinium-based MRIs when they are medical necessary.

Gadolinium Retention Lawsuits

In recent years, a growing number of product liability lawsuits have been filed in courts throughout the United States on behalf of patients who were allegedly harmed by gadolinium retention, even though their kidneys were healthy at the time they underwent an MRI.

These patients purportedly suffer from Gadolinium Deposition Disease, a debilitating disorder characterized by one or more of the following symptoms:

• Intense burning of the skin and skin substrate
• Intense boring pain in bones or joints
• Brain fog or mental confusion
• Muscle vibrations, pins and needles sensation
• Headache
• Thickening, discoloration, pain in the skin or skin substrate of the distal arms and legs.

Among other things, plaintiffs claim that gadolinium contrast dye manufacturers were aware that retention could occur in patients with normal kidney function. Yet they intentionally concealed this information and failed to warn doctors and patients about the risks allegedly associated with their products.