Scientists discover how nanoparticles of toxic metal used in MRI scans infiltrate human tissue

University of New Mexico researchers studying the health risks posed by gadolinium, a toxic rare earth metal used in MRI scans, have found that oxalic acid, a molecule found in many foods, can generate nanoparticles of the metal in human tissues.

In a new paper published in the journal Magnetic Resonance Imaging, a team led by Brent Wagner, MD, professor in the Department of Internal Medicine in the UNM School of Medicine, sought to explain the formation of the nanoparticles, which have been associated with serious health problems in the kidneys and other organs.

“The worst disease caused by MRI contrast agents is nephrogenic systemic fibrosis,” he said. “People have succumbed after just a single dose.” The condition can cause a thickening and hardening of the skin, heart and lungs and cause painful contracture of the joints.

Gadolinium-based contrast agents are injected prior to MRI scans to help create sharper images, Wagner said. The metal is usually tightly bound to other molecules and is excreted from the body, and most people experience no adverse effects. However, previous research has shown that even in those with no symptoms, gadolinium particles have been found in the kidney and the brain and can be detected in the blood and urine years after exposure.

Scientists are left with intertwined puzzles: Why do some people get sick, when most don’t, and how do gadolinium particles become pried loose from the other molecules in the contrast agent?

“Almost 50% of the patients had been exposed only a single time, which means that there’s something that is amplifying the disease signal,” Wagner said. “This nanoparticle formation might explain a few things. It might explain why there’s such an amplification of the disease. When a cell is trying to deal with this alien metallic nanoparticle within it, it’s going to send out signals that tell the body to respond to it.”

In their study, Wagner’s team focused on oxalic acid, which is found in many plant-based foods, including spinach, rhubarb, most nuts and berries and chocolate, because it binds with metal ions. The process helps lead to the formation of kidney stones, which result when oxalate binds with calcium. Meanwhile, oxalic acid also forms in the body when people eat foods or supplements containing vitamin C.

In test tube experiments the researchers found that oxalic acid caused minute amounts of gadolinium to precipitate out of the contrast agent and form nanoparticles, which then infiltrated the cells of various organs.

“Some people might form these things, while others do not, and it may be their metabolic milieu,” Wagner said. “It might be if they were in a high oxalic state or a state where molecules are more prone to linking to the gadolinium, leading to the formation of the nanoparticles. That might be why some individuals have such awful symptoms and this massive disease response, whereas other people are fine.”

The finding points to a possible way to mitigate some of the risks associated with MRI scan, he said.

“I wouldn’t take vitamin C if I needed to have an MRI with contrast because of the reactivity of the metal,” Wagner said. “I’m hoping that we’re getting closer to some recommendations for helping these individuals.”

The team is now researching ways to identify those who might be at greatest risk from gadolinium contrast agents. In a new study they’re building an international patient registry that will include a collection of blood, urine, fingernail and hair samples, which could provide evidence of gadolinium accumulation in the body.

“We want to get a lot more information to come up with the risk factors that relate to those with symptoms,” he said. “We’re going to ask about what medical conditions you had at the time of exposure, what medications are you on, and we want to include dietary supplements, because that might piece it all together—why some people have symptoms, whereas others seem to be impervious.”

University of New Mexico researchers studying the health risks posed by gadolinium, a toxic rare earth metal used in MRI scans, have found that oxalic acid, a molecule found in many foods, can generate nanoparticles of the metal in human tissues.

In a new paper published in the journal Magnetic Resonance Imaging, a team led by Brent Wagner, MD, professor in the Department of Internal Medicine in the UNM School of Medicine, sought to explain the formation of the nanoparticles, which have been associated with serious health problems in the kidneys and other organs.

“The worst disease caused by MRI contrast agents is nephrogenic systemic fibrosis,” he said. “People have succumbed after just a single dose.” The condition can cause a thickening and hardening of the skin, heart and lungs and cause painful contracture of the joints.

Gadolinium-based contrast agents are injected prior to MRI scans to help create sharper images, Wagner said. The metal is usually tightly bound to other molecules and is excreted from the body, and most people experience no adverse effects. However, previous research has shown that even in those with no symptoms, gadolinium particles have been found in the kidney and the brain and can be detected in the blood and urine years after exposure.

Scientists are left with intertwined puzzles: Why do some people get sick, when most don’t, and how do gadolinium particles become pried loose from the other molecules in the contrast agent?

“Almost 50% of the patients had been exposed only a single time, which means that there’s something that is amplifying the disease signal,” Wagner said. “This nanoparticle formation might explain a few things. It might explain why there’s such an amplification of the disease. When a cell is trying to deal with this alien metallic nanoparticle within it, it’s going to send out signals that tell the body to respond to it.”

In their study, Wagner’s team focused on oxalic acid, which is found in many plant-based foods, including spinach, rhubarb, most nuts and berries and chocolate, because it binds with metal ions. The process helps lead to the formation of kidney stones, which result when oxalate binds with calcium. Meanwhile, oxalic acid also forms in the body when people eat foods or supplements containing vitamin C.

In test tube experiments the researchers found that oxalic acid caused minute amounts of gadolinium to precipitate out of the contrast agent and form nanoparticles, which then infiltrated the cells of various organs.

“Some people might form these things, while others do not, and it may be their metabolic milieu,” Wagner said. “It might be if they were in a high oxalic state or a state where molecules are more prone to linking to the gadolinium, leading to the formation of the nanoparticles. That might be why some individuals have such awful symptoms and this massive disease response, whereas other people are fine.”

The finding points to a possible way to mitigate some of the risks associated with MRI scan, he said.

“I wouldn’t take vitamin C if I needed to have an MRI with contrast because of the reactivity of the metal,” Wagner said. “I’m hoping that we’re getting closer to some recommendations for helping these individuals.”

The team is now researching ways to identify those who might be at greatest risk from gadolinium contrast agents. In a new study they’re building an international patient registry that will include a collection of blood, urine, fingernail and hair samples, which could provide evidence of gadolinium accumulation in the body.

“We want to get a lot more information to come up with the risk factors that relate to those with symptoms,” he said. “We’re going to ask about what medical conditions you had at the time of exposure, what medications are you on, and we want to include dietary supplements, because that might piece it all together—why some people have symptoms, whereas others seem to be impervious.”