Gadolinium-Based Contrast Agents

Studies + Science

Types of GBCAs

There are many types of GBCAs, each with advantages and disadvantages. Some are more effective than others, but they may carry more risks. The chart below, created by Medscape, indicates the different types. 

Macrocyclic GBCAs – Macrocyclic GBCAs cage the gadolinium particle and have a lower risk of “dissociation” or releasing a gadolinium particle into the body. Macrocyclic GBCAs can also be less effective at creating a contrast than other GBCAs because of how tightly bound the gadolinium particles are.

Linear GBCAs – Linear GBCAs use an “open chain” structure that creates a more powerful contrast than macrocyclic GBCAs. These looser chains also pose a higher risk of dissociation. Most radiologists will use linear GBCAs to reduce the overall dosage required for the MRI.

Ionic GBCAs – Ionic GBCAs can be either linear or macrocyclic. Ionic GBCAs will dissolve in solution when they enter the bloodstream. This allows for faster delivery and dispersal but runs an increased risk of dissociation because the agent dissolves into the bloodstream. Ionic GBCAs can also create minor interferences with the heart and nerve signals.

Nonionic GBCAs – Nonionic GBCAs can also be linear or macrocyclic but do not dissolve in the bloodstream. This means that nonionic GBCAs run a lower risk of dissociation and also do not run the risk of interfering with other electrical impulses like brain and heart impulses.

Who is at risk for MRI contrast dye side effects?

Not all individuals who receive GBCAs will be affected equally. Due to the weakened ability to filter material through the kidneys, individuals with existing kidney issues have increased risk of absorbing high amounts of gadolinium.

People with allergy disorders also face a higher risk of developing complications from GBCAs, caused by increased sensitivity to heavy metals. Additionally, data shows women of European descent are more likely to experience issues.

What are the side effects of MRI contrast dye?

When GBCAs are administered, patients experience immediate effects, such as a headache, nausea, and dizziness. These effects will subside shortly after the MRI has finished.

GBCAs are harmless while in solution, but for some people, side effects may persist. When soaked into tissues, particularly the brain, there are risks of tissue damage or the development of additional diseases. Common illnesses associated with MRI contrast dyes are gadolinium deposition disease (GDD) or nephrogenic systemic fibrosis (NSF).

Gadolinium Deposition Disease

Gadolinium deposition disease (GDD) is a condition that occurs in patients with normal renal function. It develops when gadolinium is improperly filtered in the body. Instead, the metal is deposited in bone and other tissues, which can cause a variety of symptoms with differing levels of severity.

GDD may manifest as joint pain, tightness and brain fog. It also causes the skin to burn, thicken or become discolored. Symptoms that may be associated with GDD include:

• Anaphylactic reaction
• Brain fog
• Persistent headaches
• Joint and bone pain
• Skin burning, thickening or discoloration

GDD is not known to be fatal. Treatments for GDD are available through the use of diethylenetriaminepentaacetic acid (DTPA), which has a strong affinity for gadolinium and is easily filtered through the kidneys.

GDD is a relatively recent discovery, and the exact scope of symptoms and treatments is not yet known. There are several ongoing, long-term studies both in the U.S. and overseas into the effects of GDD over time.

Nephrogenic Systemic Fibrosis

Another disease, known as nephrogenic systemic fibrosis, may also be triggered by exposure to GBCAs. Nephrogenic systemic fibrosis often develops in people who already have kidney issues, regardless of dialysis. It causes changes in the skin and can be identified as thick, dark patches on the body.

Nephrogenic systemic fibrosis may damage organs, specifically the kidneys, heart, and lungs. Patients have experienced cognitive issues, such as brain fog. One of the most common complications associated with GBCAs is joint pain and tenderness, caused by contracted muscles and tendons.

Symptoms that may be associated with NSF include:

• Skin swelling, tightening
• Skin thickening, hardening
• Skin darkening
• Burning, itching
• Sharp pains
• Infection, blisters, ulcers
• Difficulty moving
• Muscle weakness
• Bone pain
• Organ function issues
• Yellow eyes
• Blood clots

Although some people may recover from NSF, the symptoms are often chronic and can result in severe injury or death if left untreated.

A 2008 study published in the European Journal of Radiology found that the three most common culprits of gadolinium-induced NSF were gadodiamide (157 of 190 cases), gadopentetate (8 of 190), and gadoversetamide (3 of 190).

That same study also found 18 other cases caused by various structures of GBCAs. Since 2008, many of these structures have been discontinued or treated with other chemical agents to drastically reduce the likelihood of developing NSF.

Regulation Recap

The first GBCAs were used in 1988, nearly 30 years ago, and were met warmly by the imaging community. Studies showed only 0.01% of patients rejected the GBCAs when given intravenously. These early successes labeled GBCAs as a safer alternative to other contrasting agents, and GBCAs became widely demanded.

In 2000, the U.S. Food and Drug Administration (FDA) and various European groups began to suspect GBCAs may have been responsible for long-term complications that patients developed after receiving GBCAs for an MRI. In Dec. 2017, the agency warned patients that GBCAs may be retained in the body. 

The Next Steps

There’s a level of complexity involved in creating and using medical tools, but it’s still paramount for people to know they’re safe and reliable. That’s why it comes as a shock when people develop adverse effects from a commonly used substance like GCBAs.

For certain individuals, complications arise from the use of GBCAs. Other individuals experience no side effects except minor headaches after administration.

The FDA doesn’t have enough clinical evidence to authorize a large-scale crackdown on GBCA use. That’s why some physicians, like Dr. Sheela Agarwal, director of medical affairs at Bayer Radiology, call for more data.

While it isn’t easy to wait for more information about the toxicity of GBCAs, many radiologists are reducing the usage of GBCAs by offering alternatives. They’re having comprehensive risk-versus-benefit conversations with their patients, and only using GBCAs when it’s critical to reaching a diagnosis.

Many members of the radiology community are dedicated to protecting their patients from potentially harmful procedures, but some individuals still sustain injuries and long-term issues.