Gadolinium is what is known as a paramagnetic metal ion, which means that it moves in a specific way when in a magnetic field. Because of this, gadolinium can enhance magnetic resonance imaging (MRI). The actual gadolinium-based contrast agents (GBCAs) are created by chelation, where large organic molecules form a stable framework around the gadolinium, which reduces the chances of toxicity you would have with regular gadolinium. The GBCA is mostly eliminated by the kidneys.
GBCAs are FDA-approved for use with MRI to create better images of bodily tissues. They’re also used with magnetic resonance angiography (MRA), which is used in evaluation of heart disease and stroke risk. Over 25 years, more than 100 million people have received GBCAs in diagnostic medical imaging because these agents improve visibility of specific tissues, allowing physicians to more efficiently diagnose many medical conditions.
Effects of Prolonged Elevated Gadolinium Levels in Tissues
The gadolinium-chleate bond is critical should any of the agent remain inside a patient after medical imaging studies. In general, GBCAs are considered safe, and up until about 10 years ago, the conventional wisdom was that most or all gadolinium left the body soon after a medical imaging exam. However, more recent research has reported that sometimes, elevated levels of gadolinium may remain in the body long term, and in patients with serious kidney disease, the result can be a condition called nephrogenic systemic fibrosis. Other studies have found residual gadolinium in the brains of patients who do not have kidney disease.
The Type of Gadolinium Contrast Agent Makes a Difference
The studies referenced above were not able to tell whether the gadolinium that remained in the body was still in chelated form, or free. But other studies, including one from the University of Heidelberg Medical Center in Germany, say that the type of GBCA may influence gadolinium retention.
There are two basic types of GBCAs, known as linear and macrocyclic. Macrocyclic GBCAs have the gadolinium more tightly bound to the chelating agent, which makes it less likely to release unbound gadolinium into the body. The Heidelberg researchers studied 100 patients, some of whom had undergone MRIs exclusively with linear GBCAs, the rest of whom underwent MRIs with macrocyclic GBCAs. All patients had undergone at least six MRIs.
MRI signal intensity was higher in certain brain regions in the linear GBCA group, but not the macrocyclic group. This supports the hypothesis that macrocyclic GBCAs are less likely to leave gadolinium behind in the body.
An Animal Study of Two Types of Gadolinium Contrast Agent
French researchers published a study in Investigative Radiology that further clarifies the long-term effects of the type of GBCA used in medical imaging studies. In healthy rats, researchers compared long term signal intensity in a part of the brain called the deep cerebellar nuclei as it relates to whether linear or macrocyclic GBCAs are used. Some rats were given a linear GBCA, others a macrocyclic GBCA (both in the same dosage per kilogram), and a control group was given saline.
They found a “significant and persistent” signal hyperintensity in the deep cerebellar nuclei only in the rats treated with the linear GBCA. These levels did not decrease significantly during a treatment-free hiatus. Researchers concluded that repeated administrations of linear GBCA in healthy rats resulted in gadolinium deposition in the cerebellum, while macrocyclic GBCA did not result in gadolinium deposition in the cerebellum. Whether the leftover GBCA caused clinical problems was not ascertained.
Radiologists Must Know When to Use GBCAs
There’s no question that GBCAs are valuable in medical imaging studies, and can provide life-saving medical data. However, based on these new findings of possible long term residual gadolinium in some patients (particularly those with kidney disease), physicians should only order contrast MRI with GBCAs when necessary and with due consideration of risks, type of contrast agent, and amount.
Radiologists like Brian Auster, MD, George Koshy, MD, Kenneth P. Morrison, MD, and Richard Spira, MD, are vigilant about staying current with the latest information and radiological developments so they can address all concerns about safety and efficiency of medical imaging procedures. SteleRAD is owned and operated by Board-certified radiologists, whose expertise is sought in medical imaging centers, physician practices, and hospitals throughout South Florida. If you’d like to learn more, we encourage you to call SteleRAD at 954-358-5250 or contact us online at any time.