Link Between Brain Abnormalities and Gadolinium-Based Contrast Agent

Researchers for the first time have confirmed an association between a common magnetic resonance imaging (MRI) contrast agent and abnormalities seen on brain MRI scans.

The new findings were published online December 2013 in the journal Radiology, and reveals the possibility that a toxic component of the contrast agent may stay in the body a long time after administration.


Brain MRI scans are frequently performed with a gadolinium-based contrast medium (Gd-CM). Gadolinium’s paramagnetic properties make it useful for MRI scanning, however, because of the toxicity of the gadolinium ion, it must be chemically bonded with nonmetal ions so that it can be moved through the kidneys and out of the body before the ion is released in tissue. Gd-CM is believed to be safe in patients with normal kidney function.

However, in recently, Japanese clinicians noticed that patients with a history of multiple administrations of Gd-CM showed areas of high intensity (hyperintensity) on MRI in two brain areas: the dentate nucleus (DN) and globus pallidus (GP). The specific clinical implications of hyperintensity are not known, but hyperintensity in the DN has been linked with multiple sclerosis, while hyperintensity of the GP is associated with hepatic dysfunction and several disorders.

The investigators compared unenhanced T1-weighted MR images (T1WI) of 19 patients who had undergone six or more contrast-enhanced MR brain scanning with 16 patients who had received six or fewer unenhanced scans. The hyperintensity of both the DN and the GP correlated with the number of Gd-CM administrations.

“Hyperintensity in the DN and GP on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations,” said lead author Tomonori Kanda, MD, PhD, from Teikyo University School of Medicine (Tokyo, Japan) and the Hyogo Cancer Center (Akashi, Japan). “Because gadolinium has a high signal intensity in the body, our data may suggest that the toxic gadolinium component remains in the body even in patients with normal renal function.”

Dr. Kanda noted that because patients with multiple sclerosis tend to undergo numerous contrast-enhanced brain MRI scans, the hyperintensity of the DN seen in these patients may have more to do with the large cumulative gadolinium dose than the disease itself.

The processes by which Gd-CM administration causes hyperintensity of the DN and GP remain not known, according to Dr. Kanda. Earlier research on animals and humans has demonstrated that the ion can be kept in bone and tissue for several days or longer after administration. “The hyperintensity of DN and GP on unenhanced T1WI may be due to gadolinium deposition in the brain independent of renal function, and the deposition may remain in the brain for a long time,” Dr. Kanda suggested.

Dr. Kanda emphasized that there is currently no evidence that gadolinium is responsible for hyperintensity on brain MRI scans. Additional studies gleaned from autopsy specimens and animal experiments will be needed to illuminate the relationship and determine if the patients with MRI hyperintensity in their brains have symptoms. “Because patients who have multiple contrast material injections tend to have severe diseases, a slight symptom from the gadolinium ion may be obscured,” Dr. Kanda said.

There are two types of Gd-CM, macrocyclic and linear, with distinct chemical configurations. Because the patients in the study received only the linear type, additional research is needed to see if the macrocyclic type can prevent MRI hyperintensity, according to Dr. Kanda.

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Teikyo University School of Medicine