High levels of gadolinium may be deposited in intracranial neuronal tissues of patients following MR scans in which the rare-earth metal is used as a contrast agent, according to results of a study published online March 5 in Radiology.

Gadolinium-based contrast agents (GBCAs) have significantly improved the diagnostic abilities of MR scans and emerged as one of the most popular and effective contrast methods utilized by radiologists, primarily due to the increased signal sensitivities they provide. Today, more than 10 million GBCA injections are performed annually for purposes of medical imaging.

While the free element is cytotoxic within the body, it is believed to be safe to administer gadolinium bonded with organic ligands as part of a GBCA to patients who do not suffer from diminished renal capacities. Recent indirect evidence, however, suggests the presence of gadolinium deposits from certain GBCAs in patients with healthy kidney function.

“Several studies have demonstrated progressive increases in T1-weighted MR signal in various central nervous system structures following repeated gadolinium administration,” according to lead author Robert McDonald, MD, PhD, and his colleagues at the Mayo Clinic in Rochester, Minn. “However, these signal intensity changes are nonspecific and can be seen with several other pathologic conditions. Follow-up studies verifying the presence of neuronal tissue deposition of gadolinium with use of direct tissue assays on human subjects have been absent from the literature.”

To fill this void, McDonald and his team set out to determine if repeated intravenous exposures to a GBCA for the purposes of MR scans is associated with gadolinium deposits in neuronal tissues. Postmortem tissue samples from the thalamus, dentate nuclei, pons and globus pallidus were harvested from 23 deceased patients—13 who underwent at least four scans using the GBCA gadodiamide (Omniscan, GE Healthcare), and a control group of 10 who had no exposure to gadolinium—and analyzed them using inductively coupled plasma mass spectrometry, transmission electron microscopy and light microscopy. Correlations between total gadolinium dose, T1-weighted MR signal intensity changes, and tissue gadolinium concentrations were investigated.

Their results showed that patients subjected to scans using the GBCA had between 0.1–58.8 μg gadolinium per gram of tissue. The deposit levels were significantly dose-dependent and associated with signal intensity changes on pre-contrast T1-weighted MR images, with gadolinium deposition in the capillary endothelium and neural interstitium only present in patients exposed to the GCBA. “Our findings suggest that intravenous administration of GBCA is associated with dose-dependent deposition in neuronal tissues that is unrelated to renal function, age, or interval between exposure and death,” the researchers concluded.

The clinical implications of the study’s results remain unclear, but McDonald and his colleagues believe subsequent research is needed to assess the safety of GBCAs, particularly linear standard relaxivity agents, for patients undergoing contrast-enhanced imaging procedures. “Given the widespread use of GBCAs, our confirmation of gadolinium within neuronal tissues, even in the setting of normal renal and hepatobiliary function, merits additional investigation,” wrote McDonald et al. “Although we were unable to clearly identify a histologic phenotype of gadolinium deposition within neuronal tissues, our findings strongly argue for future research to assess the in vivo stability and safety of GBCAs.”