Gadolinium deposition ignoring the blood-brain barrier, according to study

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Gadolinium deposition in the brain may be worse than previously feared, bypassing the blood-brain barrier and landing in regions of the brain responsible for voluntary motor control. While no negative symptoms of deposition have been established, a study published in Radiology calls for additional research into this concerning finding.

Previously believed to harmlessly exit the body, a growing body of evidence suggests the contrast agent can remain in patients’ bodies for years, triggering the European Medicines Agency to pull a handful of gadolinium contrast agents from the European market.

While the exact mechanics of deposition are not well understood, it was believed gadolinium contrast couldn’t cross the blood-brain barrier. However, much of the research into the deposition involved patients with intracranial abnormalities that could possibly compromise the barrier: a function of the types of patients who are receiving gadolinium enhanced contrast examinations in the first place.

Lead researcher Robert J. McDonald, MD, PhD, a staff neurologist at the Mayo Clinic in Rochester, MN had seen slivers of evidence pointing towards contrast material circumventing the blood-brain barrier. However, his suspicions had never been confirmed in a full study. To that end, McDonald and colleagues examined post-mortem tissue samples of patients who underwent enhance MRI exams.

They found gadolinium deposits of various sizes in all five patients with presumably intact blood brain barriers, indicating a misunderstanding of the blood-brain barrier, according to McDonald.

“Our results suggest current thinking with regard to the permeability of the blood brain barrier is greatly oversimplified, as gadolinium appears to accumulate even among patients with normal brain tissue and no history of intracranial pathology,” MacDonald told RSNA News.

Deposition was strongest in areas of the brain prone to calcification: the globus pallidus and dentate nucleus, according to the study.

“This observation could be interpreted as evidence that these neuroanatomic regions have less robust capillary basement membranes or that this deposition is a consequence of localization to areas of the brain that are susceptible to cellular stress,” wrote McDonald et al.

Reassuringly, they detected no pathological changes in tissue samples with deposition, staving off fears of cytotoxicity for now. However, they did find gadolinium deposits in the nuclei of neurons, raising questions about DNA damage.

“Although no clinical phenotype appears to be associated with our patient cohort, the expected physiologic effects and clinical significance of lanthanide metal deposition within neuronal tissues are unknown and merit additional investigation,” wrote McDonald et al.

While the study cohort was relatively small, the results show gadolinium deposition occurs regardless of intracranial abnormalities. This as-yet-unknown method of deposition could be affecting tens of millions of patients worldwide, wrote McDonald, and more research is needed to investigate any co-morbidity.