Gadolinium Toxicity

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More evidence of gadolinium deposition in children’s brains

Three recent retrospective studies have reported finding evidence of increased signal intensities in the brains of pediatric patients who had undergone multiple MRIs with a gadolinium-based contrast agent (GBCA).  The studies by Hu et al, Roberts et al, and Flood et al, add to the mounting evidence of gadolinium deposition in the brain of both children and adults exposed to GBCAs.

The study by Hu et al involved 21 patients, each of whom received multiple MRI exams with a GBCA over the course of their medical treatment.  The number of exams ranged from 5 to 37 (19 out of 21 had more than 6 serial GBCA MRI exams), and the duration of treatment from first to most recent exam ranged from 1.2 to 12.9 years.  The patients were between 0.9 and 14.4 years of age at the time of their first GBCA exam.  Signal intensity ratios in the dentate nucleus and globus pallidus increased between the first and most recent MRI exam in all 21 patients receiving a GBCA.

The authors concluded that the data provided supports the growing evidence of potential gadolinium deposition in the brain.  The observation of signal intensity increases in the dentate nucleus and the globus pallidus on unenhanced T1-weighted images are consistent with prior studies in adults.  They noted that “additional studies are warranted to determine whether intracranial gadolinium deposition is the source responsible for these hyperintense structures and whether changes in standard practice of care are needed”.

Hu, H. H., Pokorney, A., Towbin, R. B., & Miller, J. H. (2016). Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. Pediatric Radiology, 1–9.

Roberts et al found that the number of prior gadolinium-based contrast agent doses in pediatric patients is significantly correlated with progressive T1-weighted dentate hyperintensity.  Sixteen pediatric patients were included for analysis.  The patient ages ranged from 2 months to 14 years at the time of the first contrast dose.  The number of doses before the last brain MR imaging examined ranged from 4 to 16.  Hyperintensity was visible within the dentate nucleus on unenhanced images in the patients who had received at least 7 prior doses of GBCA.

The authors note that “pathologic evaluation of the brain in patients with normal renal function who were administered GBCAs has shown that gadolinium is deposited not only in the dentate nucleus but throughout the brain, including the frontal lobe white matter and frontal cortex”.  “While the clinical significance of the long-term retention of gadolinium in the brain is unknown, it is particularly concerning for pediatric patients, who are undergoing neurodevelopment.” (more…)

Study reports Increasing Signal Intensity within the Brains of Patients with Multiple Sclerosis after multiple injections of the macrocyclic GBCA Gadovist – All Patients had Normal Renal Function

On June 25, 2015, European Radiology published a new study online ahead of print that reports increasing signal intensity on brain MR images after repeated administrations of the macrocyclic agent, gadobutrol (Gadovist, Bayer Healthcare, Berlin, Germany). The study by Stojanov et al is titled, Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. This is the first study to report a correlation between the cumulative dose of a macrocyclic, gadolinium-based contrast agent (GBCA), and gadolinium deposition within the dentate nucleus (DN) and globus pallidus (GP) in patients with relapsing-remitting multiple sclerosis (RRMS).  All patients had normal renal function at the beginning and end of the study.

Liver function was also normal at the beginning of the study; however, the authors noted that at the end of the study there was a significant increase (p=0.004) in GGT, gamma-glutamyl transpeptidase.  The other liver function parameters remained normal.

Since all patients had normal renal function at the beginning and end of the study, there was no correlation between renal function and signal intensity within either dentate nucleus or globus pallidus.  The authors noted that, “This suggests that gadolinium deposition within the brain may occur even in patients with normal renal function”. (more…)

New study of Gadolinium retention in brains of rats raises more questions than it answers

On June 22, 2015, an article in Investigative Radiology was published online ahead of print.  The study by Robert et al, T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats – Difference Between Linear and Macrocyclic Agents”, describes for the first time “an animal model reproducing closely the recent clinical observations of cerebellum T1 signal hypersignal”.  “It also introduces an animal model to investigate the mechanism of the brain retention observed after repeated administrations of some GBCA.”

After 20 intravenous injections of 0.6 mmol of gadolinium per kilogram (4 injections per week for 5 weeks) of gadodiamide (Omniscan) or gadoterate meglumine (Dotarem) to healthy rats, they found that repeated injections of gadodiamide are associated with “progressive and persistent T1 signal hyperintensity in the deep cerebellar nuclei (DCN), with Gd deposition in the cerebellum in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed”.  Although repeated doses of gadoterate meglumine (Dotarem) did not cause signal increases, detectable concentrations of gadolinium were found in the cerebellum, cerebral cortex, and subcortical brain of the rats that were injected with it.  (more…)

Patients with meningioma have increased T1 hyperintensity after multiple contrast-enhanced MRI

On March 11, 2015, a retrospective study on 46 patients with a meningioma who had routinely undergone follow-up enhanced-MRI scans with gadodiamide was published online in Investigative Radiology.  The authors report a significant increase in T1 hyperintensity of the dentate nuclei of the cerebellum on unenhanced scans was observed between the first and last MRI in the group of patients with a history of at least 6 enhanced MRI.  All patients had normal renal function before intravenous administration of gadodiamide (Omniscan).

Two recent studies (Kanda and Errante), with different cohorts of patients, have shown the association between high T1 signal intensity of the dentate nucleus and history of a high number of contrast-enhanced MRI in patients with cancer and brain metastases, and in patients with Multiple Sclerosis (MS). (more…)

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