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. http://doi.org/10.1007/s00247-016-3646-3

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.”  Dr. Roberts and her colleagues said that further research is needed to determine the clinical significance, if any, of gadolinium deposition in the body of pediatric patients.

Roberts, D. R., Chatterjee, A. R., Yazdani, M., Marebwa, B., Brown, T., Collins, H., … Zhu, X. (2016). Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent. American Journal of Neuroradiology . JOUR. http://doi.org/10.3174/ajnr.A4891

A retrospective study by Flood et al found that pediatric patients who underwent multiple GBCA-enhanced exams had increased signal intensity within the dentate nucleus compared to subjects who had not received contrast. The study included 46 pediatric patients who had undergone at least three MRIs with gadopentetate dimeglumine (Magnevist, Bayer HeathCare) and 57 age-matched control subjects who had never received a GBCA.  Subjects ranged in age from older than 31 days to younger than 18 years, and had normal brain MRI results on their most recent report.

Flood and his colleagues found that there was a significant correlation between dentate nucleus signal increase and total cumulative GBCA dose.  There was no signal intensity increase in the globus pallidus in the GBCA-exposed group.  The researchers said that the “clinical significance of our findings is unknown” and that further studies with larger groups of patients with different GBCAs are needed to confirm the presence and effects of gadolinium on pediatric patients.

Flood, T. F., Stence, N. V., Maloney, J. A., & Mirsky, D. M. (2016). Pediatric Brain: Repeated Exposure to Linear Gadolinium-based Contrast Material Is Associated with Increased Signal Intensity at Unenhanced T1-weighted MR Imaging. Radiology, 160356. http://doi.org/10.1148/radiol.2016160356

Sharon Williams