Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent

Abstract

Background and purpose: While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus.

Materials and methods: We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations.

Results: During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r_s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively).

Conclusions: In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination.

Fig 1.

ROIs were defined by the SUIT template within the dentate nucleus (in red) and within the pons (A), cerebellar white matter (B), CSF (C), and cerebellar gray matter (D) (ROIs in white) to serve as potential references for normalization.

Fig 2.

A, Sagittal unenhanced T1-weighted image from the initial MR imaging of a patient who presented with a parietal lobe low-grade astrocytoma at 10 years of age. B, Sagittal unenhanced T1-weighted image from an MR imaging at 13 years of age after 6 doses of GBCAs. C, Sagittal unenhanced T1-weighted image from an MR imaging following lesion biopsy at 13 years of age after 12 doses of GBCAs. There is faint hyperintensity within the dentate nucleus (white arrow). D, Sagittal unenhanced T1-weighted image from an MR imaging at 15 years of age after 17 doses of GBCAs. Black arrows indicate the tract of a ventricular catheter. There is distinct hyperintensity within the dentate nucleus and the globus pallidus (white arrows). E, Sagittal unenhanced T1-weighted image from an MR imaging scan at 17 years of age after 27 doses of GBCAs. Hyperintensity within the dentate nucleus and the globus pallidus is again seen (white arrows).

Fig 3.

A, Sagittal unenhanced T1-weighted image from an MR imaging of a patient at 13 years of age after the 12th dose of GBCA. An arrow marks the location of the dentate nucleus. B, A computer-assigned dentate ROI reflected back into the individual patient's space.

Fig 4.

Computer-selected DN/P and DN/C ratios plotted against the number of prior contrast doses for all time points for all 13 subjects who underwent automated analysis.

Fig 5.

A, Association between DN/P ratio and the number of prior doses of GBCA. The dark solid line reflects the predicted average response among subjects' median DN/P ratio values at the given number of prior doses of GBCA, and the light solid lines represent the associated 95% confidence band. B, Association between the DN/C ratio and the number of prior doses of GBCA. The dark solid line reflects the predicted average response among subjects' median DN/C ratio values at the given number of prior doses of GBCA, and the light solid lines represent the associated 95% confidence band.