Purpose or Case Report: The long term effects of retained Gadolinium (Gd) are still under investigation, but may be of greater concern in pediatric patients.
So far several factors that appear to influence Gd retention have been described. The chemical structure of the Gadolinium based contrast agents (GBCA) plays an important role, with linear agents showing greater deposition compared with macrocyclics, attributed to lower chelate affinity. Differences in GBCA washout may also play a role.
In this study we investigated and quantified the presence of Gd bone deposits in pediatric patients receiving GBCA as well as in controls with no known exposure.
Methods & Materials: Following IRB approval, 51 bone fragments from craniotomies from 50 pediatric patients between 6 months and 20 years of age were analyzed for elemental Gadolinium using inductively coupled plasma-mass spectrometry (ICP-MS). 17 subjects had no known exposure to GBCA and were included as controls. This cohort included 17 subjects who were part of an earlier pilot study on gadolinium bone retention. Four subjects were excluded due to insufficient bone samples. Based on site and type of ossification, we analyzed 30 occipital bone samples (endochondral ossification) and 17 cranial vault samples (intramembranous ossification). Type and dose of contrast agent, number and timing of contrast-enhanced MR exams relative to bone sampling and renal function were documented for patients with known GBCA exposure.
Results: Patient exposures ranged from 1 to >19 doses of GBCA including linear agents only, macrocyclic and linear agents and macrocyclics only. Gd was found to be present in bone tissue in all exposed patients as well as in those with no GBCA exposure, likely reflecting environmental exposure. Those who received linear agents only (2 patients) or both macrocyclic and linear GBCA (4 patients) demonstrated higher levels than those only exposed to macrocyclic agents (24 patients), whose levels were similar to those found in patients with no known exposure to GBCA.
Conclusions: This study demonstrates pathologic confirmation of Gd retention in bone, both with endochondral and intramembranous ossification, of pediatric patients exposed to various GBCA, with greater accumulation seen with linear agents. Low levels of Gd were also detected in those without known GBCA exposure, suggesting some accumulation from environmental exposure to Gd. Interestingly, these levels were similar to those seen in patients exposed to macrocyclics only.