Long-Term Effects of Linear versus Macrocyclic Gadolinium-Based Contrast Agents on Gene Expression in the Central Nervous System of Mice

Motivation: Since their FDA approval in 1988, gadolinium-based contrast agents (GBCAs) have become essential in MRI diagnostics. However, recent studies reveal that gadolinium can accumulate in the brain, even in patients with normal renal function. Animal research shows that linear GBCAs can persist in brain tissue for over a year. Goal(s): This study investigates whether chronic GBCA deposits induce genetic changes in the central nervous system (CNS). Approach: Using RNA sequencing, we examined gene expression in mice after gadodiamide and gadobutrol exposure. Results: Findings reveal significant gadolinium retention with linear GBCA, linked to altered neuroinflammatory pathways, emphasizing the need for further safety studies. Impact: Our study pioneers in detecting genetic and protein-level changes in the central nervous system from prolonged gadolinium accumulation, highlighting the need for further research to understand mechanisms and assess the long-term safety of linear GBCAs.