Purpose: Concerns over the neurotoxic potential of small amounts of retained gadolinium (Gd) in brain tissues following intravenous gadolinium-based contrast agent (GBCA) administration have led to dramatic changes in clinical practice worldwide, yet the clinical implications and symptoms associated with Gd deposition remain undefined. In the current study, we used a rat model to determine if GBCA exposure was associated with adverse neurologic or cognitive findings. 

Materials and Methods: Male Wistar rats exposed to 20 intravenous injections over a 4 week period of 2.5 mmol/kg (80 human equivalent doses, HED) of various linear or macrocyclic GBCAs (gadodiamide, gadobenate dimeglumine, gadopentetate, gadoxetate disodium, gadobutrol, gadoterate meglumine, and gadoteridol) were compared to saline-exposed controls. Behavioral and cognitive tests, including novel object recognition test (assessing sensory, memory and cognitive function), open field test (motor function and mood), Y-maze test (short-term positional spatial memory and motor function), social anxiety test, and horizontal ladder rung walking test (motor coordination, planning, and balance), were performed at 6 and 34 weeks post-injection to assess for potential short- and long-term effects  of GBCA exposure on neurologic function. ANOVAs with appropriate post-hoc tests were used to compare GBCA groups to the controls. 

Results: No significant differences in any behavioral test were observed between GBCA-exposed rats and saline controls at 6 weeks post-injection (p=.11 - .99) or 34 weeks post-injection (p=.32 - .99). 

Conclusions: In this rat model, no potential clinical evidence of neurotoxicity was observed following exposure to various linear and macrocyclic GBCAs. Additional studies are necessary to further assess the potential clinical effects of Gd retention.

Assessment of Potential Neurologic Sequelae Following Intravenous Gadolinium-Based Contrast Administration in a Preclinical Animal Model

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