Gadolinium Retention in the Brain of Mother and Pup Mouse: Effect of Pregnancy and Repeated Administration of Gadolinium-Based Contrast Agents

Abstract

Background: The association of repeated administration of gadolinium-based contrast agents (GBCAs) with the gadolinium (Gd) retention in the brains of mother and fetus remains unclear.

Purpose: To investigate the effects of pregnancy and repeated administration of GBCAs on Gd retention in the brains of mother and pup mice.

Study type: Cross-sectional cohort toxicity study.

Animal model: From gestational days 16-19, pregnant (n = 48) BALB/c mice.

Field strength: A 9.4 T and fast spin echo sequence.

Assessment: Half of the mother mice (n = 24) were killed at postnatal day 1 (P1) for inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM). Besides the ICP-MS and TEM, four pups were randomly selected from each mother and killed at P1 for ultraperformance liquid chromatography mass spectrometry (UPLC-MS) and Nissl staining.

Statistical tests: One-way analysis of variance and unpaired t-test.

Results: In the group of gadodiamide, retention of Gd in the brains of pregnant mice was significantly lower than that of nonpregnant mice in the area of the deep cerebellar nuclei (DCN) (10.35 ± 2.16 nmol/g vs. 18.74 ± 3.65 nmol/g). Retention of Gd in the DCN of pups whose mothers were administered gadoterate meglumine was significantly lower than that of pups whose mothers were administered gadodiamide (0.21 ± 0.09 nmol/g vs. 6.15 ± 3.21 nmol/g) at P1. In mice treated with gadodiamide, most of the retained Gd in the brain tissue was insoluble (19.5% ± 9.5% of the recovered amount corresponded to the intact complex in the DCN).

Data conclusion: In different brain areas of the mother and pup mice, the retention of Gd after gadoterate meglumine administration was lower than that of gadodiamide and gadopentetate dimeglumine administration, and almost all the detected Gd in pups' brains was intact soluble GBCAs.

Evidence level: 1 TECHNICAL EFFICACY: Stage 2.

Keywords: gadolinium-based contrast agent; magnetic resonance imaging; pregnancy; retention.