gms | German Medical Science

Introduction: A new imaging method called locally enhanced inner ear MRI (LEIM) allows for a reliable diagnosis of Ménière’s disease by visualization of an endolymphatic hydrops using gadolinium-based contrast agents applied intratympanically. The toxicity profiles of these contrast agents for hair cells of the inner ear are still poorly understood.

Methods: The toxicities of Gadodiamide, Gadobutrol, Gadopentetate Dimeglumine, Gadobenate Dimeglumine, and Gadoterate Meglumine for hair cells of the lateral line system of Xenopus embryos were assessed in vivo using a standardized 24-hour assay. Embryos were treated with contrast agents and subsequently hair cells were fluorescently labeled with the dye FM1-43FX. The fluorescence intensity (FI) was recorded and quantitated. Gentamicin and gadolinium trichloride served as positive controls. Furthermore, potential adverse side effects on embryogenesis were monitored by visual inspection of contrast agent-treated embryos over a five-day period.

Results: None of the five contrast agents was able to reduce FI below 60% of the untreated control. Gadodiamide and Gadobutrol treatments did not interfere with Xenopus embryogenesis. However, Gadopentetate Dimeglumine, Gadobenate Dimeglumine, and Gadoterate Meglumine treatments resulted in dose- and time-dependent increases of embryonic lethality.

Conclusions: We established the lateral line system of Xenopus embryos as a rapid and convenient in vivo test system for the quantitative assessment of hair cell toxicities of contrast agents. We found that all tested contrast agents had either no or only a very modest hair cell toxicity at concentrations typically used for LEIM. This suggests that intratympanic applications of these contrast agents are generally safe, however, we favor the use of Gadodiamide and Gadobutrol. Overall, the amphibian hair cell toxicity assay system may in future replace expensive and laborious hair cell toxicity assays using mammals, such as guinea pigs.