Optimization of pharmacological interventions in the guinea pig animal model—a new approach to calculate the perilymph volume of the scala tympani
The guinea pig serves as a well-established animal model for inner ear
research, offering valuable insights into the anatomy, physiology, and therapeutic
interventions of the auditory system. However, the heterogeneity of results
observed in both in-vivo experiments and clinical studies poses challenges in
understanding and optimizing pharmacotherapy outcomes. This heterogeneity
may be due to individual differences in the size of the guinea pig cochlea and
thus in the volume of the scala tympani (ST), which can lead to different drug
concentrations in the ST, a fact that has been largely overlooked thus far. To
address this issue, we aimed to develop an approach for calculating the individual
volume of perilymph within the ST before and after cochlear implant insertion.
Method: In this study, high-resolution μCT images of a total of n = 42 guinea pig
temporal bones were used to determine the volume of the ST. We compared
fresh, frozen, and fixed tissues from both colored and albino strains to evaluate
the potential influence of tissue condition and strain on the results.
Results: Our findings demonstrate a variability in mean ST volume with a relative
standard deviation (RSD) of 14.7%, comparable to studies conducted with humans
(range RSD: 5 to 20%). This indicates that the guinea pig cochlea exhibits similar
variability to that of the human cochlea. Consequently, it is crucial to consider
this variability when designing and conducting studies utilizing the guinea pig
as an animal model. Furthermore, we successfully developed a tool capable of
estimating ST volume without the need for manual segmentation, employing
two geometric parameters, basal diameter (A) and width (B) of the cochlea,
corresponding to the cochlear footprint. The tool is available for free download
and use on our website.
Conclusion: This novel approach provides researchers with a valuable tool to
calculate individual ST volume in guinea pigs, enabling more precise dosing
strategies and optimization of drug concentrations for pharmacotherapy
studies. Moreover, our study underscores the importance of acknowledging
and accounting for inter-individual variability in animal models to enhance the
translational relevance and applicability of research outcomes in the field of inner ear investigations