Magnetic resonance imaging and computational fluid dynamics (CFD) simulations of rabbit nasal airflows for the development of hybrid CFD/PBPK models

Abstract

The percentages of total airflows over the nasal respiratory and olfactory epithelium of female rabbits were calculated from computational fluid dynamics (CFD) simulations of steady-state inhalation. These airflow calculations, along with nasal airway geometry determinations, are critical parameters for hybrid CFD/physiologically based pharmacokinetic models that describe the nasal dosimetry of water-soluble or reactive gases and vapors in rabbits. CFD simulations were based upon three-dimensional computational meshes derived from magnetic resonance images of three adult female New Zealand White (NZW) rabbits. In the anterior portion of the nose, the maxillary turbinates of rabbits are considerably more complex than comparable regions in rats, mice, monkeys, or humans. This leads to a greater surface area to volume ratio in this region and thus the potential for increased extraction of water soluble or reactive gases and vapors in the anterior portion of the nose compared to many other species. Although there was considerable interanimal variability in the fine structures of the nasal turbinates and airflows in the anterior portions of the nose, there was remarkable consistency between rabbits in the percentage of total inspired airflows that reached the ethmoid turbinate region (~50%) that is presumably lined with olfactory epithelium. These latter results (airflows reaching the ethmoid turbinate region) were higher than previous published estimates for the male F344 rat (19%) and human (7%). These differences in regional airflows can have significant implications in interspecies extrapolations of nasal dosimetry.

Acknowledgements

Research was performed in the Environmental Molecular Science Laboratory (a national scientific user facility sponsored by the US Department of Energy (DOE) Office of Biological and Environmental Research) located at Pacific Northwest National Laboratory (PNNL), and operated for DOE by Battelle. This work was funded by the Arvesta Corporation, San Francisco, CA, under BNW Project 47542. The MR imaging, airway segmentation, and computational methods were made possible by grants from the U.S. Department of Energy (Project 40403) and National Institutes of Health (NHLBI HL073598-01A1 and NIEHS ES011617).

Declaration of interest: The authors report no conflicts of interest.