Development of alveoli-distributed lung geometry for ferrets to predict particle deposition in the respiratory tract.

OBJECTIVE

Ferrets have long served as an important animal model for the study of respiratory infections, inhalation toxicology, and aerosolized therapeutics because of their anatomical and physiological similarities to humans. Despite their widespread use, quantitative models describing particle deposition within the ferret lung remain limited. In this study, we developed a mechanistic dosimetry model to predict total and regional deposition of inhaled inert particles in the ferret lower respiratory tract (LRT).

MATERIALS AND

METHODS

Two anatomically based lung geometries were constructed using available morphometric data: a modified typical-path symmetric lung geometry and a more physiologically representative 2-path symmetric lung geometry. Both models were designed to yield realistic lung volumes and airway counts while accommodating the limited availability of airway measurements. Airway dimensions were derived from published morphometric data and extended using sigmoidal curve fits to represent the complete tracheobronchial (TB) and pulmonary (PUL) regions. Lung ventilation was modeled assuming uniform pleural pressure, with airflow distributed proportionally to distal lung volume. Particle transport and deposition were simulated using a one-dimensional (1D) advection-diffusion framework incorporating gravitational settling, inertial impaction, and Brownian diffusion.

RESULTS AND DISCUSSION: The 2-path symmetric lung geometry enables more realistic predictions of particle deposition throughout the lung, particularly with respect to deposition as a function of lung depth, allowing direct comparison of predicted deposition with in vivo imaging measurements.