Aerosol dosimetry in the whole conducting zone of a murine left-lung using CF-PD and LSFM images

Abstract

Aerosol dosimetry in respiratory airways is relevant for pulmonary drug delivery and inhalation toxicology. Consequently, computational fluid-particle dynamics (CF-PD) modelling of pulmonary aerosol delivery is an active research field. Additionally, mice are the most commonly used animals in medical research. Technological advances have provided information on whole mice lung morphologies with unprecedented high resolution. Therefore, in this study, we used high-resolution light sheet fluorescent microscopy (LSFM) images of a healthy C57BL/6 mouse lung with a constant air flow rate of 72 ml/min, to extract an anatomical 3-dimensional (3D) geometry of the entire airway tree of the left lung from the primary bronchi to the most distal bronchioles excluding the trachea. The airways were segmented based on an order- and generation-based method. Also, to compare the morphological data and regional deposition, a generation-based investigation including 25 generations was employed in the present model. One-way coupling of CF-PD modeling was applied to model an intubated and mechanically-ventilated mouse. Maximum values of the velocity and vorticity magnitude of 3.2 m/s and 200,000 1/s were reached in the second order, respectively, and maximum pressure and wall shear stress levels were 30 Pa and 3.5 Pa, respectively. Finally, order- and generation-based particle deposition efficiency and dose per lung area were obtained for the particle size range of 1 μm ≤ d_p ≤ 10 μm yielding pronounced hotspot deposition patterns mainly near the proximal bifurcations. The results showed a positive correlation between deposition efficiency and particle size due to a size-dependent increase in inertial and gravitational effects. Maximum regional deposition and normalized dose was seen for 10 μm particles in the 1st order of the murine left lung. Smaller peak sizes of deposition efficiency were seen in the third and fourth orders of the mouse left lung due to almost complete loss of the largest particles in lower order airways. It also justifies the close to zero deposition efficiency in the highest orders (fifth to sixth). Both lung morphology as well as total and regional aerosol deposition showed reasonably good agreement with empirical data from the literature. The present CF-PD model with accurate realistic lung morphology, improves our knowledge of airway aerosol deposition hotspots. The obtained modeling method and the qualitative results can be implemented on human airways.