Anatomical considerations for inhaled aerosol deposition modeling: Methods, applications, challenges and opportunities

This paper, one of several in a special issue of the Journal of Aerosol Science on “Inhaled Aerosol Dosimetry”, covers selected methods for defining the respiratory tract anatomy required as input to inhaled aerosol deposition models, along with some applications and challenges. “Anatomy” refers to the study of biological structures and to the structures themselves. Quantitative anatomical data obtained by morphometric measurements are used in inhaled aerosol deposition dose models. The equations used in modeling calculations define the needed specific quantitative anatomy input, whether the model is deterministic, stochastic, semi-empirical, or computational fluid dynamics based. Replica airway casts are widely used for defining airway morphology, and for making hollow models to validate deposition calculations. The parameters measured on casts, e.g., airway lengths, diameters, branching and gravity angles, alveolar shapes, and generational linkages do not capture some important airway details, such as bifurcation shapes, airway motion, deviations from airway smoothness, and non-uniform airway tube diameters. These details can affect inhaled aerosol fates. Advances in methods for scanning airways in living subjects or in non-dissected excised lungs have overcome many of the problems associated with replica cast morphometry, but limitations remain with respect to providing linked airway regions, capturing airway motion, and resolving fine structural detail. There are also needs for cast measurements and scans that represent additional animal species and normal variations within species and individuals. Other methods for defining airway anatomy, such as serial sectioning of fixed or frozen tissue, planar x-ray imaging, and bolus aerosol inhalation, also provide useful airway anatomical data. Along with advances in aerosol dynamics, the current state of understanding airway anatomy is adequate for modeling many medical and environmental exposure cases. However, it appears that advances in understanding respiratory tract anatomy and physiology have lagged behind advances in the quality of aerosol science used in current inhaled aerosol deposition models, with the exception of dynamic and/or multi-component aerosol systems (e.g., cigarette smoke). Accordingly, for anatomists and aerosol scientists working on inhaled aerosol dose models both challenges and opportunities lie ahead for addressing remaining anatomical issues of concern.