The ultimate goal of the project is to develop a comprehensive computational fluid dynamics (CFD) model for pulmonary air flow that utilizes subject-specific airway geometries, spans spatial scales from the largest bronchial airways to alveolar sac, and employs a Computed Tomography (CT) data-driven, multistage approach to provide accurate predictions of regional ventilation and gas transport through the entire moving airway tree. The approach integrates three-dimensional (3D) and one-dimensional (1D) fluid dynamic models supplemented with dynamic CT data through numerical optimization to achieve realistic multi-scale breathing lung simulations. The model will bring about new understanding of air flow, gas transport, and aerosol particle deposition in the lungs. The specific aims of the project are: (1) Establish efficient techniques for generating subject-specific computational meshes for CFD analysis; (2) Integrate the custom developed 3D CFD model to the 1D gas transport model by developing an efficient algorithm to facilitate 3D to 1D coupling (large to small airways) or 1D to 3D coupling (bronchioles to alveolar ducts) for multi-scale simulation; (3) Develop and experimentally validate a new predictive model of ventilation distribution by linking 3D CFD models to dynamic imaging of ventilation, via 1D flow models; (4) Make available the coupling algorithms and share the databases with the research and clinical communities. We will use the custom developed segmentation software to extract airway geometries from the CT data sets. The CT-image based geometries will then be supplemented with synthetic geometries using the volume filling technique and Voronoi meshing scheme. The 3D-1D coupled CFD simulations will be performed using the above airway geometries. The coupled CFD solutions will be validated through CT experiments and compared with those of the 1D model. The coupling software and databases will be made available to both research and clinical communities through the medical image file archive system. The applications of the model include, but are not limited to, improving pharmaceutical aerosol drug delivery, predicting subject-specific regional ventilation for diagnosis of patterns related to pathologic changes in airway geometry and parenchyma destruction, and predicting long-term effects of environmental pollutants on lung function where environmental exposure has been shown to alter airway structure in early development.