UC San Diego

Understanding the fate of inhaled aerosol particles in healthy and diseased lungs may help in assessing the toxic health effects of airborne particulate matter or the efficiency of therapeutic drugs delivered through the lung. This dissertation focused on determining aerosol particle deposition patterns in healthy and emphysematous rats lungs by utilizing experimental and numerical methods. In the experimental part of the study, both airway morphometry and deposition patterns were determined by MRI. In the morphometry study, healthy rat lungs were imaged in vivo. Airway geometries were extracted from the MR images and the morphometric dimensions were validated against previous studies. In the aerosol deposition study, healthy and emphysematous rats were exposed by mechanical ventilation to iron-oxide particles with 1.22[mu]m mass mean aerodynamic diameter (MMAD). The lungs were imaged with a MR gradient echo sequence and the signal decay rate, R*₂, was calculated from the signal intensity images. Data showed a significantly higher R*₂ in the rats exposed to particles than in the control rats (no aerosol exposure) both for the healthy and emphysematous groups. A calibration experiment showed that concentration of deposited particles in tissue samples was linearly related to R*₂. Particle concentration and relative dispersion of particle deposition sites in all lung lobes tended to be higher in the emphysematous rats compared to the healthy rats. To further study particle deposition sites in the rat lungs, multi-scale computational fluid dynamics (CFD) simulations were performed. The global resistance and compliance of the rat lungs were determined by solving a global resistance/compliance (RC) model. This same RC model was then employed as Neumann boundary conditions in the 0D-3D simulations. Deposition and distribution of particles to the rat lobes was determined for particles with the same diameter as those used in the experiments. Simulations were performed representing healthy, homogeneous and localized emphysema. Emphysema location was determined by utilizing findings from the experimental data. Deposition in the 3D model was higher in the emphysematous cases compared to the healthy cases. Additionally, there was an increase in delivery of particle-laden air to the diseased regions of the lung, compared to the healthy regions. Good agreement was found when comparing the simulated normalized delivery of particles to each lobe to the normalized experimental deposition data. This work is the first to compare deposition sites found numerically and experimentally in both healthy and emphysematous lungs. In future studies, the multi-scale CFD models developed here may be advanced to include particle tracking downstream of the 3D model