The lung model integrates mechanics and cell models. The mechanics model utilizes imaging-based, high-fidelity computational technologies for three-dimensional (3D) fluid and solid mechanical systems to predict airflow-induced shear stress, tissue stress and particle deposition at a local level in the realistic human lung models. The cell model is based upon mathematical cell biology and in vitro data for epithelial cells and nucleotide metabolism to predict adenosine triphosphate nucleotide (ATP) release, cell metabolism, ion and water transport, periciliary liquid (PCL) height, and calcium ion concentration [Ca2+].
The broad objective of this research is to apply the above model to study the mechanical force resulting from the multiscale interactions between pulmonary gas flow and lung tissue mechanics, and its role in the distribution and progression of lung disease. A driving biological hypothesis providing one motivation for this work is that lung diseases alter mechanical force, which then alters stress-mediated ATP release, disturbs PCL water homeostasis, and weakens the integrated airway defense system, forming a vicious cycle of events.
Lin, C.-L., M.H. Tawhai, E.A. Hoffman. Multiscale image-based modeling and simulation of gas flow and particle transport in the human lungs. Wiley Interdiscip Rev Syst Biol Med. 2013;5(5):643-55.
Jahani, N., S. Choi, J. Choi, K. Lyer, E.A. Hoffman, and C.-L. Lin. Assessment of Regional Ventilation and Deformation Using 4D-CT Imaging for Healthy Human Lungs during Tidal Breathing. J. Applied Physiology, 2015; 119(10):1064-1074.
Wu, D., S. Miyawaki, M.H. Tawhai, E.A. Hoffman, C.-L. Lin. A numerical study of water loss rate distributions in MDCT-based human airway models. Annals of Biomedical Engineering. 2015;43(11):2708-21.
Miyawaki, S., S. Choi, E.A. Hoffman, C.-L. Lin. A 4DCT imaging-based breathing lung model with relative hysteresis. Journal of Computational Physics. 2016;326:76-90.
Miyawaki, S, M.H. Tawhai, E.A. Hoffman, S.E. Wenzel, C.-L. Lin. Automatic construction of subject-specific human airway geometry including trifurcations based on a CT-segmented airway skeleton and surface. Biomechanics and Modeling in Mechanobiology. 2016:1-14.
Wu, D., R. C. Boucher, B. Button, T. Elston, C.-L. Lin. An Integrated Mathematical Epithelial Cell Model for Airway Surface Liquid Regulation by Mechanical Forces, Journal of Theoretical Biology, 2018; 438: 34-45.