An agent-based model of fibrosis on lung architecture

Dylan T. Casey

University of Vermont, Burlington, VT

"An agent-based model of fibrosis on lung architecture"

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by remodeling and stiffening of fibrous collagen leading to septal thickening, alveolar destruction, and a stiffer lung. Little is known about how healthy parenchyma transitions to the characteristic IPF pattern seen on computed tomography (CT) scans. We investigate the morphogenesis of IPF with an agent-based model (ABM) that simulates cells interaction with extracellular matrix to imitate the progression of tissue accumulation. We incorporate alveolar architecture so that the model can simulate the conversion of real lung structure into a fibrotic environment. Lungs from mice with bleomycin-induced fibrosis and control mice were fixed at constant pressure and scanned with micro-CT at 4.9-micron slices. The lung architecture from the control serves as the scaffolding our agents traverse. Agents representing pro-fibrotic phenotypes increased tissue density by a fixed amount and were allowed to build off this tissue into airspaces while anti-fibrotic agents removed a fraction of tissue density. The ABM was run until the control lung architecture resembled the fibrotic lung architecture. The addition of agents acting on anatomically realistic alveolar architectures results in tissue remodeling reminiscent of that seen in pulmonary fibrosis, and thus can provide insight into emergent structures arising in fibrosis.
Additional authors: Alexander Sosa; Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO; Bradford J. Smith; Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO; Béla Suki; Department of Biomedical Engineering, Boston University, Boston, MA; Jason H. T. Bates; Department of Medicine, University of Vermont, Burlington, VT;

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