Topographic distribution of idiopathic pulmonary fibrosis: a hybrid physics-and agent-based model
Authored by Tyler J Wellman, Jarred R Mondonedo, Gerald S Davis, Jason H T Bates, Bela Suki
Date Published: 2018
DOI: 10.1088/1361-6579/aaca86
Sponsors:
United States National Institutes of Health (NIH)
Platforms:
No platforms listed
Model Documentation:
Other Narrative
Mathematical description
Model Code URLs:
Model code not found
Abstract
Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and
fatal disease characterized by excessive deposition of collagen and
associated stiffening of lung tissue. While it is known that
inflammation and dysfunction of fibroblasts are involved in disease
development, it remains poorly understood how cells and their
microenvironment interact to produce a characteristic subpleural pattern
of high and low tissue density variations, called honeycombing, on CT
images of patients with IPF. Since the pleura is stiffer than the
parenchyma, we hypothesized that local stiffness of the underlying
extracellular matrix can influence fibroblast activation and
consequently the deposition of collagen, which in turn influences tissue
stiffness in a positive feedback loop. Approach: We tested this
hypothesis by developing a hybrid physics-based/agent-based
computational model in which aberrant fibroblast activation is induced
when cells migrate on stiff tissue. This activation then feeds back on
itself via the altered mechanical environment that it creates by
depositing collagen. Main results: The model produces power law
distributions of both low-and high-attenuation area clusters and
predicts the development of honeycombing only when mechanical rupture is
allowed to take place in highly strained normal tissue surrounded by
stiff fibrotic tissue. These predictions compare well with histologic
data computed from CT images of patients with IPF. Significance: We
conclude that the clinical manifestation of subpleural honeycombing in
IPF may result from fibroblasts entering into a positive feedback loop
induced by the abnormally high tissue stiffness near the pleura.
Tags
Collagen
progression
disease
Stress
Fibroblasts
Stiffness
Positive feedback
Computed tomography
Elastic
network
Lung-tissue
Mouse model
Pathogenesis
Emphysema