Mathematical modeling and mechanical quantification of ventilation in healthy and diseased lungs
Abstract
OBJECTIVES: Diseases of the respiratory system are leading causes of morbidity and mortality in the United States and worldwide. Pathologies such as asthma, acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD) result in substantial impairments in lung function and declines in quality of life. However, the ability to predict functional impairments associated with lung disease is limited, given the tremendous intra- and inter-patient variability of clinical presentation. The goal of our project is to integrate mathematical modeling, computational experiments, imaging biomarkers, and histological data to simulate parenchymal pathophysiology, and predict corresponding derangements in lung function. We will couple a poroelastic description of parenchymal tissue mechanics to an airway fluid network, for the prediction of ventilation distribution in healthy lungs and those with parenchymal disease. We hypothesize that a coupled model of poroelastic parenchymal tissues interacting with airway fluid network will provide accurate mechanical descriptions of ventilation distribution and lung pathophysiology under healthy and diseased conditions. In this project, there are two specific aims: 1) For simulated healthy lungs, we will validate the physical properties of our poroelastic model, such as tissue elasticity and permeability, using existing 3D and 4D CT image data sets in different species; 2) to quantify the impact of heterogeneous alterations in parenchymal tissue mechanics associated with acute and chronic lung diseases. MERIT: Traditionally, mathematical modeling of the lung has been achieved using multi-compartmental airway networks, imposing either homogeneous or heterogeneous distributions of tissue viscoelasticity. Compared to previously published computational models, a key advantage of our model is its ability to provide far more insight into the mutual dependencies between ventilation distribution, regional deformation, and permeability. Our proposed poroelastic model with variable permeability will have potential to describe the mechanical mechanisms associated with lung diseases and syndromes of varying severity. The mechanical risk factors simulated by our model may be thus used to assess the severity of a given pathophysiologic condition, make predictions on the longitudinal course of a disease, or predict the response to therapeutic and supportive interventions such as mechanical ventilation. Such high-fidelity predictions may lead to reduced risk of catastrophic events. Our simulations will be the first quantitative attempt to link parenchymal strain and permeability using three dimensional structures that integrate proper boundary conditions. Our model thus may provide more accurate assessments and predictions for risk stratification and disease outcome. Our advanced mathematical model and numerical simulations will yield new insights and more comprehensive understanding on the mechanical behavior of the lung and its response to treatment. IMPACT: Emerging lung disease is the leading cause of outpatient illness and a major cause of infectious disease hospitalization in U.S. military personnel. The developed tools will be very useful for the diagnosis and evaluation of lung diseases for military people and therefore support the department of defense (DoD) on health care aspect. The proposed project will not only produce effective mathematical models and efficient computational tools for quantifying lung ventilation in the presence of mechanical perturbations in parenchyma mechanics but also help the investigators build strong research program at Morgan State University, a prestigious member of Historically Black Colleges and Universities, in order to promote the workforce diversity in STEM field and health care.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 22, 2022
- Source ID
- W911NF2310004
Entities
People
- Mingchao Cai
Organizations
- Army Contracting Command
- Morgan State University
- United States Army