Abstract
Pulmonary diseases, driven by pollution, industrial farming, vaping, and the infamous COVID-19 pandemic, lead morbidity and mortality rates worldwide. Computational biomechanical models can enhance predictive capabilities to understand fundamental lung physiology; however, such investigations are hindered by the lung’s complex and hierarchical structure, and the lack of mechanical experiments linking the load-bearing organ-level response to local behaviors. In this study we address these impedances by introducing a novel reduced-order surface model of the lung, combining the response of the intricate bronchial network, parenchymal tissue, and visceral pleura. The inverse finite element analysis (IFEA) framework is developed using 3-D digital image correlation (DIC) from experimentally measured non-contact strains and displacements from an ex-vivo porcine lung specimen for the first time. A custom-designed inflation device is employed to uniquely correlate the multiscale classical pressure-volume bulk breathing measures to local-level deformation topologies and principal expansion directions. Optimal material parameters are found by minimizing the error between experimental and simulation-based lung surface displacement values, using both classes of gradient-based and gradient-free optimization algorithms and by developing an adjoint formulation for efficiency. The heterogeneous and anisotropic characteristics of pulmonary breathing are represented using various hyperelastic continuum formulations to divulge compound material parameters and evaluate the best performing model. While accounting for tissue anisotropy with fibers assumed along medial-lateral direction did not benefit model calibration, allowing for regional material heterogeneity enabled accurate reconstruction of lung deformations when compared to the homogeneous model. The proof-of-concept framework established here can be readily applied to investigate the impact of assorted organ-level ventilation strategies on local pulmonary force and strain distributions, and to further explore how diseased states may alter the load-bearing material behavior of the lung. In the age of a respiratory pandemic, advancing our understanding of lung biomechanics is more pressing than ever before.
Highlights
Respiratory diseases and disorders, such as asthma, emphysema, bronchitis, pulmonary fibrosis, and lung cancer, collectively lead as the global cause of morbidity and mortality (Centers for Disease Control and Prevention, 2015; Eskandari et al, 2018)
We investigated three different material model cases to consider homogeneity versus regional heterogeneity, preferential orientation using an anisotropic versus isotropic response, and the linear versus nonlinear cases to determine optimal constitutive parameters as detailed below
The experimental displacement values were imposed on the Finite Element (FE) model using the generic homo/iso/hyper case to confirm the validity of the interpolation technique and the strain orientations against the digital image correlation (DIC) system calculations
Summary
Respiratory diseases and disorders, such as asthma, emphysema, bronchitis, pulmonary fibrosis, and lung cancer, collectively lead as the global cause of morbidity and mortality (Centers for Disease Control and Prevention, 2015; Eskandari et al, 2018). There has been notable progress to characterize the lung at the organ scale through classical pressure-volume curves and at the tissue level using indentation and uniaxial tensile tests (Lai-Fook et al, 1976; Zeng et al, 1987; Fung, 1988; Eskandari et al, 2018); these investigations remain siloed at disconnected scales Amalgamating these multiphysics and multiscale behaviors is central to understanding lung disease mechanisms, predicting disease progression, and mitigating ventilator-induced-lung-injuries (VILI) to eliminate tissue over stretching (volutrauma) and stressing (barotrauma) (Dreyfuss and Saumon, 1998; Vlahakis et al, 1999; Arora et al, 2017; Arora et al, 2021). Unless an atlas for pulmonary kinetics and kinematics can be established, current ventilation protocols will continue to be subject to trial and error approaches and hindered from advancements despite exigent demands instilled by a worldwide pandemic (The Acute Respiratory Distress Syndrome Network, 2000; Amato et al, 2015)
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