In Silico Multi-Scale Investigation of Lung Tissue Mechanics and Injury

Abstract

Biofidelity in lung tissue mechanical response and injury prediction is a critical aspect of human body modeling, since the lungs are one of the life-sustaining organs and thus present a high priority injury and fatality risk. Human body models (HBMs) are becoming integral to safety systems design across a range of industries including automotive, defense, and sports. The lungs in particular present numerous challenges to continuum scale HBMs due to their high mechanical compliance, complex heterogeneous structure, and the transient nature of respiration. Existing continuum-scale lung models in impact HBMs are limited in that they typically use properties from excised lung tissue samples, which do not consider tensile pre-strains in the alveolar walls from lung inflation to functional residual capacity (FRC) which is the nominal in vivo conditions of the lung. Furthermore, the effects of surface tension forces, which are an important aspect of lung response, have not been characterized in the existing literature for the deviatoric deformations relevant to HBMs. Additionally, existing methods for predicting pulmonary contusion (PC) are limited to using reconstructed simulations of impact scenarios, and determining empirical correlations to various response metrics in the lung (such as strain, strain rate, etc.). Consequently, the resulting injury criteria or metrics are limited in their applicability to other models or boundary conditions, and are not mechanistically linked to any injury pathology, nor are linked with the alveolar microstructure where actual lung injury occurs. The focus of the current research was to address these limitations using a multi-scale lung modeling approach to relate the macroscopic continuum scale lung response to the microstructural features of the alveoli, and that could be implemented in contemporary HBMs. The specific objectives of this work were: (O1) to develop an alveolar scale model of lung parenchyma, and to use that model to (O2) inform a continuum scale model of lung tissue, and (O3) inform a pulmonary contusion injury prediction method. A finite element model of a representative volume of lung parenchyma was developed using a generalized tetrakaidecahedron geometry to represent an alveolar cluster. The alveolar cluster model used periodic boundary constraints to model symmetry conditions on each face, and used pressure-driven and displacement-driven boundary conditions to simulate the mechanical response of the alveolar wall network. The material properties of the alveolar wall were determined from experimentally measured stress-stretch curves of excised lung tissue, and pressure-volume curves of saline-filled whole lungs that do not include surface tension forces. An explicit implementation of the surface tension membrane was included in the model, derived from experimental data of pulmonary surfactant surface tension forces, as well as from pressure-volume curves of air-filled whole lungs. The cluster model was used to simulate the macroscopic response of lung parenchyma, and predicted that both the surface tension membrane, and alveolar pre-strains at the functional residual capacity (FRC) lung volume, stiffened the macroscopic response of the cluster. The cluster model was also used to characterize the alveolar wall strains as a function of macroscopic deformation, to determine relations between continuum-scale deformations and alveolar strains at the microstructural scale. The macroscopic response of lung parenchyma predicted by the alveolar cluster model in uniaxial tension/compression and shear, was used to determine stress-stretch properties of a continuum scale lung model that included surface tension membrane forces and alveolar pre-strains at FRC, denoted as the FRC Lung model. An Ogden hyperelastic model was used to capture the deviatoric response, and the bulk properties were derived from an analysis using the rule of mixtures for porous materials. The stress-stretch response predicted by the model without alveolar pre-strains was in general agreement with the experimental data on excised lung tissue from the literature. The FRC Lung model was validated using available experimental data that directly loaded the lungs including an impact experiment by Yen et al. (1988) where the model demonstrated good agreement. The alveolar wall strain predictions and the surface area change predictions of the cluster model were validated against available data on lungs in the physiological range of motion (i.e. volume changes from respiration). Importantly, the model demonstrated that reported alveolar injury thresholds from overdistension, also generally corresponded to the physiological limits of alveolar strain. The alveolar wall strain predictions of the cluster model were used to develop injury thresholds based on alveolar overdistension, by determining thresholds of macroscopic (continuum scale) deviatoric deformation that resulted in alveolar strains that exceeded the physiological limits. The resulting continuum scale strain thresholds were assessed in full-scale HBM simulations of thoracic pendulum impacts, and resulted in contusion predictions that agreed well with expected outcomes, and also matched or outperformed existing calibrated methods. The developed model demonstrated that existing data on excised lung parenchyma, excised alveolar wall, pulmonary surfactant surface tension, whole-lung pressure-volume with saline, and whole-lung pressure-volume with air, were all in general agreement when interpreted with the alveolar-scale model. The multi-scale modeling approach for lung tissue undertaken herein, successfully related microstructural features and injury thresholds at the alveolar scale, to macroscopic lung response and an injury prediction method for input into a continuum scale human body model. Future work can extend the methods presented here to investigate additional features of lung tissue, or to other biological tissues.