Respiratory illnesses, such as bronchitis, emphysema, asthma, and COVID-19, substantially remodel lung tissue, deteriorate function, and culminate in a compromised breathing ability. Yet, the structural mechanics of the lung is significantly understudied. Classical pressure-volume air or saline inflation studies of the lung have attempted to characterize the organ’s elasticity and compliance, measuring deviatory responses in diseased states; however, these investigations are exclusively limited to the bulk composite or global response of the entire lung and disregard local expansion and stretch phenomena within the lung lobes, overlooking potentially valuable physiological insights, as particularly related to mechanical ventilation. Here, we present a method to collect the first non-contact, full-field deformation measures of ex vivo porcine and murine lungs and interface with a pressure-volume ventilation system to investigate lung behavior in real time. We share preliminary observations of heterogeneous and anisotropic strain distributions of the parenchymal surface, associative pressure-volume-strain loading dependencies during continuous loading, and consider the influence of inflation rate and maximum volume. This study serves as a crucial basis for future works to comprehensively characterize the regional response of the lung across various species, link local strains to global lung mechanics, examine the effect of breathing frequencies and volumes, investigate deformation gradients and evolutionary behaviors during breathing, and contrast healthy and pathological states. Measurements collected in this framework ultimately aim to inform predictive computational models and enable the effective development of ventilators and early diagnostic strategies.

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.

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