Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation
Abstract:Asthma, emphysema, COVID-19 and other lung-impacting diseases cause the remodeling of tissue structural properties and can lead to changes in conducting pulmonary volume, viscoelasticity, and air flow distribution. Whole organ experimental inflation tests are commonly used to understand the impact of these modifications on lung mechanics. Here we introduce a novel, automated, custom-designed device for measuring the volume and pressure response of lungs, surpassing the capabilities of traditional machines and … Show more
“…The speckled lung was then placed inside our custom electromechanical pressure–volume (PV) system within an air-tight transparent tank for imaging and DIC data collection (Trilion ARAMIS Adjustable 12M system) as seen in Fig. 1 [ 26 ]. Fig.…”
Section: Methodsmentioning
confidence: 99%
“…We do so by utilizing digital image correlation (DIC) as a novel technique for analyzing topological deformations of the inflating whole porcine lung organ. Building upon previously introduced methods, we interface two systems to simultaneously assess local strain and global pulmonary measurements throughout the lung expansion cycle [ 26 , 27 ]. Existing strain measurement studies, such as digital volume correlation (DVC), optical coherence tomography (OCT) [ 28 – 30 ], computerized tomography (CT) scans [ 31 , 32 ] and doppler elastography and speckle tracking for biological tissues [ 33 , 34 ] are limited because they are at discrete time points, retrieve 2D contour images with projected strains, or are time intensive, which affects the resulting measured lung behavior.…”
Background
Mechanical ventilation is often employed to facilitate breathing in patients suffering from respiratory illnesses and disabilities. Despite the benefits, there are risks associated with ventilator-induced lung injuries and death, driving investigations for alternative ventilation techniques to improve mechanical ventilation, such as multi-oscillatory and high-frequency ventilation; however, few studies have evaluated fundamental lung mechanical local deformations under variable loading.
Methods
Porcine whole lung samples were analyzed using a novel application of digital image correlation interfaced with an electromechanical ventilation system to associate the local behavior to the global volume and pressure loading in response to various inflation volumes and breathing rates. Strains, anisotropy, tissue compliance, and the evolutionary response of the inflating lung were analyzed.
Results
Experiments demonstrated a direct and near one-to-one linear relationship between applied lung volumes and resulting local mean strain, and a nonlinear relationship between lung pressures and strains. As the applied air delivery volume was doubled, the tissue surface mean strains approximately increased from 20 to 40%, and average maximum strains measured 70–110%. The tissue strain anisotropic ratio ranged from 0.81 to 0.86 and decreased with greater inflation volumes. Local tissue compliance during the inflation cycle, associating evolutionary strains in response to inflation pressures, was also quantified.
Conclusion
Ventilation frequencies were not found to influence the local stretch response. Strain measures significantly increased and the anisotropic ratio decreased between the smallest and greatest tidal volumes. Tissue compliance did not exhibit a unifying trend. The insights provided by the real-time continuous measures, and the kinetics to kinematics pulmonary linkage established by this study offers valuable characterizations for computational models and establishes a framework for future studies to compare healthy and diseased lung mechanics to further consider alternatives for effective ventilation strategies.
“…The speckled lung was then placed inside our custom electromechanical pressure–volume (PV) system within an air-tight transparent tank for imaging and DIC data collection (Trilion ARAMIS Adjustable 12M system) as seen in Fig. 1 [ 26 ]. Fig.…”
Section: Methodsmentioning
confidence: 99%
“…We do so by utilizing digital image correlation (DIC) as a novel technique for analyzing topological deformations of the inflating whole porcine lung organ. Building upon previously introduced methods, we interface two systems to simultaneously assess local strain and global pulmonary measurements throughout the lung expansion cycle [ 26 , 27 ]. Existing strain measurement studies, such as digital volume correlation (DVC), optical coherence tomography (OCT) [ 28 – 30 ], computerized tomography (CT) scans [ 31 , 32 ] and doppler elastography and speckle tracking for biological tissues [ 33 , 34 ] are limited because they are at discrete time points, retrieve 2D contour images with projected strains, or are time intensive, which affects the resulting measured lung behavior.…”
Background
Mechanical ventilation is often employed to facilitate breathing in patients suffering from respiratory illnesses and disabilities. Despite the benefits, there are risks associated with ventilator-induced lung injuries and death, driving investigations for alternative ventilation techniques to improve mechanical ventilation, such as multi-oscillatory and high-frequency ventilation; however, few studies have evaluated fundamental lung mechanical local deformations under variable loading.
Methods
Porcine whole lung samples were analyzed using a novel application of digital image correlation interfaced with an electromechanical ventilation system to associate the local behavior to the global volume and pressure loading in response to various inflation volumes and breathing rates. Strains, anisotropy, tissue compliance, and the evolutionary response of the inflating lung were analyzed.
Results
Experiments demonstrated a direct and near one-to-one linear relationship between applied lung volumes and resulting local mean strain, and a nonlinear relationship between lung pressures and strains. As the applied air delivery volume was doubled, the tissue surface mean strains approximately increased from 20 to 40%, and average maximum strains measured 70–110%. The tissue strain anisotropic ratio ranged from 0.81 to 0.86 and decreased with greater inflation volumes. Local tissue compliance during the inflation cycle, associating evolutionary strains in response to inflation pressures, was also quantified.
Conclusion
Ventilation frequencies were not found to influence the local stretch response. Strain measures significantly increased and the anisotropic ratio decreased between the smallest and greatest tidal volumes. Tissue compliance did not exhibit a unifying trend. The insights provided by the real-time continuous measures, and the kinetics to kinematics pulmonary linkage established by this study offers valuable characterizations for computational models and establishes a framework for future studies to compare healthy and diseased lung mechanics to further consider alternatives for effective ventilation strategies.
“…Previously established extensive experimental DIC protocols and pressure-volume tests were utilized for the ex-vivo specimen tests conducted here and will be briefly summarized ( Mariano et al, 2020 ; Sattari et al, 2020 ). Fresh porcine lungs from an abattoir were obtained (50 kg female domestic York farm minipigs, Institutional Animal Care and Use Committee approval not required) and a plastic tube was inserted through the trachea to fully inflate the lung using an airline pressure system.…”
Section: Methodsmentioning
confidence: 99%
“…A generic exfoliator pad dipped in quick-drying white enamel paint (rust-oleum) was used to create speckles ( Mariano et al, 2020 ). The specimen was loaded into our custom pressure-volume apparatus for controlled inflation tests; this device consisted of two pistons (a source and a response), a transparent tank, and a computerized controller system ( Sattari et al, 2020 ). 900 ml of air was applied to the lung, and the real-time continuous pressure and actual volumetric deformation of the lung (less than the applied volume due to the compression of air) was measured.…”
Section: Methodsmentioning
confidence: 99%
“…Here we construct the first in-silico IFEA structural representation of the whole lung as informed and validated from DIC resulting from applied evolutionary pressure-volume loading controlled by a custom-designed breathing apparatus ( Mariano et al, 2020 ; Sattari et al, 2020 ). Based on the obtained surface geometry and deformation map of the inflating lung, a corresponding reduced-order 3-D FE model is constructed using membrane elements undergoing the same experimental lung pressures.…”
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.
Increased ventilator use during the COVID-19 pandemic resurrected persistent questions regarding mechanical ventilation including the difference between physiological and artificial breathing induced by ventilators (i.e., positive- versus negative-pressure ventilation, PPV vs NPV). To address this controversy, we compare murine specimens subjected to PPV and NPV in ex vivo quasi-static loading and quantify pulmonary mechanics via measures of quasi-static and dynamic compliances, transpulmonary pressure, and energetics when varying inflation frequency and volume. Each investigated mechanical parameter yields instance(s) of significant variability between ventilation modes. Most notably, inflation compliance, percent relaxation, and peak pressure are found to be consistently dependent on the ventilation mode. Maximum inflation volume and frequency note varied dependencies contingent on the ventilation mode. Contradictory to limited previous clinical investigations of oxygenation and end-inspiratory measures, the mechanics-focused comprehensive findings presented here indicate lung properties are dependent on loading mode, and importantly, these dependencies differ between smaller versus larger mammalian species despite identical custom-designed PPV/NPV ventilator usage. Results indicate that past contradictory findings regarding ventilation mode comparisons in the field may be linked to the chosen animal model. Understanding the differing fundamental mechanics between PPV and NPV may provide insights for improving ventilation strategies and design to prevent associated lung injuries.
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