Novel Mechanical Strain Characterization of Ventilated ex vivo Porcine and Murine Lung using Digital Image Correlation

Abstract

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.

Correlating Local Volumetric Tissue Strains with Global Lung Mechanics Measurements

“…An intermediate step to achieve this goal of continuous monitoring is to link surface mapping techniques such as digital image correlation with volume methods. Our team has extensive experience with these surface strain measurement techniques [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ], and recently, groups have published studies exploiting the technique on lungs during mechanical ventilation [ 53 ]. Coupling and correlating imaging modalities can lead to more complete overviews of the mechanics and function without the need to compromise on the in situ loading regime.…”

Developing a Lung Model in the Age of COVID-19: A Digital Image Correlation and Inverse Finite Element Analysis Framework

“…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.…”

“…Advancements in biologically-oriented digital image correlation (DIC) techniques have facilitated quantifying the mechanical connections between organ-level breathing and local tissue behavior for fast, large, and non-linear deformations. DIC is a common full-field, non-contact deformation characterization technique originally applied on inert structures ( Chu et al, 1985 ), and has now been enhanced to study the behavior of intricate biological tissues, such as the cornea ( Boyce et al, 2008 ), arteries ( Sutton et al, 2008 ), knees ( Mallett and Arruda, 2017 ), and most recently, the lung ( Mariano et al, 2020 ). In this method, sequential images of a specimen’s speckled surface undergoing loading are used to obtain the topological displacement field ( Chu et al, 1985 ).…”

“…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.…”

In Vitro Measurements of Cellular Forces and their Importance in the Lung—From the Sub- to the Multicellular Scale

“…These are generated, sensed, and responded to at different scales—from subcellular structures to the tissue or organ level. At the organ scale, global lung mechanics have largely been inferred from pressure, volume, and flow relationships, as well as, very recently, digital image correlation techniques [ 2 , 3 ]. In recent years, novel imaging technologies, including intravital microscopy [ 4 , 5 , 6 ], fast synchrotron radiation CT imaging [ 7 , 8 , 9 ], and magnetic resonance elastography [ 10 , 11 ], have added information on tissue deformations on the macro- and micro-scale level and added to a better understanding of the local mechanical properties in airways and alveoli.…”