Diseased and healthy murine local lung strains evaluated using digital image correlation

Abstract

Tissue remodeling in pulmonary disease irreversibly alters lung functionality and impacts quality of life. Mechanical ventilation is amongst the few pulmonary interventions to aid respiration, but can be harmful or fatal, inducing excessive regional (i.e., local) lung strains. Previous studies have advanced understanding of diseased global-level lung response under ventilation, but do not adequately capture the critical local-level response. Here, we pair a custom-designed pressure–volume ventilator with new applications of digital image correlation, to directly assess regional strains in the fibrosis-induced ex-vivo mouse lung, analyzed via regions of interest. We discuss differences between diseased and healthy lung mechanics, such as distensibility, heterogeneity, anisotropy, alveolar recruitment, and rate dependencies. Notably, we compare local and global compliance between diseased and healthy states by assessing the evolution of pressure-strain and pressure–volume curves resulting from various ventilation volumes and rates. We find fibrotic lungs are less-distensible, with altered recruitment behaviors and regional strains, and exhibit disparate behaviors between local and global compliance. Moreover, these diseased characteristics show volume-dependence and rate trends. Ultimately, we demonstrate how fibrotic lungs may be particularly susceptible to damage when contrasted to the strain patterns of healthy counterparts, helping to advance understanding of how ventilator induced lung injury develops.

Mapping the strain-stiffening behavior of the lung and lung cancer at microscale resolution using the crystal ribcage

“…Optical elastography ( Kennedy et al, 2014 ; Kennedy et al, 2017 ; Wang et al, 2023 ) offers an alternative method for more precisely estimating the displacements throughout a biological sample. For example, recent papers have implemented optical elastography based on digital image correlation (DIC) to quantify the lung’s strain ( Nelson et al, 2023 ) and stiffness ( Maghsoudi-Ganjeh et al, 2021 ); but in each case, the empirical method does not provide physiologically realistic boundary conditions, and the measurements are not at alveolar resolution. Using optical elastography based on deformable image registration, our group recently mapped the elasticity of resected biological samples at optical resolution either by embedding them in thermo-responsive hydrogels ( Regan et al, 2023 ) or by adhering precision-cut lung slices ( Kim et al, 2023 ).…”

A Comparative Study of Ex-Vivo Murine Pulmonary Mechanics Under Positive- and Negative-Pressure Ventilation

“…Modern mechanical ventilators, for both invasive and emerging non-invasive ventilation, utilize PPV [ 19 , 44 ]. Despite the demonstrated oxygenation and hemodynamic benefits, coupled with shorter periods of support associated with NPV [ 20 , 33 , 75 ], on top of the harmful side effects of short and long term PPV (including ventilator induced lung injury (VILI), pneumonia, diaphragm atrophy, and brain injury), PPV remains the main form of ventilation [ 4 , 48 , 57 , 62 , 67 , 74 ]. Preference for PPV stems from cost-effective, compact equipment design, which is more feasible for clinical settings compared to more cumbersome negative-pressure devices that restrict patient access and care.…”