Region- and layer-specific mechanical and microstructural properties of human ascending thoracic aortic aneurysms

Ascending thoracic aortic aneurysms are pathological enlargements of the vessel at the level of the thoracic ascending aorta. Understanding the biomechanical properties of the aorta may provide complementary information to aneurysm morphology to improve risk of rupture assessment. In this research, layer- and region-specific mechanical and microstructural properties of aneurysmal and healthy tissues were studied using biaxial tensile tests and histology. Aorta consists of four regions including anterior, posterior, large and small curvatures. From each of these regions, two adjacent specimens were harvested. One of them was considered as composite wall, while two layers of intima/media and adventitia were separated for the adjacent specimen and tested individually. Our results showed no significant regional differences in mechanical characterizations and elastin contents of the both healthy and aneurysmal specimens. However, significant differences were found in mechanical and structural properties between media and adventitia layers

Characterizing Lung Mechanics at the Organ and Tissue Scale

Pulmonary diseases, a leading cause of morbidity and mortality, profoundly affect lung tissue structure, resulting in alterations in mechanical and viscoelastic properties. However, our understanding of these alterations and the underlying material properties remains limited. This dissertation focuses on studying the structural biomechanics of the lung at two levels: the whole organ and tissue level, providing a comprehensive understanding of lung functioning.At the whole organ level, a novel automated device is developed to apply volume and measure lung pressure response, surpassing conventional machines. This device enables groundbreaking viscoelastic insights of the entire lung, facilitating investigations into the mechanical differences between physiological negative pressure ventilation (NPV) and artificial positive pressure ventilation (PPV). Our findings reveal disparities in organ energetics, viscoelasticity, and local stretch between NPV and PPV, emphasizing the importance of understanding these distinctions to optimize ventilator use and enhance patient outcomes. Additionally, we explore the lung's pressure-volume response under varying inflation volumes and frequencies, discovering that lung stiffness increases with faster breathing rates and lower inflation volumes, with inflation volume exerting a stronger influence on lung behavior than frequency. These insights have practical implications for the optimization and design of mechanical ventilators. Furthermore, we investigate the tissue level by examining the mechanical properties of lung airways, where disease-induced microstructural alterations predominantly occur. Through biaxial tensile experiments, we establish baseline mechanics for the entire airway, measuring proximal and distal airways in axial and circumferential orientations simultaneously. Our investigations reveal heterogeneity and anisotropy in airway mechanics, highlighting the limitations of extrapolating proximal airway behavior to the entire bronchial tree. Additionally, we characterize the material properties of pulmonary airways using computational studies, considering the non-linear, anisotropic, and heterogeneous behavior observed experimentally. By comparing various constitutive models, we identify the most suitable model for predicting the mechanical and viscoelastic behavior of the complete bronchial tree. Furthermore, various rheological models accurately capture the lung tissue stress relaxation response in uniaxial testing. These findings significantly enhance our understanding of airway function and improve computational simulations for the diagnosis and monitoring of pulmonary diseases

Studies of the flora in Darmian area in the Southern Khorasan province

The basin area of the Furk and Darmian river is located in northern-east of the Southern Khorasan province. The whole area was 11137 hectares. The area is mountainous with mild weather and dry climate and the average precipitation is about 250 mm per year. In this study, 268 species belonging to 47 families were investigated and 194 genus were identified. The Asteraceae family with 44 species and 34 genera was the largest family in the area. The largest genera were Cousinia with 6 species and Astragalus and Ephorbia with 5 species.The largest life forms in the Darmian area belong to Therophytes with 43% and Hemicryptophytes 37%, Phanaerophytes 9%, Chamaephytes 6%, Bulbous Geophytes and Rhizomatous Geophytes each with 2% and Tuberous Geophytes 1%

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

Abstract Background Common respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date. Methods Specimens were extracted from the proximal and distal airways, namely the trachea, large bronchi, and small bronchi to facilitate evaluations of material heterogeneity, and subjected to biaxial planar loading in the circumferential and axial directions to assess airway anisotropy. Next, samples were subjected to collagenase and elastase enzymatic treatment and tensile tests were repeated. Airway tissue mechanical properties pre- and post-treatment were comprehensively characterized via measures of initial and ultimate moduli, strain transitions, maximum stress, hysteresis, energy loss, and viscoelasticity to gain insights regarding the specialized role of individual connective tissue fibers and network interactions. Results Enzymatic treatment demonstrated an increase in airway tissue compliance throughout loading and resulted in at least a 50% decrease in maximum stress overall. Strain transition values led to significant anisotropic manifestation post-treatment, where circumferential tissues transitioned at higher strains compared to axial counterparts. Hysteresis values and energy loss decreased after enzymatic treatment, where hysteresis reduced by almost half of the untreated value. Anisotropic ratios exhibited axially led stiffness at low strains which transitioned to circumferentially led stiffness when subjected to higher strains. Viscoelastic stress relaxation was found to be greater in the circumferential direction for bronchial airway regions compared to axial counterparts. Conclusion Targeted fiber treatment resulted in mechanical alterations across the loading range and interactions between elastin and collagen connective tissue networks was observed. Providing novel mechanical characterization of elastase and collagenase treated airways aids our understanding of individual and interconnected fiber roles, ultimately helping to establish a foundation for constructing constitutive models to represent various states and progressions of pulmonary disease

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

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 organs 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

Biomechanical properties of ascending aortic aneurysms: Quantification of inter- and intra-patient variability

This study investigates the biomechanical properties of ascending aortic aneurysms focusing on the inter-patient differences vs. the heterogeneity within a patient's aneurysm. Each specimen was tested on a biaxial testing device and the resulting stress-strain response was fitted to a four-parameter Fung constitutive model. We postulate that the inter-patient variability (differences between patients) blurs possible intra-patient variability (regional heterogeneity) and, thus, that both effects must be considered to shed light on the role of heterogeneity in aneurysm progression. We propose, demonstrate, and discuss two techniques to assess differences by, first, comparing conventional biomechanical properties and, second, the overall constitutive response. Results show that both inter-and intra-patient variability contribute to errors when using population averaged models to fit individual tissue behaviour. When inter-patient variability was accounted for and its effects excluded, intra-patient heterogeneity could be assessed, showing a wide degree of heterogeneity at the individual patient level. Furthermore, the right lateral region (from the patient's perspective) appeared different (stiffer) than the other regions. We posit that this heterogeneity could be a consequence of maladaptive remodelling due to altered loading conditions that hastens microstructural changes naturally occurring with age. Further validation of these results should be sought from a larger cohort study.Web of Science125art. no. 11054

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

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

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation.

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 built to range size-scales to accommodate both murine and porcine tests. The software-controlled system is capable of constructing standardized continuous volume-pressure curves, while accounting for air compressibility, yielding consistent and reproducible measures while eliminating the need for pulmonary degassing. This device uses volume-control to enable viscoelastic whole lung macromechanical insights from rate dependencies and pressure-time curves. Moreover, the conceptual design of this device facilitates studies relating the phenomenon of diaphragm breathing and artificial ventilation induced by pushing air inside the lungs. System capabilities are demonstrated and validated via a comparative study between ex vivo murine lungs and elastic balloons, using various testing protocols. Volume-pressure curve comparisons with previous pressure-controlled systems yield good agreement, confirming accuracy. This work expands the capabilities of current lung experiments, improving scientific investigations of healthy and diseased pulmonary biomechanics. Ultimately, the methodologies demonstrated in the manufacturing of this system enable future studies centered on investigating viscoelasticity as a potential biomarker and improvements to patient ventilators based on direct assessment and comparisons of positive- and negative-pressure mechanics

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation.

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 built to range size-scales to accommodate both murine and porcine tests. The software-controlled system is capable of constructing standardized continuous volume-pressure curves, while accounting for air compressibility, yielding consistent and reproducible measures while eliminating the need for pulmonary degassing. This device uses volume-control to enable viscoelastic whole lung macromechanical insights from rate dependencies and pressure-time curves. Moreover, the conceptual design of this device facilitates studies relating the phenomenon of diaphragm breathing and artificial ventilation induced by pushing air inside the lungs. System capabilities are demonstrated and validated via a comparative study between ex vivo murine lungs and elastic balloons, using various testing protocols. Volume-pressure curve comparisons with previous pressure-controlled systems yield good agreement, confirming accuracy. This work expands the capabilities of current lung experiments, improving scientific investigations of healthy and diseased pulmonary biomechanics. Ultimately, the methodologies demonstrated in the manufacturing of this system enable future studies centered on investigating viscoelasticity as a potential biomarker and improvements to patient ventilators based on direct assessment and comparisons of positive- and negative-pressure mechanics