Pulmonary Acinus Research Articles

Simulation of deformation and flow of pulmonary acinus using morphing compared with self-similar deformation

AbstractIn previous studies of the flow inside the pulmonary acinus, the deformation of acinus was limited because a relatively simple deformation methods, such as self-similar deformation, is used. However, acinus deformation may be complex and heterogeneous. The purpose of this study is to evaluate the influence of the difference in wall deformation between the morphed model and the self-similar deformation model on flow field. The heterogeneous deformation achieved in this study is more actual by using the morphing technology that continuously changes from one shape to another. STAR-CCM + Ver. 13.06 (Siemens PLM Software) was used for numerical calculation, and the governing equations of working fluid are continuous equations and Navier–Stokes equations (NS equations). As a result, the differences in deformation influenced the formation of streamlines at the distal end of the alveolar regions. In the self-similar deformation model, the flow does not change throughout a cycle, whereas in the morphed model, the flow changes during a cycle. Graphic abstract

Development of multi-generation lower respiratory tract model and insights into the transport and deposition characteristics of inhalable particles

Airborne particles can spread quickly and enter human respiratory system via inhalation, causing chronic diseases, even cancer. Although recent studies have informed of toxicity of various pollutants, understanding the transport and deposition characteristics of particles in lower respiratory tract is still challenging. The current study proposes a novel model to simulate flow field change from the entrance of lower respiratory tract to pulmonary acinus, while studying particle transport and deposition characteristics. This model for lower respiratory tract with several bronchial extensions containing virtual pulmonary acinus is calculated using computational fluid dynamics and dynamics mesh. The results showed that in the first 10 generations of the lower respiratory tract, vortices and gravity interfered with particles' trajectory, affecting particle deposition distribution. For the first to the tenth-generation respiratory tract, coarse particles were deposited throughout almost the whole respiratory tract model. In contrast, ultrafine particles did not deposit in the higher-generation respiratory tract. The particle enrichment ability of various lobes was uneven with three particle deposition fraction variation patterns. Virtual pulmonary acinus influenced particle deposition and distribution because of vortex ring's trapped ability during expansion and contraction. This new attempt to build a virtual pulmonary acinus model to simulate particle deposition effects in human respiratory system may provide a reference for studying the toxicities of inhalable particles in the exposed human body.

Three-dimensional critical points and flow patterns in pulmonary alveoli with rhythmic wall motion

The dynamics of airflow in the pulmonary acini are of broad interest in understanding respiratory diseases and the fate of inhaled particles. This study investigates the three-dimensional (3d) alveolar flows with rhythmic cavity wall motion, using a finite element method based computational fluid dynamics. This study reports the new research findings on the critical points and associated flow patterns. The locations of critical points are found based on the Brouwer degree theory and Broyden’s method. The phase portrait is used to evaluate the flow patterns around the critical points and the stability (repelling/attracting property) of the critical points on the symmetry plane of the alveolus. Based on the Poincare–Bendixson theorem, the closed orbits on the symmetry plane are found which have the capability to alter the spiral direction of the spiral streamlines. In the 3d space, the alveolar flow is symmetric about the geometric symmetry plane of the alveolus. Different types of 3d critical points, including saddle, spiral, and spiral saddle, are revealed. There are only one saddle point and at least one spiral point or spiral saddle in the alveolar flow. Spiral points and spiral saddles are located on the vortex core line and their number is dependent on the Reynolds number and varies with time. The study of critical points and their evolution helps us to understand the mechanism of irreversible transport of particle tracers from a new perspective.

High-altitude pulmonary edema: the intercellular network hypothesis

The pathophysiology of high-altitude pulmonary edema is currently attributed to exacerbated heterogeneous hypoxic pulmonary vasoconstriction. However, although other cellular mechanisms have been hypothesized, they are still poorly understood. In this review, we focused on cells of the pulmonary acinus, the distal unit for gas exchange, known to be responders to acute hypoxia, notably through many humoral or tissue factors that connect this intercellular network constituting the alveolo-capillary barrier. Hypoxia could drive alveolar edema by: 1) damaging the fluid reabsorption capacity of alveolar epithelial cells, 2) increasing the endothelial and epithelial permeability, especially by alteration of occluding junctions, 3) triggering the inflammation mainly led by alveolar macrophages, 4) increasing interstitial water accumulation by disruption of extracellular matrix architecture and tight junctions, 5) inducing pulmonary vasoconstriction through an orchestrated response of pulmonary arterial endothelial and smooth muscle cells. Hypoxia may also alter the function of fibroblasts and pericytes that contribute to the interconnection of the cells of the alveolar-capillary barrier. Due to its complex intercellular network and delicate pressure gradient equilibrium, the alveolar-capillary barrier is simultaneously affected by acute hypoxia in all its components, leading to rapid accumulation of water in the alveoli.

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology.

Within the pulmonary acini ventilation and blood perfusion are brought together on a huge surface area separated by a very thin blood-gas barrier of tissue components to allow efficient gas exchange. During ventilation pulmonary acini are cyclically subjected to deformations which become manifest in changes of the dimensions of both alveolar and ductal airspaces as well as the interalveolar septa, composed of a dense capillary network and the delicate tissue layer forming the blood-gas barrier. These ventilation-related changes are referred to as micromechanics. In lung diseases, abnormalities in acinar micromechanics can be linked with injurious stresses and strains acting on the blood-gas barrier. The mechanisms by which interalveolar septa and the blood-gas barrier adapt to an increase in alveolar volume have been suggested to include unfolding, stretching, or changes in shape other than stretching and unfolding. Folding results in the formation of pleats in which alveolar epithelium is not exposed to air and parts of the blood-gas barrier are folded on each other. The opening of a collapsed alveolus (recruitment) can be considered as an extreme variant of septal wall unfolding. Alveolar recruitment can be detected with imaging techniques which achieve light microscopic resolution. Unfolding of pleats and stretching of the blood-gas barrier, however, require electron microscopic resolution to identify the basement membrane. While stretching results in an increase of the area of the basement membrane, unfolding of pleats and shape changes do not. Real time visualization of these processes, however, is currently not possible. In this review we provide an overview of septal wall micromechanics with focus on unfolding/folding as well as stretching. At the same time we provide a state-of-the-art design-based stereology methodology to quantify microarchitecture of alveoli and interalveolar septa based on different imaging techniques and design-based stereology.

МОРФОЛОГІЧНА ОЦІНКА ПОШКОДЖЕННЯ ЛЕГЕНЬ У МОЛОДИХ ЩУРІВ, ВИКЛИКАНЕ ЧАСТКОВОЮ ОКЛЮЗІЄЮ ТРАХЕЇ

A decrease in the lumen of the upper respiratory tract (the trachea) in newborn infants is the main cause of impaired development of lungs during postnatal ontogenesis. Aim. To study the histological changes in the lung tissue of young sexually immature animals when modeling partial tracheal stenosis. Materials and methods. Young male Wistar rats aged 25-28 days and weighing 42-54 g were divided into 4 groups: 1) control (intact); 2) animals with tracheal stenosis (7 days); 3) animals with tracheal stenosis (21 days); 4) animals with tracheal stenosis (7 days after surgery followed by observation for 2 weeks). Modeling of stenosis was reproduced by applying a ligature at the level of the upper quarter of the trachea. This caused a narrowing of the tracheal lumen by 25-30%. The histological changes of the lungs in animals of all experimental groups were studied. Results. A significant structural damage to the alveoli and swelling of the alveolar acini were revealed on the 7th day of the development of tracheal stenosis. A partial reduction of pathomorphological changes was observed on day 21. The removal of the ligature from the trachea was accompanied by a gradual restoration of the normal histological structure of the animal lung tissue, while maintaining individual zones of hypoxic damage. At the same time, intra-alveolar edema, wedening of the alveolar lumen, a decrease in the thickness of their walls, structural disorders of the alveolar-capillary membrane, the accumulation of hemorrhagic contents, and destructive changes in the cells of the pulmonary acini were observed in the lung tissue. Long-term hypoxia (21 days) was accompanied by a partial regression of these damages with a simultaneous increase in the number of macrophages and massive death of pulmonary acini cells. In group 4 animals, after removing the ligature, in addition to the trachea damage the preservation of separate dystrophic changes was observed. Conclusions. In tracheal stenosis model and acute hypoxic-respiratory hypoxia, dystrophic changes in the lung tissue were revealed. With an increase in the duration of hypoxic exposure, a gradual adaptation of the cellular elements and metabolic processes to the conditions of impaired oxygenation was observed. Restoration of lung ventilation accelerates the development of compensatory and regenerative processes in lung cells against the background of the preservation of pronounced structural and morphological disorders. Keywords: hypoxia, lungs, tracheal stenosis, histological changes, acini.

Application of Machine Learning for Segmentation of the Pulmonary Acinus Imaged by Synchrotron X-Ray Tomography.

Background: To assess the effectiveness of inhalation therapy, it is important to evaluate the lungs' structure; thus, visualization of the entire lungs at the level of the alveoli is necessary. To achieve this goal, the applied visualization technique must satisfy the following two conditions simultaneously: (1) it has to obtain images of the entire lungs, since one part of the lungs is influenced by the other parts, and (2) the images have to capture the detailed structure of the alveolus/acinus in which gas exchange occurs. However, current visualization techniques do not fulfill these two conditions simultaneously. Segmentation is a process in which each pixel of the obtained high-resolution images is simplified (i.e., the representation of an image is changed by categorizing and modifying each pixel) so that we can perform three-dimensional volume rendering. One of the bottlenecks of current approaches is that the accuracy of the segmentation of each image has to be evaluated on the outcome of the process (mainly by an expert). It is a formidable task to evaluate the astronomically large numbers of images that would be required to resolve the entire lungs in high resolution. Methods: To overcome this challenge, we propose a new approach based on machine learning (ML) techniques for the validation step. Results: We demonstrate the accuracy of the segmentation process itself by comparison with previously validated images. In this ML approach, to achieve a reasonable accuracy, millions/billions of parameters used for segmentation have to be optimized. This computationally demanding new approach is achievable only due to recent dramatic increases in computation power. Conclusion: The objective of this article is to explain the advantages of ML over the classical approach for acinar imaging.

Modeling of Chronic Lung Inflammation in Rats by Repeated Intratracheal Administration of LPS.

A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.

Aerosol deposition in the pulmonary acinar region: Influence of wall motion and interparticle collisions

It is critical to accurately estimate the deposition of inhaled particles in the pulmonary acinus to reduce the damage of ambient aerosols or maximize drug particles' efficacy. However, interparticle interactions were always neglected in the simulation of aerosol deposition in human acinus. A four-generation human acinar model with varying sizes of each generation was developed. Two boundary conditions, rigid wall and moving wall were investigated to simulate the effect of wall motion on the flow field and aerosol deposition for the size range of 0.1–5 μm. Results show that wall motion has a net effect on particles' location and deposition, especially for submicron particles. Moreover, interparticle collisions were employed to gain richer aerosol particle dynamics. Results demonstrate that the minimum concentration of particles for coalescence is 8.5 × 104 particles/cm3 in the acinar region. The coalescence of particles is influenced by particle concentration and diameter, and wall motion and has a non-negligible effect on particle deposition. Furthermore, it should be noted that the influence of collision would be more significant during more respiratory cycles. Our findings demonstrate that wall motion and interparticle collisions play a non-negligible role in the aerosol deposition.

Tessellation-based modeling and flow simulation of pulmonary acinus with alveolar pore

PurposeThis study aims to perform flow simulations inside the acinus with fine alveolar pores (Kohn pores) using hexagonal cells and bottom-up geometric modeling, which enabled the elimination of invalid voids using previous top-bottom methods and spherical or circular cells.Design/methodology/approachRegular hexagonal cells were used to construct alveoli with no gaps via tessellation. Some hexagonal cells were fused to eliminate the inner boundaries to represent the structure of the bronchial tree. For the remaining hexagonal cells, the side lengths of the shared walls were adjusted to construct alveolar pores. Periodic moving boundaries with the same phase were set for all walls to describe synchronous contraction and expansion of the bronchi and alveoli.FindingsMore realistic flow characteristics in the distal lung were obtained. The effects of pore size and the mechanism of auxiliary ventilation of alveolar pores were revealed.Originality/valueTo the best of the authors’ knowledge, this is the first numerical simulation study on the function of multiple alveolar pores at the level of pulmonary acini, which will be helpful for simulating the dynamic process of cough and sputum excretion in the future.

Mathematical modeling of pulmonary acinus structure: Verification of acinar shape effects on pathway structure using rat lungs

The pulmonary acinus is the gas exchange unit in the lung and has a very complex microstructure. The structure model is essential to understand the relationship between structural heterogeneity and mechanical phenomena at the acinus level with computational approaches. We propose an acinus structure model represented by a cluster of truncated octahedra in conical, double-conical, inverted conical, or chestnut-like conical confinement to accommodate recent experimental information of rodent acinar shapes. The basis of the model is the combined use of Voronoi and Delaunay tessellations and the optimization of the ductal tree assuming the number of alveoli and the mean path length as quantities related to gas exchange. Before applying the Voronoi tessellation, controlling the seed coordinates enables us to model acinus with arbitrary shapes. Depending on the acinar shape, the distribution of path length varies. The lengths are more widely spread for the cone acinus, with a bias toward higher values, while most of the lengths for the inverted cone acinus primarily take a similar value. Longer pathways have smaller tortuosity and more generations, and duct length per generation is almost constant irrespective of generation, which agrees well with available experimental data. The pathway structure of cone and chestnut-like cone acini is similar to the surface acini's features reported in experiments. According to space-filling requirements in the lung, other conical acini may also be acceptable. The mathematical acinus structure model with various conical shapes can be a platform for computational studies on regional differences in lung functions along the lung surface, underlying respiratory physiology and pathophysiology.

Human Multi-Compartment Airways-on-Chip Platform for Emulating Respiratory Airborne Transmission: From Nose to Pulmonary Acini.

The past decade has witnessed tremendous endeavors to deliver novel preclinical in vitro lung models for pulmonary research endpoints, including foremost with the advent of organ- and lung-on-chips. With growing interest in aerosol transmission and infection of respiratory viruses within a host, most notably the SARS-CoV-2 virus amidst the global COVID-19 pandemic, the importance of crosstalk between the different lung regions (i.e., extra-thoracic, conductive and respiratory), with distinct cellular makeups and physiology, are acknowledged to play an important role in the progression of the disease from the initial onset of infection. In the present Methods article, we designed and fabricated to the best of our knowledge the first multi-compartment human airway-on-chip platform to serve as a preclinical in vitro benchmark underlining regional lung crosstalk for viral infection pathways. Combining microfabrication and 3D printing techniques, our platform mimics key elements of the respiratory system spanning (i) nasal passages that serve as the alleged origin of infections, (ii) the mid-bronchial airway region and (iii) the deep acinar region, distinct with alveolated airways. Crosstalk between the three components was exemplified in various assays. First, viral-load (including SARS-CoV-2) injected into the apical partition of the nasal compartment was detected in distal bronchial and acinar components upon applying physiological airflow across the connected compartment models. Secondly, nebulized viral-like dsRNA, poly I:C aerosols were administered to the nasal apical compartment, transmitted to downstream compartments via respiratory airflows and leading to an elevation in inflammatory cytokine levels secreted by distinct epithelial cells in each respective compartment. Overall, our assays establish an in vitro methodology that supports the hypothesis for viral-laden airflow mediated transmission through the respiratory system cellular landscape. With a keen eye for broader end user applications, we share detailed methodologies for fabricating, assembling, calibrating, and using our multi-compartment platform, including open-source fabrication files. Our platform serves as an early proof-of-concept that can be readily designed and adapted to specific preclinical pulmonary research endpoints.

Pulmonary acini exhibit complex changes during postnatal rat lung development.

Pulmonary acini represent the functional gas-exchanging units of the lung. Due to technical limitations, individual acini cannot be identified on microscopic lung sections. To overcome these limitations, we imaged the right lower lobes of instillation-fixed rat lungs from postnatal days P4, P10, P21, and P60 at the TOMCAT beamline of the Swiss Light Source synchrotron facility at a voxel size of 1.48 μm. Individual acini were segmented from the three-dimensional data by closing the airways at the transition from conducting to gas exchanging airways. For a subset of acini (N = 268), we followed the acinar development by stereologically assessing their volume and their number of alveoli. We found that the mean volume of the acini increases 23 times during the observed time-frame. The coefficients of variation dropped from 1.26 to 0.49 and the difference between the mean volumes of the fraction of the 20% smallest to the 20% largest acini decreased from a factor of 27.26 (day 4) to a factor of 4.07 (day 60), i.e. shows a smaller dispersion at later time points. The acinar volumes show a large variation early in lung development and homogenize during maturation of the lung by reducing their size distribution by a factor of 7 until adulthood. The homogenization of the acinar sizes hints at an optimization of the gas-exchange region in the lungs of adult animals and that acini of different size are not evenly distributed in the lungs. This likely leads to more homogeneous ventilation at later stages in lung development.

Reaction of eosinophilic granulocytes of guinea pigs airways to the experimental allergic inflammation according to the morphometric study

Background. After creating an animal model of experimental airways allergic inflammation using ovalbumin, scientists mainly studied the reaction of the cellular and humoral links of the acquired specific immunity. At the same time, it is known that the development of allergic inflammation of the airways to the effect of the environmental chemoattractants is primarily the result of the local innate immune system response. Pulmonary neuroendocrine cells of the airway epithelium with the help of neuropeptides activate the secretion of IL-5 and IL-13 by type 2 innate lymphoid cells IL-5 determines the eosinophilic inflammation. The question of the reaction of the components of innate immunity of the respiratory tract to the allergic inflammation in most aspects remains open. open. Objective. The purpose of the current study was to define the reaction of eosinophilic granulocytes in guinea pigs lungs as an important component of the innate immunity of the respiratory tract to experimental ovalbumin-induced allergic inflammation according to the data of a morphometric study. Methods. Histological, morphometric, statistical methods were used to study the topographic features and the number of eosinophils in the lungs of male 48 guinea pigs on the 23rd, 30th, 36th and 44th days after initiation of the experimental ovalbumin-induced allergic airway inflammation. Results. Our study demonstrates a significant reaction occurs on the part of the cellular link of innate immunity, which consists in the activation of eosinophils, in the experimental model of ovalbumin-induced airways allergic inflammation. The most significant changes were observed in the distal parts of the intrapulmonary airways and in the structures of the pulmonary acinus in the early period of the development of the inflammatory process (23rd and 30th days after the start of the experiment). The late (36th and 44th days after the start of the experiment) period of the development of an allergic inflammatory process in the lungs is accompanied by a gradual decrease in the activity of eosinophilic inflammation. At the same time, the quantitative indicators remain statistically significantly higher in the intact and control groups, which indicates the continuation of allergic inflammation in the absence of the action of the allergen and is a manifestation of the violation of the recovery and adaptation processes in the local immune system of the lung. Conclusion. After ovalbumin-sensitization and aeroallergization eosinophilic inflammation develops in the lungs of a guinea pig, as a result of the reaction of the innate immunity to the action of an allergen. Actively and first of all, allergic eosinophilic inflammation develops in the distal airways (terminal bronchioles) and in the connective tissue stroma of the pulmonary acinus.

Numerical simulation of the unsteady flow field in the human pulmonary acinus

Understanding of airflow dynamics in the human pulmonary acinus is important for increasing targeted drug effectiveness and determining the health impact of toxic aerosols. However, there is a lack of quantitative data about the pulmonary airflow in realistic and flexible idealized geometries. This paper aims to numerically analyse the flow field of the pulmonary acinus using the computational fluid dynamics (CFD) model during transient breathing. Three-dimensional models with rhythmically expanding-contracting alveolar walls were developed for representing the pulmonary region of the human lung. Three different breathing scenarios were applied in the CFD simulations. The results showed that the transient flow conditions determined the transitions between flow types. The recirculating flow in the alveoli was observed for all cases and it was determined that its intensity depended on the breathing scenario. The flow velocity in the alveoli was slower than that of the channel flow. As we moved deeper into the lung, the flow pattern inside the alveoli exhibited a radial velocity profile. It was found that the alveolar flow exhibited a typical stenotic channel flow characteristics. As a result, the acinus models used in this study takes into account the alveolar wall motion based on physiological breathing conditions. To simulate or estimate the airflow dynamics, thus, the results obtained in this study can be easily utilized in the human lung airway models.

Study on Deposition Characteristics of Microparticles in Terminal Pulmonary Acini by IB-LBM.

As an indicator of health risk, the deposition of microparticles in terminal pulmonary acini is of great significance in the medical field. To control particulate pollution and optimize aerosol delivery, it is necessary to perform an in-depth study of the microparticle deposition in terminal pulmonary acini; however, little research has been done on this topic. This paper proposes a respiratory movement model of terminal pulmonary acini using an immersed boundary–lattice Boltzmann method. In addition, we explored the effect of gravity direction, respiratory rate, microparticle diameter, and other parameters on the microparticles deposition process and distribution, under the airflow in the acinar wall. It was found that the deposition of microparticles is sensitive to gravity direction, and the growth of the respiratory rate increases the rate of microparticle migration and deposition. It was observed that the gravity effect is enhanced by increasing the diameter of microparticles, causing a high deposition and dispersion rate. The study reveals the dynamic correlation between the respiration process and the movement of microparticles, which is of reference value to figure out the pathogenicity mechanism of inhalable particles and to optimize the aerosol delivery.

Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia.

Pulmonary acinar hypoplasia (PAH) and lacrimo-auriculo-dento-digital (LADD) syndrome have both been associated with loss-of-function variants in, or deletions of FGF10. Here we report a multi-generational family with seven members manifesting varying features of LADD syndrome, with one individual dying in early infancy of PAH. Whole genome sequencing in one family member identified a 12,158 bp deletion on chromosome 5p12 that removes two of the three exons of FGF10. Allele-specific PCR demonstrated that all affected family members, including the individual with PAH, carried the 12 kb deletion. We conclude the deletion is pathogenic and expands the mutational spectrum of FGF10 variants in LADD syndrome. The common mechanism underlying the variable clinical features of LADD syndrome is defective terminal branching of salivary and lacrimal glands and pulmonary acini, regulated by the TBX4-FGF10-FGFR2 pathway. The variable phenotypic expressivity of FGF10 haploinsufficiency from relatively benign to lethal is likely due to variation at other genetic loci.

Septal destruction enhances chaotic mixing and increases cellular doses of nanoparticles in emphysematous acinus

One hallmark of emphysema is the breakdown of inter-alveolar septal walls in pulmonary acini. How the acinar dosimetry of environmental aerosols varies at different stages of emphysema remains unclear; this is specifically pertinent to users of tobacco products, which is the leading cause of emphysema. The objective of this study is to systematically assess the impacts of septal destruction on the behavior and fate of nanoparticles (1–800 nm) in a pyramid-shaped sub-acinar model consisting of 496 alveoli. Four diseased geometry variants were created by gradually removing the septal walls from the base model. Particle motions within the acinar region were tracked for particles raging 1–800 nm at four emphysema stages using a well-tested Lagrangian tracking model. Both spatial profile and temporal variation of particle deposition were predicted in healthy and diseased sub-acinar geometries on both a total and regional basis. Results show large differences in airflow and particle dynamics among different emphysema stages. Large differences in particle dynamics are also observed among different particle sizes, with one order of magnitude’s variation in the speeds of particles of 1, 10, and 200 nm. The destruction of septal walls also changed the deposition mechanisms, shifting from connective diffusion to chaotic mixing with emphysema progression. The sub-acinar dosimetry became less sensitive to particle size variation with more septal destructions. The lowest retention rate was found at 200–500 nm in the healthy sub-acinar geometry, but at 800 nm in all emphysematous models considered. The acinus-averaged dose for nanoparticles (1–800 nm) increases with aggravating septal destructions, indicating an even higher risk to the acinus at later emphysema stages.

Modeling of human conducting airways by stochastic parametric L-system

Gas exchange, particle deposition, and drug delivery in the human lungs depend on the structure of the human bronchial tree. The conducting airways occupy the main portion of the human lungs and transport air from outside into pulmonary acini where the O2–CO2 exchange with blood occurs. Therefore, the generation of three-dimensional accurate structure of the conducting airways is required for simulation of the transport phenomena in the human respiratory system. The present study proposes an intelligent method for generation of conducting airways based on stochastic parametric Lindenmayer system (L-system). The conducting airways grow into the bronchopulmonary segments simultaneously using the multi-threads parallelism approach. The proposed Lindenmayer system contains several alphabetic rules which determine how an airway should be divided into two new airways (called the daughters) and when the expansion of the string representing the growth process should be stopped. Each module in the rules of parametric L-system represents an airway and the module parameters represent the geometrical characteristics of the airway (i.e., length, diameter, and orientation). These characteristics are stochastic and found almost independently using an intelligent method. Furthermore, the proposed method uses dimensionless parameters and age-dependent terminating criteria. These two features make the model applicable to the generation of the bronchial tree with various shapes and sizes. The morphometric properties of the generated structure are very close to their corresponding experimental counterparts obtained in anatomical studies. The ability of the proposed method is compared against the other available methods both quantitatively and qualitatively. This comparison shows that the proposed method outperforms them in accuracy, flexibility, and computational demands.

Internal pressure driven finite element model of a single pulmonary acinus

A computer simulated, poroelastic, hyperelastic model was developed to replicate the pressure-volume response of a single pulmonary acinus (15th branch of the respiratory tree and daughter branches) with air flow at its core. An internal pressure driven approach was taken upon a small spherical geometry (99.2 mm3 in volume) representing this small segment of lung parenchyma. A reference porcine tracheal pressure at tidal breathing was adjusted from 1471 Pa to 998 Pa to accommodate for pressure drop, and the pressure of 998 Pa was applied to the model for parametric analysis of its pressure-volume characteristics. In targeting a proportional tidal volume change of approximately 15% while also inducing a pressure-volume hysteresis, material parameters of Young’s modulus of 4 kPa, Poisson’s ratio of 0.4, and a permeability of 5×10-5 cm3s-1cm-2 were identified as suitable. The energy loss over a single pressure-volume cycle for a pulmonary acinus was found to be 6.3×10-6 J. This model was qualitatively compared to the pressure-volume relationship of the original porcine data source, and then with experimental findings of the material parameters for lung parenchyma in medical literature, demonstrating same-order agreement.