Search

Formalin is widely used chemical substance in industry and medicine (as tissue fixative and disinfectant). It contains reactive molecules which have been known for its cytotoxic effects. Furthermore, xylene used in histological techniques during preparation of tissue and has different toxic effects on tissues. The present study was performed to investigate the effects of formaldehyde and xylene inhalation on albino rat’s lung and testes. Fifteen adult male rats were used in this study; the rats were divided randomly into three groups (A, B, and C). Group (A) comprises the control group, whereas the rats in the Group (B) were exposed to 10% formaldehyde vapor and the rats from Group (C) were exposed to xylene vapor for 4 h/day for 5 days/week for 1 month. Histological alterations were observed in the lung of formalin and xylene exposed rats manifested by lymphatic infiltration, emphysema, congestion, dilation of blood vessels, and alveolar sac and also thinning in the wall of alveolar bronchiole. On the other hand, formaldehyde and xylene affected the testes tissue of treated rats including atrophy in the seminiferous tubule cells, edematous connective tissue, degenerative of spermatogenesis, depletion in germinal layer, existing of vacuoles in the seminiferous tubules, and decrease in the number of sperms in the lumen of seminiferous tubules. Furthermore, sperms abnormalities were seen. The data of our study concluded that inhalation the vapor of formaldehyde and xylene has degenerative effects on lungs and testes of the experimental rats as well as affecting on the spermatocytes and increased the frequency of sperm abnormalities.

Introduction: Proper exposure and management of removed tooth from the alveolar sac are essential to ensure its long-term prognosis. This study aimed to assess the parents' knowledge about damaged and avulsed teeth and their immediate treatment in children aged 6-12 years in Zanjan. Collected data using a standard information questionnaire. Materials and Methods: In a cross-sectional study in 1397 from all areas of Zanjan city in a systematic circular method 19 primary schools for girls were selected. A 23-item questionnaire was distributed among all grades one through six to assess parents' awareness of how to deal with dental trauma in these schools. Chi-square statistical test was used to analyze the data. The significance level was considered 0.05. Results: 44.6% of parents had previous exposure to dental injuries, and 71.9% of them declared the removed tooth from the alveolar sac to be unsustainable. More than 50% go to the dentist if they notice looseness and bleeding with contusions, broken crowns and dislodged teeth. 92.9% of parents expressed their interest in training for more information on how to deal with dental injuries. Conclusion: Parents with the diploma and university education had more information about trauma and avulsion. Most parents were unaware of the proper intermediate environment for the location of the tooth, and most parents declared the tooth removed from the alveolar sac unsuitable. Keywords: Pediatric dentistry, Tooth injuries, Dental care for children, Parents, Awareness.

Three-dimensional microstructural analysis of human infant, adult, and diseased lungs can help us understand lung growth and disease progression. Three-dimensional analysis of alveolar sacs and alveolar ducts is fundamental. However, it has not been done completely due to technical limitations. In this study, we will acquire ultra-high resolution 3D CT images by large-field synchrotron radiation micro-CT and reveal the 3D structure of alveolar septa and alveolar sacs by CT image analysis.

Diffuse alveolar damage (DAD) is a characteristic histopathologic pattern in most cases of acute respiratory distress syndrome and severe viral pneumonia, such as COVID-19. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation followed by an organizing phase with pulmonary fibrosis and hyperplasia. The degree of pulmonary fibrosis and surface tension is different in the pathological stages of DAD. The effects of pulmonary fibrosis and surface tension on alveolar sac mechanics in DAD are investigated by using the fluid–structure interaction (FSI) method. The human pulmonary alveolus is idealized by a three-dimensional honeycomb-like geometry, with alveolar geometries approximated as closely packed 14-sided polygons. A dynamic compression-relaxation model for surface tension effects is adopted. Compared to a healthy model, DAD models are created by increasing the tissue thickness and decreasing the concentration of the surfactant. The FSI results show that pulmonary fibrosis is more influential than the surface tension on flow rate, volume, P–V loop, and resistance. The lungs of the disease models become stiffer than those of the healthy models. According to the P–V loop results, the surface tension plays a more important role in hysteresis than the material nonlinearity of the lung tissue. Our study demonstrates the differences in air flow and lung function on the alveolar sacs between the healthy and DAD models.

The determination of the particle dynamics in the human acinar airways having millions of alveoli is critical in preventing potential health problems and delivering therapeutic particles effectively to target locations. Despite its complex geometrical structure and complicate wall movements, the advanced calculation simulations can provide valuable results to accurately predict the aerosol deposition in this region. The objective of this study was to numerically investigate the aerosol particle transport and deposition in the intra-acinar region of a human lung for different breathing scenarios (i.e., light, normal, and heavy activities) during multiple breaths. Idealized intra-acinar models utilized in this study consisted of a respiratory bronchial model, an alveolar duct model, and an alveolar sac model. The particles with 5 μm in diameter released from the inlet of the model were tracked until they deposited or escaped from the computational domain. The results showed that due to the rhythmic alveolar wall movement, the flow field was divided into two regions: one is the low-speed alveolar flow and the other is the channel flow. It was found that the chaotic acinar flow irreversibility played a significant role in the aerosol transport in higher generations. During the succeeding breaths, more particles deposited or escaped to the relating acinar generation and reached the more distal regions of the lung. The number of particles remaining in the suspension at the end of the third cycle ranged from 0.016% to 3%. When the mouth flow rate increased, the number of particles remaining in the suspension reduced, resulting in higher deposition efficiency. The total deposition efficiencies for each flow rate were 24%, 47%, and 77%, respectively. The particle simulation results also showed that more breathing cycle was required for full aerosol particle deposition or escape from the model. In addition to the alveolar wall motion, the type of breathing condition and breathing cycle had a significant effect on the accurate prediction of the aerosol deposition in the intra-acinar region of the human lung.

Rainbow watersnake is a snake that can be found in ponds, has a relatively medium body, a maximum length of 80 cm, generally between 50-60 cm, small-headed, a rather large belly, and short-tailed. The aim of this study is to determine the structure of the histology of the lungs of watersnake (Enhydris enhydris). This study used a sample of 3 watersnakes (Enhydris enhydris) with a body length of ± 50 cm. This study conducted a micro technical method with hematoxylin-eosin (HE) staining. Data obtained from the results of this study were analyzed descriptively and presented in the form of images. Macroscopic observations of the warp in snakes are long, most of the trachea attaches to the warp, and there are water sacs or swimming pouches at the tip of the warp, as well as the histological features of the snakes' warp, alveolar ducts, alveolar sac and alveoli, the histological structure of the lungs in watersnakes (Enhydris enhydris) consist of type 1 alveoli epithelial cells, type 2 alveoli cells, muscle bundles, connective tissue, capillary vessels, and macrophage cells. Based on the results of the study, it can be concluded that the histological structure of the watersnake (Enhydris enhydris) lung is different from the histological structure of the reptile function in general. In the lungs of watersnakes (Enhydris enhydris) only consists of alveolar ducts, alveolar sacs, alveoli, and the presence of water sacs at the ends of the lungs.

In this article, we present a numerical framework based on continuum models for the fluid dynamics and the CO $$_2$$ gas distribution in the alveolar sacs of the human lung during expiration and inspiration, including the gas exchange to the cardiovascular system. We include the expansion and contraction of the geometry by means of the Arbitrary Lagrangian–Eulerian (ALE) method. For discretisation, we use equal-order finite elements in combination with pressure-stabilisation techniques based on local projections or interior penalties. We derive formulations for both techniques that are suitable on arbitrarily anisotropic meshes. These formulations are novel within the ALE method. Moreover, we investigate the effect of different boundary conditions, that vary between inspiration and expiration. We present numerical results on a simplified two-dimensional alveolar sac geometry and investigate the influence of the pressure stabilisations as well as the boundary conditions.

Mechanical ventilation (MV) devices help patients with lung disorders to breathe. Improper setting for MV devices lead to further lung injuries. Therefore, investigating influence of ventilator device settings on healthy and diseased alveolar sacs mechanics could prevent injuries while in use. To this aim, three-dimensional (3D) models for healthy and emphysematous alveolar sacs with and without acute respiratory distress syndrome (ARDS) were developed, and computational fluid dynamics (CFD) analysis and fluid–solid interaction (FSI) approach were employed to study the influence of alveolar sacs wall motion, tidal volume (TV) setting and disease on alveolar sac mechanics. The recirculation region was only monitored in alveolar sacs with rigid wall. Observations demonstrated an increase in compliance during air inhalation into the emphysematous alveolar sacs. Induced air penetrated deeper into healthy alveolar sacs compared to the emphysematous model and recommended TV for chronic obstructive pulmonary disease (COPD) increased applied strain, stress and wall shear stress (WSS) on emphysematous alveolar sacs. In addition, recommended TVs for patients with ARDS decreased strain and stress, but did not influence applied WSS significantly. In general, increasing TV raised stress and strain level and led to deeper air penetration into the alveolar sacs. Afterwards, lower TV decreased strain, stress and WSS for patients who had both ARDS and emphysema. This study can provide invaluable insights about diseased alveolar sacs mechanics and evaluate importance of ventilator devices setting in different disease conditions.

The chronic obstructive pulmonary disease (COPD) is a pulmo disease that is distinguished by reduction of peak expiratory flow rate and steady forced discharging of lungs. Pulmonary emphysema is one of the causes of COPD, and is due to damage in alveolar sacs that is caused due to loss in its elastic quality. An early diagnosis and it's treatment could help to take steps in controlling the symptoms. Hence, the quantification of emphysematous lesions in alveolar sac has been a significant topic of research. However, visual evaluation of computed tomography(Ct) images faces the challenge of being a tedious work and relies solely upon trained radiologist. Hence, an algorithm is proposed that would provide a reliable and automatic system that would end the dependence of radiologist and also aid in lessening time to accurately classify between normal tissue (NT), centrilobular (CL) and paraseptal (PS). The proposed novel method quantifies emphysema by congregating features: statistical features of wavelet transformed image, grey-level co-occurrence matrix(GLCM), first order texture statistical features and grey-level run length matrix(GLRLM). To validate the presented algorithm, leave-one-out cross validation technique was employed on the CT database. An accuracy and sensitivity of 91.67% and 91.89% was achieved. The specificity and precision of 95.72% and 92.22% respectively was obtained.

Embryonic development of the alveolar sac of the lung is dependent upon multiple signaling pathways to coordinate cell growth, migration, and the formation of the extracellular matrix. Here, we identify GORAB as a regulator of embryonic alveolar sac formation as genetically disrupting the Gorab gene in mice resulted in fatal saccular maturation defects characterized by a thickened lung mesenchyme. This abnormality is not associated with impairments in cellular proliferation and death, but aberrantly increased protein kinase B (AKT) phosphorylation, elevated Vcan transcription, and enhanced migration of mesenchymal fibroblasts. Genetically augmenting PDGFRα, a potent activator of AKT in lung mesenchymal cells, recapitulated the alveolar phenotypes, whereas disrupting PDGFRα partially rescued alveolar phenotypes in Gorab-deficient mice. Overexpressing or suppressing Vcan in primary embryonic lung fibroblasts could, respectively, mimic or attenuate alveolar sac-like phenotypes in a co-culture model. These findings suggest a role of GORAB in negatively regulating AKT phosphorylation, the expression of Vcan, and the migration of lung mesenchyme fibroblasts, and suggest that alveolar sac formation resembles a patterning event that is orchestrated by molecular signaling and the extracellular matrix in the mesenchyme.

This study investigated the histomorphological features of developing rabbit respiratory acini during the postnatal period. On the 1st day of postnatal life, the epithelium of terminal bronchiole consisted of clear cells which intercalated between few ciliated and abundant non-ciliated (Clara) cells. At this age, the rabbit lung was in the alveolar stage. The terminal bronchioles branched into several alveolar ducts, which opened into atria that communicated to alveolar sacs. All primary and secondary inter-alveolar septa were thick and showed a double-capillary network (immature septa). The primitive alveoli were lined largely by type-I pneumocytes and mature type-II pneumocytes. The type-I pneumocytes displayed an intimate contact with the endothelial cells of the blood capillaries forming the blood–air barrier (0.90 ± 0.03 µm in thickness). On the 3rd day, we observed intense septation and massive formation of new secondary septa giving the alveolar sac a crenate appearance. The mean thickness of the air–blood barrier decreased to reach 0.78 ± 0.14 µm. On the 7th day, the terminal bronchiole epithelium consisted of ciliated and non-ciliated cells. The non-ciliated cells could be identified as Clara cells and serous cells. New secondary septa were formed, meanwhile the inter-alveolar septa become much thinner and the air–blood barrier thickness was 0.66 ± 0.03 µm. On the 14th day, the terminal bronchiole expanded markedly and the pulmonary alveoli were thin-walled. Inter-alveolar septa become much thinner and single capillary layers were observed. In the 1st month, the secondary septa increased in length forming mature cup-shaped alveoli. In the 2nd month, the lung tissue grew massively to involve the terminal respiratory unit. In the 3rd month, the pulmonary parenchyma appeared morphologically mature. All inter-alveolar septa showed a single-capillary layer, and primordia of new septa were also observed. The thickness of the air–blood barrier was much thinner; 0.56 ± 0.16 µm. TUNEL assay after birth revealed that the apoptotic cells were abundant and distributed in the epithelium lining of the pulmonary alveoli and the interstitium of the thick interalveolar septa. On the 7th day, and onward, the incidence of apoptotic cells decreased markedly. This study concluded that the lung development included two phases: the first phase (from birth to the 14th days) corresponds to the period of bulk alveolarization and microvascular maturation. The second phase (from the 14th days to the full maturity) corresponds to the lung growth and late alveolarization.

Large airways or the central airways are composed of trachea and bronchi. The human tracheobronchial tree has 23 generations with the lobar bronchi being the first generation. The proximal, approximately, 16 generations of bronchi have conductive function, while the distal airways take part in gas exchange with a transition zone between the two where the bronchioles have both functions (Fig. 2.1). The respiratory bronchiole, alveolar duct, and alveolar sac have pure gas exchange function. The measurements of the trachea are described in Table 2.1 [1, 2]. The tracheal wall is composed of multiple rigid C-shaped hyaline cartilages covering the anterolateral wall and a collapsible membrane in posterior wall composed of muscle (trachealis) and connective tissue. CT plays an essential role in the identification of lobar and segmental bronchi as well as fissures. This is important in preoperative localization of the endobronchial and parenchymal lesion. The right bronchus is wider, shorter, and more vertical than the left lung. This leads to higher chances of right endobronchial intubation. The right bronchus, after giving rise to upper lobe bronchus, continues as bronchus intermedius and bifurcates into longer right middle lobe bronchus and shorter right lower lobe bronchus. The left bronchus divides into an upper lobe and lower lobe bronchus and subsequently to their segmental bronchi. Lingular bronchus arises from the left upper lobe bronchus. The segmental bronchi help in localizing the bronchopulmonary segments (Table 2.2).

Lung morphometry was introduced over 50 years ago to provide quantitative evaluation of the lung structure. The existing parameters, such as mean linear intercept and destructive index, suffer from simplistic data interpretation and a subjective data acquisition process. To overcome these existing shortcomings, parenchymal airspace profiling (PAP) was developed to provide a more detailed and unbiased quantitative method. Following the standard protocols of fixation, embedding, and sectioning, lung micrographs were: (1) marked with nonparenchymal area, preprocessed, and binarized under the researcher’s supervision; (2) analyzed with a statistical learning method, Gaussian mixture model, to provide an unbiased categorization of parenchymal airspace compartments, corresponding to a single alveolus, alveolar sac, and ductal/destructive airspace; and (3) further quantified into morphometric parameters, including reference volume, alveolar count, and ductal/destructive fraction (DF) based on stereological principles. PAP was performed on hematoxylin and eosin–stained lung sections from mice and rabbits. Unbiased categorization revealed differences in alveolar size among several mouse strains (NZW/LacJ

Emphysema and influenza directly affect alveolar sacs and cause problems in lung performance during the breathing cycle. In this study, the effects of Emphysema and Influenza on alveolar sac’s air flow characteristics are investigated through Computational Fluid Dynamics (CFD) simulation. Both normal and Emphysemic alveolar sac models with varying collapsed volumes resulting from influenza virus replication were developed. Maximum, area average pressure, and wall shear stress (WSS) in collapsed and open alveolar sacs models were compared. It was found that a collapse at half of the volume at the bottom of the alveolar sacs’ models would cause a decrease in average and maximum pressure values and yield higher WSS values for fluid flow during the breathing cycle. On the other hand, a quarter volume collapse at the bottom and side of the model resulted in higher values for average and maximum pressure and WSS. Additionally, results also showed that a combination of alveolar sacs closure and Emphysema would generally lead to an increase in fluid pressure and average WSS during breathing. Maximum WSS was observed during exhalation and maximum WSS decrease occurred during inhalation. Findings are in good agreement with previous studies and suggest that emphysema and influenza virus affect fluid flow and may contribute to alveolar sac closure. However, more realistic simulations should include the fluid-solid interaction studies.

The histological study of lungs in Bidri goat (Capra hircus) and Deccani sheep (Ovis aries) was carried out to know the structural differences in lungs of these animals. Lungs of both the species had respiratory bronchioles, alveolar duct, alveolar sac and alveoli. Respiratory bronchioles were lined by simple cuboidal epithelium in both the species and more number of respiratory bronchioles was seen in adult Bidri goat than adult Deccani sheep. The alveolar ducts were lined by low cuboidal to simple squamous epithelial cells. Alveoli were spherical structures lined by flat and membranous Type-I pneumocytes and large dome shaped Type-II pneumocytes. In transmission electron microscopy (TEM), more numbers of lamellar bodies were seen in cytoplasm of Type-II pneumocytes of Deccani sheep as compared to Bidri goat. Macrophages and mast cells were noticed in interalveolar septa of both the species. In scanning electron microscopy (SEM), no major structural difference was noticed.

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator‐induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator‐induced lung injuries. Two age‐related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50‐year‐old (normal) and second is for an 80‐year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80‐year‐old as compared to the 50‐year‐old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80‐year‐old decreased by about 64% (three‐fold) and 80% (four‐fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80‐year‐old in comparison to the 50‐year‐old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

The current study was carried out to investigate the toxic effects of aflatoxin B1 exposure on heart, lung, and testis of male Albino rats. Twelve healthy male Albino rats were used in the current study. They were divided equally into 2 groups (control and treated groups). The treated group was given aflatoxin B1 orally by a gastric tube at concentration 0.5 mg per kg of body weight for 7 day. The control group was given distilled water alone. At the end of experiment (1 week), the rats were killed under ether anesthesia and the internal organs(heart, lung, and testis) were collected immediately for histological examination. The histopathology examination in heart revealed that there is oedema between myocardial. In lung, there is a large number of inflammatory cells and dilated the alveolar sac with exudates. The testis revealed the excessive vacuolated cells and suppression spermatogenesis. In conclusion, oral dose of aflatoxin B1 exposure could induce a deleterious effect on the histological structure of the heart, lung, and testis of male Albino rats. High level of attention must be taken to prevent the possible contamination of our food with aflatoxin B1.

Better understanding of alveolar mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. The objective of this study was to investigate the alveolar mechanics for two different alveolar sac models, one based on actual geometry and the other an idealized spherical geometry using coupled fluid-solid computational analysis. Both the models were analyzed through coupled fluid-solid analysis to estimate the parameters such as pressures/ velocities and displacements/stresses under mechanical ventilation conditions. The results obtained from the fluid analysis indicate that both the alveolar geometries give similar results for pressures and velocities. However, the results obtained from coupled fluid-solid analysis indicate that the actual alveolar geometry results in smaller displacements in comparison to a spherical alveolar model. This trend is also true for stress/strain between the two models. The results presented indicate that alveolar geometry greatly affects the pressure/velocities as well as displacements and stresses/strains.

The aerosol bolus technique can be used to estimate the degree of convective mixing in the lung; however, contributions of different lung compartments to measured dispersion cannot be differentiated unambiguously. To estimate dispersion in the distal lung, we studied the effect of gravity and airway asymmetry on the dispersion of 1 μm-diameter particle boluses in three-dimensional computational models of the lung periphery, ranging from a single alveolar sac to four-generation (g4) structures of bifurcating airways that deformed homogeneously during breathing. Boluses were introduced at the beginning of a 2-s inhalation, immediately followed by a 3-s exhalation. Dispersion was estimated by the half-width of the exhaled bolus. Dispersion was significantly affected by the spatial orientation of the models in normal gravity and was less in zero gravity than in normal gravity. Dispersion was strongly correlated with model volume in both normal and zero gravity. Predicted pulmonary dispersion based on a symmetric g4 acinar model was 391 ml and 238 ml under normal and zero gravity, respectively. These results accounted for a significant amount of dispersion measured experimentally. In zero gravity, predicted dispersion in a highly asymmetric model accounted for ∼20% of that obtained in a symmetric model with comparable volume and number of alveolated branches, whereas normal gravity dispersions were comparable in both models. These results suggest that gravitational sedimentation and not geometrical asymmetry is the dominant factor in aerosol dispersion in the lung periphery.

Better understanding of the acute/chronic inflammation in airways is very important in to order avoid lung injuries for patients undergoing mechanical ventilation. Inflammation is a complex and dynamic process triggered by many mechanisms within the lung and involves multiple scales starting from organ level to cellular level. In this study, a multiscale modeling framework is being developed to address the cellular inflammation due to mechanical ventilation at the organ level. The developed multiscale modeling framework is illustrated through a case study to investigate inflammatory responses at the alveolar sac during mechanical ventilation. The simulation results showed that high tidal volume (1400 cc) during mechanical ventilation can cause tissue injury due to high concentration of activated immune cells. These results can be further extended to investigate the effects of mechanical ventilation parameters.

Although the major mechanisms of aerosol deposition in the lung are known, detailed quantitative data in anatomically realistic models are still lacking, especially in the acinar airways. In this study, an algorithm was developed to build multigenerational three-dimensional models of alveolated airways with arbitrary bifurcation angles and spherical alveolar shape. Using computational fluid dynamics, the deposition of 1- and 3-μm aerosol particles was predicted in models of human alveolar sac and terminal acinar bifurcation under rhythmic wall motion for two breathing conditions (functional residual capacity = 3 liter, tidal volume = 0.5 and 0.9 liter, breathing period = 4 s). Particles entering the model during one inspiration period were tracked for multiple breathing cycles until all particles deposited or escaped from the model. Flow recirculation inside alveoli occurred only during transition between inspiration and expiration and accounted for no more than 1% of the whole cycle. Weak flow irreversibility and convective transport were observed in both models. The average deposition efficiency was similar for both breathing conditions and for both models. Under normal gravity, total deposition was ∼33 and 75%, of which ∼67 and 96% occurred during the first cycle, for 1- and 3-μm particles, respectively. Under zero gravity, total deposition was ∼2–5% for both particle sizes. These results support previous findings that gravitational sedimentation is the dominant deposition mechanism for micrometer-sized aerosols in acinar airways. The results also showed that moving walls and multiple breathing cycles are needed for accurate estimation of aerosol deposition in acinar airways.

Understanding flow phenomena in the pulmonary acinus is important for predicting particle transport and deposition and hence, in designing effective drug delivery strategies for the lung. In the current study, a three-dimensional honeycomb-like geometry involving a central airspace and surrounding alveoli is used to represent an alveolar duct and sacs. Numerical results predict that flow in the presence of wall motion is characterized by the presence of a developing recirculation region within the cavity and by a flow entrainment region indicative of the weak nature of interaction between duct and cavity. Under the normal breathing condition (2.5 s) and volumetric expansion (approximately 25%) considered here, recirculation disappears for Re0.6. Alveolar flow in higher generations (at lower Reynolds number) results from significantly higher entrainment of the ductal flow, and does not exhibit any recirculation. In an asymmetric arrangement of the alveolar cluster, topological differences in cavity result in significant differences in the size of recirculation and the size of entrainment region within the alveoli of the same acinar generation, indicative of a non-uniform alveolar ventilation. The flow in the terminal alveolar sac is non-recirculating and not affected by variation in geometrical features.

The radioprotect effects of fractinated fucoidan, derived from Undaria pinnatifida sporophylls, were examined in lung injured rats treated with partial body irradiation. The right lung of Sprague-Dawley rats, eight separately grouped by including radiation only control group (ROG) and fucoidan+radiation treated group (FRG), were treated with various fraction of Undaria-derived fucoidan every other day by intraperitoneal injection 6 days prior to irradiation and during monitoring at 24 hours, 48 hours, 2 weeks, 4 weeks and 12-weeks post-irradiation of 6 Mev/2 Gy. The rats were euthanized at completion of the treatment. Tissue samples from the injured lung, fixed in formaldehyde using lung perfusion prior to extraction, were H/E stained for histological analysis using optical microscopy. Interstitial congestion (IC), hemorrhage in alveolar sac (HM), number of macrophage (MP) and alveolar wall thickness (AWT) as a measure of early indication of fibrosis were measured. AWTs in 24 hrs post-irradiation rats increased in comparison with 2.49±0.06μm of control group by 3.67± 0.09μm, 3.21± 0.08μm (p=0.013), 2.98 ± 0.08μm (p=0.00) in ROG, F1-fucoidan+ radiation, and F3-fucoidan+radiation group, respectively. AWT of the ROG was further increased by 4.30± 0.13μm in the 12 weeks post-irradiation group, but AWT on average was 2.56 ± 0.05μm in the FRG. MP in the 24 hrs post-irradiation group markedly increased in comparison with 2.6±0.34/0.14 mm 2 of the control group by 8.0± 1.48/0.14 mm 2 in the ROG, but it was only 3.6 ± 0.48/0.14 mm 2 in F3-FRG. MP in the 12 weeks post-irradiation group was 7.2±1.28/0.14 mm 2 in ROG, but it was 2.8±0.37/0.14 mm 2 or 2.4±0.4/0.14 mm 2 (p

Background Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by a proliferation of vascular endothelial and smooth muscle cells, resulting in occlusion of the lumen of small pulmonary arteries. Cilostazol, with its antiproliferative effects on vascular endothelial and smooth muscle cells, may ameliorate monocrotaline (MCT)-induced PAH in rats. Methods and Results Male Sprague - Dawley rats (n=10/each group) were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus cilostazol (20 mg ·kg-1 · day-1) (group 2) and saline injection only (group 3). Hemodynamic measurement on day 28 following MCT treatment indicated the development of significant PAH on MCT-treated groups (p

Pulmonary emphysema is usually the result of chronic exposure to cigarette smoke in at risk individuals. To investigate the hypothesis that lung damage in emphysema results from coincident weakening in the structural properties of the tissue and increased mechanical forces--as one explanation of the continued development of pulmonary emphysema after smoking cessation--we developed a three dimensional, geometric dodecahedron-based acinar model. Using the model numerical analysis of the stress distribution in normal conditions could be compared with those resulting in emphysematous conditions. Finite element analysis was used to evaluate the model at a number of lung inflation levels, using quasi-static loading of the alveolar pressure. When internal alveolar pressure was increased along with the adjustment of the material properties to represent a weakening of one wall in the acinus, increased stress resulted at the perimeters of the weakened area. In particular this increased stress was localized at the junction points of the internal alveolar septa. It was also found that under the proposed simulated emphysematous conditions, a significant disruption in the stress distribution within the acinus model occurred at low, rather than high, lung volumes. This is supportive of the physiological observation that destruction of the diseased tissue can occur under less stress than those existing in the normal state.

Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear. In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype. Deficiency in TERC or TERT causes a remarkable elevation in various proinflammatory cytokines, including IL-1, IL-6, CXCL15 (human IL-8 homolog), IL-10, TNF-α, and monocyte chemotactic protein 1 (chemokine ligand 2 (CCL2)); decrease in TGF-β1 and TGFβRI receptor in the lungs; and spillover of IL-6 and CXCL15 into the bronchoalveolar lavage fluids. In addition to increased gene expressions of α-smooth muscle actin and collagen 1α1, suggesting myofibroblast differentiation, TERC deficiency also leads to marked cellular infiltrations of a mononuclear cell population positive for the leukocyte common antigen CD45, low-affinity Fc receptor CD16/CD32, and pattern recognition receptor CD11b in the lungs. Our data demonstrate for the first time that telomerase deficiency triggers alveolar stem cell replicative senescence-associated low-grade inflammation, thereby driving pulmonary premature aging, alveolar sac formation, and fibrotic lesion.

An anatomically based finite element model of the human pulmonary microcirculation has been created and applied to simulating regional variations in blood flow. A geometric mesh of the capillary network over the surface of a single alveolar sac is created using a Voronoi meshing technique. A pressure-flow relationship that describes blood cell transit is implemented in the network. Regional flow is investigated by imposing gravity-dependent transpulmonary and transmural boundary conditions. Comparisons of red and white blood cell transit times in the upper, mid, and lower lung showed physiologically consistent trends of a decreasing average transit time and an increased homogeneity of transit time distributions as a result of increasing average capillary diameter and flow down the height of a vertical lung. The model was found to reproduce experimentally consistent trends in red blood cell transit times and relative blood flows with respect to lung height. This model enables flow properties and cell transit time behavior in the pulmonary microcirculation under varying conditions, for example in different "zones" of the lung, to be explored.

Tritiated particulate materials are of potential hazard in fission, fusion, and other tritium handling facilities. The absorbed fractions (fraction of energy emitted that is absorbed by the target region) are calculated for tritiated particles deposited in the alveolar-interstitial (AI) region of the respiratory tract. The energy absorbed by radiologically sensitive tissue irradiated by tritiated particles, in regions of the lung other than in the AI region, is negligible. The ICRP Publication 71 assumes the absorbed fraction is unity for tritium deposited in the AI region. We employed Monte Carlo methods in a model to evaluate the energy deposition in the wall of the alveolar sac from particles of tritiated beryllium, tritiated graphite, titanium tritide, tritiated iron hydroxide and zirconium tritide. For the five materials examined, the absorbed fraction in alveolar tissue ranged from 0.31 to 0.61 for particles of 1 microm physical diameter and 0.07 to 0.21 for 5 microm diameter particles. The dose to alveolar tissue, for an acute inhalation of tritiated particles by an adult male worker, was calculated based on the ICRP 66 lung model and the particle dissolution model of Mercer (1967). For particles of 5 microm activity median aerodynamic diameter (AMAD), the committed equivalent dose to alveolar tissue, calculated for the five materials, ranged from 32-42%, respectively, of the committed equivalent dose derived assuming the absorbed fractions were unity.

The alveolar septum consists of a skeleton of fine collagen and elastin fibers, which are interlaced with a capillary network. Its mechanical characteristics play an important role in the overall performance of the lung. An alveolar sac model was developed for numerical analysis of the internal stress distribution and septal displacements within the alveoli of both normal and emphysematic saline-filled lungs. A scanning electron micrograph of the parenchyma was digitized to yield a geometric replica of a typical two-dimensional alveolar sac. The stress-strain relationship of the alveolar tissue was adopted from experimental data. The model was solved by using commercial finite-element software for quasi-static loading of alveolar pressure. Investigation of the state of stresses and displacements in a healthy lung simulation yielded values that compared well with experimentally reported data. Alteration of the mechanical characteristics of the alveolar septa to simulate elastin destruction in the emphysematic model induced significant stress concentrations (e.g., at a lung volume of 60% total capacity, tensions at certain parts in an emphysematic lung were up to 6 times higher than those in a normal lung). The combination of highly elevated stress sites together with the cyclic loading of breathing may explain the observed progressive damage to elastin fibers in emphysematic patients.

An effective technique of phase contrast synchrotron radiation computed tomography was established for the quantitative analysis of the microstructures in the respiratory zone of a mouse lung. Heitzman's method was adopted for the whole-lung sample preparation, and Canny's edge detector was used for locating the air-tissue boundaries. This technique revealed detailed morphology of the respiratory zone components, including terminal bronchioles and alveolar sacs, with sufficiently high resolution of 1.74 mu m isotropic voxel size. The technique enabled visual inspection of the respiratory zone components and comprehension of their relative positions in three dimensions. To check the method's feasibility for quantitative imaging, morphological parameters such as diameter, surface area and volume were measured and analyzed for sixteen randomly selected terminal branching units, each consisting of a terminal bronchiole and a pair of succeeding alveolar sacs. The four types of asymmetry ratios concerning alveolar sac mouth diameter, alveolar sac surface area, and alveolar sac volume are measured. This is the first ever finding of the asymmetry ratio for the terminal bronchioles and alveolar sacs, and it is noteworthy that an appreciable degree of branching asymmetry was observed among the alveolar sacs at the terminal end of the airway tree, despite the number of samples was small yet. The series of efficient techniques developed and confirmed in this study, from sample preparation to quantification, is expected to contribute to a wider and exacter application of phase contrast synchrotron radiation computed tomography to a variety of studies.

Emphysema is a progressive lung disease that involves permanent destruction of the alveolar walls. Fluid mechanics in the pulmonary region and how they are altered with the presence of emphysema are not well understood. Much of our understanding of the flow fields occurring in the healthy pulmonary region is based on idealized geometries, and little attention has been paid to emphysemic geometries. The goal of this research was to utilize actual replica lung geometries to gain a better understanding of the mechanisms that govern fluid motion and particle transport in the most distal regions of the lung and to compare the differences that exist between healthy and emphysematous lungs. Excised human healthy and emphysemic lungs were cast, scanned, graphically reconstructed, and used to fabricate clear, hollow, compliant models. Three dimensional flow fields were obtained experimentally using stereoscopic particle image velocimetry techniques for healthy and emphysematic breathing conditions. Measured alveolar velocities ranged over two orders of magnitude from the duct entrance to the wall in both models. Recirculating flow was not found in either the healthy or the emphysematic model, while the average flow rate was three times larger in emphysema as compared to healthy. Diffusion dominated particle flow, which is characteristic in the pulmonary region of the healthy lung, was not seen for emphysema, except for very small particle sizes. Flow speeds dissipated quickly in the healthy lung (60% reduction in 0.25 mm) but not in the emphysematic lung (only 8% reduction 0.25 mm). Alveolar ventilation per unit volume was 30% smaller in emphysema compared to healthy. Destruction of the alveolar walls in emphysema leads to significant differences in flow fields between the healthy and emphysemic lung. Models based on replica geometry provide a useful means to quantify these differences and could ultimately improve our understanding of disease progression.

Optical coherence tomography (OCT) is an emerging technology for non-invasive cross-sectional imaging of biological tissue and material with um resolution. Recently, non-invasive high resolution cross-sectional imaging is desired for investigation of diseases in lung in the field of pulmonary medicine. So far, a few works have been reported about OCT imaging of lung. Since the lung consists of alveoli separated by thin wall, ultrahigh resolution (UHR) OCT is supposed to be effective for the imaging of fine structure in lung tissue. In this work, ex vivo cross-sectional imaging of isolated rat lungs was demonstrated using UHR-OCT. A 120 nm-wide, high-power, Gaussian-like supercontinuum (SC) was generated at wavelength of 0.8 um region and it was used as the light source in time domain UHR-OCT. An ultrahigh resolution of 2.1 um in tissue was obtained and the achieved sensitivity was 105 dB. For the UHR-OCT imaging of trachea, the detailed structures of the tracheal cartilage and tracheal mucosa overlying the cartilage were observed clearly. The epithelium and lamina propria were also distinguishable. For the imaging of visceral pleura and alveoli, when saline was instilled into the lung, the penetration depth was improved, and clear images of the fine structure of the lung, including alveoli, were observed owing to the index matching effect. The clear images of up to about 4 alveoli were observed below the visceral pleura. The shape of the alveolar septum was clearly observed, and the alveolar sac was clearly visible.

Traditionally, the assessment of the effects of radiation on living tissue has been made in terms of absorbed dose. This concept, however, might not be the most appropriate when considering the effects arising from the inhalation of insoluble radioactive particulates in inhomogeneous tissue such as the lung. We have therefore applied microdosimetric methods to this problem and, in particular, investigated in detail how energy depositions are distributed when alpha particles travel through parenchymal lung tissue. Sections of material derived from rat, beagle and human lung were examined in an image analyzer, and an imaginary plutonium dioxide particulate was placed on the surface of an alveolar sac. The hypothetical alpha particles emitted from it were followed to the ends of their tracks so that the effects of the material's real structure could be followed in detail. It was found that, taking such detail into account, the alpha particles traveled much greater distances than might have been thought on the basis of a uniform, structureless lung. It was also found that the specific energy distributions can cover several orders of magnitude and can differ significantly between tissue as a whole, cells and nuclei at low exposures. Attempts are made to correlate these results with recently published data on beagle dogs that had inhaled graded exposure levels of plutonium dioxide aerosols.

Particles depositing on alveolar walls is of concern due to their potential to migrate through the blood-gas barrier. Whole-lung dosimetry models do not account for the flow field inside the alveoli and therefore may not accurately describe alveolar deposition. Studies that quantify the flow patterns in realistic geometries are limited and results inconsistent. This study aims to better understand the fluid characteristics in the terminal air sacs; specifically, alveolar mouth to depth flow rate ratio, penetration depth of residual air, and diffusive versus convective particle motion. A terminating alveolar sac with expanding alveolar walls was constructed using 13 truncated sphere-shaped alveoli, with dimensions consistent with published morphometry data. The flow field was governed by a measured in vivo breathing curve for normal volumes over periods of 2 and 4 seconds, analyzed numerically and compared to previous literature. Recirculation was not present, consistent with prior studies. Flow rate ratios (0.18-0.36) were within the range (0.057-1) previously reported. Penetration depths were less than 33% into the air sac during inhalation, decreasing in length for air inside the sac to zero near the wall. Peclet numbers indicated diffusion dominated flow for all submicron-sized particles. However, convection was significant at the duct entrance for particles >0.5 micron and inside the sac for particles >1 micron. Wall motion induced convection may not always be negligible, and if neglected could affect the accuracy of deposition predictions for certain particle sizes and flow conditions.

Particulates that deposit in the acinus region of the lung have the potential to migrate through the alveolar wall and into the blood stream. However, the fluid mechanics governing particle transport to the alveolar wall are not well understood. Many physiological conditions are suspected to influence particle deposition including morphometry of the acinus, expansion and contraction of the alveolar walls, lung heterogeneities, and breathing patterns. Some studies suggest that the recirculation zones trap aerosol particles and enhance particle deposition by increasing their residence time in the region. However, particle trapping could also hinder aerosol particle deposition by moving the aerosol particle further from the wall. Studies that suggest such flow behavior have not been completed on realistic, nonsymmetric, three-dimensional, expanding alveolated geometry using realistic breathing curves. Furthermore, little attention has been paid to emphysemic geometries and how pathophysiological alterations effect deposition. In this study, fluid flow was examined in three-dimensional, expanding, healthy, and emphysemic alveolar sac model geometries using particle image velocimetry under realistic breathing conditions. Penetration depth of the tidal air was determined from the experimental fluid pathlines. Aerosol particle deposition was estimated by simple superposition of Brownian diffusion and sedimentation on the convected particle displacement for particles diameters of 100–750 nm. This study (1) confirmed that recirculation does not exist in the most distal alveolar regions of the lung under normal breathing conditions, (2) concluded that air entering the alveolar sac is convected closer to the alveolar wall in healthy compared with emphysematous lungs, and (3) demonstrated that particle deposition is smaller in emphysematous compared with healthy lungs.

Following the demonstration of morphologic changes induced by a sulphur(IV) aerosol inthe extrapulmonary airways (Takenaka et al., 1990), the pulmonary airways were examined in order to evaluate pulmonary effects. After continuous exposure for 290 days to a respirable sulphur(IV) aerosol at a concentrationequivalent to a sulphur dioxide concentration of 0.6 mg m-3, lung samples from 8 exposed and 3 unexposed beagle dogs were prepared according to the modified cascade sampling and vertical section methods, and bronchial glands and alveolar regions were analyzed morphometrically. No differences were observed in the ratio of bronchial glands to bronchial walls between the exposure and control groups. However, the exposure group showed a slight decrease in the volume density of the septum. This decrease resulted in a reduction in the septal surface area, indicating enlargement of the alveolar air space. One of 8 exposed dogs showed clear morphologic evidence of focal dilation of the alveoli and alveolar sac. There was a significant decrease in the calculated diffusing capacity in the exposure group. These findings indicate that long-term exposure to airborne sulphur(IV) has adverseeffects on both the upper and lower parts of the respiratory system of beagle dogs.

A validated lattice-Boltzmann code has been developed based on the Bhatnagar–Gross–Krook formulation to simulate and analyze transient laminar two-dimensional airflow in alveoli and bifurcating alveolated ducts with moving walls, representative of the human respiratory zone. A physically more realistic pressure boundary condition has been implemented, considering a physiological Reynolds number range, i.e., 0 < Re < 11, which covers the inhalation scenarios from resting mode to moderate exercise. Axial velocity contours, vortex propagation, and streamlines as well as mid-plane pressure variations in different alveolar geometries and shapes are illustrated and discussed. The results show that the influence of the geometric structure on the airflow fields in the human alveolar region is very important. Furthermore, the effect of a moving alveolus wall is significant, i.e., the vortices in the duct or alveolar sacs may change in size. In summary, for a given set of realistic inlet conditions, the airflow velocity and vortical flows are greatly dependent on the different alveolar sac shapes, local geometric structures, and sac expansion rates. The pressure distributions are less influenced by the alveolus shape and wall movement. The present results provide new physical insight and are important for the simulation of particle transport/deposition in the deep lung region.

Myofibroblast-like cells containing smooth muscle actin have been identified in lung injury and repair. These cells differ from typical smooth muscle cells by architectural configuration, location and lack of smooth muscle myosin. Their progenitors are unknown. We hypothesized that these cells might have a developmental analog critical to lung morphogenesis. Lung tissue from developing and adult human lungs was studied using a highly specific monoclonal antibody directed against alpha smooth muscle actin (ASMA). Cells immunoreactive for ASMA (ASMA cells) were identified prenatally in the form of smooth muscle investing the developing vasculature and airway structures. ASMA was not expressed in undifferentiated mesenchymal cells at any prenatal stage. Late in development, ASMA cells within the lung acinus increased proportionally to terminal airway and vascular complexity. In the early postnatal period, the specific distribution of ASMA cells within inflated lung became clearer, and three populations were identified: (1) typical smooth muscle investing the large airways and blood vessels; (2) small clusters of cells within the acinus distributed at the tips of septa protruding into the alveolar duct; (3) individual cells within the alveolar sac sparsely distributed near the junctions of individual alveoli, frequently in association with small blood vessels. We conclude that ASMA cells appear only in developing small and large airways and pulmonary vessels and that they may play a critical role in branching morphogenesis during development.

Background Development of lung alveolar sacs of normal structure and size at late gestation is necessary for the gas exchange process that sustains respiration at birth. Mice lacking the lung differentiation gene T1α [T1α(-/-)] fail to form expanded alveolar sacs, resulting in respiratory failure at birth. Since little is known about the molecular pathways driving alveolar sacculation, we used expression microarrays to identify genes altered in the abnormal lungs and, by inference, may play roles in normal lung morphogenesis. Results Altered expression of genes related to cell-cell interaction, such as ephrinA3, are observed in T1α(-/-) at E18.5. At term, FosB, Egr1, MPK-1 and Nur77, which can function as negative regulators of the cell-cycle, are down-regulated. This is consistent with the hyperproliferation of peripheral lung cells in term T1α (-/-) lungs reported earlier. Biochemical assays show that neither PCNA nor p21 are altered at E18.5. At term in contrast, PCNA is increased, and p21 is decreased. Conclusion This global analysis has identified a number of candidate genes that are significantly altered in lungs in which sacculation is abnormal. Many genes identified were not previously associated with lung development and may participate in formation of alveolar sacs prenatally.

In partial liquid ventilation (PLV), perfluorocarbon (PFC) acts as a diffusion barrier to gas transport in the alveolar space since the diffusivities of oxygen and carbon dioxide in this medium are four orders of magnitude lower than in air. Therefore convection in the PFC layer resulting from the oscillatory motions of the alveolar sac during ventilation can significantly affect gas transport. For example, a typical value of the Peclet number in air ventilation is Pe approximately 0.01, whereas in PLV it is Pe approximately 20. To study the importance of convection, a single terminal alveolar sac is modeled as an oscillating spherical shell with gas, PFC, tissue and capillary blood compartments. Differential equations describing mass conservation within each compartment are derived and solved to obtain time periodic partial pressures. Significant partial pressure gradients in the PFC layer and partial pressure differences between the capillary and gas compartments (P(C)-Pg) are found to exist. Because Pe>> 1, temporal phase differences are found to exist between P(C)-Pg and the ventilatory cycle that cannot be adequately described by existing non-convective models of gas exchange in PLV The mass transfer rate is nearly constant throughout the breath when Pe>>1, but when Pe<

Here we explain the reasons why we have a bronchial tree with 23 levels of bifurcation. Based on Bejan’s Constructal Principle we found that the best oxygen access to the alveolar tissues as well as carbon dioxide removal is provided by a flow structure composed of ducts with 23 levels of bifurcation (bronchial tree) that ends with spaces (alveolar sacs) from where oxygen diffuses into the tissues. The model delivers the dimensions of the alveolar sac, the total length of the airways, the total alveolar surface area, and the total resistance to oxygen transport in the respiratory tree. A constructal law also emerges: the length defined by the ratio of the square of the airway diameter to its length is constant for all individuals of the same species and is related to the characteristics of the space allocated to the respiratory process and determines univocally the branching level of the respiratory tree.

Experimental studies have shown that high pulmonary pressures occurring during ventilation may damage the capillary walls and lead to pulmonary edema. Knowledge of the structural stress distribution within the alveolar septa is a basic first step towards understanding this phenomenon. A two-dimensional alveolar sac model was developed for analysis of stress distribution in septal walls of a saline-filled lung. A parenchymal micrograph was digitized to yield a geometric replica of a typical alveolar sac. Stress concentrations were shown to develop near curved regions, where both tension and compression values may be as high as 20 times that of average stresses. These stresses and the cyclic loading of mechanical ventilation may increase the gaps between the endothelial cells of the capillary walls, and thereby, give rise to pulmonary edema.

The power spectrum of acoustic A-mode backscattering was used to determine size of small scatterers. The mean acoustic size of scatterers and histological measurement of mean alveolar sac size were determined from alveolar regions of the normal preterm lamb lung. Comparisons between these data showed no statistical difference (/spl alpha/=0.05, p value=0.144), and suggested that A-mode ultrasound could provide important information about the anatomical changes of the developing alveolus.

The power spectrum of acoustic A-mode backscattering was used to determine size of small scatterers. Mean acoustic size of scatterers and histological measurement of mean alveolar sac size were determined from alveolar regions of the normal preterm lamb lung. Comparisons between these date showed no statistical difference (/spl alpha/=0.05, p value=0.144), and suggested that A-mode ultrasound could provide important information about the anatomical changes of the developing alveolus.

Mechanical ventilation has been associated with pulmonary edema in the clinical setting, but the pathophysiological mechanisms of this process have not been clearly defined. Experimental studies have shown that high transpulmonary pressures resulting from ventilation may damage the capillary walls, thereby leading to edema. Knowledge of the stress distribution within the alveolar septa would be an important step in understanding this phenomenon. A newly developed saline-filled alveolar sac model was utilized for analysis of septal stresses in young and aging healthy lungs, in order to examine their vulnerability to pulmonary edema during ventilation. Significant stress concentrations were shown to develop near highly curved regions (small local radii of less than 4 mum in a lung inflated to 80% could be as high as 25 times that of average septal stresses. The combination of elevated stress sites that are formed in the stiffer parenchyma of the aging lung, together with the cyclic loading of ventilation, may explain the gaps and breaks previously observed in pulmonary edema.

We have applied a synchrotron radiation computed tomography (SRCT) system to the lung specimens and evaluated its resolving power compared with the histopathologic appearances, precisely. An SRCT system has been constructed in the bending magnet beamline at the SPring-8. The system consists of a double-crystal monochromator, a rotating sample stage, a fluorescent screen, and a charge-coupled device (CCD) array detector (1024 X 1024 pixels with 12 X 12 micrometers 2 pixel size). The energy of the x-ray beam was tuned to 9 - 12 keV. The lungs obtained at autopsy were inflated and fixed by Heitzman's method. A cylindrical specimen (diameter, approximately 8 mm; height, 15 - 25 mm) was rotated in the plane parallel to the beam. The detected signal was transferred to a workstation; then, SRCT images (matrix size, 800 X 800 pixels) were reconstructed by a filtered back- projection. Finally, 6 - 12 micrometer-thick microscopic sections were obtained and stained with hematoxylin and eosin for histopathologic examination. SRCT images well depicted the terminal bronchiole, respiratory bronchiole, alveolar duct, alveolar sac, and alveolar septum. Different pathologic processes (alveolar hemorrhage, alveolitis) demonstrated on SRCT images were well correlated with the histopathologic appearances.