Morphometry of the human pulmonary acinus

The geometry and morphometry of intraacinar airways in human lungs were studied on silicone rubber casts from two adult lungs. We defined acini as the complex of alveolated airways distal to the terminal bronchioles--that is, beginning with the first-order respiratory or transitional bronchiole. The morphological properties of pulmonary acini are described. The acinar volume averages 187 mm3 (SD +/- 79 mm3). Intraacinar airways branch dichotomously over about 9 generations (range 6-12). The internal airway diameter falls from 500 micron to 270 micron between acinar generations 0 and 10, whereas the outer diameter (including the sleeve of alveoli) remains constant at 700 micron. Towards the periphery the size of alveoli increases and clusters of alveoli become more numerous. The longitudinal path length of acinar airways (defined as the distance along the ducts from the transitional bronchiole to the alveolar sacs) averages 8.8 mm (+/- 1.4 mm). The morphometric data collected in this study are used to construct an idealized model of human acinar airways that can be related to existing models of the human bronchial tree.     

Bronchial tree of the human embryo: Examination based on a mammalian model

The symmetry of the right and left bronchi, proposed in a previous comparative anatomical study as the basic model of the mammalian bronchial tree, was examined to determine if it applied to the embryonic human bronchial tree. Imaging data of 41 human embryo specimens at Carnegie stages (CS) 16–23 (equivalent to 6–8 weeks after fertilization) belonging to the Kyoto collection were obtained using phase-contrast X-ray computed tomography. Three-dimensional bronchial trees were then reconstructed from these images. Bronchi branching from both main bronchi were labeled as dorsal, ventral, medial, or lateral systems based on the branching position with numbering starting cranially. The length from the tracheal bifurcation to the branching point of the labeled bronchus was measured, and the right-to-left ratio of the same labeled bronchus in both lungs was calculated. In both lungs, the human embryonic bronchial tree showed symmetry with an alternating pattern of dorsal and lateral systems up to segmental bronchus B9 as the basic shape, with a more peripheral variation. This pattern is similar to that described in adult human lungs. Bronchial length increased with the CS in all labeled bronchi, whereas the right-to-left ratio was constant at approximately 1.0. The data demonstrated that the prototype of the human adult bronchial branching structure is formed and maintained in the embryonic stage. The morphology and branching position of all lobar bronchi and B6, B8, B9, and the subsegmental bronchus of B10 may be genetically determined. On the other hand, no common structures between individual embryos were found in the peripheral branches after the subsegmental bronchus of B10, suggesting that branch formation in this region is influenced more by environmental factors than by genetic factors.     

Study of the three-dimensional geometry of the central conducting airways in man using computed tomographic (CT) images

Clinical research on the deposition of inhaled substances (e.g. inhaled medications, airborne contaminants, fumes) in the lungs necessitates anatomical models of the airways. Current conducting airway models lack three‐dimensional (3D) reality as little information is available in the literature on the distribution of the airways in space. This is a limitation to the assessment or predictions of the particle deposition in relation to the subject’s anatomy. Detailed information on the full topology and morphology of the airways is thus required to model the airway tree realistically. This paper presents the length, diameter, gravity, coronal and sagittal angles that together describe completely the airways in 3D space. The angle at which the airways branch out from their parent (branching angle) and the rotation angle between successive bifurcation planes are also included. These data are from the study of two sets of airways computed tomography (CT) images. One CT scan was performed on a human tracheobronchial tree cast and the other on a healthy male volunteer. The airways in the first nine generations of the cast and in the first six conducting generations of the volunteer were measured using a computer‐based algorithm. The data contribute to the knowledge of the lung anatomy. In particular, the spatial structure of the airways is shown to be strongly defined by the central airways with clear angular lobar patterns. Such patterns tend to disappear with a mean gravity, coronal and sagittal angles of 90° in each generation higher than 13–15. The mean branching angle per generation appears independent of the lobe to which the airways belong. Non‐planar geometry at bifurcation is observed with the mean (± SD) bifurcation plane rotation angle of 79 ± 41° (n = 229). This angle appears constant over the generations studied. The data are useful for improving the 3D realism of the conducting airway structure modelling as well as for studying aerosol deposition, flow and biological significance of non‐planar airway trees using analytical and computational flow dynamics modelling.     

Three-dimensional segmentation and skeletonization to build an airway tree data structure for small animals

Quantitative analysis of intrathoracic airway tree geometry is important for objective evaluation of bronchial tree structure and function. Currently, there is more human data than small animal data on airway morphometry. In this study, we implemented a semi-automatic approach to quantitatively describe airway tree geometry by using high-resolution computed tomography (CT) images to build a tree data structure for small animals such as rats and mice. Silicon lung casts of the excised lungs from a canine and a mouse were used for micro-CT imaging of the airway trees. The programming language IDL was used to implement a 3D region-growing threshold algorithm for segmenting out the airway lung volume from the CT data. Subsequently, a fully-parallel 3D thinning algorithm was implemented in order to complete the skeletonization of the segmented airways. A tree data structure was then created and saved by parsing through the skeletonized volume using the Python programming language. Pertinent information such as the length of all airway segments was stored in the data structure. This approach was shown to be accurate and efficient for up to six generations for the canine lung cast and ten generations for the mouse lung cast.     

Use of micro-CT to determine tracheobronchial airway geometries in three strains of mice used in inhalation toxicology as disease models

Aerosol dosimetry estimates for mouse strains used as models for human disease are not available, primarily because of the lack of tracheobronchial airway morphometry data. By using micro-CT scans of in-situ prepared lung casts, tracheobronchial airway morphometry for four strains of mice were obtained: Balb/c, AJ, C57BL/6, and Apoe^−/−. The automated tracheobronchial airway morphometry algorithms for airway length and diameter were successfully verified against previously published manual and automated tracheobronchial airway morphometry data derived from two identical in-situ Balb/c mouse lung casts. There was also excellent agreement in tracheobronchial airway length and diameter between the automated and manual airway data for the AJ, C57BL/6, and Apoe^−/− mice. Differences in branch angle measurements were partially due to the differences in definition between the automated algorithms and manual morphometry techniques. Unlike the manual airway morphometry techniques, the automated algorithms were able to provide a value for inclination to gravity for each airway. Inclusion of an inclination to gravity angle for each airway along with airway length, diameter, and branch angle make the current automated tracheobronchial airway data suitable for use in dosimetry programs that can provide dosimetry estimates for inhaled material. The significant differences in upper tracheobronchial airways between Balb/c mice and between C57BL/6 and Apoe^−/− mice highlight the need for mouse strain-specific aerosol dosimetry estimates.     

Airway Morphology From High Resolution Computed Tomography in Healthy Subjects and Patients With Moderate Persistent Asthma

Models of the human respiratory tract developed in the past were based on measurements made on human tracheobronchial airways of healthy subjects. With the exception of a few morphometric characteristics such as the bronchial wall thickness (WT), very little has been published concerning the effects of disease on the tree structure and geometrical features. In this study, a commercial software package was used to segment the airway tree of seven healthy and six moderately persistent asthmatic patients from high resolution computed tomography images. The process was assessed with regards to the treatment of the images of the asthmatic group. The in vivo results for the bronchial length, diameter, WT, branching, and rotation angles are reported and compared per generation for different lobes. Furthermore, some popular mathematical relationships between these morphometric characteristics were examined in order to verify their validity for both groups. Our results suggest that, even though some relationships agree very well with previously published data, the compartmentalization of airways into lobes and the presence of disease may significantly affect the tree geometry, while the tree structure and airway connectivity is only slightly affected by the disease. Anat Rec, 296:852–866, 2013. © 2013 Wiley Periodicals, Inc.     

A proposed mechanism for the early development of the human tracheobronchial tree

The development of the lung in 25 human embryos and early fetuses up to 140 mm crown–rump length was studied by examination of serial histologic sections, morphometry, and selected reconstructions. The proportion of pulmonary tissue consisting of tracheobronchial tree increases during this period. Bronchial cross-sectional diameter, length of the most distal bronchial branches, and thickness of the distal mesenchyme decline during development. The results are consistent with the concept that the dichotomous branching of the growing tracheobronchial tree occurs because of resistance to forward growth of the bronchial branch by compressed mesenchyme, pleura, or adjacent structures. Division and further growth of the bronchus takes place in areas of lower resistance. This process produces a “filling in” of space available for lung development and brings the epithelial and mesenchymal elements into their definitive relationships.     

Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction

BACKGROUNDS: Approximately half of the Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the present study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and to investigate the ensuing mechanisms. METHODS: Human tissue samples were prepared from the lungs resected from patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the chemical mediators released. RESULTS: Acetaldehyde (>3 x 10(-4) M) increased airway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B2 or cysteinyl-leukotrienes. A histamine (H1 receptor) antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells and degranulation of mast cells. CONCLUSIONS: The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, which may be involved in bronchial smooth muscle contraction following alcohol consumption.     

肺内支气管动脉分布的应用解剖

目的：为选择性支气管动脉造影提供解剖学依据。方法：选用40例肺血管灌注标本和8例肺腐蚀铸型标本进行观测。结果：40侧成人肺标本中．共有59支支气管动脉,左肺l～3支．右肺为1-2支。支气管动脉分为3型．左肺2支型最多．右肺1支型最多。肺门支气管动脉平均外径．右肺1支型口径显著大于2支型．左肺各型口径无显著性差别。支气管动脉进入肺门后,一支动脉分布到几个肺叶者：左侧占72．7％,右侧占92．3％．专入某一肺叶者：左侧占27．3％,右侧占7．7％。肺叶支气管动脉和肺段支气管动脉均以2支最常见。结论：对于肺内支气管动脉的去向应引起重视。     

Detecting alterations in pulmonary airway development with airway-by-airway comparison

Neonatal and postnatal exposures to air pollutants have adverse effects on lung development resulting in airway structure changes. Usually, generation-averaged analysis of airway geometric parameters is employed to differentiate between pulmonary airway trees. However, this method is limited, especially for monopodial branching trees such as in rat airways, because both quite proximal and less proximal airways that have very different structure and function may be in the same generation. To avoid limitations inherent in generation averaging, we developed a method that compares two trees airway-by-airway using micro CT image data from rat lungs. This computerized technique (1) identifies the geometry and architecture of the conducting airways from CT images, (2) extracts the main tree, (3) associates paired airways from the two different trees, and (4) develops summary statistics on the degree of similarity between populations of animals. By comparing the trees airway-by-airway, we found that the variance in airway length of the group exposed to diffusion flame particles (DFP) is significantly larger than the group raised in filtered air (FA). This method also found that rotation angle of the DFP group is significantly larger than FA, which is not as certain in the generation-based analysis. We suggest that airway-by-airway analysis complements generation-based averaging for detecting airway alterations.     

Predicted Tracheobronchial and Pulmonary Deposition in a Murine Asthma Model

Particulate matter dosimetry provides the critical link between exposures and initial doses reaching various sites in the respiratory tract. To extrapolate findings from animal models to humans, quantitative respiratory‐tract anatomical data dosimetry in these animal models is required. The goal of this study was to provide anatomical information for the tracheobronchial and pulmonary region so predictions of particle deposition could be performed for a widely used model of asthma; the sensitized Balb/c mouse. Tracheobronchial airway morphometry of sensitized male Balb/c mice was generated from three in situ prepared lung casts. Distribution of the number of generations to terminal bronchiole for each lung lobe was determined by assigning a unique binary number to each airway. This strategy enabled the median path length to terminal bronchiole to be determined. A total of 25 median length paths to terminal bronchiole were measured (airway length, diameter, and branch angle) in each lung cast. These 25 paths were proportionately distributed among the six lobes based upon the number of median length pathways in each cast. Airway length, diameter, and branch angle were measured for each airway in the 25 median length pathways. Measurements of airway length, diameter, and branch angle for each generation were averaged to create a typical path tracheobronchial anatomy model. A pulmonary airway model was also developed so that particle deposition predictions could be performed for particle diameters of 0.2–10 micrometers. Particle deposition efficiency predictions were consistent with in vivo measured deposition. Anat Rec, 290:1309–1314, 2007. © 2007 Wiley‐Liss, Inc.     

Stochastio morphological model of the rat lung

The laboratory rat is often used as a human surrogate in aerosol inhalation studies. Here we present a new stochastic model for the rat lung analogous to that for the human lung. Morphometric data on the tracheobronchial geometry of the rat lung provided by the Lovelace Inhalation Toxicology Research Institute were analyzed. The results of this statistical analysis reveal significant differences in diameters and branching angles between major and minor daughter tubes starting from the same bifurcation. As a consequence of the more monopodial airway branching in the rat lung compared to the more dichotomous structure of the human lung, we recommend classifying the rat lung airways by their diameters and not by generation numbers. The distributions of the gemetric airway parameters and the correlations among them will be used for Monte Carlo deposition calculations.     

Stochastic morphological model of the rat lung

The laboratory rat is often used as a human surrogate in aerosol inhalation studies. Here we present a new stochastic model for the rat lung analogous to that for the human lung. Morphometric data on the tracheobronchial geometry of the rat lung provided by the Lovelace Inhalation Toxicology Research Institute were analyzed. The results of this statistical analysis reveal significant differences in diameters and branching angles between major and minor daughter tubes starting from the same bifurcation. As a consequence of the more monopodial airway branching in the rat lung compared to the more dichotomous structure of the human lung, we recommend classifying the rat lung airways by their diameters and not by generation numbers. The distributions of the geometric airway parameters and the correlations among them will be used for Monte Carlo deposition calculations.     

多层螺旋CT三维成像行国人气道径线分析

目的探讨国人气管和主支气管各种解剖径线的长度与角度.方法用多层螺旋CT三维成像法测定300例成年健康体检者锁骨胸骨端水平气管内径、锁骨胸骨端水平到隆突的气管长度,左、右主支气管和右中间支气管内径与长度,以及左、右主支气管长轴与矢状面的夹角.结果男性气管、左、右主支气管、右中间支气管内径与长度,以及右上肺叶支气管开口内径均大于女性,而女性左、右主支气管长轴与矢状面夹角均大于男性(p<0.05或0.01).成年人与老年人上述各解剖径线值差异无显著(p>0.05).左主支气管内径值与右主支气管内径值呈高度相关,且分别与气管内径值和身高呈高度相关(p<0.01).结论通过多层螺旋CT三维成像法测定国人气管、左和右主支气管径线值,获左、右主支气管内径值与患者身高和气管内径测量值的回归方程,可预测其左、右主支气管内径值.     

Postnatal growth of tracheobronchial airways of Sprague-Dawley rats

Rats are widely used for the studies of pulmonary toxicology in both juveniles and adults. To facilitate such studies, investigators have developed models of lung architecture based on manual or computerized airway measurements. However, postnatal growth of conducting airways of rat lungs has never been reported. In this paper, we present conducting airway architecture statistics for male Sprague-Dawley rat lungs at ages 15, 28, 40, and 81 days by analyzing CT images from airway silicon casts. Detailed branching characteristics and intersubject variance are presented. This study shows that (i) airway growth in diameter and length is not linear with age, (ii) growth of airway length is faster than that of diameter during the 15-81-day postnatal period, and (iii) asymmetry in airway diameter (ratio of major to minor daughter diameter) increases with age.     

Constructal theory of flow architecture of the lungs

Here we explain the reasons why we have a bronchial tree with 23 levels ofbifurcation. 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 inthe 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 thebranching level of the respiratory tree.     

Optimality in the Variation of Average Branching Angle with Generation in the Human Bronchial Tree

In the human bronchial tree the branching angle becomes larger with generation or for the smaller branches. Previous theories based on single parameter optimization have not been successful at all in predicting the consistent increasing trend of branching angle with continued bifurcation. In this study a new theory for the optimality of the branching angle is proposed, which is based on the optimization between dual competing performances, the maximum space-filling capability at the expense of minimum energy loss. A large-angle branching gives an effect of delivering air into a new direction away from the preceding airways. It then has an effect of utilizing the lung volume with better uniformity, but at the same time inevitably requires a high pressure loss. It is shown in this paper that the ever increasing branching angle with generation can be well explained as the optimum branching structure where the dual opposing performance of space filling and pressure loss is optimized. In estimating the pressure loss, branching loss is considered in addition to the Poiseuille loss. Change of predicted optimum branching angle with generation shows an excellent agreement with the observed data found in the human conducting airways.     

Species-Specific Pulmonary Arterial Asymmetry Determines Species Differences in Regional Pulmonary Perfusion

The functional significance of differences in pulmonary vascular branching and diameter asymmetry between the human and quadruped lung has not previously been addressed. To evaluate the contribution of branching asymmetry to observable species differences in blood flow gradients, computed distributions of blood flow were compared in structure-based models of the human and ovine pulmonary arteries. The models were derived using a combination of computed tomography and a volume-filling algorithm. Pressure, flow, and deformed vessel diameter were calculated in both species models using equations representing conservation of mass and momentum, and a pressure–diameter relationship. The major difference between the human and ovine results was the presence of a large region of “zone 4” flow and higher mean flows in the central region of the ovine lung compared to that in the human. Heterogeneity in tissue perfusion and the contribution of gravity were similar in both species models; however, the gravitationally directed gradients of perfusion in the human and ovine models were different and each consistent with human and quadruped measurements, respectively. The results suggest that measured species differences in pulmonary perfusion gradients are largely determined by differences in branching asymmetry.     

Diameters of arteries, veins, and airways in isolated dog lung

Triple resin casts were made of the pulmonary arteries, veins, and airways from six dog lungs. The airways were cast at a pressure of 25 cm resin in all six. In the first three, both vessels were cast at a pressure of 30 cm resin, and in the second three, arteries were at 10 cm resin and veins at 5 cm resin. Measurements were made of luminal airway diameters down to 1 mm and of the luminal diameters of the corresponding segments of the vascular trees. The relation of one to the other was shown by calculating the regression lines for the corresponding diameters. Intrapulmonary arteries and veins are of approximately equal diameter when cast at 30 cm resin, while the veins are 20% larger than the arteries when cast at 5 cm and 10 cm of resin, respectively. Both vessel diameters are 75% of bronchial at the higher pressure, while at the lower pressures arteries are 59%, and veins 71% of bronchial. In any individual, vessel diameters are a relatively constant proportion of airway diameter. This constant of proportionality varies considerably between dogs, its value ranging from 0.48 to 1.03. It is concluded that in any individual all three trees have similar diameter ratios--that is, the ratio between mean diameters of branches in successive orders.