Development and Assessment of a Low-Cost 3D-printed Airway Model for Bronchoscopy Simulation Training.

We report upon the techniques used to create a plastic 3-dimensional-printed bronchoscopy trainer from an actual patient computed tomography scan. The formatting methods to create the printable file, using free open access software, are outlined. The resulting high anatomic fidelity part-task trainer is described, as well as experienced bronchoscopists' perception of its realism and utility as a training tool. A discussion of the current state of knowledge about the role of simulation in bronchoscopy training, as well as the potential contribution of this device, is presented.

Quantitative assessment of bronchiolar smooth muscle in healthy and diseased porcine lungs.

Smooth muscle cells are major components of bronchiolar wall. Bronchiolar smooth muscle is reported to increase in some veterinary pulmonary disorders, but such assumption is not supported by detailed morphometric analyses. The present investigation aimed at quantitatively evaluating bronchiolar smooth muscle in healthy and diseased pig lungs. Our results suggest that bronchiolar smooth muscle cells significantly modify in size and number under different disease conditions, namely parasitic bronchopneumonia and Mycoplasma hyopneumoniae-induced enzootic pneumonia. Further studies are needed in order to understand the pathogenesis and the functional impact of such changes.

3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: direct versus bystander effects.

PURPOSE: The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies. MATERIALS AND METHODS: State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation. RESULTS: The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities. When damage propagation via bystander signalling was assessed, it produced more cell killing and cell transformation events than did direct effects. If bystander signalling was considered, variations of the average probabilities of cell killing and cell transformation were supra-linear over time. CONCLUSIONS: Our results are very sensitive to the radiobiological parameters, derived from in vitro experiments (e.g., range of bystander signalling), applied in this work and suggest that these parameters may not be directly applicable to realistic three-dimensional (3D) epithelium models.

Simulated annealing implementation with shorter Markov chain length to reduce computational burden and its application to the analysis of pulmonary airway architecture.

A new way to implement the Simulated Annealing (SA) algorithm was developed and tested that improves computation performance by using shorter Markov chain length (inner iterations) and repeating the entire SA process until the final function value meets the solution criterion. The new approach coupled with the adaptive neighborhood method was tested on the Rosenbrock function in 4 and 13 dimensions. This implementation significantly improved the computation speed without degrading solution quality. The proposed implementation was used to characterize pulmonary architecture from micro CT image data demonstrating the algorithm's effectiveness especially for problems with high computational demand and when the solution quality requirement can be pre-specified. Using this implementation, detailed statistics of the morphometry of conducting airways from 12 male Sprague Dawley rats were obtained for each lobe.

Stochastic morphometric model of the BALB/c mouse lung.

The laboratory mouse is often used as a human surrogate in aerosol inhalation studies. Morphometric data on the tracheobronchial geometry of three in situ lung casts of the Balb/c mouse lung produced by the Air Pollution Health Effects Laboratory were analyzed in terms of probability density functions and correlations among the different airway parameters. The results of this statistical analysis reveal significant differences in diameters and branching angles between major and minor progeny branching off from the same parent airway at a given airway bifurcation. Number of bronchial airways generations along a given path, expressed by the termination probability, branching angles, and daughter-to-parent diameter ratios indicate that the location of an airway with defined linear airway dimensions within the lung is more appropriately identified by its diameter (or its parent diameter) than by an assigned generation number. We, therefore, recommend classifying the mouse lung airways by their diameters and not by generation numbers, consistent with our previous analysis of the rather monopodial structure of the rat lung (Koblinger et al., J Aerosol Med 1995;8:7­19; Koblinger and Hofmann, J Aerosol Med 1995;8:21­32). Because of lack of corresponding information on respiratory airways, a partly stochastic symmetric acinar airway model was attached to the tracheobronchial model, in which the number of acinar airways along a given path was randomly selected from a measured acinar volume distribution. The computed distributions of the geometric airway parameters and their correlations will be used for random pathway selection of inhaled particles in subsequent Monte Carlo deposition calculations.

Assessment of bronchial wall thickness and lumen diameter in human adults using multi-detector computed tomography: comparison with theoretical models.

A thickened bronchial wall is the morphological substratum of most diseases of the airway. Theoretical and clinical models of bronchial morphometry have so far focused on bronchial lumen diameter, and bronchial length and angles, mainly assessed from bronchial casts. However, these models do not provide information on bronchial wall thickness. This paper reports in vivo values of cross-sectional wall area, lumen area, wall thickness and lumen diameter in ten healthy subjects as assessed by multi-detector computed tomography. A validated dedicated software package was used to measure these morphometric parameters up to the 14th bronchial generation, with respect to Weibel's model of bronchial morphometry, and up to the 12th according to Boyden's classification. Measured lumen diameters and homothety ratios were compared with theoretical values obtained from previously published studies, and no difference was found when considering dichotomic division of the bronchial tree. Mean wall area, lumen area, wall thickness and lumen diameter were then provided according to bronchial generation order, and mean homothety ratios were computed for wall area, lumen area and wall thickness as well as equations giving the mean value of each parameter for a given bronchial generation with respect to its value in generation 0 (trachea). Multi-detector computed tomography measurements of bronchial morphometric parameters may help to improve our knowledge of bronchial anatomy in vivo, our understanding of the pathophysiology of bronchial diseases and the evaluation of pharmacological effects on the bronchial wall.

[Monte-Carlo-Model for the aerosol bolus dispersion in the human lung--part 1: theoretical model description and application]. / Monte-Carlo-Modell der Aerosolbolusdispersion in der menschlichen Lunge--Teil 1: Theoretische Modellbeschreibung und Anwendung.

Aerosol bolus dispersion, which has excited enormous interest in lung medicine due to its possible use as an efficient toolfor the non-invasive clinical diagnosis of lung function, was simulated by a Monte Carlo model based on the concept of effective diffusivities and a stochastic lung geometry. The mathematical approach enabled the computation of essential characteristics of the exhaled bolus (half width, standard deviation, skewness, and mode shift) as well as the estimation of their dependence upon the volumetric lung depth (VLD) of the inhaled bolus. Results of the dispersion model generally show a very good correspondence with preliminary published experimental data. Half width and standard deviation of the exhaled bolus increase with VLD according to specific functions, whereas skewness and mode shift are subject to a decrease. While no correlation between bolus dispersion and flow rate could be worked out with the model, dispersion linearly increased with total lung capacity (TLC).

Assessment of airways with three-dimensional quantitative thin-section CT: in vitro and in vivo validation.

PURPOSE: To prospectively validate the ability of customized three-dimensional (3D) software to enable bronchial tree skeletonization, orthogonal reconstruction of the main bronchial axis, and measurement of cross-sectional wall area (WA) and lumen area (LA) of any visible bronchus on thin-section computed tomographic (CT) images. MATERIALS AND METHODS: Institutional review board approval and patient agreement and informed consent were obtained. Software was validated in a phantom that consisted of seven tubes and an excised human lung obtained and used according to institutional guidelines. In vivo validation was performed with multi-detector row CT in six healthy subjects (mean age, 47 years; range, 20-55 years). Intra- and interobserver agreement and reproducibility over time for bronchial tree skeletonization were evaluated with Bland-Altman analysis. Concordance in identifying bronchial generation was assessed with the kappa statistic. WA and LA obtained with the manual method were compared with WA and LA obtained with validated software by means of the Wilcoxon test and Bland-Altman analysis. RESULTS: WA and LA measurements in the phantom were reproducible over multiple sessions (P > .90) and were not significantly different from WA and LA assessed with the manual method (P > .62). WA and LA measurements in the excised lung and the subjects were not different from measurements obtained with the manual method (intraclass correlation coefficient > 0.99). All lobar bronchi and 80.8% of third generation bronchi, 72.5% of fourth generation bronchi, and 37.7% of fifth generation bronchi were identified in vivo. Intra- and interobserver agreement and reproducibility over time for airway skeletonization and concordance in identifying bronchial generation were good to excellent (intraclass correlation coefficient > 0.98, kappa > 0.54, respectively). CONCLUSION: This method enables accurate and reproducible measurement of WA and LA on reformatted CT sections perpendicular to the main axis of bronchi visible on thin-section CT scans.

The effect of morphological variability on surface deposition densities of inhaled particles in human bronchial and acinar airways.

Deposition fractions in human airway generations were computed with a stochastic deposition model, which is based on a randomly, asymmetrically dividing lung morphology, applying Monte Carlo techniques. Corresponding uncorrelated surface deposition densities were obtained by dividing the average deposition fraction in a given generation by the average total surface area of that generation. In order to consider the statistical correlation between deposition probability and linear airway dimensions in each airway, correlated surface deposition densities were calculated by dividing the deposition fraction in a randomly selected bronchial or acinar airway by the surface area of that airway and by the total number of bronchial or acinar airways in that generation. Average surface deposition densities are relatively constant throughout bronchial airway generations, while average acinar surface deposition densities exhibit a distinct decrease with rising penetration into the acinar region. Due to the correlation between deposition fraction and surface area in a given airway generation, average correlated surface deposition densities are consistently higher than average uncorrelated densities, particularly in the acinar region, where differences can be as high as a few orders of magnitude. Already significant statistical fluctuations of the deposition fractions in individual airway generations are even exacerbated for surface deposition densities, with coefficients of variation about twice as high as for correlated deposition fractions.

Generation of an anatomically based three-dimensional model of the conducting airways.

An anatomically accurate model of the conducting airways is essential for adequately simulating gas mixing, particle deposition, heat and water transfer, and fluid distribution. We have extended a two-dimensional tree-growing algorithm to three dimensions for generation of a host-shape dependent three-dimensional conducting airway model. Terminal branches in the model are both length limited and volume-supplied limited. A limit is imposed on the maximum possible branch angle between a daughter and parent branch. Comparison of the resulting model with morphometric data shows that the algorithm produces branching and length ratios, path lengths, numbers of branches, and branching angles very close to those from the experimental data. The correlation between statistics from the generated model and those from morphometric studies suggests that the conducting airway structure can be described adequately using a "supply and demand" algorithm. The resulting model is a computational mesh that can be used for simulating transport phenomena.

Is there a better right-sided tube for one-lung ventilation? A comparison of the right-sided double-lumen tube with the single-lumen tube with right-sided enclosed bronchial blocker.

UNLABELLED: Anatomic variation between tracheal carina and the take-off of the right upper bronchus often makes the use of a right-sided double-lumen tube (R-DLT) or a single-lumen tube with right-sided enclosed bronchial blocker tube (R-UBB) (Univent) undesirable. This study compared the R-DLT with the R-UBB to determine whether there was any advantage of one over the other during anesthesia with one-lung ventilation (OLV) for right-sided thoracic surgeries. Forty patients requiring right lung deflation were randomly assigned to one of two groups. Twenty patients received a right-sided BronchoCath double-lumen tube, and 20 received a Univent tube with a bronchial blocker placed in the right mainstem bronchus. The following were studied: 1) time required to position each tube until satisfactory placement was achieved; 2) number of times that fiberoptic bronchoscopy was required (including one with the patient supine and one in lateral decubitus position); 3) number of malpositions after initial confirmation of tube placement; 4) time required until lung collapse; 5) surgical exposure; and 6) cost of tubes per case. No differences were found with any of these variables except that the cost of acquisition overall was greater for the R-UBB than for the R-DLT. No right upper lobe collapse was observed in the postoperative period in the chest radiograph in any of the patients studied. We conclude that either tube can be used safely and effectively for right-sided thoracic surgeries that require anesthesia for OLV. IMPLICATIONS: In this study, right-sided double-lumen tubes were compared with the Univent with right-sided bronchial blockers. The results indicate that either tube can be used for right-sided thoracic surgery.

Método no invasivo para explorar la actividad de la musculatura bronquial. valoración de la resistencia de las vías aéreas / Non-invasive trial for the assessment of the brinchial musculature. An evaluation of the airway resistance

Se presenta un método sencillo para explorar las funciones de la musculatura bronquial en el hombre. Fueron empleados individuos sanos voluntarios y algunos pacientes neumológicos. La respiración fue registrada con un neumógrafo colocado en la base del tórax y el flujo de aire con un neumotacógrafo de Fleisch acoplado a una mascarilla ordinaria. Se midió la amplitud máxima de los trazos: en condiciones de reposo; durante y después de una inspiración profunda, de un periodo breve de apnea voluntaria, de la maniobra de Valsalva, o de la aplicación de un ruido súbito. Con las medidas se estableció la relación P/V (presión intra-torácica/volumen pulmonar) se graficaron los datos obtenidos. Se encontró que la musculatura bronquial cambia en su resitencia al flujo de aire, tanto en las condiciones de control como en las manifestaciones reflejas evocadas por las maniobras experimentales empleadas y los estados emocionales, siguiendo las reacciones del sistema nervioso autónomo. Se concluye que a pesar de los diversos factores de error, el método puede ser muy útil para explorar la reactividad del músculo liso de los bronquios en situaciones normales y eventualmente en algunas patológicas

Pediatric lobar lung transplantation.

The disparity between available donors and potential recipients of lung transplants has demanded a certain degree of flexibility on the part of transplantation surgeons. Marginal donors are now being used more frequently, and downsizing lungs from larger donors to fit into small recipients is quite common. In some instances, particularly in the circumstances of children, a single lobe from a much larger donor may serve very well as an entire lung in the recipient. Although either the upper or lower lobes from either side may be used, the lower lobes, especially the left, are better suited for this purpose because of the anatomy of the arterial, venous, and bronchial systems. As an extension of this concept, living-donor lung transplantation is now an accepted practice in carefully selected patients. Most children are best treated with bilateral lobar transplantation, particularly when cystic fibrosis is the indication. For living-donor transplantation, this obviously involves engaging two willing donors able to pass a rigorous physical and psychological evaluation. Although the recipients are generally sicker than the average cadaveric lung transplant recipient, early results to date have been similar to those receiving cadaveric lungs. In this article, we will describe our experience with this procedure, including the evaluation process, the technical aspects of the donor and recipient operations, and the results in the donors and recipients.

Stochastic model of the pulmonary airway tree and its implications for bronchial responsiveness.

The resistance of the pulmonary conducting airway tree (Raw) is a consequence of the resistances of its component airways and how they are connected together. To date, theoretical calculations of Raw have been performed with the aid of mathematical models of the airway tree that are purely deterministic. That is, the mechanical properties of the component airways in these models are precisely defined functions of generation number. Such models take no account of the fact that the airways of a given generation are not all exactly the same but rather exhibit a spectrum of wall thicknesses, amounts of smooth muscle, and number of parenchymal attachments. In the present study, the properties of a 10-generation stochastic airway tree model are investigated. The lengths and radii of the airways in the tree are drawn randomly from probability distribution functions (PDFs), the means of which are deterministic functions of generation number and the standard deviations are assigned various values. Monte Carlo simulation is used to estimate the PDF of Raw itself in various conditions. We show that the relative width of the PDF of Raw may be comparable to that of the PDFs from which the individual airway radii were drawn. It is also shown that when bronchoconstriction is simulated by narrowing each airway by a random amount the resulting PDF for Raw may increase in width many times. We conclude that the variations in airway responsiveness seen in nature can only be properly understood when the distribution of airway properties within the lung are taken into account.

Assessment of methacholine-induced airway constriction by ultrafast high-resolution computed tomography.

Assessment of changes in airway dimensions during bronchoconstriction is conventionally based on measurements of respiratory mechanics. We evaluated the efficacy of ultrafast high-resolution computed tomography (UHRCT) to directly determine the dynamic changes in cross-sectional area (CSA) of airways in response to methacholine (MCh). UHRCT scans were obtained at functional residual capacity before (baseline) and after intravenous bolus injections of MCh (10(-8.5)-10(-7.0) mol/kg) to seven mechanically ventilated pigs. Changes in CSA of bronchi of varying baseline size (1-10 mm diam) were determined by using a customized image processing software package (VIDA) based on a user-directed computer-adjusted edge-finding algorithm. MCh induced dose-dependent decreases in CSA, which were paralleled by increases in airway opening pressure at higher doses of MCh; at lower doses of MCh, decreases in CSA of smaller airways were detected without concomitant changes in airway opening pressure. Changes in CSA were heterogeneous and variable, especially in the smaller airway ranges. The results of the present study support the concept that UHRCT can be used in conjunction with bolus challenges to effectively determine dose-response changes in airway caliber in both large and small airways. This technique provides data that may not be reflected by conventional lung function measurements and, hence, is a useful tool to study airway reactivity.

A comparative study of the accuracy of area assessment by point counting for bronchial mucous glands.

The accuracy with which areas of bronchial mucous gland on histological sections may be determined has been investigated with respect to inherent statistical variability in the point counting procedure used, and with respect to variations between the histological stains and observers employed. Very good argeement was obtained between areas determined by point counting and by planimetry. It was shown empirically that for sections of well-defined gland-like structures the accuracy (coefficient of area) of area determination was inversely proportional to the 3/4 power of the mean point count. The constant of proportionality depended on the structure's shape and on the point geometry of the grid used. Using the relationship the count needed to achieve a required accuracy of area determination could be established. It was shown that in general a smaller count was required for a given accuracy than would be the case using randomly dispersed tissue. On histological sections the accuracy of area determination is also dependent upon gland boundary definition, and our experiments showed that a recticulin Alcian Blue stain best defined mucous gland acini, and that a PBS stain gave the most accurate results for whole gland. These experiments also showed that there were small but significant differences in mean areas determined by different observers. The observers were shown to be equally consistent in their judgment of what constituted whole mucous gland and acini, but since they differed over mean counts it is recommended that studies should be designed to use either a single observer or to assign observers randomly among groups. With these considerations point counting can be made an accurate method of area determination for these or similar tissues.

Cartilage in children's lungs: a quantitative assessment using the right middle lobe.

The amount and development of cartilage in the lungs of 150 children dying between 24 week's gestation and 12 years has been studied using standard sections of the right middle lobe. Both the cartilage-bearing bronchi and the cartilage fragments increase in number until approximately two months after birth, after which time a constant level is maintained. There is a progressive increase in the total area of cartilage in the child's lung during infancy and childhood, and this appears to be more directly related to the crown-rump length of the child than to its age. Percentiles of the quantity of cartilage found in the standard lung sections are presented.