Morphometric Model Research Articles

Stochastic model of particle clearance in human bronchial airways.

A stochastic bronchial clearance model, based on a stochastic morphometric model of the human bronchial tree, has been developed, which simulates the combined action of fast and slow bronchial clearance mechanisms by Monte Carlo methods. To model fast bronchial clearance, mucus velocities in individual airways were based on a correlation between mucus velocity and airway diameter, considering conservation of mucus flow. In addition, mucus transport was assumed to be delayed at bronchial bifurcation zones. The size dependence of the slow bronchial clearance phase was considered by a linear relationship between the slow bronchial clearance fraction, f(s), and the geometric particle diameter, derived from bolus inhalation experiments. Potential variations of f(s) from proximal to distal airway generations were simulated by five different scenarios, which allocated slow bronchial clearance to successively peripheral bronchial regions. Alveolar clearance, which contributes only to longterm particle retention, was modeled by transfer rates supplied by the ICRP respiratory tract model. To test the different components of the clearance model, modeling predictions were compared with experimental retention data from bolus inhalation experiments, using various particle sizes and bolus front depths, as well as from slow inhalation experiments, with a flow rate of only 0.045 L sec(-1). The overall good agreement between modeling results and experimental data indicate that the present model correctly predicts bronchial clearance, suggesting that slow bronchial clearance mechanisms are most effective in smaller bronchial airways.

A hybrid 3D watershed algorithm incorporating gradient cues and object models for automatic segmentation of nuclei in confocal image stacks.

Automated segmentation of fluorescently-labeled cell nuclei in 3D confocal microscope images is essential to many studies involving morphological and functional analysis. A common source of segmentation error is tight clustering of nuclei. There is a compelling need to minimize these errors for constructing highly automated scoring systems. A combination of two approaches is presented. First, an improved distance transform combining intensity gradients and geometric distance is used for the watershed step. Second, an explicit mathematical model for the anatomic characteristics of cell nuclei such as size and shape measures is incorporated. This model is constructed automatically from the data. Deliberate initial over-segmentation of the image data is performed, followed by statistical model-based merging. A confidence score is computed for each detected nucleus, measuring how well the nucleus fits the model. This is used in combination with the intensity gradient to control the merge decisions. Experimental validation on a set of rodent brain cell images showed 97% concordance with the human observer and significant improvement over prior methods. Combining a gradient-weighted distance transform with a richer morphometric model significantly improves the accuracy of automated segmentation and FISH analysis.

A MATHEMATICAL MODEL OF NEONATAL TIDAL LIQUID VENTILATION FOR THE OPTIMIZATION OF AIRWAY MECHANICS AND GAS TRANSFER

Tidal Liquid Ventilation (TLV) was demonstrated to improve lung mechanics and ventilation/perfusion matching in neonatal animal models with respiratory distress. Benefits derive from removing the liquid-gas interface in alveoli, by filling the lungs with liquid perfluorocarbon (PFC). The effects of ventilator settings on blood arterialization and lung mechanics have been scarcely studied quantitatively up to now. We developed a mathematical model describing the course of a neonatal TLV treatment as a function of the ventilator settings (breathing frequency (f), tidal volume (TV), inspiration-to-expiration ratio, PFC flow waveform and PFC pO2). In the overall model, a morphometric lumped-parameter model of airway mechanics (M1) and a model describing O2 and CO2 transport in PFC (M2) are coupled. M1 outputs the pressure and wall shear stress acting at all airway generations, accounting for nonlinear hydraulic airway resistance, inertance, and non-linear compliance, the latter allowing prediction of possible airway collapse phenomena. M2 calculates the diffusive and convective gas transfer through the PFC-filled lungs and the alveolus-capillary gas transfer by describing transport and kinetics of respiratory gases in pulmonary blood. Through the results of model simulations, strategies were defined to increase gas transfer taking the mechanical stresses into account. The model predicts that improving gas exchange without increasing maximum airway pressure is possible by increasing f and decreasing TV. Different strategies were also drawn to limit airway collapse danger or maximum airway shear stress.

Analysis of Histological and Immunohistochemical Patterns of the Liver in Posthepatitic and Alcoholic Cirrhosis by Computerized Morphometry

To assess the degree of fibrosis and the structural changes affecting parenchymal and extraparenchymal components in liver cirrhosis, a computerized morphometric model has been applied to liver specimens from patients with posthepatitic and alcoholic cirrhosis. All specimens have been stained with chromotrope-aniline blue method and monoclonal antibodies against cytokeratin 7, CD31, and VIII factor. Volume fractions of parenchymal compartment and fibrosis have been determined stereologically on CAB slices; moreover, volume fractions of portal bile ducts and proliferated bile ductules, hepatocytes with biliary metaplasia, capillary units, and vascular structures have been measured. Volume fraction of fibrosis was higher in alcoholic cirrhosis when compared with the case of posthepatitic cirrhosis. Volume fractions describing parenchymal compartment showed a similar trend in both viral groups. The main differences were related to immunohistochemical stainings. Volume fraction of hepatocytes with biliary metaplasia was higher in hepatitis C virus-related cirrhosis, whereas volume fractions of biliary structures were more prominent in hepatitis B virus-related cirrhosis. Capillary units were more prominent in posthepatitic cirrhosis than in alcoholic cirrhosis. Interestingly, both forms of posthepatitic cirrhosis show similar features when compared with alcoholic cirrhosis. Our computerized morphometric model well describes and quantifies the morphological alterations of the liver, and it could represent an adjunctive tool to evaluate the degree of dysplastic phenomena involving parenchymal and extraparenchymal components.

Pressure volume curve and alveolar recruitment/de-recruitment. A morphometric model of the respiratory cycle.

The changes in pulmonary volume taking place during respiration are accompanied by the opening and closing of the alveoli, with the number of alveoli open, at the same transpulmonary pressure (TPP) differing, depending on whether the lung is insufflated or deflated. Seventy 344 Fischer rats divided into five groups. Group 1 lungs were fixed by instilling 10% formalin through the trachea to a pressure of 25 cm H2O. The lungs of the next four groups were air-filled and fixed via the pulmonary artery: group 2 lungs were fixed in inflation at 10 cm H2O TPP; group 3 lungs were fixed in inflation at 20 cm. H2O TPP; the lungs of groups 4 and 5 were fixed in deflation and, therefore, were inflated with air up to 27 cm. H2O to drop to 20 cm in group 4 and to 10 cm in group 5. The lungs were processed for light microscopy, carrying out a morphometric study. The results were statistically processed. The lungs insufflated with liquid fixative at 25 cm of TPP reached higher values in the variables Pulmonary Volume, Internal Alveolar Surface (IAS) and Number of Alveoli, being statistically significant (p < 0.05) in comparison with the other four groups. In the lungs fixed in deflation, the pulmonary volume, IAS and number of alveoli were greater than in those fixed in inflation. The lungs fixed to 20 cm in deflation displayed significant statistical differences compared with those fixed to 20 cm in inflation. The IAS and number of alveoli gave good rates in relation with the pulmonary volume (r > or = 0.65). Three variables were used to measure the size of the alveoli, alveolar cord, alveolar surface and Lm, but none showed significant modifications. This study supports the hypothesis that changes in lung volume are related to the increase/decrease in the number of alveoli that are open/closed and not to the modification in the size of the alveoli. Alveolar recruitment is the microscopic expression of pulmonary hysteresis, since the number of alveoli open in deflation is greater than the number open during inflation.

A morphometric model of lung mechanics for time-domain analysis of alveolar pressures during mechanical ventilation.

In this study we propose, and implement in the time domain, an anatomically consistent model of the respiratory system in critical care conditions that allows us to evaluate the impact of different ventilator strategies as well as of constrictive pathologies on the time course of acinar pressures and flows. We discuss the simplifications of the original Horsfield structure (Horsfield, K., et al. Models of the human bronchial tree. J. Appl. Physiol. 31:207-217, 1971), which were needed to enable the model implementation. The model has a binary tree structure including large airways represented as a combination of wall compliance and laminar resistance, small airways that have the same arrangement but can be heterogeneously constricted, and alveolar compartments that are viscoelastic second-order models to represent the stress adaptation behavior of lung tissue. We have described patient-ventilator interactions modeling the ventilator and the endotracheal tube. In conclusion this model makes it possible to investigate realistically the effect of homogeneous versus heterogeneous constrictive pathologies and the impact of different ventilatory patterns on pressure and flow distribution at the acinar level in the mechanically ventilated patient.

Exact morphometric modeling of rat lungs for predicting mechanical impedance

We have developed a computational approach that allows for one-to-one mapping of the airway anatomy when predicting the overall lung mechanical properties and their response to explicit constriction patterns imposed on the airway tree. Specifically, we have exploited the database from Raabe et al. (LF-53 Albuquerque, NM: Lovelace foundation for radical Education and Research), to build the first anatomically based computational model of the rat. The model was then used to predict the response to homogeneous and heterogeneous peripheral airway constriction. Unlike in humans, the inherent asymmetry in the airway tree of rats is predicted to be a dominant contributor to the frequency dependence of lung resistance and elastance even if the constriction is imposed homogeneously. A similar approach would, in principal, be applicable for humans, but the Raabe data is not sufficiently complete to permit this.

Detection of cryptic species in the Tabanus nigrovittatus (Diptera: Tabanidae) complex in Massachusetts by morphometric and cuticular hydrocarbon analysis.

Greenhead flies of the Tabanus nigrovittatus complex from Massachusetts salt marshes were identified as T. nigrovittatus Macquart and T. conterminus Walker using the morphometric model developed by Sofield et al. Four body measurements from a total of 5,983 female flies collected over 2 consecutive years yielded canonical scores producing a unimodal rather than the expected bimodal distribution. The lack of bimodality indicated that both species were not present at the study site. This was substantiated by cuticular hydrocarbon (CHC) analysis of a subsample of these specimens. Fifteen, female flies of the Tabanus nigrovittatus complex from the same site were identified to species using the Sofield et al. morphometric model and validated using CHC analysis. Two individuals of the T. nigrovittatus complex were identified incorrectly as T. conterminus by the morphometric model. The tendency of this model to incorrectly classify some individuals of T. nigrovittatus as T. conterminus brings into question the identity of the Walker syntypes of T. conterminus. Based on CHC analysis, our study shows that both species coexist within our study area.

Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness.

Although airway remodeling and inflammation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflammation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction.

How heterogeneous bronchoconstriction affects ventilation distribution in human lungs: a morphometric model.

Convective dependent flow heterogeneities associated with airways proximal to the acini are the dominant cause of abnormal ventilation distribution during induced bronchoconstriction (Verbanck, S., D. Schuermans, A. Van Muylem, M. Paira, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83:1907-1916, 1997). We applied a morphometric model of the human lung to predict flow distributions among the acini during heterogeneous bronchoconstriction and relate these distributions to impairments in the mechanical properties of the lung. The model has an asymmetrical branching airway system. Heterogeneous constriction was invoked by defining an airway constriction distribution with a mean (mu) and coefficient of variation (CV) and either a Gaussian or log normal distribution. The lung resistance (RL) and elastance (EL) were most sensitive to severely heterogeneous constriction that produced a few highly constricted or closed airways dispersed randomly throughout the periphery. Ventilation distribution in the healthy lung was effectively homogeneous over the frequency range of 0.1-5.0 Hz. With homogeneous or mildly heterogeneous constriction (CV< or =20%) ventilation remained fairly homogeneous at low frequencies (< or =0.1 Hz) but rapidly became heterogeneous as frequency increased. Conversely, a low mean but severely heterogeneous constriction that produced random airway closure produced abnormal ventilation distribution in most acini at all frequencies, and some acini received up to 25 times the normal ventilation. This suggests that certain forms of heterogeneity can lead to shear induced lung injury even at common mechanical ventilation rates.

A predictive morphometric model for the obstructive sleep apnea syndrome.

Mathematical formulas have been used to clinically predict whether patients will develop the obstructive sleep apnea syndrome (OSAS). However, these models do not take into account the disproportionate craniofacial anatomy that accompanies OSAS independently of obesity. To determine the accuracy of a morphometric model, which combines measurements of the oral cavity with body mass index and neck circumference, in predicting whether a patient has OSAS. 6-month prospective study. University-based tertiary referral sleep clinic and research center. 300 consecutive patients evaluated for sleep disorders for the first time. Body mass index, neck circumference, and oral cavity measurements were obtained, and a model value was calculated for each patient. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. Sleep apnea was defined as more than five episodes of apnea or hypopnea per hour of sleep. The morphometric model had a sensitivity of 97.6% (95% CI, 95% to 98.9%), a specificity of 100% (CI 92% to 100%), a positive predictive value of 100% (CI, 98.5% to 100%), and a negative predictive value of 88.5% (CI, 77% to 95%). No significant discrepancies were revealed in tests of intermeasurer and test-retest reliability. The morphometric model provides a rapid, accurate, and reproducible method for predicting whether patients in an ambulatory setting have OSAS. The model may be clinically useful as a screening tool for OSAS rather than as a replacement for polysomnography.

Should Everyone Be Monitored for Upper-Airway Resistance and How?

Preliminary data indicate that the use of a morphometric model, an expert system with standardized questions, and an evaluation of snoring can be effective tools for diagnosing upper-airway sleep-disordered breathing (UASDB) in many cases. This eliminates the need for many sleep recordings.

Enterocyte Functional Adaptation Following Intestinal Resection

Following massive small bowel resection, the remaining intestine undergoes compensatory adaptation to maintain absorptive capacity. The purpose of this study was to determine the relative importance of mucosal hyperplasia and functional adaptation by individual enterocytes in this process. Distal ileum was harvested from rats 2 weeks following 70% small bowel resection or transection with reanastomosis. Transport parameters were determined in Üssing chambers. Short-circuit current (Isc) responses to additions of 3-O-methylglucose were measured to assess Na+/glucose cotransporter kinetics. Microvillus absorptive surface areas were calculated with computer-assisted morphometric modeling. These surface area values were used to normalize transport parameters. Ileal absorptive surface area was 70% greater in resection tissues than in transection tissues (P< 0.05). Na+and Cl−fluxes were generally lower in the resection group. Na+/glucose cotransporter ΔIscmax (an index of cotransporter quantity) for resection and transection tissues were 0.3 ± 0.1 and 1.8 ± 0.3, respectively (P< 0.05).Km(an index of cotransporter affinity for substrate) did not differ significantly. Following intestinal resection, ileal surface area increases; however, transport parameters, when normalized to absorptive surface area values, diminish. During early postresection adaptation, expansion of ileal absorptive surface area due to hyperplasia seems to play a greater role than upregulation of enterocyte Na+, Cl−, and glucose absorption.

Incorporation of biological variability into lung dosimetry by stochastic modeling techniques

The inherent variability of morphometric, physiologic, and histologic parameters involved in radon progeny lung dosimetry may cause significant statistical variations in cellular doses. Such parameter variability can be treated mathematically by stochastic models, in which these parameters are selected randomly from their probability distributions by Monte Carlo techniques. This stochastic simulation of particle deposition and clearance in bronchial airways is based on a stochastic morphometric model of the human lung. Inhaled particles are transported through this stochastic airway structure by randomly selecting a sequence of airways for each particle until deposition occurs. The subsequent upstream transport of deposited radon decay products by mucociliary clearance is simulated for the same random pathway until the radioactive nuclides decay. For the computation of cellular doses in bronchial epithelium, the variability of the position of basal and secretory cell nuclei within the bronchial epithelium must be considered as well. In addition to a more realistic determination of average cellular doses, a stochastic dosimetric model provides information about the statistical uncertainty of such dose calculations.

Aerosol Inhalation in the Rat Lung Part I: Analysis of the Rat Acinus Morphometry and Construction of a Stochastic Rat Lung Model

ABSTRACT Morphometric data of four ventilatory units of the lung of a male Sprague-Dawley rat were statistically analyzed. Because of the rather monopodial structure of the rat lung, airways were classified by their diameters rather than by their generation numbers, as is general practice. The statistical analyses provided information on the distributions of a variety of geometric parameters of a rat acinus and the correlations among them. Together with the previously analyzed tracheobronchial morphometric data they form the basis of a stochastic morphometric model of the whole rat lung. This morphometric model can then be used for Monte Carlo simulations of the transport and deposition of inhaled aerosol particles in the rat lung.

Calculation of pulsatility index of flow volume independent of vessel diameter and flow profile

An application of a morphometric model is used to study the stroma epithelial interface in human cervical epithelium. This model derived by Okagaki and associates estimates from two dimensional transmission electron photomicrographs the number of basal cell pseudopodia per basal cell. The investigation of the full spectrum of cervical intraepithelial neoplasia (CIN) focusing on the basal cell-stroma interface with the “multiple cell-single section” model is discussed. Significant decreases in histopathologic grades of CIN are noted in the number of pseudopodia per basal cell (N¯) and the ratio (F¯) of the area of the stems of pseudopodia to the area of the base of the basal cell.

Hydrologic and morphometric model of a mountain river

Hydrologic and morphometric model of a mountain river

Morphometric model of normal rabbit dorsal root ganglia.

The rabbit dorsal root ganglion is an important model of pain mechanisms in the human spine. A morphometric model of the normal rabbit dorsal root ganglion was constructed to provide quantitative comparisons with injured ganglia. Lumbar ganglia were studied under light and electron microscopy using simple stereologic methods. Neuronal diameter ranged from 18 to 85 microns, with 60% between 30 and 50 microns. Neurons constituted approximately 30% of dorsal root ganglion volume, and neuronal nuclei accounted for 14% of neuronal volume and 4% of dorsal root ganglion volume. Contributions from organelles to dorsal root ganglion volume were: mitochondria, 1.5%; rough endoplasmic reticulum, 9.4%; lysosomes, 0.2%; golgi, 0.5%. This morphometric model facilitates quantitative analysis of ganglia exposed to direct or indirect stimuli, providing important information on the structural changes that influence pain production.

Acyclic Directed Graphs for Automatic Image Analysis of Lung Parenchymal Geometry

We have developed a simple method for encoding pulmonary alveolar geometry suitable for morphometric analysis and modeling. The approach involves the use of 8-bit video microscopic images of lung which are thresholded to produce binary images. Each alveolar wall was thinned to its midline to produce a skeletonized image, We present an algorithm for converting such an image to an acyclic directed graph. Such a representation is quite suitable for mathematical treatment, lending itself to problems involving simulation or modeling. We present as an example application, the measurement of dihedral angles in rat lung using conventional histological sections.

Morphometric model for pulmonary diffusing capacity I. Membrane diffusing capacity

The pulmonary diffusing capacity is related to the quantitative design characteristics of the pulmonary gas exchanger. The current model for estimating D l O 2 from morphometric data breaks the diffusion path for O 2 into four steps, three of which represent the membrane part of D l O 2. A critique of this model on the basis of newer evidence leads to a modification of the model where the path from the alveolar surface to the erythrocyte membrane is considered as a single step. The structural determinant of this model for D m O 2 is the ratio of effective diffusion surface to effective total barrier thickness. The effective surface is formulated as a fraction of the alveolar surface area, the most robust measure of lung design, whereas the effective barrier thickness is the harmonic mean distance - or mean proximity - between alveolar surface and erythrocyte surface. The methods for obtaining the morphometric measurements are discussed. The results show that the new morphometric estimates of D m O 2 are 33% lower than those obtained with the old model, resulting in a reduction of the estimates of D l O 2 by 10–20%.