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Diameter-based analysis of the branching geometry of four mammalian bronchial trees.

A diameter-based classification technique, which we have previously used to analyse human bronchial geometry (Phillips et al., Respir. Physiol. 98: 193-217, 1994) is applied also to the partial measurements of the dimensions of dog, rat and hamster conducting airways, made by Raabe et al. (Tracheobronchial Geometry: Human, Dog, Rat, Hamster, 1976). The local branching patterns are characterised by means of three parameters, which reflect the asymmetry and the degree of expansion at each bifurcation, and the ratio of the length of each branch to its diameter. The mean values of these parameters as functions of diameter, calculated from the raw morphometric data, are shown for the four species. A statistical reconstruction technique is then used to estimate from the incomplete measurements of Raabe and coworkers some geometrical properties of the whole system of conducting airways, which are likely to influence transport processes in the lung. These include the distribution of the total airway volume between branches of different diameters, the mean and variance of the total lengths of different pathways through the bronchial tree, and a simple model for the variation of flow velocity with airway diameter. Our results show significant differences between the branching structures of all four species. In particular, the human differs from the others in branching much more symmetrically, and in that branches of a given diameter are typically much longer than in the other species; together, these observations imply that the human bronchial tree is geometrically very different from those of the other species.

Animals↗

Effect of macroscopic deformation on lung microstructure.

Using an anisotropic theory of diffuse light scattering in lungs, we measured the fractional changes in geometric mean linear intercepts in orthogonal directions when freshly excised rabbit lungs were subjected to isovolume uniaxial strains. Results from the optical technique were compared with morphometric estimates of fractional changes in mean linear intercepts from the same strained and unstrained (control) lobes, with the conclusion that diffuse light scattering is adequate to estimate changes in mean free paths in different directions. We compared optical estimates of fractional changes in mean linear intercepts with the macroscopic strain field measured by displacements of pleural markers; this relationship did not significantly differ from the line of identity. We conclude that the microscopic strain field is closely matched to the macroscopic strain field during uniaxial distortion. This suggests that surface reorientation may not play a large role in the origin of the low shear modulus of the lung, but this cannot be definitively stated without comparison of these experimental results to specific model predictions of the changes in mean linear intercepts in shear deformation.

Animals↗

Computerized morphometric analysis of human leukemic and lymphomatous cells in various histological environments of central nervous system.

The leukemic and lymphomatous cells appear within the central nervous system (CNS) in 5 different environments: in CNS vessels, perivascular spaces, meninges, nervous tissue and in CNS hemorrhages. A computerized analysis of geometric and densitometric parameters of neoplastic cells in these compartments were done for better recognition of penetration and spreading of leukemia and lymphoma within the CNS. A post-mortem neuropathological investigations were carried out on 16 patients deceased due to acute myeloblastic leukemias (M1, M2), blastic phase of chronic myelogenous leukemia, lymphoblastic lymphoma and acute lymphoblastic leukemia. Following nuclear parameters of neoplastic cells were analyzed: area, "form factor", mean, minimal and maximal density. An evident differentiation of nuclear parameters within the CNS environments was found. The nuclei within the perivascular spaces and especially in CNS hemorrhages were significantly shrunken and dense (p < 0.01), but not evidently deformed. The intracerebral infiltrates appeared to be most differentiated group (p < 0.01). Morphometric values of leukemic and lymphomatous cells show regressive changes of neoplastic cells within the CNS perivascular spaces, nervous tissue and in CNS hemorrhages. These changes depend on unfavorable factors in the mentioned CNS environments, and also on time of cell persistence in these regions. Meninges were found to be the only CNS structure facilitating the survival and proliferation of leukemic and lymphomatous cells.

Central Nervous System Neoplasms↗

Morphometric data concerning the great arterial trunks and their branches.

In a total of 496 fetuses and newborns ranging in body weight from 60 to 5000 g, we performed a morphometric study of the vascular complex, that is the orifices of the great arterial trunks, ascending aorta, aortic arch, vessels branching from the aortic arch, the aortic isthmus, descending aorta, pulmonary trunk, orifices of the pulmonary arteries and arterial duct. In all, 17 different parameters were measured in each specimen, using several new parameters in addition to the measurements classically used in the aortic isthmus, arterial duct and pulmonary trunk. Anatomo-geometric models of these structures were developed, and stereometric formulas used to calculate the real volumes of the aortic isthmus, arterial duct and pulmonary trunk. The variations in the correlations between two measurable characteristics, that is, body weight and each of the morphometric parameters were analyzed, and the minimum, normal and maximum patterns of normality for each parameter were obtained with regression equations. The results show that the volume of the aortic isthmus increases by 0.03 ml for each millilitre increase in left ventricular volume. The isthmic volume increases by 0.32 ml for each millilitre increase in volume of the arterial duct and the volume of the pulmonary trunk increases by 6.4 ml for each increase of 1 millilitre in the volume of the aortic isthmus. The inner circumference of the aortic isthmus is greater than that of the arterial duct, whereas the former vessel is always shorter than the latter. We believe that these morphological data, when appropriately interpreted, have immediate clinical and surgical applications in the treatment of fetal and perinatal cardiovascular disorders.

Aorta↗

Contribution of tree structures in the lung to lung elastic recoil.

The direct contribution of forces in tree structures in the lung to lung recoil pressure and changes in recoil pressure induced by alterations of the forces are analyzed. The analysis distinguishes the contributions of axial and circumferential tensions in the trees and indicates that only axial tensions directly contribute to static recoil. This contribution is derived from analysis of the axial forces transmitted across a random plane transecting the lung. The change in recoil pressure induced by changes in axial tension is similarly derived. Alterations of circumferential tensions in the trees indirectly change recoil by causing nonuniform deformations of the surrounding lung parenchyma, and a continuum elasticity solution for the stress induced by the deformations is derived. Sample calculations are presented for the airway tree based on available data on airway morphometric and mechanical properties. The increase in recoil pressure accompanying increases in axial and circumferential tensions with contraction of airway smooth muscle is also analyzed. The calculations indicate that axial stresses in the airway tree out to bronchioles directly contribute only a small fraction of the static recoil pressure. However, it is found that contraction of smooth muscle in these airways can increase recoil pressure appreciably (10-20%), mainly by the deformation of the parenchyma with increases in circumferential tension in smaller airways. The results indicate that the geometric and mechanical properties of the airway tree are such that only peripheral elements of the tree can substantially affect the elastic properties of the lung. The possible contributions of vascular trees for which data on mechanical and morphometric properties are more limited are also discussed.

Lung↗

Computer-optimization of vascular trees.

Arterial branchings closely fulfill several "bifurcation rules" which are deemed to optimize blood flow. The question is whether these local criteria in conjunction with a general optimization principle can explain the overall structure of an arterial tree. We present a model of an arterial vascular tree which is grown on the computer by successively adding terminal vessel segments. Each new terminal segment is connected to the optimum site within the preexisting tree, and the new bifurcation is optimized geometrically. After each step of adding and optimizing, the whole tree is rescaled to meet invariant boundary conditions of pressure and flow at each terminal site. Thus, local geometric optimization is used to induce simultaneously an optimized global structure. The comparison between the model and real coronary arterial trees shows good agreement regarding structural appearance, morphometric parameters, and pressure profiles.

Arteries↗

[Automated morphometric evaluation of the chromatin structure of liver cell nuclei after vagotomy].

The morphometric analysis of the interphase chromatine structure of the hepatic cells nuclei was carried out on the automated TV installation for the quantitative analysis of images "IBAS-2" (by the OPTON firm, the FRG) according to 50 optical and geometric parameters during various periods (1.2 and 4 weeks) after the vagotomy operation. It is determined that upper-molecular organisation of chromatine undergoes the biggest changes one week after operation, and changes of granular component are more informative than changes of the nongranular component (with the difference 15-20%). It was also revealed that chromatine components differ in tinctorial properties, which are evidently dependent on physicochemical characteristics of the chromatine under various functional conditions of the cell. As a result of the correlation analysis the group of morphometric indices of chromatine structure was revealed, which are highly correlated with level of transcription activity of chromatine during various terms after denervation. The correlation quotient of these parameters is 0.85-0.97. The summing up: vagus denervation of the liver causes changes in the morphofunctional organisation of the chromatine.

Animals↗

The quantitative anatomy of the normal human heart in fetal and perinatal life.

A total of 367 human fetuses and newborn subjects weighing from 60 to 5000 g provided the material for a morphometric study of the heart. A total of 17 interventricular parameters were measured in each specimen, one of the parameters representing an innovation with regard to the classically used set of measurements. A new anatomo-geometric configuration is described for each ventricle along with a new component for the left ventricular outflow tract, designated as the aortic outflow tract. The appropriate stereometric formulas were used to calculate real ventricular volumes rather than the previously studied volumetric indices. Additionally, correlation indices were calculated for ventricular wall thickness as well as the circumferences and diameters of the atrioventricular and arterial valves. The results show that, in fetuses of up to 2700 g in body weight, ventricular wall thickness is greater in the right than in the left ventricle, although the opposite is true in fetuses weighing above 2700 g. Throughout the range of weights studied, ventricular volume was greater in the left than in the right chamber. Tricuspid and pulmonary valve circumference and diameter were consistently greater than in the mitral and aortic valves, respectively. We believe the new morphometric data and their innovative interpretation to have immediate applications in both the morphological and functional areas of cardiology.

Aortic Valve↗

Morphometric evaluation of populations of neuronal profiles (cell bodies, dendrites, and nerve terminals) in the central nervous system.

Morphometric techniques have been developed to quantitatively characterize groups of transmitter-identified neuronal profiles, such as cell groups, dendrite and nerve terminal fields. These morphometric techniques will be illustrated by introducing some general tools for image analysis which can be considered as a background for the present specific applications. The following methods have been included: (1) methods to identify and quantitatively characterize, from both numerical and geometrical standpoints, groups of profiles in a two- and three-dimensional frame; (2) methods to evaluate the evenness of a certain distribution of profiles in the plane; (3) methods to identify subgroups of profiles based on their different spatial or optical density; and (4) methods to compare the distributions of two or more groups of profiles. The applications of these general tools to some neuroanatomical problems, such as cell group definition and description, have been illustrated. Practical examples performed on immunocytochemical preparations of neuronal profile populations are also given. Finally, the potentiality of numerical classification to classify and compare morphometric data has been shown. As an example, numerical classification methods have been applied to the morphometric and microdensitometric analysis of adrenaline/neuropeptide Y costoring neuronal systems of the brainstem in adult and aged rats.

Animals↗

A dynamic morphometric model of the normal lung for studying expiratory flow limitation in mechanical ventilation.

A nonlinear dynamic morphometric model of breathing mechanics during artificial ventilation is described. On the basis of the Weibel symmetrical representation of the tracheo-bronchial tree, the model accurately accounts for the geometrical and mechanical characteristics of the conductive zone and packs the respiratory zone into a viscoelastic Voigt body. The model also accounts for the main mechanisms limiting expiratory flow (wave speed limitation and viscous flow limitation), in order to reproduce satisfactorily, under dynamic conditions, the expiratory flow limitation phenomenon occurring in normal subjects when the difference between alveolar pressure and tracheal pressure (driving pressure) is high. Several expirations characterized by different levels of driving pressure are simulated and expiratory flow limitation is detected by plotting the isovolume pressure-flow curves. The model is used to study the time course of resistance and total cross-sectional area as well as the ratio of fluid velocity to wave speed (speed index), in conductive airway generations. The results highlight that the coupling between dissipative pressure losses and airway compliance leads to onset of expiratory flow limitation in normal lungs when driving pressure is increased significantly by applying a subatmospheric pressure to the outlet of the ventilator expiratory channel; wave speed limitation becomes predominant at still higher driving pressures.

Airway Resistance↗

Remodeling of the alveolar structure in the paraquat lung of humans: a morphometric study.

To correlate the progression of fibrosing lung lesions with an impediment of respiratory function, autopsy lungs from 15 patients who died after ingesting paraquat were submitted to histopathologic and morphometric analysis. The basic lung lesion proved to be a remodeling of alveolar structure caused by deposition of matrix on the septal surface, with proliferating mesenchymal cells. Morphometry, using a geometric model, and stereology showed that the mean thickness D of septa, including the matrix, enlarged after an exponential function of days after ingestion, reaching the alveolar breadth of 200 microns on day 22 and showing the alveoli totally obliterated. The exponential nature of this finding suggested that the paraquat lung is a self-accelerating and therefore a malignant lesion, in contrast to the slowly progressing fibrosis that follows usual interstitial pneumonia. In a whole-lung distribution analysis performed in three cases, D was shown to become increasingly heterogenous over time, with ordinary alveolar tissue remaining in at least part of the lung even in the most advanced case. Thus, heterogenous distribution of the disease was considered to be a sine qua non for a lung disease to run a chronic course.

Adult↗

Ultrastructural quantitative stereology on 'mixed' cell populations: problems and possibilities.

Contrary to homogeneous tissues, "mixed" tissues or cell suspensions are composed of different cell individuals. They have been characterized as heterogeneous cell populations (composed of cells of different cytogenetical source) and heteromorphous or inhomogeneous cell populations (of cells of the same type but of different individual functional state). Certain problems may arise during ultrastructural morphometrical investigations of heteromorphous populations. Because of the different size of planes of sectioning of individual cells, morphometrical results should be treated by means of modifications of the t-test [4]. Furthermore, the unambiguous classification of individual cell profiles necessitates a conscious selection of cell profiles containing a nuclear profile. This non-random sampling approach leads to systematic errors of computed parameters for the whole cell as the nuclear volume fraction and the specific cell surface area which should be corrected. Besides correction procedures derived from regular geometrical models we have presented correction methods for cells with non-spherical nucleus and a cell surface with marked surface projections [13, 21]. On the other hand, on heteromorphous cell populations, more detailed information about functional events can be gained, in comparison the customary stereological mean values, by means of frequency distributions of morphometrical data of individual cell profiles as well as by correlation of data of different cell organelles.

Animals↗

Statistical determinants of dendritic morphology in hippocampal pyramidal neurons: A hidden Markov model.

Dendritic structure is traditionally characterized by distributions and interrelations of morphometric parameters, such as Sholl-like plots of the number of branches versus dendritic path distance. However, how much of a given morphology is effectively captured by any statistical description is generally unknown. In this work, we assemble a small number of standard geometrical parameters measured from experimental data in a simple stochastic algorithm to describe the dendrograms of hippocampal pyramidal cells. The model, consistent with the hidden Markov framework, is feedforward, local, and causal. It relies on two "hidden" local variables: the expected number of terminal tips in a given subtree, and the current path distance from the soma. The algorithm generates dendrograms that statistically reproduce all morphological essentials of dendrites observed in real neurons, including the distributions of branching and termination points, branch lengths, membrane area, topological asymmetry, and (assuming passive membrane parameters within physiological range) electrotonic characteristics. Thus, this algorithm and the small number of its morphometric parameters constitute a remarkably complete description of the dendrograms of hippocampal pyramidal cells. Specifically, it is found that CA3 and CA1 basal dendrites and CA3 apical dendrites can each be described as homogeneous morphological classes. In contrast, the accurate generation of CA1 apical dendrites necessitates the separate sampling of two types of branches, main and oblique, suggesting their derivations from different developmental mechanisms (terminal and interstitial growth, respectively). We further offer a plausible biophysical interpretation of the model hidden variables, relating them to microtubules and other intracellular resources.

Algorithms↗

Patterning of embryonic blood vessels.

Morphometric methods were developed to characterize the geometry of vascular patterns in avian and murine embryos. By using these methods, we found that networks of blood vessels formed during vasculogenesis share similar geometric properties (i.e., mean blood vessel diameters and avascular space diameters) regardless of developmental stage, location, or species in which they form. We also found that endothelial cell density within a unit area of an embryonic vasculature could be used to accurately distinguish between a small diameter, capillary-like vascular network (low endothelial cell density) and a large diameter, presinusoidal network (high endothelial cell density). Furthermore, we show that endothelial cell size remains constant in small and large diameter vessels, indicating that increased endothelial cell size is not the basis for diversity in vessel diameter. These observations serve as a foundation for future studies seeking to evaluate the effects of agents or genetic mutations on aspects of vasculogenesis.

Allantois↗

Structural differences between human and rat lungs: implications for Monte Carlo modeling of aerosol deposition.

The geometrical structure of the lung is one of the main factors governing inhaled particle deposition; structural differences among different species are, therefore, of great importance for extrapolation modeling. A statistical analysis of morphometric data for the human and rat tracheobronchial tree reveals significant interspecies differences in airway branching patterns: compared to the relatively dichotomous and symmetric structure of the human lung, the rat lung displays a more monopodial airway branching pattern. Thus, for the rat lung, we recommend characterizing the properties of a given airway, i.e., its size, physiologic function, and distance from the trachea, by its diameter rather than by a theoretically assigned generation number. A Monte Carlo method is used to construct an airway geometry along each inhaled particle's path by randomly selecting airway parameters from their frequency distributions and the correlations among them. While the airway geometry is selected randomly, particle deposition in individual airways is calculated analytically. These stochastic deposition calculations allow for structural differences between the human and rat lung, and the variability of the airway system within each species.

Aerosols↗

Morphometric analysis of granule cell dendrites in the mouse dentate gyrus.

We devised a computer program to analyze the dendritic geometry of dentate granule cells as seen in rapid Golgi impregnations from the mouse. Three dimensional coordinates were recorded by using a computer-assisted microscope. Geometric parameters are of two general types: (1) LINEAR parameters include the number of dendritic segments per branch order and their individual and aggregate lengths. (2) ANGULAR parameters define the spatial relationships of branch points and segment terminals with each other and with the axis of symmetry derived for all the dendrites. We find that values for linear parameters are highly variable and more susceptible to artifacts. Values for most angular parameters are more highly constrained and are presumably the best descriptors of the class-characteristic conical shape of granule cell dendrites. Additional features which are necessary to describe granule cell dendrites fully are: (1) Branching frequency is highest proximal to the cell soma, (2) deviant segments are kept "on course" to ensure axial symmetry, and (3) terminal segments end at the plane of the cortical surface. A critical analysis of the various parameters suggests the hypothesis that the characteristic and uniform geometry of granule cell dendrites is controlled largely by factors residing in the molecular layer where growth and differentiation are sustained. An additional finding of potential interest is that there are two subpopulations of granule cells with a twofold difference in spine density.

Animals↗

Aerosol measurement of airspace diameter correlates with morphometry in normal and papain-exposed air dried lungs.

Aerosol measures of effective airspace diameter (EAD) were correlated with morphometric parameters in a series of 8 canine lungs, 5 of which had been exposed to papain in order to cause experimental emphysema. In an effort to preserve alveolar dimensions without shrinkage, the lungs were fixed by air drying at total lung capacity. EAD was measured with 400-cm2 boluses, with mean penetration index (Pen), defined as volumetric bolus penetration/total lung capacity, equal to 0.34 (EAD400), and with 800-cm2 aerosol boluses, with mean Pen equal to 0.59 (EADdeep). Morphometric analysis, following measurement of EADs, determined the mean linear intercept and other parameters of the chordlength distribution, including the 90th, 95th, and 99th percentiles (p90, p95, p99), the standard deviation, and the geometric standard deviation (GSD). EAD400 was significantly correlated with Lm (r2 = .68, P < .05), p95, (r2 = .85, P < .01), p99 (r2 = .94, P < .001), and GSD (r2 = .94, P < .001). Similar results were found with EADdeep. In general, correlations were stronger between EAD and p95, p99, or GSD than between EAD and Lm. A comparison with a previous similar study relating EAD to morphometry in a series of lungs fixed by formalin fixation found closer agreement between EAD and morphometry when lungs were fixed by air drying. Overall, the data support the validity of EAD as an in vivo method of determining airspace size at total lung capacity.

Aerosols↗

Spatial normalization of 3D brain images using deformable models.

PURPOSE: The spatial normalization and registration of tomographic images from different subjects is a major problem in several medical imaging areas, including functional image analysis, morphometrics, and computer-aided neurosurgery. The focus of this article is the development of a computerized methodology for the spatial normalization of 3D images. METHOD: We propose a technique that is based on geometric deformable models. In particular, we first describe a deformable surface algorithm that finds a mathematical representation of the outer cortical surface. Based on this representation, a procedure for obtaining a map between corresponding regions of the outer cortex in two different images is established. This map is subsequently used to derive a 3D elastic warping transformation, which brings two images into register. RESULTS: The performance of our algorithm is demonstrated on several datasets. In particular, we first test our deformable surface algorithm on MR images. We then register MR images to atlas images. In our third experiment, we apply a procedure for matching distinct cortical features identified through the curvature map of the outer cortex. Finally, we apply our technique to images from elderly individuals with substantial ventricular enlargement, and we show a good registration in the ventricular area and the surrounding brain structures. CONCLUSION: We present a highly automated methodology for spatial normalization of images, using deformable models. Applications of our methodology include stereotactic normalization of functional and structural images, morphological analysis of the brain, and computer-aided neurosurgery.

Algorithms↗