Quantification of Pulmonary Arterial Wall Distensibility Using Parameters Extracted from Volumetric Micro-CT Images

Stiffening, or loss of distensibility, of arterial vessel walls is among the manifestations of a number of vascular diseases including pulmonary arterial hypertension. We are attempting to quantify the mechanical properties of vessel walls of the pulmonary arterial tree using parameters derived from high-resolution volumetric x-ray CT images of rat lungs. The pulmonary arterial trees of the excised lungs are filled with a contrast agent. The lungs are imaged with arterial pressures spanning the physiological range. Vessel segment diameters are measured from the inlet to the periphery, and distensibilities calculated from diameters as a function of pressure. The method shows promise as an adjunct to other morphometric techniques such as histology and corrosion casting. It possesses the advantages of being nondestructive, characterizing the vascular structures while the lungs are imaged rapidly and in a near-physiological state, and providing the ability to associate mechanical properties with vessel location in the intact tree hierarchy

Microfocal Computed Tomography for Quantification of Pulmonary Arterial Structure and Function

To better understand the mechanisms of disease progression and the efficacy of interventions there is a need to develop and refine imaging methods for phenotyping animal models of complex traits associated with pulmonary hypertension. To investigate pulmonary arterial tree structure-function in this context, a high resolution micro-CT scanner has been utilized for imaging anesthetized small animals and excised organs maintained in a near-physiologic state. In this study, the X-ray CT system and image reconstructions were used to evaluate hypoxia induced changes in vascular architecture and mechanics in Fawn Hooded rats from which the lungs were removed after three weeks in an exposure chamber with inspired O2 of 21.0% (normoxic) or 11.5% (hypoxic). The pulmonary arterial tree was filled with perfluorooctyl bromide (Perflubron) for x-ray contrast and the isolated lungs were imaged with the intravascular pressure, P, ranging from 5 to 30mmHg. Methods were developed to identify and locate individual vessel segments within the pulmonary arterial tree and to measure their diameters as a function of pressure. The complexity of the pulmonary arterial tree is remarkable. Thus, three-dimensional volumetric images provide very complex data sets. A method for summarizing the image data for more than a million vessel segments is necessary. An approach based on the fractal characteristics of the pulmonary arterial network is developed herein. It involves measuring the diameters of the larger trunk vessel and the smaller branch at each bifurcation and the distances between bifurcations along the longest pulmonary arterial pathway, beginning at the pulmonary artery and ending with the terminal arteriole. Then, assuming self-consistency within the pulmonary arterial tree, the whole tree structure may be extrapolated. This is accomplished by measuring the diameter, D, versus length, x, from the main pulmonary arterial inlet over the range of pressures. The equations D(x,P) = D(0,P)(1 + αP)(1 - x/Ltot)c and D BR (x,P) = DBR (0,P)(1 + αP)(1 - x/Ltot) c are then fit to the data, where α is vascular distensibility and D, DBR , Ltot and c are morphometric parameters descriptive of the tree architecture. The parameters also provide inputs to a hemodynamic model that can be used to determine how the structural features represented by the parameters influence pressure-flow relationships within the pulmonary arterial tree. Morphometric analysis of lungs from normal and chronically hypoxic Fawn Hooded rats indicated that decreased vessel distensibility was the key feature of hypoxic remodeling. This type of analysis promises to be a useful tool for providing insight into pulmonary arterial structure-function relationships associated with pulmonary hypertension

Microfocal computed tomography for quantification of pulmonary arterial structure and function

To better understand the mechanisms of disease progression and the efficacy of interventions there is a need to develop and refine imaging methods for phenotyping animal models of complex traits associated with pulmonary hypertension. To investigate pulmonary arterial tree structure-function in this context, a high resolution micro-CT scanner has been utilized for imaging anesthetized small animals and excised organs maintained in a near-physiologic state. In this study, the X-ray CT system and image reconstructions were used to evaluate hypoxia induced changes in vascular architecture and mechanics in Fawn Hooded rats from which the lungs were removed after three weeks in an exposure chamber with inspired O2 of 21.0% (normoxic) or 11.5% (hypoxic). The pulmonary arterial tree was filled with perfluorooctyl bromide (Perflubron) for x-ray contrast and the isolated lungs were imaged with the intravascular pressure, P, ranging from 5 to 30mmHg. Methods were developed to identify and locate individual vessel segments within the pulmonary arterial tree and to measure their diameters as a function of pressure. The complexity of the pulmonary arterial tree is remarkable. Thus, three-dimensional volumetric images provide very complex data sets. A method for summarizing the image data for more than a million vessel segments is necessary. An approach based on the fractal characteristics of the pulmonary arterial network is developed herein. It involves measuring the diameters of the larger trunk vessel and the smaller branch at each bifurcation and the distances between bifurcations along the longest pulmonary arterial pathway, beginning at the pulmonary artery and ending with the terminal arteriole. Then, assuming self-consistency within the pulmonary arterial tree, the whole tree structure may be extrapolated. This is accomplished by measuring the diameter, D, versus length, x, from the main pulmonary arterial inlet over the range of pressures. The equations D(x,P) = D(0,P)(1 + αP)(1 - x/Ltot)c and D BR (x,P) = DBR (0,P)(1 + αP)(1 - x/Ltot) c are then fit to the data, where α is vascular distensibility and D, DBR , Ltot and c are morphometric parameters descriptive of the tree architecture. The parameters also provide inputs to a hemodynamic model that can be used to determine how the structural features represented by the parameters influence pressure-flow relationships within the pulmonary arterial tree. Morphometric analysis of lungs from normal and chronically hypoxic Fawn Hooded rats indicated that decreased vessel distensibility was the key feature of hypoxic remodeling. This type of analysis promises to be a useful tool for providing insight into pulmonary arterial structure-function relationships associated with pulmonary hypertension

Branching Exponent Heterogeneity and Wall Shear Stress Distribution in Vascular Trees

A bifurcating arterial system with Poiseuille flow can function at minimum cost and with uniform wall shear stress if the branching exponent (z) = 3 [where z is defined by (D 1)z = (D 2)z + (D 3)z;D 1 is the parent vessel diameter andD 2 and D 3 are the two daughter vessel diameters at a bifurcation]. Because wall shear stress is a physiologically transducible force, shear stress-dependent control over vessel diameter would appear to provide a means for preserving this optimal structure through maintenance of uniform shear stress. A mean z of 3 has been considered confirmation of such a control mechanism. The objective of the present study was to evaluate the consequences of a heterogeneous distribution of z values about the mean with regard to this uniform shear stress hypothesis. Simulations were carried out on model structures otherwise conforming to the criteria consistent with uniform shear stress whenz = 3 but with varying distributions of z. The result was that when there was significant heterogeneity inz approaching that found in a real arterial tree, the coefficient of variation in shear stress was comparable to the coefficient of variation in z and nearly independent of the mean value of z. A systematic increase in mean shear stress with decreasing vessel diameter was one component of the variation in shear stress even when the mean z = 3. The conclusion is that the influence of shear stress in determining vessel diameters is not, per se, manifested in a mean value of z. In a vascular tree having a heterogeneous distribution in zvalues, a particular mean value of z (e.g.,z = 3) apparently has little bearing on the uniform shear stress hypothesis

Exploiting Self-Similarity of Arterial Trees to Reduce the Complexity of Analysis

Vascular structures such as the pulmonary arterial tree contain hundreds of thousands of vessel segments, making structural and functional analysis of an entire 3D image volume very difficult. Currently-available methods for segmentation and morphometry of 3D vascular tree images require user interaction making the task very tedious and sometimes impossible. Our aim is to exploit the self-similar nature of arterial trees to simplify morphometric analysis. The structure of pulmonary arterial trees exhibits self- similarity in the sense that the segment length and diameter data from different pathways are statistically indistinguishable for subtrees distal to a given segment diameter. We analyze 3D micro-CT images of mouse and rat pulmonary arterial trees by measuring the lengths and diameters of the vessel segments of the several longest arterial pathways and their immediate branches interactively. Since measurements made on the longest pathways are representative of the tree as a whole, and there are less than 30 branches off the main trunk, the morphometry of the complex tree can be characterized by less than 100 length and diameter measurements

3D X-Ray Microtomography Applied to Structural and Mechanical Characterization of Arterial Trees

We applied micro-CT imaging to arterial trees in rodent lungs. Morphometric features derived from the images are sensitive to interspecies differences in vascular structure and can reflect the distensibility of arterial walls

Structure-function relationships in the pulmonary arterial tree

Knowledge of the relationship between structure and function of the normal pulmonary arterial tree is necessary for understanding normal pulmonary hemodynamics and the functional consequences of the vascular remodeling that accompanies pulmonary vascular diseases. In an effort to provide a means for relating the measurable vascular geometry and vessel mechanics data to the mean pressure-flow relationship and longitudinal pressure profile, we present a mathematical model of the pulmonary arterial tree. The model is based on the observation that the normal pulmonary arterial tree is a bifurcating tree in which the parent-to-daughter diameter ratios at a bifurcation and vessel distensibility are independent of vessel diameter, and although the actual arterial tree is quite heterogeneous, the diameter of each route, through which the blood flows, tapers from the arterial inlet to essentially the same terminal arteriolar diameter. In the model the average route is represented as a tapered tube through which the blood flow decreases with distance from the inlet because of the diversion of flow at the many bifurcations along the route. The taper and flow diversion are expressed in terms of morphometric parameters obtained using various methods for summarizing morphometric data. To help put the model parameter values in perspective, we applied one such method to morphometric data obtained from perfused dog lungs. Model simulations demonstrate the sensitivity of model pressure-flow relationships to variations in the morphometric parameters. Comparisons of simulations with experimental data also raise questions as to the “hemodynamically” appropriate ways to summarize morphometric data