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