Kelly L. Karau

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.

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.

Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

3D X-ray microtomography applied to structural and mechanical characterization of arterial trees

The authors 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.

Complexity in pulmonary arterial tree structure-function

In attempting to understand the complexity of pulmonary arterial tree structure and function relationships, the authors have made morphometric measurements on the lungs of mice, rats, and dogs. The authors constructed a morphometrically based hemodynamic model for which the measured morphometric parameters can be used as inputs to examine the sensitivity of model hemodynamic function to morphometry. The results suggest that, insofar as the model embodies the important structure function relationships in the pulmonary arterial tree, neither shear stress equalization nor minimization of hydraulic plus metabolic work can explain the tree design. Minimization of perfusion heterogeneity may be another selective force contributing to the evolution of the structure.