Automation Process for Morphometric Analysis of Volumetric CT Data from Pulmonary Vasculature in Rats

With advances in medical imaging scanners, it has become commonplace to generate large multidimensional datasets. These datasets require tools for a rapid, thorough analysis. To address this need, we have developed an automated algorithm for morphometric analysis incorporating A Visualization Workshop computational and image processing libraries for three-dimensional segmentation, vascular tree generation and structural hierarchical ordering with a two-stage numeric optimization procedure for estimating vessel diameters. We combine this new technique with our mathematical models of pulmonary vascular morphology to quantify structural and functional attributes of lung arterial trees. Our physiological studies require repeated measurements of vascular structure to determine differences in vessel biomechanical properties between animal models of pulmonary disease. Automation provides many advantages including significantly improved speed and minimized operator interaction and biasing. The results are validated by comparison with previously published rat pulmonary arterial micro-CT data analysis techniques, in which vessels were manually mapped and measured using intense operator intervention

Automation Process for Morphometric Analysis of Volumetric CT Data from Pulmonary Vasculature of Rats

This thesis designs an automated algorithm for the morphometric analysis of the rat lung vascular structure. The primary objective of our group is to develop a structural and functional understanding of pulmonary vascular remodeling (PVR). PVR can be defined as certain structural as well as biomechanical changes in the normal architecture of the walls of pulmonary vessels, which causes an increase in the pulmonary vascular resistance. The increased resistance causes an increase in the intravascular pressure, which then perpetuates the remodeling. Thus, PVR induces a vicious cycle, which leads to cor pulmonale and death. In order to design therapies, there has be a clear understanding of the development of PVR. For this purpose, our lab is studying the pulmonary arterial structure in the rat using micro-CT images obtained at various intravascular pressures. Currently, the morphometric analysis is performed using a combination of manual and semi-automated methods that require hours of constant user interaction for each rat studied. The automated algorithm provides many advantages, such as improved speed and repeatability and significantly reduced user interaction. Chapter I provides an introduction by describing motivation behind the work and specifies the thesis objectives. Chapter 2 reviews literature from previous studies that have addressed similar issues. Chapter 3 provides a detailed explanation of the currently used method for morphometric analysis. This chapter also explains the functionality of the commercially available Analyze® software package for the purpose of analyzing the pulmonary vascular structure. Chapter 4 describes the algorithms designed to automate the morphometric analysis using the AVW library of functions for biomedical images along with the C, Tel and Tk programming languages. Chapter 5 presents work done for the validation of the algorithm by comparing the algorithm results to data obtained with the manual quantification technique. Chapter 6 documents a discussion based on the validation and presents future considerations for the algorithm. Appendix A describes the animal preparation and also provides a description of the image acquisition procedure. Appendix B describes the micro-CT scanner that has been utilized to obtain the volumetric images

Arterial Morphology Responds Differently to Captopril then N-Acetylcysteine in a Monocrotaline Rat Model of Pulmonary Hypertension

Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days aftcr MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR). vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21,12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values