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

Mitigation of Radiation Induced Pulmonary Vascular Injury by Delayed Treatment with Captopril

Background and Objective: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2 months post-exposure. In this study, we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods: Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2 months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2 weeks after radiation exposure, with two doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary haemodynamics, lung ACE activity, pulmonary arterial distensibility and peripheral vessel density. Results: Captopril, given at a vasoactive, but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly, these beneficial effects were observed even if drug therapy was delayed for up to 2 weeks after exposure. Conclusions: Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident

A Large-Scale Mathematical Model of the Rat Pulmonary Circulation and the Effect of Chronic Hypoxia

Mathematical models are useful for developing understanding of the behavior of complex biological systems. Recent work on a “physiome” project is aimed at using computational modeling to analyze integrative biological function by developing a simulation system for hypothesis testing (Borg & Hunter, 2003). To date, extensive work on cardiovascular, endocrine and nervous system models has been undertaken. Our objective here is to contribute to this effort by further developing a comprehensive integrative model of the pulmonary circulation. A computational model of the dog pulmonary circulation was originally developed by Haworth et al. (Haworth S. T., 1996; Haworth, Linehan, Bronikowski, & Dawson, 1991). In this thesis, their work was extended to the rat pulmonary circulation. The rat model geometry is characterized by 18 orders of arteries and 19 orders of veins. The average distensibility (% increase in diameter over the undistended diameter) for the model arteries and veins are 2.8 %/mmHg and 1.6 %/mmHg. These arterial and venous trees are connected by a capillary sheet with an area of 0.123 cm2. The model was validated and the calculated pressures, arterial-capillary-venous resistances, volumes, and compliances of the model agree well with the experimental estimates in the rat lung under zone 3 conditions. The model was used to evaluate the common structural hallmarks of pulmonary vascular remodeling as a result of exposure to chronic hypoxia (low inspired oxygen levels), such as the decrease in arterial and venous distensibility, reduction in capillary surface area and reduction in the number of small arteries. Our results show that these factors are not alone sufficient to account for the reported increase in pulmonary arterial pressure in response to chronic hypoxia induced pulmonary hypertension. This extended model provides a graphical user interface for choosing parameters, simulation models, and numerical options for performing either steady state or dynamic simulations, and for displaying model simulation results. The results of this study demonstrate the potential utility of this model for furthering the understanding of the underling mechanisms of pulmonary hypertension, and the effects of other lung disorders on the pulmonary circulation