Date of Award
Summer 2004
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Mathematics, Statistics and Computer Science
First Advisor
Clough, Anne V.
Second Advisor
Johnson, Roger H.
Third Advisor
Ropella, Kristina M.
Abstract
Primary bronchogenic carcinomas are thought to be supplied with nutrients via the bronchial circulation of the lung. The high demand of such tumors has been previously shown to stimulate angiogenesis within the bronchial circulation. We developed a single photon emission computed tomography (SPECT) method for imaging and quantifying bronchial angiogenesis by examining pulmonary perfusion changes stimulated by left pulmonary artery (LPA) ligation in rats. SPECT and micro-CT imaging are reviewed and the construction and implementation of a dual-modality imaging system is described. An ordered subset-expectation maximization reconstruction utilizing a voxel-driven approach that incorporates the detector response and a 5 mm pinhole collimator was evaluated using in silico and experimental test phantoms. Geometric reconstruction error was less than 10% for activity distributions within resolution limits. Activity measurements showed a reconstruction accuracy between 5% and 12%. A rigid, geometry-based method was implemented to co-register the acquired SPECT and micro-CT data. Segmentation of the micro-CT data was used to identify the activity regions within the SPECT volume with an error between 11% and 22%. SPECT and micro-CT images of rats were acquired post ligation surgery using two injections of 99m Tc labeled macroaggregated albumin (MAA). First an aortic MAA injection labeled the systemic circulation, including the bronchial circulation. After all activity decayed, MAA was injected intravenously via a femoral vein labeling the pulmonary circulation. The methods developed using the phantoms were then used to reconstruct the SPECT and micro-CT volumes, co-register the two image volumes, identify the lungs in the SPECT volume using the segmented micro-CT volume, and quantify the change in SPECT activity in the lungs. MAA accumulation within each lung was determined and the ratio between the aortic and intravenous injections was computed as a measure of bronchial flow. Bronchial flow as a percentage of cardiac output increased from 2% for control rats to 4%, 8% and 14% for LPA ligated rats at 10, 20 and 40 days post surgery, respectively. A novel imaging method for quantification of bronchial circulation angiogenesis in small animals was developed and used to quantify the time course of the angiogenesis. This model will be useful for evaluating antiangiogenic treatments in the future.