Estimation of Pulmonary Arterial Volume Changes in the Normal and Hypertensive Fawn-Hooded Rat from 3D Micro-CT data

In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model

SPECT Imaging of Pulmonary Blood Flow in a Rat

Small animal imaging is experiencing rapid development due to its importance in providing high-throughput phenotypic data for functional genomics studies. We have developed a single photon emission computed tomography (SPECT) system to image the pulmonary perfusion distribution in the rat. A standard gamma camera, equipped with a pinhole collimator, was used to acquire SPECT projection images at 40 sec/view of the rat thorax following injection of Tc99m labeled albumin that accumulated in the rat\u27s lungs. A voxel-driven, ordered-subset expectation maximization reconstruction was implemented. Following SPECT imaging, the rat was imaged using micro-CT with Feldkamp conebeam reconstruction. The two reconstructed image volumes were fused to provide a structure/function image of the rat thorax. Reconstruction accuracy and performance were evaluated using numerical simulations and actual imaging of an experimental phantom consisting of Tc99m filled chambers with known diameters and count rates. Full-width half-maximum diameter measurement errors decreased with increasing chamber diameter, ranging from \u3c 6% down to 0.1%. Errors in the ratio of count rate estimates between tubes were also diameter dependent but still relatively small. This preliminary study suggests that SPECT will be useful for imaging and quantifying the pulmonary blood flow distribution and the distribution of Tc99m labeled ligands in the lungs of small laboratory animals

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Bronchial Circulation Angiogenesis in the Rat Quantified with SPECT and Micro-CT

Introduction As pulmonary artery obstruction results in proliferation of the bronchial circulation in a variety of species, we investigated this angiogenic response using single photon emission computed tomography (SPECT) and micro-CT. Materials and methods After surgical ligation of the left pulmonary artery of rats, they were imaged at 10, 20, or 40 days post-ligation. Before imaging, technetium-labeled macroaggregated albumin (99mTc MAA) was injected into the aortic arch (IA) labeling the systemic circulation. SPECT/micro-CT imaging was performed, the image volumes were registered, and activity in the left lung via the bronchial circulation was used as a marker of bronchial blood flow. To calibrate and to verify successful ligation, 99mTc MAA was subsequently injected into the left femoral vein (IV), resulting in accumulation within the pulmonary circulation. The rats were reimaged, and the ratio of the IA to the IV measurements reflected the fraction of cardiac output (CO) to the left lung via the bronchial circulation. Control and sham-operated rats were studied similarly. Results The left lung bronchial circulation of the control group was 2.5% of CO. The sham-operated rats showed no significant difference from the control. However, 20 and 40 days post-ligation, the bronchial circulation blood flow had increased to 7.9 and 13.9%, respectively, of CO. Excised lungs examined after barium filling of the systemic vasculature confirmed neovascularization as evidenced by tortuous vessels arising from the mediastinum and bronchial circulation. Conclusion Thus, we conclude that SPECT/micro-CT imaging is a valuable methodology for monitoring angiogenesis in the lung and, potentially, for evaluating the effects of pro- or anti-angiogenic treatments using a similar approach