Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT

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Abstract
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. 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. 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. 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.