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

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Abstract

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.

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Acknowledgment

This work was supported by the National Institutes of Health grants HL-19298 and 64368, and the Department of Veterans’ Affairs.

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Authors and Affiliations

  1. MC-2026 Department of Radiology, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL, 60637, USA

    Christian Wietholt

  2. Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA

    David L. Roerig

  3. Zablocki VA Medical Center, Research Service 151, 5000 W. National Avenue, Milwaukee, WI, 53295, USA

    David L. Roerig, John B. Gordon, Steven T. Haworth, Robert C. Molthen & Anne V. Clough

  4. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    John B. Gordon

  5. Children’s Hospital Research Institute, Milwaukee, WI, USA

    John B. Gordon

  6. Division of Pulmonary and Critical Care, Medical College of Wisconsin, Milwaukee, WI, USA

    Steven T. Haworth, Robert C. Molthen & Anne V. Clough

  7. Department of Mathematics, Statistics and Computer Science, Marquette University, Milwaukee, WI, USA

    Anne V. Clough

Authors
  1. Christian Wietholt
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  2. David L. Roerig
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  3. John B. Gordon
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  4. Steven T. Haworth
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  5. Robert C. Molthen
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  6. Anne V. Clough
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Correspondence to Anne V. Clough.

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Wietholt, C., Roerig, D.L., Gordon, J.B. et al. Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT. Eur J Nucl Med Mol Imaging 35, 1124–1132 (2008). https://doi.org/10.1007/s00259-007-0684-y

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  • DOI: https://doi.org/10.1007/s00259-007-0684-y

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