Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2008

01-06-2008 | Original article

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

Authors: Christian Wietholt, David L. Roerig, John B. Gordon, Steven T. Haworth, Robert C. Molthen, Anne V. Clough

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2008

Login to get access

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.
Literature
1.
go back to reference Deffebach ME, Charan NB, Lakshminarayan S, Butler J. The bronchial circulation. Small, but a vital attribute of the lung. Am Rev Respir Dis. 1987;135:463–81.PubMed Deffebach ME, Charan NB, Lakshminarayan S, Butler J. The bronchial circulation. Small, but a vital attribute of the lung. Am Rev Respir Dis. 1987;135:463–81.PubMed
2.
3.
go back to reference Charan NB, Carvalho P. Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction. J Appl Physiol. 1997;82:284–91.PubMed Charan NB, Carvalho P. Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction. J Appl Physiol. 1997;82:284–91.PubMed
4.
go back to reference Kamler M, Nowak K, Bock M, Herold U, Motsch J, Hagl S, et al. Bronchial artery revascularization restores peribronchial tissue oxygenation after lung transplantation. J Heart Lung Transplant. 2004;23:763–6.PubMedCrossRef Kamler M, Nowak K, Bock M, Herold U, Motsch J, Hagl S, et al. Bronchial artery revascularization restores peribronchial tissue oxygenation after lung transplantation. J Heart Lung Transplant. 2004;23:763–6.PubMedCrossRef
5.
go back to reference Ohta Y, Ohta N, Tamura M, Wu J, Tsunezuka Y, Oda M, et al. Vascular endothelial growth factor expression in airways of patients with lung cancer: a possible diagnostic tool of responsive angiogenic status on the host side. Chest. 2002;121:1624–7.PubMedCrossRef Ohta Y, Ohta N, Tamura M, Wu J, Tsunezuka Y, Oda M, et al. Vascular endothelial growth factor expression in airways of patients with lung cancer: a possible diagnostic tool of responsive angiogenic status on the host side. Chest. 2002;121:1624–7.PubMedCrossRef
6.
go back to reference Inoue K, Kawahito Y, Sano H, Takano H, Yoshikawa T. New diagnostic tool for tumor angiogenesis. Chest. 2003;123:966–7.PubMedCrossRef Inoue K, Kawahito Y, Sano H, Takano H, Yoshikawa T. New diagnostic tool for tumor angiogenesis. Chest. 2003;123:966–7.PubMedCrossRef
7.
go back to reference Hirsch FR, Franklin WA, Gazdar AF, Bunn PA Jr. Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clin Cancer Res. 2001;7:5–22.PubMed Hirsch FR, Franklin WA, Gazdar AF, Bunn PA Jr. Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clin Cancer Res. 2001;7:5–22.PubMed
8.
go back to reference Hirsch FR, Merrick DT, Franklin WA. Role of biomarkers for early detection of lung cancer and chemoprevention. Eur Respir J. 2002;19:1151–8.PubMedCrossRef Hirsch FR, Merrick DT, Franklin WA. Role of biomarkers for early detection of lung cancer and chemoprevention. Eur Respir J. 2002;19:1151–8.PubMedCrossRef
9.
10.
go back to reference Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29:15–8.PubMed Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29:15–8.PubMed
11.
go back to reference Gross DJ, Reibstein I, Weiss L, Slavin S, Stein I, Neeman M, et al. The antiangiogenic agent linomide inhibits the growth rate of von Hippel–Lindau paraganglioma xenografts to mice. Clin Cancer Res. 1999;5:3669–75.PubMed Gross DJ, Reibstein I, Weiss L, Slavin S, Stein I, Neeman M, et al. The antiangiogenic agent linomide inhibits the growth rate of von Hippel–Lindau paraganglioma xenografts to mice. Clin Cancer Res. 1999;5:3669–75.PubMed
12.
go back to reference Michel RP, Hakim TS. Increased resistance in postobstructive pulmonary vasculopathy: structure–function relationships. J Appl Physiol. 1991;71:601–10.PubMed Michel RP, Hakim TS. Increased resistance in postobstructive pulmonary vasculopathy: structure–function relationships. J Appl Physiol. 1991;71:601–10.PubMed
13.
go back to reference Michel RP, Hakim TS, Petsikas D. Segmental vascular resistance in postobstructive pulmonary vasculopathy. J Appl Physiol. 1990;69:1022–32.PubMed Michel RP, Hakim TS, Petsikas D. Segmental vascular resistance in postobstructive pulmonary vasculopathy. J Appl Physiol. 1990;69:1022–32.PubMed
14.
go back to reference Simon BA, Tsuzaki K, Venegas JG. Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J Appl Physiol. 1997;82:882–91.PubMed Simon BA, Tsuzaki K, Venegas JG. Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J Appl Physiol. 1997;82:882–91.PubMed
15.
go back to reference Kim H, Yung GL, Marsh JJ, Konopka RG, Pedersen CA, Chiles PG, et al. Pulmonary vascular remodeling distal to pulmonary artery ligation is accompanied by upregulation of endothelin receptors and nitric oxide synthase. Exp Lung Res. 2000;26:287–301.PubMedCrossRef Kim H, Yung GL, Marsh JJ, Konopka RG, Pedersen CA, Chiles PG, et al. Pulmonary vascular remodeling distal to pulmonary artery ligation is accompanied by upregulation of endothelin receptors and nitric oxide synthase. Exp Lung Res. 2000;26:287–301.PubMedCrossRef
16.
go back to reference Shi W, Cernacek P, Hu F, Michel RP. Endothelin reactivity and receptor profile of pulmonary vessels in postobstructive pulmonary vasculopathy. Am J Physiol. 1997;273:H2558–64.PubMed Shi W, Cernacek P, Hu F, Michel RP. Endothelin reactivity and receptor profile of pulmonary vessels in postobstructive pulmonary vasculopathy. Am J Physiol. 1997;273:H2558–64.PubMed
17.
go back to reference Wang HY, Ng B, Ahrens C, Burt M. Unilateral pulmonary artery occlusion inhibits growth of metastatic sarcoma in the rat lung. J Surg Oncol. 1994;57:183–6.PubMedCrossRef Wang HY, Ng B, Ahrens C, Burt M. Unilateral pulmonary artery occlusion inhibits growth of metastatic sarcoma in the rat lung. J Surg Oncol. 1994;57:183–6.PubMedCrossRef
18.
go back to reference Weibel ER. Early stages in the development of collateral circulation to the lung in the rat. Circ Res. 1960;8:353–76.PubMed Weibel ER. Early stages in the development of collateral circulation to the lung in the rat. Circ Res. 1960;8:353–76.PubMed
19.
go back to reference Mitzner W, Lee W, Georgakopoulos D, Wagner E. Angiogenesis in the mouse lung. Am J Pathol. 2000;157:93–101.PubMed Mitzner W, Lee W, Georgakopoulos D, Wagner E. Angiogenesis in the mouse lung. Am J Pathol. 2000;157:93–101.PubMed
20.
go back to reference Mitzner W, Srisuma S, Wagner E. Genetic regulation of systemic angiogenesis in the mouse lung. Arch Physiol Biochem. 2003;111:357–9.PubMedCrossRef Mitzner W, Srisuma S, Wagner E. Genetic regulation of systemic angiogenesis in the mouse lung. Arch Physiol Biochem. 2003;111:357–9.PubMedCrossRef
21.
go back to reference Kim H, Park HA, Suh GY, Chung MP, Kwon OJ. Quantitative analysis of endothelin and nitric oxide synthase in rat model of postobstructive pulmonary vasculopathy. Exp Lung Res. 2002;28:351–9.PubMedCrossRef Kim H, Park HA, Suh GY, Chung MP, Kwon OJ. Quantitative analysis of endothelin and nitric oxide synthase in rat model of postobstructive pulmonary vasculopathy. Exp Lung Res. 2002;28:351–9.PubMedCrossRef
22.
go back to reference Iwasaki K, Kusachi S, Hina K, Murakami M, Matano S, Ohnishi N, et al. Coronary to bronchial artery anastomosis in patients with noncyanotic cardiopulmonary disease: report of seven cases. Can J Cardiol. 1997;13:898–900.PubMed Iwasaki K, Kusachi S, Hina K, Murakami M, Matano S, Ohnishi N, et al. Coronary to bronchial artery anastomosis in patients with noncyanotic cardiopulmonary disease: report of seven cases. Can J Cardiol. 1997;13:898–900.PubMed
23.
go back to reference Hudson H, Larkin R. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imag. 1994;13:601–9.CrossRef Hudson H, Larkin R. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imag. 1994;13:601–9.CrossRef
24.
go back to reference Wietholt C, Molthen RC, Johnson RH, Dawson CA, Clough AV. SPECT imaging of pulmonary blood flow in a rat. In: Clough A, Amini AA, editors. Proc. SPIE Medical Imaging 2003: Physiology and function: methods, systems, and applications, Vol. 5031. SPIE; 2003. pp 252–61. Wietholt C, Molthen RC, Johnson RH, Dawson CA, Clough AV. SPECT imaging of pulmonary blood flow in a rat. In: Clough A, Amini AA, editors. Proc. SPIE Medical Imaging 2003: Physiology and function: methods, systems, and applications, Vol. 5031. SPIE; 2003. pp 252–61.
25.
go back to reference Shepp L, Vardi Y. Maximum likelihood reconstruction for emission tomography. IEEE Trans Med Imag. 1982;1:113–22. Shepp L, Vardi Y. Maximum likelihood reconstruction for emission tomography. IEEE Trans Med Imag. 1982;1:113–22.
26.
go back to reference Abramowitz M, Stegun IA. Handbook of mathematical functions. Washington, DC: US Government Printing Office; 1972. Abramowitz M, Stegun IA. Handbook of mathematical functions. Washington, DC: US Government Printing Office; 1972.
27.
go back to reference Barrett H, Swindell W. Radiological imaging: the theory of image formation, detection, and processing, Vol. 1. San Diego, CA: Academic; 1981. Barrett H, Swindell W. Radiological imaging: the theory of image formation, detection, and processing, Vol. 1. San Diego, CA: Academic; 1981.
28.
go back to reference Wietholt C, Molthen RC, Roerig DL, Haworth ST, Dawson CA, Clough AV. Quantification of bronchial circulation perfusion in rats. In: Amini A, Manduca A, editors. Proc. SPIE Medical Imaging 2004: Physiology and function: methods, systems, and applications, Vol. 5370. Bellingham, WA: SPIE; 2004. Wietholt C, Molthen RC, Roerig DL, Haworth ST, Dawson CA, Clough AV. Quantification of bronchial circulation perfusion in rats. In: Amini A, Manduca A, editors. Proc. SPIE Medical Imaging 2004: Physiology and function: methods, systems, and applications, Vol. 5370. Bellingham, WA: SPIE; 2004.
29.
go back to reference Molthen R, Wietholt C, Haworth ST, Dawson CA. Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data. In: Chen C, Clough AV, editors. Proc. SPIE Medical Imaging 2002: Physiology and function from multidimensional images, vol. 4683. Bellingham, WA: SPIE; 2002. pp 266–75. Molthen R, Wietholt C, Haworth ST, Dawson CA. Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data. In: Chen C, Clough AV, editors. Proc. SPIE Medical Imaging 2002: Physiology and function from multidimensional images, vol. 4683. Bellingham, WA: SPIE; 2002. pp 266–75.
30.
go back to reference Karau KL, Molthen RC, Dhyani A, Haworth ST, Hanger CC, Roerig DL, et al. Pulmonary arterial morphometry from microfocal X-ray computed tomography. Am J Physiol Heart Circ Physiol. 2001;281:H2747–56.PubMed Karau KL, Molthen RC, Dhyani A, Haworth ST, Hanger CC, Roerig DL, et al. Pulmonary arterial morphometry from microfocal X-ray computed tomography. Am J Physiol Heart Circ Physiol. 2001;281:H2747–56.PubMed
31.
go back to reference Feldkamp L, Davis L, Kress J. Practical cone-beam algorithm. J Opt Soc Am A. 1984;1:612–9.CrossRef Feldkamp L, Davis L, Kress J. Practical cone-beam algorithm. J Opt Soc Am A. 1984;1:612–9.CrossRef
32.
go back to reference Gonzalez RC, Woods RE. Digital image processing. 2nd ed. Upper Saddle River, NJ: Prentice Hall; 2002. Gonzalez RC, Woods RE. Digital image processing. 2nd ed. Upper Saddle River, NJ: Prentice Hall; 2002.
33.
go back to reference Buschmann I, Schaper W. Arteriogenesis versus angiogenesis: two mechanisms of vessel growth. News Physiol Sci. 1999;14:121–5.PubMed Buschmann I, Schaper W. Arteriogenesis versus angiogenesis: two mechanisms of vessel growth. News Physiol Sci. 1999;14:121–5.PubMed
34.
go back to reference Carvalho P, Thompson WH, Riggs R, Carvalho C, Charan NB. Management of bronchopleural fistula with a variable-resistance valve and a single ventilator. Chest. 1997;111:1452–4.PubMedCrossRef Carvalho P, Thompson WH, Riggs R, Carvalho C, Charan NB. Management of bronchopleural fistula with a variable-resistance valve and a single ventilator. Chest. 1997;111:1452–4.PubMedCrossRef
35.
go back to reference Charan NB, Baile EM, Pare PD. Bronchial vascular congestion and angiogenesis. Eur Respir J. 1997;10:1173–80.PubMedCrossRef Charan NB, Baile EM, Pare PD. Bronchial vascular congestion and angiogenesis. Eur Respir J. 1997;10:1173–80.PubMedCrossRef
36.
go back to reference Seret A, Bleeser F. Intrinsic uniformity requirements for pinhole SPECT. J Nucl Med Technol. 2006;34:43–7.PubMed Seret A, Bleeser F. Intrinsic uniformity requirements for pinhole SPECT. J Nucl Med Technol. 2006;34:43–7.PubMed
37.
go back to reference Wu M, Hasegawa BH, Daw MW. Performance evaluation of a pinhole SPECT system for myocardial perfusion imaging of mice. Med Phys. 2002;29:2830–9.PubMedCrossRef Wu M, Hasegawa BH, Daw MW. Performance evaluation of a pinhole SPECT system for myocardial perfusion imaging of mice. Med Phys. 2002;29:2830–9.PubMedCrossRef
38.
go back to reference Schramm N, Wirrwar A, Sonnenberg F, Halling H. Compact high resolution detector for small animal SPECT. IEEE Trans Nucl Sci. 2000;47:1163–7.CrossRef Schramm N, Wirrwar A, Sonnenberg F, Halling H. Compact high resolution detector for small animal SPECT. IEEE Trans Nucl Sci. 2000;47:1163–7.CrossRef
39.
go back to reference Rutao Y, Seidel J, Johnson C, Daube-Witherspoon M, Green M, Carson R. Performance characteristics of the 3D OSEM algorithm in the reconstruction of small animal PET images. IEEE Trans Med Imag. 2000;19:798–804.CrossRef Rutao Y, Seidel J, Johnson C, Daube-Witherspoon M, Green M, Carson R. Performance characteristics of the 3D OSEM algorithm in the reconstruction of small animal PET images. IEEE Trans Med Imag. 2000;19:798–804.CrossRef
40.
go back to reference Hwang AB, Hasegawa BH. Attenuation correction for small animal SPECT imaging using x-ray CT data. Med Phys. 2005;32:2799–804.PubMedCrossRef Hwang AB, Hasegawa BH. Attenuation correction for small animal SPECT imaging using x-ray CT data. Med Phys. 2005;32:2799–804.PubMedCrossRef
41.
go back to reference Ritman EL. Molecular imaging in small animals—roles for micro-CT. J Cell Biochem Suppl 2002;39:116–24.PubMedCrossRef Ritman EL. Molecular imaging in small animals—roles for micro-CT. J Cell Biochem Suppl 2002;39:116–24.PubMedCrossRef
Metadata
Title
Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT
Authors
Christian Wietholt
David L. Roerig
John B. Gordon
Steven T. Haworth
Robert C. Molthen
Anne V. Clough
Publication date
01-06-2008
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0684-y

Other articles of this Issue 6/2008

European Journal of Nuclear Medicine and Molecular Imaging 6/2008 Go to the issue