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  • Review Article
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Imaging myocardial angiogenesis

Nature Reviews Cardiology volume 6, pages 648–658 (2009)Cite this article

Abstract

Imaging myocardial angiogenesis presents a major technical challenge because the ideal spatial resolution required is substantially higher than that available with standard X-ray angiography and nuclear medicine imaging. Moreover, these clinical imaging methods are currently inadequate (because of insufficient resolution) for clinical trials of angiogenic agents for the treatment of ischemic heart disease. Specialized techniques in MRI, ultrasonography, echocardiography and CT that are under development might provide improved means of imaging myocardial angiogenesis. Molecular imaging technologies are also being developed to improve resolution and to provide a better mechanistic insight into angiogenic therapies for ischemic heart diseases. This Review examines advanced methods for imaging angiogenesis. These technologies might soon permit data to be obtained directly from scientific studies and clinical trials.

Key Points

  • Progress has been made in imaging technologies to assess myocardial angiogenesis

  • The development of molecular probes specific for different stages of angiogenesis might further improve the resolution of clinical imaging

  • Two-photon emission microscopy is an excellent example of combining activated probes to examine subcellular processes in the myocardium in vivo

  • Generation of molecular beacons for receptors, proteins and markers of angiogenesis conjugated to iron and gadolinium allows for even more accurate magnetic resonance imaging

  • Objective imaging end points will limit placebo effects seen in patients with chronic ischemia when subjective clinical outcome measures such as angina and quality of life questionnaires are used

  • Large-scale clinical studies should be undertaken using new imaging technologies with higher sensitivity and specificity

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Figure 1: Vascular corrosion casts of epicardial arteries.
Figure 2: Immunohistochemical analysis.
Figure 3: PET-CT imaging of integrin expression.
Figure 4: Coronary angiography in a patient with ischemic heart disease.
Figure 5: CT myocardial perfusion 64-slice MSCT imaging in a patient referred for invasive angiography and SPECT evidence of fixed perfusion defect in the inferior and inferolateral territory.
Figure 6: MRI perfusion imaging in a patient with 90% LAD stenosis showing a regional perfusion defect without late gadolinium enhancement and a lesion on magnetic resonance angiography in the proximal vessel.

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References

  1. AHA. AHA statistics. American Heart Association [online], (2004).

  2. Jolicoeur, E. M. et al. Clinical and research issues regarding chronic advanced coronary artery disease: Report from a think tank. Part 1: Contemporary and emerging therapies. Am. Heart J. 155, 418–434 (2008).

    PubMed  Google Scholar 

  3. Folkman, J. Angiogenic therapy of the human heart. Circulation 97, 628–629 (1998).

    CAS  PubMed  Google Scholar 

  4. Henry, T. D. Can we really grow new blood vessels? Lancet 351, 1826–1827 (1998).

    CAS  PubMed  Google Scholar 

  5. Simons, M. Angiogenesis: Where do we stand now? Circulation 111, 1556–1566 (2005).

    PubMed  Google Scholar 

  6. Carmeliet, P. Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 6, 389–395 (2000).

    CAS  PubMed  Google Scholar 

  7. Carmeliet, P. Basic concepts of (myocardial) angiogenesis: role of vascular endothelial growth factor and angiopoietin. Curr. Interv. Cardiol. Rep. 1, 322–335 (1999).

    CAS  PubMed  Google Scholar 

  8. Losordo, D. W. & Dimmeler, S. Therapeutic angiogenesis and vasculogenesis for ischemic disease: Part I: Angiogenic cytokines. Circulation 109, 2487–2491 (2004).

    PubMed  Google Scholar 

  9. Losordo, D. W. & Dimmeler, S. Therapeutic angiogenesis and vasculogenesis for ischemic disease: Part II: Cell-based therapies. Circulation 109, 2692–2697 (2004).

    PubMed  Google Scholar 

  10. Eliceiri, B. P. & Cheresh, D. A. The role of αV integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J. Clin. Invest. 103, 1227–1230 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Eliceiri, B. P. & Cheresh, D. A. The role of αV integrins during angiogenesis. Mol. Med. 4, 741–750 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Eliceiri, B. P. et al. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol. Cell 4, 915–924 (1999).

    CAS  PubMed  Google Scholar 

  13. Varner, J. A., Brooks, P. C. & Cheresh, D. A. Review: the integrin αVβ3: angiogenesis and apoptosis. Cell Adhes. Commun. 3, 367–374 (1995).

    CAS  PubMed  Google Scholar 

  14. Lindahl, P. et al. Role of platelet-derived growth factors in angiogenesis and alveogenesis. Curr. Top. Pathol. 93, 27–33 (1999).

    CAS  PubMed  Google Scholar 

  15. Gohongi, T. et al. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor β1. Nat. Med. 5, 1203–1208 (1999).

    CAS  PubMed  Google Scholar 

  16. Schaper, W. & Ito, W. D. Therapeutic targets in cardiovascular disorders. Curr. Opin. Biotechnol. 7, 635–640 (1996).

    CAS  PubMed  Google Scholar 

  17. Schaper, W. & Ito, W. D. Molecular mechanisms of coronary collateral vessel growth. Circ. Res. 79, 911–919 (1996).

    CAS  PubMed  Google Scholar 

  18. Semenza, G. L. Hypoxia-inducible factor 1: master regulator of O2 homeostasis. Curr. Opin. Genet. Dev. 8, 588–594 (1998).

    CAS  PubMed  Google Scholar 

  19. Li, J. et al. PR39, a peptide regulator of angiogenesis. Nat. Med. 6, 49–55 (2000).

    CAS  PubMed  Google Scholar 

  20. Kodama, K. et al. Collateral channels that develop after an acute myocardial infarction prevent subsequent left ventricular dilation. J. Am. Coll. Cardiol. 27, 1133–1139 (1996).

    CAS  PubMed  Google Scholar 

  21. Schumacher, B., Pecher, P., von Specht, B. U. & Stegmann, T. Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. Circulation 97, 645–650 (1998).

    CAS  PubMed  Google Scholar 

  22. Laham, R. J. et al. Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery: results of a phase I randomized, double-blind, placebo-controlled trial. Circulation 100, 1865–1871 (1999).

    CAS  PubMed  Google Scholar 

  23. Simons, M. et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation 105, 788–793 (2002).

    CAS  PubMed  Google Scholar 

  24. Henry, T. D. et al. The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation 107, 1359–1365 (2003).

    CAS  PubMed  Google Scholar 

  25. Henry, T. D. et al. Effects of Ad5FGF-4 in patients with angina. An analysis of pooled data from the AGENT-3 and AGENT-4 trials. J. Am. Coll. Cardiol. 50, 1038–1046 (2007).

    CAS  PubMed  Google Scholar 

  26. Kastrup, J. et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris: a randomized double-blind placebo-controlled study: the Euroinject One Trial. J. Am. Coll. Cardiol. 45, 982–988 (2005).

    CAS  PubMed  Google Scholar 

  27. Losordo, D. W. et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind randomized controlled trial. Circulation 115, 3165–3172 (2007).

    PubMed  Google Scholar 

  28. Miettinen, M., Lindenmayer, A. E. & Chaubal, A. Endothelial cell markers CD31, CD34, and BNH9 antibody to H- and Y-antigens--evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor. Mod. Pathol. 7, 82–90 (1994).

    CAS  PubMed  Google Scholar 

  29. Montanez, E., Casaroli-Marano, R. P., Vilaro, S. & Pagan, R. Comparative study of tube assembly in three-dimensional collagen matrix and on Matrigel coats. Angiogenesis 5, 167–172 (2002).

    CAS  PubMed  Google Scholar 

  30. Lamping, K. G., Christensen, L. P. & Tomanek, R. J. Estrogen therapy induces collateral and microvascular remodeling. Am. J. Physiol. Heart Circ. Physiol. 285, H2039–H2044 (2003).

    CAS  PubMed  Google Scholar 

  31. Wang, X., Zheng, W., Christensen, L. P. & Tomanek, R. J. DITPA stimulates bFGF, VEGF, angiopoietin, and Tie-2 and facilitates coronary arteriolar growth. Am. J. Physiol. Heart Circ. Physiol. 284, H613–H618 (2003).

    CAS  PubMed  Google Scholar 

  32. Laham, R. J. et al. Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia. J. Pharmacol. Exp. Ther. 292, 795–802 (2000).

    CAS  PubMed  Google Scholar 

  33. Reinhardt, C. P., Dalhberg, S., Tries, M. A., Marcel, R. & Leppo, J. A. Stable labeled microspheres to measure perfusion: validation of a neutron activation assay technique. Am. J. Physiol. Heart Circ. Physiol. 280, H108–H116 (2001).

    CAS  PubMed  Google Scholar 

  34. Ruel, M. et al. Inhibition of the cardiac angiogenic response to surgical FGF-2 therapy in a swine endothelial dysfunction model. Circulation 108, II335–II340 (2003).

    PubMed  Google Scholar 

  35. Pearlman, J. D., Laham, R. J. & Simons, M. Coronary angiogenesis: detection in vivo with MR imaging sensitive to collateral neocirculation—preliminary study in pigs. Radiology 214, 801–807 (2000).

    CAS  PubMed  Google Scholar 

  36. Yang, M. et al. Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells. Proc. Natl Acad. Sci. USA 100, 14259–14262 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Rubart, M. Two-photon microscopy of cells and tissue. Circ. Res. 95, 1154–1166 (2004).

    CAS  PubMed  Google Scholar 

  38. Rubart, M. et al. Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ. Res. 92, 1217–1224 (2003).

    CAS  PubMed  Google Scholar 

  39. Rubart, M., Soonpaa, M. H., Nakajima, H. & Field, L. J. Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation. J. Clin. Invest. 114, 775–783 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Levene, M. J., Dombeck, D. A., Kasischke, K. A., Molloy, R. P. & Webb, W. W. In vivo multiphoton microscopy of deep brain tissue. J. Neurophysiol. 91, 1908–1912 (2004).

    PubMed  Google Scholar 

  41. Peters, N. S., Coromilas, J., Severs, N. J. & Wit, A. L. Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation 95, 988–996 (1997).

    CAS  PubMed  Google Scholar 

  42. Kleinfeld, D., Mitra, P. P., Helmchen, F. & Denk, W. Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc. Natl Acad. Sci. USA 95, 15741–15746 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Freedman, S. B., Dunn, R. F., Bernstein, L., Morris, J. & Kelly, D. T. Influence of coronary collateral blood flow on the development of exertional ischemia and Q wave infarction in patients with severe single-vessel disease. Circulation 71, 681–686 (1985).

    CAS  PubMed  Google Scholar 

  44. Pearlman, J. D., Laham, R. J., Post, M., Leiner, T. & Simons, M. Medical imaging techniques in the evaluation of strategies for therapeutic angiogenesis. Curr. Pharm. Des. 8, 1467–1496 (2002).

    CAS  PubMed  Google Scholar 

  45. Simons, M. et al. Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary. Circulation 102, E73–E86 (2000).

    CAS  PubMed  Google Scholar 

  46. Muzik, O. et al. Assessment of diagnostic performance of quantitative flow measurements in normal subjects and patients with angiographically documented coronary artery disease by means of nitrogen-13 ammonia and positron emission tomography. J. Am. Coll. Cardiol. 31, 534–540 (1998).

    CAS  PubMed  Google Scholar 

  47. Anagnostopoulos, C. et al. Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity. Eur. J. Nucl. Med. Mol. Imaging 35, 1593–1601 (2008).

    PubMed  PubMed Central  Google Scholar 

  48. Meoli, D. F. et al. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J. Clin. Invest. 113, 1684–1691 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Johnson, L. L. et al. Radiolabeled arginine-glycine-aspartic acid peptides to image angiogenesis in swine model of hibernating myocardium. JACC Cardiovasc. Imaging 1, 511–514 (2008).

    Google Scholar 

  50. Wei, L. et al. 64Cu-labeled CB-TE2A and diamsar-conjugated RGD peptide analogs for targeting angiogenesis: comparison of their biological activity. Nucl. Med. Biol. 36, 277–285 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Wei, K. et al. Noninvasive quantification of coronary blood flow reserve in humans using myocardial contrast echocardiography. Circulation 103, 2560–2565 (2001).

    CAS  PubMed  Google Scholar 

  52. Jayaweera, A. R. et al. Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography. Am. J. Physiol. 277, H2363–H2372 (1999).

    CAS  PubMed  Google Scholar 

  53. Villanueva, F. S. et al. Myocardial contrast echocardiography can be used to assess the microvascular response to vascular endothelial growth factor-121. Circulation 105, 759–765 (2002).

    CAS  PubMed  Google Scholar 

  54. Kaufmann, B. A. & Lindner, J. R. Molecular imaging with targeted contrast ultrasound. Curr. Opin. Biotechnol. 18, 11–16 (2007).

    CAS  PubMed  Google Scholar 

  55. Gibson, C. M. et al. Angiographic methods to assess human coronary angiogenesis. Am. Heart J. 137, 169–179 (1999).

    CAS  PubMed  Google Scholar 

  56. Asahara, T. et al. Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 92, II365–II371 (1995).

    CAS  PubMed  Google Scholar 

  57. Yanagisawa-Miwa, A. et al. Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor. Science 257, 1401–1403 (1992).

    CAS  PubMed  Google Scholar 

  58. Rentrop, K. P., Cohen, M., Blanke, H. & Phillips, R. A. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J. Am. Coll. Cardiol. 5, 587–592 (1985).

    CAS  PubMed  Google Scholar 

  59. Chittenden, T. W. et al. Transcriptional profiling in coronary artery disease: indications for novel markers of coronary collateralization. Circulation 114, 1811–1820 (2006).

    CAS  PubMed  Google Scholar 

  60. Kyriakides, Z. S., Antoniadis, A., Kolettis, T. M. & Kremastinos, D. T. Coronary flow reserve in the contralateral artery increases after successful coronary angioplasty in patients with spontaneously visible collateral vessels. Heart 80, 493–498 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Werner, G. S. & Figulla, H. R. Direct assessment of coronary steal and associated changes of collateral hemodynamics in chronic total coronary occlusions. Circulation 106, 435–440 (2002).

    PubMed  Google Scholar 

  62. De Bruyne, B. et al. Fractional flow reserve in patients with prior myocardial infarction. Circulation 104, 157–162 (2001).

    CAS  PubMed  Google Scholar 

  63. Montisci, R. et al. Non-invasive coronary flow reserve is correlated with microvascular integrity and myocardial viability after primary angioplasty in acute myocardial infarction. Heart 92, 1113–1118 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Wikstrom, J., Gronros, J., Bergstrom, G. & Gan, L. M. Functional and morphologic imaging of coronary atherosclerosis in living mice using high-resolution color Doppler echocardiography and ultrasound biomicroscopy. J. Am. Coll. Cardiol. 46, 720–727 (2005).

    PubMed  Google Scholar 

  65. Lee, T. Y., Purdie, T. G. & Stewart, E. CT imaging of angiogenesis. Q. J. Nucl. Med. 47, 171–187 (2003).

    PubMed  Google Scholar 

  66. Miles, K. A. et al. Application of CT in the investigation of angiogenesis in oncology. Acad. Radiol. 7, 840–850 (2000).

    CAS  PubMed  Google Scholar 

  67. Rybicki, F. J. et al. Initial evaluation of coronary images from 320-detector row computed tomography. Int. J. Cardiovasc. Imaging 24, 535–546 (2008).

    PubMed  Google Scholar 

  68. Choi, S, I, et al. Recent developments in wide-detector cardiac computed tomography. Int. J. Cardiovasc. Imaging 25, 23–29 (2009).

    PubMed  Google Scholar 

  69. George, R. T. et al. Quantification of myocardial perfusion using dynamic 64-detector computed tomography. Invest. Radiol. 42, 815–822 (2007).

    PubMed  Google Scholar 

  70. Kitagawa, T. et al. Characterization of noncalcified coronary plaques and identification of culprit lesions in patients with acute coronary syndrome by 64-slice computed tomography. J. Am. Coll. Cardiol. 2, 153–160 (2009).

    Google Scholar 

  71. Pearlman, J. D., Laham, R. J., Simons, M., Gladstone, S. & Raptopoulos, V. Extent of myocardial collateralization: determination with three-dimensional elastic-subtraction spiral CT. Acad. Radiol. 4, 680–686 (1997).

    CAS  PubMed  Google Scholar 

  72. Bremer, C. et al. Steady-state blood volume measurements in experimental tumors with different angiogenic burdens a study in mice. Radiology 226, 214–220 (2003).

    PubMed  Google Scholar 

  73. Turetschek, K. et al. MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model. Eur. J. Nucl. Med. Mol. Imaging 30, 448–455 (2003).

    CAS  PubMed  Google Scholar 

  74. Bhujwalla, Z. M., Artemov, D., Natarajan, K., Ackerstaff, E. & Solaiyappan, M. Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. Neoplasia 3, 143–153 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Pearlman, J. D., Gertz, Z. M., Wu, Y., Simons, M. & Post, M. J. Serial motion assessment by reference tracking (SMART): application to detection of local functional impact of chronic myocardial ischemia. J. Comput. Assist. Tomogr. 25, 558–562 (2001).

    CAS  PubMed  Google Scholar 

  76. Pearlman, J. D. et al. Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis. Nat. Med. 1, 1085–1089 (1995).

    CAS  PubMed  Google Scholar 

  77. Vallee, J. P. et al. Quantification of myocardial perfusion with FAST sequence and Gd bolus in patients with normal cardiac function. J. Magn. Reson. Imaging 9, 197–203 (1999).

    CAS  PubMed  Google Scholar 

  78. Bassingthwaighte, J. B. Physiology and theory of tracer washout techniques for the estimation of myocardial blood flow: flow estimation from tracer washout. Prog. Cardiovasc. Dis. 20, 165–189 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Beard, D. A. & Bassingthwaighte, J. B. The fractal nature of myocardial blood flow emerges from a whole-organ model of arterial network. J. Vasc. Res. 37, 282–296 (2000).

    CAS  PubMed  Google Scholar 

  80. Laham, R. J. et al. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study. J. Am. Coll. Cardiol. 36, 2132–2139 (2000).

    CAS  PubMed  Google Scholar 

  81. Laham, R. J., Simons, M., Pearlman, J. D., Ho, K. K. & Baim, D. S. Magnetic resonance imaging demonstrates improved regional systolic wall motion and thickening and myocardial perfusion of myocardial territories treated by laser myocardial revascularization. J. Am. Coll. Cardiol. 39, 1–8 (2002).

    PubMed  Google Scholar 

  82. Schachinger, V. et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J. Am. Coll. Cardiol. 44, 1690–1699 (2004).

    PubMed  Google Scholar 

  83. Wollert, K. C. & Drexler, H. Clinical applications of stem cells for the heart. Circ. Res. 96, 151–163 (2005).

    CAS  PubMed  Google Scholar 

  84. Lin, P. C. Optical imaging and tumor angiogenesis. J. Cell Biochem. 90, 484–491 (2003).

    CAS  PubMed  Google Scholar 

  85. Neeman, M. & Dafni, H. Structural, functional, and molecular MR imaging of the microvasculature. Annu. Rev. Biomed. Eng. 5, 29–56 (2003).

    CAS  PubMed  Google Scholar 

  86. Jayson, G. C. et al. Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. J. Natl Cancer Inst. 94, 1484–1493 (2002).

    CAS  PubMed  Google Scholar 

  87. Weissleder, R., Bogdanov, A. Jr, Tung, C. H. & Weinmann, H. J. Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging. Bioconjugate Chem. 12, 213–219 (2001).

    CAS  Google Scholar 

  88. Kang, H. W., Josephson, L., Petrovsky, A., Weissleder, R. & Bogdanov, A. Jr. Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjugate Chem. 13, 122–127 (2002).

    CAS  Google Scholar 

  89. Winter, P. M. et al. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel α(nu)β3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res. 63, 5838–5843 (2003).

    CAS  PubMed  Google Scholar 

  90. Lazarous, D. F. et al. Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation 91, 145–153 (1995).

    CAS  PubMed  Google Scholar 

  91. Giordano, F. J. et al. Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat. Med. 2, 534–539 (1996).

    CAS  PubMed  Google Scholar 

  92. Unger, E. F. et al. Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am. J. Physiol. 266, H1588–H1595 (1994).

    CAS  PubMed  Google Scholar 

  93. Hendel, R. C. et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dose-dependent effect. Circulation 101, 118–121 (2000).

    CAS  PubMed  Google Scholar 

  94. Henry, T. D. & Satran, D. in Coronary Artery Disease: New Approaches without Traditional Revascularization (eds Barsness, G. W. & Holmes, D. R.) (Springer, New York City, 2007).

    Google Scholar 

  95. Udelson, J. E. et al. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease. Circulation 102, 1605–1610 (2000).

    CAS  PubMed  Google Scholar 

  96. Grines, C. L. et al. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J. Am. Coll. Cardiol. 42, 1339–1347 (2003).

    CAS  PubMed  Google Scholar 

  97. Pijls, N. H., Bos, H. S., Uijen, G. J. & Van der Werf, T. Is nonionic isotonic iohexol the contrast agent of choice for quantitative myocardial videodensitometry? Int. J. Card. Imaging 3, 117–126 (1988).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Thoraxcenter, Erasmus Medical Centre, Rotterdam, The Netherlands

    Joanna J. Wykrzykowska

  2. Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN, USA

    Timothy D. Henry, John R. Lesser & Robert S. Schwartz

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Correspondence to Robert S. Schwartz.

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Supplementary information

Supplementary Table 1

Spatial resolution of different imaging modalities (DOC 40 kb)

Supplementary Figure 1

Diagram of the multiple factors leading to production of new vessels (DOC 174 kb)

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Wykrzykowska, J., Henry, T., Lesser, J. et al. Imaging myocardial angiogenesis. Nat Rev Cardiol 6, 648–658 (2009). https://doi.org/10.1038/nrcardio.2009.157

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