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The Role of Positron Emission Tomography

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Abstract

The link between myocardial ischemia and obstructive atherosclerosis of the epicardial coronary arteries is well established, and coronary angiography has demonstrated a relationship between the severity and extent of coronary artery disease (CAD) and survival. In the past 20 years technological advances in positron emission tomography (PET) have enabled the noninvasive measurement of absolute (ml/min/g) myocardial blood flow (MBF) and flow reserve. In the absence of detectable CAD, a reduced maximum MBF and CFR can be ascribed to coronary microvascular dysfunction.

PET MBF studies have contributed significantly to the understanding of the pathophysiology of chest pain in patients with angiographically normal coronary arteries. These studies have highlighted the role of coronary microvascular dysfunction as a potential mechanism of myocardial ischemia in many conditions, from patients with risk factors for CAD to those with myocardial diseases. Quantification of absolute MBF with PET can be used clinically to demonstrate coronary microvascular dysfunction and how treatment can improve the function of the small coronary vessels. Therefore, the use of the term cardiac syndrome X to describe patients with chest pain and normal coronary angiograms is probably inappropriate in most cases and should be confined to those cases where no obvious risk factors for coronary microvascular dysfunction can be demonstrated.

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References

  1. Prinzen FW, Bassingthwaighte JB. Blood flow distributions by microsphere deposition methods. Cardiovasc Res. 2000;45(1):13–21.

    Article  PubMed  CAS  Google Scholar 

  2. Hermansen F, et al. Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols. Eur J Nucl Med. 1998;25(7):751–9.

    Article  PubMed  CAS  Google Scholar 

  3. Nagamachi S, et al. Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. J Nucl Med. 1996;37(10):1626–31.

    PubMed  CAS  Google Scholar 

  4. Koepfli P, et al. CT attenuation correction for myocardial perfusion quantification using a PET/CT hybrid scanner. J Nucl Med. 2004;45(4):537–42.

    PubMed  Google Scholar 

  5. Gaemperli O, Bengel FM, Kaufmann PA. Cardiac hybrid imaging. Eur Heart J. 2011;32(17):2100–8.

    Article  PubMed  Google Scholar 

  6. Bergmann SR, et al. Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. J Am Coll Cardiol. 1989;14(3):639–52.

    Article  PubMed  CAS  Google Scholar 

  7. Araujo LI, et al. Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. Circulation. 1991;83(3):875–85.

    Article  PubMed  CAS  Google Scholar 

  8. Iida H, et al. Measurement of absolute myocardial blood flow with H2 15O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect. Circulation. 1988;78(1):104–15.

    Article  PubMed  CAS  Google Scholar 

  9. Schaefers K, et al. Absolute quantification of myocardial blood flow with H2 15O and 3-dimensional PET: an experimental validation. J Nucl Med. 2002;43(8):1031–40.

    Google Scholar 

  10. Schelbert HR, et al. N-13 ammonia as an indicator of myocardial blood flow. Circulation. 1981;63(6):1259–72.

    Article  PubMed  CAS  Google Scholar 

  11. Hutchins GD, et al. Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging. J Am Coll Cardiol. 1990;15(5):1032–42.

    Article  PubMed  CAS  Google Scholar 

  12. Muzik O, et al. Validation of nitrogen-13-ammonia tracer kinetic model for quantification of myocardial blood flow using PET. J Nucl Med. 1993;34(1):83–91.

    PubMed  CAS  Google Scholar 

  13. Herrero P, et al. Noninvasive quantification of regional myocardial perfusion with rubidium-82 and positron emission tomography. Exploration of a mathematical model. Circulation. 1990;82(4):1377–86.

    Article  PubMed  CAS  Google Scholar 

  14. El Fakhri G, et al. Reproducibility and accuracy of quantitative myocardial blood flow assessment with (82)Rb PET: comparison with (13)N-ammonia PET. J Nucl Med. 2009;50(7):1062–71.

    Article  PubMed  Google Scholar 

  15. Huang SC, et al. Quantitative measurement of myocardial blood flow with oxygen-15 water and positron computed tomography: an assessment of potential and problems. J Nucl Med. 1985;26(6):616–25.

    PubMed  CAS  Google Scholar 

  16. Santana CA, et al. Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database. J Nucl Med. 2007;48(7):1122–8.

    Article  PubMed  Google Scholar 

  17. Iida H, et al. Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography. J Nucl Med. 1992;33(9):1669–77.

    PubMed  CAS  Google Scholar 

  18. Bergmann SR, et al. Quantification of regional myocardial blood flow in vivo with H2 15O. Circulation. 1984;70(4):724–33.

    Article  PubMed  CAS  Google Scholar 

  19. Krivokapich J, et al. 13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography. Circulation. 1989;80(5):1328–37.

    Article  PubMed  CAS  Google Scholar 

  20. Hove JD, et al. Dual spillover problem in the myocardial septum with nitrogen-13-ammonia flow quantitation. J Nucl Med. 1998;39(4):591–8.

    PubMed  CAS  Google Scholar 

  21. Choi Y, et al. Quantification of myocardial blood flow using 13N-ammonia and PET: comparison of tracer models. J Nucl Med. 1999;40(6):1045–55.

    PubMed  CAS  Google Scholar 

  22. Hutchins GD, Caraher JM, Raylman RR. A region of interest strategy for minimizing resolution distortions in quantitative myocardial PET studies. J Nucl Med. 1992;33(6):1243–50.

    PubMed  CAS  Google Scholar 

  23. Bellina CR, et al. Simultaneous in vitro and in vivo validation of nitrogen-13-ammonia for the assessment of regional myocardial blood flow. J Nucl Med. 1990;31(8):1335–43.

    PubMed  CAS  Google Scholar 

  24. Rosenspire KC, et al. Metabolic fate of [13N]ammonia in human and canine blood. J Nucl Med. 1990;31(2):163–7.

    PubMed  CAS  Google Scholar 

  25. Bol A, et al. Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres. Circulation. 1993;87(2):512–25.

    Article  PubMed  CAS  Google Scholar 

  26. Nitzsche EU, et al. Noninvasive quantification of myocardial blood flow in humans. A direct comparison of the [13N]ammonia and the [15O]water techniques. Circulation. 1996;93(11):2000–6.

    Article  PubMed  CAS  Google Scholar 

  27. Marinho NV, et al. Pathophysiology of chronic left ventricular dysfunction. New insights from the measurement of absolute myocardial blood flow and glucose utilization. Circulation. 1996;93(4):737–44.

    Article  PubMed  CAS  Google Scholar 

  28. Lammertsma AA, et al. Measurement of regional myocardial blood flow using C15O2 and positron emission tomography: comparison of tracer models. Clin Phys Physiol Meas. 1992;13(1):1–20.

    Article  PubMed  CAS  Google Scholar 

  29. Kaufmann PA, et al. Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. J Nucl Med. 1999;40(11):1848–56.

    PubMed  CAS  Google Scholar 

  30. Camici PG, Rimoldi OE. Myocardial blood flow in patients with hibernating myocardium. Cardiovasc Res. 2003;57(2):302–11.

    Article  PubMed  CAS  Google Scholar 

  31. Schepis T, et al. Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET. J Nucl Med. 2007;48(11):1783–9.

    Article  PubMed  CAS  Google Scholar 

  32. Hoffman JI. Maximal coronary flow and the concept of coronary vascular reserve. Circulation. 1984;70(2):153–9.

    Article  PubMed  CAS  Google Scholar 

  33. Austin Jr RE, et al. Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow. Circ Res. 1990;67(2):319–31.

    Article  PubMed  Google Scholar 

  34. Bassingthwaighte JB, King RB, Roger SA. Fractal nature of regional myocardial blood flow heterogeneity. Circ Res. 1989;65(3):578–90.

    Article  PubMed  CAS  Google Scholar 

  35. Chareonthaitawee P, et al. Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans. Cardiovasc Res. 2001;50(1):151–61.

    Article  PubMed  CAS  Google Scholar 

  36. Czernin J, et al. Influence of age and hemodynamics on myocardial blood flow and flow reserve. Circulation. 1993;88(1):62–9.

    Article  PubMed  CAS  Google Scholar 

  37. Uren NG, et al. Effect of aging on myocardial perfusion reserve. J Nucl Med. 1995;36(11):2032–6.

    PubMed  CAS  Google Scholar 

  38. Duvernoy CS, et al. Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects. J Am Coll Cardiol. 1999;33(2):463–70.

    Article  PubMed  CAS  Google Scholar 

  39. Lorenzoni R, Rosen SD, Camici PG. Effect of alpha 1-adrenoceptor blockade on resting and hyperemic myocardial blood flow in normal humans. Am J Physiol. 1996;271(4 Pt 2):H1302–6.

    PubMed  CAS  Google Scholar 

  40. Heusch G, et al. Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation. 2000;101(6):689–94.

    Article  PubMed  CAS  Google Scholar 

  41. Rimoldi O, et al. Limitation of coronary reserve after successful angioplasty is prevented by oral pretreatment with an alpha1-adrenergic antagonist. J Cardiovasc Pharmacol. 2000;36(3):310–5.

    Article  PubMed  CAS  Google Scholar 

  42. Schindler TH, et al. PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography. J Nucl Med. 2004;45(3):419–28.

    PubMed  Google Scholar 

  43. Kaufmann PA, et al. Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation. 2000;102(11):1233–8.

    Article  PubMed  CAS  Google Scholar 

  44. Kaufmann PA, et al. Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol. 2000;36(1):103–9.

    Article  PubMed  CAS  Google Scholar 

  45. Dayanikli F, et al. Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation. 1994;90(2):808–17.

    Article  PubMed  CAS  Google Scholar 

  46. Campisi R, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation. 1998;98(2):119–25.

    Article  PubMed  CAS  Google Scholar 

  47. Iwado Y, et al. Decreased endothelium-dependent coronary vasomotion in healthy young smokers. Eur J Nucl Med Mol Imaging. 2002;29(8):984–90.

    Article  PubMed  CAS  Google Scholar 

  48. Sdringola S, Patel D, Gould KL. High prevalence of myocardial perfusion abnormalities on positron emission tomography in asymptomatic persons with a parent or sibling with coronary artery disease. Circulation. 2001;103(4):496–501.

    Article  PubMed  CAS  Google Scholar 

  49. Momose M, et al. Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus. Eur J Nucl Med Mol Imaging. 2002;29(12):1675–9.

    Article  PubMed  Google Scholar 

  50. Rajappan K, et al. Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries. Circulation. 2002;105(4):470–6.

    Article  PubMed  Google Scholar 

  51. Rimoldi O, et al. Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation. J Nucl Med. 2006;47(1):163–72.

    PubMed  Google Scholar 

  52. Vermeltfoort IA, et al. Feasibility of subendocardial and subepicardial myocardial perfusion measurements in healthy normals with (15)O-labeled water and positron emission tomography. J Nucl Cardiol. 2011;18(4):650–6.

    Article  PubMed  Google Scholar 

  53. Jagathesan R, et al. Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: implications for pharmacologic stress testing in coronary artery disease. J Nucl Cardiol. 2006;13(3):324–32.

    Article  PubMed  Google Scholar 

  54. Nagamachi S, Czernin J, Kim AS. Reproducibility of measurement of regional resting and hyperemic myocardial blood flow assessed with PET. J Nucl Med. 1996;37:1626–31.

    PubMed  CAS  Google Scholar 

  55. Siegrist PT, et al. Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET. J Nucl Med. 2006;47(9):1420–6.

    PubMed  Google Scholar 

  56. Jagathesan R, et al. Assessment of the long-term reproducibility of baseline and dobutamine-induced myocardial blood flow in patients with stable coronary artery disease. J Nucl Med. 2005;46(2):212–9.

    PubMed  Google Scholar 

  57. Klein R, et al. Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 pet and a highly automated analysis program. J Nucl Cardiol. 2010;17(4):600–16.

    Article  PubMed  Google Scholar 

  58. Kaufmann PA, Camici PG. Myocardial blood flow measurement by PET: technical aspects and clinical applications. J Nucl Med. 2005;46(1):75–88.

    PubMed  Google Scholar 

  59. Uren NG, et al. Relation between myocardial blood flow and the severity of coronary-artery stenosis. N Engl J Med. 1994;330(25):1782–8.

    Article  PubMed  CAS  Google Scholar 

  60. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007;356(8):830–40.

    Article  PubMed  CAS  Google Scholar 

  61. Higuchi T, et al. Effect of the angiotensin receptor blocker Valsartan on coronary microvascular flow reserve in moderately hypertensive patients with stable coronary artery disease. Microcirculation. 2007;14(8):805–12.

    Article  PubMed  CAS  Google Scholar 

  62. Camici PG. From microcirculation to cardiac event: protection with Preterax. J Hypertens Suppl. 2008;26(2):S8–10.

    Article  PubMed  CAS  Google Scholar 

  63. Naoumova RP, et al. Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2007;50(21):2051–8.

    Article  PubMed  CAS  Google Scholar 

  64. Neglia D, et al. Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy. Heart. 2007;93(7):808–13.

    Article  PubMed  CAS  Google Scholar 

  65. Kaski JC, et al. Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol. 1995;25(4):807–14.

    Article  PubMed  CAS  Google Scholar 

  66. Pupita G, et al. Long-term variability of angina pectoris and electrocardiographic signs of ischemia in syndrome X. Am J Cardiol. 1989;64(3):139–43.

    Article  PubMed  CAS  Google Scholar 

  67. Camici PG, et al. Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms. Circulation. 1992;86(1):179–86.

    Article  PubMed  CAS  Google Scholar 

  68. Cannon 3rd RO, et al. Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol. 1983;1(6):1359–73.

    Article  PubMed  Google Scholar 

  69. Rosen SD, Camici PG. Syndrome X: background, clinical aspects, pathophysiology & treatment. G Ital Cardiol. 1994;24(6):779–90.

    PubMed  CAS  Google Scholar 

  70. Rosen SD, Camici PG. Syndrome X: radionuclide studies of myocardial perfusion in patients with chest pain and normal coronary arteriograms. Eur J Nucl Med. 1992;19(5):311–4.

    Article  PubMed  CAS  Google Scholar 

  71. Vermeltfoort IA, et al. Is subendocardial ischemia present in patients with chest pain and normal coronary angiograms? a cardiovascular MR study. Eur Heart J. 2007;28(13):1554–8.

    Article  PubMed  Google Scholar 

  72. Vermeltfoort IA, et al. Association between anxiety disorder and the extent of ischemia observed in cardiac syndrome X. J Nucl Cardiol. 2009;16(3):405–10.

    Article  PubMed  CAS  Google Scholar 

  73. Vermeltfoort IA, et al. Definitions and incidence of cardiac syndrome X: review and analysis of clinical data. Clin Res Cardiol. 2010;99(8):475–81.

    Article  PubMed  CAS  Google Scholar 

  74. Marcus ML, et al. Alterations in the coronary circulation in hypertrophied ventricles. Circulation. 1987;75(1 Pt 2):I19–25.

    PubMed  CAS  Google Scholar 

  75. Laine H, et al. Early impairment of coronary flow reserve in young men with borderline hypertension. J Am Coll Cardiol. 1998;32(1):147–53.

    Article  PubMed  CAS  Google Scholar 

  76. Olsen MH, et al. Association between vascular dysfunction and reduced myocardial flow reserve in patients with hypertension: a LIFE substudy. J Hum Hypertens. 2004;18:445–52.

    Article  PubMed  CAS  Google Scholar 

  77. Quinones MJ, et al. Coronary vasomotor abnormalities in insulin-resistant individuals. Ann Intern Med. 2004;140(9):700–8.

    PubMed  Google Scholar 

  78. Prior JO, et al. Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. Circulation. 2005;111(18):2291–8.

    Article  PubMed  CAS  Google Scholar 

  79. Arbogast R, Bourassa MG. Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms. Comparison with patients having significant coronary artery disease. Am J Cardiol. 1973;32(3):257–63.

    Article  PubMed  CAS  Google Scholar 

  80. Maseri A, et al. Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol. 1991;17(2):499–506.

    Article  PubMed  CAS  Google Scholar 

  81. Lombardi F, et al. Global versus regional myocardial ischemia: differences in cardiovascular and sympathetic responses in cats. Cardiovasc Res. 1984;18(1):14–23.

    Article  PubMed  CAS  Google Scholar 

  82. Lanza GA, et al. Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy. Circulation. 1997;96(3):821–6.

    Article  PubMed  CAS  Google Scholar 

  83. Panting JR, et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med. 2002;346(25):1948–53.

    Article  PubMed  Google Scholar 

  84. Panza JA, et al. Investigation of the mechanism of chest pain in patients with angiographically normal coronary arteries using transesophageal dobutamine stress echocardiography. J Am Coll Cardiol. 1997;29(2):293–301.

    Article  PubMed  CAS  Google Scholar 

  85. Storey P, et al. Band artifacts due to bulk motion. Magn Reson Med. 2002;48(6):1028–36.

    Article  PubMed  Google Scholar 

  86. Di Bella EV, Parker DL, Sinusas AJ. On the dark rim artifact in dynamic contrast-enhanced MRI myocardial perfusion studies. Magn Reson Med. 2005;54(5):1295–9.

    Article  PubMed  Google Scholar 

  87. Rosen SD, et al. Coronary vasodilator reserve, pain perception, and sex in patients with syndrome X. Circulation. 1994;90(1):50–60.

    Article  PubMed  CAS  Google Scholar 

  88. Rosen SD, et al. Central nervous pathways mediating angina ­pectoris. Lancet. 1994;344(8916):147–50.

    Article  PubMed  CAS  Google Scholar 

  89. Neglia D, et al. Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension. J Hypertens. 2011;29(2):364–72.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Paolo G. Camici MD, FACC, FESC, FAHA, FRCP .

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Camici, P.G., Rimoldi, O.E. (2013). The Role of Positron Emission Tomography. In: Kaski, J., Eslick, G., Bairey Merz, C. (eds) Chest Pain with Normal Coronary Arteries. Springer, London. https://doi.org/10.1007/978-1-4471-4838-8_20

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