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Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis

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Abstract

Purpose

Absolute quantification of myocardial blood flow expands the diagnostic potential of PET for assessment of coronary artery disease. 82Rb has significantly contributed to increasing utilization of PET; however, clinical studies are still mostly analysed qualitatively. The aim of this study was to reevaluate the feasibility of 82Rb for flow quantification, using hybrid PET-CT in an animal model of coronary stenosis.

Methods

Nine dogs were prepared with experimental coronary artery stenosis. Dynamic PET was performed for 8 min after 82Rb(1480–1850 MBq) injection during adenosine-induced vasodilation. Microspheres were injected simultaneously for reference flow measurements. CT angiography was used to determine the myocardial regions related to the stenotic vessel. Two methods for flow calculation were employed: a two-compartment model including a spill-over term, and a simplified retention index.

Results

The two-compartment model data were in good agreement with microsphere flow (y = 0.84x + 0.20; r = 0.92, p<0.0001), although there was variability in the physiological flow range <3 ml/g per minute (y = 0.54x + 0.53; r = 0.53, p = 0.042). Results from the retention index also correlated well with microsphere flow (y = 0.47x + 0.52; r = 0.75, p = 0.0004). Error increased with higher flow, but the correlation was good in the physiological range (y = 0.62x + 0.29; r = 0.84, p = 0.0001).

Conclusion

Using current state-of-the-art PET-CT systems, quantification of myocardial blood flow is feasible with 82Rb. A simplified approach based on tracer retention is practicable in the physiological flow range. These results encourage further testing of the robustness and usefulness in the clinical context of cardiac hybrid imaging.

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References

  1. Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA, Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol 2006;13:24–33.

    Article  PubMed  Google Scholar 

  2. Machac J, Bacharach SL, Bateman TM, Bax JJ, Beanlands R, Bengel F, et al. Positron emission tomography myocardial perfusion and glucose metabolism imaging. J Nucl Cardiol 2006;13:e121–e151.

    Article  PubMed  Google Scholar 

  3. Gould KL, Pan T, Loghin C, Johnson NP, Guha A, Sdringola S. Frequent diagnostic errors in cardiac PET/CT due to misregistration of CT attenuation and emission PET images: a definitive analysis of causes, consequences, and corrections. J Nucl Med 2007;48:1112–1121.

    Article  PubMed  Google Scholar 

  4. Santana CA, Folks RD, Garcia EV, Verdes L, Sanyal R, Hainer J, et al. Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database. J Nucl Med 2007;48:1122–1128.

    Article  PubMed  Google Scholar 

  5. Sampson UK, Dorbala S, Limaye A, Kwong R, Di Carli MF. Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. J Am Coll Cardiol 2007;49:1052–1058.

    Article  PubMed  CAS  Google Scholar 

  6. Yoshinaga K, Chow BJ, Williams K, Chen L, deKemp RA, Garrard L, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography. J Am Coll Cardiol 2006;48:1029–1039.

    Article  PubMed  Google Scholar 

  7. Kaufmann PA. 82-Rubidium – the dawn of cardiac PET in Europe. Eur J Nucl Med Mol Imaging 2007;34:1963–1964.

    Article  PubMed  Google Scholar 

  8. Groves AM, Speechly-Dick ME, Dickson JC, Kayani I, Endozo R, Blanchard P, et al. Cardiac (82)rubidium PET/CT: initial European experience. Eur J Nucl Med Mol Imaging 2007;34:1965–1972.

    Article  PubMed  Google Scholar 

  9. Mullani NA, Goldstein RA, Gould KL, Marani SK, Fisher DJ, O’Brien HA Jr, et al. Myocardial perfusion with rubidium-82. I. Measurement of extraction fraction and flow with external detectors. J Nucl Med 1983;24:898–906.

    PubMed  CAS  Google Scholar 

  10. Mullani NA, Gould KL. First-pass measurements of regional blood flow with external detectors. J Nucl Med 1983;24:577–581.

    PubMed  CAS  Google Scholar 

  11. Huang SC, Williams BA, Krivokapich J, Araujo L, Phelps ME, Schelbert HR. Rabbit myocardial 82Rb kinetics and a compartmental model for blood flow estimation. Am J Physiol 1989;256:H1156–H1164.

    PubMed  CAS  Google Scholar 

  12. Herrero P, Markham J, Shelton ME, Weinheimer CJ, Bergmann SR. Noninvasive quantification of regional myocardial perfusion with rubidium-82 and positron emission tomography. Exploration of a mathematical model. Circulation 1990;82:1377–1386.

    PubMed  CAS  Google Scholar 

  13. Stewart RE, Schwaiger M, Molina E, Popma J, Gacioch GM, Kalus M, et al. Comparison of rubidium-82 positron emission tomography and thallium-201 SPECT imaging for detection of coronary artery disease. Am J Cardiol 1991;67:1303–1310.

    Article  PubMed  CAS  Google Scholar 

  14. Parkash R, deKemp RA, Ruddy TD, Kitsikis A, Hart R, Beauchesne L, et al. Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease. J Nucl Cardiol 2004;11:440–449.

    Article  PubMed  CAS  Google Scholar 

  15. Schindler TH, Nitzsche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, et al. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol 2005;45:1505–1512.

    Article  PubMed  Google Scholar 

  16. Schindler TH, Nitzsche E, Magosaki N, Brink I, Mix M, Olschewski M, et al. Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation. Heart 2003;89:517–526.

    Article  PubMed  CAS  Google Scholar 

  17. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899–1906.

    PubMed  CAS  Google Scholar 

  18. Herrero P, Markham J, Shelton ME, Bergmann SR. Implementation and evaluation of a two-compartment model for quantification of myocardial perfusion with rubidium-82 and positron emission tomography. Circ Res 1992;70:496–507.

    PubMed  CAS  Google Scholar 

  19. Yoshida K, Mullani N, Gould KL. Coronary flow and flow reserve by PET simplified for clinical applications using rubidium-82 or nitrogen-13-ammonia. J Nucl Med 1996;37:1701–1712.

    PubMed  CAS  Google Scholar 

  20. El Fakhri G, Sitek A, Guerin B, Kijewski MF, Di Carli MF, Moore SC. Quantitative dynamic cardiac 82Rb PET using generalized factor and compartment analyses. J Nucl Med 2005;46:1264–1271.

    PubMed  Google Scholar 

  21. Lortie M, Beanlands RS, Yoshinaga K, Klein R, Dasilva JN, deKemp RA. Quantification of myocardial blood flow with 82Rb dynamic PET imaging. Eur J Nucl Med Mol Imaging 2007;34:1765–1774.

    Article  PubMed  Google Scholar 

  22. Kemp BJ, Kim C, Williams JJ, Ganin A, Lowe VJ. NEMA NU 2–2001 performance measurements of an LYSO-based PET/CT system in 2D and 3D acquisition modes. J Nucl Med 2006;47:1960–1967.

    PubMed  Google Scholar 

  23. Lautamaki R, Brown TL, Merrill J, Bengel FM. CT-based attenuation correction in (82)Rb-myocardial perfusion PET-CT: incidence of misalignment and effect on regional tracer distribution. Eur J Nucl Med Mol Imaging 2008;35:305–310.

    Article  PubMed  Google Scholar 

  24. Schwaiger M, Ziegler S, Nekolla SG. PET/CT: challenge for nuclear cardiology. J Nucl Med 2005;46:1664–1678.

    PubMed  Google Scholar 

  25. Glover DK, Ruiz M, Edwards NC, Cunningham M, Simanis JP, Smith WH, et al. Comparison between 201Tl and 99mTc sestamibi uptake during adenosine-induced vasodilation as a function of coronary stenosis severity. Circulation 1995;91:813–820.

    PubMed  CAS  Google Scholar 

  26. Nekolla SG, Miethaner C, Nguyen N, Ziegler SI, Schwaiger M. Reproducibility of polar map generation and assessment of defect severity and extent assessment in myocardial perfusion imaging using positron emission tomography. Eur J Nucl Med 1998;25:1313–1321.

    Article  PubMed  CAS  Google Scholar 

  27. Machac J. Cardiac positron emission tomography imaging. Semin Nucl Med 2005;35:17–36.

    Article  PubMed  Google Scholar 

  28. Marwick TH, Shan K, Patel S, Go RT, Lauer MS. Incremental value of rubidium-82 positron emission tomography for prognostic assessment of known or suspected coronary artery disease. Am J Cardiol 1997;80:865–870.

    Article  PubMed  CAS  Google Scholar 

  29. Di Carli MF, Bianco-Batlles D, Landa ME, Kazmers A, Groehn H, Muzik O, et al. Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus. Circulation 1999;100:813–819.

    PubMed  Google Scholar 

  30. Laine H, Raitakari OT, Niinikoski H, Pitkanen OP, Iida H, Viikari J, et al. Early impairment of coronary flow reserve in young men with borderline hypertension. J Am Coll Cardiol 1998;32:147–153.

    Article  PubMed  CAS  Google Scholar 

  31. Sundell J, Laine H, Luotolahti M, Kalliokoski K, Raitakari O, Nuutila P, et al. Obesity affects myocardial vasoreactivity and coronary flow response to insulin. Obes Res 2002;10:617–624.

    Article  PubMed  CAS  Google Scholar 

  32. Pitkanen OP, Nuutila P, Raitakari OT, Porkka K, Iida H, Nuotio I, et al. Coronary flow reserve in young men with familial combined hyperlipidemia. Circulation 1999;99:1678–1684.

    PubMed  CAS  Google Scholar 

  33. Pitkanen OP, Raitakari OT, Niinikoski H, Nuutila P, Iida H, Voipio-Pulkki LM, et al. Coronary flow reserve is impaired in young men with familial hypercholesterolemia. J Am Coll Cardiol 1996;28:1705–1711.

    Article  PubMed  CAS  Google Scholar 

  34. Momose M, Abletshauser C, Neverve J, Nekolla SG, Schnell O, Standl E, et al. Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus. Eur J Nucl Med Mol Imaging 2002;29:1675–1679.

    Article  PubMed  Google Scholar 

  35. Dorbala S, Hassan A, Heinonen T, Schelbert HR, Di Carli MF. Coronary vasodilator reserve and Framingham risk scores in subjects at risk for coronary artery disease. J Nucl Cardiol 2006;13:761–767.

    Article  PubMed  Google Scholar 

  36. Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA, et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation 2002;106:653–658.

    Article  PubMed  Google Scholar 

  37. Higuchi T, Abletshauser C, Nekolla SG, Schwaiger M, Bengel FM. Effect of the angiotensin receptor blocker Valsartan on coronary microvascular flow reserve in moderately hypertensive patients with stable coronary artery disease. Microcirculation 2007;14:805–812.

    Article  PubMed  CAS  Google Scholar 

  38. Lautamaki R, Airaksinen KE, Seppanen M, Toikka J, Harkonen R, Luotolahti M, et al. Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease. Diabetes 2006;55:511–516.

    Article  PubMed  CAS  Google Scholar 

  39. Guethlin M, Kasel AM, Coppenrath K, Ziegler S, Delius W, Schwaiger M. Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin. Circulation 1999;99:475–481.

    PubMed  CAS  Google Scholar 

  40. Slart RH, Bax JJ, de Jong RM, de Boer J, Lamb HJ, Mook PH, et al. Comparison of gated PET with MRI for evaluation of left ventricular function in patients with coronary artery disease. J Nucl Med 2004;45:176–182.

    PubMed  Google Scholar 

  41. Chander A, Brenner M, Lautamaki R, Voicu C, Merrill J, Bengel FM. Comparison of measures of left ventricular function from electrocardiographically gated 82Rb PET with contrast-enhanced CT ventriculography: a hybrid PET-CT analysis. J Nucl Med 2008;49:1643–1650.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Martin Lodge for his excellent technical assistance. The study was supported by Donald W. Reynolds Foundation. Dr. Lautamäki is supported by grants from The Finnish Cardiac Research Foundation, The Finnish Medical Foundation, The Instrumentarium Foundation for Science, and by the Bracco/SNM Research Fellowship in Cardiovascular Molecular Imaging.

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Authors and Affiliations

  1. Department of Radiology, Division of Nuclear Medicine, Johns Hopkins Medical Institutions, 601 N Caroline St, Baltimore, MD, 21210, USA

    Riikka Lautamäki, Takahiro Higuchi, Jennifer Merrill, Corina Voicu & Frank M. Bengel

  2. Department of Medicine, Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Richard T. George, Kakuya Kitagawa, Anthony DiPaula, João A. C. Lima & Albert C. Lardo

  3. Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Albert C. Lardo

  4. Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technischen Universität München, Munich, Germany

    Stephan G. Nekolla

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  1. Riikka Lautamäki
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Correspondence to Frank M. Bengel.

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Drs. Lautamäki and George contributed equally to this study.

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Lautamäki, R., George, R.T., Kitagawa, K. et al. Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis. Eur J Nucl Med Mol Imaging 36, 576–586 (2009). https://doi.org/10.1007/s00259-008-0972-1

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  • DOI: https://doi.org/10.1007/s00259-008-0972-1

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