Skip to main content
SpringerLink
Log in

Feasibility and operator variability of myocardial blood flow and reserve measurements with 99mTc-sestamibi quantitative dynamic SPECT/CT imaging

  • Original Article
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Purpose

Myocardial blood flow (MBF) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging. This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with 99mTc-sestamibi (MIBI) dynamic SPECT imaging using a standard dual-head SPECT camera.

Methods

Twenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition. Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest (ROI) were defined semi-automatically. A compartmental model was fitted to these ROI-sampled time-activity-curves, and flow-dependent MIBI extraction correction was applied to derive regional MBF values. Myocardial flow reserve (MFR) was estimated as stress/rest MBF ratio. MBF and MFR in low and high risk populations were evaluated for ability to detect disease. Images were each processed twice (≥7 days apart) by one expert and one novice operator to evaluate intra- and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories.

Results

Mean rest flow, stress flow, and MFR values were 0.83, 1.82 mL·minute−1·g−1, and 2.45, respectively. For stress/rest MFR, the inter-operator reproducibility was r 2 = 0.86 with RPC = 1.1. Stress MBF and MFR were significantly reduced (P < .05) in high risk (n = 9) vs low risk populations (n = 19), indicating ability to detect disease. For expert and novice operators very good intra-operator correlations of r 2 = 0.98 and 0.95 (n = 168, P < .001) were observed for combined rest and stress regional flow values. Bland-Altman reproducibility coefficients (RPC) were 0.25 and 0.47 mL·minute−1·g−1 for the expert and novice operators, respectively (P < .001). Inter-operator correlation was r 2 = 0.91 and Bland-Altman RPC = 0.58 mL·minute−1·g−1 (n = 336).

Conclusions

MBF and reserve measurements using 99mTc-sestamibi on a traditional, two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible, warranting further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Uren NG, Marraccini P, Gistri R, de Silva R, Camici PG. Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. J Am Coll Cardiol 1993;3:650-8.

    Article  Google Scholar 

  2. Gould KL. Does coronary flow trump coronary anatomy? JACC Cardiovasc Imaging 2009;8:1009-23.

    Article  Google Scholar 

  3. Yoshinaga K, Katoh C, Noriyasu K, Iwado Y, Furuyama H, Ito Y, et al. Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET. J Nucl Cardiol 2003;3:275-83.

    Article  Google Scholar 

  4. Parkash R, deKemp RA, Ruddy TD, Kitsikis A, Hart R, Beauschene L, et al. Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease. J Nucl Cardiol 2004;4:440-9.

    Article  Google Scholar 

  5. Ziadi MC, deKemp RA, Williams K, Guo A, Renaud JM, Chow BJ, et al. Does quantification of myocardial flow reserve using rubidium-82 positron emission tomography facilitate detection of multivessel coronary artery disease? J Nucl Cardiol 2012;4:670-80.

    Article  Google Scholar 

  6. Zeintl J, Vija AH, Yahil A, Hornegger J, Kuwert T. Quantitative accuracy of clinical 99mTc SPECT/CT using ordered-subset expectation maximization with 3-dimensional resolution recovery, attenuation, and scatter correction. J Nucl Med 2010;6:921-8.

    Article  Google Scholar 

  7. Bailey DL, Willowson KP. An evidence-based review of quantitative SPECT imaging and potential clinical applications. J Nucl Med 2013;1:83-9.

    Article  Google Scholar 

  8. Gulberg GT, Reutter BW, Sitek A, Maltz JS, Budinger TF. Dynamic single photon emission tomography: Basic principles and cardiac applications. Phys Med Biol 2010;55:R111-91.

    Article  Google Scholar 

  9. Klein R, Beanlands RS, deKemp RA. Quantification of myocardial blood flow and flow reserve: Technical aspects. J Nucl Cardiol 2010;17:555-70.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. Herrero P, Markham J, Shelton M, Weinheimer C, Bergmann S. Noninvasive quantification of regional myocardial perfusion with rubidium-82 and positron emission tomography. Exploration of a mathematical model. Circulation 1990;82:1377-86.

    CAS  Google Scholar 

  12. Hutchins GD, Schwaiger M, Rosenspire KC, Krivokapich J, Schelbert H, Kuhl DE. 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;5:1032-42.

    Article  Google Scholar 

  13. Iida H, Kanno I, Takahashi A, Miura S, Murakami MT, Takahashi K, et al. Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect. Circulation 1988;78:104-15.

    Article  CAS  PubMed  Google Scholar 

  14. Iida H, Yokoyama I, Agostini D, Banno T, Kato T, Ito K, et al. Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: A multicentre evaluation in Japan. Eur J Nucl Med 2000;21:192-201.

    Article  Google Scholar 

  15. Katoh C, Yoshinaga K, Klein R, Kasai K, Tomiyama Y, Manabe O, et al. Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model. J Nucl Cardiol 2012;4:763-74.

    Article  Google Scholar 

  16. Lortie M, Beanlands RSB, Yoshinaga K, Klein R, Da Silva JN, deKemp RA. Quantification of myocardial blood flow with 82Rb dynamic PET imaging. Eur J Nucl Med Mol Imaging 2007;11:1765-74.

    Article  Google Scholar 

  17. Nekolla SG, Miethaner C, Nguyen N, Ziegler SI, Schwaiger M. Reproducibility of polar map generation and assessment of defect severity and extent in myocardial perfusion imaging using positron emission tomography. Eur J Nucl Med 1998;9:1313-21.

    Article  Google Scholar 

  18. Tahari AK, Lee A, Rajaram M, Fukushima K, Lodge MA, Lee BC, et al. Absolute myocardial blood flow quantification with 82-Rb PET/CT: Comparison of different software packages and methods. Eur J Nucl Med Mol Imaging 2014;41:126-35.

    Article  PubMed  Google Scholar 

  19. deKemp R, Declerck J, Klein R, Pan XB, Nakazato R, Tonge C, et al. Multisoftware reproducibility study of stress and rest myocardial blood flow assessed with 3D dynamic PET/CT and a 1-tissue-compartment model of 82Rb kinetics. J Nucl Med 2013;54:571-7.

    Article  CAS  PubMed  Google Scholar 

  20. Ben-Haim S, Murthy VL, Breault C, Allie R, Sitek A, Nathaniel R, et al. Quantification of myocardial perfusion reserve using dynamic SPECT imaging in humans: A feasibility study. J Nucl Med 2013;54:873-9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Brambilla M, Cannillo B, Dominietto M, Leva L, Secco C, Inglese E. Characterization of ordered-subsets expectation maximization with 3D post-reconstruction Gauss filtering and comparison with filtered backprojection in 99mTc SPECT. Ann Nucl Med 2005;19:75-82.

    Article  PubMed  Google Scholar 

  22. Seret A, Forthomme J. Comparison of different types of commercial filtered backprojection and ordered-subset expectation maximization SPECT reconstruction software. J Nucl Med Technol 2009;37:179-87.

    Article  PubMed  Google Scholar 

  23. Klein R, Renaud JM, Ziadi MC, Thorn SL, Adler A, Beanlands RS, et al. Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 PET and highly automated analysis program. J Nucl Cardiol 2010;17:600-16.

    Article  PubMed  Google Scholar 

  24. Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging. ACC/AHA practice guidelines. Circulation 2013;108:1404–18. http://circ.ahajournals.org/content/108/11/1404.full.

  25. Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Gropler RJ, et al. ASNC imaging guidelines for nuclear cardiology procedures. PET myocardial perfusion and metabolism clinical imaging. J Nucl Cardiol 2009. http://www.asnc.org/imageuploads/imagingguidelinespetjuly2009.pdf.

  26. Efseaff M, Klein R, Beanlands RSB, deKemp RA. Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging. J Nucl Cardiol 2012;19:997-1006.

    Article  PubMed  Google Scholar 

  27. Leppo JA, Meerdink DJ. Comparison of the myocardial uptake of a technetium-labeled isonitrile analogue and thallium. Circ Res 1989;65:632-9.

    Article  CAS  PubMed  Google Scholar 

  28. Nagamachi S, Czernin J, Kim AS, et al. Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. J Nucl Med 1996;10:1626-31.

    Google Scholar 

  29. Schindler TH, Zhang XL, Prior JO, Cadenas J, Dahlbom M, Sayre J, et al. Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with 13N-ammonia and PET. Eur J Nucl Med Mol Imaging 2007;34:1178-88.

    Article  PubMed  Google Scholar 

  30. Nichols K, DePuey EG, Gooneratne N, Salensky H, Friedman M, Cochoff S. First-pass ventricular ejection fraction using a single-crystal nuclear camera. J Nucl Med 1994;35:1292-300.

    CAS  PubMed  Google Scholar 

  31. Nichols K, DePuey EG, Rozanski A. First-pass radionuclide angiocardiography with single-crystal gamma cameras. J Nucl Cardiol 1997;4(1):61-73.

    Article  CAS  PubMed  Google Scholar 

  32. Johnson NP, Gould KL. Integrating noninvasive absolute flow, coronary flow reserve, and ischemic thresholds into a comprehensive map of physiological severity. J Am Coll Cardiol Imaging 2012;4:430-40.

    Article  Google Scholar 

  33. Ziadi MC, Beanlands RSB. The clinical utility of assessing myocardial blood flow using positron emission tomography. J Nucl Cardiol 2010;4:571-81.

    Article  Google Scholar 

  34. Ziadi MC, deKemp RA, Williams KA, Guo A, Chow BJ, Renaud JM, et al. Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia. J Am Coll Cardiol 2011;58:740-8.

    Article  PubMed  Google Scholar 

  35. Prior JO, Allenbach G, Valenta I, Kosinski M, Burger C, Verdun FR, et al. Quantification of myocardial blood flow with 82Rb positron emission tomography: Clinical validation with 15O-water. Eur J Nucl Med Mol Imaging 2012;39:1037-47.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Nestrov SV, Han C, Mäki M, Kajander S, Naum AG, Helenius H, et al. Myocardial perfusion quantification with 15O-labeled water PET: High reproducibility of the new cardiac analysis software Carimas™). Eur J Nucl Med Mol Imaging 2009;10:1594-602.

    Article  Google Scholar 

  37. Taylor R. Interpretation of the correlation coefficient: A basic review. J Diagn Med Sonogr 1990;6:35-9.

    Article  Google Scholar 

  38. Bocher M, Blevis IM, Tsukerman L, Shrem Y, Kovalski G, Volokh L. A fast cardiac gamma camera with dynamic SPECT capabilities: Design, system validation and future potential. Eur J Nucl Med Mol Imaging 2010;37:1887-902.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Gerwitz H. PET measurement of adenosine stimulated absolute myocardial blood flow for physiological assessment of the coronary circulation. J Nucl Cardiol 2012;2:347-54.

    Article  Google Scholar 

  40. Wyss CA, Koepfli P, Mikolajczyk K, Burger C, von Schulthess GK, Kaufmann PA. Bicycle exercise stress in PET for assessment of coronary flow reserve: Repeatability and comparison with adenosine stress. J Nucl Med 2003;2:146-54.

    Google Scholar 

  41. Crane P, Laliberte R, Heminway S, Thoolen M, Orlandi C. Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention. Eur J Nucl Med 1993;20:20-5.

    Article  CAS  PubMed  Google Scholar 

  42. Hurwitz GA, Ghali SK, Husni M, Slomka PJ, Mattar AG, Reid RH, et al. Pulmonary uptake of technetium-99m-sestamibi induced by dipyridamole-based stress or exercise. J Nucl Med 1998;39:339-45.

    CAS  PubMed  Google Scholar 

  43. El Fakhri G, Kardan A, Sitek A, Dorbala S, Abi-Hatem N, et al. Reproducibility and accuracy of quantitative myocardial blood flow assessment with 82Rb PET: Comparison with 13N-ammonia PET. J Nucl Med 2009;7:1062-71.

    Article  Google Scholar 

  44. Renaud JM, Da Silva JN, Beanlands RSB, deKemp RA. Characterizing the normal range of myocardial blood flow with 82rubidium and 13N-ammonia PET imaging. J Nucl Cardiol 2013;20:578-91.

    Article  PubMed  Google Scholar 

  45. Kaufmann PA, Gnecchi-Ruscone T, Yap JT, Rimoldi O, Camici PG. Assessment of reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. J Nucl Med 1999;11:1848-56.

    Google Scholar 

  46. Orton EJ, Al-Harbi I, Klein R, Beanlands R, deKemp R, Wells RG. Prevalence of extra-cardiac interference in 82Rb PET myocardial perfusion imaging. J Nucl Med 2013;54:1689.

    Article  Google Scholar 

Download references

Acknowledgments

Research grant support was provided from Chang Bing Show Chwan Memorial Hospital (NO: CBSH-10010002).

Disclosure

Ran Klein receives license revenues from the sale of FlowQuant. Consultant for Jubilant-DraxImage and receives royalties from rubidium generator technology licenses. Robert deKemp receives license revenues from the sale of FlowQuant. Consultant for Jubilant-DraxImage and receives royalties from rubidium generator technology licenses. Guang-Uei Hung, Tao-Cheng Wu, Wen-Sheng Huang, Dianfu Li, Bailing Hsu have nothing to declare.

Author information

Authors and Affiliations

  1. University of Ottawa Heart Institute, Cardiac PET Centre, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada

    Ran Klein PhD & Robert A. deKemp PhD

  2. Department of Nuclear Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan

    Guang-Uei Hung MD

  3. Section of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Tao-Cheng Wu MD

  4. Departments of Medical Research & Nuclear Medicine, Changhua Christian Hospital, Changhua, Taiwan

    Wen-Sheng Huang MD

  5. Section of Nuclear Cardiology, Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

    Dianfu Li MD, PhD

  6. Nuclear Science and Engineering Institute, University of Missouri-Columbia, Columbia, MO, 65211, USA

    Bailing Hsu PhD

Authors
  1. Ran Klein PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guang-Uei Hung MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao-Cheng Wu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-Sheng Huang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dianfu Li MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert A. deKemp PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bailing Hsu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ran Klein PhD.

Additional information

Ran Klein, Guang-Uei Hung, and Bailing Hsu have contributed equally to this study.

See related editorials, doi:10.1007/s12350-014-9996-z and doi:10.1007/s12350-014-0002-6.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klein, R., Hung, GU., Wu, TC. et al. Feasibility and operator variability of myocardial blood flow and reserve measurements with 99mTc-sestamibi quantitative dynamic SPECT/CT imaging. J. Nucl. Cardiol. 21, 1075–1088 (2014). https://doi.org/10.1007/s12350-014-9971-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-014-9971-8

Keywords

Search

Navigation