Skip to main content
SpringerLink
Log in

15-O-water myocardial flow reserve PET and CT angiography by full hybrid PET/CT as a potential alternative to invasive angiography

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89–97%) versus 76% (64–88%), p = 0.0004; positive predictive value 71% (55–86%) versus 51% (37–65%), p = 0.0001; accuracy 90% (84–95%) versus 77% (69–84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Johnson NP, Kirkeeide RL, Gould KL (2012) Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology? JACC Cardiovasc Imaging 5:193–202

    Article  Google Scholar 

  2. Kajander S, Joutsiniemi E, Saraste M, Pietila M, Ukkonen H, Saraste A et al (2010) Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease. Circulation 122:603–613

    Article  CAS  Google Scholar 

  3. Danad I, Raijmakers PG, Appelman YE, Harms HJ, de Haan S, van den Oever ML et al (2013) Hybrid imaging using quantitative H215O PET and CT-based coronary angiography for the detection of coronary artery disease. J Nucl Med 54:55–63

    Article  CAS  Google Scholar 

  4. Thomassen A, Petersen H, Diederichsen AC, Mickley H, Jensen LO, Johansen A et al (2013) Hybrid CT angiography and quantitative 15O-water PET for assessment of coronary artery disease: comparison with quantitative coronary angiography. Eur J Nucl Med Mol Imaging 40:1894–1904

    Article  Google Scholar 

  5. Danad I, Raijmakers PG, Driessen RS, Leipsic J, Raju R, Naoum C et al (2017) Comparison of coronary CT angiography, SPECT, PET, and hybrid imaging for diagnosis of ischemic heart disease determined by fractional flow reserve. JAMA Cardiol 2:1100–1107

    Article  Google Scholar 

  6. Joutsiniemi E, Saraste A, Pietila M, Maki M, Kajander S, Ukkonen H et al (2014) Absolute flow or myocardial flow reserve for the detection of significant coronary artery disease? Eur Heart J Cardiovasc Imaging 15:659–665

    Article  Google Scholar 

  7. Diamond GA, Forrester JS (1979) Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med 300:1350–1358

    Article  CAS  Google Scholar 

  8. Nesterov SV, Han C, Maki M, Kajander S, Naum AG, Helenius H et al (2009) Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas). Eur J Nucl Med Mol Imaging 36:1594–1602

    Article  Google Scholar 

  9. Harms HJ, Nesterov SV, Han C, Danad I, Leonora R, Raijmakers PG et al (2014) Comparison of clinical non-commercial tools for automated quantification of myocardial blood flow using oxygen-15-labelled water PET/CT. Eur Heart J Cardiovasc Imaging 15:431–441

    Article  Google Scholar 

  10. Thomassen A, Petersen H, Johansen A, Braad PE, Diederichsen AC, Mickley H et al (2015) Quantitative myocardial perfusion by O-15-water PET: individualized vs. standardized vascular territories. Eur Heart J Cardiovasc Imaging 16:970–976

    PubMed  Google Scholar 

  11. Searle SR, Casella G, McCulloch CE (1992) Variance components. Wiley, New York

    Book  Google Scholar 

  12. Rabe-Hesketh S, Skrondal A (2012) Multilevel and longitudinal modeling using Stata, 3rd edn. Stata Press Publication, College Station

    Google Scholar 

  13. Miller DP, editor Obtain robust confidence intervals for any statistic. Proceedings of the Twenty-Ninth Annual SAS (R) User Group International Conference 2004

  14. Steichen TJCN (2008) Concordance correlation coefficient. Stata Tech Bull 35–39

  15. Dai N, Zhang X, Zhang Y, Hou L, Li W, Fan B et al (2016) Enhanced diagnostic utility achieved by myocardial blood analysis: a meta-analysis of noninvasive cardiac imaging in the detection of functional coronary artery disease. Int J Cardiol 221:665–673

    Article  Google Scholar 

  16. Danad I, Uusitalo V, Kero T, Saraste A, Raijmakers PG, Lammertsma AA et al (2014) Quantitative assessment of myocardial perfusion in the detection of significant coronary artery disease: cutoff values and diagnostic accuracy of quantitative [(15)O]H2O PET imaging. J Am Coll Cardiol 64:1464–1475

    Article  Google Scholar 

  17. Namdar M, Hany TF, Koepfli P, Siegrist PT, Burger C, Wyss CA et al (2005) Integrated PET/CT for the assessment of coronary artery disease: a feasibility study. J Nucl Med 46:930–935

    PubMed  Google Scholar 

  18. Gaemperli O, Schepis T, Valenta I, Husmann L, Scheffel H, Duerst V et al (2007) Cardiac image fusion from stand-alone SPECT and CT: clinical experience. J Nucl Med 48:696–703

    Article  Google Scholar 

  19. Klein R, Renaud JM, Ziadi MC, Thorn SL, Adler A, Beanlands RS et al (2010) 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 17:600–616

    Article  Google Scholar 

  20. Javadi MS, Lautamaki R, Merrill J, Voicu C, Epley W, McBride G et al (2010) Definition of vascular territories on myocardial perfusion images by integration with true coronary anatomy: a hybrid PET/CT analysis. J Nucl Med 51:198–203

    Article  Google Scholar 

  21. El Fakhri G, Kardan A, Sitek A, Dorbala S, Abi-Hatem N, Lahoud Y et al (2009) Reproducibility and accuracy of quantitative myocardial blood flow assessment with (82)Rb PET: comparison with (13)N-ammonia PET. J Nucl Med 50:1062–1071

    Article  Google Scholar 

  22. Knesaurek K, Machac J, Zhang Z (2009) Repeatability of regional myocardial blood flow calculation in 82Rb PET imaging. BMC Med Phys 9:2

    Article  Google Scholar 

  23. Schindler TH, Zhang XL, Prior JO, Cadenas J, Dahlbom M, Sayre J et al (2007) Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with (13)N-ammonia and PET. Eur J Nucl Med Mol Imaging 34:1178–1188

    Article  Google Scholar 

  24. Sawada S, Muzik O, Beanlands RS, Wolfe E, Hutchins GD, Schwaiger M (1995) Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography. J Nucl Cardiol 2:413–422

    Article  CAS  Google Scholar 

  25. Adachi I, Gaemperli O, Valenta I, Schepis T, Siegrist PT, Treyer V et al (2007) Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: validation of a new fast factor analysis. J Nucl Cardiol 14:698–705

    Article  Google Scholar 

  26. Kaufmann PA, Gnecchi-Ruscone T, Yap JT, Rimoldi O, Camici PG (1999) Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. J Nucl Med 40:1848–1856

    CAS  PubMed  Google Scholar 

  27. de Vet HC, Terwee CB, Knol DL, Bouter LM (2006) When to use agreement versus reliability measures. J Clin Epidemiol 59:1033–1039

    Article  Google Scholar 

  28. Kottner J, Audige L, Brorson S, Donner A, Gajewski BJ, Hrobjartsson A et al (2011) Guidelines for reporting reliability and agreement studies (GRRAS) were proposed. J Clin Epidemiol 64:96–106

    Article  Google Scholar 

  29. Stuijfzand WJ, Uusitalo V, Kero T, Danad I, Rijnierse MT, Saraste A et al (2015) Relative flow reserve derived from quantitative perfusion imaging may not outperform stress myocardial blood flow for identification of hemodynamically significant coronary artery disease. Circ Cardiovasc Imaging 8:e002400

    Article  Google Scholar 

  30. Williams MC, Mirsadraee S, Dweck MR, Weir NW, Fletcher A, Lucatelli C et al (2017) Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve. Eur Radiol 27:1114–1124

    Article  Google Scholar 

  31. Bergmann SR, Fox KA, Rand AL, McElvany KD, Welch MJ, Markham J et al (1984) Quantification of regional myocardial blood flow in vivo with H215O. Circulation 70:724–733

    Article  CAS  Google Scholar 

  32. Johnson NP, Gould KL (2011) Physiological basis for angina and ST-segment change PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve. JACC Cardiovasc Imaging 4:990–998

    Article  Google Scholar 

  33. Morton G, Chiribiri A, Ishida M, Hussain ST, Schuster A, Indermuehle A et al (2012) Quantification of absolute myocardial perfusion in patients with coronary artery disease: comparison between cardiovascular magnetic resonance and positron emission tomography. J Am Coll Cardiol 60:1546–1555

    Article  Google Scholar 

  34. Naya M, Murthy VL, Taqueti VR, Foster CR, Klein J, Garber M et al (2014) Preserved coronary flow reserve effectively excludes high-risk coronary artery disease on angiography. J Nucl Med 55:248–255

    Article  Google Scholar 

  35. Fiechter M, Ghadri JR, Gebhard C, Fuchs TA, Pazhenkottil AP, Nkoulou RN et al (2012) Diagnostic value of 13N-ammonia myocardial perfusion PET: added value of myocardial flow reserve. J Nucl Med 53:1230–1234

    Article  CAS  Google Scholar 

  36. Sciagra R, Passeri A, Bucerius J, Verberne HJ, Slart RH, Lindner O et al (2016) Clinical use of quantitative cardiac perfusion PET: rationale, modalities and possible indications. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM). Eur J Nucl Med Mol Imaging 43:1530–1545

    Article  Google Scholar 

  37. Lee JM, Kim CH, Koo BK, Hwang D, Park J, Zhang J et al (2016) Integrated myocardial perfusion imaging diagnostics improve detection of functionally significant coronary artery stenosis by 13N-ammonia positron emission tomography. Circ Cardiovasc Imaging 9:e004768

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, 5000, Odense, Denmark

    Anders Thomassen, Poul-Erik Braad, Kasper T. Pedersen, Henrik Petersen, Allan Johansen, Oke Gerke & Poul F. Høilund-Carlsen

  2. Department of Cardiology, Odense University Hospital, Odense, Denmark

    Axel C. P. Diederichsen, Hans Mickley & Lisette O. Jensen

  3. Turku University Hospital and University of Turku, Turku, Finland

    Juhani Knuuti

Authors
  1. Anders Thomassen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Poul-Erik Braad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kasper T. Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henrik Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Allan Johansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Axel C. P. Diederichsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hans Mickley
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lisette O. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Juhani Knuuti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Oke Gerke
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Poul F. Høilund-Carlsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anders Thomassen.

Ethics declarations

Conflict of interest

Authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thomassen, A., Braad, PE., Pedersen, K.T. et al. 15-O-water myocardial flow reserve PET and CT angiography by full hybrid PET/CT as a potential alternative to invasive angiography. Int J Cardiovasc Imaging 34, 2011–2022 (2018). https://doi.org/10.1007/s10554-018-1420-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-018-1420-3

Keywords

Search

Navigation