Skip to main content
Top
Published in: Journal of Nuclear Cardiology 3/2018

Open Access 01-06-2018 | Original Article

Consistent tracer administration profile improves test–retest repeatability of myocardial blood flow quantification with 82Rb dynamic PET imaging

Authors: Ran Klein, PhD, Adrian Ocneanu, MSc, Jennifer M. Renaud, MSc, Maria C. Ziadi, MD, Rob S. B. Beanlands, MD, Robert A. deKemp, PhD

Published in: Journal of Nuclear Cardiology | Issue 3/2018

Login to get access

Abstract

Objectives

Quantification of myocardial blood flow (MBF) and stress/rest flow reserve is used increasingly to diagnose multi-vessel coronary artery disease and micro-vascular disease with PET imaging. However, variability in the measurements may limit physician confidence to direct revascularization therapies based on specific threshold values. This study evaluated the effects of rubidium-82 (82Rb) tracer injection profile using a constant-activity-rate (CA) vs a constant-flow-rate (CF) infusion to improve test–retest repeatability of MBF measurements.

Method

22 participants underwent single-session 82Rb dynamic PET imaging during rest and dipyridamole stress using one of 2 test–retest infusion protocols: CA–CA (n = 12) or CA–CF (n = 10). MBF was quantified using a single-tissue-compartment model (1TCM) and a simplified retention model (SRM). Non-parametric test–retest repeatability coefficients (RPCnp) were compared between groups. Myocardium-to-blood contrast and signal-to-noise ratios of the late uptake images (2 to 6 minutes) were also compared to evaluate standard myocardial perfusion image (MPI) quality.

Results

MBF values in the CA–CA group were more repeatable (smaller RPCnp) than the CA–CF group using the 1TCM at rest alone, rest and stress combined, and stress/rest reserve (21% vs 36%, 16% vs 19%, and 20% vs 27%, P < 0.05, respectively), and using the SRM at Rest and Stress alone, Rest and Stress combined, and stress/rest reserve (21% vs 38%, 15% vs 25%, 22% vs 38%, and 23% vs 49%, P < 0.05, respectively). In terms of image quality, myocardium-to-blood contrast and signal-to-noise ratios were not significantly different between groups.

Conclusions

Constant-activity-rate ‘square-wave’ infusion of 82Rb produces more repeatable tracer injection profiles and decreases the test–retest variability of MBF measurements, when compared to a constant-flow-rate ‘bolus’ administration of 82Rb, especially with SRM, and without compromising standard MPI quality.
Appendix
Available only for authorised users
Literature
1.
go back to reference El Fakhri G, Kardan A, Sitek A, Dorbala S, Abi-Hatem N, Lahoud Y, et al Reproducibility and accuracy of quantitative myocardial blood flow assessment with 82Rb PET: Comparison with 13N-ammonia PET. J Nucl Med 2009;50:1062–71.CrossRefPubMedPubMedCentral El Fakhri G, Kardan A, Sitek A, Dorbala S, Abi-Hatem N, Lahoud Y, et al Reproducibility and accuracy of quantitative myocardial blood flow assessment with 82Rb PET: Comparison with 13N-ammonia PET. J Nucl Med 2009;50:1062–71.CrossRefPubMedPubMedCentral
2.
go back to reference Nesterov SV, Deshayes E, Sciagrà R, Settimo L, Declerck JM, Pan XB, et al Quantification of myocardial blood flow in absolute terms using (82)Rb PET imaging: The RUBY-10 Study. JACC Cardiovasc Imaging 2014;7:1119–27.CrossRefPubMedPubMedCentral Nesterov SV, Deshayes E, Sciagrà R, Settimo L, Declerck JM, Pan XB, et al Quantification of myocardial blood flow in absolute terms using (82)Rb PET imaging: The RUBY-10 Study. JACC Cardiovasc Imaging 2014;7:1119–27.CrossRefPubMedPubMedCentral
3.
go back to reference Ziadi MC, deKemp RA, Williams KA, Guo A, Chow BJW, 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.CrossRefPubMed Ziadi MC, deKemp RA, Williams KA, Guo A, Chow BJW, 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.CrossRefPubMed
4.
go back to reference Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, et al Improved cardiac risk assessment with non-invasive measures of coronary flow reserve. Circulation. 2011;124:2215–24.CrossRefPubMedPubMedCentral Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, et al Improved cardiac risk assessment with non-invasive measures of coronary flow reserve. Circulation. 2011;124:2215–24.CrossRefPubMedPubMedCentral
5.
go back to reference 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 a highly automated analysis program. J Nucl Cardiol. 2010;17:600–16.CrossRefPubMed 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 a highly automated analysis program. J Nucl Cardiol. 2010;17:600–16.CrossRefPubMed
6.
go back to reference deKemp RA, Declerck J, Klein R, Pan X-B, 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.CrossRefPubMed deKemp RA, Declerck J, Klein R, Pan X-B, 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.CrossRefPubMed
7.
go back to reference Kolthammer JA, Muzic RF. Optimized dynamic framing for PET-based myocardial blood flow estimation. Phys Med Biol 2013;58:5783–801.CrossRefPubMed Kolthammer JA, Muzic RF. Optimized dynamic framing for PET-based myocardial blood flow estimation. Phys Med Biol 2013;58:5783–801.CrossRefPubMed
8.
go back to reference Klein R, Beanlands RS, Wassenaar RW, Thorn SL, Lamoureux M, DaSilva JN, et al Kinetic model-based factor analysis of dynamic sequences for 82-rubidium cardiac positron emission tomography. Med Phys 2010;37:3995–4010.CrossRefPubMed Klein R, Beanlands RS, Wassenaar RW, Thorn SL, Lamoureux M, DaSilva JN, et al Kinetic model-based factor analysis of dynamic sequences for 82-rubidium cardiac positron emission tomography. Med Phys 2010;37:3995–4010.CrossRefPubMed
9.
go back to reference Raylman RR, Caraher JM, Hutchins GD. Sampling requirements for dynamic cardiac PET studies using image-derived input functions. J Nucl Med 1993;34:440–7.PubMed Raylman RR, Caraher JM, Hutchins GD. Sampling requirements for dynamic cardiac PET studies using image-derived input functions. J Nucl Med 1993;34:440–7.PubMed
10.
go back to reference Efseaff M, Klein R, Ziadi MC, Beanlands RS, deKemp RA. Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging. J Nucl Cardiol 2012;19:997–1006.CrossRefPubMed Efseaff M, Klein R, Ziadi MC, Beanlands RS, deKemp RA. Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging. J Nucl Cardiol 2012;19:997–1006.CrossRefPubMed
11.
go back to reference Sdringola S, Johnson NP, Kirkeeide RL, Cid E, Gould KL. Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers. JACC Cardiovasc Imaging. 2011;4:402–12.CrossRefPubMed Sdringola S, Johnson NP, Kirkeeide RL, Cid E, Gould KL. Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers. JACC Cardiovasc Imaging. 2011;4:402–12.CrossRefPubMed
12.
go back to reference Johnson NP, Gould KL. Regadenoson versus dipyridamole hyperemia for cardiac PET imaging. J Am Coll Cardiol Imaging 2015;8:438–47.CrossRef Johnson NP, Gould KL. Regadenoson versus dipyridamole hyperemia for cardiac PET imaging. J Am Coll Cardiol Imaging 2015;8:438–47.CrossRef
13.
go back to reference Moody J, Murthy V, Lee B, Corbett J, Ficaro E. Variance estimation for myocardial blood flow by dynamic PET. IEEE Trans Med Imaging 2015;34:2343–53.CrossRefPubMed Moody J, Murthy V, Lee B, Corbett J, Ficaro E. Variance estimation for myocardial blood flow by dynamic PET. IEEE Trans Med Imaging 2015;34:2343–53.CrossRefPubMed
14.
go back to reference Klein R, Adler A, Beanlands RS, deKemp RA. Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion imaging with positron emission tomography. Phys Med Biol 2007;52:659–73.CrossRefPubMed Klein R, Adler A, Beanlands RS, deKemp RA. Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion imaging with positron emission tomography. Phys Med Biol 2007;52:659–73.CrossRefPubMed
15.
go back to reference Lortie M, Beanlands RSB, 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;34:1765–74.CrossRefPubMed Lortie M, Beanlands RSB, 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;34:1765–74.CrossRefPubMed
16.
go back to reference 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;37:1701–12.PubMed 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;37:1701–12.PubMed
17.
go back to reference Renaud JM, DaSilva JN, Beanlands RS, deKemp RA. Characterizing the normal range of myocardial blood flow with 82rubidium and 13N-ammonia PET imaging. J Nucl Cardiol 2013;20(4):578–91.CrossRefPubMed Renaud JM, DaSilva JN, Beanlands RS, deKemp RA. Characterizing the normal range of myocardial blood flow with 82rubidium and 13N-ammonia PET imaging. J Nucl Cardiol 2013;20(4):578–91.CrossRefPubMed
18.
go back to reference Gibbons RJ, Balady GJ, Beasley JW, Faafp JW, Bricker JT, Duvernoy WFC, et al ACC/AHA guidelines for exercise testing: Executive summary: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on exercise testing). Circulation 1997;96:345–54.CrossRefPubMed Gibbons RJ, Balady GJ, Beasley JW, Faafp JW, Bricker JT, Duvernoy WFC, et al ACC/AHA guidelines for exercise testing: Executive summary: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on exercise testing). Circulation 1997;96:345–54.CrossRefPubMed
19.
go back to reference Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S, et al ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. PET myocardial perfusion and metabolism clinical imaging. J Nucl Cardiol 2016;23:1187–226. Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S, et al ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. PET myocardial perfusion and metabolism clinical imaging. J Nucl Cardiol 2016;23:1187–226.
20.
go back to reference Kaster T, Mylonas I, Renaud JM, Wells GA, Beanlands RS, deKemp RA. Accuracy of low-dose rubidium-82 myocardial perfusion imaging for detection of coronary artery disease using 3D PET and normal database interpretation. J Nucl Cardiol 2012;19:1135–45.CrossRefPubMed Kaster T, Mylonas I, Renaud JM, Wells GA, Beanlands RS, deKemp RA. Accuracy of low-dose rubidium-82 myocardial perfusion imaging for detection of coronary artery disease using 3D PET and normal database interpretation. J Nucl Cardiol 2012;19:1135–45.CrossRefPubMed
21.
go back to reference Renaud JM, Yip K, Guimond J, Trottier M, Pibarot P, Turcotte E, et al Characterization of 3D PET systems for accurate quantification of myocardial blood flow. J Nucl Med. 2016. doi:10.2967/jnumed.116.174565. Renaud JM, Yip K, Guimond J, Trottier M, Pibarot P, Turcotte E, et al Characterization of 3D PET systems for accurate quantification of myocardial blood flow. J Nucl Med. 2016. doi:10.​2967/​jnumed.​116.​174565.
22.
go back to reference Peck R, Olsen C, Devore J. Introduction to statistics and data analysis. Toronto: Nelson Education; 2011. Peck R, Olsen C, Devore J. Introduction to statistics and data analysis. Toronto: Nelson Education; 2011.
23.
go back to reference Tahari AK, Lee A, Rajaram M, Fukushima K, Lodge MA, Lee BC, et al Absolute myocardial flow quantification with (82)Rb PET/CT: Comparison of different software packages and methods. Eur J Nucl Med Mol Imaging 2014;41:126–35.CrossRefPubMed Tahari AK, Lee A, Rajaram M, Fukushima K, Lodge MA, Lee BC, et al Absolute myocardial flow quantification with (82)Rb PET/CT: Comparison of different software packages and methods. Eur J Nucl Med Mol Imaging 2014;41:126–35.CrossRefPubMed
24.
go back to reference Kaufmann PA, Gnecchi-Ruscone T, Yap JT, Rimoldi O, Camici PG. Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. J Nucl Med 1999;40:1848–56.PubMed Kaufmann PA, Gnecchi-Ruscone T, Yap JT, Rimoldi O, Camici PG. Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. J Nucl Med 1999;40:1848–56.PubMed
25.
go back to reference 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;44:146–54.PubMed 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;44:146–54.PubMed
26.
go back to reference Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al Repeatability of cold pressor test-induced flow increase assessed with H2[15O] and PET. J Nucl Med. 2006;47:1420–6.PubMed Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al Repeatability of cold pressor test-induced flow increase assessed with H2[15O] and PET. J Nucl Med. 2006;47:1420–6.PubMed
27.
go back to reference Schindler TH, Zhang X-L, Prior JO, Cadenas J, Dahlbom M, Sayre J, Schelbert HR. 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. 2007;34:1178–88.CrossRefPubMed Schindler TH, Zhang X-L, Prior JO, Cadenas J, Dahlbom M, Sayre J, Schelbert HR. 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. 2007;34:1178–88.CrossRefPubMed
28.
go back to reference Nagamachi S, Czernin J, Kim AS, Sun KT, Böttcher M, Phelps ME, et al Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. J Nucl Med. 1996;37:1626–31.PubMed Nagamachi S, Czernin J, Kim AS, Sun KT, Böttcher M, Phelps ME, et al Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. J Nucl Med. 1996;37:1626–31.PubMed
29.
go back to reference Manabe O, Yoshinaga K, Katoh C, Naya M, deKemp RA, et al Repeatability of Rest and Hyperemic Myocardial Blood Flow Measurements with 82Rb Dynamic PET. J Nucl Med. 2009;50:68–71.CrossRefPubMed Manabe O, Yoshinaga K, Katoh C, Naya M, deKemp RA, et al Repeatability of Rest and Hyperemic Myocardial Blood Flow Measurements with 82Rb Dynamic PET. J Nucl Med. 2009;50:68–71.CrossRefPubMed
30.
go back to reference Hunter CRRN, Hill J, Ziadi MC, Beanlands RSB, deKemp RA. Biodistribution and radiation dosimetry of 82Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging. Eur J Nucl Med Mol Imaging. 2015;42:1032–42.CrossRefPubMed Hunter CRRN, Hill J, Ziadi MC, Beanlands RSB, deKemp RA. Biodistribution and radiation dosimetry of 82Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging. Eur J Nucl Med Mol Imaging. 2015;42:1032–42.CrossRefPubMed
Metadata
Title
Consistent tracer administration profile improves test–retest repeatability of myocardial blood flow quantification with 82Rb dynamic PET imaging
Authors
Ran Klein, PhD
Adrian Ocneanu, MSc
Jennifer M. Renaud, MSc
Maria C. Ziadi, MD
Rob S. B. Beanlands, MD
Robert A. deKemp, PhD
Publication date
01-06-2018
Publisher
Springer US
Published in
Journal of Nuclear Cardiology / Issue 3/2018
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI
https://doi.org/10.1007/s12350-016-0698-6

Other articles of this Issue 3/2018

Journal of Nuclear Cardiology 3/2018 Go to the issue