Skip to main content
Top
Published in: Journal of Nuclear Cardiology 4/2020

01-08-2020 | Molecular Imaging | Original Article

Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals

Authors: Carlos Velasco, MSc, Adriana Mota-Cobián, MSc, Rubén A. Mota, DVM, PhD Dip., ECLAM, Juan Pellico, PhD, Fernando Herranz, PhD, Carlos Galán-Arriola, DVM, Borja Ibáñez, MD, PhD, Jesús Ruiz-Cabello, PhD, Jesús Mateo, PhD, Samuel España, PhD

Published in: Journal of Nuclear Cardiology | Issue 4/2020

Login to get access

Abstract

Background

Here we evaluated the feasibility of PET with Gallium-68 (68Ga)-labeled DOTA for non-invasive assessment of myocardial blood flow (MBF) and extracellular volume fraction (ECV) in a pig model of myocardial infarction. We also aimed to validate MBF measurements using microspheres as a gold standard in healthy pigs.

Methods

8 healthy pigs underwent three sequential 68Ga-DOTA-PET/CT scans at rest and during pharmacological stress with simultaneous injection of fluorescent microspheres to validate MBF measurements. Myocardial infarction was induced in 5 additional pigs, which underwent 68Ga-DOTA-PET/CT examinations 7-days after reperfusion. Dynamic PET images were reconstructed and fitted to obtain MBF and ECV parametric maps.

Results

MBF assessed with 68Ga-DOTA-PET showed good correlation (y = 0.96x + 0.11, r = 0.91) with that measured with microspheres. MBF values obtained with 68Ga-DOTA-PET in the infarcted area (LAD, left anterior descendant) were significantly reduced in comparison to remote ones LCX (left circumflex artery, P < 0.0001) and RCA (right coronary artery, P < 0.0001). ECV increased in the infarcted area (P < 0.0001).

Conclusion

68Ga-DOTA-PET allowed non-invasive assessment of MBF and ECV in pigs with myocardial infarction and under rest-stress conditions. This technique could provide wide access to quantitative measurement of both MBF and ECV with PET imaging.
Appendix
Available only for authorised users
Literature
1.
go back to reference Benjamin EJ, Blaha MJ, Chiuve SE, et al (2017) Heart disease and stroke statistics’ 2017 Update: A Report from the American Heart Association. Benjamin EJ, Blaha MJ, Chiuve SE, et al (2017) Heart disease and stroke statistics’ 2017 Update: A Report from the American Heart Association.
2.
go back to reference Schindler TH, Schelbert HR, Quercioli A, Dilsizian V. Cardiac PET imaging for the detection and monitoring of coronary artery disease and microvascular health. JACC: Cardiovasc Imaging. 2010;3:623–40. Schindler TH, Schelbert HR, Quercioli A, Dilsizian V. Cardiac PET imaging for the detection and monitoring of coronary artery disease and microvascular health. JACC: Cardiovasc Imaging. 2010;3:623–40.
3.
go back to reference Dilsizian V, Bacharach SL, Beanlands RS, et al. PET myocardial perfusion and metabolism clinical imaging. J Nucl Cardiol. 2009;16:651.CrossRef Dilsizian V, Bacharach SL, Beanlands RS, et al. PET myocardial perfusion and metabolism clinical imaging. J Nucl Cardiol. 2009;16:651.CrossRef
4.
go back to reference Heller GV, Calnon D, Dorbala S. Recent advances in cardiac PET and PET/CT myocardial perfusion imaging. J Nucl Cardiol. 2009;16:962–9.CrossRef Heller GV, Calnon D, Dorbala S. Recent advances in cardiac PET and PET/CT myocardial perfusion imaging. J Nucl Cardiol. 2009;16:962–9.CrossRef
5.
go back to reference Packard RRS, Huang S-C, Dahlbom M, et al. Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET. J Nucl Med. 2014;55:1438–45.CrossRef Packard RRS, Huang S-C, Dahlbom M, et al. Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET. J Nucl Med. 2014;55:1438–45.CrossRef
6.
go back to reference Breeman WAP, Verbruggen AM. The 68Ge/68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging. 2007;34:978–81.CrossRef Breeman WAP, Verbruggen AM. The 68Ge/68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging. 2007;34:978–81.CrossRef
7.
go back to reference Shetty D, Lee YS, Jeong JM. 68Ga-labeled radiopharmaceuticals for positron emission tomography. Nucl Med Mol Imaging. 2010;44:233–40.CrossRef Shetty D, Lee YS, Jeong JM. 68Ga-labeled radiopharmaceuticals for positron emission tomography. Nucl Med Mol Imaging. 2010;44:233–40.CrossRef
8.
go back to reference Tarkia M, Saraste A, Saanijoki T, et al. Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. Nucl Med Biol. 2012;39:715–23.CrossRef Tarkia M, Saraste A, Saanijoki T, et al. Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. Nucl Med Biol. 2012;39:715–23.CrossRef
9.
go back to reference Ley S, Ley-Zaporozhan J. Pulmonary perfusion imaging using MRI: Clinical application. Insights Imaging. 2012;3:61–71.CrossRef Ley S, Ley-Zaporozhan J. Pulmonary perfusion imaging using MRI: Clinical application. Insights Imaging. 2012;3:61–71.CrossRef
10.
go back to reference Velasco C, Mateo J, Santos A, et al. Assessment of regional pulmonary blood flow using 68Ga-DOTA PET. EJNMMI Res. 2017;7:7.CrossRef Velasco C, Mateo J, Santos A, et al. Assessment of regional pulmonary blood flow using 68Ga-DOTA PET. EJNMMI Res. 2017;7:7.CrossRef
11.
go back to reference Autio A, Saraste A, Kudomi N, et al. Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: A validation study using (15)O-water. Am J Nucl Med Mol Imaging. 2014;4:571–9.PubMedPubMedCentral Autio A, Saraste A, Kudomi N, et al. Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: A validation study using (15)O-water. Am J Nucl Med Mol Imaging. 2014;4:571–9.PubMedPubMedCentral
12.
go back to reference Medical Advisory Secretariat. Positron emission tomography for the assessment of myocardial viability: An evidence-based analysis. Ont Health Technol Assess Ser. 2005;5:1–167.PubMedCentral Medical Advisory Secretariat. Positron emission tomography for the assessment of myocardial viability: An evidence-based analysis. Ont Health Technol Assess Ser. 2005;5:1–167.PubMedCentral
13.
go back to reference Ugander M, Oki AJ, Hsu LY, et al. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J. 2012;33:1268–78.CrossRef Ugander M, Oki AJ, Hsu LY, et al. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J. 2012;33:1268–78.CrossRef
14.
go back to reference Kim H, Lee SJ, Davies-Venn C, et al. 64Cu-DOTA as a surrogate positron analog of Gd-DOTA for cardiac fibrosis detection with PET: Pharmacokinetic study in a rat model of chronic MI. Nucl Med Commun. 2016;37:188–96.CrossRef Kim H, Lee SJ, Davies-Venn C, et al. 64Cu-DOTA as a surrogate positron analog of Gd-DOTA for cardiac fibrosis detection with PET: Pharmacokinetic study in a rat model of chronic MI. Nucl Med Commun. 2016;37:188–96.CrossRef
15.
go back to reference Glenny RW, Bernard S, Brinkley M. Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion. J Appl Physiol. 1993;74:2585–97.CrossRef Glenny RW, Bernard S, Brinkley M. Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion. J Appl Physiol. 1993;74:2585–97.CrossRef
16.
go back to reference Fernández-Jiménez R, García-Prieto J, Sánchez-González J, et al. Pathophysiology underlying the bimodal edema phenomenon after myocardial ischemia/reperfusion. J Am Coll Cardiol. 2015;66:816–28.CrossRef Fernández-Jiménez R, García-Prieto J, Sánchez-González J, et al. Pathophysiology underlying the bimodal edema phenomenon after myocardial ischemia/reperfusion. J Am Coll Cardiol. 2015;66:816–28.CrossRef
17.
go back to reference Hein TW, Belardinelli L, Kuo L. Adenosine A(2A) receptors mediate coronary microvascular dilation to adenosine: Role of nitric oxide and ATP-sensitive potassium channels. J Pharmacol Exp Ther. 1999;291:655–64.PubMed Hein TW, Belardinelli L, Kuo L. Adenosine A(2A) receptors mediate coronary microvascular dilation to adenosine: Role of nitric oxide and ATP-sensitive potassium channels. J Pharmacol Exp Ther. 1999;291:655–64.PubMed
18.
go back to reference Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents. Incl Gadolinium Depos. 2009;1267:1259–67. Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents. Incl Gadolinium Depos. 2009;1267:1259–67.
19.
go back to reference Sourbron SP, Buckley DL. On the scope and interpretation of the tofts models for DCE-MRI. Magnetic Resonance in Medicine. 2011;745:735–45.CrossRef Sourbron SP, Buckley DL. On the scope and interpretation of the tofts models for DCE-MRI. Magnetic Resonance in Medicine. 2011;745:735–45.CrossRef
20.
go back to reference Nordström J, Kero T, Harms HJ, et al. Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET. EJNMMI Phys. 2017;4:26.CrossRef Nordström J, Kero T, Harms HJ, et al. Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET. EJNMMI Phys. 2017;4:26.CrossRef
21.
go back to reference van der Weerdt AP, Klein LJ, Boellaard R, et al. Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans. J Nucl Med. 2001;42:1622–9.PubMed van der Weerdt AP, Klein LJ, Boellaard R, et al. Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans. J Nucl Med. 2001;42:1622–9.PubMed
22.
go back to reference Nesterov SV, Han C, Mäki M, et al. Myocardial perfusion quantitation with15O-labelled water PET: High reproducibility of the new cardiac analysis software (CarimasTM). Eur J Nucl Med Mol Imaging. 2009;36:1594–602.CrossRef Nesterov SV, Han C, Mäki M, et al. Myocardial perfusion quantitation with15O-labelled water PET: High reproducibility of the new cardiac analysis software (CarimasTM). Eur J Nucl Med Mol Imaging. 2009;36:1594–602.CrossRef
23.
go back to reference Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the cardiac imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circ J Am Hear Assoc. 2002;105:539–42. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the cardiac imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circ J Am Hear Assoc. 2002;105:539–42.
24.
go back to reference Renkin EM. Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles. Am J Physiol. 1959;197:1205–10.CrossRef Renkin EM. Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles. Am J Physiol. 1959;197:1205–10.CrossRef
25.
go back to reference Crone C. The permeability of capillaries in various organs as determined by use of the “Indicator Diffusion” method. Acta Physiol Scand. 1963;58:292–305.CrossRef Crone C. The permeability of capillaries in various organs as determined by use of the “Indicator Diffusion” method. Acta Physiol Scand. 1963;58:292–305.CrossRef
26.
go back to reference Fernández-Jiménez R, Galán-Arriola C, Sánchez-González J, et al. Effect of ischemia duration and protective interventions on the temporal dynamics of tissue composition after myocardial infarction. Circ Res. 2017;121:439–50.CrossRef Fernández-Jiménez R, Galán-Arriola C, Sánchez-González J, et al. Effect of ischemia duration and protective interventions on the temporal dynamics of tissue composition after myocardial infarction. Circ Res. 2017;121:439–50.CrossRef
27.
go back to reference Serrat MA. Measuring bone blood supply in mice using fluorescent microspheres. Nat Protoc. 2009;4:1749–58.CrossRef Serrat MA. Measuring bone blood supply in mice using fluorescent microspheres. Nat Protoc. 2009;4:1749–58.CrossRef
28.
go back to reference Fan FC, Schuessler GB, Chen RY, Chien S. Determinations of blood flow and shunting of 9- and 15-micrometer spheres in regional beds. Am J Physiol: Hear Circ Physiol. 1979;237:H25–33. Fan FC, Schuessler GB, Chen RY, Chien S. Determinations of blood flow and shunting of 9- and 15-micrometer spheres in regional beds. Am J Physiol: Hear Circ Physiol. 1979;237:H25–33.
29.
go back to reference Bland JM, Altman D. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;327:307–10.CrossRef Bland JM, Altman D. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;327:307–10.CrossRef
30.
go back to reference McGraw KO, Wong SP. Forming inferences about some intraclass correlation coefficients. Psychol Methods. 1996;1:30–46.CrossRef McGraw KO, Wong SP. Forming inferences about some intraclass correlation coefficients. Psychol Methods. 1996;1:30–46.CrossRef
31.
go back to reference Harms HJ, Nesterov SV, Han C, et al. 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. 2014;15:431–41.CrossRef Harms HJ, Nesterov SV, Han C, et al. 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. 2014;15:431–41.CrossRef
32.
go back to reference White SK, Sado DM, Flett AS, Moon JC. Characterising the myocardial interstitial space: The clinical relevance of non-invasive imaging. Heart. 2012;98:773–9.CrossRef White SK, Sado DM, Flett AS, Moon JC. Characterising the myocardial interstitial space: The clinical relevance of non-invasive imaging. Heart. 2012;98:773–9.CrossRef
33.
go back to reference Maddahi J, Packard RRS. Cardiac PET perfusion tracers: Current status and future directions. Semin Nucl Med. 2014;44:333–43.CrossRef Maddahi J, Packard RRS. Cardiac PET perfusion tracers: Current status and future directions. Semin Nucl Med. 2014;44:333–43.CrossRef
34.
go back to reference Jaarsma C, Leiner T, Bekkers SC, et al. Diagnostic performance of noninvasive myocardial perfusion imaging using single-photon emission computed tomography, cardiac magnetic resonance, and positron emission tomography imaging for the detection of obstructive coronary artery disease: A meta-anal. J Am Coll Cardiol. 2012;59:1719–28.CrossRef Jaarsma C, Leiner T, Bekkers SC, et al. Diagnostic performance of noninvasive myocardial perfusion imaging using single-photon emission computed tomography, cardiac magnetic resonance, and positron emission tomography imaging for the detection of obstructive coronary artery disease: A meta-anal. J Am Coll Cardiol. 2012;59:1719–28.CrossRef
35.
go back to reference Sampson UK, Dorbala S, Limaye A, et al. 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;49:1052–8.CrossRef Sampson UK, Dorbala S, Limaye A, et al. 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;49:1052–8.CrossRef
Metadata
Title
Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals
Authors
Carlos Velasco, MSc
Adriana Mota-Cobián, MSc
Rubén A. Mota, DVM, PhD Dip., ECLAM
Juan Pellico, PhD
Fernando Herranz, PhD
Carlos Galán-Arriola, DVM
Borja Ibáñez, MD, PhD
Jesús Ruiz-Cabello, PhD
Jesús Mateo, PhD
Samuel España, PhD
Publication date
01-08-2020
Publisher
Springer International Publishing
Published in
Journal of Nuclear Cardiology / Issue 4/2020
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI
https://doi.org/10.1007/s12350-019-01694-z

Other articles of this Issue 4/2020

Journal of Nuclear Cardiology 4/2020 Go to the issue