Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals
- 59 Downloads
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.
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.
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).
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.
KeywordsPET myocardial blood flow perfusion agents tracers molecular imaging agents molecular imaging
Coronary artery disease
Cardiac magnetic resonance
Extracellular volume fraction
Myocardial blood flow
Positron emission tomography
The authors would like to thank Dr. Stuart Pocock (London School of Hygiene and Tropical Medicine, UK) for his help and advice regarding statistical analysis.
All authors have reported that they have no relationships relevant to the contents of this paper to disclose. This work was supported by grants from the Ministerio de Economía, Industria y Competitividad (MEIC) (SAF2014-58920-R), from the Carlos III Institute of Health of Spain and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (FIS-FEDER PI14-01427), and from the Comunidad de Madrid (2016-T1/TIC-1099). C. Velasco holds a fellowship from the Spanish Ministry of Education (FPU014/01794). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720).
- 1.Benjamin EJ, Blaha MJ, Chiuve SE, et al (2017) Heart disease and stroke statistics’ 2017 Update: A Report from the American Heart Association.Google Scholar
- 2.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.Google Scholar
- 12.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.Google Scholar
- 17.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.Google Scholar
- 18.Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents. Incl Gadolinium Depos. 2009;1267:1259–67.Google Scholar
- 21.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.Google Scholar
- 23.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.Google Scholar
- 28.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.Google Scholar
- 34.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.CrossRefGoogle Scholar