Abstract
Positron emission tomography (PET) myocardial perfusion imaging (MPI) has high diagnostic accuracy and prognostic value. PET-MPI can also be used to quantitatively evaluate regional myocardial blood flow (MBF). This technique also allows the calculation of the coronary flow reserve (CFR)/myocardial flow reserve (MFR), which is the ratio of MBF at peak hyperemia to resting MBF. Coronary computed tomography angiography (CTA) is a non-invasive method for accurate detection and exclusion of high-grade coronary stenoses, when compared to an invasive coronary angiography reference standard. However, CTA assessment of coronary stenoses tends toward overestimation, and CTA cannot determine physiologic significance of lesions. Recent advances in computational fluid dynamics and image-based modeling permit calculation of non-invasive fractional flow reserve derived from CT (FFRCT), without the need for additional imaging, modification of acquisition protocols, or administration of medications. In this review, we cover the CFR/MFR assessment by PET and FFR assessment by CT.
Similar content being viewed by others
Abbreviations
- CAD:
-
Coronary artery disease
- CFD:
-
Computational fluid dynamics
- CFR:
-
Coronary flow reserve
- CTA:
-
Computed tomographic angiography
- FFR:
-
Fractional flow reserve
- FFRCT :
-
Fractional flow reserve derived from CT
- MBF:
-
Myocardial blood flow
- MFR:
-
Myocardial flow reserve
- NPV:
-
Negative predictive value
- PET:
-
Positron emission tomography
- PPV:
-
Positive predictive value
- SPECT:
-
Single-photon emission computed tomography
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Di Carli MF, Murthy VL. Cardiac PET/CT for the evaluation of known or suspected coronary artery disease. Radiographics. 2011;31(5):1239–54.
Senthamizhchelvan S, Bravo PE, Lodge MA, Merrill J, Bengel FM, Sgouros G. Radiation dosimetry of 82Rb in humans under pharmacologic stress. J Nucl Med Off Publ Soc Nucl Med. 2011;52(3):485–91. doi:10.2967/jnumed.110.083477.
Stabin MG. Proposed revision to the radiation dosimetry of 82Rb. Health Phys. 2010;99(6):811–3. doi:10.1097/HP.0b013e3181e47b33.
Di Carli MF, Dorbala S, Meserve J, El Fakhri G, Sitek A, Moore SC. Clinical myocardial perfusion PET/CT. J Nucl Med Off Publ Soc Nucl Med. 2007;48(5):783–93. doi:10.2967/jnumed.106.032789.
Stabin MG. Radiopharmaceuticals for nuclear cardiology: radiation dosimetry, uncertainties, and risk. J Nucl Med Off Publ Soc Nucl Med. 2008;49(9):1555–63. doi:10.2967/jnumed.108.052241.
Bergmann SR, Herrero P, Markham J, Weinheimer CJ, Walsh MN. Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. J Am Coll Cardiol. 1989;14(3):639–52.
Knuuti J, Kajander S, Mäki M, Ukkonen H. Quantification of myocardial blood flow will reform the detection of CAD. J Nucl Cardiol. 2009;16(4):497–506. doi:10.1007/s12350-009-9101-1.
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(6):623–40. doi:10.1016/j.jcmg.2010.04.007.
Dilsizian V, Taillefer R. Journey in evolution of nuclear cardiology: will there be another quantum leap with the F-18-labeled myocardial perfusion tracers? JACC Cardiovasc Imaging. 2012;5(12):1269–84. doi:10.1016/j.jcmg.2012.10.006.
Maddahi J. Properties of an ideal PET perfusion tracer: new PET tracer cases and data. J Nucl Cardiol. 2012;19 Suppl 1:S30–7. doi:10.1007/s12350-011-9491-8.
Maddahi J, Czernin J, Lazewatsky J, Huang S-C, Dahlbom M, Schelbert H, et al. Phase I, first-in-human study of BMS747158, a novel F-18-labeled tracer for myocardial perfusion PET: dosimetry, biodistribution, safety, and imaging characteristics after a single injection at rest. J Nucl Med. 2011;52(9). doi:10.2967/jnumed.111.092528.
Maddahi J, Huang S, Truong D, Lazewatsky J, Ehlgen A, Schelbert H, et al. Preliminary results of absolute quantification of rest and stress myocardial blood flow with flurpiridaz F-18 PET in normal and coronary artery disease patients in a single-center study. J Nucl Cardiol. 2010;17:743. abstract.
Berman DS, Maddahi J, Tamarappoo BK, Czernin J, Taillefer R, Udelson JE, et al. Phase II safety and clinical comparison with single-photon emission computed tomography myocardial perfusion imaging for detection of coronary artery disease: flurpiridaz F 18 positron emission tomography. J Am Coll Cardiol. 2013;61(4):469–77. doi:10.1016/j.jacc.2012.11.022.
Klein R, Beanlands R, deKemp R. Quantification of myocardial blood flow and flow reserve: technical aspects. J Nucl Cardiol. 2010;17(4):555–70. doi:10.1007/s12350-010-9256-9.
Slomka PJ, Alexanderson E, Jácome R, Jiménez M, Romero E, Meave A, et al. Comparison of clinical tools for measurements of regional stress and rest myocardial blood flow assessed with 13N-ammonia PET/CT. J Nucl Med. 2012;53(2):171–81. doi:10.2967/jnumed.111.095398.
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(4):600–16. doi:10.1007/s12350-010-9225-3.
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 (82)Rb PET: comparison with (13)N-ammonia PET. J Nucl Med. 2009;50(7):1062–71. doi:10.2967/jnumed.104.007831.
Kajander S, Joutsiniemi E, Saraste M, Pietilä M, Ukkonen H, Saraste A, et al. Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease. Circulation. 2010;122(6):603–13. doi:10.1161/CIRCULATIONAHA.109.915009.
Dekemp RA, 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(4):571–7. doi:10.2967/jnumed.112.112219.
Beanlands RS, Ziadi MC, Williams K. Quantification of myocardial flow reserve using positron emission imaging the journey to clinical use. J Am Coll Cardiol. 2009;54(2):157–9. doi:10.1016/j.jacc.2009.03.049.
Parkash R, deKemp RA, Ruddy TD, Kitsikis A, Hart R, Beauchesne L, et al. Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease. J Nucl Cardiol. 2004;11(4):440–9.
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;19(4):670–80. doi:10.1007/s12350-011-9506-5. This study provides usefulness of myocardial flow reserve (MFR) for 3-vessel coronary artery disease.
Fiechter M, Ghadri JR, Gebhard C, Fuchs TA, Pazhenkottil AP, Nkoulou RN, et al. Diagnostic value of 13N-ammonia myocardial perfusion PET: added value of myocardial flow reserve. J Nucl Med. 2012;53(8):1230–4. doi:10.2967/jnumed.111.101840. This study provides substantial added diagnostic value of myocardial flow reserve (MFR) for detection of coronary artery disease.
Santana CA, Folks RD, Garcia EV, Verdes L, Sanyal R, Hainer J, et al. Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database. J Nucl Med. 2007;48(7):1122–8. doi:10.2967/jnumed.107.039750.
Nakazato R, Berman DS, Dey D, Le Meunier L, Hayes SW, Fermin JS, et al. Automated quantitative Rb-82 3D PET/CT myocardial perfusion imaging: normal limits and correlation with invasive coronary angiography. J Nucl Cardiol. 2012;19(2):265–76. doi:10.1007/s12350-011-9496-3.
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. doi:10.1007/s12350-012-9621-y.
Hajjiri MM, Leavitt MB, Zheng H, Spooner AE, Fischman AJ, Gewirtz H. Comparison of positron emission tomography measurement of adenosine-stimulated absolute myocardial blood flow versus relative myocardial tracer content for physiological assessment of coronary artery stenosis severity and location. JACC Cardiovasc Imaging. 2009;2(6):751–8. doi:10.1016/j.jcmg.2009.04.004.
Anagnostopoulos C, Almonacid A, El Fakhri G, Curillova Z, Sitek A, Roughton M, et al. Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity. Eur J Nucl Med Mol Imaging. 2008;35(9):1593–601. doi:10.1007/s00259-008-0793-2.
Nesterov SV, Han C, Maki M, Kajander S, Naum AG, Helenius H, et al. Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas). Eur J Nucl Med Mol Imaging. 2009;36(10):1594–602. doi:10.1007/s00259-009-1143-8.
Kajander SA, Joutsiniemi E, Saraste M, Pietila M, Ukkonen H, Saraste A, et al. Clinical value of absolute quantification of myocardial perfusion with (15)O-water in coronary artery disease. Circ Cardiovasc Imaging. 2011;4(6):678–84. doi:10.1161/CIRCIMAGING.110.960732.
Schindler TH, Cardenas J, Prior JO, Facta AD, Kreissl MC, Zhang XL, et al. Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function. J Am Coll Cardiol. 2006;47(6):1188–95. doi:10.1016/j.jacc.2005.10.062.
Prior JO, Quinones MJ, Hernandez-Pampaloni M, Facta AD, Schindler TH, Sayre JW, et al. Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. Circulation. 2005;111(18):2291–8. doi:10.1161/01.CIR.0000164232.62768.51.
Kaufmann PA, Gnecchi-Ruscone T, Schäfers KP, Lüscher TF, Camici PG. Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol. 2000;36(1):103–9.
Quiñones MJ, Hernandez-Pampaloni M, Schelbert H, Bulnes-Enriquez I, Jimenez X, Hernandez G, et al. Coronary vasomotor abnormalities in insulin-resistant individuals. Ann Intern Med. 2004;140(9):700–8.
Herzog BA, Husmann L, Valenta I, Gaemperli O, Siegrist PT, Tay FM, et al. Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography added value of coronary flow reserve. J Am Coll Cardiol. 2009;54(2):150–6. doi:10.1016/j.jacc.2009.02.069.
Fukushima K, Javadi MS, Higuchi T, Lautamäki R, Merrill J, Nekolla SG, et al. Prediction of short-term cardiovascular events using quantification of global myocardial flow reserve in patients referred for clinical 82Rb PET perfusion imaging. J Nucl Med. 2011;52(5):726–32. doi:10.2967/jnumed.110.081828.
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(7):740–8. doi:10.1016/j.jacc.2011.01.065.
Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, et al. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. 2011;124(20):2215–24. doi:10.1161/CIRCULATIONAHA.111.050427. This study provides incremental prognostic significance of coronary flow reserve (CFR) for coronary artery disease.
Schindler TH, Nitzsche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, et al. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol. 2005;45(9):1505–12.
Dorbala S, Vangala D, Sampson U, Limaye A, Kwong R, Di Carli MF. Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: a 82Rb PET/CT study. J Nucl Med. 2007;48(3):349–58.
Dorbala S, Hachamovitch R, Curillova Z, Thomas D, Vangala D, Kwong RY, et al. Incremental prognostic value of gated Rb-82 positron emission tomography myocardial perfusion imaging over clinical variables and rest LVEF. JACC Cardiovasc Imaging. 2009;2(7):846–54. doi:10.1016/j.jcmg.2009.04.009.
Slomka PJ, Dey D, Duvall WL, Henzlova MJ, Berman DS, Germano G. Advances in nuclear cardiac instrumentation with a view towards reduced radiation exposure. Curr Cardiol Rep. 2012;14(2):208–16. doi:10.1007/s11886-012-0248-z.
Pan T, Mawlawi O, Nehmeh SA, Erdi YE, Luo D, Liu HH, et al. Attenuation correction of PET images with respiration-averaged CT images in PET/CT. J Nucl Med. 2005;46(9):1481–7.
Bacharach SL. PET/CT attenuation correction: breathing lessons. J Nucl Med. 2007;48(5):677–9. doi:10.2967/jnumed.106.037499.
Gould KL, Pan T, Loghin C, Johnson NP, Guha A, Sdringola S. Frequent diagnostic errors in cardiac PET/CT due to misregistration of CT attenuation and emission PET images: a definitive analysis of causes, consequences, and corrections. J Nucl Med. 2007;48(7):1112–21. doi:10.2967/jnumed.107.039792.
Slomka PJ, Le Meunier L, Hayes SW, Acampa W, Oba M, Haemer GG, et al. Comparison of myocardial perfusion 82Rb PET performed with CT- and transmission CT-based attenuation correction. J Nucl Med. 2008;49(12):1992–8. doi:10.2967/jnumed.108.056580.
Kim H, Vignon-Clementel I, Coogan J, Figueroa C, Jansen K, Taylor C. Patient-specific modeling of blood flow and pressure in human coronary arteries. Ann Biomed Eng. 2010;38(10):3195–209.
Taylor CA, Fonte TA, Min JK. Computational fluid dynamics applied to cardiac computed tomography for noninvasive quantification of fractional flow reserve: scientific basis. J Am Coll Cardiol. 2013;61(22):2233–41. doi:10.1016/j.jacc.2012.11.083. This review provides a thorough description of how FFR CT can be calculated.
Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation. 1993;87(4):1354–67. doi:10.1161/01.cir.87.4.1354.
Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol. 2011;58(19):1989–97.
Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012;308(12):1237–45. doi:10.1001/2012.jama.11274. This study provides substantial diagnostic value of FFR CT for the detection of hemodynamically significant coronary artery disease.
Nakazato R, Park HB, Berman DS, Gransar H, Koo BK, Erglis A, et al. Noninvasive Fractional flow reserve derived from computed tomography angiography for coronary lesions of intermediate stenosis severity: results from the DeFACTO study. Circ Cardiovasc Imaging. 2013;6(6):881–9. doi:10.1161/CIRCIMAGING.113.000297. This study provides the ability of FFR CT to effectively rule out intermediate stenosis lesions that cause ischemia.
Min J, Shaw L, Berman D. The present state of coronary computed tomography angiography a process in evolution. J Am Coll Cardiol. 2010;55(10):957–65. doi:10.1016/j.jacc.2009.08.087.
Meijboom WB, Van Mieghem CA, van Pelt N, Weustink A, Pugliese F, Mollet NR, et al. Comprehensive assessment of coronary artery stenoses: computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina. J Am Coll Cardiol. 2008;52(8):636–43. doi:10.1016/j.jacc.2008.05.024.
Schuijf JD, Bax JJ. CT angiography: an alternative to nuclear perfusion imaging? Heart. 2008;94(3):255–7. doi:10.1136/hrt.2006.105833.
Leber AW, Knez A, White CW, Becker A, von Ziegler F, Muehling O, et al. Composition of coronary atherosclerotic plaques in patients with acute myocardial infarction and stable angina pectoris determined by contrast-enhanced multislice computed tomography. Am J Cardiol. 2003;91(6):714–8.
Hoffmann U, Moselewski F, Nieman K, Jang IK, Ferencik M, Rahman AM, et al. Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am Coll Cardiol. 2006;47(8):1655–62. doi:10.1016/j.jacc.2006.01.041.
Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol. 2007;50(4):319–26. doi:10.1016/j.jacc.2007.03.044.
Nakazato R, Shalev A, Doh JH, Koo BK, Dey D, Berman DS, et al. Quantification and characterisation of coronary artery plaque volume and adverse plaque features by coronary computed tomographic angiography: a direct comparison to intravascular ultrasound. Eur Radiol. 2013;23(8):2109–17. doi:10.1007/s00330-013-2822-1.
Ziadi MC, Beanlands RS. The clinical utility of assessing myocardial blood flow using positron emission tomography. J Nucl Cardiol. 2010;17(4):571–81. doi:10.1007/s12350-010-9258-7.
Min JK, Berman DS, Budoff MJ, Jaffer FA, Leipsic J, Leon MB, et al. Rationale and design of the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic AngiOgraphy) study. J Cardiovasc Comput Tomogr. 2011;5(5):301–9. doi:10.1016/j.jcct.2011.08.003.
Acknowledgments
This study was funded by grants from the National Institutes of Health (R01HL11515002 and R01HL11801901). This study was also funded by a gift from the Dalio Institute of Cardiovasular Imaging and the Michael Wolk Foundation.
Compliance with Ethics Guidelines
ᅟ
Conflict of Interest
Ryo Nakazato declares that he has no conflict of interest.
Ran Heo declares that he has no conflict of interest.
Jonathon Leipsic has received grant support from and been a consultant for HeartFlow. He has received payment for development of educational presentations including service on speakers' bureaus from GE Healthcare.
James K. Min has received grant support from HeartFlow. He serves as a consultant to HeartFlow.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is part of the Topical Collection on Nuclear Cardiology
Rights and permissions
About this article
Cite this article
Nakazato, R., Heo, R., Leipsic, J. et al. CFR and FFR Assessment with PET and CTA: Strengths and Limitations. Curr Cardiol Rep 16, 484 (2014). https://doi.org/10.1007/s11886-014-0484-5
Published:
DOI: https://doi.org/10.1007/s11886-014-0484-5