Coronary Flow Reserve

The seminal concept of coronary flow reserve (CFR) was proposed experimentally by Dr. Lance K. Gould in 1974. 1 Coronary reserve is the capacity of the coronary circulation to dilate following an increase in myocardial metabolic demand and can be expressed by the difference between the hyperemic flow and the resting flow curve. In 1979, this data was validated by Dr. Gould using PET imaging techniques utilizing radiolabeled microspheres. 2 N-13 Ammonia coronary flow reserve measurements are very well established in the medical literature.

Superior Diagnostic Accuracy

Quantitative PET perfusion images show the entire range of absolute flows and coronary flow reserves of each artery down to small branches with single or multiple stenosis, diffuse disease, and/or myocardial steal indicating collateralization. PET imaging has become integral to and inseparable from management of CAD—integrated diagnosis, treatment, and procedural guide. 3-4

Coronary flow reserve is a reproducible, reliable and accurate method across the spectrum of coronary artery disease. The following image demonstrates reproducibility and accuracy.

How accurate and reproducible is PET derived FLOW?

  • Robust literature
  • > 250 papers, ~15,000 patients, > 25yrs 8
Test-retest variability of common cardiovascular measurements
Test-retest measurement Coefficient of variation
PET flow cc/min/gm 14%
Anglogram % DS 17%
LDL cholesterol 9.5%
C-reactive protein 4%
Graded absolute flow and coronary flow across spectrum of disease (N = 14,962)
Population a Rest flow
Stress flow
Normal controls 3,484 0.82 ± 0.06 2.89 ± 1.07 3.55 ± 1.36
Risk factors only 3,592 0.85 ± 0.08 2.25 ± 1.07 2.80 ± 1.39
Established coronary artery disease 1,550 0.83 ± 0.10 1.71 ± 0.71 2.02 ± 0.70
Mixed (risk factors and/or known coronary artery disease) 4,765 0.97 ± 0.10 1.86 ± 0.58 1.93 ± 0.48
Cardiomyopathy 594 0.73 ± 0.07 1.47 ± 0.56 2.02 ± 0.67
Hypertrophic cardiomyopathy 345 0.90 ± 0.10 1.57 ± 0.33 1.84 ± 0.36
Syndrome X 348 1.06 ± 0.11 2.65 ± 1.31 2.54 ± 1.31
After cardiac transplant 184 1.14 ± 0.18 2.44 ± 1.34 2.29 ± 0.86
Gould et a. JACC. 62 (18) 1639-1653

Imaging Techniques

Methods of measuring coronary blood flow by quantitative PET imaging requires measuring the arterial input function as well as assessing the retention of the radiopharmaceutical uptake.

The arterial input function is obtained by region of interest during the first 120 seconds of acquisition. Several locations of the region of interest are practical. However, some are better than others.

Most software packages are automated for the determination of the arterial input function (AIF).

  • selection typically at basal plane of LV and LA
  • some software allows for manual choice
  • best AIF could differ between stress and rest

For each site percent with optimal arterial input (highest arterial input without spillover)

vasquez et ai. JACC cardiovascular imaging 2013:6559-68

Clinical Implications of CFR

CFR measurement is a key clinical application and diagnostic tool that assists in: 5

  • functional assessment of intermediate stenosis
  • detection of critical stenosis and specific coronary artery stenosis
  • localization monitoring of coronary flow after revascularization procedures
  • quantifying post infarct blood flow
  • assessing coronary graft patency

Including noninvasive quantitative assessment of coronary vasodilator function with positron emission tomography is a powerful, independent predictor of cardiac mortality in patients with known or suspected coronary artery disease and provides meaningful incremental risk stratification over clinical and gated myocardial perfusion imaging variables. 6 The accompanying table demonstrates the risk reclassification after coronary flow imaging is added to the qualitative assessment.

Annual Event Rate 3

Risk increases with decreasing CFR

The calculation of myocardial blood flow has some variability across scanner manufacturers, radiopharmaceuticals and software programs. The calculation of coronary flow reserve is considerably more consistent, with similar relationships between coronary flow reserve and cardiac mortality, regardless of technique used. The accompanying image demonstrates the increased risk in cardiac mortality with a decreasing flow reserve. 7

References & Articles


  1. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis: instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. The American journal of cardiology. 1974 Jan 31;33(1):87-94.
  2. Gould KL, Schelbert HR, Phelps ME, Hoffman EJ. Noninvasive assessment of coronary stenoses with myocardial perfusion imaging during pharmacologic coronary vasodilatation: V. Detection of 47 percent diameter coronary stenosis with intravenous nitrogen-13 ammonia and emission-computed tomography in intact dogs. The American journal of cardiology. 1979 Feb 1;43(2):200-8.
  3. Gould KL. Assessing progression or regression of CAD: the role of perfusion imaging. Journal of Nuclear Cardiology. 2005 Nov 1;12(6):625-38.
  4. Gould KL. Cardiac positron emission tomography. In: Willerson JT, Cohn JN, Wellens HJJ, Holmes DR, editors. Cardiovascular Medicine. 3rd edition. London, United Kingdom: Springer, 2007:855– 69.
  5. Johnson NP, Gould KL. Physiological basis for angina and ST-segment change: PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve. JACC: Cardiovascular Imaging. 2011 Sep 30;4(9):990-8.
  6. 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 ReserveClinical Perspective. Circulation. 2011 Nov 15;124(20):2215-24.
  7. Murthy VL, Lee BC, Sitek A, Naya M, Moody J, Polavarapu V, et al. Comparison and prognostic validation of multiple methods of quantification of myocardial blood flow with 82Rb PET. J Nucl Med 2014;55:1952-8.
  8. Gould et. al JACC Cardiovascular Imaging. 62(18), 1639-53.


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