The Clinical Value of Myocardial Blood Flow Measurement*

PET provides robust and reproducible measurements of regional myocardial blood flow in milliliters per minute per gram of tissue, providing unique pathophysiologic and diagnostic information on the function of the coronary macro- and microcirculation. There is compelling evidence to suggest that in many instances abnormalities of global myocardial perfusion are demonstrated in individuals with either coronary risk factors for coronary artery disease or different myocardial diseases in the absence of angiographically demonstrable stenosis of the epicardial coronary arteries. In this context, measurement of myocardial blood flow gives unique diagnostic information regarding the function of the coronary microcirculation and provides a quantitative surrogate endpoint against which the efficacy of treatments can be established.

[1]  R. Berne,et al.  The cardiac effects of adenosine. , 1989, Progress in cardiovascular diseases.

[2]  R. Bache,et al.  Regulation of coronary blood flow during exercise. , 2008, Physiological reviews.

[3]  T. Gnecchi-Ruscone,et al.  Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses. , 2007, American journal of physiology. Heart and circulatory physiology.

[4]  P. Kellman,et al.  Imaging sequences for first pass perfusion --a review. , 2007, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[5]  A. Folsom,et al.  Coronary risk factors and myocardial perfusion in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA). , 2006, Journal of the American College of Cardiology.

[6]  Igor Klem,et al.  mproved Detection of Coronary rtery Disease by Stress Perfusion ardiovascular Magnetic Resonance With he Use of Delayed Enhancement Infarction Imaging , 2006 .

[7]  A. L'Abbate,et al.  Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: a study with nitrogen-13 ammonia and positron emission tomography. , 1991, Journal of the American College of Cardiology.

[8]  H A O'Brien,et al.  Relation between regional myocardial uptake of rubidium-82 and perfusion: absolute reduction of cation uptake in ischemia. , 1982, The American journal of cardiology.

[9]  M. Robson,et al.  Evidence for Microvascular Dysfunction in Hypertrophic Cardiomyopathy: New Insights From Multiparametric Magnetic Resonance Imaging , 2007, Circulation.

[10]  John O. Prior,et al.  Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with 13N-ammonia and PET , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  H. Schelbert,et al.  Coronary vasodilator reserve and Framingham risk scores in subjects at risk for coronary artery disease , 2006, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[12]  O. Hess,et al.  alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. , 2000, Circulation.

[13]  A. Folsom,et al.  Variability of Myocardial Blood Flow Measurements by Magnetic Resonance Imaging in the Multi-Ethnic Study of Atherosclerosis , 2008, Investigative radiology.

[14]  R. Cury,et al.  Diagnostic performance of stress perfusion and delayed-enhancement MR imaging in patients with coronary artery disease. , 2006, Radiology.

[15]  P. Camici,et al.  Effect of alpha 1-adrenoceptor blockade on resting and hyperemic myocardial blood flow in normal humans. , 1996, The American journal of physiology.

[16]  William Wijns,et al.  Relation Between Myocardial Blood Flow and the Severity of Coronary-Artery Stenosis , 1995 .

[17]  Adriaan A. Lammertsma,et al.  Noninvasive Quantification of Regional Myocardial Blood Flow in Coronary Artery Disease With Oxygen‐15–Labeled Carbon Dioxide Inhalation and Positron Emission Tomography , 1991, Circulation.

[18]  W. Chilian,et al.  Coronary microcirculation: autoregulation and metabolic control , 1995, Basic Research in Cardiology.

[19]  A. Folsom,et al.  Lower Myocardial Perfusion Reserve Is Associated With Decreased Regional Left Ventricular Function in Asymptomatic Participants of the Multi-Ethnic Study of Atherosclerosis , 2006, Circulation.

[20]  P. Vanhoutte.  Endothelial control of vasomotor function: from health to coronary disease. , 2003, Circulation journal : official journal of the Japanese Circulation Society.

[21]  E. Wellnhofer,et al.  Noninvasive Determination of Coronary Blood Flow Velocity With Cardiovascular Magnetic Resonance in Patients After Stent Deployment , 2003, Circulation.

[22]  Robert Elashoff,et al.  Coronary Vasomotor Abnormalities in Insulin-Resistant Individuals , 2004, Annals of Internal Medicine.

[23]  O. Ratib,et al.  Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction , 2007, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[24]  EikeNagel,et al.  Noninvasive Determination of Coronary Blood Flow Velocity With Cardiovascular Magnetic Resonance in Patients After Stent Deployment , 2003 .

[25]  Hatem Alkadhi,et al.  Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  N. Geller,et al.  Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain. , 2006, Journal of the American College of Cardiology.

[27]  Cyrill Burger,et al.  Bicycle exercise stress in PET for assessment of coronary flow reserve: repeatability and comparison with adenosine stress. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Filippo Crea,et al.  Coronary microvascular dysfunction. , 2013, The New England journal of medicine.

[29]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2009, Circulation.

[30]  T. Shiga,et al.  Smoking cessation normalizes coronary endothelial vasomotor response assessed with 15O-water and PET in healthy young smokers. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[31]  M. Phelps,et al.  Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  O. Rimoldi,et al.  Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans. , 2001, Cardiovascular research.

[33]  Klassen Ga,et al.  Coronary circulatory pressure gradients. , 1987 .

[34]  Keiichiro Yoshinaga,et al.  What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? , 2006, Journal of the American College of Cardiology.

[35]  John O. Prior,et al.  Improvement in coronary vascular dysfunction produced with euglycaemic control in patients with type 2 diabetes , 2006, Heart.

[36]  S. Higano,et al.  Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. , 2000, Circulation.

[37]  H. Oswald,et al.  Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance. , 2000, Circulation.

[38]  Michael Kreissl,et al.  Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. , 2005, Journal of the American College of Cardiology.

[39]  A. Arai,et al.  Estimation of absolute myocardial blood flow during first‐pass MR perfusion imaging using a dual‐bolus injection technique: Comparison to single‐bolus injection method , 2008, Journal of magnetic resonance imaging : JMRI.

[40]  Haosen Zhang,et al.  Fast mapping of myocardial blood flow with MR first‐pass perfusion imaging , 2008, Magnetic resonance in medicine.

[41]  J. Ornato,et al.  ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult—Summary Article , 2005 .

[42]  W. Chilian.  Coronary microcirculation in health and disease. Summary of an NHLBI workshop. , 1997, Circulation.

[43]  Herbert Köstler,et al.  Comparison of different contrast agents and doses for quantitative MR myocardial perfusion imaging , 2008, Journal of magnetic resonance imaging : JMRI.

[44]  P. Kellman,et al.  Nonlinear myocardial signal intensity correction improves quantification of contrast‐enhanced first‐pass MR perfusion in humans , 2008, Journal of magnetic resonance imaging : JMRI.

[45]  M. Mongillo,et al.  Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study. , 2007, Journal of the American College of Cardiology.

[46]  H. Alkadhi,et al.  13N-ammonia myocardial perfusion imaging with a PET/CT scanner: impact on clinical decision making and cost-effectiveness , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[47]  F. Prato,et al.  Measurement of the extraction efficiency and distribution volume for Gd‐DTPA in normal and diseased canine myocardium , 1993, Magnetic resonance in medicine.

[48]  Ornella Rimoldi,et al.  Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[49]  A. Gavazzi,et al.  Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy , 2007, Heart.

[50]  Ran Klein,et al.  Quantification of myocardial blood flow with 82Rb dynamic PET imaging , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[51]  R. Boellaard,et al.  Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy. , 2008, American journal of physiology. Heart and circulatory physiology.

[52]  G. V. von Schulthess,et al.  Assessment of Myocardial Perfusion in Coronary Artery Disease by Magnetic Resonance: A Comparison With Positron Emission Tomography and Coronary Angiography , 2001, Circulation.

[53]  M. Robson,et al.  Cardiovascular magnetic resonance perfusion imaging at 3-tesla for the detection of coronary artery disease: a comparison with 1.5-tesla. , 2007, Journal of the American College of Cardiology.

[54]  M E Phelps,et al.  Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease. , 1995, Circulation.

[55]  P. Marraccini,et al.  Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. , 1993, Journal of the American College of Cardiology.

[56]  Daniel C. Lee,et al.  Magnetic Resonance Versus Radionuclide Pharmacological Stress Perfusion Imaging for Flow-Limiting Stenoses of Varying Severity , 2004, Circulation.

[57]  G. Fakhri,et al.  Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[58]  H. Drexler,et al.  Endothelial Dysfunction of the Coronary Microvasculature Is Associated With Impaired Coronary Blood Flow Regulation in Patients With Early Atherosclerosis , 1991, Circulation.

[59]  Frank J. Rybicki,et al.  Interrelation of Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease: A Combined Positron Emission Tomography/Computed Tomography Study , 2008, Circulation.

[60]  O. Rimoldi,et al.  Assessment of the long-term reproducibility of baseline and dobutamine-induced myocardial blood flow in patients with stable coronary artery disease. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[61]  Stephan G Nekolla,et al.  Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography. , 2002, Journal of the American College of Cardiology.

[62]  F. Girolami,et al.  Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy. , 2006, Journal of the American College of Cardiology.

[63]  W. Wijns,et al.  Intracoronary and Intravenous Adenosine 5′-Triphosphate, Adenosine, Papaverine, and Contrast Medium to Assess Fractional Flow Reserve in Humans , 2003, Circulation.

[64]  D. Pennell,et al.  Mechanisms of Coronary Microcirculatory Dysfunction in Patients With Aortic Stenosis and Angiographically Normal Coronary Arteries , 2002, Circulation.

[65]  T. Lüscher,et al.  Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans , 2004, Circulation.

[66]  E. Antman,et al.  ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionucl , 2003, Journal of the American College of Cardiology.

[67]  A. van Rossum,et al.  MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial. , 2008, European heart journal.

[68]  R. Körfer,et al.  Effect of cardiac resynchronization therapy on global and regional oxygen consumption and myocardial blood flow in patients with non-ischaemic and ischaemic cardiomyopathy. , 2005, European heart journal.

[69]  I. Olivotto,et al.  Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. , 2003, The New England journal of medicine.

[70]  M. Trivella,et al.  Time-dependent response of coronary flow to prolonged adenosine infusion: doubling of peak reactive hyperaemic flow. , 1981, Cardiovascular research.

[71]  W. Burchert,et al.  Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[72]  S. Nekolla,et al.  Effect of the Angiotensin Receptor Blocker Valsartan on Coronary Microvascular Flow Reserve in Moderately Hypertensive Patients with Stable Coronary Artery Disease , 2007, Microcirculation.

[73]  P. Camici,et al.  From microcirculation to cardiac event: protection with Preterax. , 2008, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[74]  John O. Prior,et al.  Coronary Circulatory Dysfunction in Insulin Resistance, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus , 2005, Circulation.

[75]  P. Kellman,et al.  Quantitative myocardial perfusion analysis with a dual‐bolus contrast‐enhanced first‐pass MRI technique in humans , 2006, Journal of magnetic resonance imaging : JMRI.

[76]  M. Jerosch-Herold,et al.  Myocardial blood flow quantification with MRI by model-independent deconvolution. , 2002, Medical physics.

[77]  C. Higgins,et al.  Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents. , 1997, Journal of the American College of Cardiology.

[78]  K. Furie,et al.  Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2007, Circulation.

[79]  W. Stanley.  Myocardial Energy Metabolism During Ischemia and the Mechanisms of Metabolic Therapies , 2004, Journal of cardiovascular pharmacology and therapeutics.

[80]  Sebastian Kelle,et al.  Prognostic Value of Cardiac Magnetic Resonance Stress Tests: Adenosine Stress Perfusion and Dobutamine Stress Wall Motion Imaging , 2007, Circulation.

[81]  P. Kaufmann,et al.  Myocardial blood flow measurement by PET: technical aspects and clinical applications. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[82]  Nico Westerhof,et al.  Cross-talk between cardiac muscle and coronary vasculature. , 2006, Physiological reviews.

[83]  J. Yap,et al.  Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[84]  John O. Prior,et al.  PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[85]  R. Foale,et al.  Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: implications for pharmacologic stress testing in coronary artery disease , 2006, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.