Review
Assessment of myocardial perfusion and viability by Positron Emission Tomography

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Abstract

An important evolution has taken place recently in the field of cardiovascular Positron Emission Tomography (PET) imaging. Being originally a highly versatile research tool that has contributed significantly to advance our understanding of cardiovascular physiology and pathophysiology, PET has gradually been incorporated into the clinical cardiac imaging portfolio contributing to diagnosis and management of patients investigated for coronary artery disease (CAD). PET myocardial perfusion imaging (MPI) has an average sensitivity and specificity around 90% for the detection of angiographically significant CAD and it is also a very accurate technique for prognostication of patients with suspected or known CAD. In clinical practice, Rubidium-82 (82Rb) is the most widely used radiopharmaceutical for MPI that affords also accurate and reproducible quantification in absolute terms (ml/min/g) comparable to that obtained by cyclotron produced tracers such as Nitrogen-13 ammonia (13N-ammonia) and Oxygen-15 labeled water (15O-water). Quantification increases sensitivity for detection of multivessel CAD and it may also be helpful for detection of early stages of atherosclerosis or microvascular dysfunction. PET imaging combining perfusion with myocardial metabolism using 18F-Fluorodeoxyglucose (18F FDG), a glucose analog, is an accurate standard for assessment of myocardial hibernation and risk stratification of patients with left ventricular dysfunction of ischemic etiology. It is helpful for guiding management decisions regarding revascularization or medical treatment and predicting improvement of symptoms, exercise capacity and quality of life post-revascularization. The strengths of PET can be increased further with the introduction of hybrid scanners, which combine PET with computed tomography (PET/CT) or with magnetic resonance imaging (PET/MRI) offering integrated morphological, biological and physiological information and hence, comprehensive evaluation of the consequences of atherosclerosis in the coronary arteries and the myocardium.

Introduction

Positron Emission Tomography (PET) is a nuclear medicine modality, which for many years has been employed as a highly sophisticated research tool only in centers with access to cyclotron facilities. A shift in the use of PET imaging from the research to clinical setting has taken place recently, as a result of the greater availability of PET scanners (mainly to support cancer services) and the increasing documentation of PET's clinical efficacy. PET scanners are currently available in a hybrid form, combining PET with computed tomography (CT) or magnetic resonance imaging (MRI) offering a unique opportunity for a comprehensive noninvasive evaluation of the consequences of atherosclerosis both in the coronary arteries and the myocardium and translating advances in molecular imaging into humans. This review covers the current developments and future directions of PET imaging, emphasizing the role of PET on the assessment of myocardial perfusion and viability. It discusses the radiopharmaceuticals which are used for performance of clinical studies and also the stress tests and imaging protocols as well as the modality's usefulness in the evaluation of coronary artery disease (CAD), from its early detection to heart failure. Issues around cost effectiveness and comparisons with other imaging modalities are also discussed.

Section snippets

Selection of patients for PET myocardial perfusion imaging

Both the ACC/AHA/ASNC clinical guidelines and the position statement on advanced noninvasive [1] cardiac imaging produced jointly by the Canadian Cardiovascular and Imaging societies [2] recommend PET myocardial perfusion imaging (MPI) for diagnosis and/or risk stratification of CAD patients who have had nondiagnostic, noninvasive imaging tests, or when there is discrepancy between a test's results and clinical diagnosis (Class I and evidence level B). Patients with left bundle brunch block

Physiology and tracers

The myocardium has one of the highest energy demands of any tissue. It uses a variety of metabolic substrates, but under physiological conditions most of the energy required for contraction comes from the oxidation of free fatty acids. Glucose, lactate, pyruvate, ketone bodies and amino acids are also used depending on availability, hormonal factors, and myocardial oxygen demand. Under conditions of ischemia, oxidation of fatty acids is suppressed and there is increased glycolysis and glycogen

Radiation exposure from PET studies

The main advantage of the positron emitting tracers is the shorter physical half-life, compared to SPECT tracers. Therefore, the radiation burden to the patient and the nuclear medicine personnel is lower. The estimated effective radiation dose to the patient is 3.8 mSv for 82Rb (rest and stress) and less than 3 mSV for 13N-ammonia and 15O-water (rest and stress) [83], [84], [85], [86]. Even when the additional burden of 0.04 mSv for scout/localizing CT and 0.35 mSv for CT attenuation correction is

Economic evaluation

There is limited information on the cost effectiveness of PET based strategies for the diagnosis and management of stable CAD. Patterson et al. [88] have compared the cost-effectiveness and cost-utility of exercise ECG, SPECT, PET and coronary angiography, to diagnose obstructive CAD. Effectiveness was defined as the number of patients with diagnosed CAD, and utility as the number of quality-adjusted life years (QALY) extended by therapy after the diagnosis. They observed that in patients with

Hybrid PET/CT and PET/MRI imaging

Combined assessment of coronary anatomy and function is an attractive option that is feasible with the new PET/CT systems. A number of reports have demonstrated improved specificity and positive predictive value (PPV) in the detection of angiographically significant stenoses when perfusion data from PET and angiographic data from CT angiography were combined. The largest of these studies has included 107 patients with chest pain and intermediate likelihood of CAD. The study compares hybrid 15O-H

Conclusion

Cardiac PET is currently undergoing a paradigm shift. Being originally a highly versatile research tool, it has gradually become a valuable imaging modality that is currently used in a variety of clinical scenarios ranging from early detection of coronary atherosclerotic disease to heart failure. Experience with PET was accumulated over decades and there is a wide body of evidence, including cost effectiveness data, to support its integration into investigative strategies of CAD. The modality's

Acknowledgments

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

References (96)

  • B.A. Mc Ardle et al.

    Does Rubidium-82 PET have superior accuracy to SPECT perfusion imaging for the diagnosis of obstructive coronary disease? A systematic review and meta-analysis

    J Am Coll Cardiol

    (2012)
  • T.H. Marwick et al.

    Incremental value of Rubidium-82 Positron Emission Tomography for prognostic assessment of known or suspected coronary artery disease

    Am J Cardiol

    (1997)
  • K. Yoshinaga et al.

    What is the prognostic value of myocardial perfusion imaging using Rubidium-82 Positron Emission Tomography?

    J Am Coll Cardiol

    (2006)
  • S. Dorbala 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)
  • M.M. Hajjiri et al.

    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)
  • B.A. Herzog 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)
  • M.C. Ziadi 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)
  • R.J. Golub et al.

    Interpretive reproducibility of stress Tc-99m sestamibi tomographic myocardial perfusion imaging

    J Nucl Cardiol

    (1999)
  • J.P. Goulle et al.

    MRI gadolinium-based contrast agents. Radiologists beware!

    Ann Pharm Fr

    (2009)
  • C. Jaarsma 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

    J Am Coll Cardiol

    (2012)
  • P. Bernhardt et al.

    Blood oxygen-level dependent magnetic resonance imaging using T2-prepared steady-state free-precession imaging in comparison to contrast-enhanced myocardial perfusion imaging

    Int J Cardiol

    (2011)
  • R. Gebker et al.

    High spatial resolution myocardial perfusion imaging during high dose dobutamine/atropine stress magnetic resonance using k–t SENSE

    Int J Cardiol

    (2012)
  • G. Morton et al.

    Quantification of absolute myocardial perfusion in patients with coronary artery disease: comparison between cardiovascular magnetic resonance and positron emission tomography

    J Am Coll Cardiol

    (2012)
  • M.C. Ziadi 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)
  • G.B. Saha et al.

    Present assessment of myocardial viability by nuclear imaging

    Semin Nucl Med

    (1996)
  • P. Camici et al.

    Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by Positron Emission Tomography

    Prog Cardiovasc Dis

    (1989)
  • F.M. Bengel et al.

    Cardiac Positron Emission Tomography

    J Am Coll Cardiol

    (2009)
  • A.N. Kitsiou et al.

    13N-ammonia myocardial blood flow and uptake: relation to functional outcome of asynergic regions after revascularization

    J Am Coll Cardiol

    (1999)
  • A.F. Schinkel et al.

    Clinical relevance of hibernating myocardium in ischemic left ventricular dysfunction

    Am J Med

    (2010)
  • A.F. Schinkel et al.

    Hibernating myocardium: diagnosis and patient outcomes

    Curr Probl Cardiol

    (2007)
  • D. Eitzman et al.

    Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography

    J Am Coll Cardiol

    (1992)
  • R. Rohatgi et al.

    Utility of positron emission tomography in predicting cardiac events and survival in patients with coronary artery disease and severe left ventricular dysfunction

    Am J Cardiol

    (2001)
  • H.M. Siebelink et al.

    No difference in cardiac event free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium

    J Am Coll Cardiol

    (2001)
  • R.S. Beanlands et al.

    F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease: a randomized controlled trial (PARR-2)

    J Am Coll Cardiol

    (2007)
  • G. D'Egidio et al.

    Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial

    JACC Cardiovasc Imaging

    (2009)
  • Y. Inaba et al.

    Quantity of viable myocardium required to improve survival with revascularization in patients with ischemic cardiomyopathy: a meta-analysis

    J Nucl Cardiol

    (2010)
  • R.C. Bourge et al.

    Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study

    J Am Coll Cardiol

    (2008)
  • M.F. Di Carli et al.

    Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction

    Am J Cardiol

    (1994)
  • T.H. Marwick et al.

    Prediction by postexercise fluoro-18 deoxyglucose positron emission tomography of improvement in exercise capacity after revascularization

    Am J Cardiol

    (1992)
  • F. Haas et al.

    Preoperative positron emission topographic viability assessment and perioperative and postoperative risk in patients with advanced ischemic heart disease

    J Am Coll Cardiol

    (1997)
  • T. Shukla et al.

    Does FDG PET-assisted management of patients with left ventricular dysfunction improve quality of life? A substudy of the PARR-2 trial

    Can J Cardiol

    (2012)
  • J.G. Howlett et al.

    The 2010 Canadian Cardiovascular Society guidelines for the diagnosis and management of heart failure update: heart failure in ethnic minority populations, heart failure and pregnancy, disease management, and quality improvement/assurance programs

    Can J Cardiol

    (2010)
  • P.B. Jacklin et al.

    Cost-effectiveness of preoperative positron emission tomography in ischemic heart disease

    Ann Thorac Surg

    (2002)
  • F.P. Esteves et al.

    Absent coronary artery calcium excludes inducible myocardial ischemia on computed tomography/positron emission tomography

    Int J Cardiol

    (2011)
  • F. Klocke 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 Radionuclide Imaging)

    Circulation

    (2003)
  • M.F. Di Carli et al.

    Clinical myocardial perfusion PET/CT

    J Nucl Med

    (2007)
  • G. EL Fakhri et al.

    Reproducibility and accuracy of quantitative myocardial blood flow assessment with 82Rb PET: comparison with 13N-Ammonia PET

    J Nucl Med

    (2009)
  • J.O. Prior et al.

    Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

    Eur J Nucl Med Mol Imaging

    (2012)
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