PET as an Essential Component of Every Modern-Day Clinical Nuclear Laboratory
Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been a mainstay of the noninvasive assessment of coronary artery disease (CAD) for more than 30 years. It has occupied a pivotal role between treadmill exercise and invasive coronary angiography (Figure 1), providing statistical improvements in diagnostic accuracy and helping to better identify patients needing a coronary intervention as opposed to medical therapy alone.1 SPECT MPI is practiced widely in 2016 much as it was in the early 1990s. The Anger camera predominates despite limited count statistics; the protocols require radiation exposures no longer in favor; attenuation correction is rarely used; there have been no new tracers and none in late-phase development; and provision of the service is expensive due largely to through-put inefficiencies. In the current era, a nuclear cardiology service will be called upon to assess myocardial perfusion in a wide array of patients, from those with no known CAD but low-intermediate pretest probability, to the most complicated patients with long histories of CAD with, perhaps, prior revascularizations or infarctions, cardiomyopathies, co-existent valve diseases, and numerous comorbidities. Furthermore, nuclear cardiac imaging today is increasingly used for non-perfusion indications such as myocardial viability,2 device infections,3 endocarditis,4,5 and cardiac sarcoidosis.6 I will argue here that SPECT will continue to be an important tool; however, providers will need to upgrade their SPECT scanners and will use them for a smaller percent of myocardial perfusion referrals. Furthermore, absence of cardiac positron emission tomography (PET) will impede a program's obligations for training tomorrow's nuclear specialists and will adversely affect the needs of heart failure and electrophysiology specialists.
Figure 1: The "old paradigm" in which SPECT MPI is viewed as an ideal test for a broad array of patients regardless of clinical complexity, ability to exercise, or physical characteristics. (TMET = treadmill exercise test; ICA = invasive coronary angiography)
Strengths of PET/Computed Tomography for MPI
The advantages of PET for MPI are many (Table 1). Higher diagnostic accuracy has been shown in several meta-analyses.7-9 Image quality is consistently high and superior to SPECT when performed in the same patients. PET images are count-rich and reliably corrected for tissue attenuation and scatter, so that image quality and interpretive certainty are relatively unaffected by patient gender, body size, or body shape. Scan acquisition times are in the range of 5 minutes versus 1525 minutes for SPECT. The shorter acquisition times are ideal for acutely ill patients and those who find it difficult to lay still. A full rest/stress study using rubidium-82 can be completed in less than 35 minutes, compared to several hours for a rest/stress SPECT.10,11 Radiation exposures are in the range of 2 mSv for a rest/stress PET MPI, about 15% of typical SPECT exposures and far below any levels known to connote risk for adverse effects.12,13 The lower radiation is important because many patients with chronic CAD undergo a large number of radiation-associated diagnostic and therapeutic procedures during the course of their lifetime battle with CAD. Finally, most PET scanners include a computed tomography (CT) component. For MPI studies, the CT is usually set at low tube current and voltage settings because the scans are used primarily for attenuation correction. These CT scans expose patients to only about 0.2 mSv of radiation but are adequate to visualize presence of coronary calcium and accurately estimate its Agatston score14 while also permitting recognition of pericardial and pleural effusions, thoracic aortic aneurysms, chamber sizes, valvular calcifications, and pulmonary pathologies. Studies such as those of Dorbala et al.15,16 have demonstrated independent and incremental improvements in risk stratification when PET-derived indices are considered in addition to myocardial perfusion patterns.
Table 1: Advantages of PET/CT Compared With Traditional SPECT for MPI
- Higher diagnostic accuracy with pharmacologic stress
- Consistent high image quality, independent of patient characteristics
- Short acquisition times, reduced study times
- Lower radiation exposure
- Myocardial blood flow quantification
- Improved risk stratification versus spatially relative MPI
A Unique Capability of PET MPI Compared With SPECT
A major limitation of SPECT is its dependency on differential perfusion of vascular territories in order to recognize functionally significant CAD. This so-called spatially relative interpretation of data opens the potential to under-detection of multivessel CAD. Especially with vasodilator stress, balanced flow reduction can go completely undiagnosed. PET is currently the only modality that permits routine quantification of myocardial blood flow, providing a patient-centric assessment of perfusion. Because myocardial blood flow is dependent on the functional integrity of the epicardial coronary arteries as well as the microvasculature, this measurement adds incrementally to perfusion defect analysis for risk stratification. In daily practice, myocardial blood flow quantification assures adequacy of vasodilator stress, improves recognition of multivessel CAD, rules out multivessel CAD, and in many instances results in different and more cost-effective management than would have occurred if this only depended on perfusion defect detection.17-23
The Expanding Applications of PET/CT for Cardiac Patients
In most cardiology programs, a PET/CT camera finds diverse uses beyond MPI. For example, even a relatively low-end device such as a PET/16-slice CT will be used for coronary artery calcium scoring, thoracic and abdominal aortic studies, run-off studies, left atrial imaging prior to atrial fibrillation ablation procedures, identification of cardiac sarcoidosis, and work-up of device infections. On a daily basis in our practice, PET/CT is used 5.5 times as often as a SPECT camera in the same testing unit.
A Modern-Day Clinical Cardiology Nuclear Laboratory
Design of a modern-day clinical nuclear laboratory needs to consider the diversity of patients needing nuclear cardiovascular imaging procedures. The paradigm of one camera and one protocol for all MPI needs has passed (Figure 1). An ideal laboratory today (Figure 2) will have a cardiac-dedicated SPECT camera for low-intermediate CAD-likelihood patients who need an MPI but can exercise. Such a device might be a solid-state camera with high sensitivity and high resolution, such that micro-dosages of tracer can be used. The same laboratory will have a PET/CT for more complicated patients as described above, predominantly those requiring vasodilator stress. Because of the high efficiency of the PET/CT, numerous other imaging applications will be possible each day. Some might argue that a SPECT camera in a cardiology department and a PET/CT in a radiology/nuclear medicine department could accomplish the same end-point as a revised nuclear cardiology laboratory that included both SPECT and a PET/CT. However, this would require duplication of stress-testing facilities and stress-test clinical teams and would impede ability of the imaging teams making on-the-fly decisions about best test after actually seeing the referred patient. An example might be recognizing on presentation that a patient admitted from the emergency department overnight had a caffeinated beverage 8 hours earlier and is unable to exercise. Only a PET study with blood flow quantification would be able to determine if a normal scan can be trusted or if the patient's A2a receptors did not respond to vasodilation stress. An alternative model is to have the PET/CT situated within the stress-test area that includes SPECT. The PET/CT can easily be assigned throughout the day, via either block scheduling or interspersed with cardiac indications, for oncologic or central nervous system studies.
Figure 2: The "new paradigm" in which newer SPECT protocols (solid-state cameras, advanced software options, stress-only imaging) optimized for low-intermediate risk patients share MPI referrals with PET/CT reserved for higher-risk, higher-complexity patients.
Imaging technology is expensive to purchase and maintain, and provision of PET radionuclides adds additional cost. However, PET/CT has a much greater potential than SPECT to add value and reduce the costs of care. Its rapid acquisition times and ability to complete studies in 3035 minutes makes it ideal for improving the efficiency of diagnosing inpatients and those in chest pain units, facilitating timely discharges or same-day coronary angiograms depending on the findings. The costs are largely fixed, such that costs do not rise in proportion to volume as with SPECT. The radionuclide most commonly used, rubidium-82, is onsite and immediately available, as opposed to the technetium-99m-based SPECT tracers that from time of order may take an hour or more to arrive onsite. Greater diagnostic certainty by virtue of several markers not available from SPECT such as peak stress versus rest global and regional function, coronary calcium presence and extent, attenuation correction, scatter compensation, and blood flow quantification can all expedite correct diagnoses, limit unnecessary downstream testing, and provide an opportunity to inform both patients and referring physicians in a far more comprehensive way about the state of myocardial perfusion. As indicated, opportunities for shared usage are enabled by the rapid acquisition protocols; SPECT imaging takes longer and the rest/stress protocols are longer, making economically feasible sharing of a camera more challenging.
With all the Advantages, Why do Some Cardiology Programs Still not Have Access to Cardiac PET?
Few nuclear cardiologists today would argue that cardiac SPECT alone is sufficient to address the radionuclide imaging needs of a contemporary cardiology practice. In time, virtually all sizeable programs will need to have access to cardiac PET imaging. The impediments are financial, educational, and political. The economic barrier to entry is high for small practices but not so for larger programs, for which the high utilization for diverse purposes makes it more attractive than SPECT. Providers (technologists, physicians, and nurses) do need opportunities for both education and training because PET tracers and instrumentation differ significantly from SPECT. PET scanners are widely available in the United States. In some settings, a PET scanner can and should be shared for oncologic and cardiac imaging. In others, the scanner might be dedicated for cardiac imaging. In my opinion, a cardiology program in an advanced center that does not have access to cardiac PET is most likely laboring under political constraints concerning inter-specialty cooperation that is standing in the way of best patient care. The reader is encouraged to browse two recent joint publications10,11 of the American Society of Nuclear Cardiology and the Society of Nuclear Medicine and Molecular Imaging to understand the professional societal viewpoint on the role of PET in the contemporary care of cardiac patients.
- Bateman TM. Twelfth annual Mario S. Verani, MD memorial lecture: Vision, leadership, and change-A reflection on the challenges and opportunities in the community-based practice of nuclear cardiology. J Nucl Cardiol 2015;22:435-49.
- Beanlands RS, Nichol G, Huszti E, 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;50:2002-12.
- Kim J, Feller ED, Chen W, Dilsizian V. FDG PET/CT imaging for LVAD associated infections. JACC Cardiovasc Imaging 2014;7:839-42.
- Saby L, Laas O, Habib G, et al. Positron emission tomography/computed tomography for diagnosis of prosthetic valve endocarditis: increased valvular 18F-fluorodeoxyglucose uptake as a novel major criterion. J Am Coll Cardiol 2013;61:2374-82.
- Pizzi MN, Roque A, Fernández-Hidalgo N, et al. Improving the Diagnosis of Infective Endocarditis in Prosthetic Valves and Intracardiac Devices With 18F-Fluordeoxyglucose Positron Emission Tomography/Computed Tomography Angiography: Initial Results at an Infective Endocarditis Referral Center. Circulation 2015;132:1113-26.
- Osborne MT, Hulten EA, Singh A, et al. Reduction in 18F-fluorodeoxyglucose uptake on serial cardiac positron emission tomography is associated with improved left ventricular ejection fraction in patients with cardiac sarcoidosis. J Nucl Cardiol 2014;21:166-74.
- Nandular KR, Dwamena BA, Choudhri AF, Nandalur SR, Reddy P, Carlos RC. Diagnostic performance of positron emission tomography in the detection of coronary artery disease: A meta-analysis. Acad Radiol 2008;15:444-51.
- Mc Ardle BA, Dowsley TF, deKemp RA, Wells GA, Beanlands RS. 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;60:1828-37.
- Parker MW, Iskandar A, Limone B, et al. Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis. Circ Cardiovasc Imaging 2012;5:700-7.
- Dilsizian V, Bacharach SL, Beanlands RS, et al. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol 2016;23:1187-226.
- Bateman TM, Dilsizian V, Beanlands RS, DePuey EG, Heller GV, Wolinsky DA. American Society of Nuclear Cardiology and Society of Nuclear Medicine and Molecular Imaging Joint Position Statement on the Clinical Indications for Myocardial Perfusion PET. J Nucl Med 2016;57:1654-6.
- Hunter CR, Hill J, Ziadi MC, Beanlands RS, deKemp RA. Biodistribution and radiation dosimetry of (82)Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging. Eur J Nucl Med Mol Imaging 2015;42:1032-42.
- Mattsson S, Johansson L, Leide Svegborn S, et al. Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances. Ann ICRP 2015;44(2 Suppl):7-321.
- Einstein AJ, Johnson LL, Bokhari S, et al. Agreement of visual estimation of coronary artery calcium from low-dose CT attenuation correction scans in hybrid PET/CT and SPECT/CT with standard Agatston score. J Am Coll Cardiol 2010;56:1941-21.
- Dorbala S, Hachamovitch R, Curillova Z, 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;2:846-54.
- Dorbala S, DiCarli MF, Beanlands RS, et al. Prognostic value of stress myocardial perfusion positron emission tomography: results from a multicenter observational registry. J Am Coll Cardiol 2013;61:176-84.
- 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;2:751-8.
- Herzog BA, Husmann L, Valenta I, 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;54:150-6.
- Ziadi MC, DeKemp RA, Williams KA, 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;58:740-8.
- Murthy VL, Naya M, Foster CR, et al. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation 2011;124:2215-24.
- Merhige ME, Breen WJ, Shelton V, Houston T, D'Arcy BJ, Perna AF. Impact of myocardial perfusion imaging with PET and (82)Rb on downstream invasive procedure utilization, costs, and outcomes in coronary disease management. J Nucl Med 2007;48:1069-76.
- Gould KL, Johnson NP, Bateman TM, et al. Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making. J Am Coll Cardiol 2013;62:1639-53.
- Taqueti VR, Hachamovitch R, Murthy VL, et al. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation 2015;131:19-27.
Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Nuclear Imaging
Keywords: Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Echocardiography, Electrocardiography, Electrons, Magnetic Resonance Imaging, Myocardial Perfusion Imaging, Physical Exertion, Positron-Emission Tomography, Rubidium, Sarcoidosis, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed
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