1. 7G.V. Heller, R.C. Hendel (eds.), Handbook of Nuclear Cardiology,
DOI 10.1007/978-1-4471-2945-5_2, © Springer-Verlag London 2013
2.1 Introduction
In many laboratories, Single Photon Emission Computed Tomography (SPECT)
imaging is the test of choice for nuclear cardiology procedures. Despite this, cardiac
Positron Emission Tomography (PET) perfusion imaging has been recognized as
superior to standard SPECT imaging due to higher image quality and a greater
efficiency [1]. However, it has been infrequently used due to limited availability of
camera systems, radiopharmaceuticals and technical difficulties in cardiac acquisi-
tion and processing. Recently, the number of PET Camera systems has increased
substantially and acquisition, processing and display of Cardiac PET studies has
vastly improved. Thus, since its introduction in the early 1980s [2], the use of
Cardiac PET perfusion imaging has greatly increased within the last 8 years. Its
superior sensitivity and specificity over SPECT myocardial perfusion imaging [3],
as well as the routine availability of Rubidium-82 (Rb-82), has made cardiac PET
an important tool in the detection and risk stratification of coronary artery disease.
This chapter will discuss some of the technical differences between PET and SPECT
cameras, particularly as it relates to choice of technologies, and provide insights as
to when PET might be preferable to SPECT for individual patients. A more detailed
description of PET radiopharmaceuticals is provided in Part III (Chap. 13) and PET
instrumentation in Part III (Chap. 14).
J. Lundbye, M.D., FACC
The Hospital of Central Connecticut,
100 Grand Street, New Britain, CT 06050, USA
e-mail: jlundbye@thocc.org
Chapter 2
Cardiac Positron Emission Tomography
Justin Lundbye

2. 8 J. Lundbye
2.2 Instrumentation: Cardiac PET
PET technology makes use of the decay of radioactive tracers, most commonly
Rb-82 that are taken up by the organ (the heart) of interest. During the course of
Rb-82 decay, positrons are emitted which collide with electrons (annihilation). This
collision creates an energy discharge in the form of photons moving in 180° oppo-
site directions which the PET camera can register using multiple specialized detec-
tors around the patient. Compared to SPECT, PET uses coincidence detection and
time of flight to localize and event. Hence this makes PET very accurate (Fig. 2.1).
Recently radiation exposure from medical imaging has become an important
topic. Both SPECT and PET will, albeit low, expose the patient to radiation. However
by following simple protocols this exposure can be minimized. In regards to SPECT,
tracer and protocol choice can substantially reduce the radiation expose. Thallium
results in 15–20 mSv of exposure while Technetium results in 8–10. In contrast,
cardiac PET can reduce the exposure to as low as 3–5 mSv primarily due to the
more efficient protocol and better suited isotope [4] (Table 2.1). These data demon-
strate PET perfusion imaging has favorably radiation dosimetry and should be con-
sidered for the appropriate patient.
Annihilation
γγ
P
P
B+
B+
PP
P
N
N
N
N
511 KeV
511 KeV
Fig. 2.1 Annihilation. As Rb-82 decay occurs the positrons are emitted which collide with elec-
trons to (annihilation). The collision results in energy discharge in the form of photons moving in
180° opposite. PET camera can register these photons using multiple specialized detectors around
the patient
Table 2.1 Common radiation exposure in millisievert based on testing modality
Imaging modality Exposure in millisieverts (mSv)
Dual isotope imaging 25–30
Thallium stress-rest 20
Diagnostic catheterization 10
Rest-stress single isotope Technetium 8–10
PET, dedicated, Rb-82 4–6
PET, F-18 4–8
CT angiography 2–25

3. 92 Cardiac Positron Emission Tomography
2.3 Diagnosis and Risk Stratification: Cardiac PET
Single-photon emission computed tomography (SPECT) myocardial perfusion
imaging is a well established method of evaluating for coronary artery disease
with over 30 years of experience supported by literature validating its diagnostic
and prognostic value. The excellent procedural and clinical guidelines published
by ACCF and ASNC have made this testing modality widely available in the out-
patient and in-patient setting. And although it has valuable role for the diagnosis
and determining the prognosis of coronary artery disease its sensitivity ranges
from 70–85%, frequently underestimating the degree of ischemia and also
the presence of multivessel coronary artery disease. In addition, the prolonged
procedure and acquisition times (estimate 2½–4 h) makes this procedure less
attractive.
Cardiac Positron Emission Tomography (PET) is quickly gaining popularity
offering many advantages over SPECT. The diagnostic accuracy, risk stratification
utility and a faster protocol has made cardiac PET an attractive alternative to SPECT.
Several studies have demonstrated that PET offers a superior diagnostic accuracy
in detecting CAD. A recent systematic review of PET by Al Moudi et al. [5], dem-
onstrated a superior sensitivity and specificity of PET when compared to SPECT
leading to increased diagnostic accuracy (Fig. 2.2). Importantly this diagnostic
95
90
85
82
76
83
91 89 89
Sensitivity Specificity Accuracy
80
75
70
65
SPECT PET
Fig. 2.2 Overall diagnostic accuracy of PET versus SPECT (Adapted from al Moudi et al. [5], and
demonstrates the superior sensitivity, specificity and diagnostic accuracy of PET when compared
to SPECT)

4. 10 J. Lundbye
performance has been shown to be similar between gender and body mass index
thus making PET superior when compared to SPECT [1]. Similarly, PET is also
better able to detect multivessel coronary disease hence making it an important tool
in managing these patients [1]. Moreover, Al Moudi and colleagues also demon-
strated that PET has the highest diagnostic value when assessing individual coro-
nary arteries for disease [5] (Fig. 2.3).
Cardiac PET imaging acquisition protocols are much more efficient than SPECT
(Fig. 2.4). Most cardiac PET perfusion laboratory protocols can be completed in
25–40 min. This is a greater than 50% reduction in procedure time when compared
to SPECT (Fig. 2.5).
Recently, the assessment of regional and global myocardial blood flow using
objective quantification techniques for both common PET tracers of Rb-82 and N13
ammonia has entered the clinical arena. This procedure can aid the clinician in
assessing the physiologic significant of known coronary artery stenosis, determine
balanced ischemia and also assist in identifying microvascular disease. There are
active research studies exploring other utilities of PET blood flow quantification.
The technology takes advantage of kinetic analysis of the transit of the radiotracer
through the cardiac chambers and the myocardium. From this, time activity curves
are generated and since the dose of radioactivity injected and the time it takes to
reach the myocardium is known, using mathematical modeling techniques, myocar-
dial blood flow in ml/g/min can be computed.
100
80
60
40
20
0
Sensitivity
Specificity
Accuracy
Sensitivity
Specificity
Accuracy
Sensitivity
Specificity
Accuracy
LAD LCx RCA
PET SPECT
Fig. 2.3 Diagnostic accuracy of PET versus SPECT based on epicardial vessel (Adapted from al
Moudi et al. [5]), and demonstrates the sensitivity, specificity and diagnostic accuracy in PET and
SPECT in the epicardial coronary arteries (LAD left anterior descending, LCx left circumflex, RCA
right coronary artery)

5. 112 Cardiac Positron Emission Tomography
Figure 2.6 demonstrates a normal blood flow pattern with a flow reserve at rest
(>0.7 mL/g/min) and at peak hyperemia using dipyridamole (2.0–3.0 mL/g/min) [6].
This virtually eliminates “balanced ischemia” in this patient. In contrast Fig. 2.7 dem-
onstrates a patient with normal PET images but severely decreased blood flow at peak
hyperemia of 1.21 mL/g/min suggesting endothelial dysfunction or balanced ischemia.
Finally several of the newer PET cameras offer a hybrid system with CT imaging
available as well. Coronary calcification scoring as well as non-invasive coronary
angiography can be obtained using the hybrid PET cameras.
0 45
Radiopharmaceutical
Injection
(rest)
Radiopharmaceutical
Injection
(stress)
60 90
Stress ImagingRest Imaging
Imaging time: 30 minutes
Elapsed Time: 21/2 –4 hours
120 135
Fig. 2.4 Stress test using SPECT can be time consuming for the patient and staff. Schematic
demonstrating a usual stress test SPECT protocol
Rb–82
20–60 mCi
CT
attenuation
correction
CT
attenuation
correction
70–90 sec
Approx 1 min Approx 7 min Approx 7 min Approx 1
min
Approx 6 min
Elapsed Time: 25 Minutes
70–90 sec
Rb–82
20–60
mCi
gated
rest
gated
stress
pharmacologic
stress*
PET/CT Protocol
Fig. 2.5 Pharmacologic stress test (Dipyridamole, regadenoson or dobutamine) using PET can be
completed in 25 min. Schematic demonstrating a usual pharmacologic stress test PET protocol
with Rb-82. CT, Computed tomography

6. 12 J. Lundbye
Stress
Stress
Stress
LAD
3.16
(mI/g/min)
0
1.27
0
4.6420
15
10
5
0
Time(sec)
Myo
Myo
0
25
50
75
100
125
Frame
Slice
BOUNDARY BP ROI 0
2.74
2.69
2.88
2.77
0.88
1.09
1.02
0.97
3.11
2.46
2.81
2.89
RCA
Global
LCx
LAD
RCA
Global
LCx
LAD
RCA
Global
LCx
Stress
Stress
Print/Export
Rest
Rest
Rest
Rest
Stress BP IBP:8.64 (mCi/mI)min
IBP:10.63 (mCi/mI)minBPRest
Reserve
Rest
Fig. 2.6 Patient with normal flow. This example demonstrate a patient with normal stress and rest of all
epicardial vessels (Courtesy, James Case, Cardiovascular Imaging Technologies, Kansas City, MO)
LAD 1.10
1.31
1.31
1.21
0.82
1.15
0.95
0.93
1.34
1.14
1.39
1.31
RCA
Global
LCx
LAD
RCA
Global
LCx
LAD
RCA
Global
LCx
Stress
Reserve
20
15
(vCi/mI)
Print/Export
Options
Tools
10
5
0
Time(sec)
Myo
Myo
0
25
50
75
100
125
Stress IBP:2.14 (mCi/mI)min.
IBP:2.13 (mCi/mI)min.Rest
Rest
Stress
Bloos Pool ROI
Arterial Input Function
QMP Quality Review QMP Results
Rest
Stress
Boundary
Rest
BP
BP
Frame
Reposition ROIs Reposition ROIs
Slice
Apply 1st frame subtraction
3.16
0
1.27
0
4.64
0
(mI / g / min)
(mI / g / min)
(ratio)
Fig. 2.7 Patient with normal perfusion in setting of decreased flow reserve suggestive of endothe-
lial dysfunction (Courtesy, James Case, Cardiovascular Imaging Technologies, Kansas City, MO)

7. 132 Cardiac Positron Emission Tomography
2.4 Patient Selection
There are several important roles for cardiac PET, (Table 2.2) however it is most
commonly used for perfusion imaging to diagnose and risk stratify coronary
artery disease. In addition, cardiac PET is used to identify viable myocardium in
patients with ischemic cardiomyopathy. Lastly, though with increasing utiliza-
tion, cardiac PET is used to identify cardiac sarcoidosis. These topics will be
discussed separately.
Although there are currently no specific guidelines to indicate which patients are
best suited for a cardiac PET perfusion study, there are evidence based published
AmericanCollegeofCardiology(ACC)andAmericanSocietyofNuclearCardiology
(ASNC) Appropriate Use Criteria for Cardiac Radionuclide Imaging [7], which
addresses indications. These may be helpful in directing the clinician toward which
imaging study is most appropriate for their patients.
Equivocal SPECT study results are a relatively common occurrence rooting from•
attenuation artifact and improper testing protocol. Since cardiac PET has supe-
rior image quality, as well as better sensitivity and specificity, most equivocal
SPECT images that undergo cardiac PET will have a conclusive read after the
PET study. Studies have shown that as little as 2% of studies that were equivocal
by SPECT are also non-diagnostic by PET. Thus, it is recommended that patients
that have undergone a cardiac SPECT with inconclusive or equivocal test results
should be considered for cardiac PET to more effectively exclude or diagnose
coronary artery disease.
Obese patients suspected of having coronary artery disease may also benefit•
from a Cardiac PET perfusion study for diagnosis or risk stratification. Patients
weighing over 250 lb, with a BMI greater than 30 should be considered for car-
diac PET rather than SPECT. Cardiac PET isotopes generate a three-fold higher
energy emission than SPECT can capture and therefore offer better diagnostic
accuracy without the attenuation artifact that is often seen with SPECT in this
patient population. In addition, PET has a much more robust attenuation correc-
tion protocol making it more reliable in this patient population.
Patients with known coronary artery disease in which a specific coronary artery•
territory is being assessed for ischemia may also benefit from cardiac PET perfu-
sion study. One of the important qualities of cardiac PET is its higher accuracy
Table 2.2 Utility of cardiac PET myocardial perfusion imaging
Patient selection for cardiac PET
1 Equivocal SPECT study
2 Obese patients
3 Patient with known coronary artery disease
4 Myocardial viability
5 Pharmacologic stress tests
6 Evaluation for cardiac sarcoidosis

8. 14 J. Lundbye
in detecting multivessel disease. When contrasted to SPECT for the detection of
multivessel disease, the sensitivity is 71% for PET as compared to 48% for
SPECT. For this reason, cardiac PET may be a better option for not only identify-
ing territories that would benefit from revascularization, but also for risk stratify-
ing patients that may have multivessel coronary artery disease.
Viability assesment is another important utility of culiac PET. It is well recognized•
that among patients with ischemic cardiomyopathy, LV systolic dysfunction can
result from myocardial necrosis, myocardial hibernation, or repetitive myocardial
stunning. Whereas myocardial necrosis is irreversible, systolic dysfunction result-
ing from hibernation and stunning are potentially reversible states that may recover
with reperfusion. Identification of myocardial viability can be assessed with
fluorine-18 labeled deoxyglucose (FDG) PET study. This study takes advantage of
the fact that ischemic myocytes utilize glucose as a source of energy rather than
fatty acids. Thus, the myocytes will take up a glucose analog, fluorine-18 labeled
deoxyglucose (FDG) in an area of dysfunctional myocardium. This study can iden-
tify metabolic activity and therefore, viability. The cardiac, FDG-PET is an impor-
tant tool for providers in identifying viable myocardium in which revascularization
should be considered. This topic is more completely discussed in Chap. 7.
Patients who are undergoing pharmacologic stress test, we believe, should also•
be considered for cardiac PET as it is well known that cardiac PET offers better
diagnostic accuracy with a much faster imaging protocol and lower radiation
exposure than SPECT.
Sarcoidosis is a systemic disease that primarily affects the lungs and lymphatic•
system. In 5–30% of cases however, the heart can be involved. The course of car-
diac sarcoidosis is variable and ranges from benign arrhythmias or high-degree
heart block to sudden death. Thus cardiac sarcoidosis warrants evaluation to
confirmthepresenceorabsenceofdisease.Anemergingmodalityusing18
Fluorine-
2-fluoro-2-deoxy-d-glucose (FDG) PET has become an important testing modal-
ity to diagnose the disease with reports of higher sensitivity and specificity than
other testing modalities.
In Summary, cardiac PET is an important new imaging tool in cardiovascular
disease management. With superior sensitivity and specificity cardiac PET plays an
important role in identifying and risk stratifying ischemic heart disease in patients
as well as identifying hibernating myocardium, and cardiac sarcoidosis and viabil-
ity assessment.
2.5 Conclusion
Cardiac PET is an emerging non-invasive imaging technology with faster imaging
and acquisition protocol, less radiation exposure and with a superior diagnostic
accuracy. Although its usage has primarily been limited due to availability, these
procedures are gaining in popularity.

9. 152 Cardiac Positron Emission Tomography
References
1. Bateman TM, Heller GV, McGhie AI, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82
myocardial perfusion PET: comparison with ECG-gated Tc-99 m sestamibi SPECT. J Nucl
Cardiol. 2006;13(1):24–33.
2. Schelbert HR, Wisenberg G, Phelps ME, et al. Noninvasive assessment of coronary stenoses by
myocardial imaging during pharmacologic coronary vasodilation. VI. Detection of coronary
artery disease in human beings with intravenous N-13 ammonia and positron computed tomog-
raphy. Am J Cardiol. 1982;49(5):1197–207.
3. Nandalur 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(4):444–51.
4. Cerqueira MD, Allman KC, Ficaro EP, et al. Recommendations for reducing radiation exposure
in myocardial perfusion imaging. J Nucl Cardiol. 2010;17(4):709–18.
5. al Moudi M, Sun Z, Lenzo N. Diagnostic value of SPECT, PET and PET/CT in the diagnosis of
coronary artery disease: a systematic review. Biomed Imaging Interv J. 2010;7(2):e9.
6. DeKemp RA, Yoshinaga K, Beanlands RS. Will 3-dimensional PET-CT enable the routine
quantification of myocardial blood flow? J Nucl Cardiol. 2007;14(3):380–97.
7. Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM
2009 appropriate use criteria for cardiac radionuclide imaging: a report of the American College
of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear
Cardiology, the American College of Radiology, the American Heart Association, the American
Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society
for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. J Am Coll
Cardiol. 2009;53(23):2201–29.

10. http://www.springer.com/978-1-4471-2944-8