Dilsizian2016 Article ASNCImagingGuidelinesSNMMIProc

ASNC IMAGING GUIDELINES/SNMMI
PROCEDURE STANDARD
ASNC imaging guidelines/SNMMI procedure

standard for positron emission tomography
(PET) nuclear cardiology procedures
Vasken Dilsizian, MD,a Stephen L. Bacharach, PhD,b Rob S. Beanlands, MD,c
Steven R. Bergmann, MD, PhD,d Dominique Delbeke, MD,e
Sharmila Dorbala, MD, MPH,f Robert J. Gropler, MD,g Juhani Knuuti, MD, PhD,h
Heinrich R. Schelbert, MD, PhD,i and Mark I. Travin, MDj
a
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of
Medicine, Baltimore, MD
b
Department of Radiology, University of California–San Francisco, San Francisco, CA
c
Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada
d
Pat and Jim Calhoun Cardiology Center, UConn Health, Farmington, CT
e
Department of Radiology, Vanderbilt University Medical Center, Nashville, TN
f
Division of Nuclear Medicine, Brigham and Women’s Hospital, Boston, MA
g
Division of Nuclear Medicine, Washington University School of Medicine, St. Louis, MO
h
Turku PET Centre, Turku University Hospital, Turku, Finland
i
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at
UCLA, Los Angeles, CA
j
Department of Radiology, Montefiore Medical Center, Bronx, NY
Received Mar 25, 2016; accepted Mar 25, 2016

doi:10.1007/s12350-016-0522-3
INTRODUCTION tomography (PET) measurements of myocardial blood

flow (MBF) in absolute terms (milliliters per gram per
Stress-induced myocardial perfusion defects have
minute) offer a paradigm shift in the evaluation and
been firmly established as an important diagnostic and
management of patients with CAD. The latter is con-
prognostic technique for identifying flow-limiting epi-
current with the recent shift in the management of CAD
cardial coronary artery disease (CAD). However,
from an anatomical gold standard (i.e., coronary
interpretation of such myocardial perfusion imaging
angiogram) to a functional one. Moreover, non-invasive
(MPI) studies has been primarily qualitative or semi-
quantification of MBF extends the scope of conventional
quantitative in nature, assessing regional perfusion
MPI from detection of end-stage, advanced, and flow-
defects in relative terms. Quantitative positron emission
limiting epicardial CAD to early stages of atheroscle-
rosis or microvascular dysfunction and assessment of
balanced reduction of MBF in all three major coronary
This article is co-sponsored by the American Society of Nuclear
Cardiology and the Society of Nuclear Medicine and Molecular arteries. Quantitative approaches that measure MBF
Imaging. The full set of guidelines can be found within this article, with PET identify multivessel CAD and offer the
published in the Journal of Nuclear Cardiology; a related Editorial, opportunity to monitor responses to lifestyle and/or risk
published in the Journal of Nuclear Medicine, can be found at: factor modification and to therapeutic interventions.
https://doi.org/10.2967/jnumed.116.176214.
PET utilizes radionuclide tracer techniques to pro-
Reprint requests: Vasken Dilsizian, MD, Department of Diagnostic
Radiology and Nuclear Medicine, University of Maryland Medical duce images of in vivo radionuclide distribution using
Center, South Greene Street, Rm N2W78, Baltimore, MD 21201- an external detector system. Similar to computed
1595; [email protected] tomography (CT), the images acquired with PET rep-
J Nucl Cardiol 2016;23:1187–226. resent cross-sectional slices through the heart. However,
1071-3581/$34.00
with PET, the image intensity reflects organ function
Copyright 2016 American Society of Nuclear Cardiology & Society
of Nuclear Medicine and Molecular Imaging. and physiology as opposed to anatomy. The functional
1187
1188 Dilsizian et al Journal of Nuclear Cardiology
PET myocardial perfusion and metabolism clinical imaging September/October 2016
information that can be obtained from PET images (low radiation exposure), efficient (short image acqui-
depends upon the radiopharmaceutical employed. PET sition times), and patient-centered (accommodates ill or
allows non-invasive evaluation of MBF, function, and higher risk patients, as well as those with large body
metabolism using physiological substrates prepared with habitus), providing equitable and timely care.
positron-emitting radionuclides, such as carbon, oxygen, Recent advances in hybrid PET/CT instrumentation
nitrogen, and fluorine. These radionuclides have half- and multichannel spiral CT allow detailed, non-invasive
lives that are often considerably shorter than those used visualization of the coronary arteries, as an adjunct to
in single photon emission computed tomography PET imaging. Whereas multichannel CT angiography
(SPECT). Positron-emitting radionuclides can be pro- provides information on the presence and extent of
duced using a cyclotron (e.g., 18F-fluoro-2-deoxyglucose anatomical luminal narrowing of epicardial coronary
[18F-FDG] with a 110-minute half-life) or using a arteries, stress myocardial perfusion PET provides
generator (e.g., rubidium-82 [82Rb] with a 75-second information on the downstream functional consequences
half-life from a strontium-82 [82Sr] generator). of such anatomic lesions. Thus, with hybrid PET/CT
PET radionuclides reach a more stable configuration systems, complementary information of anatomy and
by the emission of a positron. Positrons are the anti- physiology can be obtained during the same imaging
matter of electrons. They are positively charged particles session. The ability to evaluate CAD, myocardial
with the same rest mass as electrons. When a positron perfusion, metabolic viability, and ventricular function
spends time near an electron, the two annihilate—they from a hybrid PET/CT image makes such systems an
both disappear and in their place two 511-keV gamma important tool in the clinical practice of cardiology.
rays are emitted. Because the gamma rays are nearly In the last few years, not only have combined PET/
collinear (discharged at 180 to each other) and travel in CT scanners proliferated, but PET combined with
opposite directions, the PET detectors can be pro- magnetic resonance (MR) imaging scanners have been
grammed to register only events with temporal introduced (PET/MR). While the main use for these
coincidence of photons that strike directly at opposing scanners continues to be for oncological applications,
detectors.1 The result is improved spatial (4- to 6-mm) cardiac CT and MR are now well established. The
resolution when compared with SPECT, as well as melding of CT or MR to a PET camera increases the
temporal resolution. The high temporal resolution of complexity of scanning protocols, quality maintenance
PET is also explained by the fact that the imaging device and assurance but also expands imaging to correlate
is stationary compared with the rotating imaging gantry anatomy, molecular biology, and metabolism with
for SPECT. Moreover, the PET system is more sensitive nuclear imaging thereby providing comprehensive eval-
than a SPECT system due to the higher count rate and uation of the heart. For example, co-registration of 18F-
provides the possibility of attenuation correction. The FDG metabolic imaging with morphological, functional,
result of these advantages with PET is the potential for and tissue imaging attributes of MR presents new
quantitation of tracer concentration in absolute units. opportunities for disease characterization, such as car-
Quantification of MBF may provide diagnostic and diac sarcoidosis, hallmarked by inflammatory injury,
prognostic information earlier than visual interpretation non-caseating granuloma formation, and organ dysfunc-
of relative radiotracer uptake, which is a fundamental tion which could be the first clinical application of PET/
disadvantage of the conventional SPECT technique. MR in cardiology.2 18F-FDG PET in cardiac sarcoidosis
The PET detectors are placed in a ring, surrounding produces ‘‘hot spot’’ images. MR is particularly helpful
the patient, and are configured to register only photon for anatomic co-localization of the 18F-FDG PET signal
pairs that strike opposing detectors at approximately the within the heart, reflecting the inflammatory phase of
same time, termed coincidence detection. Over the cardiac sarcoidosis. MR delayed enhancement, on the
course of a typical scan, millions of coincidence events other hand, provides information on areas of fibrosis and
are recorded, and projections of the activity distribution scar as a consequence of cardiac sarcoidosis. It is
are measured at all angles around the patient. These reasonable, therefore, to have a hybrid system in which
projections are subsequently used to reconstruct an MR can show the focus of prior injury or scar from
image of the in vivo radionuclide distribution using the sarcoidosis superimposed on inflammatory markers seen
same algorithms as those used in SPECT and x-ray CT. with 18F-FDG.3
The resulting PET images have improved spatial and The current document is an update of an earlier
temporal resolution when compared to SPECT. Hence, version of PET guidelines that was developed by the
the imaging properties of PET meet some of the Centers American Society of Nuclear Cardiology (ASNC).4 The
for Medicare & Medicaid Services (CMS) implementa- publication is designed to provide imaging guidelines for
tion of quality initiatives to assure quality health care. physicians and technologists who are qualified to prac-
PET MPI is effective (high diagnostic accuracy), safe tice nuclear cardiology. While the information supplied
Journal of Nuclear Cardiology Dilsizian et al 1189
Volume 23, Number 5;1187–226 PET myocardial perfusion and metabolism clinical imaging
in this document has been carefully reviewed by experts Some scanners have retractable septa, permitting
in the field, the document should not be considered the user to choose between 2D and 3D operation. Many
medical advice or a professional service. We are cog- PET/CT manufacturers have opted for scanners that
nizant that PET, PET/CT, and PET/MR technology is operate only in 3D mode, because these allow maximum
evolving rapidly and that these recommendations may patient throughput for multi-bed position oncology
need further revision in the near future. Hence, the studies. Situations in which 3D mode may be advanta-
imaging guidelines described in this publication should geous include the following:
not be used in clinical studies until they have been
1. Whole-body patient throughput is important (e.g., a
reviewed and approved by qualified physicians and
busy oncology practice).
technologists from their own particular institutions.
2. Radiation exposure is critical, so that reductions in
injected activity are desired.
PET, PET/CT, AND PET/MR INSTRUMENTATION 3. Special (i.e., usually research) radiopharmaceuticals
are being used, which can only be produced in low-
PET Imaging Systems radioactivity quantities.
The majority of dedicated PET cameras consist of As noted above, although 3D acquisition is in principle
rings of small detectors that are typically a few many times more sensitive than 2D, ‘‘accidental,’’ or
millimeters on a side, and tens of millimeters deep. random coincidences (termed randoms), dead time, and
Coincidences between detectors in a single ring produce scatter can greatly reduce the effective sensitivity of images
one tomographic slice of data. Usually, one or more acquired in 3D, especially at high doses. Thus, in order to
adjacent rings may also contribute to counts in that slice. prevent poor-quality images, lower doses are often admin-
In a 2-dimensional (2D) or ‘‘septa-in’’ PET scanner, istered in 3D mode. Accordingly, 3D imaging can be used
there is a septum (e.g., lead or tungsten) between when the dose must be minimized (e.g., in normal
adjacent rings. This septum partially shields coinci- volunteers, in children, or when multiple studies are
dences from occurring between detectors in one ring and planned) or when scatter is minimal (e.g., brain imaging).
detectors in a non-adjacent or more distant ring. By The advent of lutetium-based crystals, such as lutetium
minimizing coincidences between a ring and its more oxyorthosilicate (LSO) and lutetium yttrium orthosilicate
distant neighboring rings, the septa greatly reduce (LYSO) along with gadolinium oxyorthosilicate (GSO)-
scattered events. based PET scanners, and even bismuth germanate (BGO)
A scanner with no septa in place is referred to as a scanners with new-generation optimized photomultiplier/
3-dimensional (3D) or ‘‘septa-out’’ scanner. This crystal coupling schemes and high-speed electronics, has
nomenclature is somewhat confusing as both septa-in made 3D imaging more practical. Improvements in soft-
and septa-out modes produce 3D images. The septa-out ware, coupled with improvements in electronics and crystal
(3D) mode, however, permits coincidences between all technology, can, in part, compensate for the increase in
possible rings, greatly increasing sensitivity but also randoms, dead time, and scattered events associated with
greatly increasing scatter, as well as the count rate for 3D imaging.10 The use of 3D-cardiac imaging with new-
each individual detector. This increase in count rate can generation machines continues to be evaluated. The degree
increase dead time and random events. The increased to which any of these improvements in 3D is achieved in
sensitivity is the greatest for the central slice and falls practice for cardiac imaging may vary between manufac-
rapidly and roughly linearly, for slices more distant from turers and between applications (high-count rate versus
the central slice. The slices near the edge have a normal count rate studies).
sensitivity about the same as in a 2D scanner but with
greater scatter. Scatter is measured with standards
PET Imaging: Crystal Types
provided by the National Electrical Manufacturers
Association (NEMA)5–9 and is typically in the order of Three different crystal types are commonly
10 to 15% for 2D scanners and 30-40% or more for 3D employed in PET, including BGO, GSO, and lutetium-
scanners. In chest slices encompassing the heart, as based crystals, such as LSO and LYSO, although other
opposed to the relatively small NEMA phantom, there is crystal types have also been used. The technical spec-
an even larger increase in scattered counts for 3D ifications of each crystal type have been well
imaging. For cardiac applications, scatter tends to documented.11 Each type of crystal has been used
artifactually increase the counts in cold areas surrounded successfully for cardiac imaging. BGO has the highest
by higher activity regions (e.g., a defect surrounded by stopping power, but relatively poor energy resolution
normal uptake, or near the liver). (which limits energy-based scatter reduction) and poor
timing resolution (limiting its ability to reduce randoms the machine, the two photons would reach their respec-
at high count rates). GSO, LSO, and LYSO have better tive detectors at exactly the same time, while if the
timing resolution and, in theory, better energy resolu- annihilation occurred closer to one detector than the
tion. For 2D imaging, GSO, LSO, and LYSO may not other, the photon would reach the closer detector first. If
offer significant advantages over BGO, given the inher- the time difference could be measured accurately
ently high sensitivity of BGO and the lower count rates enough, it would be possible to determine exactly where
encountered in 2D versus 3D studies. The main advan- the annihilation event is originated.
tage of the GSO and lutetium-based crystals is reduced Unfortunately, current detector and instrumentation
dead time, which enables them to acquire data at higher technology is not nearly good enough to achieve this
count rates associated with operating in 3D mode, and to level of accuracy. However, it has been shown that
better minimize the effects of randoms. One minor adding TOF capability can improve the statistical
disadvantage of LSO and LYSO is their intrinsic quality of the data (i.e., the noise).12–14 For example,
radioactivity, which contributes to a small increase in recent reports indicate that TOF imaging can improve
the random event rate. noise and image quality in 13N-ammonia perfusion
The better energy resolution of GSO, LSO, or imaging,15 and therefore potentially improve image
LYSO compared to BGO, and consequent reduction of quality or even perhaps, in the future, reduce the dose
scatter, would in principal make these detector types needed to achieve a given image quality. In addition, as
advantageous in 3D mode. At present, the theoretical mentioned above, performing high-count rate cardiac
energy resolution for these detectors does not seem to studies with 3D scanners presents difficulties. Prelimi-
have been fully realized in practice, leaving all four nary studies indicate that some of these difficulties may
crystal types with similar energy-based scatter rejection be reduced with TOF imaging; however, much work
(i.e., GSO and lutetium-based crystals giving an remains to be done. As most users do not use machines
improvement, but not a great one, over BGO) and in the TOF mode, quality control (QC) of this feature
making 2D imaging still the method of choice if scatter should follow recommendations of the manufacturer and
rejection is critical. NEMA NU 2-2012 testing procedures.5
Modern image reconstruction algorithms incorpo-
rate improved models for scatter correction, and as a
Hybrid PET/CT and PET/MR Cameras
result, the impact of scatter for state-of-the-art scanners
operating in 3D mode is usually acceptable for clinical For many years, most PET scanners have been sold
imaging. In cardiac imaging, areas of low uptake (e.g., combined with a CT scanner. In all cases, the manufac-
perfusion defects) may still be slightly overestimated turer starts with a state-of-the-art PET scanner, whose
with 3D compared to 2D when these defects are near characteristics have been described in the section above.
regions of high tracer uptake. The suitability of 3D mode The manufacturer then adds a CT system, with 64 or
for cardiac PET imaging should be evaluated by the more slices. These combined systems, in practice,
user. For studies with a wide range of count rates, such demonstrate a range of integration. At one end of the
as quantitative 82Rb scans, 3D acquisitions can be spectrum, the hardware and software of the CT systems
problematic unless great care is taken to address the high are completely integrated within the PET scanner. A
count rates achieved during and immediately after common, unified gantry is used and a single, unified
infusion. Therefore, for 3D 82Rb acquisitions, GSO software system with an integrated PET/CT interface is
and lutetium-based crystals are thought to have an provided. At the other end of the spectrum, the hardware
advantage over BGO. Improvements in crystal manu- and software of the CT system are less integrated. In
facture and design, as well as the development of some machines, a separate CT gantry is carefully placed
scanners with new crystal types, may further improve in front of or behind the PET gantry, and a separate
3D scatter rejection and 3D imaging during bolus workstation is used to control the CT system. Although
injections (e.g., quantitative 82Rb studies). originally the CT component of the hybrid PET/CT
camera was developed for attenuation correction and
anatomical co-localization purposes, more modern
PET Time-of-Flight (TOF) Imaging
machines have CT scanners that are of diagnostic
Machines that incorporate time-of-flight (TOF) quality, which allows the assessment of both coronary
information in the acquisition process have been devel- artery calcium scoring and CT angiography. The scope
oped and are available. TOF refers to the time difference of these CT procedures is beyond the purview of these
between when the two 511-keV annihilation photons PET guidelines, and has been covered in a recent
reach their respective detectors, 180 apart. For exam- SNMMI/ASNC/SCCT guideline.16 More recently, PET
ple, if the positron annihilation occurred at the center of scanners have also been introduced combined with MR.
Two different types of systems are available—in-line many respiratory cycles. The respiratory misalignment
systems and simultaneous systems. The first uses a between the CT image and emission data can produce
common gantry for both imaging modalities, and is very significant artifacts and errors in apparent uptake in the
similar to PET/CT devices with the CT replaced by MR. myocardial segments adjacent to lung tissue.17 Errors in
In-line systems allow existing state-of-the-art PET and attenuation correction from misregistration are typically
MR scanners to be combined adjacently, although much worse if the CT is acquired at full inspiration, and
alterations may be necessary to accommodate the nearby so the CT is often acquired at either end-expiration or
high magnetic fields. The so-called ‘‘simultaneous’’ during shallow breathing. Software realignment must be
systems allow both image sets to be acquired at the same performed to minimize any remaining misalignment.
time—although depending on their design there may be Other techniques (e.g., slow CT, respiratory gating, and
some performance limitations. Attenuation correction 4D-CT) are under development for compensating for
with either type of system can be problematic. Unlike respiratory motion, but are still in the research phase and
CT images, MR images do not necessarily produce are not further described here.
images from which PET attenuation correction factors MR images, unlike CT or rotating rod images, do
can be derived. MR imaging is, of course, quite valuable not directly measure attenuation values. Instead, MR-
in cardiology, so it is possible that the combination of based attenuation correction usually must rely on indi-
MR with PET will result in interesting new clinical rect methods, for example using the MR image to
applications. PET/MR is still in its early stages and separate tissue types (e.g., lung, soft tissue, and bone).
much work remains before its full clinical potential in The segmented images are then used to assign each
cardiology is recognized. tissue type a pre-determined attenuation value. Use of
this method for organs, such as the heart, with a tissue/
lung interface, still requires further study.
PET Imaging: Attenuation Correction
PET AND PET/CT OR PET/MR IMAGING QC
For dedicated PET scanners (without CT or MR),
rotating rod sources or rings of germanium-68
PET QC Procedures
(68Ge)/gallium-68 (68Ga) or cesium-137 (137Cs) are
used to acquire a transmission scan for attenuation The procedures below should be suitable for ensur-
correction. A typical transmission scan with rotating ing overall proper basic operation of a PET scanner.
rods adds about 60 to 600 seconds to the overall Table 1 lists the recommended PET imaging QC
imaging time. This is acceptable for cardiac imaging, schedules.4 Note that, unlike planar and SPECT imag-
but is a significant drawback for multi-bed position ing, there are no widely accepted, published QC
oncology scans. Because oncology applications con- procedures for PET. Some additional procedures may
tinue to drive sales of PET scanners, manufacturers be required by particular manufacturers.
looked for a way to reduce this transmission scan time. Acceptance testing. It is recommended that the
For this reason, and because of other advantages of CT, NEMA performance measurements, as defined by NU 2-
nearly all current commercially available PET scanners 2012,5 be made before accepting the PET scanner. Many
are hybrid PET/CT systems. These scanners, in gen- of these tests can be performed by the company
eral, have eliminated the rotating rod source and supplying the PET scanner. If so, it is recommended
instead rely on CT scans for attenuation correction. that the purchaser’s representatives work with the
The Hounsfield units (HU) generated by the CT manufacturer’s representatives during these tests. The
scanner can usually be accurately converted into PET NU 2-2012 recommendations have superseded the NU
attenuation values. 2-2007 recommendations.8 In scope, the tests are nearly
CT-based attenuation correction typically adds less equivalent between NU 2-2012 and NU 2-2007.5,8 For
than 10 seconds to the cardiac scan time. The use of cardiac imaging, these QC performance standards
either CT or the rotating rod for attenuation correction should be performed.
requires precise alignment between the transmission There are two reasons for making these perfor-
image and the emission image. An advantage of CT over mance measurements:
transmission sources is a much reduced scan time, which 1. To ensure the new PET scanner meets specifications
helps reduce overall patient motion. The high speed of published by the manufacturer and
CT scans, however, freezes the heart and lungs at one 2. To provide a standard set of measurements that
phase of the respiratory cycle, causing potential allows the user to document the limitations of the
misalignment between the CT-based transmission and scanner and to provide a standard against which to
emission scans. The latter, of course, are averaged over track changes that may occur over time.
Table 1. Suggested QC procedures: dedicated PET imaging devices
Procedure Frequency
Acceptance testing (NU 2-2012)5 Once upon delivery and upon major
hardware upgrades
Daily QC, as recommended by vendor (attenuation blank Daily
scan, phantom scan, etc.)
Sensitivity and overall system performance Weekly preferred (or at least monthly)
Accuracy (corrections for count losses and randoms) At least annually
Scatter fraction At least annually
Accuracy of attenuation correction At least annually
Image quality At least annually
Measurements specified by the manufacturer As per the manufacturer
Daily QC scan. Each day the PET detectors well as some material simulating lung tissue to ensure
should be evaluated to ensure proper operation before proper performance in the presence of non-uniform
commencing with patient injections or scans. The daily attenuating substances.
quality procedure varies according to the design of the Variations among manufacturers. The
scanner and recommendations of the vendor. For exam- above recommendations regarding PET scanner quality
ple, some scanners use an attenuation blank scan to assurance are general guidelines. In addition, each
evaluate detector constancy, and others may use a scan manufacturer has its own periodic QC recommendations
of a standard phantom. In addition to numerical output for parameters such as ‘‘singles’’ sensitivity, coinci-
of the scanners (chi-square, uniformity, etc.), the raw dence timing, energy calibration, and overall system
sinogram data also should be inspected to evaluate performance. These, by necessity, require different
detector constancy. measurement protocols that may vary even between
Sensitivity. NEMA NU 2-2012 provides recom- models for the same manufacturer. These measurements
mended procedures for measuring system sensitivity.5 must be performed as detailed by the manufacturer.
Subtle changes in PET system sensitivity may occur However, the measurements specified above are not
slowly over time. More dramatic changes in sensitivity intended to replace these basic system-specific QC
may reflect hardware or software malfunction. There are measurements.
simple tests designed to monitor such changes in
sensitivity. Ideally, these tests should be performed
CT QC Procedures
weekly, but no less than monthly. For many systems, the
daily QC scan also provides a measure useful for The procedures below should be suitable for ensur-
tracking changes in sensitivity. ing overall proper basic operation of a CT scanner.
Spatial resolution. Spatial resolution is mea- Table 2 lists recommended CT imaging QC schedules.
sured using a point source as specified in the NEMA NU Some additional procedures may be required by partic-
2-2012.5 ular manufacturers.
Scatter fraction. Intrinsic scatter fraction is Calibration. The reconstructed CT image must
measured according to NEMA NU 2-2012 exhibit accurate, absolute CT numbers in HU. This is
specifications.5 critical for the use of CT images for PET attenuation
Accuracy of attenuation correction and correction, because the quantitative CT values are
overall clinical image quality. Attenuation correc- transformed, usually via a bilinear or trilinear function
tion should be assessed using the IEC phantom, as with one hinge at or near the CT value for water, to
specified in the NU 2012 recommendations.5 If this attenuation coefficients at 511 keV. Any errors in CT
phantom is not readily available, it is suggested that numbers will be propagated as errors in estimated 511-
similar measurements be performed with a phantom keV attenuation coefficients, which in turn will
approximating a typical human body shape and size adversely affect the attenuation-corrected PET values.
(e.g., a 20- by 30-cm elliptical phantom or anthropo- CT system calibration is performed with a special
morphic phantom). It should have at least one cold calibration phantom that includes inserts of known CT
sphere or cylinder and one hot sphere or cylinder, as numbers. This calibration is done by the manufacturer’s
Table 2. CT QC procedures
Test Requirement Frequency
Calibration Mandatory Monthly*
Field uniformity Mandatory Monthly*
*or as recommended by the manufacturer
field-service engineers. The CT calibration is then Combined PET/CT QC Procedures

checked daily with a water-filled cylinder, usually 24
The PET and CT portions of the combined system
cm in diameter provided by the manufacturer. In
should be assessed as described for the dedicated PET
practice, if the error is greater than 5 HU (i.e., different
and CT imaging devices. In addition to the independent
than the anticipated value of 0 HU), the CT system is
QC tests for the PET and CT portions of the combined
considered to be out of calibration. The technologist will
system, it is necessary to perform additional tests that
then usually perform an air calibration, to determine if
assess the combined use of PET and CT. Table 4 lists
this corrects the overall calibration (i.e., brings the CT
recommended QC procedures for combined PET/CT
number for water back to within 5 HU of 0). If it does
units.
not, the manufacturer’s field-service engineer must be
Registration. The reconstructed PET and CT
called. On an annual basis, or after any major repair or
images must accurately reflect the same 3D locations
calibration, calibration is checked by the manufacturer’s
(i.e., the two images must be in registration). Such
service engineer.
registration is often difficult because the PET and CT
Field uniformity. The reconstructed CT image
portions of all commercial combined PET/CT systems
must exhibit uniform response throughout the field of
are not coincident (i.e., the PET and CT ‘‘slices’’ are not
view (FOV). In practice, this means a reconstructed
in the same plane) and the PET and CT gantries are
image or a uniform water-filled cylinder must demon-
contiguous. In practice, this means that the PET and CT
strate low variation in CT number throughout this
acquisitions do not simultaneously image the same slice.
image. In practice, small circular regions of interest
In fact, because the bed must travel different distances
(ROIs) are placed at the four corners of the cylinder
into the gantry to image the same slice in the patient for
image, and the mean CT number is compared to that
PET versus CT, there is ample opportunity for misreg-
from a region in the center of the phantom; the
istration via x, y, z misalignment of bed motion—or, of
difference in mean region CT number should not exceed
perhaps even greater concern, because of differential
5 HU. Non-uniformities greater than this may produce
‘‘bed sag’’ for the PET and CT portions, depending on
sufficient quantitative inaccuracies so as to affect PET
the table design.
attenuation correction based on the CT image.
In addition, electronic drift can influence the ‘‘po-
Table 3 lists recommended CT QC schedules for
sition’’ of each image, so that calibrations for
combined PET/CT units. Users should consult the
mechanical registration can become inaccurate over
manufacturer regarding the specific manner and fre-
time. Thus, it is imperative to check PET-to-CT regis-
quency with which tests should be performed for the CT
tration on an ongoing basis. This is usually performed
component of their PET/CT device. Both the American
with a specific phantom or jig containing an array of
College of Radiology (ACR) and American Association
point sources visible in both PET and CT. Errors in co-
of Physicists in Medicine (AAPM) have published CT
location in the fused PET/CT images are assessed, such
testing procedural guidelines.18
as by means of count profiles generated across transaxial
Table 3. Schedule of CT QC for PET/CT units
Test Frequency
Water phantom QA Daily
Tube warm-up Daily
Air calibration (“fast QA) Daily
Water phantom checks: slice thickness, Monthly
accuracy, positioning
Table 4. Combined PET/CT QC procedures

Combined PET/CT QC procedures
Test Requirement
Registration Mandatory
Attenuation correction accuracy Mandatory
slices. Such errors, after software registration correc- reconstruction errors. Because these scanners are still in
tions, should be less than 1 mm. It is important to image evolution, QC from the manufacturer should be
this registration jig in a number of positions along the followed.
bed. It may also be helpful to place a weight on the end
of the bed to produce some bed sag and repeat the
assessment. The above considerations are in addition to PET ACQUISITION AND PROCESSING
the patient-specific alignment QC clinically necessary to PARAMETERS
assess possible patient or respiratory motion.
The acquisition and processing parameters defined
Attenuation correction accuracy. The use of
in this section apply to both the perfusion and metabolic
the CT image for PET attenuation correction requires a
PET tracers in the sections that follow.
transformation of the observed CT numbers in HU to
attenuation coefficients at 511 keV. This transformation
is usually accomplished with a bilinear or trilinear
calibration curve, with one ‘‘hinge’’ at a CT value of 0 Patient Positioning
(i.e., hinged at the CT value for water). Ideally, the patient should be placed in the supine
At a minimum, it is important to image a water-filled position, with the arms out of the camera’s FOV.
cylinder to assess PET field uniformity and PET activity Nearly all patients can tolerate this position, provided
concentrations after CT-based PET attenuation correc- that some care is given to a method to support the
tion. Errors in CT-to-PET attenuation transformations are arms. Alternatively, an overhead bar has often been
usually manifest as a corrected PET image without a used as a handhold for arm support. In patients with
‘‘flat’’ profile from edge to center (i.e., the activity at the severe arthritis, whose arms cannot be positioned
edge is either too high or too low relative to that at the outside the camera’s FOV, cardiac images should be
center of the phantom) and with resulting attenuation- obtained with the patient’s arms resting on his/her
corrected absolute PET values that are incorrect (although side. In the latter case, the transmission scan time may
these values depend on absolute PET scanner calibration have to be increased, and it is of critical importance
as well as accurate CT-based PET attenuation correction). that the arms not move between the transmission and
If possible, the CT-based attenuation-corrected PET emission scans, or artifacts will result. When perform-
values should be compared with those from the rotating ing perfusion/metabolism PET studies, it is imperative
rod source-based attenuation-corrected PET values in the to keep the patient positioned similarly for both
same phantom. Moreover, if available, more sophisticated studies. In patients undergoing PET/CT imaging, arms
phantoms with variable attenuation and variable activity resting inside the FOV will result in beam-hardening
distributions can be used to more comprehensively assess artifacts on the CT-based transmission scan, which
any errors in CT-based PET attenuation correction. usually lead to streak artifacts on the corrected
The accuracy of CT attenuation-corrected PET emission scans.
images is still under investigation. Recent work has
reported that even after correcting for potential PET/CT
misalignment, tracer uptake maps derived from CT- Dose Considerations
based attenuation correction differ from those derived In determining appropriate patient doses, the fol-
using transmission source correction.17,19,20 lowing issues should be considered:
1. Staff exposure could be high because of the limited
PET-MR QC Procedure effectiveness of shielding and the potential for large
doses (e.g., 82Rb PET). Thus, standing in close
Many of the principles outlined above for PET/CT proximity to an 82Rb generator or the patient during
apply to hybrid PET/MR systems. Co-localization is injection should be avoided. It is also important to
especially important. Errors in misregistration of CT or point out that a lead apron is not helpful in shielding
MR and PET emission images can result in significant the 511-keV photons. In fact, it may increase staff
exposure due to secondary electrons emitted from the absolute MBF measurement to the visual interpretation
511-keV photon interaction with lead. of relative radiotracer uptake, it is strongly recom-
2. Large patients may benefit from higher doses. mended that the data be acquired in dynamic mode (i.e.,
3. 3D imaging requires less dosage than 2D imaging binning the data with time).
due to the improved sensitivity of the system. Usually, PET tracer counts are sufficiently high to
yield a good-quality ventricular function study. Electro-
cardiographic (ECG)-gated images are acquired in 8 to
Total Counts 16 time frames per R-to-R interval, in a manner similar
to SPECT-gated perfusion studies but at higher spatial
The counts per slice necessary to yield adequate
resolution. Given that ventricular contraction and thick-
quality images will vary from camera to camera
ening are often clinically useful for assessing viability,
depending, in part, on scatter and randoms corrections,
gating should be performed when possible. It is impor-
as well as the amount of smoothing that is performed. If
tant that the gating software does not adversely affect
one tries to achieve on the order of 7 mm full width at
the ungated images (e.g., by loss of counts as a result of
half maximum (FWHM) in-plane resolution and has 10
beat length rejection). Monitoring the length and number
to 15% scatter, then a typical good-quality study in 2D
of the accepted beats is critical to assure the accuracy of
mode might have on the order of 50,000 true counts per
the gated data. Arrhythmias, such as atrial fibrillation,
millimeter of transaxial distance over the region of the
frequent premature ventricular contractions (PVCs), or
heart (e.g., for a 4.25-mm slice separation, the number of
other abnormal rhythms can lead to highly erroneous
counts would be 50,000 9 4.25 = 250,000 counts per
gated information. List-mode acquisition may obviate
slice). These numbers are approximate and may differ
most of these problems.
from one scanner to the other. If one is willing to accept
For a dynamic acquisition, PET data are acquired in
a lower resolution (e.g., more smoothing) or more noise,
multiple time-sequenced frames. A potential advantage
imaging time can be reduced. 3D scanners have greater
of the dynamic over static acquisition is patient motion
scatter, and therefore they usually require more counts
artifact. For example, if a patient should move at the end
than a 2D scanner to achieve the same noise level.
of the study, select and utilize only those dynamic
frames with no motion (i.e., summing them together to
make one static image). This is easily implemented and
Pixel Size
takes almost no additional operator time. A more
It is recommended that 2–3 mm/pixel be used. A elaborate dynamic acquisition beginning just prior to
rule of thumb in nuclear medicine physics is that one the bolus injection of the tracer may be used optionally
should have at least 3 pixels for every FWHM of when kinetic analysis is to be performed (e.g., compart-
resolution in the image. For example, if the data are mental analysis or Patlak analysis). Kinetic analysis,
reconstructed to 8 mm FWHM, then this corresponds to which typically requires only the initial 3 to 5 minutes of
roughly 8 mm/3 = 2.7 mm/pixel. Many institutions data acquisition, permits absolute quantification of the
achieve a 3 mm sampling rate or better with a 256 9 256 tracer’s kinetic properties (e.g., blood flow for 82Rb and
13
array over the entire FOV of the camera. Other N-ammonia, rate of 18F-FDG utilization). Interpreta-
institutions choose to use a 128 9 128 array over a tion of quantitative MBF (or metabolic) data requires
limited FOV (e.g., 25 to 35 cm diameter) centered over appropriate training and expertise beyond that necessary
the heart, in which case, 2 to 3 mm/pixel is easy to for visual inspection of static, summed images.
achieve, cutting out extraneous structures in the FOV, List-mode acquisitions are now available with
even with a 128 9 128 array. Either method is nearly all cameras, which enable simultaneous dynamic
acceptable to achieve the desired 2 to 3 mm/pixel. and ECG-gated acquisitions. It is the optional acquisi-
Greater than 3 mm/pixel may be acceptable for older tion mode, and is routinely used with many vendors’
PET cameras with resolution worse than 1 cm FWHM. data processing software.
Imaging Mode (Static, Gated, or Dynamic) Image Reconstruction
Static PET acquisition produces images that allow Several corrections are required for creating datasets
relative assessment of tracer uptake on a regional basis. that can be used for reconstruction. PET data must be
Comparison of regional tracer uptake in relation to the corrected for randoms, scatter, dead time, attenuation,
normal tracer distribution is the current standard for the and decay before reconstruction can begin. Once these
identification of regional abnormalities. However, given corrections are applied, the data can be reconstructed
the growing literature regarding the incremental value of with either filtered backprojection (FBP) or iterative
algorithms. FBP is the standard method used for recon- and emission scans is not recommended unless the high
struction on older PET systems. FBP images are subject count rate and rapidly changing distribution of the emission
to streak artifacts, especially when the subject is obese or tracer can be assured to not adversely affect the transmis-
large. This can affect visual analysis but usually does not sion scan. If the transmission scan is performed at the
adversely affect quantitative analysis with regions of beginning of the study, attention should be made for
interest (i.e., the streaks tend to average out properly over potential misregistration with the emission scans, possibly
typical volumes of interest). Newer PET systems employ due to gradual upward creep of the diaphragm, due to
iterative reconstruction methods (such as ordered subset pressure from visceral fat.21
expectation maximization [OSEM]) yielding images For PET/CT or PET/MR systems, CT or MR can be
with superior noise properties. Although high-uptake used for acquiring a transmission scan for attenuation
structures, such as the heart, may not improve their noise correction. An advantage of this approach is the rapid
characteristics with iterative reconstruction approaches, acquisition of the transmission scan, which can be
the surrounding lower uptake structures do improve, and repeated for each imaging session, rest and stress
streak artifacts are nearly eliminated, thus greatly perfusion studies, as well as for subsequent metabolic
improving the visual appearance of the image. However, imaging, if necessary. The CT or MR scan can be
low-uptake areas, such as myocardial defects and the left reviewed for additional, independent diagnostic infor-
ventricular (LV) cavity at late times, may have slightly or mation, such as coronary calcium visualization and other
artificially elevated activity levels unless sufficient iter- extra-cardiac anatomic information. To acquire a CT- or
ations are performed. It is recommended that a cardiac MR-based transmission scan, it is necessary to first
phantom be used to characterize a PET machine and its acquire a planar scout acquisition. This scan is used to
reconstruction algorithm’s behavior. measure the axial limits of the full acquisition. Follow-
For rest/stress comparisons, the rest/stress images ing this acquisition, the transmission scan is acquired.
must have matched resolution. Filtering is usually The best approach for CT transmission scanning is still
necessary to achieve adequate noise properties. Care evolving, and therefore this guideline can only suggest
must be taken to match reconstructed resolution when some considerations. Some of the considerations for CT
making pixel-by-pixel comparisons of paired myocar- scanning are as follows (see Table 5):
dial perfusion and metabolism data.
1. If CT is used for either attenuation correction or
anatomical evaluation, it will have an effect on the
Attenuation Correction kVp and mAs used in the acquisition. A transmission
Cardiac PET imaging should only be performed with scan usually requires only a low CT current, as
attenuation correction. Attenuation correction can be opposed to calcium scoring or CT angiography,
accomplished with a rotating line source or ring in a which require higher CT currents.
dedicated PET system or with CT or MRI in a hybrid system. 2. Breathing protocols are not fully established. Recent
For dedicated PET systems, two techniques are data suggest that respiratory averaging may be a
typically used for creating the patient-specific transmis- useful method of reducing breathing-related artifacts.
sion scans: direct measurement of patient attenuation Other methods, such as free breathing with a slow CT
with a rotating line source of either 68Ge or 137Cs or scan or ultra-rapid CT acquisition (depending on the
segmentation of patient-specific attenuation maps. The CT device available), have also been proposed.
former are very sensitive to the choice of reconstruction Current practice discourages breath holding, partic-
algorithm and, depending on the reconstruction algo- ularly in end-inspiration because of the potential for
rithm used, could require 60 to 600 seconds acquisition it to cause uncorrectable misregistration. A CT
time to produce a reasonable attenuation map. Segmen- transmission scan performed at the same speed, as
tation algorithms are relatively insensitive to noise but for whole-body PET/CT images, frequently produces
are very dependent on the quality of the program used to artifacts at the lung-liver interface and can sample
perform the transmission scan segmentation and are parts of the heart and diaphragm in different
influenced by lung-attenuation inhomogeneity (e.g., positions, causing misregistration and an artifact
partial volume effects from the liver). where pieces of the diaphragm appear to be sus-
Transmission scans are typically acquired sequen- pended in the lung. Although specifics vary among
tially, so it is essential that the patient remains still between laboratories, the duration of the CT transmission scan
transmission and emission images. Either pre- or post- is typically from 10 to 30 seconds. CT attenuation
transmission scanning is acceptable, providing that the correction with 64-slice devices can achieve an ultra-
system’s software can adequately correct for residual rapid CT scan in 1.5 seconds, which appears to
emission activity. Simultaneous acquisition of transmission reduce such CT artifacts. Therefore, it is imperative
Table 5. General guidelines for CT-based transmission PET imaging
CT parameter General principle Effect on patient dose

Slice collimation Should approximate the slide thickness of No effect
PET (e.g. 4-5 mm)
Gantry rotation speed Slower rotation speed helps blur cardiac Slower gantry rotation
motion (e.g. 1 sec/revolution of slower increase radiation dose
Table feed per gantry Relatively high pitch (e.g. 1:1) Inversely related to pitch
rotation (pitch)
ECG gating ECG gating is not recommended Decreases without ECG
gating
Tube potential 80-140 kVp, depending on manufacturer Increases with higher
specification kVp
Tube current Because the scan is only acquire for AC, Increases with higher
low tube current is preferred (10-20 mA) mA
Breathing instructions End-expiration breathhold or shallow free- No effect
breathing is preferred
Reconstruction slice Should approximate the slice thickness of No effect
thickness PET (e.g. 4-5 mm)
to ensure proper registration between transmission suspected CAD. The goal of evaluating myocardial
and emission scans for quality assurance and proper perfusion with PET imaging is to detect physiologically
interpretation of PET images. Several approaches are significant coronary artery narrowing to guide clinical
currently being devised to reduce misregistration management of patients with known or suspected CAD
artifacts, such as reducing CT tube current and and those without overt CAD but with cardiovascular
increasing the duration CT acquisition to better risk factors in order to:
match the temporal resolution between the attenua-
• evaluate the progression of atherosclerosis,
tion and emission maps.22,23
• determine cause of ischemic symptoms and recom-
3. Metal artifacts can present a challenge for the
mend medical or revascularization therapy,
reconstruction algorithm and must be compensated
• estimate the potential for future adverse events, and
for to produce accurate attenuation maps.24,25
• improve patient survival.
Although pacemaker leads do not appear to cause
Stress and rest paired myocardial perfusion studies are
artifacts in cardiac PET/CT images, automatic
commonly performed to assess myocardial ischemia and/
implantable cardioverter defibrillator leads frequently
or infarction. Current Food and Drug Administration
do result in artifacts of sufficient magnitude to impact
(FDA)-approved and CMS-reimbursable PET MBF trac-
clinical image interpretation.24 Ideally, stress transmis-
ers are limited to 82Rb and 13N-ammonia. While 15O-water
sion scans should be acquired during peak stress or
is also used clinically in Europe, it is not FDA approved in
vasodilation, although this is not practical.
the United States. There are also 18F-labeled MBF agents
As such, the technologist and physician must care-
that are currently investigational and in clinical trials.
fully inspect the transmission and emission image sets to
Normal myocardial perfusion on stress images
ensure that they are properly registered in the transaxial,
implies the absence of physiologically significant
sagittal, and coronal planes. For patients undergoing PET/
CAD. Abnormal myocardial perfusion on stress images
CT, a separate, CT-based transmission scan for correction
suggests the presence of significantly narrowed coronary
of the stress images is standard. For 82Rb, a post-stress
arteries. However, it is important to point out that such
transmission scan is preferred to minimize misregistration
visual interpretation of relative radiotracer uptake may
artifacts on the corrected 82Rb images when misregistra-
underestimate balanced reduction in blood flow in all
tion compensation software is not available.
three vascular territories, also termed ‘‘balanced ische-
mia.’’ Routine assessment of absolute quantitative MBF
may identify such patients as well as those with
PET MYOCARDIAL PERFUSION IMAGING
equivocal or borderline radiotracer uptake defects. If
PET MPI is an important diagnostic and prognostic the stress-induced regional perfusion defect persists on
technique in the assessment of patients with known or the corresponding paired rest images, it suggests the
presence of an irreversible myocardial injury. On the commercially available generator by decay from 82Sr
other hand, if the defect on the stress images resolves attached to an elution column. 82Sr has a half-life of 25.5
completely or partially on the rest images, it suggests the days and decays to 82Rb by electron capture. 82Rb
presence of stress-induced myocardial ischemia. Abso- decays with a physical half-life of 75 seconds by
lute quantitative MBF may provide further insight into emission of several possible very high-energy positrons.
coronary steal phenomenon, defined as an absolute The resulting long positron range worsens image reso-
decrease in vasodilator stress perfusion from resting lution compared to 18F and 13N. The daughter product is
blood flow in collateral-dependent myocardium as well krypton-82, which is stable. The 82Sr-containing gener-
as in hibernation. Low resting MBF may or may not ator is commercially available and is replaced every 6
increase with stress but is nonetheless viable requiring weeks, thus obviating the need for a cyclotron.
82
an assessment of myocardial metabolism. In the case of Rb is eluted from the generator with 10 to 50 mL
hibernation, imaging of myocardial perfusion can be of normal saline by a computer-controlled elution pump,
combined with myocardial metabolism imaging with connected by intravenous (IV) tubing to the patient. The
18
F-FDG for the assessment of myocardial viability in generator is fully replenished every 10 minutes. While
areas of resting hypoperfusion and dysfunctional the short half-life of 82Rb challenges the performance
myocardium. limits of PET scanners, it facilitates the rapid completion
of a series of rest and stress myocardial perfusion studies.
82
Rb is extracted from plasma with high efficiency
Patient Preparation
by myocardial cells via the Na/K adenosine triphos-
Patient preparation is similar to preparation for stress phatase pump. Its first-pass extraction is considerably
and rest myocardial perfusion SPECT imaging. This less than that of 13N-ammonia, and decreases rapidly
includes fasting for 6 hours or more, with the exception with increasing blood flow. 82Rb extraction can be
of water intake. Patients should avoid caffeinated bev- decreased by severe acidosis, hypoxia, and ische-
erages for at least 12 hours, and avoid theophylline- mia.35–37 Thus, while uptake of 82Rb predominantly
containing medications for at least 48 hours.26 depends on MBF, it may be modulated by metabolism
and cell membrane integrity.
Dosimetry. The radiation dosimetry from 82Rb in
Cardiac Stress Testing
an adult may vary from 1.1 to 3.5 mSv total effective
Details of pharmacologic or exercise stress testing dose for a maximal allowable activity of 60 mCi
are beyond the goals of this document. Nonetheless, injection for each rest and stress study.38,39 With current
stress protocols are, for the most part, generic for all advances in PET instrumentation, diagnostic quality
perfusion agents.26 The specific differences in acquisi- PET images can be acquired using only 20 to 40 mCi of
tion protocols for 82Rb and 13N-ammonia imaging are 82
Rb for each of the rest and stress images of the study
related to the duration of uptake and clearance of these resulting in lower radiation exposure.
radiopharmaceuticals, their physical half-lives, and the Scout scanning. Scout scanning is recom-
characteristics of the vasodilators used for the study. For mended before each injection to ensure that the patient
example, the time course of action of the A2A-selective is correctly positioned and is not exposed to unnecessary
adenosine receptor agonist, regadenoson, is longer than radiation. This can be done with a fast transmission scan
that of adenosine (peak-effect onset at *1 min post or with a low-dose 82Rb injection (10 to 20 mCi). The
bolus injection with a duration of approximately 8 to 10 low-dose 82Rb scout scan is also used to estimate
minutes at C80% peak effect).27 As such, accurate circulation times and cardiac blood pool clearance times,
quantification of MBF is critically dependent on the which assist in selection of the optimum injection-to-
interplay between the vasodilator and the timing of the imaging delay time between 82Rb injection and initiation
radiotracer injection in relation to the peak coronary of acquisition of myocardial 82Rb images. However,
vasodilation achieved by the drug.28–31 In addition, all given the growing literature regarding the incremental
contraindications for performing cardiac stress testing value of absolute MBF measurement to the visual
with SPECT also apply to PET.31 interpretation of relative radiotracer uptake, it is strongly
recommended that the default acquisition be set at
82 dynamic list mode, thereby allowing the user to have the
Rb Perfusion Imaging
option of interpreting visual and/or quantitative data.
Tracer properties. 82Rb PET MPI is a well- With PET/CT systems, a low-dose x-ray scout scan is
established and highly accurate technique for the diag- routinely used for patient positioning.
nosis of hemodynamic CAD.32–34 82Rb is a monovalent Imaging parameters. Rest imaging should be
cationic analog of potassium. It is produced in a performed before stress imaging to reduce the impact of
residual stress effects (e.g., stunning and steal). For of absolute MBF, dynamic acquisition from time of
82
Rb, about 80% of the useful counts are acquired in the injection is required, followed by applying 2- and 3-
first 3 minutes, 95% of the useful counts are obtained in compartment kinetic models that incorporate both
the first 5 minutes, and 97% are obtained in the first 6 extraction and retention rate constants. In a clinical
minutes. The patient should be infused with 82Rb for a setting, 13N-ammonia PET myocardial perfusion images
maximum of 30 seconds. After the dose is delivered, are assessed visually or semiquantitatively along with
patients with normal ventricular function, or left ven- absolute MBF measurements with commercially avail-
tricular ejection fraction (LVEF) [50%, are typically able software for the evaluation of regional myocardial
imaged starting 70 to 90 seconds after the injection. For perfusion defects.42–46
13
those with reduced ventricular function, or LVEF from N-ammonia is an extractable myocardial perfu-
30 to 50%, imaging usually is begun 90 to 110 seconds sion tracer that has been used extensively in scientific
after termination of the infusion. Those with poor investigations with PET for more than three decades. At
function, or LVEF \30%, are typically imaged at 110 to physiologic pH, 13N-ammonia is in its cationic form
130 seconds. Excessive blood pool counts can scatter with a physical half-life of 10 minutes. Its relatively
into myocardial counts, impacting defect size and short half-life requires an on-site cyclotron and radio-
severity (Tables 6 and 7). chemistry synthesis capability. 13N decays by positron
emission. The daughter product is carbon-13, which is
13 stable. Myocardial uptake of 13N-ammonia depends on
N-Ammonia Perfusion Imaging
flow, extraction, and retention. First-pass myocardial
13
N-ammonia is a valuable agent for measuring extraction of 13N-ammonia is related inversely and non-
either absolute or relative MBF.40,41 For measurements linearly to blood flow47 Following this initial extraction
82
Table 6. Rb rest/stress myocardial perfusion imaging guideline for BGO and LSO (LYSO) PET imaging systems
Feature BGO Systems LSO (LYSO) Systems Technique

Stress testing Pharmacologic agents Standard
Tracer dose
2D scanner 40-60 mCi (1480-2220 MBq) Standard
3D scanner 10-20 mCi (370-740 MBq) 30-40 mCi (110-1480 MBq) Standard
Injection rate Bolus of ≤30 seconds Standard
Imaging delay LVEF >50%: 70-90 seconds Acceptable
after injection LVEF <50% or unknown: 90-130 seconds
List mode: acquire immediately
Patient positioning
PET Use scout scan: 10-20 mCi (370-740 MBq) 82Rb Standard
Use transmission scan Optional
PET/CT CT scout Standard
Imaging mode List mode: gated/dynamic (no delay after injection) Preferred
Gated acquisition (delay after injection Optional
Imaging 3-6 minutes Standard
duration 3-10 minutes Optional
Attenuation Measure attenuation correction, before or after Standard
correction
Reconstruction FBP or iterative expectation maximization (e.g. OSEM) Standard
method
Reconstruction Sufficient to achieve desired resolution/smoothing, matched Standard
filter stress to rest
Reconstructed 2-3 mm Preferred
pixel size
82
Table 7. Rb rest/stress myocardial perfusion imaging guideline for GSO PET imaging systems
Feature GSO Systems Technique

Tracer dose (3D) 20 mCi (740 MBq) Standard
Injection rate Bolus of ≤30 seconds Standard
Imaging delay LVEF >50%: 70-90 seconds Standard
after injection LVEF <50% or unknown: 90-130 seconds
List mode: acquire immediately
Longer delays than the above must be used if count rate at these
times exceeds the maximum value specified by the manufacturer
Patient positioning
PET Use scout scan: 10-20 mCi (370-740 MBq) 82Rb Standard
Use transmission scan Optional
Imaging mode List mode: gated/dynamic (no delay after injection) Standard
Imaging duration 3-6 minutes Standard
3-10 minutes Optional
Attenuation Measure attenuation correction, before or after Standard
correction
Reconstruction Iterative row-action maximum likelihood algorithm (3D-RAMLA) Standard
method
Reconstruction None Standard
filter
Reconstructed 4 mm Standard
pixel size
across the capillary membrane, 13N-ammonia may cross Dose. Typically, 10 to 20 mCi of 13N-ammonia is
myocardial cell membranes by passive diffusion or as an injected. Large patients may benefit from higher, 25 to
ammonium ion by the active sodium-potassium trans- 30 mCi, doses. In addition, the dose of radioactivity
port mechanism. Once in the myocyte, 13N-ammonia is administered will also depend on whether images are
either incorporated into the amino acid pool as 13N- obtained in 2D or 3D imaging mode.
glutamine or back-diffuses into the blood. The myocar-
dial tissue retention of ammonia as 13N-glutamine is
Non-FDA-Approved Myocardial Perfusion
mediated by adenosine triphosphate and glutamine
Agents
synthetase. Thus, uptake and retention can both be
15
altered by changes in the metabolic state of the O-water is often considered the ideal radiotracer
myocardium, although the magnitude of metabolic for quantifying MBF in absolute terms.49–53 Because the
effects on the radiotracer retention appears to be small. capillary and sarcolemmal membranes do not exert a
Dosimetry. The radiation dosimetry from a 20 barrier effect on the exchange of water, the activity of
15
mCi dose of 13N-ammonia is 1.48 mSv total effective O-labeled water observed in an assigned region of
dose in an adult.48 The critical organ is the urinary interest to the myocardium on the serially acquired
bladder, which receives 6 mSv from a 20 mCi dose of images can be described by a one-compartment tracer
13
N-ammonia.48 The dosimetry is relatively low, due to kinetic model. 15O-water is not FDA approved, and
the short half-life of 13N and the low energy of the therefore it is not used clinically in the United States. It
emitted positrons. is, however, used in Europe for clinical imaging. Initial
Acquisition parameters. Table 8 summarizes studies with 18F-labeled MBF agent, flurpiridaz, in
the recommended guidelines for performing 13N-ammo- humans has shown a very good diagnostic accuracy for
nia perfusion scans with dedicated, multicrystal PET or the detection of significant CAD.34 Regarding its
PET/CT cameras for rest and stress PET MPI for the potential for quantification of absolute MBF, in an
diagnosis and evaluation of CAD, or as part of an experimental study, measurement of the standardized
assessment of myocardial viability. uptake value (SUV) obtained at 5 to 10 minutes after
13
Table 8. N-ammonia cardiac PET perfusion studies
Feature Acquisition parameters Technique

Tracer dose (2D or 3D) 10-20 mCi (370-740 MBq) typical Standard
Injection rate Over 20-30 second infusion Preferred
Imaging delay for static 1.5-3 minutes after end of infusion
images
Imaging delay for Start camera prior to dose infusion Preferred
dynamic images
Patient positioning
PET Use scout scan: 1-2 mCi (37-74 MBq) Optional
Use transmission scan Standard
Imaging mode ECG gating of myocardium Preferred
Static Optional
List mode: gated/dynamic Preferred
Imaging duration 10-15 minutes Standard
Attenuation correction Measure attenuation correction, before or after Standard
Reconstruction method FBP or iterative expectation maximization (e.g. OSEM) Standard
Reconstruction filter Sufficient to achieve desired resolution/smoothing, Standard
matched stress to rest
Reconstructed pixel size 2-3 mm Preferred
4 mm Optional
18
F-flurpiridaz IV injection showed a linear correlation instances image data can be transferred to a standalone
with adenosine hyperemia MBF as quantified by radio- PC that has realignment software.
labeled microspheres.54 The reoriented images should be displayed as
follows:
IMAGE DISPLAY, NORMALIZATION, AND 1. A short-axis view, by slicing perpendicular to the
EVALUATION FOR TECHNICAL ERRORS long axis of the LV from apex (left) to base,
2. A vertical long-axis view, by slicing vertically from
Recommendations for display of PET perfusion
septum (left) to lateral wall, and
rest-stress and/or perfusion/metabolism images are con-
3. A horizontal long-axis view, by slicing from the
sistent with those listed in previous guidelines for rest-
inferior (left) to the anterior wall.
stress SPECT MPI.55 It is necessary to examine the
transaxial, coronal, and sagittal views for assessing the For interpretation and comparison of perfusion and
alignment of the emission images acquired during stress, metabolism images, slices of all datasets should be
rest, and metabolism, as well as the transmission images. displayed aligned and adjacent to each other. In the
Fused transmission and emission images are preferred. absence of motion artifact, combined assessment of
Images that are not aligned (e.g., due to patient or perfusion and metabolism within a single PET session
cardiac motion) may cause serious image artifacts, offers the advantage of copying the ventricular long axis
especially when only one set of attenuation correction defined during image orientation from one image set to
images has been applied to all emission images for the second set, thereby optimizing the matching of the
attenuation correction. This is a problem particularly perfusion with the metabolism images. Normalization of
when CT is used for attenuation correction.19 It is the stress and rest perfusion image set is commonly
important that the fusion images be reviewed for performed using the maximal myocardial pixel value in
potential misalignment problems and appropriate adjust- each of the two or three image sets, or, for example, the
ments are made. Some vendors’ systems now provide average pixel value with the highest 5% of activity of
software that allows realignment of transmission CT and the perfusion images. Each perfusion study is then
emission PET images before processing, and in other normalized to its own maximum.
The metabolism images are normalized to the polar maps should not be considered a substitute for the
counts in the same myocardial region on the resting examination of the standard short-axis and long-axis
perfusion images (e.g., with the highest count rates that cardiac tomographic slices.
were obtained on the perfusion study).56,57 An important
limitation of this approach, however, is that glucose
3D Display
metabolism may be enhanced or abnormally increased
in regions with apparently normal resting myocardial If suitable software is available, reconstructed
perfusion, if such regions are subtended by significantly myocardial perfusion and metabolism datasets can be
narrowed coronary arteries and are in fact ischemic on displayed in a 3D static or cine mode, which may be
stress myocardial perfusion studies.58 Moreover, visual convenient for morphologic correlation with angio-
assessment of resting myocardial uptake of the radio- graphic correlation derived from CT, MR, or
tracer reflects the distribution of MBF in ‘‘relative’’ conventional angiography. Some of the software may
terms (i.e., relative to their regions of the LV myocar- allow the overlay of the coronary anatomy on the 3D
dium) and not in ‘‘absolute’’ terms (i.e., mL/min/gm reconstructed perfusion and metabolism images of the
myocardial tissue). Thus, in some patients with multi- heart. An advantage of 3D over conventional 2D
vessel CAD, it is possible that all myocardial regions are displays with regard to accuracy of PET image inter-
in fact hypoperfused at rest in ‘‘absolute’’ terms (i.e., pretation has not been demonstrated.
characterized as balanced reduction in blood flow) and
yet appear normal in ‘‘relative’’ terms. Quantitative
Recommended Medium for Display
resting MBF may be used to define the region with the
highest absolute MBF for normalization of the metabo- It is strongly recommended for the interpreting
lism data. Whether absolute quantification of regional physician to use the computer monitor rather than film
myocardial glucose utilization may also aid in this hard copies for interpretation of myocardial perfusion
distinction is not well established in the literature. If and metabolism images. The latter would be especially
stress myocardial perfusion PET images are available, it important for gated PET images, where dynamic wall
is recommended that the normal reference region on motion data are viewed for proper interpretation of
stress perfusion images be utilized.40 In the presence of regional abnormalities. A linear gray scale, monochro-
left bundle branch block (LBBB), where the septal 18F- matic color scale, or multicolor scale can be used as the
FDG uptake is spuriously decreased, the septum should type of display, depending on user experience and
not be used as the site for normalization. Accordingly, preference.
the ECG should be reviewed in conjunction with
perfusion/viability imaging.
Image Evaluation for Technical Sources of
Errors
Standard Segmentation and Polar Map
Patient motion. PET images are typically gen-
Display
erated with non-moving circular arrays of scintillation
The standard segmentation model divides the LV into detectors that acquire all projection data simultaneously.
three major short-axis slices: apical, mid-cavity, and In contrast, SPECT imaging with rotating gamma
basal. The apical short-axis slice is divided into four cameras—in which patient motion leads to a typical
segments, whereas the mid-cavity and basal slices are misalignment between adjacent projection images—can
divided into six segments. The apex is analyzed sepa- be identified by viewing a projection movie. Movement
rately, usually from a vertical long-axis slice. Although during static PET imaging affects all projections and is
the anatomy of coronary arteries may vary in individual therefore more difficult to identify. Substantial patient
patients, the anterior, septal, and apical segments are motion can produce blurring of image contours. There-
usually ascribed to the left anterior descending coronary fore, attention to patient motion during image
artery, the inferior and basal septal segments to the right acquisition is essential to minimize motion artifacts.
coronary artery, and the lateral segments to the left Patient positioning before and immediately after
circumflex coronary artery. The apex can also be supplied image acquisition should be carefully evaluated (e.g., by
by the right coronary and left circumflex artery. Data from checking the alignment of the camera’s positioning laser
the individual short-axis tomograms can be combined to beams with ink markers on the patient’s skin). Acqui-
create a polar map display, representing a 2D compilation sition of a scout scan after injection of a small dose,
of all the 3D short-axis perfusion data. The 2D compila- usually one-third of the standard dose of 82Rb, may
tion of perfusion and metabolism data can then easily be facilitate accurate patient positioning. With PET/CT
assigned to specific vascular territories. These derivative systems, a low-dose x-ray scout scan (10 mA) is
routinely used for accurate patient positioning. In myocardium. For example, intense focal activity in the
instances of patient discomfort and likely patient liver or the gastrointestinal tract may lead to spillover of
motion, especially during longer image acquisition residual activity from imperfect scatter compensation,
times, one approach to reduce the potential for motion resulting in artificially elevated counts, or cause a
artifacts is to acquire a series of 3 to 4 sequential image reconstruction (i.e., ramp filter) artifact resulting in
frames instead of a single static image of longer apparent low count rates in adjacent myocardium. While
duration. Dynamic imaging would also be effective for these artifacts are common in SPECT imaging, they are
this purpose. If the quality of one of the serially acquired rare in PET imaging. Additional artifacts can result from
frames is compromised by motion, then that frame can problems with CT transmission images, such as streaks
be rejected and only frames that are of acceptable quality caused by insufficient x-ray tube intensity in obese
and are free of motion artifacts are summed for the final individuals, truncations, beam hardening resulting from
image analysis. bone (e.g., arms down) or metal adjacent to the heart
Vertical and transaxial displacement of the heart (e.g., pacemakers and internal defibrillators), and breath-
can occur even in the absence of chest movement. The ing leading to disconnected pieces of liver in the lungs
latter is perhaps related to the change of breathing or misalignment between CT and PET data. CT artifacts
pattern, which may occur during pharmacologic stress. are propagated into the PET images through the use of
This could be thought of as analogous to the ‘‘upward CT image for attenuation and scatter corrections. These
creep’’ phenomenon seen in SPECT imaging. As a artifacts are less of a problem with 137Cs attenuation
result, under-correction artifacts due to the lower atten- correction.
uation coefficient of the overlapping lung tissue may Image count statistics. The final count density
appear in the anterior or anterolateral regions, or over- of PET images is influenced by additional factors, such
correction artifacts due to the higher attenuation coef- as body habitus and weight, radionuclide dose, scanner
ficients of the overlapping subdiaphragmatic tissues may performance, acquisition time, and in the case of
appear in the inferior region as hot spots. Inspection of metabolic imaging, the dietary and neurohormonal state
fused emission-transmission images for possible of the patient. Image count density directly affects the
misalignment is essential because the resulting artifacts diagnostic quality and reliability of the study.
would greatly affect image interpretation. Fused images
should be inspected in the axial (lateral displacement),
Image Analysis and Interpretation of PET
coronal (vertical displacement), and sagittal (vertical
Images
displacement) slices. Alternatively, displacement can be
detected on transaxial images by counting the number of The rest and stress perfusion and/or metabolism
pixels by which the cardiac image is displaced between images should be interpreted initially without clinical
resting-and-stress transaxial acquisitions. Identification information in order to minimize any bias in study
of vertical and lateral displacements that result in interpretation. All relevant clinical data should be
misalignment between the emission and transmission reviewed after a preliminary impression is formed.
images is relatively straightforward. LV and RV size. The reader should note whether
The degree of co-registration of transmission and there is an enlargement of the right ventricle (RV) or LV
emission images should be carefully examined using the at rest or whether there is transient stress-induced LV
fusion software available on integrated PET/CT systems cavity dilatation. Ventricular enlargement seen on the
to assess the reliability of images with attenuation stress and rest perfusion or metabolic images generally
correction. If there is patient motion, the cardiac indicates left, right, or bi-ventricular dysfunction. LV
silhouette may not superimpose perfectly on the trans- and RV sizes, as well as any changes associated with
mission and emission images. If the transmission or stress, are typically described qualitatively. A number of
emission scans are degraded by motion during the commercially developed software packages originally
acquisition, software may not correct the image quality developed for SPECT have the ability to quantify mean
and the scan may have to be repeated. In general, LV volumes and end-diastolic and end-systolic volumes
vertical misalignment is easier to resolve by offsetting for gated PET images, but not all such packages have
the alignment between the emission and transmission been validated for all PET instruments. Among other
scans, but this option is not generally available. When considerations, PET stress images are acquired at the
the transmission scans are acquired using CT, the peak of pharmacologic stress, as opposed to SPECT for
incidental findings in the portion of the chest in the which images are acquired 15 to 45 minutes after stress.
FOV should be reported, when relevant to patient care. Lung uptake. Increased tracer activity in the
Reconstruction artifacts. Image artifacts may lungs should be reported qualitatively. Increased lung
occur if extra-cardiac activity is present, adjacent to the uptake on the perfusion images, particularly when
severe, may reflect severe LV dysfunction with a partial volume artifact due to apical thinning relative
increased LV end-diastolic and capillary wedge pres- to the remainder of the myocardium. This may be seen
sures. It can also reflect infiltrative diseases of the lungs, with 82Rb or 13N ammonia—often more evident with
13
and can be seen in smokers. Increased lung uptake can N-ammonia and with TOF cameras. Persistent reduc-
adversely affect image quality, and in particular may tion at stress and rest in the lateral wall is a common
interfere with interpretation of the lateral wall. It may be variant in 13N-ammonia imaging, more evident in a
necessary to increase the time between injection and normal-sized and functioning ventricle. The precise
image acquisition from 4-5 minutes to 7-8 minutes.59,60 explanation of this finding has been elusive but appears
RV uptake. Increased RV tracer uptake may be to be unique to 13N-ammonia and may relate to
seen both on perfusion and metabolism images in the differences in retention or wall motion of the lateral
presence of pulmonary hypertension with or without wall versus the septum.62
significant RV hypertrophy. Increased RV uptake is
usually assessed relative to the radiotracer uptake in the
LV myocardium. Because the septum is shared by both
Interpretation of PET Perfusion Data
ventricles, assessment of increased RV uptake should be
made in relation to other regions of the LV myocardium. Perfusion defect location, severity, and
Abnormally increased RV tracer uptake is a qualitative extent. Myocardial perfusion defects should be iden-
assessment. When RV uptake relative to the LV is tified through careful visual analysis of the reoriented
increased at stress compared to rest, this may indicate myocardial slices. Perfusion defects should be charac-
three-vessel or left main disease and balanced ischemia terized by extent, severity, and location relative to the
(indicating a relative reduction in LV perfusion rather specific myocardial territory, such as the anterior,
than increased RV perfusion).61 lateral, inferior, septal, and/or apical walls. Standardized
Blood pool activity. Visualization of persistent nomenclature should be used, according to previously
blood pool activity on either perfusion or metabolism published guidelines.63 RV defects due to scarring and
images is usually a sign of relatively poor myocardial ischemia should be noted.
uptake of the radiotracer, insufficient time for uptake of Qualitative scoring. Defect extent should be
the radiotracer into the myocardium, or diminished qualitatively estimated by describing the location of the
clearance of the radiotracer from blood. A major cause abnormal segments involved (e.g., anterior, inferior, or
of increased blood pool activity, especially for perfusion lateral) as well as the extent in the LV (e.g., ‘mid-to-
imaging with 82Rb, is impairment of cardiac systolic distal’ or ‘extending from base to the apex’). The extent
function that prolongs the circulation time. This is of the defect may also be qualitatively described as
especially relevant when only static images are acquired, small (5 to 10% of the LV), medium (10 to 20% of the
because vasodilators typically increase cardiac output LV), or large (20% of the LV). A defect of more than
and shorten the circulation time. List-mode acquisition 10% of the LV is associated with a higher risk of cardiac
allows for the reprocessing of images with varying delay events. Defect severity is typically expressed qualita-
times and may be useful for optimizing the quality of tively as mild, moderate, or severe. Severe defects may
reconstructed images. be considered as those having a tracer concentration
Extra-cardiac findings. The tomographic images equal or similar to background activity, and moderate
should be carefully examined for uptake of the radiotracer defects are considered definitely abnormal but visually
in organs other than the myocardium, particularly in the discernable activity above the background. Mild defects
lungs and the mediastinum. Extra-cardiac uptake of a flow are those with a subtle but definite reduction in regional
tracer may be of clinical significance, as it may be myocardial tracer uptake.
associated with malignancy and/or an inflammatory Stress and rest myocardial perfusion image sets are
process. The 3D maximum intensity projection display, compared in order to determine the presence, extent, and
a method of displaying acquired PET images as a rotating severity of stress-induced perfusion defects and to
3D display, can be particularly helpful in this regard. determine whether such defects represent regions of
When using PET/CT systems, review of the low-resolu- myocardial ischemia or infarction. Regions with stress-
tion CT-based transmission image can be useful to induced perfusion abnormalities, which have normal
delineate potentially important ancillary findings, such perfusion at rest, are termed reversible perfusion defects
as pleural and pericardial effusion, coronary and/or aortic and represent ischemia. Perfusion abnormalities on
calcification, breast, mediastinal, or lung mass, and others. stress, which remain unchanged on rest images, are
Normal variants. Apparent persistent reduction termed irreversible or fixed defects, and most often
of activity at stress and rest can be seen at the apex on represent areas of prior myocardial infarction. When
PET perfusion images and is a normal variant related to both ischemia and scar are present, the defect
Table 9. Semiquantitative scoring system of defect severity and extent
Grade Interpretation Score

Normal counts Normal perfusion 0
Mild reduction in counts Mildly abnormal 1
Moderate reduction in counts Definitely abnormal 2
Severe reduction in counts Definitely abnormal 3
Absent counts Definitely abnormal 4
reversibility is incomplete, giving the appearance of stress score (SSS) is the sum of the stress scores of all
partial reversibility. segments, the summed rest score (SRS) is the sum of
Semiquantitative scoring system. In addition the resting scores of all segments, and the summed
to the qualitative assessment of perfusion defects, a well- difference score (SDS) is the difference between the
accepted 5-point scale semiquantitative visual scoring summed stress and summed rest scores and serves as a
method is used in direct proportion to the observed count measure of reversibility. The summed scores incorpo-
density of the segment, as follows: 0 = no defect; 1 = rate the global extent and severity of perfusion
mildly reduced; 2 = moderately reduced; 3 = severely abnormality. For example, the SSS reflects the extent
reduced; 4 = absent activity (Table 9). This approach and severity of perfusion defects at stress and is
standardizes the visual interpretation of scans, reduces the affected by prior myocardial infarction as well as by
likelihood of overlooking clinically significant defects, stress-induced ischemia.
and provides a semiquantitative index that is applicable to On the other hand, the SRS reflects the amount of
diagnostic and prognostic assessments. infarcted and/or hibernating myocardium. The SDS is a
A 17-segment model for semiquantitative visual measure of the extent and severity of stress-induced
analysis can also be employed.63 The model is based on ischemia.
three short-axis slices (apical, mid, and basal) to represent Before scoring, it is necessary for the interpreting
most of the LV and one vertical long-axis slice to better physician to be familiar with the normal regional
represent the LV apex (Figure 1). The basal and mid- variation in count distribution of myocardial perfusion
short-axis slices are divided into six segments. The apical PET. No regional variation in tracer uptake has been
short-axis slice is divided into four segments. A single reported for 82Rb, except for a mild reduction in the
apical segment is taken from the vertical long-axis slice. apex and base of the LV, consistent with segmentation
Each segment has a specific name. The extent of stress artifact and/or thinning of the LV myocardium in these
and rest perfusion abnormalities, as well as an estimate of locations. Regarding 13N-ammonia, unlike 82Rb and
the extent of scarring and ischemia, can be performed by other SPECT perfusion tracers, the lateral wall uptake
counting the number of segments. may not necessarily be the region with the highest
Myocardial segments may be assigned to coronary counts, serving as the reference region for normaliza-
artery territories. Caution should be exercised because the tion. This normal variation should be kept in mind
coronary anatomy varies widely among patients. For exam- when visually interpreting lateral perfusion defects with
13
ple, it is not uncommon to find segments 9, 10, and 15 (of the N-ammonia PET.62 Absolute quantitative MBF of the
17-segment model) involved in left anterior descending lateral wall has been shown to further differentiate a
artery disease. Similarly, segments 5 and 11 of the model true perfusion defect from normal variant in the
may be affected by disease of the right coronary artery. clinical setting. In addition, apical thinning may be
more pronounced with TOF 13N-ammonia imaging.
Degree of abnormality by % myocardium stress Given the variability in the normal distribution of
(17-segment model) various radiotracers, the patient’s polar map may be
Normal SSS = 0-3 compared with a reference polar map derived from
(<5% myocardium)
radiotracer and gender-specific normal database. Ide-
Mildly abnormal SSS = 4-7
(5%-10% myocardium) ally, each camera system and acquisition protocol
Moderately or severely SSS > 8 should have its own ‘‘normal’’ file but such normal
abnormal (>10% myocardium) databases are not widely available. The semiquantita-
tive analysis system provided by a specific vendor
In addition to individual scores, calculation of should be validated by appropriate studies published in
summed scores is recommended, in which the summed peer-reviewed journals.
Absolute quantification of myocardial deciding whether a finding is normal or abnormal, as

blood flow. Quantitative blood flow approaches offer well as when repeat images are done for a patient using
an objective interpretation that is inherently more different analytic software.70
reproducible than visual analysis.64–66 Absolute quan- Quantitative absolute hyperemic MBF in mL/min/
tification may aid in assessing the physiologic gm tissue and flow reserve (representing the ratio of
significance of known coronary artery stenosis, espe- hyperemic and resting MBF)—derived from dynamic
cially when of intermediate severity. Both relative and acquisition with measurements of resultant myocardial
absolute quantification are particularly useful in and blood pool time-activity curves—is a potentially
describing changes between two studies in the same powerful adjunct to PET perfusion imaging. It is
patient. In addition, quantitative measurements of MBF important to recognize, however, that myocardial flow
may identify balanced reductions in MBF due to reserve (MFR) ratio can be spuriously lowered by
balanced multivessel CAD or diffuse small-vessel elevated resting blood flow in the denominator, as seen
disease. in patients with hypertension or high resting rate-
Software packages that are commonly used for pressure product. Thus, it is important to interpret both
quantitative analysis of SPECT perfusion images have hyperemic MBF and flow reserve in all subjects. Among
been developed for PET.67 These analyses portray the promises of quantitative blood flow measurements
relative uptake of tracer in reference to limits derived are improved diagnostic accuracy, including the ability
from PET images (82Rb or 13N-ammonia) of patients to overcome false-negative studies in the setting of
with a low likelihood of coronary disease, but do not balanced ischemia and improved risk stratifica-
present true blood flow quantitation values. High diag- tion.63,71–75 Quantitative MBF can be assessed globally
nostic accuracy for detecting obstructive CAD has been and regionally.
reported.68,69 Similar to SPECT, PET total perfusion As with all nuclear cardiology techniques, atten-
deficit values for stress, rest, and defect reversibility tion to quality control (e.g., assessment of time-
(i.e., ischemia) can be derived, but use of these param- activity curves) and use of validated methodology and
eters to guide patient management has not been software packages are crucial. It is also important to
established. The various analytic software packages also recognize the potential pitfalls when interpreting and
provide quantitative data for LV volumes and ejection reporting derived quantitative values, including the
fractions. As is the case with SPECT, it must be influence of various forms of stress, different radio-
recognized that different packages do not provide the tracers, characteristics of particular software packages,
same values, something that must be understood when and even unique patient idiosyncrasies. In addition, as
Figure 1. LV myocardial segmentation, standard nomenclature, and vascular territories. PET

images are interpreted on the basis of the presence, location, extent, and severity of myocardial
perfusion and metabolic defects using a standard 17-segment model and visual scoring. (A) The
standard segmentation model divides the LV into three major short-axis slices: apical, mid-cavity,
and basal. The apical short-axis slice is divided into four segments, whereas the mid-cavity and
basal slices are divided into six segments. The apex is analyzed separately, usually from a vertical
long-axis slice. (B) Data from the individual short-axis tomograms can be combined to create a
polar map plot, representing a 2D compilation of all the 3D short-axis perfusion data. Standard
nomenclature for the 17 segments is outlined. (C) The 2D compilation of perfusion data can then
easily be assigned to specific vascular territories. (From Dilsizian V.; reprinted with permission).55
with most imaging parameters, MBF values should be While some variations in cut-off values have been
supplements to be considered in conjunction with reported for different tracers and different software, at
patient clinical characteristics and other image find- the present time it is generally accepted that MFR values
ings when used to diagnose and direct patient can be interpreted as follows (with small variation
management. depending on software):
At the present time, quantitative absolute MBF
1. MFR [2.3 indicates a favorable prognosis (assuming
measurements with PET appear most helpful in:
that there is no lower regional value).
1. Patients without known prior history of cardiac
2. MFR \1.5 suggests significantly diminished flow
disease who present with symptoms suspicious for
reserve (in the absence of concomitant elevated
myocardial ischemia.
resting blood flow), and is associated with elevated
2. Patients with known CAD, in whom more specific
cardiac risk.
physiological assessment is desired.
3. Identifying an increased suspicion for multivessel Quantitative assessment of MBF in absolute units
CAD. (e.g., mL/min/gm tissue) has been well established
4. Situations with a disparity between visual perfusion in the literature with 13N-ammonia and 15O-
abnormalities and apparently normal coronary water.40–42,44,49–51,64 It requires the acquisition of
angiography, in order to assess possible microvascu- images in dynamic mode. The use of list-mode acqui-
lar dysfunction. sition enables flow quantification in conjunction with
5. Heart transplant when there is a question of perfusion and gated LV and regional function. The
vasculopathy. added value in terms of diagnosis and prognosis is the
subject of active investigation in several centers.
In contrast, there are particular patients for whom
Regions of interest are placed on the LV myocardium
reporting hyperemic blood flow or flow reserve may not
and the LV blood pool and are copied to all serially
add diagnostic value or can be ambiguous or mislead-
acquired images for generation of myocardial tissue and
ing, including:
blood pool time-activity curves. The time-activity
1. Patients post-CABG who can have diffuse reduction
curves are corrected for activity spillover from the
on MBF despite patent grafts.
blood pool to the myocardium and for radioactive decay.
2. Patients with large transmural infarcts where resting
They are then fitted with a validated tracer kinetic
flow may be severely reduced such that small
model, and estimates of MBF are obtained. Software
increases in flow lead to normal or near-normal flow
programs are also available for generating parametric
reserve.
polar maps that display regional MBF in absolute units.
3. Patients with advanced severe chronic renal dysfunc-
Quantification of MBF with 82Rb has been more
tion who likewise often have diffuse coronary
challenging because of its 75-second half-life resulting
disease.
in noisy myocardial and blood pool time-activity
4. Patients with severe LV dysfunction.
curves.76,77 Newer software packages have incorporated
While hyperemic blood flow and flow reserve mathematical correction and improved quantitation of
82
values may predict worse prognosis, it is already known Rb perfusion images. The kinetic behavior 82Rb in
that patients with prior CABG, prior MI, chronic renal tissue can be described by a one- or two-compartment
failure, and/or severe LV dysfunction are at higher risk. model that can be fitted using the arterial input function
Because many patients are referred for diagnosis and (i.e., obtained from the blood pool concentration of the
detection of ischemia to determine if revascularization LV cavity or left atrium) and myocardial time-activity
therapy is an option, reporting flow and flow reserve curves at each segment, or even (with sufficient statis-
under the above circumstances may mislead the refer- tics) at each pixel.77–82 The parameters of the model,
ring physician or healthcare provider. which include flow, can be estimated using non-linear
In addition, because of various potential patient regression or other techniques. The variability of flow
(e.g., receptor peculiarities) and external reasons (e.g., estimates can be reduced by fixing certain parameters to
unappreciated caffeine intake), a patient can be a non- physiologically realistic values.83
responder to vasodilator stress, with a global MFR at or Gated PET images. The ability to acquire cardiac
about 1. In such circumstances, the visual perfusion PET images in conjunction with ECG gating is an
image findings may be invalid. Also, the stress portion important development that has not always been avail-
of the test may need to be repeated ensuring no caffeine, able, particularly on 3D scanners. As with SPECT,
or using another pharmacologic stress imaging agent. accurate gating with PET requires regular R-R intervals.
Some systems, however, support ECG-gated imaging via occur in response to sustained abnormal stimuli.89–91 For
list-mode acquisition that may allow accurate assessment example, the chronic reduction of MBF levels that occur
of gated LV function in patients with irregular rhythms. with myocardial hibernation leads to an overdependence
In such a mode, the positions of all coincidence pairs are on glucose metabolism by the cardiac myocyte. In
recorded along with timing information and input from general, this metabolic change is adaptive and preserves
an electrocardiogram. These data can be retrospectively cardiac myocyte health. In contrast, the sustained
processed to produce ECG-gated images, ungated increases in plasma fatty acids that occur in diabetes
images, and if necessary, dynamic images, which repre- mellitus result in a chronic increase in fatty acid
sent the activity distribution as a function of time. The metabolism and a reduction in glucose use. Although
flexibility of this mode of acquisition is particularly initially adaptive, this change in metabolism eventually
convenient for quantitative analysis. becomes maladaptive and leads to cardiac dysfunction.
ECG gating of the rest and peak-stress myocardial
perfusion images can provide additional information
Glucose Metabolism by Pro-inflammatory
regarding changes in LV function and volumes.84 Unlike
Cells
ECG gating of the post-stress SPECT images, PET
acquisitions take place during peak pharmacologic Increased glucose metabolism is a hallmark of
vasodilation.84,85 ECG gating of 18F-FDG PET images activation of immune cells involved in both innate (e.g.,
can also provide additional information regarding monocytes and macrophages) and adaptive (e.g., T and
regional and global LV function and volumes. B cells) immunity.92 The increase in glucose metabo-
lism is triggered to meet the higher energy demands of
immune cell activation and reflects the stimulation of
PET IMAGING OF GLUCOSE METABOLISM
key transcriptional and other signaling pathways. Thus,
18
F-FDG PET imaging is the only FDA-approved under pro-inflammatory conditions, such as sarcoidosis
technique for the assessment of myocardial viability. or device infection that are discussed below, the pres-
Other disease entities in which metabolic imaging with ence of immune cell infiltration and activation can be
18
F-FDG PET can play an important role include the measured.
detection of inflammation, as in cardiac sarcoidosis, and There are numerous radiotracers that can measure
for the detection of infections, as in cardiovascular cellular glucose metabolism either directly, such as with
18
devices and prosthetic valves. Depending on the disease F-FDG and 11C-glucose, or indirectly, such as 11C-
process, measurements of glucose metabolism can palmitate and the various 18F fatty acid analogs. How-
reflect the rates of cellular glucose use from either ever, this document will only focus on measurements of
cardiac myocytes or from pro-inflammatory cells that glucose metabolism using 18F-FDG because it is the
infiltrated either the myocardium or the vasculature. only metabolic radiotracer that is FDA approved and is
Consequently, PET with 18F-FDG can be used to detect used routinely for clinical purposes. 18F-FDG is used for
the increase in glucose metabolism in these cell types in the detection of viable myocardium where the increased
a host of cardiovascular diseases. cardiac myocyte glucose metabolism is a marker of
cellular viability. More recently, 18F-FDG is used to
manage patients with potential cardiac sarcoidosis,
Glucose Metabolism by the Cardiac
medium-to-large vessel vasculitis, and cardiac device
Myocyte
infection, where cellular inflammation is central to the
For a given physiologic environment, the cardiac pathogenesis of these disease processes. The perfor-
myocyte consumes the most efficient metabolic fuel as mance of 18F-FDG in these cardiac diseases is discussed
an adaptive response to meet its energy demands. Under below. It should be noted that 18F-FDG is being used
fasting and aerobic conditions, long-chain fatty acids are with increasing frequency to evaluate other cardiovas-
the preferred fuel in the heart as they supply 65 to 70% cular diseases, such as right ventricular imaging due to
of the energy for the working heart, and some 15 to 20% pulmonary hypertension and vascular imaging in
of the total energy supply comes from glucose.86 In post- atherosclerosis. These applications, however, are pri-
prandial conditions, glucose becomes the preferred marily investigational in nature and will not be
energy substrate. This rapid adaptation in substrate use discussed further.
is an essential component of maintaining normal cardiac
function and is dependent on a host of variables such as 18
F-FDG metabolic imaging
substrate availability, hormonal status, cardiac work-
load, and other factors.86–88 In contrast, chronic Tracer properties. FDG competes with glucose
adaptations in cardiac myocyte substrate metabolism for transport and for phosphorylation by hexokinase.
Different from glucose, the phosphorylated radiotracer, medications. Combining the information from the glu-
18
F-FDG-6-phosphate does not proceed into glycogen cose metabolism and blood flow studies generate
synthesis or aerobic glycolysis with only minimal de- metabolism-flow patterns indicative of viable and non-
phosphorylation and return of radiotracer to blood; it is viable myocardium.
thus metabolically trapped in tissue. Consequently, its Patient preparation. Because of the marked
uptake is reflective of overall glucose uptake. CMS has flexibility in substrate use by the myocardium, stan-
approved reimbursement of 18F-FDG for the evaluation dardization of the substrate environment is of critical
of myocardial viability. 18F is produced in a cyclotron importance when performing cardiac 18F-FDG PET
through the (p, n) reaction, consisting of bombardment imaging. The goals and protocols for standardization of
of 18O-enriched water,93 and decays by the emission of a the substrate environment differ depending upon whe-
positron with a half-life of 110 minutes. The low kinetic ther the clinical indication for the study is to detect
energy of the positron, 511 keV, allows the highest myocardial viability or inflammation. For the evaluation
spatial resolution among all PET radionuclides. The of myocardial viability with 18F-FDG, the substrate and
110-minute physical half-life of 18F-FDG allows suffi- hormonal levels in the blood need to favor metabolism
cient time for synthesis and purification, with its of glucose over fatty acids by the myocardium.56,87,95,96
commercial distribution in a radius of several hours This maximizes the 18F-FDG uptake in the myocardium,
from the production. resulting in superior image quality, and reduces the
Tracer dosimetry. The effective dose for a 10- regional variations in 18F-FDG uptake that can occur
mCi dose of 18F-FDG administered intravenously is 7 when imaging under fasting conditions.57 Protocols to
mSv. The critical organ is the urinary bladder wall standardize the substrate environment for viability
which receives an effective dose of 48 mSv.94 Frequent imaging are shown in Tables 10 and 11.
voiding 1 to 3 hours post-administration is recom- Standardization is usually accomplished by loading
mended in order to reduce radiation exposure. the patient with glucose after a fasting period of at least
6 hours to induce an endogenous insulin response. The
temporary increase in plasma glucose levels stimulates
Detection of viable myocardium
pancreatic insulin production, which in turn reduces
Study protocol. Acute and chronic metabolic plasma fatty acid levels through its lipogenetic effects of
adaptation to a temporary or sustained reduction in adipocytes and also normalizes plasma glucose levels.
coronary blood flow is designed to protect the structural The most common method of glucose loading is
and functional integrity of the myocardium. Reversible with an oral load of 25 to 50 grams, but IV loading is
metabolic changes, as an adaptive measure to sustain also used. The IV route avoids potential problems due to
myocardial viability, will occur in the setting of dimin- variable gastrointestinal absorption times or inability to
ished, but not absent, regional MBF. When MBF is tolerate oral dosage. Because of its simplicity, most
absent, irreversible metabolic changes will occur fol- laboratories utilize the oral glucose-loading approach,
lowed by myocardial infarction and cell death. with supplemental insulin administered as needed. The
Consequently, demonstration of preserved glucose meta- physician should take into account whether or not the
bolism by 18F-FDG is a marker of myocardial viability. patient is taking medications that may either antagonize
In general, the lack of glucose metabolism is indicative or potentiate the effects of insulin.
of non-viable myocardium. Accurate detection of viable Diabetic patients. Diabetic patients pose a
myocardium is achieved by referencing the level of unique challenge, either because they have limited
myocardial glucose metabolism to the level of MBF. ability to produce endogenous insulin or because their
Typically, the measurements of MBF are performed cells are less able to respond to insulin stimulation. For
with either 82Rb or 13N-ammonia using procedures this reason, the simple fasting/oral glucose-loading
described in the PET myocardial perfusion section. If paradigm is often not effective in diabetic patients.
these radiotracers are not available, MBF can be Use of insulin along with close monitoring of blood
separately determined using technetium-99m-labeled glucose (Table 11) yields satisfactory results. Improved
18
myocardial perfusion SPECT radiotracers. Measure- F-FDG images can also be seen when image acqui-
ments of flow should be obtained in the same imaging sition is delayed 2 to 3 hours after injection of the 18F-
session as measurements of myocardial glucose meta- FDG dose. Of course, the latter comes at the expense of
bolism, regardless of the blood flow radiotracer that is increased decay of the radiopharmaceutical. An alter-
used. If blood flow and metabolism data are acquired native technique is the euglycemic-hyperinsulinemic
within a few weeks or months apart, it is important to clamp, which is a rigorous and time-consuming proce-
verify that the patient has been stable during that time dure.96 However, it allows close titration of the
interval and there has been no change in symptoms or metabolic substrates and insulin levels, which results
18
Table 10. Patient preparation for F-FDG PET cardiac viability assessment
Procedure Steps for standardization Technique

Fasting Step 1: Fast patient
period 6-12 hours Preferred
<6 hours Suboptimal
Step 2: Check blood glucose (BG) and the glucose load
(choose one of the following 3 options)
Oral glucose Option 1: Oral glucose loading
load IF: fasting BG <~250 mg/dL (13.9 mmol/L) Standard
THEN:
1) oral glucose load: typically 25-100 g orally, (see Table 11)
2) monitor BG (see Table 11)
IF: fasting BG > ~250 mg/dL (13.9 mmol/L) Standard
THEN: see Table 11
IV protocol Option 2: Dextrose IV infusion Optional
See details, sample protocol, Appendix
Acipimox Option 3: Acipimox
Acipimox, 250 mg orally not available in the US
Step 3: Administer18 F-FDG
18
F-FDG Time: Dependent on which option was selected Standard
injection Standard IV administration of 18F-FDG, see Table 12, item 1
Begin PET 0-90 minutes post 18F-FDG injection, see Table 12
imaging
18
Table 11. Guidelines for BG maintenance (after glucose administration) for optimal F-FDG cardiac uptake, BG of
approximately 100-140 mg/dL (5.55-7.77 mmol/L) at time of injection of 18F-FDG
BG at 45-60 min after administration Restorative measure Technique

130-140 mg/dL (7.22-7.78 mmol/L) 1 U regular insulin IV Standard
140-160 mg/dL (7.78-8.89 mmol/L) 2 U regular insulin IV
160-180 mg/dL (8.89-10 mmol/L) 3 U regular insulin IV
180-200 mg/dL (10-11.11 mmol/L) 5 U regular insulin IV
> 200 mg/dL (>11.11 mmol/L) Notify physician
BG = blood glucose; FDG = fluorodeoxyglucose; IV = intravenous; mg = milligram; mmol = millimoles;
L = liter; dL = deciliter; U = unit
in excellent image quality in most patients and allows perfusion, there is no need to delay the 18F-FDG PET
absolute quantification of myocardial glucose utiliza- images. 201Tl and 99mTc will not interfere with the higher
tion. Shorter IV glucose/insulin-loading procedures of energy 18F photons. However, with 3D PET imaging, the
30 minutes have also been used with some success.58 99m
Tc activity can increase dead time and thus decrease
(see ‘‘Protocol’’ section, Appendix). the true counts from the 18F-FDG. If 18F-FDG PET
Acquisition parameters. Acquisition parame- images are acquired first, then it is necessary to wait at
ters for 18F-FDG PET cardiac imaging are itemized in least 5 half-lives, depending on the dose of 18F admin-
Table 12. If 18F-FDG PET metabolic images are com- istered, before a low-energy (e.g., 201Tl or 99mTc) SPECT
pared to perfusion images acquired by SPECT, the study is performed. This is because the 511-keV photons
interpreter should be mindful that there will be differ- from the PET tracers easily penetrate the collimators that
ences in soft tissue attenuation, image resolution, and are commonly used for 201Tl or 99mTc imaging. Iterative
registration problems of images acquired on different reconstruction (ordered subset expectation maximiza-
instruments. It should be noted that if a 201Tl- or a 99mTc- tion, OSEM, 21 subsets, 2 iterations) is the recommended
labeled perfusion tracer is used to assess myocardial method of image reconstruction.
18
Table 12. F-FDG PET cardiac imaging acquisition guidelines for PET/CT and dedicated PET
Feature Technique Requirement

Tracer dose (2D or 3D) 5-15 mCi (185-555 MBq) Standard
Injection rate (Static) Not critical, bolus to 2 min Standard
Injection rate (Dynamic) Bolus for glucose quantification Optional
Image delay after injection 45-60 min after injection Standard
(keep constant for repeat studies)
Patient positioning
PET Use an 18F-FDG scout scan Optional
Use transmission scan Standard
PET/CT CT scout scan Standard
Imaging mode 2D or 3D Standard
Static or list mode Standard
Dynamic Optional
Image duration 10-30 min (depending on count rate and dose)
Attenuation correction Measure attenuation correction: before or Standard
immediately after scan
Reconstruction method Iterative expectation maximization (e.g. OSEM) or Standard
FBP
Reconstruction filter Sufficient to achieve desired resolution/smoothing, Standard
matched between consecutive studies
Reconstructed pixel size 2-3 mm Preferred
4-5 mm Acceptable
Note: If metabolism imaging is combined with PET perfusion imaging, the same parameters for
patient positioning, attenuation correction, and image reconstruction should be applied.
Dose. Typically, 5 to 15 mCi of 18F-FDG is certain dose, the 3D mode will actually produce poorer
injected in a peripheral vein. Injection speed is not quality images for the same dose and imaging time than
critical (i.e., bolus to 2 minutes). To reduce patient dose 2D mode. For this reason, it is critical to have fully
to the bladder, patients should be encouraged to void characterized the performance of the PET system.
frequently for 3 to 4 hours after the study. Assessment of myocardial viability. Detec-
Scan start time and duration. It is suggested tion of viable myocardium plays a central role in the
to wait for a minimum of 45 minutes before starting the management of patients with LV dysfunction due to
static 18F-FDG scan acquisition. Myocardial uptake of CAD.97 It is based on the recognition that resting LV
18
F-FDG may continue to increase, and blood pool dysfunction may be reversible, attributable to myocar-
activity to decrease, even after 45 minutes. While dial hibernation/stunning, and not necessarily due to
waiting for 90 minutes after the injection of 18F-FDG myocardial scar. As a consequence, its presence signifies
may give better blood pool clearance and myocardial a different prognosis and mandates a different treatment
uptake, especially in diabetics or subjects with high paradigm compared with the presence of predominantly
blood glucose levels, this comes at the expense of non-viable or irreversible damaged tissue. Indeed, the
reduced count rate. If target-to-background ratio is poor importance of differentiating viable from non-viable
at 45 to 60 minutes, injecting an additional 1 to 3 units tissue is highlighted by the plethora of techniques
of insulin (depending on the blood glucose level) and currently available to perform this task. Myocardial
then waiting for an additional 45 to 60 minutes may metabolism imaging with PET and 18F-FDG uses the
improve the image quality substantially. Scan duration is preservation of myocardial glucose metabolism, partic-
typically 10 to 30 minutes. If acquired in 3D mode, ularly in the presence of resting hypoperfusion as a
compared with 2D mode with the same machine, a scintigraphic marker of viable myocardium. It is accom-
smaller dose is typically required to achieve the same plished with 18F-FDG as a tracer of exogenous glucose
total count rate, but the imaging time may or may not be utilization. The regional myocardial concentrations of
reduced as a result of count rate limitations and this tracer are compared with the regional distribution of
increased scatter. With some PET cameras, beyond a myocardial perfusion. Regional increases in 18F-FDG
uptake relative to regional MBF (i.e., perfusion-meta- For myocardial 18F-FDG images acquired with
bolism mismatch) signify myocardial viability. In ultra-high-energy collimators or with SPECT-like coin-
contrast, a regional reduction in 18F-FDG uptake in cidence detection systems, additional problems may be
proportion to regional reductions in myocardial perfu- encountered, especially when the images are not cor-
sion (i.e., perfusion-metabolism match) signifies rected for photon attenuation.100–103 Attenuation of the
myocardial scar or non-viable tissue. Areas with main- high-energy 511-keV photons is less than that for the
tained perfusion, but diminished 18F-FDG uptake, also 140-keV photons of 99mTc or the 60- to 80-keV photons
likely reflect regions of jeopardized but viable myocar- of 201Tl, so that attenuation artifacts are less prominent
dium as the perfusion tracers reflect active metabolic for 18F-FDG images and may result in an apparent
trapping. mismatch. Furthermore, the lower spatial resolution of
Comparison of myocardial metabolism to SPECT imaging systems for 18F-FDG imaging, espe-
perfusion. The comparison of perfusion and metabo- cially when using high-energy photon collimation and
lism images obtained with PET is relatively then comparing with 99mTc or 201Tl images, causes
straightforward because both image sets are attenuation apparent mismatches for small defects, at the base of the
corrected. Thus, a relative increase in myocardial LV, or at the edges or borders of large perfusion defects.
metabolism in regions of reduced perfusion by one Such artifacts resulting from the use of different photon
grade or more reflects the presence of perfusion- energies can be avoided using dedicated PET systems
metabolism mismatch, hence myocardial viability. In for both perfusion and metabolism imaging. Again, use
contrast, a relative decrease in myocardial metabolism of ECG-gated imaging to demonstrate normal wall
that is in proportion to reductions in regional perfusion motion, quantitative analysis through polar map dis-
reflects the presence of perfusion-metabolism match, plays with comparison to radiotracer- and gender-
hence myocardial scar or non-viable tissue. Areas with specific databases of normal may aid in the visual
maintained perfusion, but diminished 18F-FDG uptake interpretation.
(termed reverse mismatch), also likely reflect regions of Absolute myocardial glucose utiliza-
jeopardized but viable myocardium since the perfusion tion. Quantitative estimates of myocardial glucose
tracers reflect active metabolic trapping (Na-K ATPase utilization in absolute units of micromoles of glucose per
system for 82Rb and 13N-glutamine mediated by ATP minute per gram of myocardium have not been found to aid
and glutamine synthetase for 13N-ammonia).43 in the assessment or characterization of myocardial viabil-
Special considerations for combining ity due to the variability in substrate utilization by the
SPECT perfusion with PET metabolism ima- myocardium, even when 18F-FDG images are acquired
ges. In current clinical practice, 18F-FDG PET images during a hyperinsulinemic-euglycemic clamp.95,96,104
are often read in combination with SPECT myocardial Methods for deriving quantitative estimates of
perfusion images. The interpreting physician should be myocardial metabolism require acquisition of serial
careful when comparing the non-attenuation-corrected images for 60 minutes that begin with tracer injec-
SPECT images with attenuation-corrected 18F-FDG PET tion.93,105 ROIs are placed on the myocardium and the
images. Myocardial regions showing an excessive reduc- LV blood pool and are copied to all serially acquired
tion in tracer concentration as a result of attenuation images in order to generate myocardial tissue and blood
artifacts, such as the inferior wall in men or the anterior pool time-activity curves. The time-activity curves are
wall in females, may be interpreted as perfusion-metabo- corrected for spillover activity from the blood pool into
lism mismatches, resulting in falsely positive perfusion- the myocardium and for radioactive decay. The time-
metabolism mismatches. Two approaches have proved activity curves are then fitted with a validated tracer
useful for overcoming this limitation: kinetic model, and estimates of regional myocardial
glucose utilization are obtained in micromoles of glucose
1. Because assessment of viability is relevant only in
per minute per gram of myocardium. Measurements of
myocardium with regional contractile dysfunction,
glucose metabolic rates further require determination of
gated SPECT or PET images offer means for
glucose concentrations in arterial or arterialized venous
determining whether apparent perfusion defects are
blood. Similar to myocardial perfusion, parametric
associated with abnormal regional wall motion.
images and polar maps are also available for display of
2. Quantitative analysis with polar map displays that are
rates of regional myocardial glucose utilization. Regio-
compared with tracer- and gender-specific databases
nal metabolic rates on such parametric images are coded
(for SPECT images) may be a useful aid to the visual
by a color scale and can be determined non-invasively for
interpretation. SPECT perfusion images with atten-
any myocardial region through ROIs assigned to the
uation correction are helpful; however, neither
polar map.106
approach is infallible.98,99
Integration of perfusion and metabolism In circumstances where only stress perfusion imag-
results. The combined evaluation of regional myocar- ing is available in combination with 18F-FDG metabolic
dial perfusion and 18F-FDG metabolism images allows imaging, the following patterns can be found in
identification of specific flow-metabolism patterns that segments with contractile dysfunction:
are useful to differentiate viable from non-viable myo-
1. Stress perfusion defect with preserved 18F-FDG
cardium.107–112 It is useful to start with a functional
uptake indicates ischemic but viable myocardium.
assessment, ideally from gated PET or SPECT imaging, as
Revascularization is generally appropriate as
dysfunctional segments are those suitable for evaluation
myocardial ischemia is a very strong predictor for
of myocardial viability. If stress perfusion images as well
recovery of perfusion and function after a successful
as resting perfusion images are available, jeopardized
revascularization. With stress perfusion and 18F-FDG
myocardium can be distinguished from normal myocar-
metabolic paired images, it is not possible to
dium, and myocardium perfused normally at rest, but
differentiate between myocardial ischemia, stunning,
dysfunctional as a result of repetitive stunning, can be
and hibernation.
distinguished from myopathic or remodeled myocardium.
2. Stress perfusion defects associated with proportion-
Differences in blood pool concentration of tracers
ately decreased or lack of 18F-FDG uptake indicates
can impact the apparent match or mismatch of perfusion
18 scarred or non-viable myocardium, and revascular-
F-FDG images. The separate adjustment of threshold
ization is not recommended.
and contrast settings can help compensate for these
discrepancies. Qualitative or semiquantitative approaches can be
Four distinct resting perfusion-metabolism patterns applied to the interpretation of perfusion-metabolism
may be observed in dysfunctional myocardium. Patterns patterns. When comparing 18F-FDG metabolism with
1–2 are all indicative of viable myocardium, whereas perfusion images, it is important to first identify the
pattern 3 represents non-viable tissue (Table 13). normal reference region (the region with the highest
If stress and rest perfusion imaging information is tracer uptake), preferably on the stress myocardial per-
available, it is useful to add an estimate of the extent of fusion images. The extent of mismatch or match defect
stress-inducible ischemia in regions of normal resting may be small (5 to 10% of the LV), moderate (10 to
perfusion and 18F-FDG uptake, in regions with matched 20% of the LV), or large ([20% of the LV). The
resting perfusion 18F-FDG defects, or in regions with severity of a match defect can be expressed as mild,
resting perfusion 18F-FDG metabolic mismatch. The moderate, or severe in order to differentiate between
simultaneous display of stress and rest perfusion and non-transmural and transmural myocardial infarction.
18
F-FDG metabolic images is most helpful but not Interpretation of 18F-FDG images when
available on all display workstations. In circumstances perfusion images have not been obtained. In-
where only resting perfusion imaging is performed terpretation of 18F-FDG images without perfusion images
alongside 18F-FDG metabolic imaging, besides report- and/or angiographic information and/or without informa-
ing on the extent of scar and extent of hibernating tion on regional wall motion is discouraged. The
myocardium, it is useful to indicate that in the absence presence of relatively well-preserved 18F-FDG uptake
of corresponding stress myocardial perfusion images, in dysfunctional myocardium does not differentiate
one cannot rule out stress-induced myocardial ischemia. ischemic from non-ischemic cardiomyopathy. The
18
Table 13. Interpretation of myocardial perfusion and glucose loaded F-FDG patterns
18
Myocardial blood flow F-FDG uptake Interpretation
Normal blood flow Normal 18F-FDG uptake Normal
Reduced blood flow Preserved or enhanced 18F-FDG Perfusion-metabolism mismatch
uptake
Normal or near-normal Reduced 18F-FDG uptake Reversed perfusion-metabolism
blood flow mismatch
May occur in the septum of
patients with LBBB114
Proportionally reduced Proportionally reduced 18F-FDG Perfusion-metabolism match
blood flow uptake
The first 3 patterns represent viable myocardium. Only the last pattern, where both perfusion and
metabolism defects are matched, represents nonviable (scarred) tissue
degree of 18F-FDG accumulation over and above meta-analysis of 7 studies.128 18F-FDG PET may be
regional perfusion helps assess the relative amount of positive earlier than MR reflecting inflammatory activity
scar and metabolically viable myocardium. The latter of the disease.130 In addition, strong risk-stratification
information may significantly influence the power of the power has been demonstrated for 18F-FDG PET that is
test for predicting functional recovery. Therefore, it is beyond that provided by the JMHW criteria.131
recommended that 18F-FDG metabolic images be ana- Study protocol. When 18F-FDG PET is used for
lyzed in conjunction with perfusion images, obtained the detection of cardiac sarcoidosis, a rest perfusion
either with SPECT or, preferably, with PET. imaging study is also required for both co-localization
with the myocardium and to determine whether there are
inflammatory cells present (termed mismatched defect) or
absent (termed matched defect) in hypoperfused regions.
DETECTION OF INFLAMMATION AND
For imaging of a cardiovascular device or prosthetic
INFECTION
infections, or medium-to-large vessel vasculitis, however,
18
F-FDG imaging is becoming an accepted tool for a myocardial perfusion study is not required. Other than this
diagnosing active cardiac inflammation.114,115 While the difference in the requirement for a myocardial perfusion
technique is potentially useful in a variety of inflamma- scan, the acquisition, reconstruction, image review, and
tory conditions, such as giant cell myocarditis116 and viral reporting of the 18F-FDG PET scan for infection/vasculitis
myocarditis,117 currently the predominant use is for are the same as for cardiac sarcoidosis.
identification of active cardiac sarcoidosis. Another For cardiac sarcoidosis, it is important to exclude
emerging application is for identification of cardiovascu- significant obstructive CAD and prior myocardial infarc-
lar infections, particularly prosthesis and device infection. tion. CAD is excluded, prior to 18F-FDG PET, preferably
by a coronary angiogram (invasive or CT) or rest and
stress MPI. The rest MPI study can be performed with
Assessment of Cardiac Sarcoidosis
either PET or SPECT methods. Rest MPI can be
Sarcoidosis with cardiac involvement indicates a high performed on the same day (typically) or on a different
risk of mortality and morbidity, accounting for 13% to 25% day (as needed) from the 18F-FDG study. If SPECT MPI
of fatal cases118,119 with a reported five-year mortality is used, attenuation-corrected images are recommended.
ranging from 25% to 66%.119,120 Signs and symptoms can MPI is required at baseline and at follow-up scans.
be non-specific with autopsies showing more prevalent Patient preparation. A key aspect of cardiac
cardiac involvement than is appreciated clinically.121 sarcoidosis imaging is proper dietary preparation that
While a clinical diagnosis of cardiac sarcoidosis had suppresses physiological cardiomyocyte uptake of 18F-
customarily been established based on the Japanese FDG, such that tracer uptake is limited to active
Ministry of Health and Welfare Diagnostic Guidelines inflammatory cells in the myocardium (Table 14). The
(JMHW)122 as revised by the Japan Society of Sarcoidosis primary dietary preparation consisting of avoidance of
and other Granulomatous Disorders in 2006,123 this carbohydrate-containing foods should begin about 24
standard relies on biopsy-proven cardiac involvement or hours prior to the test, with an intake of high-fat and high-
histologically proven extra-cardiac disease with indirect protein foods for at least two meals 24 hours prior, and
findings of cardiac inflammation.124 Unfortunately, car- then an overnight fast.132–136 Interpreting physicians
diac biopsy has limited sensitivity. Indirect evidence should also be aware of potential confounding factors
consisted of cardiac 67Ga (gallium citrate) uptake, a such as administration of glucose-containing IV medica-
perfusion defect consistent with myocardial scarring, tions and preparations to hospitalized patients, and less
cardiac wall motion abnormalities, conduction abnormal- common activities, such as peritoneal dialysis. Suppres-
ities on ECG, and more recently abnormalities on cardiac sion of myocyte glucose uptake can be assisted by giving
MR.125 Most recently, the value of cardiac 18F-FDG PET IV unfractionated heparin (10 IU/kg 30 minutes prior ? 5
imaging for assessment of active cardiac sarcoidosis has IU/kg 15 minutes prior or 50 IU/kg 15 minutes prior to
been demonstrated and in many places is becoming an radiotracer administration)137, which results in ele-
established technique.126–128 The Heart Rhythm Society vated138 plasma levels of free fatty acids and increasing
has established new criteria for clinical diagnosis of cardiac utilization of free fatty acids instead of glucose,
cardiac sarcoidosis that includes PET imaging.129 without increasing partial thromboplastin time. Lower
The underlying pathophysiologic principle involves doses of IV heparin (15 IU/kg) appear to be effective in
an upregulation of glucose metabolism at sites of suppressing physiological uptake of 18F-FDG without
macrophage-mediated inflammation. Diagnostic accu- significant prolongation of partial thromboplastin time.
racy has been shown to be high, with a reported Although not systematically validated, a combina-
sensitivity of 89% and a specificity of 78%125 from tion of one or more of the above methods appears to be
Table 14. Methods to suppress glucose utilization by normal myocardium
Methods Technique Comments

Prolonged fast Fast of 12-18 hours Preferred for patients on tube
feeds or patients scheduled for
procedures requiring NPO
High fat/low carbohydrate diet Two meals 24 hours prior to High fat, protein permitted,
the study, followed by an low-to-no carbohydrate diet
overnight fast
IV unfractionated heparin 15-50 units of regular IV Ensure patient has no
heparin 15 min prior to IV 18F- contraindications to
FDG administration or 500 IU administration of IV heparin.*
of IV heparin 45 minutes and IV regular heparin drip is
15 minutes (total 1000 IU) prior frequently prepared in D5W
to IV 18F-FDG and should be discontinued
whenever possible prior to the
sarcoid protocol 18F-FDG
study.
Combined methods High fat/low-carbohydrate diet
for 2 meals, one day prior,
followed by overnight fast,
and IV regular heparin prior to
administration of 18F-FDG
* including bleeding tendencies, allergy or history heparin-induced thrombocytopenia with thrombosis (HIT);
IV = intravenous; NPO = Nil per os, nothing by mouth
better than any single method alone.130 The success rates uptake values. It is important to keep the dose, injection-
of these various methods to suppress the myocardial to-scan time, method of radiotracer dose (with or without
glucose utilization are not uniform, and may be difficult residual subtraction), and the acquisition parameters
depending on the other factors, such as dietary compli- similar for any follow-up scans.
ance, medications, metabolic milieu, co-existing Scan start time and duration. 18F-FDG imag-
medical conditions, such as diabetes mellitus, etc. ing is started 90 minutes (minimum of 60 minutes) after
18
F-FDG acquisition parameters. The acquisi- injection of radiotracer to allow for accumulation of
tion parameters for 18F-FDG cardiac scans are similar to radiotracer in the inflamed tissue. The acquisition
those used for myocardial viability. Because a majority of includes a partial whole-body scan to include the lungs
these individuals also have cardiac devices, when hybrid and mediastinum (3 minutes per bed position for 3D
PET/CT imaging is used, focal hot spots may be noted imaging, and 4 minutes per bed position for 2D scans)
corresponding to the device leads. For this reason, both followed by a dedicated cardiac scan (10 minutes per
attenuation-corrected and non-attenuation-corrected images bed position for 3D, 20 to 30 minutes for 2D imaging).
are reconstructed. Whenever feasible, a hybrid PET/CT scan The whole-body scan is repeated at follow-up.
may be preferable compared to a dedicated PET scan to Image interpretation of cardiac inflamma-
localize region of 18F-FDG uptake. tion: sarcoidosis. As with viability studies, an
Dose. Typically, about 8 to 10 mCi of 18F-FDG is accompanying MPI study, preferably with a PET tracer,
injected intravenously into a peripheral vein manually or such as 82Rb or 13N-ammonia, is important and consid-
using an automatic injection system. Use of an automatic ered essential by most practitioners. If a SPECT tracer is
injection system (1 mL/s) may significantly reduce used for perfusion imaging, attenuation correction
occupational radiation exposure to the technologists.139 should be performed. Perfusion and 18F-FDG slices
The height and weight of the patient and the preinjection should be displayed side by side using a conventional
and the post-injection doses (subtracting residual activity) cardiac display, i.e., standard short-axis, horizontal long-
are logged into the acquisition computer. This informa- axis, and vertical long-axis views. A semiquantitative
tion is critical for estimating standardized radiotracer scoring system, such as that used for perfusion and
viability studies, can be employed. 18F-FDG ‘‘hot in the tissue divided by the injected dose of tracer adjusted
spots’’ identify areas of abnormal cardiac inflammation, for body weight.144 A maximal SUV greater than mean
as opposed to ‘‘cold spots,’’ which identify abnormal- values plus two standard deviations from control patients
ities of perfusion or metabolic viability. have been suggested as an abnormal threshold,141 with
Several methods of image interpretation pattern one report describing a sensitivity of 85% and a speci-
classification have been described, but none of these are ficity of 90% in reference to JMHW criteria.132 SUV
formally established or validated with histological find- values have been shown potentially useful in following
ings. One method focuses on 18F-FDG uptake, and patient response to therapy, having been shown to be
classifies findings as no uptake, diffuse uptake, focal associated with response to immunosuppressive ther-
uptake, and focal-on-diffuse uptake. Another incorpo- apy145 and improvement in LV function.146 A coefficient
rates perfusion and 18F-FDG information, and classifies of variation of regional myocardial SUV, which repre-
as normal perfusion and normal (i.e., absent) 18F-FDG, sents 18F-FDG uptake heterogeneity, may also help
either abnormal perfusion or abnormal 18F-FDG, and increase diagnostic accuracy, with a value [0.18 in one
both abnormal perfusion and abnormal 18F-FDG.140 Yet study demonstrating a sensitivity of 100% and a speci-
another group has classified in terms of perfusion and ficity of 97%, with a decrease in coefficient of variance
FDG patterns.141 These classification schemes can help seen after corticosteroid therapy.124
not only with initial diagnosis, but also to follow up A whole-body 18F-FDG PET, as well as CT transmis-
disease progression and response to therapy. sion image (for hybrid scanning), should also be reviewed
Observation of 18F-FDG limited to the cardiac and reported for evidence of extra-cardiac sarcoid disease
blood pool suggests proper preparation and more con- activity. Non-cardiac areas of 18F-FDG uptake are poten-
fidently rules out active cardiac sarcoidosis. On the other tially accessible biopsy sites for a definitive diagnosis of
hand, diffuse homogeneous cardiac uptake of 18F-FDG, sarcoidosis. Whole-body scans can also provide a ratio of
particularly in the absence of defects on accompanying cardiac 18F-FDG uptake to other regions, such as liver,
perfusion imaging, may indicate inadequate suppression cerebellum, and blood pool that may assist in diagnosing
of cardiomyocyte 18F-FDG uptake and may lead to a cardiac sarcoidosis and following response to therapy.
false-positive conclusion.
As with metabolic images, interpretation of images for
Assessment of Cardiovascular Device
the presence of active sarcoidosis inflammation must
Infections
consider clinical data that might confound image findings.
An important caveat to consider is some of the aforemen- Use of cardiac implantable electronic devices
tioned patterns, such as regions with perfusion abnormalities (CIEDs), including pacemakers, cardiac resynchroniza-
that have increased 18F-FDG uptake, could potentially tion therapy devices, and implantable cardiac
indicate myocardial hibernation in the setting of ischemic defibrillators (ICDs), as well as left ventricular assist
heart disease. Thus, a diagnosis of active cardiac sarcoidosis devices (LVADs), and prostheses, such as valves and
may be difficult, if not impossible, in patients who also have annular ring implants, have become key aspects of
coronary disease with ongoing ischemia. cardiac care. Despite well-established benefits in appro-
Another issue is how to interpret diffuse 18F-FDG priate situations, there is a risk of device infection that
uptake, which may be a consequence of poor dietary has been increasing, with a reported CIED infection rate
preparation. A focal-on-diffuse pattern suggests disease, of 1.9/1000 device-years and associated blood stream
having been reported in about 31% of patients with infection or device-related endocarditis at 1.14/1000
sarcoidosis.142 On the other hand, focal 18F-FDG uptake device-years.147,148 There are both intravascular and
in the lateral wall and a diffuse basal pattern have been extravascular components, and infection can involve the
observed in healthy humans.143 generator, device leads, or native cardiac structures.148
It is also important to recognize that in this type of Device infection carries a high risk of death if not
study, cardiac 18F-FDG uptake indicates inflammation, identified and treated appropriately.149 While trans-
which, while consistent with active sarcoidosis, can also esophageal echocardiography is customarily the initial
be caused by a variety of inflammatory disease processes diagnostic approach, imaging of localized inflammation
other than sarcoidosis. This concept needs to be indi- using radionuclide techniques shows potential for improv-
cated in the report. Findings may be ‘‘consistent with’’ ing diagnostic accuracy.150–156 One approach is to use
but are never diagnostic of cardiac sarcoidosis, as tissue white blood cells labeled with indium-111 or 99mTc.
is required for diagnostic certainty. Factors that may limit the sensitivity of a radio-labeled
Image interpretation may be enhanced by quantify- white blood cell scan include the viability of the white
ing 18F-FDG uptake using an SUV within each segment blood cells after in vitro labeling process and the migration
of the heart. SUVs represent the decay-corrected uptake rate of the cells to the infection site. The latter becomes a
particular concern in patients who are on antibiotic 5. Fused PET/CT images can be used to provide
treatment, in whom cell chemotaxis is decreased. In anatomic location for tracer uptake sites in relation
addition, this technique can be cumbersome and costly, to device components, i.e., generator, leads. The
and images are often count-poor with low spatial resolu- anatomic overlay can help distinguish device from
tion. Different from radio-labeled white blood cell superficial skin infection.
scintigraphy, 18F-FDG PET/CT imaging is based on 6. Distribution and pattern of tracer uptake may be more
in vivo 18F-FDG labeling of the pre-existing inflammatory important than intensity of uptake. Focal or hetero-
cells at the infection site. With the stimulation of cytokines, geneous uptake favors infection, while mild diffuse
these cells (macrophages, neutrophils, and lymphocytes) uptake along a device or lead may favor non-specific
overexpress the glucose transporter-1 and accumulate 18F- inflammatory changes.
FDG with high concentration.150 Thus, 18F-FDG PET/CT
Regarding PET/CT imaging for LVAD-associated
for in vivo labeling of metabolically active inflammatory
infections, the literature is sparse, consisting of case
cells at the infection site has the advantage of superior
reports.152 Infection can be identified on and around the
tomographic images with higher spatial and contrast
pump, and along drivelines and cannula; however,
resolution, being less labor intensive, and giving less
specific criteria for image interpretation have not been
radiation exposure. 18F-FDG PET/CT can accurately
developed.
diagnose infection and, for devices such as an ICD or
Diagnosis of prosthetic valve endocarditis is challeng-
pacemaker, may help distinguish deep pocket from super-
ing. While customarily echocardiographic techniques and
ficial infections.150–152 Lead infection can sometimes also
blood cultures are the major criteria for making the
be identified, but is less diagnostically reliable.
diagnosis, each of these has limitations. 18F-FDG PET/
Use of 18F-FDG PET/CT for diagnosing cardiovas-
CT can facilitate the diagnosis of prosthetic valve endo-
cular device infection is based mainly on studies with
carditis increasing sensitivity from 70% to 97% in relation
relatively small patient cohorts, and needs further
to the modified Duke criteria, without decreasing speci-
development. Although there are no accepted interpre-
ficity.107,153 The following are issues to consider when
tation standards at this time, for CIEDs the following are
performing and interpreting 18F-FDG PET/CT imaging for
techniques and issues to consider:152
suspected prosthetic valve endocarditis:
1. Proper dietary preparation, as described in the prior
• Inflammatory activity may cause false-positive 18F-
sarcoidosis section, is to avoid confusing myocardial
FDG PET/CT results, such as early after prosthetic
uptake from radiotracer activity in devices or pros-
implantation.
theses next to or within the heart. Patients should
• Surgical adhesive used to seal an aortic root graft may
avoid carbohydrates in the meal for 24 hours before
produce inflammation resulting in false-positive tracer
the test and then fast overnight.
uptake.154
2. Both CT attenuation-corrected and non-attenuation-
• Small vegetations may cause false-negative results.
corrected images should be reviewed to help recog-
• Physiologic myocardial uptake of 18F-FDG PET/CT
nize artifacts of increased tracer uptake related to the
and cardiac motion can interfere with proper image
high-density metal in devices. Any ‘‘positive’’ 18F-
interpretation.
FDG uptake on attenuation-corrected images should
be confirmed on non-attenuation-corrected images. Currently, 18F-FDG PET/CT imaging is not con-
3. Sites of abnormal 18F-FDG PET/CT uptake should be sidered an initial or confirmatory study for prosthetic
noted as well as sites of maximal uptake. valve endocarditis.155 At this time, the technique
4. Site of abnormal uptake should be separated by areas: appears most useful for patients with suspicion of
skin (superficial), subcutaneous tissue, region sur- endocarditis but with indeterminate or negative clinical,
rounding the generator, overlying leads, and echocardiographic, or microbiological findings.
intravascular/intracardiac.
A qualitative visual score can be used:
REPORTING OF MYOCARDIAL PERFUSION AND
Tracer uptake Score METABOLISM PET STUDIES
No tracer uptake 0
Mild tracer uptake 1 Patient Information
(≤ lung parenchyma score) The report should start with the date of the study,
Moderate tracer uptake 2 patient’s age, sex, height, and weight or body surface
(more intense than lung parenchyma) area, as well as the patient’s medical identification
Intense tracer uptake 3 number.
Indication for Study to the specific clinical question asked by the referring
clinician and the procedural approach chosen for
Understanding the reason(s) why the study was
answering this question.
requested helps in focusing the study interpretation on
the clinical question asked by the referring clinician. In
addition, a clear statement for the indication of the study Summary of Stress Data
has become an important component of billing for
If myocardial perfusion has been evaluated during
services rendered. For sarcoidosis and infection studies,
stress, the type of the stressor, the stress agent, the dose,
list prior clinical findings or correlative imaging results
route of administration, and time of infusion should be
that led to consideration of the 18F-FDG PET scan.
specified. Side effects and symptoms experienced during
stress should be reported. If pharmacologic stress was
History and Key Clinical Findings discontinued prematurely, the reasons should be
provided.
A brief description of the patient’s clinical history
Hemodynamic and ECG responses during the stress
and findings can contribute to a more appropriate and
study, including changes in heart rate, blood pressure,
comprehensive interpretation of the rest (and stress)
development of arrhythmias, conduction abnormalities,
perfusion and of the metabolism images. This informa-
and ST-T wave changes and their location, should be
tion may include past myocardial infarctions and their
detailed. Symptoms such as chest pain, shortness of
location, revascularization procedures, the patient’s
breath, and others during the administration of the stressor
angina-related and congestive heart failure-related
and in the recovery phase should be documented.
symptoms, presence of diabetes or hypertension, and
other coronary risk factors. Information on regional and
global LV function can similarly be important for the Summary of Clinical Laboratory Data and
interpretation of regional perfusion and metabolism Dietary State
patterns.
Information about the dietary state (e.g., fasting or
A description of the ECG findings may serve as an
postprandial) and about interventions for manipulating
aid in the study interpretation, such as the presence of Q-
plasma glucose levels through, for example, oral or IV
waves and their location or conduction abnormalities
administration of glucose or use of the euglycemic-
(e.g., LBBB) for exploring septal perfusion and/or
hyperinsulinemic clamp, should be given. If pharmaco-
metabolic abnormalities. A list of current cardiac med-
logic measures, such as nicotinic acid derivatives, have
ications should be included. For sarcoidosis and
been used, this should be described. Furthermore, blood
cardiovascular infection studies, identify if this is the
glucose levels, if obtained at baseline or after intervention,
initial study or follow-up study and list current immuno-
should be listed, as they are useful for the interpretation of
suppressive and infection therapy, respectively.
the metabolic images. If there is an expected abnormal
response to a glucose load, this should also be reported.
Type of Study For sarcoidosis and cardiovascular infection studies,
list the dietary preparation used to suppress glucose
The imaging protocols should be stated concisely.
utilization by normal myocardium and the method used
This should include the type of camera utilized for
to interpret 18F-FDG uptake (relative or SUV values).
imaging myocardial perfusion and/or metabolism, for
example, PET or PET/CT system, or SPECT perfusion
and 18F-FDG PET metabolism. For stress myocardial
Image Description and Interpretation:
perfusion PET studies, the type of stressor should be
Perfusion
clearly indicated, such as treadmill, dipyridamole, ade-
nosine, regadenoson (A2A adenosine receptor agonist), or A statement regarding image quality is important.
dobutamine. Radiopharmaceuticals and their radioactiv- Reduced quality may affect the accuracy of the inter-
ity doses used for the perfusion and the metabolism PET pretation. If the cause of the reduced quality is known or
imaging studies should be identified. The acquisition suspected, then it should be stated accordingly. This
modes and image sequences should be described, such as information may prove useful when repeat images are
static or dynamic image acquisition, for stress and rest obtained in the same patient.
perfusion imaging, perfusion and metabolism imaging on The report should first describe the relative distri-
different days, and the use of gating. bution of the perfusion tracer on the stress images and
The main body of the report following this intro- provide details on regions with decreased radiotracer
ductory descriptive information should then be tailored uptake in terms of the location, extent, and severity of
defects that may be supplemented by a diagram. The Segments with regional dysfunction that exhibit patterns
authors should then describe whether regional myocar- of viable myocardium (i.e., preserved perfusion or
dial defects seen on stress images become reversible or decreased perfusion with relatively increased 18F-FDG
persist on the corresponding paired rest images. Other uptake) should be identified. Similar reporting should be
findings, such as LV cavity dilatation at rest, transient performed for segments exhibiting a flow-metabolism
(stress-induced) LV cavity dilatation, lung uptake, matched pattern, that is, decreased regional 18F-FDG
concentric LV hypertrophy, asymmetric septal hyper- uptake in proportion to decreased regional myocardial
trophy, pericardial photopenia, prominent RV cavity perfusion. The presence of viable and non-viable tissue
size and hypertrophy, and extra-cardiac abnormalities, should be reported as a continuum (e.g., predominantly
should be included in the report. Regional and global LV viable or admixture of viable and non-viable tissues).
function should be described from gated PET perfusion Findings on semiquantitative or quantitative image
and/or metabolism images. The scintigraphic pattern on analysis, supplemented by a diagrammatic approach,
the stress/rest myocardial perfusion images should then may be added. Location and, in particular, extent of
be reported in clinical terms as: viable and non-viable tissues, expressed as a percentage
of the LV, is important because it provides important
1. Normal.
prognostic information on future cardiac events
2. Ischemic.
and predictive information on potential outcomes in
3. Fixed defect. This should be considered scarred if
regional and global LV function, congestive heart
there is a history of prior myocardial infarction or
failure-related symptoms, and long-term survival after
pathologic Q-waves on the ECG. However, in the
revascularization. Finally, the description of the perfu-
absence of prior myocardial infarction or ECG Q-
sion-metabolism findings may include a correlation to
waves, particularly in patients with new-onset heart
regional wall motion abnormalities and should indicate
failure, hibernating but viable myocardium should be
the potential for a post-revascularization improvement
considered and assessed with additional myocardial
in the regional and global LV function. The potential for
viability study.
outcome benefit may also be reported.
4. An admixture of scarred and ischemic but viable 18
F-FDG sarcoidosis/infection study. A
myocardium.
statement regarding image quality and adequacy of
5. Non-ischemic cardiomyopathy.
suppression of glucose utilization by normal myocar-
Quantitative assessment of absolute regional MBF dium is important. Incomplete suppression of glucose
can be presented as an adjunct to the visual interpreta- utilization by normal myocardium may reduce the
tion in the proper patient population. accuracy of the interpretation.
For sarcoidosis and infection 18F-FDG studies
wherein whole-body images are obtained, the whole-
body 18F-FDG findings should be reported. Sarcoidosis
Image Description and Interpretation:
is a systemic disease and systemic disease activity may
Metabolism for Myocardial Viability,
be important for management. Regions of abnormal 18F-
Sarcoidosis, and Cardiovascular Infection
FDG uptake that may be accessible for biopsy should be
18
F-FDG myocardial viability study. The reported. For infection studies, if distal septic emboliza-
report should describe the relative distribution of tion sites are identified, they should be reported.
myocardial perfusion at rest, and the location, extent, Final interpretation. Results should be suc-
and severity of regional perfusion defects. The report cinctly summarized and first addressed whether the
should continue with a description of the 18F-FDG study is normal or abnormal. On rare occasions where a
uptake in the myocardium and indicate the tracer definitive conclusion cannot be made, the interpreter
activity concentrations in normally perfused and in should aid the referring clinician by suggesting other
hypoperfused myocardium. The adequacy of achieving a tests that may provide further insight into the clinical
glucose-loaded state, as evident from the radiotracer dilemma. The report should always take into consider-
uptake in normally perfused myocardium and also from ation the clinical question that is being asked: is the study
blood pool activity, should then be reported and be requested for CAD detection or myocardial viability
related to the presence of insulin resistance, including assessment? Any potential confounding artifacts or other
impaired glucose tolerance and type 2 diabetes. This quality concerns that significantly impact the clinical
should be related to the residual blood pool activity as interpretation of the PET study should be mentioned.
additional evidence for inadequate clearance of 18F- A statement on the extent and severity of perfusion
FDG from blood into tissue and provide the information defects, reversibility and mismatch in relation to 18F-FDG
for low tracer uptake in normally perfused myocardium. metabolism, and their implication regarding ischemia,
scar, or hibernating myocardium should be made. It may APPENDIX: SAMPLE IV PROTOCOL

be useful to conclude the report with a summary of the
A sample protocol for IV glucose loading, based on
extent and location of myocardial ischemia in relation to
one in use at Vanderbilt University Medical Center,
vascular territories, as well as the presence and extent of
Nashville, TN, and adapted from Martin et al58 is
perfusion-metabolism mismatch in patients with chronic
presented.
ischemic LV dysfunction. LV cavity size, function, and
regional wall motion should be reported at rest and during 1. IV glucose/insulin loading for non-diabetic patients
stress with special note of transient ischemic cavity with a blood glucose (BG) level \110mg/dL (\6.11
dilatation, if present. A statement as to the implication of mmol/L) under fasting condition.
the findings should be made.
a. Prepare dextrose/insulin solution: 15 U of regular
Comparison should be made to prior studies, and
insulin in 500 mL of 20% dextrose in a glass
interim changes regarding the presence and extent of
bottle. The initial 50 mL is discarded through the
myocardial ischemia, scar, or hibernation should be
plastic IV tubing (no filter) to decrease adsorption
highlighted. On the basis of the scintigraphic findings
of the insulin to the tubing.
(e.g., extent of perfusion-metabolism mismatch), the like-
b. Prime the patient with 5 U of regular insulin and
lihood of recovery of function after revascularization can
50 mL of 20% dextrose (10g) IV bolus.
be estimated. The potential for a post- revascularization
c. Infuse dextrose/insulin solution at a rate of 3 mL
improvement in contractile function is low for perfusion-
kg-1 h-1 for 60 minutes (corresponding to an
metabolism matched defects, even if the regional reduc-
insulin infusion of 1.5 mU kg-1 min-1 and a
tions in perfusion and in 18F-FDG uptake are only mild or
glucose infusion of 10 mg kg-1 min-1). Monitor
moderate. Conversely, the potential for improvements in
BG every 10 minutes (goal BG, 100 to 200 mg/dL
regional contractile dysfunction is high if perfusion is
[5.56 to 11.11 mmol/L]).
normal, if both perfusion and 18F-FDG uptake are normal,
d. If BG at 20 min is 100-200 mg/dL (5.56 to 11.11
or if 18F-FDG uptake is significantly greater than regional
mmol/L), preferably \150 mg/dL (8.33 mmol/L),
perfusion (i.e., mismatch). Finally, the potential of a post-
administer 18F-FDG intravenously.
revascularization improvement in the LVEF by at least 5 or
e. If BG is [200 mg/dL ([11.11 mmol/L), admin-
more EF units is high if the mismatch affects 20% or more
ister small IV boluses of 4 to 8 U of regular insulin
of the LV myocardium,108,156 although lesser amounts of
until BG decreased to \200 mg/dL (\11.11
mismatch (5 to 20% of the LV myocardium) may also have
mmol/L). Administer 18F-FDG intravenously.
potential outcome benefit, with or without improvement in
f. Stop dextrose/insulin infusion at 60 minutes and
the LVEF.157,158 The latter may be included in the report at
start 20% dextrose at 2 to 3 mL kg-1 h-1.
the reporting physician’s discretion.
g. During image acquisition, continue infusion of
For sarcoidosis and infection studies which are hot
20% dextrose at 2 to 3 mL kg-1 h-1.
spot images, comparison to prior studies is based on SUV
h. At completion of the acquisition of the images,
values or ratio of relative uptake in relation to another
discontinue infusion, give a snack to the patient,
organ. Changes in response to therapy are indicated as
and advise him or her regarding the risk of late
changes in SUV. Comparison to prior studies, cardiac
hypoglycemia.
MR or echocardiography, when available may be helpful.
i. ALERT:
If additional diagnostic clarification seems to be
needed, the physician may recommend an alternative (i) If BG is [400 mg/dL ([22.22 mmol/L), call
modality. If a CT transmission scan was performed for the supervising physician immediately.
attenuation correction, clinically relevant CT findings (ii) If BG is \55 mg/dL (\3.06 mmol/L) or if the
must be reported. patient develops symptoms of hypoglycemia
with BG \ 75 mg/dL (\4.17 mmol/L),
discontinue dextrose/insulin infusion, admin-
Disclosure
ister one amp of 50% dextrose intravenously,
Dr. Rob S. Beanlands is a consultant to Lantheus Medical and call the supervising physician.
Imaging and Jubilant DRAXImage and receives grant support
from Lantheus Medical Imaging, Jubilant DRAXImage, and 2. IV glucose/insulin loading for diabetic patients or
GE Healthcare; Dr. Robert J. Gropler is a consultant to fasting BG is [110 mg/dL ([6.11 mmol/L):
Biomedical Systems; Dr. Juhani Knuuti is a consultant to
a. Prepare insulin solution: 100 U of regular insulin
Lantheus Medical Imaging and serves on the speakers bureaus
of GE Healthcare and Philips. All other contributors have in 500 mL of normal saline solution in a glass
nothing relevant to disclose. bottle. The initial 50 mL is discarded through the
plastic IV tubing (no filter) to decrease adsorption c. If the BG is [200 mg/dL ([11.11 mmol/L), an
of the insulin to the tubing. additional bolus of insulin is given. An exogenous
b. Prime patient with regular insulin: If fasting BG is 20% glucose infusion is started at an initial rate of
[140 mg/dL ([7.76 mmol/L), prime the patient 0.25 mg kg-1 min-1 and adjusted until stead state
with 10 U of regular insulin IV bolus. If fasting is achieved. The BG concentrations are measured
BG is \140 mg/dL (\7.76 mmol/L), prime the every 5 minutes during the insulin clamp. The
patient with 6 U of regular insulin IV bolus. glucose infusion is adjusted according to the
c. Infuse insulin solution at a rate of 1.2 mL kg-1 plasma glucose over the preceding 5 minutes.
h-1 for 60 minutes (corresponding to an insulin
infusion of 4 mU kg-1 min-1) or for the entire
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ASNC IMAGING GUIDELINES/SNMMI

ASNC imaging guidelines/SNMMI procedure

Received Mar 25, 2016; accepted Mar 25, 2016

INTRODUCTION tomography (PET) measurements of myocardial blood

Table 1. Suggested QC procedures: dedicated PET imaging devices

field-service engineers. The CT calibration is then Combined PET/CT QC Procedures

Table 3. Schedule of CT QC for PET/CT units

Table 4. Combined PET/CT QC procedures

Imaging Mode (Static, Gated, or Dynamic) Image Reconstruction

Table 5. General guidelines for CT-based transmission PET imaging

CT parameter General principle Effect on patient dose

Feature BGO Systems LSO (LYSO) Systems Technique

Feature GSO Systems Technique

Feature Acquisition parameters Technique

Table 9. Semiquantitative scoring system of defect severity and extent

Grade Interpretation Score

Absolute quantification of myocardial deciding whether a finding is normal or abnormal, as

Figure 1. LV myocardial segmentation, standard nomenclature, and vascular territories. PET

Procedure Steps for standardization Technique

BG at 45-60 min after administration Restorative measure Technique

Feature Technique Requirement

Table 14. Methods to suppress glucose utilization by normal myocardium

Methods Technique Comments

scar, or hibernating myocardium should be made. It may APPENDIX: SAMPLE IV PROTOCOL

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