The continual innovation of commercial PET/CT solutions in nuclear cardiology: Siemens Healthineers
The continual innovation of commercial PET/CT solutions in nuclear cardiology: Siemens Healthineers
Bernard Bendriem 0
Kathryn McCullough 0
Mohammad Raza Khan
Anne M. Smith 0
Damita Thomas 0
0 Siemens Healthcare GmbH , MI, Knoxville, TN , USA
Cardiac PET/CT is an evolving, non-invasive imaging modality that impacts patient management in many clinical scenarios. Beyond offering the capability to assess myocardial perfusion, inflammatory cardiac pathologies, and myocardial viability, cardiac PET/CT also allows for the non-invasive quantitative assessment of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recognizing the need for an enhanced comprehension of coronary physiology, Siemens Healthineers implemented a sophisticated solution for the calculation of MBF and MFR in 2009. As a result, each aspect of their innovative scanner and image-processing technology seamlessly integrates into an efficient, easy-to-use workflow for everyday clinical use that maximizes the number of patients who potentially benefit from this imaging modality.
MPI Æ Hybrid imaging Æ PET Æ CAD
Positron emission tomography, combined
with computed tomography
Myocardial blood flow
Myocardial flow reserve
Blood input function
Myocardial perfusion imaging
Coronary artery disease
Non-invasive cardiac imaging plays a major role in
the assessment of patients with known, or suspected,
CAD. In addition to evaluating the existence, extent, and
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s12350-018-1262-3) contains
supplementary material, which is available to authorized users.
The authors of this article have provided a PowerPoint file, available
for download at SpringerLink, which summarises the contents of the
paper and is free for re-use at meetings and presentations. Search for
the article DOI on SpringerLink.com.
Prompt gamma correction
Siemens molecular & anatomical
severity of CAD, cardiac imaging provides risk
estimates for major adverse cardiac events and guides
Currently there are several imaging modalities in
clinical use, including: Single photon emission
tomography (SPECT), Magnetic resonance imaging (MRI),
Computed tomography (CT), and Positron emission
tomography (PET). The latter captures the in vivo
distribution of intravenously injected positron-emitting
radiopharmaceuticals that reflect biochemical pathways
of the target organ(s). Dependent on the injected
radiopharmaceutical and selected protocol, PET is able
to assess myocardial viability, myocardial perfusion, and
various inflammatory cardiac pathologies. Cardiac PET
is also able to provide absolute quantification of MBF
and MFR.1 The ability to derive these values from
noninvasive imaging represents a major breakthrough in
cardiac imaging and demonstrates the potential of these
measures to have a strong prognostic value. Most PET
scanners combine with a CT to form a PET/CT hybrid
device. The co-registered CT images provide anatomical
information that the system uses for the attenuation and
scatter correction of the PET data. In addition, the latest
CT features enable non-invasive assessment of the
coronary arteries and further enhance the PET
According to the American Society of Nuclear
Cardiology (ASNC) and the Society of Nuclear
Medicine and Molecular Imaging (SNMMI), the following
qualities emphasize the clinical usefulness of PET/CT in
the management of patients with CAD.
• MPI PET/CT demonstrates a high diagnostic
accuracy and provides consistently high-quality images.
Also, compared to most diagnostic cardiac imaging
modalities that utilize radiation, cardiac PET/CT has a
relatively low radiation exposure.
• MPI PET/CT is time-efficient and, dependent on the
injected radiopharmaceutical, a complete cardiac rest/
stress study can be acquired in less than 1 hour.
Typical acquisition times are 5 minutes compared to
1- to 2-day protocols with 20- to 30-minute
acquisition times for rest and stress SPECT MPI.1,3
• The combination of MPI PET/CT with MBF
quantification can further improve risk and treatment
stratification, disease detection, and the ability to
monitor lifestyle modifications or therapeutic
• The capability to routinely and non-invasively
quantify MBF in mL/min/gram is unique to PET/CT.4
An announcement from the American Medical
Association (AMA) recognizes the increasing clinical
importance of functional imaging and MBF
quantification. The announcement regards the Current Procedural
Terminology (CPT ) Editorial Panel’s approval of a
category III billing code for PET-based absolute MBF
quantification that took effect on January 1st, 2018.5
Given this recent reimbursement support and the
aforementioned strengths of PET/CT, the clinical availability
of MBF quantification is now poised to further play an
important role in the evaluation of vascular
dysfunction.4 A positive impact on CAD patient management in
the next few years will facilitate the continued clinical
adoption and growth of cardiac PET/CT.
The availability and regulatory approval of
suitable radiopharmaceuticals are requirements for the
clinical adoption of any PET- or SPECT-based
technology. While different regions of the world have their own
regulations, the following three tracers are currently
approved by the Food and Drug administration (FDA):
• Fluorine-18 fluorodeoxyglucose (FDG) for viability
and inflammation imaging
• Rubidium-82 chloride and Nitrogen-13 ammonia for
perfusion imaging and estimating MPI and MBF2,6
Rubidium-82 chloride (produced in a Strontium-82
generator) and Nitrogen-13 ammonia (produced in an
onsite cyclotron) show promising clinical results as both
allow the application of compartment model kinetics to
produce more reliable MBF quantification. (Table 1)
Although currently not approved by the FDA,
Oxygen-15 water is perfectly suited for MBF
quantification due to its 100% extraction rate.3 Fluorine-18
flurpiridaz, also not currently FDA approved, has the
potential to overcome some of cardiac imaging’s
limitations. Fluorine-18 flurpiridaz’s MBF quantification is
expected to be very similar to Nitrogen-13 ammonia,
and also potentially close to Oxygen-15 water, due to its
high extraction fraction. It is an attractive radiotracer
because, like FDG, it does not require an onsite
cyclotron or generator for production and it yields high
count images. Table 1 summarizes the main
characteristics of the radiopharmaceuticals used in cardiac PET/
Widespread clinical adoption of non-invasive
cardiac PET/CT depends not only on the growing evidence
of impact on patient management and the expansion of
clinical expertise, but also on the availability of this
state-of-the-art technology. Since cardiac PET/CT MPI
is technically challenging, it is critical that the clinical
workflow be efficient and provides accurate and
reproducible results. As a trendsetter in cardiovascular
imaging, Siemens Healthineers offers a variety of
PET/CT platforms that provide a complete set of tools
to support a comprehensive clinical workflow for the
assessment of cardiac diseases. These functionalities are
accessible across all of the available Siemens
Healthineers PET/CT products, thereby addressing all market
0 r o
o g 1 i m c
ufl (re 10 /A .–5 /A /A se euq fo lug o
1 N 3 N N Y R
/724 ./15 /001 /09 saPeh irsce sseo
101 /62 (22 .44 5 5
9 5 I E
xe d o
n r o
g g 5 te tr 0
in y 1 a lo 4 00
iagm xO w(ccy .20 /0220 (/7074 ../7007 /100
o a o
1 0 N R N
iz l a
im ia i
tp ra u
ls le d
ira isb an
t s t
II o s
I p re
ite e s
s d d
n ; n
o le a
roa isb tse
f n s r
8 u o
- g lc
e y y
n x c
r o l
o e a
u d n
lF ro io
) A ito o
70 D c p en
N u e e
0 /3 .0 0
/1 0 /1 /10 /90 ,sA rdo irsc tew
10 10 (37 .10 5 0 e p xe b o
9 5 Y E N
e m e o
ca u id ta
m iid 82 lro re
h u ch en
THE SCANNER: BIOGRAPH mCT
Siemens Healthineers utilize LSO scintillators in all
of their PET detectors. As shown in Table 2, LSO offers
the best combination of properties of any PET
scintillator known today. Present-day PET/CT scanners now
operate in 3D mode (without septa) and can register
coincidence events between all possible detector rings.
The resulting increase in sensitivity comes at the
expense of more scatter, randoms, and dead time. In
cardiac PET/CT, scatter and randoms have a tendency to
artificially increase counts in areas with low uptake that
are surrounded by higher activity, thereby making the
identification of subtle perfusion defects challenging.2
The high light output and fast decay time of LSO
facilitate better rejection rates of scatter and random
events due to optimized energy discrimination and a fast
coincidence timing of 4.5 ns. Existing 3D-vs-2D
comparative studies show that Lutetium-based crystals,
combined with improvements in electronics and
software, can overcome the challenges of 3D-scanner
acquisitions.2,7 The inherent properties of LSO utilized
in Siemens Healthineers’ 4 9 4 mm crystals, paired with
time of flight (ToF), translates to high spatial sampling
and resolution as well as an improvement in image
Due to the combination of 3D-acquisition mode and
ToF, Biograph mCT requires less injected activity which
translates to a reduction in the patient’s effective dose.
For short-lived tracers, such as Rubidium-82 chloride,
adequate activities are needed to ensure satisfactory
myocardial perfusion image quality within an
Defines detection efficiency of detector
Effective atomic number
Decay time (ns)
Influences detector dead time and randoms rejection
Impacts spatial and energy resolution
Energy resolution Influences scatter rejection Non-hygroscopic Simplifies manufacturing, improves reliability and reduces service costs
LSO’s fast scintillation decay time of 40 ns reduces the detector’s dead time and enables the use of ToF information: a crucial
advantage for imaging Rubidium-82 chloride studies. LSO’s high density ensures optimal detection efficiency. High relative light
output allows the use of small detector crystals (4 9 4 mm) that provide the base for outstanding isotropic spatial resolution.19
acceptable acquisition time.8,9 A PET/CT system with
the ability to perform a single-injection protocol for
MBF and MPI—without detector saturation—is ideal as
detector saturation causes an incorrect elevation of MBF
values.8,9 To reduce the possibility of detector saturation
an adequate dynamic range of the detection system,
combined with the ability to obtain high-quality images
with lower doses of Rubidium-82 chloride, is essential.
Among ten commercially available systems, Biograph
mCT provides the highest-tolerated maximal activity of
0.39 mCi/kg (14.4 MBq/kg) and is also one among four
PET/CT scanners that is considered suitable for the
clinically efficient single-injection protocol using 0.3
mCi/kg (10 MBq/kg) of Rubidium-82 chloride.9
Gantry Configuration and Ease of Use
The body habitus of patients with CAD varies
significantly and the industry-standard bore size of 70
cm is often inadequate to accommodate some patients.
In addition, some patients can cause a vertical deflection
of the bed that results in a misalignment of the PET and
CT data. This misalignment can cause potential image
artifacts due to AC errors.
For these patients, the 78 cm bore size of Biograph
mCT is an advantage over the industry-standard 70 cm
bore size. Combined with a short tunnel and a patient
handling system (PHS) that supports up to 500 lb (227
kg), the wide bore enhances patient comfort and
supports the study of a broad patient population. Due
to the unique cantilever design of the PHS, the pedestal
and the table move as one unit. Such movement results
in zero differential deflection between the CT and the
Desired outcome LSO BGO GSO NaI
PET acquisition. This unique concept eliminates the risk
of registration artifacts between the CT and PET due to
table flexion (Figure 1).
For MBF studies, the PET acquisition must start
before the injection bolus reaches the right ventricular
cavity to ensure the system accurately captures the
BIF.10 For most conventional PET/CT systems, this
would require two technologists: one to start the
acquisition and one to manage the radiopharmaceutical
injection. To simplify the acquisition, Biograph mCT
has control buttons on the front and the back of the
gantry. This design enables one technologist to safely
begin the acquisition and trigger the
radiopharmaceutical injection simultaneously, thereby eliminating the
need for additional resources and increasing optimal
synchronization between injection and scan initiation.
PET Image Formation
In a PET/CT scanner, each pair of parallel and
opposite detectors produces a coincidence line, or line of
response (LOR), that localizes a positron annihilation
event along a specific line. A PET dataset is formed by a
large number of LORs that reconstruct a cross-sectional
image once they are fully processed.
Biograph mCT’s optional fourth detector ring,
TrueV, offers an extended field of view (FoV). With
this extended FoV, Biograph mCT’s noise equivalent
count rate (NECR) increases by 70% and delivers
improvements in sensitivity and image quality
Biograph mCT’s dedicated hardware and software
tools, such as uniquely designed detector crystals,
sophisticated coincidence electronics, and a diversity
of signal-correction algorithms, help establish and
reinforce the important role of cardiac PET/CT in clinical
routine. Cardiac CT innovations complement Biograph
mCT’s tools to offer optimal temporal and spatial
resolution as well as flexible, yet straightforward,
Rubidium-82 chloride is commonly used in clinical
practice, yet the additional 776 keV prompt gamma ray
emission produces significant background activity in the
emission data. Without correction, the prompt gamma
ray can result in loss of image contrast, increased noise,
and quantitative errors.11 Biograph mCT’s PGC
algorithm automatically addresses the impact of this
nonpure isotope positron emission within integrated scatter
correction.12,13 Such an improvement in image quality
and quantification specifically supports prompt gamma
isotope studies such as MPI and MBF examinations with
In addition to providing attenuation correction for
cardiac PET imaging, the CT of Biograph mCT
functions as a high-end, stand-alone CT scanner to
noninvasively assess coronary artery morphology.
Highquality cardiac CT requires optimal temporal and spatial
resolution as well as flexible acquisition techniques. The
CT has a gantry rotation time of 0.33 seconds which
allows for virtually motion-free imaging of the heart.
The Combined Applications to Reduce Exposure
(CARE) feature includes CARE Dose and CARE KV
which automatically adjust parameters to optimize
image quality and reduce dose. CT bolus tracking and
CARE contrast optimize the CT scan and contrast media
injection, which increases process efficiency and
standardization of care.
SMART Auto Cardiac Registration
Attenuation correction helps compensate for the
attenuation of photons emitted by the human body, but
requires an optimal alignment between the emission
(PET) and the transmission (CT) scans. Due to the
sequential nature of the acquisition protocol, there is a
risk of misalignment between the functional PET and
anatomical CT images of the heart. The resulting
mismatch can ultimately affect the attenuation-corrected
data: for example, by suggesting a false-positive
perfusion defect.14 Conventional correction methods require
the user to perform a manual alignment of the data,
which is time consuming and often causes inter- and
intra-user variability.14–16 In response, Siemens
Healthineers developed an automatic registration algorithm:
SMART Auto Cardiac Registration. SMART Auto
Cardiac Registration integrates into the cardiac
acquisition workflow and automatically registers cardiac PET
and CT data for optimal attenuation correction. The
algorithm focuses solely on the optimal alignment of the
heart in both datasets (Figure 3).
SMART Auto Cardiac Registration shows optimal
results using a translation-only registration algorithm.17
The algorithm was evaluated on 413 PET/CT image
pairs and the results confirmed the robustness,
consistency, and accuracy of the algorithm. The findings also
underlined the algorithm’s potential to reduce the
processing time and remove inter-operator variability.14
In a more recent review,18 the authors concluded that
Siemens Healthineers’ registration solution significantly
improves PET/CT AC alignment and the diagnostic
accuracy of Rubidium-82 chloride PET/CT perfusion
imaging when compared to data with no CT–AC
alignment or with manual alignment.
Optimized PET Image Reconstruction
In order to optimize image reconstruction and
improve signal-to-noise (SNR) ratio, Biograph mCT
incorporates detector point spread function (PSF) and
ToF into its standard iterative reconstruction
algorithms.12,19–21 The serial reconstruction time for all
images (static, gated, dynamic), within one PET
acquisition, is approximately 9 minutes post acquisition. In an
effort to reduce reconstruction times, Siemens
Healthineers introduced a software solution that allows parallel
processing of PET data. This innovative approach
allows the PET data reconstruction process to begin
during an active PET acquisition. PET images
reconstruct, and are available for viewing, in less than
4 minutes post acquisition. Figures 4A and B show the
gain in processing time compared to serial
Since today’s PET/CTs produce more complex data
than ever before, managing such a volume of
information can present challenges. Designed to address these
challenges, syngo.via is Siemens Healthineers’
integrated multimodality imaging solution. As an open
platform it allows the user to extend and customize the
interface for an optimal reading experience in cardiac
applications as well as oncological, neurological, and
general nuclear medicine applications. Siemens
Healthineers offers three well-known cardiac post-processing
solutions: Corridor4DM,22 Cedars Cardiac Suite,23 and
syngo.PET MBF. All seamlessly integrate into the
syngo.via platform and allow users to compute
semiquantitative and quantitative metrics for MPI. Users may
read all Siemens Healthineers’ cardiac PET/CT data on
any other industry-standard cardiac post-processing
solution. Furthermore, syngo.via supports structured
reporting (SR) to facilitate information sharing.
The current practice of managing patients with
CAD observed a recent paradigm shift to include
functional diagnostic and therapeutic strategies. Several
invasive coronary pressure- and flow-measurement
options show value in diagnostic and therapeutic
decision making. To avoid the increased risk of adverse
events that come with the invasive nature of those
procedures, a non-invasive technology that allows a
comprehensive, physiological assessment of the
coronary status could be of utmost clinical relevance. The
option to detect diseases from advanced, flow-limiting
epicardial CAD to earlier stages of atherosclerosis or
microvascular dysfunction has the potential to optimize
patient management and risk stratification.3,4,24
The importance of non-invasive quantification of
MBF as a parameter to establish an understanding of the
physiology of the coronary arteries was recognized
about 30 years ago.25 Since then, development in
scanner instrumentation and software makes it possible
to envision a broad clinical use of MBF and MFR
measurements that help guide clinical management and
advance research. While an ideal perfusion tracer for
MBF quantification would have a 100% extraction rate
from blood to tissue and no washout from the
myocardial cells, Rubidium-82 chloride and Nitrogen-13
ammonia both have a non-linear net-tracer uptake in
the myocardium, especially in the higher coronary flow
range.8,26 This uptake leads to an underestimation of the
calculated MBF at high flow levels and therefore
requires the application of proper physiological
compensation algorithms.26,27 Software programs for MBF
and MFR calculation should take into account the
nonlinear extraction of the clinically available
radiopharmaceuticals. Siemens Healthineers was among the first
to provide PET/CT cardiology customers with a
regulatory-approved MBF application: syngo.PET MBF. The
application is based on the work of several leading
academic institutions who demonstrate the feasibility of
MBF and MFR calculations based on dynamic
Nitrogen13 ammonia and Rubidium-82 chloride PET data.10,28,29
The provided solution seamlessly integrates the
compartmental kinetic analysis of dynamic PET data into the
For input, the application uses the reconstructed
dynamic stress and rest cardiac Nitrogen-13 ammonia or
Rubidium-82 chloride images. The principals of
compartmental modeling form the basis of the MBF
calculation; syngo.PET MBF uses a one-compartment
model30 for Rubidium-82 chloride and a
two-compartment model for Nitrogen-13 ammonia to compensate for
the non-linear tracer uptake.31 The software
automatically applies LV motion correction to the later frames
and offers an additional motion correction option in the
case of severe motion artifacts. When using Nitrogen-13
ammonia, a first-frame-subtraction method compensates
for residual activity from a previous study.32 For output,
the application provides quantitative and visual
information about the perfusion capabilities of the major
coronary arteries. The quantitative MBF values for
stress, rest, and MFR display in table form; visualization
of MBF and MFR displays in polar plot form; and the
blood input function, as well as the stress and rest time
activity curves (TAC), display in graphical form. The
application groups the information by coronary artery
territory to aid the physician in the localization of any
noted pathology (Figure 5). The software also allows the
creation of hospital-specific normal databases.
A multicenter study comparing ten software
packages, including syngo.PET MBF, concludes that MBF
and MFR values computed from Rubidium-82 chloride
correlate well when using the one-compartment
model.30,33 A similar study comparing three software
tools, including syngo.PET MBF, concludes that MBF
and MFR values derived from Nitrogen-13 ammonia
demonstrate excellent correlation.34 Such a conclusion
underlines syngo.PET MBF’s potential use in both
routine clinical settings as well as clinical research
projects for Rubidium-82 chloride and Nitrogen-13
NEW CLINICAL HORIZONS USING MOTION
FREE LIST MODE DATA
Given that PET data acquisitions are not
instantaneous, PET images often appear blurred as a result of
patient motion. Image blurring can impact the
visualization of the myocardial tracer distribution or the
assessment of wall thickness. Conventional dual gating
options use electrocardiogram (ECG) leads and a variety
of respiratory gating instrumentation. The latter often
requires a time-intensive setup, can cause measurement
artifacts, and captures only external body motion as a
surrogate for the actual motion of the internal organs. To
further expand respiratory and cardiac motion
correction, Siemens Healthineers recently introduced their new
motion management feature: CardioFreeze.
CardioFreeze simultaneously detects and compensates for
respiratory motion by analyzing the PET list mode
data and applying a deblurring algorithm to gated
images based on mass preservation optical flow.12,35,36
Compared to conventional dual gating, CardioFreeze
enables each individual image to reconstruct using all
counts: up to 24 times the number of counts in each
gated image, depending upon the number of gates in the
reconstruction (Figure 6). Since the scanner takes 100%
of the PET statistics into account there is a possibility of
improved image quality and SNR, or a reduction in PET
scan time, or injected dose.37 Viability assessment,
perfusion imaging, and the evaluation of inflammatory
processes—such as Sarcoidosis or intravascular
infections—are likely to benefit from this feature.
CONCLUSION AND OUTLOOK
As an innovator in medical imaging, Siemens
Healthineers strives to continuously improve existing
products and create new solutions that address
challenges specific to cardiac imaging. Siemens
Healthineers’ Biograph mCT provides innovative,
reliable, and easy-to-use capabilities that ensure an optimal
quantitative and qualitative PET/CT acquisition and
image formation workflow. A seamless integration of
post-processing and viewing applications enables the
completion of an efficient, high-quality cardiac and
PET/CT examination that includes MBF and MFR
calculations. Once clinical practices further integrate
MPI and MBF assessments into their routine and
Fluorine-18 labeled perfusion tracers receive regulatory
approval, the resulting physiological information can
apply to many additional clinical scenarios. Such
scenarios include the management of heart failure, detailed
assessment of coronary vasodilator function, and
monitoring of coronary endothelial function in response to
statin therapy.3 As for the future of PET/CT technology,
Siemens Healthineers’ innovative Biograph Vision*
recently introduced the Optiso Ultra Dynamic Range
(UDR) detector. The detector’s unique design enables
high spatial resolution, increased sensitivity, and an
unmatched temporal resolution.38 By complementing
the effects of the reduced dead time with high sensitivity
and resolution, this new detector intends to capture more
image detail in single-injection protocols for MBF and
MPI assessment. Siemens Healthineers’ Biograph
family, in combination with syngo.via, continually evolves
to meet emerging clinical needs and offers effective
tools to assess a wide spectrum of CAD.
* Biograph Vision is currently under development and is not
yet commercially available in the European Union, the U.S. or
any other country.
We thank Dr. Kristin Schmiedehausen, Richard Powers,
Chuck Hayden, Jonathan Frey, and Mike Bonfig for their
contributions to the development of this manuscript.
Bernard Bendriem, Jessie Reed, Kathryn McCullough,
Mohammad Raza Khan, Anne M. Smith, Damita Thomas, and
Misty Long are regular Siemens Healthineers employees.
This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s)
and the source, provide a link to the Creative Commons
license, and indicate if changes were made.
1. Bengel FM , Berman DS , Calnon DA , Paolo Camici MD , James A , Cerqueira MD , et al. American society of nuclear cardiology and society of nuclear medicine and molecular imaging joint position statement on the clinical indications for myocardial perfusion PET . J Nucl Cardiol 2016 ; 23 : 1227 - 31 . https://doi.org/10.1007/ s12350-016-0626-9.
2. Dilsizian V , Bacharach SL , Beanlands RS , Bergmann SR , Delbeke D , Dorbala S , et al. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures . J Nucl Cardiol 2016 ; 23 : 1187 - 226 . https://doi. org/10.1007/s12350-016-0522-3.
3. Gewirtz H , Dilsizian V . Integration of quantitative positron emission tomography absolute myocardial blood flow measurements in the clinical management of coronary artery disease . Circulation 2016 ; 133 : 2180 - 96 . https://doi.org/10.1161/ CIRCULATIONAHA.115.018089.
4. Ziadi MC . Myocardial flow reserve (MFR) with positron emission tomography (PET)/computed tomography (CT): Clinical impact in diagnosis and prognosis . Cardiovasc Diagn Ther 2017 ; 7 : 206 - 18 . https://doi.org/10.21037/cdt. 2017 . 04 .10.
5. ASNC AMA announces new CPT category III code for PET absolute quantification of myocardial blood flow [Blog] . Jul 31 , 2017 . https://www.asnc.org/blog_home. asp?display=159. Accessed Jan 31 2018 .
6. Iskandrian AE , Dilsizian V , Garcia EV , Beanlands RS , Cerqueira M , Soman P , et al. Myocardial perfusion imaging: Lessons learned and work to be done-update . J Nucl Cardiol 2018 ; 25 : 39 - 52 . https://doi.org/10.1007/s12350-017-1093-7.
7. deKemp RA , Yoshinaga K , Beanlands RSB . Will 3-dimensional PET-CT enable the routine quantification of myocardial blood flow ? J Nucl Cardiol 2007 ; 14 : 380 - 97 . https://doi.org/10.1016/j. nuclcard. 2007 . 04 .006.
8. Murthy VL , Bateman TM , Beanlands RS , Berman DS , BorgesNeto S , Chareonthaitawee P , et al. Clinical quantification of myocardial blood flow using PET: Joint position paper of the SNMMI cardiovascular council and the ASNC . J Nucl Med 2018 ; 59 : 273 - 93 . https://doi.org/10.2967/jnumed.117.201368.
9. Renaud JM , Yip K , Guimond J , Trottier M , Pibarot P , Turcotte E , et al. Characterization of 3-dimensional PET systems for accurate quantification of myocardial blood flow . J Nucl Med 2017 ; 58 : 103 - 9 . https://doi.org/10.2967/jnumed.116.174565.
10. Pan XB , Declerck J , Burckhardt DD . Cardiac positron emission tomography: overview of myocardial perfusion, myocardial blood flow and myocardial flow reserve imaging [Whitepaper] . Siemens Medical Solutions USA , Inc. 2011 .
11. Moncayo VM , Garcia EV . Prompt-gamma compensation in Rb-82 myocardial perfusion 3D PET/CT: Effect on clinical practice . J Nucl Cardiol 2016 . https://doi.org/10.1007/s12350-016-0672-3.
12. Siemens Medical Solutions USA , Inc. Biograph mCT [Product Brochure] . 2016 .
13. Hayden Jr CH , Casey ME , Watson CC , inventors; Siemens Medical Solutions USA, Inc., assignee. Prompt gamma correction for non-standard isotopes in a pet scanner . US patent 7 , 894 , 652 . 2011 Feb 22 .
14. Bond S , Declerck J. AutoCardiac: Registration of PET to CTAC for attenuation correction [Whitepaper] . Siemens Medical Solutions USA , Inc. 2013 .
15. Martinez-Moller A , Souvatzoglou M , Navab N , Schwaiger M , Nekolla SG . Artifacts from misaligned CT in cardiac perfusion PET/CT studies: Frequency, effects and potential solutions . J Nucl Med 2007 ; 48 : 188 - 93 .
16. Goetze S , Brown TL , Lavely WC , Zhang Z , Bengel FM . Attenuation correction in myocardial perfusion SPECT/CT: Effects of misregistration and value of reregistration . J Nucl Med 2007 ; 48 : 1090 - 5 . https://doi.org/10.2967/jnumed.107.040535.
17. Bond S , Kadir T , Hamill J , Casey M , Platsch G , Burckhardt D , et al. Automatic registration of cardiac PET/CT for attenuation correction . IEEE Nuclear Science Symposium Conference Record; 2008 Oct 19 - 25; Dresden, Germany. 2008 : 5512 - 17 . http://ieeexplore.ieee.org/xpl/ mostRecentIssue.jsp?punumber=4747668& filter%3DAND(p_IS_ Number%3A4774073)&pageNumber=41. Accessed Dec 12 2017 .
18. Slomka PJ , Diaz-Zamudio M , Dey D , Motwani M , Brodov Y , Choi D , et al. Automatic registration of misaligned CT attenuation correction maps in Rb-82 PET/CT improves detection of angiographically significant coronary artery disease . J Nucl Cardiol 2015 ; 22 : 1285 - 95 . https://doi.org/10.1007/s12350-014-0060-9.
19. Siemens Medical Solutions USA , Inc. Inside Biograph TruePoint PET .CT [Product Brochure] 2009 .
20. Jakoby BW , Bercier Y , Conti M , Casey ME , Bendriem B , Townsend DW . Physical and clinical performance of the mCT time-of-flight PET/CT scanner . Phys Med Biol 2011 ; 56 : 2375 - 89 . https://doi.org/10.1088/ 0031 -9155/56/8/004.
21. Germino M , Ropchan J , Mulnix T , Fontaine K , Nabulsi N , Ackah E , et al. Quantification of myocardial blood flow with (82)Rb: Validation with (15)O-water using time-of-flight and point-spreadfunction modeling . EJNMMI Res 2016 ; 6 : 68 . https://doi.org/10. 1186/s13550-016-0215-6.
22. Invia Solutions . Invia 4DM Software . 2017 . http://www. inviasolutions. com/4dm-software. Accessed Dec 20 2017 .
23. Cedars-Sinai. Cedars-Sinai Projects . 2017 . https://www.cedarssinai.edu/Patients/Programs-and-Services/Medicine-Department/ Artificial-Intelligence-in-Medicine-AIM/Projects/. Accessed Dec 20 2017 .
24. Gould KL , Johnson NP , Bateman TM , Beanlands RS , Bengel FM , Bober R , et al. Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making . J Am Coll Cardiol 2013 ; 62 : 1639 - 53 . https://doi.org/10.1016/j.jacc. 2013 . 07 .076.
25. Soufer R , Zaret BL . Positron emission tomography and the quantitative assessment of regional myocardial blood flow . J Am Coll Cardiol 1990 ; 15 : 128 - 30 . https://doi.org/10.1016/ 0735 - 1097 ( 90 ) 90187 - T .
26. Schindler , TH. Quantitative PET / CT Measures of coronary flow reserve with existing and novel tracers . [Presentation 2013 SNMMI Midwinter Meeting]; 2013 Jan 24 -27; New Orleans, Louisana. http:// www.snm.org/docs/mwm13/Presentations/Saturday/Quantitative% 20PET -CT%20Measures%20of%20Coronary%20Flow%20Reserve% 20with%20Existing%20and%20Novel%20Tracers % 20 - % 20Schindler. pdf. Accessed Dec 13 2017 .
27. Hsu B. PET tracers and techniques for measuring myocardial blood flow in patients with coronary artery disease . J Biomed Res 2013 ; 27 : 452 - 9 . https://doi.org/10.7555/JBR.27.20130136.
28. El Fakhri G , Kardan A , Sitek A , Dorbala S , Abi-Hatem N , Lahoud Y , et al. Reproducibility and accuracy of quantitative myocardial blood flow using 82Rb-PET: comparison with 13N-ammonia PET . J Nucl Med 2009 ; 50 : 1062 - 71 . https://doi.org/10.2967/jnumed.104. 007831.
29. Camici PG , Gropler RJ , Jones T , L'Abbate A , Maseri A , Melin JA , et al. The impact of myocardial blood flow quantitation with PET on the understanding of cardiac diseases . Eur Heart J 1996 ; 17 : 25 - 34 .
30. Lortie M , Beanlands RS , Yoshinaga K , Klein R , Dasilva JN , DeKemp RA . Quantification of myocardial blood flow with 82Rb dynamic PET imaging . Eur J Nucl Med Mol Imaging 2007 ; 34 : 1765 - 74 . https://doi.org/10.1007/s00259-007-0478-2.
31. Hutchins GD , Schwaiger M , Rosenspire KC , Krivokapich J , Schelbert H , Kuhl DE . Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging . J Am Coll Cardiol 1990 ; 15 : 1032 - 42 . https://doi.org/10.1016/ 0735 - 1097 ( 90 ) 90237 - J .
32. Pan XB , Alexanderson E , Le Meunier L , Declerck J . Residual activity correction for computing myocardial blood flow from dynamic 13NH3 studies [abstract] . J Nucl Med 2013 ; 52 Suppl 1 .
33. Nesterov SV , Deshayes E , Sciagra` R, Settimo L , Declerck JM , Pan XB , et al. Quantification of myocardial blood flow in absolute terms using 82Rb PET imaging: Results of RUBY-10-a multicenter study comparing ten computer analysis programs . JACC Cardiovasc Imaging 2014 ; 7 : 1119 - 27 . https://doi.org/10.1016/j. jcmg. 2014 . 08 .003.
34. Slomka PJ , Alexanderson E , Jacome R , Jimenez M , Romero E , Meave A , et al. Comparison of clinical tools for measurements of regional stress and rest myocardial blood flow assessed with 13Nammonia PET/CT . J Nucl Med 2012 ; 53 : 171 - 81 . https://doi.org/10. 2967/jnumed.111.095398.
35. Dawood M , Gigengack F , Jiang X , Schafers KP . A mass conservation-based optical flow method for cardiac motion correction in 3D-PET . Med Phys 2013 . https://doi.org/10.1118/1.4770276.
36. Buther F , Dawood M , Stegger L , Wubbeling F , Schafers M , Schober O , et al. List mode-driven cardiac and respiratory gating in PET . J Nucl Med 2009 ; 50 : 674 - 81 . https://doi.org/10.2967/ jnumed.108.059204.
37. Siemens Medical Solutions USA , Inc. CardioFreeze. Advanced motion management delivers virtually motion-free images [Marketing Brochure] . 2017 .
38. Siemens Medical Solutions USA , Inc. Biograph vision. See a whole new world of precision [Marketing Brochure] . 2017 .
39. Nuclear medicine radiation dose tool. Society of nuclear medicine and molecular imaging . http://www.snmmi.org/ClinicalPractice/ doseTool.aspx?ItemNumber= 11216 &navItemNumber= 11218 . Updated May 16, 2015 . Accessed March 6 2018 .