Comparison of CTAC and prone imaging for the detection of coronary artery disease using CZT SPECT
Ann Nucl Med
Comparison of CTAC and prone imaging for the detection of coronary artery disease using CZT SPECT
Shimpei Ito 0 1
Akihiro Endo 0 1
Taiji Okada 0 1
Taku Nakamura 0 1
Takashi Sugamori 0 1
Nobuyuki Takahashi 0 1
Hiroyuki Yoshitomi 0 1
Kazuaki Tanabe 0 1
0 Clinical Laboratory Department, Shimane University Hospital , Izumo , Japan
1 & Shimpei Ito
Background Cadmium-zinc-telluride (CZT) cameras have improved the evaluation of patients with chest pain. However, inferior/inferolateral attenuation artifacts similar to those seen with conventional Anger cameras persist. We added prone acquisitions and CT attenuation correction (CTAC) to the standard supine image acquisition and analyzed the resulting examinations. Methods and results Seventy-two patients referred for invasive coronary angiography (CAG), and who also underwent rest/stress myocardial perfusion imaging (MPI) on a CZT camera in the supine and prone positions plus CTAC imaging, to examine known or suspected CAD between April 2013 and March 2014 were included. A sixteen-slice CT scan acquired on a SPECT/CT scanner between rest and stress imaging provided data for iterative reconstruction. Sensitivity, specificity, accuracy, and positive and negative likelihood ratios (LRs) were calculated to compare MPI with CAG on a per-patient basis. Per-patient sensitivity, specificity, and accuracy of supine images to predict coronary abnormalities on CAG were 35% [95% confidence interval (CI) 19-52], 86% (95% CI 80-92), and 74% (95% CI 66-82); those of prone imaging were 65% (95% CI 45-81), 82% (95% CI 76-87), and 78% (95% CI 68-85); and those of CTAC were 59% (95% CI 41-71), 93% (95% CI 87-97), and 85% (95% CI 76-91), respectively.
Single-photon emission computed tomography; Myocardial ischemia; Coronary artery disease
Division of Cardiology, Shimane University Faculty of
Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan
Conclusions Prone acquisition and CTAC images improve
the ability to assess the inferior/inferolateral area.
Myocardial perfusion imaging (MPI) is useful for
evaluating patients for coronary artery disease (CAD), assessing
patients’ risk of future cardiac events, and evaluating
A recently developed high-efficiency ultrafast
multipinhole cardiac camera with cadmium-zinc-telluride (CZT)
detectors shows higher photon sensitivity and spatial
resolution compared with conventional Anger cameras. Its
overall accuracy has improved compared with the Anger
]. The increased sensitivity allows a lower dose
and shorter image acquisition times .
Soft tissue attenuation of tracer activity, mainly in the
inferior/inferolateral area, can result in artifactual perfusion
abnormalities in the right coronary artery (RCA) and left
circumflex (LCx) territories. The CZT camera, as with the
Anger camera, displays these artifacts as inferior wall
defects. As with the Anger camera [
] attempts to
eliminate artifacts by imaging in the prone position have
been reported [
]. Computed tomographic attenuation
correction (CTAC) has also been reported to be a useful
method to improve the specificity of a diagnosis of inferior
wall ischemia [
], and as for the use of a CZT camera,
one study showed improvement of diagnostic accuracy
with vascular territory analysis . However, clinical
experience using the CZT camera is limited, and there are
few reports on using both prone acquisition and CTAC to
reduce attenuation artifact, and no report has compared
these measures employed as part of the same examination.
We evaluated how addition of both prone imaging and
CTAC might improve diagnostic accuracy in the inferior/
The study population consisted of 85 consecutive patients
who were referred for invasive coronary angiography
(CAG), including planned routine follow-up after
percutaneous coronary interventions (PCI), and also underwent
rest/stress MPI on a CZT camera (Discovery NM 530c, GE
Healthcare, Haifa, Israel) in the supine and prone positions
and a 16-slice CT scan (Discovery NM/CT 670, GE
Healthcare, Haifa, Israel) at Shimane University Hospital,
Shimane, Japan, to examine known or suspected CAD
between April 2013 and March 2014. Exclusion criteria
were prior coronary artery bypass grafting (n = 4),
hemodialysis (n = 3), and inability to lie prone (n = 6).
The remaining 72 patients were investigated. This
prospective study was approved by the Ethics Committee
of Shimane University (No. 1242), and all patients
provided written informed consent.
Myocardial perfusion imaging protocol
All patients underwent 1-day rest/stress 99mTc-tetrofosmin
myocardial single-photon emission computed tomography
(SPECT) pharmacologic protocol with adenosine (6-min
infusion using a dose of 0.14 mg/kg/min) (Fig. 1). All
patients were instructed to avoid caffeine-containing food
and beverages for 14 h before the MPI study. The patients
were injected with a dose of 296 MBq at rest and 888 MBq
Study protocol for myocardial perfusion imaging
of 99mTc-tetrofosmin during stress, in the arm opposite to
the site of adenosine injection, after the first 3 min of
adenosine infusion. The interval between the resting
isotope infusion and stress radiopharmaceutical injections was
3 h. After a waiting period of 20 min after injection of the
isotope, rest and stress images were acquired using the
CZT camera in both the supine and prone positions with
arms fully abducted, without any detector or collimator
motion. All images were acquired with a 32 9 32 matrix
and 20% energy window centered at the 140 keV
photopeak of 99mTc. Images were ECG-gated and acquired in list
mode with a 5-min scan time for rest and a 3-min scan time
for stress in each position. All SPECT images were
reconstructed on a standard workstation (Xeleris Ver 3.0;
GE Healthcare, Haifa, Israel).
CT attenuation correction
An attenuation map was acquired on a Hybrid SPECT/CT
system (Discovery NM/CT 670, GE Healthcare, Haifa,
Israel) based on one CT scan in the supine position
between rest and stress imaging. The CT image acquisition
parameters were as follows: 120 kV, 10 mAs, field of view
500 mm, slice thickness 5 mm, image reconstruction filter
SOFT, and adaptive statistical iterative reconstruction
Myocardial perfusion image analysis
SPECT images were iteratively reconstructed using the
transmission data generated from the 16-slice CT (Fig. 1).
Reversible perfusion defects on MPI were assumed to be
cardiac ischemia until CAG was performed. The findings
of inferior/inferolateral wall ischemia on MPI were
compared with the findings in the RCA or LCx on CAG.
Images were analyzed with commercially available
software (Cedars QPS/QGS, Cedars-Sinai Medical Center,
Los Angeles, CA, USA). Two experienced cardiologists
99mTc-TF i.v. 296 MBq
99mTc-TF i.v. 888 MBq
(supine 3 min, prone 3 min)
after 3 h
Adenosine 0.14 mg/kg/min 6 min
(supine 5 min, prone 5 min)
Projection Data, CZT SPECT
performed quality analysis of myocardial perfusion images
until CAG was performed. Reversible perfusion defects
were visually diagnosed on MPI as cardiac ischemia. All
fixed defects in this study were assumed to represent scar.
We also performed semi-quantitative analysis using
summed stressed score (SSS), summed rest score (SRS), and
summed difference score (SDS). Cardiac ischemia was
defined as a SDS C2 in each coronary territory. With
respect to definition of inferior/inferolateral wall ischemia,
the following American Heart Association (AHA)
17-segment model was used: LCx = segments 3, 4, 9, 10,
and 15; RCA = segments 5, 6, 11, 12, and 16; and for
anterior wall ischemia, LAD = segments 1, 2, 7, 8, 13, 14,
The findings of inferior/inferolateral wall ischemia on
MPI were categorized as normal, ischemia (reversible
defect), infarction (typical fixed defect), or equivocal
(atypical fixed defect was classified as ‘‘normal without
confidence’’) based on the supine images. Changes in
diagnosis of inferior/inferolateral wall ischemia after
viewing prone and CTAC images as secondary validation
CAG was conducted following standard techniques.
Caffeinated drinks and foods were discontinued for at least
14 h before the procedure. Cardiac ischemia was defined as
a luminal narrowing of C90% by CAG using visual
estimation. In all cases of intermediate stenosis (C75%,
B90%), fractional flow reserve (FFR) was measured and
the presence of myocardial ischemia was determined when
Continuous variables were expressed as mean ± SD, and
categorical variables as percentages. Sensitivity,
specificity, accuracy, and positive and negative likelihood ratios
(LR) were calculated to predict the ability of MPI (each
method) to identify myocardial ischemia in comparison
with an ischemic result of CAG or FFR on a per-patient
basis. Calculated 95% confidence intervals that were not
overlapped were considered significant. All statistical
analyses were performed using SPSS 19.0 (IBM, Armonk,
All patients successfully underwent rest/stress imaging
with the CZT camera and invasive CAG one day after MPI.
Between MPI and CAG, there were no signs of ischemia
progression such as chest pain in any patient. The patient
characteristics are shown in Table 1. Twenty-four patients
(33%) were diagnosed with cardiac ischemia and 35
vessels were interpreted as abnormal with CAG and/or FFR.
Two patients had triple-vessel disease. The number of
patients with left anterior descending artery (LAD)
stenosis, LCx stenosis, or RCA stenosis were 17 (24%), 14
(19%), and 9 (13%), respectively. Two patients had both
LCx and RCA stenosis. There were no patients with left
main trunk disease. Seventeen (24%) patients had LCx and/
or RCA stenoses. Per-patient comparison of MPI with
invasive CAG was assessed (Table 2). Visual per-patient
analysis of MPI revealed reversible perfusion defects in 16
patients (22%) with standard supine images, 23 patients
(32%) with prone images, and 15 patients (21%) with
CTAC images. Per-patient sensitivity, specificity, and
accuracy of supine images to predict cardiac ischemia on
CAG were 35% [95% confidence interval (CI) 19–52],
86% (95% CI 80–92), and 74% (95% CI 66–82); those of
prone images were 65% (95% CI 45–81), 82% (95% CI
76–87), and 78% (95% CI 68–85), and those of CTAC
images were 59% (95% CI 41–71), 93% (95% CI 87–97),
72 ± 9
24 ± 4
Sensitivity, % (95% CI)
Specificity, % (95% CI)
Accuracy, % (95% CI)
Positive LR (95% CI)
Negative LR (95% CI)
and 85% (95% CI 76–91), respectively. Positive LRs were
2.4 (95% CI 1.6–3.7) in supine, 3.6 (95% CI 2.8–4.4) in
prone, and 8.1 (95% CI 4.7–13.8) in CTAC images,
showing significant differences between supine and CTAC
images to predict cardiac ischemia. Negative LR s were
0.76 (95% CI 0.71–0.81) in supine, 0.43 (95% CI
0.35–0.54) in prone, and 0.44 (95% CI 0.38–0.53) in
CTAC image, showing significant difference between
supine images and other two images. According to
semiquantitative analysis, per-patient sensitivity, specificity,
and accuracy of supine images to predict cardiac ischemia
on CAG were 24% (95% CI 11–38), 91% (95% CI 87–95),
and 75% (95% CI 69–83); those of prone images were 35%
(95% CI 19–50), 91% (95% CI 86–95), and 78% (95% CI
70–85), and those of CTAC images were 35% (95% CI
19–52), 87% (95% CI 82–92), and 75% (95%CI 67–83),
respectively. Thus, results based on a semi-quantitative
analysis were inferior to those based on quality analysis.
We present a case in which the CTAC image was more
useful for diagnosing inferior wall ischemia than the
supine and prone images. A 72-year-old man experienced
chest pain, and cardiac catheterization was planned. MPI
was performed the day before CAG. CTAC images
showed inferior ischemia that could not be seen on the
supine and prone images. CAG showed 90% stenosis of
#4PL (Fig. 2).
FFR was measured in the RCA or LCx in 12 patients
because of intermediate coronary artery stenosis. Three
patients were positive; the other nine patients, including
one triple-vessel disease (TVD) patient, were negative.
With respect to FFR-positive patients, all images were
positive in MPI in one patient, but all images were negative
in the other patients. In regard to FFR-negative patients,
four patients were positive in supine images, while in prone
and CTAC images one patient with triple-vessel disease
was positive, and the others were negative.
On the other hand, diagnostic evaluation for anterior
wall ischemia was as follows: sensitivity, specificity, and
accuracy with visual estimation were 55% (95% CI 33–77),
82% (95% CI 78–86), and 78% (95% CI 70–85); those of
semi-quantitative analysis were 73% (95% CI 47–90), 85%
(95% CI 81–88), and 83% (95% CI 75–89), respectively.
We evaluated how a diagnosis based on supine images
changed when adding prone and CTAC images in each
case (Fig. 3a, b).
Forty cases judged to be equivocal based on supine
images decreased to 28 cases on prone images and eight
cases on CTAC images. There were 17 cases in which
diagnosis varied from equivocal to normal in prone images,
and 30 cases in which diagnosis varied from equivocal to
normal in CTAC images. There were five cases that varied
from an equivocal diagnosis in the supine images to an
ischemia diagnosis in the prone images. Three of these
cases were shown to have cardiac ischemia by
catheterization. Likewise from the supine position images to CTAC
images, the diagnosis of three cases changed from
equivocal to ischemia. All three cases were shown to have
myocardial ischemia by catheterization.
We analyzed the diagnostic accuracy for inferolateral wall
ischemia on MPI in the prone position and with CTAC and
the usual supine position images individually, in
comparison with CAG performed the next day. There are several
reports that compare CZT MPI with invasive CAG
8, 13, 14
]. However, the interval between the two
examinations in these studies was 2–3 months, while in our
study it was only 1 day. No ischemic symptoms occurred
in the patients between the examinations.
In this study, adding prone and CTAC images had
favorable outcomes in terms of the ability to diagnose
inferior/inferolateral wall ischemia. In particular, CTAC
images showed significantly better performance to predict
cardiac ischemia based on inferior/inferolateral wall
ischemia compared usual supine images. Use of both prone
and CTAC images decreased the number of
inferior/inferolateral equivocal interpretations.
Nuclear cardiology is one of the most useful tests in the
stratification of risk for cardiac events and treatment
assessment. MPI is a useful examination to determine that
patients will likely benefit from invasive CAG followed by
coronary revascularization, which may be well suited to
medical therapy, and which are not suffering from CAD
]. Recently, the new CZT cameras have made a
significant difference in evaluation of patients for CAD.
However, troublesome artifact effects of the inferior wall
exist similarly to those on images obtained with
conventional Anger cameras. There is a possibility that the
arrangement of the 19 pinhole collimators of the CZT
camera may be more sensitive to the presence of hepatic
and bowel activity compared with the standard Anger
camera with a 360 arc acquisition [
The use of prone imaging can reduce diaphragmatic
attenuation and improve inferior wall image quality. The
rationale for prone imaging is that the heart shifts slightly
superiorly and the diaphragm is more inferior in the prone
position, increasing the distance between the diaphragm
and the inferior wall of the left ventricle. It is said to be
useful to add a prone image to diagnose inferior wall
ischemia with a conventional camera [
] and a similar
report has been published for the CZT camera [
study also shows the improvement in diagnostic
performance for inferior lateral wall ischemia.
Attenuation correction refers to automated methods in
which the intensity of the myocardial perfusion image is
adjusted to reflect the estimated magnitude of soft tissue
attenuation on different regions of the heart, resulting in
improved SPECT MPI diagnostic [
] and prognostic [
accuracy. Attenuation correction methods include either
line-source or CT techniques. CTAC correction is reported
to be one of the most useful methods to solve the artifactual
problems in the inferior wall that appear in images obtained
with Anger cameras. With respect to Discovery NM 530c,
a study using this method was recently reported by Emory
]. Several studies with respect to utility of
CTAC in CZT have been conducted. Caoballi et al.
assessed 44 patients comparing MPI in stress-first with
CZT camera using CTAC and CAG within 6 months, and
they showed CTAC improved diagnostic accuracy by
improving specificity over uncorrected images [
also assessed the diagnostic quality of images using
CTbased transmission data generated with 16-slice CT for
iterative reconstruction of data acquired with the CZT
camera. This method significantly enhanced the ability to
diagnose inferior/inferolateral wall ischemia.
In our study, the addition of prone images or CTAC
images turned out to be useful. In addition, this was the first
report in which the diagnostic quality of images based on
prone images and CTAC, in addition to simple supine
images, obtained with the CZT camera was estimated. It
was clear that the diagnostic quality was better than the
supine images alone for detecting inferior/inferolateral wall
ischemia. The lower dose used with the CZT camera
allows a lower radiation dose to the patient and faster
throughput. Further studies are warranted to develop a
database of normal prone and CTAC images as this method
The reported overall sensitivity of vasodilator stress
perfusion SPECT for the detection of angiographically
significant (C50% stenosis) CAD is 87%, and specificity is
]. Although our analysis was limited to the
inferior/inferolateral area, the sensitivity was poor. We
were not able to determine clearly whether an image on
MPI indicated ischemia or not, because of the problem of
artifact in the inferior/inferolateral area. It is important in
assessing a moderately fixed defect that we cannot consider
‘‘equivocal’’ as normal in clinical practice. The percentage
of equivocal interpretations of supine images in this study
was higher (69%) than that reported in other studies
(approximately 20–40%) [
]. We also assessed how these
equivocal findings changed when prone and CTAC images
were added. Equivocal interpretations decreased to 39 and
11% when using prone and CTAC images, respectively.
Three of 5 cases of prone imaging and all three cases of
CTAC images that varied from equivocal to ischemia in
supine images corresponded to significant stenosis on
catheterization. These changes led to an increase in
sensitivity. These changes are the main point in emphasizing the
use of adding prone and CTAC images.
If the use of CTAC is established, prone imaging may
not always be needed in assessing the inferior/inferolateral
area, and examination time will be reduced. Another
advantage of CTAC imaging is that it can perform well in
elderly people with kyphosis, who may have difficulty
assuming the prone position. Aging is universal, and it
seems that the use of assessment of the
inferior/inferolateral area by CTAC imaging will increase. Cardiac CT is
used widely to assess for coronary artery disease. In cases
where CT images were recently obtained, we hope that
these images will be useful for CTAC. We expect this to
offer improvement over the simple supine position protocol
in artifact problems of the inferior/inferolateral area. The
radiation exposure for CTAC is much lower than that for
routine chest CT. The radiation dose of a conventional
chest CT is approximately 20 mGy (CT dose index;
CTDI). The CTDI for the CT attenuation acquisition is
Studies comparing CAG and high-efficiency CZT
camera SPECT detecting CAD have been reported. Few
studies have been reported with respect to assessment of
diagnostic performance of a CZT camera using FFR
]. Tanaka et al. reported that with addition of prone
imaging, CZT SPECT had a high diagnostic yield in
detecting significant coronary stenosis as assessed using
FFR . However, there are no studies regarding the
addition of both prone and CTAC imaging. FFR is another
well-established index for investigating the physiological
significance of a coronary stenosis. Large clinical trials
such as the FAME trial have also adopted the more
inclusive FFR threshold of 0.80 in main epicardial vessels
]. We assessed cardiac ischemia based on FFR in all
cases where intermediate stenosis was confirmed by CAG.
There have been few CZT MPI studies based on a ‘‘gold
standard’’ for the diagnosis of CAD, which may involve
both anatomical and functional assessments such as FFR,
positron emission tomography, or magnetic resonance
imaging. Assessments with FFR enhance the value of the
present study to the extent of performing FFR to all
branches with intermediate stenosis.
This study was limited by the single-site clinical
experience, and by a small study population. The study included
a mixed population of patients, including those in whom
CAG was performed as follow-up. Furthermore, there
were two cases of triple-vessel disease, and it was thought
that there is a limit in the diagnosis of multivessel disease
based on images obtained using the CZT camera. In such
cases, where there is widespread myocardial ischemia,
perfusion imaging techniques preferentially identify only
the myocardial perfusion defect in the most ischemic
territory. The timing of injection was relatively early in
our protocol, and thus effects from the liver were rather
strong. This problem may have decreased sensitivity in the
supine position. In most cases where we were unable to
diagnose ischemia, there were effects of hepatic
accumulation. We often encountered soft tissue attenuation due
to increased radionuclide tracer in the liver. Further
examination of the timing of the imaging after injection is
needed, and no gated MPI analysis was conducted, which
may have helped differentiate between artifacts and
infarction in this study.
Adding prone acquisition and CTAC–corrected supine
images improved the ability to identify
inferior/inferolateral area defects.
Compliance with ethical standards
Conflict of interest There is no financial support to declare.
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