\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{The effect of separate and combined visual evaluation of imaging
performed in supine and prone positions in
\textsuperscript{99m}Tc-methoxy-isobutyl-isonitrile (MIBI) myocardial
perfusion stress study on the need for rest study in men without a known
history of coronary artery disease.}



\author[1]{Ozan Kandemir}%
\affil[1]{Affiliation not available}%


\vspace{-1em}



  
  \date{June 08, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\textbf{Introduction:}

\textsuperscript{99m}Tc-methoxy-isobutyl-isonitrile myocardial perfusion
imaging (\textsuperscript{99m}Tc-MIBI MPI), is the most commonly used
noninvasive stress imaging method for the diagnosis of coronary artery
disease (CAD) (J1). However, despite its overall effectiveness, the
interpretation of MPI is complex due to potential imaging artifacts,
including those related to the patient and equipment (J). Soft tissue
attenuation, such as that caused by breast position or the diaphragm, is
one of the most common factors that can reduce the test accuracy for
detecting CAD and affect image quality. (G4).~To reduce the factors that
decrease quality, methods such as electrocardiography-gated imaging,
attenuation correction software, and changing the patient's position
have been proposed (G4, G5). MPI is conventionally performed in the
supine position (Y). However, different positions are now being used to
achieve better imaging quality (G).

One approach that has been reported to improve the diagnostic accuracy
of MPI is the use of a supine-prone combination rather than supine MPI
alone (C).

In recent years, numerous studies have shown significant reductions in
both diagnostic performance and patient radiation exposure when using
''stress-first'' imaging, such that a normal stress study can eliminate
the need for subsequent rest imaging (A31, A32, A33, A34).~The normal
stress study will eliminate the need for subsequent rest imaging,
thereby reducing the examination time, radiation dose, and the doses of
radiopharmaceuticals used.

In cases of diaphragmatic or breast attenuation, the absence of
perfusion defects in stress-prone imaging can help exclude ischemic
heart disease, especially when combined with a supine study, thereby
reducing the need for rest imaging (O).

It has been reported that the addition of prone MPI to supine MPI
increases the diagnostic accuracy in populations consisting of both
women and men (C6, C7, C8). However, data directly comparing these two
imaging strategies, especially in cohorts consisting solely of men, are
limited (C).

Despite its potential to increase diagnostic accuracy, the combined
supine-prone MPI is not widely utilized.

In our study, we retrospectively investigated the effect of stress
supine-only, stress prone-only, and combined stress supine-prone MPS
studies on the need for rest imaging in male patients without known
coronary artery disease in whom there is limited data in the literature.

\textbf{Methods:}

\textbf{Patients Population:}

In this retrospective study, we included 378 male patients older than 18
years of age without known CAD who underwent stress MPI in supine and
prone positions between December 2020 and June 2022 in our clinic and
whose files and MPS images were available. Women, patients younger than
18 years of age, patients with known coronary artery disease, and
patients whose follow-ups were not available were excluded.

Institutional ethics committee approval was obtained for this
retrospective study. The study was conducted by the principles outlined
in the Helsinki Declaration of 1964 regarding biomedical research
involving human subjects. Informed consent was not obtained due to the
retrospective nature of the study.

.

\textbf{Patient Preparation, Exertional Stress/Pharmacologic Stress
Protocols:}

The patients were instructed to refrain from consuming nicotine or
caffeine-containing beverages for 12 hours and to discontinue taking
persantine 24 hours before the screening. They were informed about the
discontinuation of nitrate, beta blocker, and calcium antagonist
medications based on their half-lives. Before the radionuclide study,
all patients had fasted for at least 4 hours. We implemented the
procedural guidelines of the European Association of Nuclear Medicine
(EANM) for radionuclide myocardial perfusion imaging protocol (Z). We
followed the one-day stress-optional-rest protocol. For the initial
injection, a dose of 250-400 MBq of radiopharmaceutical was
administered, while for the second injection, three times more
radiopharmaceutical was administered. The stress treadmill test was
performed using the Bruce/modified Bruce protocol. The
radiopharmaceutical injection was administered when the target heart
rate reached a minimum of 85\%. Afterward, the exercise was continued
for at least 1-2 minutes before being terminated. Dipyridamole was used
for pharmacological stress. Dipiridamol was continuously infused at a
rate of 140 \selectlanguage{greek}μ\selectlanguage{english}g/kg/min for a duration of 4 minutes, and the
radiopharmaceutical was injected 3-5 minutes after the completion of the
dipiridamol infusion.

\textbf{Imaging Protocol:}

We performed imaging on a Siemens symbia E gamma camera (Hoffman
Estates, IL, USA) with a LEHR collimator. The shots were taken with a
64x64 matrix, in 16 projections, with each image for 20 seconds.
Detectors moved on a 180\selectlanguage{ngerman}° arc from 45° right anterior oblique to 45°
left posterior oblique. The zooming factor was 1.45. Images were
reconstructed using a back projection algorithm and a Butterworth filter
with a cutoff frequency of 0.45 cycles per pixel and order 5.

The imaging was initiated 15-45 minutes after the radiopharmaceutical
injection. The patients were initially scanned in the supine position
with their arms above their heads. They were then scanned in the prone
position with their arms extended forward. The patient's chest was
positioned near the SPECT detectors, ensuring that the heart was within
the center of the field of view. After evaluating the supine and prone
images, patients who were determined to require rest imaging underwent a
subsequent radiopharmaceutical injection. The images were evaluated
using the Siemens Syngo.via MI apps program (Erlangen, Germany).

\textbf{Image analysis:} We used a 17-segment myocardial map for
semiquantitative visual assessment. We coded according to which coronary
vessel territory supplied the corresponding myocardial segment (Z1)

Two different evaluators assessed the images. Evaluator 1 first
evaluated the supine image alone (Supine1) and noted whether rest
imaging was required/not required. At a different time, he assessed the
prone image alone (Prone1) and noted rest imaging was required/not
required. He then evaluated the supine and prone images together at
different times (supine1+prone1). He noted whether rest imaging was
necessary or not. The same process was followed for evaluator 2
(supine2, prone2, supine+prone2). If neither supine nor prone image was
judged to have a perfusion defect, it was coded as no defect (no need
for rest imaging). If a defect was seen in only one of the supine or
prone images and no defect was seen in the other image, it was coded as
no defect (no need for rest imaging)(Figure 1).

If a defect was seen in both supine and prone images, supine+prone
images were evaluated together; a) if the perfusion defect originated
from different vessel regions (e.g., RCA region in supine image, LAD
region in prone image), it was interpreted as a mismatch defect and
coded as no need for rest imaging; b) if the perfusion defect originated
from the same segment(s), it was interpreted as a match defect and coded
as need for rest imaging (Z).

We performed a cohens-kappa agreement analysis between the supine+prone
assessment results of both evaluators. We observed strong agreement
between the final results of the two assessors (Kappa =0.846,
p\textless{}0.001). Therefore, we accepted the supine+prone evaluation
result as the reference standard. Our image evaluation algorithm is
shown in Figure 3.

\textbf{Statistical analysis}

Statistical analyses were performed with IBM SPSS Statistics, Version
23.0 (SPSS Inc., Chicago, USA) and MedCalc® Statistical Software version
22.009 (MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc.org;
2023). Variables belonging to the groups were reported as n (\%) and
standard deviation according to data types. The distribution of
dichotomized data between groups was evaluated by the Chi-square test.
Pearson Chi-Square or Fisher's Exact Test p values were used for
significance considering the number of patients in the categories. Kappa
analysis was used for inter-evaluator agreement. For performance
measures, ROC Curve analyses were performed to measure sensitivity,
specificity, positive predictive value (PPV), negative predictive value
(NPV), and accuracy. The significance limit was accepted as p
\textless{} 0.05.

\textbf{Results:}

We analyzed 378 male patients (mean age 56.47 ± 12.940) with stress
supine and prone imaging. We applied pharmacologic stress in 287
patients (75.9\%) and exertional stress in 67 patients (24.1\%).

\textbf{Evaluator 1:}

Supine1 decided on the need for a rest study in 230 patients (60.8\%).
In 150 patients (65.2\%) it made a false positive decision. The false
positivity of supine1 was 33.4\%. Prone1 decided to rest in 204 patients
(54\%). It gave a false positive decision in 124 (60.8\%) patients. The
false positive rate of prone1 was 29.4\%.

With supine1+prone1 evaluation (number of patients with actual need for
rest study), rest was decided in 80 patients (21.2\%). In 76 (33\%) of
230 patients in whom supine1 decided to rest, prone1 said no need for
rest (Corrected). In 50 (24.5\%) of 204 patients in whom prone 1 decided
to rest, supine 1 said no need for rest. Supine1+prone1 assessment
reduced the need for rest by 65\% compared with supine1 and 60\%
compared with prone1.\textbf{Evaluator 2:}

Supine2 made a rest work needed decision in 193 patients (51.1\%). In
118 patients (61.1\%) it gave a false positive decision. The false
positivity of supine2 was 28\%. Prone2 decided to rest in 202 patients
(53.9\%). It gave a false positive decision in 127 patients (62.9\%).
The false positive rate of prone2 was 29.7\%\textbf{.}

With supine2+prone2 evaluation (number of patients with actual need for
rest study), rest was decided in 75 patients (19.8\%). In 63 (32.6\%) of
193 patients in whom supine2 decided to rest, prone 2 said no rest was
needed (Corrected). In 72 (35.6\%) of 202 patients in whom prone2
decided to rest, supine2 said no need for rest. Supine2+prone2 reduced
the need for rest by 60.4\% compared to supine1 and 62.8\% compared to
prone1.

The sensitivity, specificity, positive predictive value, negative
predictive value, and accuracy results of the evaluators in deciding the
need for rest are given in Table 1.

The need for rest was significantly more likely to originate from the
RCA (inferior wall) region by evaluators 1 and 2 based on supine+prone
images.

The information on which vascular territory the need for rest originated
from is given in Table 2.

False positive rates were higher in favor of RCA in the supine
evaluation compared to the prone evaluation. False positive rates at the
LAD site were higher in prone imaging than in supine imaging. False
positive rates in the LAD and RCA sites were similar in the prone
imaging.

False positive rates are given in Table 3.

\textbf{Intra-evaluator Agreement:} There was a low-level agreement
between supine 1 and prone 1, supine1 and supine1+prone1, and prone 1
and supine1+prone1. We also observed low agreement between supine 2 and
prone 2, supine2 and supine2+prone2, and prone 2 and supine+prone2.

\textbf{Inter-evaluator Agreement:} We observed moderate to strong
agreement between supine1 and supine 2, between prone1 and prone 2, and
between supine1+prone1 and supine2+prone2.

Intra-evaluator and interevaluator agreement in rest decision-making is
given in Table 4.

\textbf{Follow-up}

80 patients underwent rest imaging. In 36 patients, stress and rest
images were evaluated together and it was concluded that there was no
perfusion defect. Coronary angiography was performed in the remaining 44
patients. 5 patients had no stenosis, 15 patients had less than 50\%
stenosis and medical follow-up was recommended, 13 patients had 50-99\%
occlusion and stenting was performed, 5 patients underwent by-pass due
to total occlusion, 1 patient had a muscular bridge, 2 patients had slow
flow in the LAD, and the information of 3 patients was not available.
There was no cardiac or noncardiac death.

\textbf{Discussion}

MPI is known to have a negative predictive accuracy to rule out ischemic
heart disease and future cardiac events (O12 ). However, to improve the
accuracy of scintigraphic evaluation, it is necessary to distinguish
between artifacts and true perfusion abnormalities.

Combined supine-prone myocardial perfusion imaging has been shown to
reduce artifacts compared with supine-only MPI in mixed-sex populations
with different risks for coronary artery disease, with patients often
serving as their controls. However, direct comparison of these imaging
strategies in men is limited (C).

Arsanjani et al. reported that in a mixed-sex population, combined
supine/prone imaging improved specificity and accuracy compared to
supine imaging alone, and Nishina et al. reported that combined
supine-prone stress imaging had higher specificity than prone or supine
imaging alone. (J, Y)

Taasan et al. reported that the use of combined supine-prone MPI reduced
the rate of suspicious interpretations from 18\% to 4\%, and Gutstein et
al. reported that pron imaging reduced the rate of suspicious scans from
40.7\% to 15.4\% and the rate of ischemic studies from 34.1\% to 7.7\%.
(N, C)

In the study by Ceylan et al, prone imaging eliminated the need for rest
perfusion study in 76 of 98 patients (77.5\%). In 76 (85.4\%) of the
patients reported as normal (n=89), there was no need to perform resting
perfusion studies thanks to pron study results. (O).

Our study differs from studies conducted on mixed-gender populations,
was conducted only on male patients, and for both observers, visual
assessment alone eliminated the need for a resting study in at least
60\% of the patients, thanks to the combined supine-prone examination.

The advantage of the stress-first protocol is that it can be optionally
converted to stress-only when the stress MPI is normal, thus avoiding
the need for a resting isotope dose and significantly reducing radiation
exposure and increasing laboratory throughput (I). Performing
stress-only MPI saves 30\% to 60\% in radiation exposure (M). Recent
studies have shown that a normal stress-only MPI study carries the same
prognosis for event-free survival as traditional stress-rest or
rest-stress protocols. (M6, M7, A31, M10, M11)

The interpretation of MPI involves the visual and semi-quantitative
analysis of stress supine and prone perfusion images to determine
differences in perfusion, which is subjective and can lead to
inter-evaluator variability (J2). Differences in analyses performed by
different evaluators can lead to significant differences in
decision-making; therefore, inter-evaluator agreement plays an important
role in the diagnostic performance of a diagnostic test (C6, J4).

In our study, when evaluators were evaluated internally, Cohen's kappa
analysis results indicate that the final decisions for supine1, prone1,
supine1+prone1, and supine2, prone2, supine2+prone2 are characterized by
low concordance. However, the inter-evaluator final decisions for
supine1-supine2 and prone1-prone2 show moderate concordance, while the
final decisions for supine1+prone and supine2+prone2 demonstrate strong
concordance (kappa: 0.846, p\textless{}0.001). Inter-evaluator
concordance significantly improves when two-position supine/prone
imaging is used, as compared to supine or prone imaging alone.

Inferior wall defects may cause more false positives in the supine study
and anteroseptal defects in the prone study. It has been reported that
the proximity of the heart to the anterior chest wall in prone imaging
and diaphragmatic attenuation in supine imaging probably produce these
defects. (O, O5) In our study, consistent with the literature, false
positive rates were higher in favor of RCA in supine imaging than in
prone imaging, and false positive rates in the LAD area were higher in
prone imaging than in supine imaging. False positivity rates in LAD and
RCA sites were similar in prone imaging The false positive rates in the
LAD and RCA regions are similar in prone imaging. Furthermore, the
evaluation of supine1+prone1 and supine2+prone2 images reveals that the
need for rest is significantly attributed to the RCA vessel region for
both evaluators. We believe that artifacts are the most important factor
that impairs correlation and agreement within and between evaluators.

The attenuation artifact is one of the most common artifacts in MPI and
is typically related to the diaphragm affecting the inferior wall in
males, as in our study (J).

This study has several limitations. First, it is a retrospective study.
Secondly, we did not use CAG as the gold standard. This may seem like a
limitation, but in our study, we did not try to detect CAD in these
patients, we did not examine the prognosis, and we only tried to
determine the need for rest after stress imaging. There should be a
strong clinical or MPI suspicion to perform CAG. However, only 11\% of
our patients underwent CAG after stress + rest imaging. Third, the
differences in results between our expert raters, especially for single
supine and single prone images, reflect the different reading styles of
our expert physicians and show the overall limitation of visual
assessment\textbf{.} (J).

\textbf{Conclusion:} In men, we observed that supine and prone imaging
were not superior to each other in deciding the need for rest.
Supine+prone imaging reduced the need for rest by at least 60 percent
compared to supine-only or prone-only imaging. While supine imaging
alone caused more false positives in the RCA territory, we observed
similar false positive results with prone imaging in the LAD and RCA
territories. Supine+prone imaging may be preferred over supine-only and
prone-only imaging due to reduced cost, time, and radiation exposure for
patients.

\textbf{References}

1.~Underwood SR, Anagnostopoulos C, Cerqueira M, et al. Myocardial
perfusion scintigraphy: the evidence.~\emph{Eur. J. Nucl. Med. Mol.
Imaging.~} 2004; 31: 261--291. doi: 10.1007/s00259-003-1344-5.

2. Arsanjani R, Hayes SW, Fish M, et al. Two-position supine/prone
myocardial perfusion SPECT (MPS) imaging improves visual inter-observer
correlation and agreement. \emph{J Nucl Cardiol.} 2014; 21: 703-711.
doi: 10.1007/s12350-014-9895-3.

3. Hendel RC, Corbett JR, Cullom SJ, et al. The value and practice of
attenuation correction for myocardial perfusion SPECT imaging: A joint
position statement from the American Society of Nuclear Cardiology and
the Society of Nuclear Medicine. \emph{J Nucl Med.} 2002; 43: 273-280.
doi: 10.1067/mnc.2002.120680.

4. Huang JY, Huang CK, Yen RF, et al. Diagnostic performance of
attenuation-corrected myocardial perfusion imaging for coronary artery
disease: A systematic review and meta-analysis\emph{. J Nucl Med.} 2016;
57: 1893-1898. doi: 10.2967/jnumed.115.171462.

5. Nishiyama Y, Miyagawa M, Kawaguchi N, et al. Combined supine and
prone myocardial perfusion single-photon emission computed tomography
with a cadmium zinc telluride camera for detection of coronary artery
disease. \emph{Circ J.} 2014; 78: 1169-1175. doi:
10.1253/circj.cj-13-1316.

6. Mirshahvalad SA, Chavoshi M, Hekmat S. Diagnostic performance of
prone-only myocardial perfusion imaging versus coronary angiography in
the detection of coronary artery disease: A systematic review and
meta-analysis. \emph{J Nucl Cardiol} . 2022; 29: 1339-1351. doi:
10.1007/s12350-020-02376-x.

7. Taasan V, Wokhlu A, Taasan MV, et al. Comparative accuracy of
supine-only and combined supine-prone myocardial perfusion imaging in
men. \emph{J Nucl Cardiol} . 2016; 23: 1470-1476. doi:
10.1007/s12350-015-0358-2.

8. Chang SM,~Nabi F,~Xu J,~et al. Normal stress-only versus standard
stress/rest myocardial perfusion imaging: similar patient mortality with
reduced radiation exposure. \emph{J~Am Coll Cardiol.} 2010; 55: 221-230.
doi: 10.1016/j.jacc.2009.09.022.

9. Duvall WL, Wijetunga MN,~Klein TM,~et al. The prognosis of a normal
stress-only Tc-99m myocardial perfusion imaging study\emph{. J~Nucl
Cardiol.} 2010; 17: 370-377. doi: 10.1007/s12350-010-9210-x.

10. Einstein AJ, Johnson LL,~DeLuca AJ,~et al. Radiation dose and
prognosis of ultra-low-dose stress-first myocardial perfusion SPECT in
patients with chest pain using a high-efficiency camera. \emph{J~Nucl
Med.} 2015; 56: 545-551. doi: 10.2967/jnumed.114.150664.

11. Perrin M,~Djaballah W,~Moulin F,~et al. Stress-first protocol for
myocardial perfusion SPECT imaging with semiconductor cameras: high
diagnostic performances with significant reduction in patient radiation
doses. \emph{Eur J Nucl Med Mol Imaging} . 2015; 42: 1004-1011. doi:
10.1007/s00259-015-3016-7.

12. Gunay CE, Erdogan A, Yalcin H, et al. Prone imaging allows efficient
radiopharmaceutical usage by obviating the necessity of a rest study in
Tc-99m-methoxyisobutylisonitrile myocardial perfusion
scintigraphy.\emph{Nucl Med Commun.} 2011; 32: 284-288. doi:
10.1097/MNM.0b013e32834462ee.

13. Berman DS, Kang XP, Nishina H, et al. Diagnostic accuracy of gated
Tc-99m sestamibi stress myocardial perfusion SPECT with combined supine
and prone acquisitions to detect coronary artery disease in obese and
non-obese patients. \emph{J Nucl Cardiol.} 2006; 13: 191-201. doi:
10.1007/BF02971243.

14. Hayes SW, DeLorenzo A, Hachamovich R, et al. Prognostic implications
of combined prone and supine acquisitions in patients with equivocal or
abnormal supine myocardial perfusion SPECT. \emph{J Nucl Med.} 2003; 44:
1633-1640.

15. Malkemeker D, Brenner R, Martin WH, et al. CT-based attenuation
correction versus prone imaging to decrease equivocal interpretation of
rest/stress TC-99m tetrofosmin SPECT MPI. \emph{J Nucl Cardiol.} 2007;
14: 314-323. doi: 10.1016/j.nuclcard.2007.02.005.

16. Verberne HJ., Acampa W, Anagnostopoulos, et al. EANM procedural
guidelines for radionuclide myocardial perfusion imaging with SPECT and
SPECT/CT. \emph{Eur J Nucl Med Mol Imaging.} 2015; 42: 1929-40.~doi:
10.1007/s00259-015-3139-x.

17. Cerqueira MD, Weissman NJ, Dilsizian V, et al. American Heart
Association Writing Group on Myocardial Segmentation and Registration
for Cardiac Imaging. Standardized myocardial segmentation and
nomenclature for tomographic imaging of the heart. A statement for
healthcare professionals from the Cardiac Imaging Committee of the
Council on Clinical Cardiology of the American Heart
Association.\emph{Circulation.} 2002; 29:105(4): 539-42. doi:
10.1161/hc0402.102975.

18. Marcassa C, Bax JJ, Bengel F, et al. Clinical value, cost
effectiveness, and safety of myocardial perfusion scintigraphy: a
position statement. \emph{Eur Heart J.} 2008; 29: 557--563.

19. Gutstein A, Solodky A, Mats I, et al. Feasibility of myocardial
perfusion SPECT with prone and half-time imaging. \emph{Nucl Med
Commun.} 2011; 32: 386-391. doi: 10.1097/MNM.0b013e328343d68e.

20. Sharir T, Pinskiy M, Pardes A, et al. Comparison of the diagnostic
accuracies of very low stress-dose with standard-dose myocardial
perfusion imaging: Automated quantification of one-day, stress-first
SPECT using a CZT camera. \emph{J Nucl Cardiol.} 2016; 23: 11-20. doi:
10.1007/s12350-015-0130-7.

21. Gutstein A, Bental T, Solodky A, et al. Prognosis of stress-only
SPECT myocardial perfusion imaging with prone imaging. \emph{J Nucl
Cardiol.} 2018; 25: 809-816. doi: 10.1007/s12350-016-0617-x.

22. Mahmarian JJ. Stress only myocardial perfusion imaging: Is it time
for a change? \emph{J Nucl Cardiol.} 2010; 17: 529-535. doi:
10.1007/s12350-010-9249-8.

23. Iskandrian AE. Stress-only myocardial perfusion imaging a new
paradigm. \emph{J Am Coll Cardiol.} 2010; 55: 231-233. doi:
10.1016/j.jacc.2009.10.007.

24. Gibson PB, Demus D, Noto R, et al. Low event rate for stress-only
perfusion imaging in patients evaluated for chest pain. \emph{J Am Coll
Cardiol.} 2002; 39: 999-1004. doi: 10.1016/s0735-1097(02)01720-5.

25. Mathur S, Heller GV, Bateman TM, et al. Clinical value of
stress-only Tc-99m SPECT imaging: Importance of attenuation
correction.\emph{J Nucl Cardiol.} 2013; 20: 27-37. doi:
10.1007/s12350-012-9633-7.

26.~Danias PG, Ahlberg AW, Travin MI, et al. Visual assessment of left
ventricular perfusion and function with electrocardiography-gated SPECT
has high intraobserver and interobserver reproducibility among
experienced nuclear cardiologists and cardiology trainees.~\emph{J Nucl
Cardiol.~} 2002; 9: 263--270.~doi: 10.1067/mnc.2002.121233.

27.~Slomka PJ, Nishina H, Abidov A, et al. Combined quantitative
supine-prone myocardial perfusion SPECT improves detection of coronary
artery disease and normalcy rates in women.~\emph{J Nucl Cardiol.~}
2007; 14: 44--52.~doi: 10.1016/j.nuclcard.2006.10.021.

28. Dogruca Z, Kabasakal L, Yapar F, Nisil C, Vural VA, Onsel C. A
comparison of Tl-201 stress-reinjection-prone SPECT and Tc-99m-sestamibi
gated SPECT in the differentiation of inferior wall defects from
artifacts. \emph{Nucl Med Commun} . 2000; 21: 719--727. doi:
10.1097/00006231-200008000-00004.

\textbf{Figure 1.} Combined stress supine-prone myocardial perfusion
imaging\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

A 51-year-old obese male patient initially underwent stress supine
imaging, which showed marked hypoperfusion in the inferior wall (RCA
territory) (a). Stress prone imaging was then performed to investigate
whether this appearance was due to soft tissue attenuation and activity
uptake in this area was within physiologic limits (b). After combined
stress supine-prone imaging, this area was considered to be a soft
tissue artifact, thus eliminating the need for rest imaging after stress
imaging.

\textbf{Figure 2.} Image evaluation algorithm

\textbf{Supine Imaging Evaluation Prone Imaging Evaluation}

------------------------------------

Decision: No need for rest imaging

-------------------------------------

Decision: No need for rest imaging

--------------------------------------

Desicion: Supine+Prone Imaging Evaluation

Desicion: No need for rest imaging Desicion: Rest imaging is required.

\textbf{Table 1.} The evaluators' results of sensitivity, specificity,
positive predictive value (PPV), negative predictive value (NPV) and
accuracy in determining the need for rest work.\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
Parameter & Sensitivity(\%) & Specificity (\%) & PPV(\%) & NPV(\%) &
Accuracy(\%)\tabularnewline
\midrule
\endhead
\textbf{Supine1} & 100 & 66.5 & 34.8 & 100 & 71.6\tabularnewline
\textbf{Prone1} & 100 & 70.6 & 39.2 & 100 & 75.3\tabularnewline
\textbf{Supine2} & 100 & 72 & 32.9 & 100 & 76.2\tabularnewline
\textbf{Prone2} & 100 & 70.2 & 37.1 & 100 & 74.7\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2.} Vascular territory where the need for rest originates\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& \textbf{LAD n (\%)} & \textbf{RCA n (\%)} & \textbf{Cx n (\%)} &
\textbf{LAD+RCA n (\%)} & \textbf{Total n}\tabularnewline
\midrule
\endhead
\textbf{Supine1} & 31 (13.5) & 193 (83.9) & 2 (1) & 4 (2) &
230\tabularnewline
\textbf{Prone1} & 69 (33.8) & 128 (62.7) & 1 & 6 (3) &
204\tabularnewline
\textbf{Supine1+prone1} & 12 (15) & 66 (82.5) & 1 & 1 &
80\tabularnewline
\textbf{Supine2} & 32 (16.6) & 154 (79.8) & 3 & 4 & 193\tabularnewline
\textbf{Prone2} & 69 (34.3) & 125 (62.5) & 2 & 5 & 202\tabularnewline
\textbf{Supine2+prone2} & 11 (14.9) & 60 (81.1) & 1 (1.4) & 2 (2.7) &
75\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3.} False positive rates of evaluators in the whole group
and by vessel site.

\textbf{False Positivity Ratio}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Vessel} & \textbf{Supine1} & \textbf{Prone1} & \textbf{Supine2}
& \textbf{Prone2}\tabularnewline
\textbf{Whole grup} & 33.4 & 29.4 & 28 & 29.7\tabularnewline
\textbf{LAD zone} & 11.2 & 35.4 & 14 & 30.7\tabularnewline
\textbf{RCA zone} & 46.4 & 31 & 45 & 35\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4.} Cohen's kappa agreement analysis results within each
evaluator and between evaluators

\textbf{INTRA-EVALUATOR AGREEMENT}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Parameter} & \textbf{kappa} & \textbf{p}\tabularnewline
Supine1 - prone1 & 0.322 & \textless{}0.001\tabularnewline
Supine1 - supine1+prone1 & 0.295 & \textless{}0.001\tabularnewline
Prone1 - supine1+prone1 & 0.373 & \textless{}0.001\tabularnewline
Supine2 - prone2 & 0.278 & \textless{}0.001\tabularnewline
Supine2 - supine2+prone2 & 0.384 & \textless{}0.001\tabularnewline
Prone2 - supine2+prone2 & 0.353 & \textless{}0.001\tabularnewline
\textbf{INTER-EVALUATOR AGREEMENT} & \textbf{INTER-EVALUATOR AGREEMENT}
& \textbf{INTER-EVALUATOR AGREEMENT}\tabularnewline
Supine1 - supine2 & 0.623 & \textless{}0.001\tabularnewline
Prone1 - prone2 & 0.635 & \textless{}0.001\tabularnewline
Supine1+prone1 - supine2+prone2 & 0.846 &
\textless{}0.001\tabularnewline
\bottomrule
\end{longtable}

\textbf{Figure Legends}

\textbf{Figure 1. Combined stress supine-prone myocardial perfusion
imaging}

A 51-year-old obese male patient initially underwent stress supine
imaging, which showed marked hypoperfusion in the inferior wall (RCA
territory) (a). Stress prone imaging was then performed to investigate
whether this appearance was due to soft tissue attenuation and activity
uptake in this area was within physiologic limits (b). After combined
stress supine-prone imaging, this area was considered to be a soft
tissue artifact, thus eliminating the need for rest imaging after stress
imaging.

\textbf{Figure 2. Image evaluation algorithm}

\textbf{Table 1. The evaluators' results of sensitivity, specificity,
positive predictive value (PPV), negative predictive value (NPV), and
accuracy in determining the need for rest work.}

\textbf{Table 2. Vascular territory where the need for rest originates}

\textbf{Table 3. False positive rates of evaluators in the whole group
and by vessel site.}

\textbf{Table 4.} \textbf{Cohen's kappa agreement analysis results
within each evaluator and between evaluators}

\selectlanguage{english}
\FloatBarrier
\end{document}

