ORIGINAL ARTICLE

Head-to-head comparison of diagnosticaccuracy of stress-only myocardial perfusionimaging with conventional and cadmium-zinctelluride single-photon emission computedtomography in women with suspected coronaryartery disease

Teresa Mannarino, MD,a Roberta Assante, MD, PhD,a Carlo Ricciardi, MSc,a

Emilia Zampella, MD, PhD,a Carmela Nappi, MD, PhD,a Valeria Gaudieri, MD,

PhD,a Ciro Gabriele Mainolfi, MD,a Eugenio Di Vaia, MD,a

Mario Petretta, MD,b Mario Cesarelli, MSc,c Alberto Cuocolo, MD,a

and Wanda Acampa, MD, PhDa,d

a Department of Advanced Biomedical Sciences, University Federico II, Naples, Italyb Department of Translational Medical Sciences, University Federico II, Naples, Italyc Department of Electrical Engineering and Information Technology, University Federico II,

Naples, Italyd Institute of Biostructure and Bioimaging, National Council of Research, Naples, Italy

Received Apr 23, 2019; accepted Jun 11, 2019

doi:10.1007/s12350-019-01789-7

Background. Breast attenuation may impact the diagnostic accuracy of stress myocardialperfusion imaging (MPI) with single-photon emission computed tomography (SPECT). Wecompared the performance of conventional (C)-SPECT and cadmium-zinc-telluride (CZT)-SPECT systems in women with low-intermediate likelihood of coronary artery disease (CAD).

Methods andResults. A total of 109 consecutivewomenunderwent stress-optional restMPI byboth C-SPECT and CZT-SPECT. In the overall study population, a weak albeit significant cor-relation between total perfusion defect (TPD) measured by C-SPECT and CZT-SPECT wasobserved (r = 0.38, P < .001) and at Bland-Altman analysis the mean difference in TPD (C-SPECTminus CZT-SPECT) was 2.40% (P < .001). Overall concordance of semi-quantitative diagnosticperformance between C-SPECT and CZT-SPECT was observed in 52 (48%) women with a j

value of 0.09. Normalcy rate was significantly higher using CZT-SPECT compared to C-SPECT(P < .001). Machine learning analysis performed through the implementation of J48 algorithmproved that CZT-SPECT has higher sensitivity, specificity, and accuracy than C-SPECT.

Conclusions. Inwomenwith low-intermediate likelihood ofCAD, there is a poor concordanceof diagnostic performance between C-SPECT and CZT-SPECT, and CZT-SPECT allows betternormalcy rate detection compared to C-SPECT. (J Nucl Cardiol 2019)

Key Words: CAD Æ SPECT Æ MPI Æ Diagnostic application

Electronic supplementary material The online version of this

article (https://doi.org/10.1007/s12350-019-01789-7) contains sup-

plementary material, which is available to authorized users.

Teresa Mannarino and Roberta Assante are the first two authors shared

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Biomedical Sciences, University Federico II, Via Pansini 5, 80131

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Copyright � 2019 American Society of Nuclear Cardiology.

AbbreviationsSPECT Single-photon emission computed

tomography

MPI Myocardial perfusion imaging

CAD Coronary artery disease

C Conventional

CZT Cadmium-zinc-telluride

ECG Electrocardiography

SSS Summed stress score

TPD Total perfusion defect

LV Left ventricular

INTRODUCTION

Stress single-photon emission computed tomogra-

phy (SPECT) myocardial perfusion imaging (MPI)

represents the most widely used non-invasive cardiac

imaging tool for diagnosis and risk stratification of

patients with suspected or known coronary artery

disease (CAD).1,2 However, conventional (C)-SPECT

systems utilize large sodium iodide crystals, photomul-

tiplier tubes, and parallel-hole collimation, and are

therefore inherently insensitive, necessitating prolonged

imaging times and relatively large radioisotope doses.

Novel dedicated gamma cameras with semiconductor

cadmium-zinc-telluride (CZT) detectors have been

introduced in the clinical practice for cardiac imaging.3

These new CZT-SPECT cameras, characterized by

improved spatial, temporal, and energy resolution as

compared to C-SPECT cameras, provided better image

quality and shorter acquisition time, translating into

higher diagnostic accuracy.4,5 The characteristics of

heart-oriented geometry and higher energy resolution

related to CZT-SPECT are expected to reduce soft tissue

attenuation. Prior studies compared the diagnostic per-

formance of CZT-SPECT with that of C-SPECT

cameras in patients with suspected CAD and showed a

good correlation of the semi-quantitative perfusion

scores and functional parameters between the two

systems.6-8 These findings support the use of the novel

gamma cameras in clinical routine practices also con-

sidering the improvements in acquisition time and

radiation exposure reduction. A low-dose protocol with

a CZT-SPECT can be used in women with known or

suspected CAD without loss of accuracy compared to

men.9 However, no data are available comparing C-

SPECT and CZT-SPECT findings in women with

suspected CAD.

This study was designed to directly compare the

results of C-SPECT and CZT-SPECT stress-only MPI in

women with low-intermediate likelihood of CAD. In a

subgroup of women with low likelihood of CAD we also

assessed the prevalence of attenuation defects using C-

SPECT and CZT-SPECT according to semi-quantitative

analysis.

MATERIALS AND METHODS

Patients

We studied 109 consecutive women with low-intermedi-

ate likelihood of CAD submitted by referring physicians to

stress MPI for atypical angina, uninterpretable electrocardiog-

raphy (ECG) stress testing, or inability to exercise.1 Patients’

clinical history was collected, and cardiac risk factors were

assessed before testing. Atypical angina was defined as the

presence of two criteria including substernal chest pain or

discomfort, with characteristic quality and duration, provoked

by exertion or emotional stress and relieved by rest and/or

nitrates.10 The review committee of our institution approved

the study and all patients gave informed consent (Protocol

Number 110/17).

Pre-scan Likelihood of CAD

As part of the baseline examination, clinical teams

collected information on traditional cardiovascular risk factors,

including age, gender, blood pressure, smoking history, serum

cholesterol, family history of CAD, rest electrocardiographic

characteristics, diabetes and its complications (including neu-

ropathy, nephropathy, peripheral vascular disease, and

retinopathy), as well as the results of ECG stress testing.

Hypertension was defined as a known history of systolic blood

pressure[ 140 mmHg or the use of antihypertensive medica-

tion. Hypercholesterolemia was defined as a known history of

dyslipidemia or treatment with cholesterol-lowering medica-

tion. Patients were classified as having diabetes if they had a

previous diagnosis of diabetes or were receiving treatment with

oral hypoglycemic drugs or insulin. A positive family history

of CAD was defined as the presence of CAD in first-degree

relatives. These data were verified and complemented with

demographic and clinical information collected from medical

records. From these clinical variables, the pre-test CAD

likelihood was calculated for each patient by dedicated

software based on Bayesian analysis of pre-scan patients’ data

(Cadenza, version 5.04.3, Advanced Heuristics, Inc., Bain-

bridge Island, Washington).11 For patients who underwent

pharmacologic stress testing, pre-test likelihood was calculated

without using the stress test parameters. According to pre-test

likelihood of CAD, patients with a likelihood score \ 0.15

were considered at low risk of CAD, while those with a score

between 0.15 and 0.85 were considered at intermediate risk of

disease.

Study Protocol

Patients underwent stress 99mTc sestamibi gated MPI by

physical exercise or dipyridamole stress test, according to the

recommendations of the European Association of Nuclear

Mannarino et al Journal of Nuclear Cardiology�Conventional and CZT cameras in women

Medicine.12 In all patients, beta-blocking medications and

calcium antagonists were withheld for 48 hours and long-

acting nitrates for 12 hours before testing. For patient

undergoing exercise test, symptom-limited treadmill standard-

ized protocols were performed, with monitoring of heart rate

and rhythm, blood pressure, and ECG. Test endpoints were

achievement of 85% maximal predicted heart rate, horizontal

or down-sloping ST-segment depression[ 2 mm, ST-segment

elevation [1 mm, moderate to severe angina, systolic blood

pressure decrease[ 20 mm Hg, blood pressure[ 230/120 mm

Hg, dizziness, or clinically important cardiac arrhythmia. For

dipyridamole stress test, patients were instructed not to

consume products containing caffeine for 24 hours before the

test. Dipyridamole was infused at dose of 0.142 mg�kg-1 9

minute-1 intravenous over 4 minutes. A dose of 100 mg of

aminophylline was administered intravenously in the event of

chest pain or other symptoms, or after significant ST depres-

sion. At peak exercise, or 4 minutes after completion of

dipyridamole infusion, a bolus of 370 MBq of 99mTc-sestamibi

was intravenously injected. For both types of stress, heart rate,

blood pressure, and 12-lead ECG data were recorded at rest, at

the end of each stress stage, at peak stress and in the delay

phases at rest. Maximal degree of ST-segment changes at 80

ms after the J-point of the ECG was measured and assessed as

horizontal, down-sloping, or up-sloping. Horizontal or down-

sloping ST-segment depression C 0.1 mV, persisting for at

least 0.06 to 0.08 seconds after the J-point in one or more ECG

lead, were considered diagnostic for ischemia, whereas up-

sloping ST depressions C1.0 mm were considered non-

diagnostic. All ST depression \ 1.0 mm additional from

baseline was defined as negative.13

MPI

All patients underwent stress-optional rest MPI by both

C-SPECT and CZT-SPECT systems according to a random-

ized scheme in 1:1 ratio that determined which camera was

used for first acquisition. The study protocol is shown in

Figure 1.

For C-SPECT a dual-head rotating gamma Anger camera

(E.CAM, Siemens Medical Systems, Hoffman Estates, IL,

USA) equipped with a low-energy, high-resolution collimator

and connected with a dedicated computer system was used.14

No attenuation or scatter correction was used. For gating, a

cardiac cycle was divided into eight frames. Perfusion imaging

was reconstructed by summing the gated data at each projec-

tion into an ‘‘ungated’’ raw data file before low phase pre-

filtering and ramp filtered back projection.

For CZT-SPECT (D-SPECT, Spectrum Dynamics, Cae-

sarea, Israel) recordings were obtained using 9 pixilated CZT

crystal detector columns mounted vertically spanning a 90�geometry.15 Each of the columns consists of 1,024 (16 9 64)

5-mm thick CZT crystal elements (2.46 9 2.46 mm). Square-

hole tungsten collimators are fitted to each of the detectors,

which are shorter than conventional low-energy, high-resolu-

tion collimators, yielding significantly better geometric speed.

Data were acquired focusing on the heart by the detectors

rotating in synchrony and saved in list mode. Images were

obtained with the patient in a semi recumbent position. A 10-s

pre-scan acquisition was performed to identify the location of

the heart and to set the angle limits of scanning for each

detector (region of interest—centric scanning). Using the

myocardial count rate from the pre-scan acquisition, the time

per projection was set to target the recording of 1000

myocardial kcounts; the duration of the scans was less than

10 minutes for stress and 4 minutes for rest. Summed and gated

projections were reconstructed with an iterative maximum

likelihood expectation maximization algorithm using 7 and 4

iterations, respectively.

Imaging Interpretation

An automated software program (e-soft 2.5, QGS/QPS,

Cedars-Sinai Medical Center, Los Angeles, CA) was used to

calculate left ventricular (LV) volumes, ejection fraction, wall

motion, wall thickening, and the scores incorporating both the

extent and severity of perfusion defects, using standardized

segmentation of 17 myocardial regions.16 The total perfusion

defect (TPD) of the stress images was also generated,

representing the defect extent and severity and expressed as

a percentage of the LV myocardium.17 A post-stress LV

ejection fraction[ 45% and a summed stress score (SSS)\ 3

were considered normal.18 All studies were visually reviewed

and interpreted by two nuclear medicine physicians with[6

years of experience in nuclear cardiology blinded to clinical

information. A third nuclear medicine physician resolved any

discrepant readings. At reporting clinical interpretation, a

patient was defined as normal when a SSS [ 3 at semi-

quantitative analysis was associated with the preserved wall

thickening into the defect and visual over-read.19 Therefore, all

segments defined as normal at reporting but showing reduced

tracer uptake in the anterior wall at semi-quantitative analysis

at C-SPECT and/or CZT-SPECT were considered as false

defects due to breast attenuation rather than to true perfusion

abnormalities.

Statistical Analysis and Supervised MachineLearning

Statistical analysis was performed with a commercially

available software package (SPSS, version 20.0 for Windows,

SPSS Inc., Chicago, IL, USA). Continuous variables were

expressed as mean ± standard deviation and categorical data as

frequencies or percentage. Correlations between C-SPECT and

CZT-SPECT were evaluated by linear regression analysis, and

the agreement between the two SPECT systems was assessed

by Bland-Altman analysis.20 Comparison of continuous data

between groups was performed using the two-sided Student’s t

test. Concordance between the methods was also expressed as

exact agreement by the j statistics using the following grading

system: B 0.40 poor agreement, 0.41 to 0.60 moderate

agreement, 0.61 to 0.80 good agreement, and[ 0.80 excellent

agreement. Normalcy rate, defined as percentage of normal

result at semi-quantitative analysis (SSS\ 3) in the subgroup

of subjects with low (\ 0.15) likelihood of CAD, was

determined for both C-SPECT and CZT-SPECT considering

Journal of Nuclear Cardiology� Mannarino et al

Conventional and CZT cameras in women

normal MPI at reporting imaging interpretation and compared

by using McNemar Test. The effect of randomization sequence

on results was assessed by Cochran-Mantel-Haenszel test for

stratified cross-tabulations. A P value \ .05 was considered

statistically significant.

Supervised machine learning analysis was performed by

Knime analytics platform whose validity has been widely

acknowledged.21-25 In this study, J48 was implemented

through Knime analytics platform in its Java version. Cross-

validation was also implemented to exploit different combi-

nations of training and test sets.26 Parameters of global and

regional LV function and the scores incorporating both the

extent and severity of perfusion defects were employed to

conduct the analysis with J48 algorithm to assess the classi-

fications related to the two cameras. End-point for the analysis

of sensitivity, specificity, and diagnostic accuracy was the

classification of normal at reporting clinical interpretation

(including in the evaluation of semi-quantitative analysis the

presence of preserved wall thickening and the overall visual

over-read). The intraclass coefficient of correlation (ICC) was

used to assess intra- and interobserver reproducibility for

reporting clinical interpretation.27 The diagnostic perfor-

mances of the algorithm were the mean of the cycles coming

from 10 folds cross-validation. McNemar test was used to

evaluate the differences between the accuracy of the two

systems. In addition, the Matthews correlation coefficient

(MCC) was computed for each camera as it involves values of

all the four quadrants of a confusion matrix, and it is

considered a balanced measure. It is a quality indicator for

binary-class classification that ranges from - 1, when there is

perfect disagreement between actuals and prediction, to ? 1

for the perfect agreement. Receiver operating characteristics

(ROC) curve area was used to assess the goodness of a model

in distinguishing two classes ranging from 0 to 1.

RESULTS

The clinical characteristics of patient population are

shown in Table 1. Of the total 109 patients enrolled, 72

(66%) were at low and 37 (34%) at intermediate

likelihood of CAD. Sixty (55%) patients underwent

physical exercise stress test and 49 (45%) dipyridamole

stress test. Stress test results are reported in Table 2.

Comparison Between C-SPECT and CZT-SPECT in Overall Patient Population

In the overall study population, SSS (6.4 ± 4.2 vs

3.1 ± 3.2) and TPD (6.6 ± 4.9 % vs 4.2 ± 3.8 %) were

significantly higher (both P \ .0001) by C-SPECT

Figure 1. Study protocol for stress myocardial perfusion imaging. AC, Anger camera; CZT,cadmium-zinc-telluride camera.

Table 1. Clinical characteristics of 109 womenwith suspected CAD referred for stress MPI

Characteristic

Age (years) 62 ± 10

Body mass index (kg/m2) 28 ± 5

Diabetes mellitus, n (%) 26 (24)

Hypertension, n (%) 92 (84)

Smoking, n (%) 38 (35)

Hypercholesterolemia, n (%) 70 (64)

Family history of CAD, n (%) 60 (55)

Pharmacologic stress testing, n (%) 49 (45)

Values are expressed as mean value ± standard deviation oras number (percentage) of subjectsCAD, Coronary artery disease

Mannarino et al Journal of Nuclear Cardiology�Conventional and CZT cameras in women

compared to CZT-SPECT. No significant correlation

between SSS measured by C-SPECT and by CZT-

SPECT was found (r = 0.18, P = .06). At Bland-Altman

analysis, the mean difference in SSS (C-SPECT minus

CZT-SPECT) was 3.25 and the lower and upper limits

of agreement between the two SPECT systems were - 6

to 12 (Figure 2). Despite a weak but significant corre-

lation between TPD measured by C-SPECT and CZT-

SPECT (r = 0.38, P \ .001), the mean difference

between the two techniques was statistically significant

(2.40%, P \ .001) and at Bland-Altman analysis the

lower and upper limit of agreement between the two

SPECT systems were - 7% to 12% (Figure 3). Mean

values of post-stress LV ejection fraction were signif-

icantly higher by C-SPECT compared to CZT-SPECT

(74 ± 15% vs 66 ± 10, P\ .001). Agreement between C-

SPECT and CZT-SPECT for the classification of women

as normal or abnormal according to semi-quantitative

analysis is depicted in Figure 4. The difference between

the measurements obtained by the same examiner and

two different examiners for reporting clinical interpre-

tation was negligible with excellent intra- and

interobserver ICC (both [ 0.90). The overall concor-

dance of diagnostic performance between the two

SPECT systems was 48% with a very low j value of

0.09. Stress MPI was normal in 24 (22%) women by C-

SPECT and in 69 (63%) by CZT-SPECT and abnormal

in 85 (78%) at C-SPECT and in 40 (37%) by CZT-

SPECT. ECG stress test results were not correlated to

the presence of abnormal MPI results. Moreover, the

Cochran-Mantel-Haenszel test showed that randomiza-

tion sequence had no significant influence on the

differences between C-SPECT and CZT-SPECT (chi

square 1.76, P = .18). The 18 patients with concordant

normal results were all classified as normal at reporting

clinical interpretation. Of the 34 women with concordant

abnormal results, 13 were confirmed as abnormal at

reporting clinical interpretation and showed perfusion

defects in anterior (n = 8), lateral (n = 1) and inferior

(n = 4) walls. The remaining 21 women with concordant

abnormal results and classified as normal at reporting

clinical interpretation, all showed perfusion defects in

the anterior wall. The overall 57 patients with discordant

results showed myocardial perfusion defects in the

anterior wall associated with preserved wall thickening

and were classified as normal at reporting clinical

interpretation. Thus, 96 (88%) women were considered

normal and 13 (12%) abnormal at reporting clinical

interpretation. Figure 5 shows a woman with discordant

results between C-SPECT and CZT-SPECT and classi-

fied as normal at reporting clinical interpretation.

Comparison Between C-SPECT and CZT-SPECT in Women at Low CAD Likelihood

Considering the 72 women at low CAD likelihood,

at semi-quantitative analysis 14 (20%) had normal and

58 (80%) abnormal MPI by C-SPECT and 43 (60%) had

normal and 29 (40%) abnormal MPI by CZT-SPECT.

Normalcy rate was significantly higher using CZT-

SPECT compared to C-SPECT (P\ .001).

Machine Learning Analysis

The diagnostic performances of two cameras,

according to the reporting clinical interpretation, are

summarized in Table 3. J48 showed accuracies of 91%

for C-SPECT and 96% for CZT-SPECT. CZT-SPECT

exhibited a sensitivity of 77%, a higher capacity of

detecting abnormal women than C-SPECT (61%).

Moreover, the ability to classify women according to

the clinical interpretation was proved to be better

through CZT-SPECT because of a higher specificity

(99%) than C-SPECT (95%). MCC and ROC curve area

Table 2. Stress test results according to stress type

Exercise (n = 60) Dipyridamole (n = 49) P value

Baseline heart rate (bpm) 78 ± 11 72 ± 13 \ .05

Peak heart rate (bpm) 140 ± 18 92 ± 15 \ .001

Baseline systolic blood pressure (mmHg) 132 ± 14 149 ± 22 \ .001

Peak systolic blood pressure (mmHg) 159 ± 18 133 ± 23 \ .001

Baseline diastolic blood pressure (mmHg) 82 ± 8 87 ± 10 \ .01

Peak diastolic blood pressure (mmHg) 92 ± 8 76 ± 10 \ .001

Symptoms, n (%) 3 (5%) 1 (2%) 0.36

Non-diagnostic ECG changes, n (%) 22 (37%) 12 (24%) 0.17

Values are expressed as mean value ± standard deviation or as number (percentage) of subjectsECG, Electrocardiography

Journal of Nuclear Cardiology� Mannarino et al

Conventional and CZT cameras in women

confirmed the difference that can be clearly observed

between the previous metrics. Confusion matrix of J48

for C-SPECT and CZT-SPECT are reported in Table 4.

A McNemar test was also performed, and the P value of

.017 enhanced a 95% statistically significant difference

between the accuracy of the two systems.

DISCUSSION

To our knowledge, this is the first study comparing

semi-quantitative results between C-SPECT and CZT-

SPECT in women with low-intermediate likelihood of

CAD. The results of the present investigation highlight a

poor concordance in diagnostic performance comparing

C-SPECT and CZT-SPECT. It also emerged that CZT-

SPECT leads to a better interpretation of the MPI results

in women with low likelihood of CAD. MPI with

SPECT represents a non-invasive accurate method for

the diagnostic evaluation of patients with suspected or

known CAD.1,2 However, C-SPECT using Anger cam-

era has poor energy resolution, long acquisition time,

and low spatial resolution. A high percentage of atten-

uation defect visible as reduction of tracer uptake

relative to soft tissue attenuation has been demon-

strated.28 A reverse distribution pattern, characterized by

new perfusion defect or a worsening of a pre-existing

defect on the rest images, may be frequent in patients

with a low likelihood of CAD and is frequently related

to soft tissue attenuation artifacts.29 It may be relevant in

women, where breast attenuation may adversely affect

diagnostic accuracy.30 In our study, imaging was per-

formed without attenuation correction and this might

have had an impact on the high number of perfusion

artifacts revealed by C-SPECT camera. However, it has

been reported that the diagnostic performance does not

change if comparing attenuation correction data with

non-corrected data in female patients.31 The new CZT-

SPECT are characterized by higher energy and spatial

resolution with a shorter time acquisition. In a previous

study, Liu et al.32 compared the performance of CZT-

SPECT and C-SPECT camera, by using phantoms and

water bags to simulate breasts and evaluate artifacts

Figure 2. Agreement between C-SPECT and CZT-SPECT byBland-Altman analysis for SSS measurement. The differencesbetween the two SPECT systems are plotted against the meansof the two systems. The horizontal black line indicates themean difference between the two systems and the red linesindicate the limits of agreements.

Figure 3. Agreement between C-SPECT and CZT-SPECT byBland-Altman analysis for TPD measurement. The differencesbetween the two SPECT systems are plotted against the meansof the two systems. The horizontal black line indicates themean difference between the two systems and the red linesindicate the limits of agreements.

Figure 4. Agreement between C-SPECT and CZT-SPECT forthe classification of women with normal and abnormal stressMPI. CI, confidence interval.

Mannarino et al Journal of Nuclear Cardiology�Conventional and CZT cameras in women

derived from soft tissue attenuation. In that study, the

authors demonstrated that CZT-SPECT provides better

physical performance and image quality and results in

lower artificial defects than C-SPECT. In particular,

false perfusion defect in anterior wall derived from

breast attenuation resulted less prominent with novel

CZT-SPECT.32 However, no data are available

comparing semi-quantitative results between C-SPECT

and CZT-SPECT in women. Several studies have

demonstrated a high correlation between quantitative

measure of perfusion abnormality and functional param-

eters using novel CZT-SPECT and C-SPECT systems,

with a good concordance between the two methods.8,32

A recent multicenter study evaluating a new solid-state

Figure 5. Discordant semi-quantitative analysis in a 48-year-old woman with hypertension,dyslipidemia, family history of CAD, and suspected CAD. Stress MPI shows a myocardialperfusion defect in the apical segment of the antero-septal region at C-SPECT (A) and normalmyocardial perfusion at CZT-SPECT (B).

Table 3. Machine learning analysis

Accuracy (%) Error (%) Sensitivity (%) Specificity (%) MCC ROC curve area

C-SPECT 91 9 61 95 0.56 0.763

CZT-SPECT 96 4 77 99 0.82 0.928

MCC, Matthews correlation coefficient; ROC, receiver operating characteristic

Table 4. Confusion matrix per algorithm

C-SPECT CZT-SPECT

Negative Positive Negative Positive

Negative 91 5 Negative 95 1

Positive 5 8 Positive 3 10

Journal of Nuclear Cardiology� Mannarino et al

Conventional and CZT cameras in women

cardiac camera showed diagnostic performance compa-

rable to that of C-SPECT camera, with superior image

quality and significantly shorter acquisition time.7 It has

also been demonstrated that a CZT-SPECT can be

routinely used in women with suspected or known CAD

with a good accuracy associated with lower radiation

exposure.9,33

In our study population, including only women with

suspected CAD, we found a not significant correlation in

both SSS and TPD value between conventional and

CZT-SPECT. Moreover, a poor concordance (48%) of

diagnostic performance between the two methods was

found, considering semi-quantitative results for the

classification of abnormal perfusion. These findings are

related to the presence of higher values of SSS,

indicating a larger myocardial perfusion defect in

correspondence of anterior wall in our population, when

images were acquired by C-SPECT. These counts

reduction visible at conventional images likely corre-

spond to a false myocardial defect due to the breast

attenuation. A different gantry geometry of the CZT-

SPECT in association with patient position (upright or

supine) and the position of the detectors closer to patient

body reduce attenuation artifacts, limiting the overesti-

mation of the perfusion defect scores obtained by C-

SPECT. Yet, CZT-SPECT demonstrated a significant

progressive increase in count rate related to decreasing

size of the imaged object and this can have an impact on

the evaluation of the anterior wall in women.34 To

compare semi-quantitative data between the two sys-

tems, we selected a study population including only

women with suspected CAD and low-intermediate pre-

scan likelihood of disease. Moreover, all images were

analyzed by using visual method with the addition of

examination of gated results. Using cinematic display of

wall motion and wall thickening from gated MPI has

been demonstrated to improve diagnostic certainty and

effectively differentiate artifacts from true perfusion

defects. Thus, we have a high level of confidence that

normal MPI at reporting imaging interpretation can be

considered truly negative. Indeed, it has been demon-

strated that overall diagnostic accuracy provided using

visual analysis by experts is comparable to automatic

quantitative analysis of CZT-SPECT, when compared to

coronary angiography.35 As well, it has been demon-

strated that also using semi-quantitative analysis, visual

over-read remains important in the final interpretation of

results.36 Also, prognostic information derived by using

visual analysis resulted comparable to quantitative

analysis.37 Thus, visual interpretation remains an impor-

tant tool to classify patients as normal or abnormal at

MPI.

In our study, we had a high prevalence of perfusion

artifacts by C-SPECT camera. The large majority of

defects were considered as false positive due to breast

attenuation according to reporting clinical interpretation.

The incidence of false positive results without evalua-

tion of gated images was comparable between our

investigation and prior studies.38,39 The addition of

SPECT gated imaging reduces the degree of uncertainty

in the interpretation of myocardial perfusion studies with

a significant increase in the normalcy rate in patients

with a low likelihood of CAD.39 In agreement with

published data,40 we also observed a higher value of

mean post-stress LV ejection fraction by C-SPECT

compared to CZT-SPECT. LV ejection fraction mea-

surement by CZT-SPECT is more comparable to that

obtained by cardiac magnetic resonance imaging rather

than by C-SPECT.41,42

In our study a separate analysis was performed in 72

women with low likelihood of CAD and normal MPI,

where normalcy rate was also calculated. We demon-

strated that the use CZT-SPECT improves normalcy rate

in women with a low likelihood of CAD. Finally, a

machine learning analysis was performed through the

implementation of J48 algorithm proving that CZT-

SPECT has higher values of accuracy, sensitivity, and

specificity than C-SPECT. These data suggest that CZT-

SPECT may be more appropriate than C-SPECT in

women with suspected CAD, leading to a better diag-

nostic accuracy and better discrimination between

perfusion artifacts and true perfusion defects.

In this study SPECT acquisitions with both cameras

have been performed with a high dose. Thus, it was not

possible to outline the additional potential advantage of

a lower dose in female population using a stress-only

protocol by CZT-SPECT compared to the use by C-

SPECT.

NEW KNOWLEDGE GAINED

Our study adds new information about the use of

CZT-SPECT in women with low-intermediate likeli-

hood of CAD. In particular, it indicates that CZT-

SPECT might allow a better diagnostic performance in

the identification of false positive results due to breast

attenuation defect in women.

CONCLUSION

In women with low-intermediate likelihood of

CAD, there was a poor concordance in myocardial

perfusion scores between C-SPECT and CZT-SPECT.

In particular, discordance was observed in the identifi-

cation of myocardial perfusion defects in the anterior

wall. In women with low likelihood of CAD, CZT-

SPECT allows a higher normalcy rate compared to C-

SPECT, showing a better diagnostic performance.

Mannarino et al Journal of Nuclear Cardiology�Conventional and CZT cameras in women

Disclosure

T. Mannarino, R. Assante, C. Ricciardi, E. Zampella, C.

Nappi, V. Gaudieri, C.G. Mainolfi, E. Di Vaia, M. Petretta, M.

Cesarelli, A. Cuocolo and W. Acampa declare that they have

no conflict of interest.

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