Diagnostic Performance of a Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography System With Low-Dose Technetium-99m as Assessed by Fractional Flow Reserve

Abstract

Background: Although stress single-photon emission computed tomography (SPECT) using a cadmium-zinc-telluride (CZT) camera facilitates radiation dose reduction, only a few studies have evaluated its diagnostic accuracy in Japanese patients by applying fractional flow reserve (FFR) measurements.

Methods and Results: We prospectively evaluated 102 consecutive patients with suspected or known coronary artery disease with a low-dose stress/rest protocol (^99mTc radiotracer 185/370 MBq) using CZT SPECT. Within 3 months, coronary angiography was performed and a significant stenosis was defined as ≥90% diameter narrowing on visual estimation, or as a lesion of <90% and ≥ 50% stenosis with FFR ≤0.80. To detect individual coronary stenosis, the respective sensitivity, specificity, and accuracy were 86%, 75%, and 82% for left anterior descending artery stenosis, 76%, 81%, and 79% for left circumflex artery stenosis, and 87%, 92%, and 90% for right coronary artery stenosis. When limited to 92 intermediate stenotic lesions in which FFR was measured, stress SPECT showed 77% sensitivity, 91% specificity, and 84% accuracy, whereas the diagnostic value decreased to 52% sensitivity, 68% specificity, and 58% accuracy based only on visual estimation of ≥75% diameter narrowing.

Conclusions: CZT SPECT demonstrated a good diagnostic yield in detecting hemodynamically significant coronary stenoses as assessed by FFR, even when using a low-dose ^99mTc protocol with an effective dose ≤5 mSv. (Circ J 2016; 80: 1217–1224)

In recent years, significant concerns have been raised worldwide over ionizing radiation exposure associated with cardiac imaging procedures.^1–5 In 2010, the American Society of Nuclear Cardiology (ASNC) published a statement regarding radiation reduction, because myocardial perfusion imaging is one of the major procedures causing radiation burden.² The National Heart, Lung, and Blood Institute also sponsored a symposium in 2012 for cardiac imaging procedures with exposure to ionizing radiation, focusing on patient-physician shared decision making.³

Concurrently, a newly developed cadmium-zinc-telluride (CZT) ultrafast gamma camera system was reported to facilitate the reduction of the scan time or radiotracer dose owing to its high energy and spatial resolution.^6–10 Considering the aforementioned requirement for radiation dose reduction, we reported that a reduced dose of ^99mTc-tetrofosmin (555 MBq), half of the standard dose for myocardial perfusion imaging, using CZT single-photon emission computed tomography (SPECT) could obtain good image quality in Japanese patients.¹¹ Although ensuring the patient benefits related to the use of this low-dose ^99mTc protocol is necessary, the diagnostic accuracy of this protocol for coronary artery disease (CAD) in Japanese patients has not yet been established. Thus, we prospectively evaluated the diagnostic value of this low-dose ^99mTc protocol in patients with suspected or known CAD by coronary angiography (CAG) and fractional flow reserve (FFR) measurements, as the importance of a physiological definition using FFR has been recently emphasized.^12–14

Methods

Subjects

We prospectively enrolled 102 consecutive patients with suspected or known CAD who had undergone stress myocardial SPECT using the CZT SPECT system with a low-dose ^99mTc radiotracer (555 MBq) 1-day protocol, and who had also given written informed consent to participate in this study between July 2013 and December 2015. The clinical grounds for suspected or known CAD were based on clinical symptoms, coronary risk profiles, ECG findings, or past medical history. Patients requiring routine angiographic follow-up after successful percutaneous coronary intervention were also included. The exclusion criteria were as follows: (1) age <20 years, (2) acute myocardial infarction or unstable angina, (3) acute heart failure, (4) recent history of acute coronary syndrome within 1 month before the SPECT study, (5) history of coronary artery bypass grafting, (6) hypertrophic or dilated cardiomyopathy, (7) severe valvular heart disease requiring surgical operation, (8) advanced atrioventricular block or bronchial asthma, (9) history of drug allergy to ^99mTc radiotracers, (10) serious concomitant hepatic or renal disease, and (11) malignancy or any other acute illnesses requiring intensive treatment. There were 80 men and 22 women aged 69±10 years (range, 46–89 years) assessed in this study. Hypertension was observed in 79% of the patients, diabetes mellitus in 45%, and dyslipidemia in 63% (Table 1). This study was approved by the institutional ethics committee (No. 2386).

Table 1. Clinical Characteristics of the Study Patients With CAD

n	102
Age (years)	69±10
Sex (M/F) [%]	80/22 [78/22]
Height (cm)	162±8
Body weight (kg)	64±11
Body mass index (kg/m2)	24±3
Coronary risk factors
Hypertension	81 (79)
Diabetes mellitus	46 (45)
Dyslipidemia	64 (63)
Current smoking	12 (12)
Medications
β-blocker	50 (49)
Calcium-channel blocker	49 (48)
Nitrates	7 (7)
Nicorandil	23 (23)
Statin	57 (56)
Prior myocardial infarction	30 (29)
Prior PCI	59 (58)
Prior CABG	0 (0)
Type of stress (exercise/ATP) [%]	42/60 [41/59]
Radiotracer for SPECT study
99mTc-tetrofosmin	68 (67)
99mTc-sestamibi	34 (33)

Data are expressed as mean±SD or n (%). ATP, adenosine triphosphate disodium; CABG, coronary artery bypass grafting; CAD, coronary artery disease; PCI, percutaneous coronary intervention.

Stress Myocardial SPECT Imaging

The study protocol during the 1-day schedule for stress myocardial SPECT is shown in Figure 1. This protocol, which is designed with a half-dose of ^99mTc-labeled radiotracer and doubled scan time compared with the standard protocol using 1110 MBq of ^99mTc-labeled radiotracer, has been validated in previous studies based on image quality and the myocardial counts of the radiotracer.^10,11 Exercise stress using symptom-limited multistep exercise with a bicycle ergometer was performed by 42 patients.¹⁵ Technetium-99m tetrofosmin or sestamibi (185 MBq) was given intravenously at 85% of age-adjusted predictive maximal heart rate (target heart rate), or when chest pain or ST-segment depression ≥0.1 mV or leg fatigue developed. Exercise was then continued for 1 min at the same previous level. At 1 h after the last exercise session, ECG-gated SPECT was performed and 4 h later, the patients were given ^99mTc-tetrofosmin or sestamibi (370 MBq) while at rest. A further 60 min later, ECG-gated SPECT images at rest were obtained.

Figure 1.

Study protocol of stress myocardial perfusion imaging. ATP, adenosine triphosphate disodium; Ex, exercise.

Adenosine triphosphate (ATP) loading SPECT with a ^99mTc-labeled radiotracer (^99mTc-tetrofosmin or sestamibi) was performed in 60 patients. Anti-ischemic agents were withdrawn 24 h before the SPECT examination. Patients were also requested not to drink any beverage containing caffeine for at least 12 h before the test. ATP disodium (0.16 mg·kg^–1·min^–1) was administered intravenously for 6 min, and 3 min after its administration, ^99mTc-tetrofosmin or sestamibi (185 MBq) was given intravenously.^16,17 Image acquisition was started 60 min later. After 4 h, the patients were given ^99mTc-tetrofosmin or sestamibi (370 MBq) while at rest and 1 h later, ECG-gated SPECT images were acquired at rest. The estimated total radiation exposure with this protocol was in the range of 4.24–4.79 mSv. The effective dose was determined on the basis of the data in ICRP publication 106.¹⁸

Data were acquired in the list mode using the CZT SPECT system (Discovery NM 530c; GE Healthcare, Haifa, Israel). This new gamma camera system is equipped with a multiple-pinhole collimator and 19 stationary CZT semiconductor detectors, which simultaneously focus on the heart to maximize the efficiency of SPECT imaging.^19,20 The CZT elements were 2.46×2.46 mm in size, and each detector contained 32×32 pixelated 5-mm thick elements. The stationary-arrayed semiconductor detectors simultaneously acquire all the views necessary for tomographic reconstruction, saving the time required by conventional cameras for acquisition while rotating around the subject.²¹ Image acquisition was performed in the supine and prone positions after stress for 10 min and 6 min, respectively, and in the supine position at rest for 6 min. For prone position imaging, patients lay prone on the table and the detectors were positioned underneath the table. Interpretation of perfusion abnormality in the inferior wall was judged by the combination of supine and prone position images, which can decrease the frequency of attenuation artifacts in the inferior wall.²²

SPECT images were reconstructed on a workstation (Xeleris; GE Healthcare) that utilizes a new dedicated iterative algorithm with integrated collimator geometric modeling, using maximum penalized likelihood iterative reconstruction to obtain perfusion images in standard axes.²³ For both stress and rest image reconstructions, 70 iterations were performed. A Butterworth filter (order 15; cut-off frequency 0.28 cycles/cm) was applied to the reconstructed slices. When obtaining ECG-gated images, the R-R interval was divided by the R wave trigger into 8 equal portions. End-diastolic and end-systolic myocardial perfusion images were obtained using this method. All the patients were in sinus rhythm during image acquisition. No scatter or attenuation corrections were applied.

Image Analysis

In accordance with a previous method, each SPECT image was divided into 17 segments.²⁴ Radiotracer accumulation in the myocardium was visually evaluated by 2 cardiologists who were blinded to the clinical data, using a 5-grade scale: 0 (normal), 1 (slight reduction of uptake), 2 (moderate reduction of uptake), 3 (severe reduction of uptake), or 4 (absence of radioactive uptake). Although horizontal SPECT images are not incorporated into the 17-segment model, they were taken into account for assistance in image analysis. The total scores for all the segments during exercise and at rest were designated as the summed stress score (SSS) and the summed rest score (SRS), respectively. SSS minus SRS was defined as the summed difference score (SDS). Myocardial SPECT was considered as positive for myocardial ischemia in individual coronary territories when the SDS in each territory was ≥1. Disagreements in image interpretation were resolved by consensus after extensive discussion. Each reconstructed short-axis ECG-gated SPECT image was processed, and left ventricular (LV) functional parameters (ie, LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction) were automatically obtained using a quantitative gated SPECT program.²⁵

CAG and FFR Measurements

All patients underwent CAG within 3 months of the SPECT study. Multidirection CAG was performed according to Judkins’ method. The degree of coronary artery stenosis was visually rated according to the criteria of the American Heart Association (AHA),²⁶ and intracoronary pressure was measured in cases of intermediate lesions on CAG, which were defined as lesions of <90% and ≥50% diameter narrowing by visual estimation.

A 0.014-in guidewire with a mounted pressure sensor (PressureWire^TM; St. Jude Medical Inc, St. Paul, MN, USA) was placed across the lesion. To induce a maximal hyperemic vascular response, 8 mg and 12 mg of papaverine hydrochloride, a vasodilator of resistance vessels, were injected into the right and left coronary arteries, respectively. Under conditions of maximal hyperemia, simultaneous recording of aortic pressure and distal coronary pressure was performed. FFR was calculated as the ratio of hyperemic mean distal coronary pressure to mean aortic pressure.¹⁴ A significant coronary stenosis was defined as ≥90% diameter narrowing on visual estimation or as a lesion of <90% and ≥50% stenosis with an FFR of ≤0.80.^27–29

Statistical Analysis

Results are expressed as mean±SD, or number and frequency. Student’s t-test was used to compare the means of the continuous variables, and the chi-square test was used to analyze the contingency tables. The sensitivity, specificity, and accuracy of the CZT SPECT system using a low-dose ^99mTc radiotracer in detecting significant coronary restenosis were analyzed on a per-vessel basis. A P-value <0.05 was considered to indicate a statistically significant difference. Statistical analyses were performed using the SPSS-PC+ computation program (version 22.0, IBM SPSS Statistics, New York, NY, USA).

Results

Patients Characteristics

The clinical characteristics of the patients, including medications at the time of the study, are summarized in Table 1. The mean age of the patient population was 69 years, and 78% were men. The mean body mass index was 24 kg/m². Previous myocardial infarction had occurred in 30 patients (29%). Remote percutaneous coronary intervention was performed in 59 patients (58%). Of the classical coronary risk factors, the prevalence of hypertension was the highest, and that of diabetes mellitus was 45%.

All of the 102 patients successfully underwent both stress myocardial SPECT using CZT SPECT and CAG. Of these 102 patients, 57 (56%) had intermediate lesions in at least one of the 3 major coronary arteries. In the per-vessel analysis, 92 coronary vessels out of the 306 coronary arteries were regarded to have intermediate lesions and were measured with myocardial FFR. Of these 92 intermediate lesions, the average FFR was 0.79±0.11, with 48 lesions having an FFR ≤0.80. The remaining 214 arteries were judged to have either a severe stenosis with ≥90% diameter narrowing (n=85) or a mild stenosis with <50% diameter narrowing (n=129) by visual estimation (Table 2). Based on these anatomic and physiologic analyses of coronary arteries, left main or 3-vessel CAD was observed in 14 patients (14%), 2-vessel CAD in 30 (29%), 1-vessel CAD in 31 (30%), and insignificant lesions in the remaining 27 (27%). Patients with left main CAD were considered to have stenosis in both the left anterior descending (LAD) and left circumflex (LCx) coronary arteries. The distribution of significant stenoses was 66 in the LAD, 29 in the LCx, and 38 in the right coronary artery (RCA) (Table 2).

Table 2. Coronary Angiographic Findings in the Study Patients With CAD

Angiographic findings
Insignificant lesion	27 (27)
1-vessel disease	31 (30)
2-vessel disease	30 (29)
3-vessel disease	14 (14)
Stenotic coronary arteries
Diameter narrowing ≥90%
Left anterior descending	34 (33)
Left circumflex	26 (26)
Right coronary	25 (25)
Intermediate lesion (n=92) and FFR ≤0.80
Left anterior descending	32 (31)
Left circumflex	3 (3)
Right coronary	13 (13)
Diameter narrowing ≥90% or FFR ≤0.80
Left anterior descending	66 (65)
Left circumflex	29 (28)
Right coronary	38 (37)

Data are expressed as n (%). CAD, coronary artery disease; FFR, fractional flow reserve.

CZT SPECT Findings

Among the 102 patients, the ^99mTc radiotracers used were tetrofosmin in 68 patients and sestamibi in 34 (Table 1). The average SSS, SRS, and SDS in all the patients was 12.4±9.2 (range 0–51), 7.5±8.2 (range 0–39), and 4.9±5.0 (range −9 to 18), respectively. Among these patients, an abnormal perfusion area in the LAD coronary arterial territory was observed in 66 (65%), in the LCx territory in 36 (35%), and in the RCA territory in 38 (36%) (Table 3).

Table 3. Scintigraphic Findings in the Study Patients With CAD

Myocardial ischemia
LAD territory	66 (65)
LCx territory	36 (35)
RCA territory	38 (36)
Summed scores
Summed stress score	12.4±9.2
Summed rest score	7.5±8.2
Summed difference score	4.9±5.0
LV volumetric and functional analysis
LV end-diastolic volume (ml)	90.0±34.3
LV end-systolic volume (ml)	40.9±30.3
LV ejection fraction (%)	58.4±12.9

Data are expressed as mean±SD or n (%). CAD, coronary artery disease; LAD, left anterior descending coronary artery; LCx, left circumflex artery; LV, left ventricular; RCA, right coronary artery.

LV volumetric and functional analyses with ECG-gated SPECT were successfully completed in all of the patients. The average LV end-diastolic volume, LV end-systolic volume, and LVEF was 90.0±34.3 ml (range 38–233), 40.9±30.3 ml (range 8–183), and 58.5±12.9% (range 20–77), respectively (Table 3).

Diagnostic Performance of CZT SPECT

The diagnostic performance of the CZT SPECT myocardial imaging on a per-vessel basis is shown in Figure 2. To detect individual coronary stenosis, by applying a cut-off value of 0.80 in FFR, the respective sensitivity, specificity, and accuracy were 86%, 75%, and 82% for LAD stenosis, 76%, 81%, and 79% for LCx stenosis, and 87%, 69%, and 76% for RCA stenosis (Figure 2A). The combination of supine and prone imaging resulted in a higher specificity for RCA disease than supine imaging alone (92% vs. 69%) with an improvement in accuracy from 76% to 90% (Figure 2B). When the diagnostic value of CZT SPECT imaging was limited to 92 intermediate stenotic lesions in which FFR was measured, stress SPECT showed 77% sensitivity, 91% specificity, and 84% accuracy, whereas the diagnostic value decreased to 52% sensitivity, 68% specificity, and 58% accuracy based only on visual estimation of ≥75% diameter narrowing derived from the AHA criterion (Figure 3). Figure 4 shows an example of CZT SPECT imaging in a patient with normal myocardial perfusion on SPECT imaging but intermediate coronary lesions in the LAD and RCA on invasive CAG, which were functionally insignificant by FFR measurement.

Figure 2.

Diagnostic yield of CZT SPECT in detecting a significant coronary stenosis. (A) Sensitivities, specificities, and accuracies for the detection of significant coronary artery disease on a per-vessel basis, by applying a cut-off value of 0.80 in fractional flow reserve. (B) Comparison of sensitivity, specificity, and accuracy of supine only vs. combined supine and prone imaging for the detection of RCA disease. CZT, cadmium-zinc-telluride; LAD, left anterior descending coronary artery; LCx, left circumflex artery; RCA, right coronary artery; SPECT, single-photon emission computed tomography.

Figure 3.

Comparison of diagnostic accuracy of CZT SPECT in limiting to 92 intermediate stenotic coronary lesions. CZT, cadmium-zinc-telluride; FFR, fractional flow reserve.

Figure 4.

Exercise stress myocardial SPECT images and coronary angiography of a 60-year-old man who underwent follow-up examination 1 year after successful percutaneous coronary intervention. (A) Normal myocardial perfusion on the SPECT image. (B) Subsequent coronary angiogram shows intermediate coronary lesions in the proximal segment of the left anterior descending coronary artery (LAD) (arrowhead), and in the distal segment of the right coronary artery (RCA) (arrows), which were shown to be physiologically insignificant by FFR measurements (0.82 for LAD and 0.91 for RCA). LCA, left coronary artery; RCA, right coronary artery; SPECT, single-photon emission computed tomography.

Discussion

Major Findings

To achieve radiation dose reduction, we recently developed a low-dose ^99mTc 1-day protocol for myocardial perfusion SPECT imaging for Japanese patients, in which the acquisition time is still shorter than that of the conventional Anger camera system (Figure 1),^11,20 as cardiac imaging procedures have come under increasing scrutiny because of the potential risks attributable to ionizing radiation.^1–5 The present study demonstrated good diagnostic performance of CZT SPECT using 555 MBq of a ^99mTc radiotracer, with sensitivities of 76%, 86%, and 87%, specificities of 75%, 81%, and 92%, and accuracies of 79%, 82%, and 90% in detecting an individual coronary artery stenosis defined by anatomic and physiologic assessments with FFR measurements (Figure 2). With this low-dose ^99mTc protocol, the estimated total radiation exposure is in the range of 4.24–4.79 mSv, which is less than the effective dose estimate of 8 mSv related to conventional chest computed tomography.³⁰

Radiation Dose Reduction

Considerable attempts have made in reducing the ionizing radiation associated with cardiac imaging procedures.^2–4 In 2012, a meeting of experts was organized by the International Atomic Energy Agency (IAEA), and they developed criteria for best practice in nuclear cardiology laboratories such as avoidance of ²⁰¹Tl stress imaging protocols, avoidance of excessive ^99mTc administration, and utilization of camera-based dose-reduction strategies, among others.⁵ The ASNC also recommends that 50% or more patients undergoing myocardial SPECT receive a total effective dose of ≤9 mSv.²

Despite these recommendations, recent surveillance has revealed disappointing results. In the United States, the Intersocietal Accreditation Committee data showed that the average effective dose in 1,074 laboratories was 14.9±5.8 mSv, and only 1.5% of the participating laboratories met current recommendations for an average laboratory radiation exposure ≤9 mSv.⁴ By contrast, almost half of the participating laboratories in Europe fulfilled the aforementioned radiation dose reduction, although only 102 institutions were involved in the report.⁵ In 2012, the 7th Nationwide Survey was conducted to investigate the status of nuclear medicine practice in Japan. In contrast to the IAEA criteria for best practice, 52.4% of myocardial SPECT studies were performed using ²⁰¹Tl in Japan.³¹ Regarding the dose of ^99mTc radiotracers, a large Japanese multicenter study involving 4,629 patients disclosed that almost two-thirds of the registered patients were exposed to ionizing radiation ≤9 mSv, and a ^99mTc-tetrofosmin dose ≤700 MBq was administered only in 1.3% of the patients.³²

Although these reports are informative for the accumulation of data on radiation exposure from myocardial perfusion imaging, the quality of SPECT imaging and the diagnostic accuracy of the individual study protocols were not evaluated in those surveys.^4,5,31,32 In other words, to assure a good diagnostic yield of stress myocardial SPECT, the recommendations issued by the ASNC and IAEA may be too difficult to achieve.^2,5 In the context of these problems associated with the balance between radiation dose reduction and diagnostic accuracy, the present results showing good diagnostic performance of CZT SPECT applying a low-dose ^99mTc protocol with a radiation exposure ≤5 mSv is encouraging.

Diagnostic Value of CZT SPECT

In the present study, CZT SPECT with a low-dose ^99mTc protocol showed the highest sensitivity of 87% in detecting RCA stenosis, and the highest specificity of 81% was observed in detecting LCx stenosis based only on SPECT imaging performed while the patient was supine. Although the diagnosis of coronary stenosis in the RCA based only on data acquired in the supine position was problematic for the CZT SPECT system, owing to the presence of hepatic and bowel isotope activity,^33,34 prone image acquisition helped to improve the diagnostic specificity and accuracy from 69% to 92% and from 76% to 90%, respectively (Figure 2).

Apart from another type of CZT SPECT (D-SPECT; Spectrum Dynamics, Caesarea, Israel),^35,36 several studies have evaluated the relation of stress SPECT imaging using Discovery NM 530c with invasive CAG, although only a few reports have addressed individual vessel detection with this new CZT SPECT.^33,37–40 Nishiyama et al³³ and Duvall et al⁴⁰ have reported respective sensitivities and specificities of 53–56% and 66–81% for LAD stenosis, 66–72% and 66–74% for LCx stenosis, and 64–74% and 68–70% for RCA stenosis, but radiation dose reduction was not attempted in those studies. Using low-dose ^99mTc-tetrofosmin myocardial perfusion CZT SPECT, Esteves et al reported 68% sensitivity and 69% specificity for LAD stenosis, 63% sensitivity and 81% specificity for LCx stenosis, and 58% sensitivity and 78% specificity for RCA stenosis, and with their protocol, the estimated effective radiation dose was 6.0 mSv.⁴¹ Using a low-dose ^99mTc-tetrofosmin protocol with an effective dose range of 4.55–6.84 mSv, Gimelli et al reported a higher sensitivity of 92% and a specificity of 85% for LAD stenosis, 88% and 74% for LCx stenosis, and 86% and 73% for RCA stenosis, respectively.⁴² In line with that report,⁴² the current study demonstrated high diagnostic accuracy of a low-dose ^99mTc protocol, although the gold standard for CAD diagnosis was different: by anatomic analysis only in the previous study vs. by combined anatomic and physiologic analyses with FFR measurements in the current study.

Importance of FFR Measurements for CAD Diagnosis

Using a prospective approach to invasive coronary evaluation, more than half of the patients in the present study had intermediate lesions in at least one of the 3 major coronary arteries. This is in contrast to the study by Gimelli et al in which only 6 of 137 patients showed an intermediate stenosis as assessed by quantitative CAG.⁴² In terms of per-vessel analysis, almost one-third of the major arteries were shown to have intermediate lesions and required investigation by FFR measurement. When the diagnostic value of CZT SPECT imaging was limited to these intermediate lesions, the analysis showed 77% sensitivity, 91% specificity, and 84% accuracy, whereas the diagnostic value decreased to 52% sensitivity, 68% specificity, and 58% accuracy based only on visual estimation of ≥75% stenosis defined by the AHA criterion (Figure 3). In actuality, making a correct diagnosis of whether a given intermediate lesion is significant or not according to the AHA criterion using a caliper is subjective and difficult. Indeed, the diagnosis of coronary artery stenosis in a representative case might have differed according to individual investigators if FFR had not been measured (Figure 4). Thus, obtaining an FFR value that is objective and highly reproducible by experienced hands is of utmost importance for evaluating an intermediate stenotic coronary lesion.¹⁴

Study Limitations

Although the present study was prospectively performed with a well-characterized group of patients, the number of the patients included in a single center was small. Therefore, a multicenter study of a large patient group is necessary.

In addition, although the fixed dose of 555 MBq was administered to all of the patients in the current study, further radiation dose reduction may be possible, particularly in patients with a small body size. To pursue this end, it is considered appropriate to construct another stress myocardial SPECT protocol based on retrospective analysis of the list mode data of the current study, and then to evaluate its efficacy prospectively.

Conclusions

CZT SPECT imaging demonstrated good diagnostic yield in detecting a hemodynamically significant coronary stenosis as assessed by FFR even with the use of a low-dose ^99mTc (185/370 MBq) 1-day protocol with an effective dose ≤5 mSv.

Acknowledgments

This research was supported by a Grant-in-Aid for Scientific Research (JSPS KAKENHI No. 25461072) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

We are indebted to Dr Edward F. Barroga (PhD), Associate Professor and Senior Editor from the Department of International Medical Communications of Tokyo Medical University for editing the manuscript.

Disclosures

A.Y. has established endowed departments at Tokyo Medical University supported by Medtronic Japan Corporation, and has received a research grant from Fujifilm RI Pharma Corporation. N.T. serves as a consultant to St. Jude Medical Japan Corporation. All other authors have no potential relationships to disclose relevant to the contents of this paper.

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