High efficiency gamma camera enables ultra-low fixed dose stress/rest myocardial perfusion imaging

High efficiency gamma camera enables ultra-low fixed dose stress/rest myocardial perfusion imaging Abstract Aims We validated a 1-day myocardial perfusion imaging (MPI) protocol using an ultra low-dose(ULD) equal for stress and rest on a cadmium zinc telluride (CZT). Methods and results Fifty-six patients underwent a 1-day MPI protocol using a standard (SD) 99mTc-tetrofosmin dose at stress (320 MBq) and rest (960 MBq) with 5 min acquisition time each (SD). Within 2 weeks MPI was repeated using ULD 99mTc-tetrofosmin equal for stress and rest (160 MBq) with 15 min acquisition time each (ULD). All scans were performed on a CZT camera (DNM 570c, GE Healthcare). Background subtraction was applied on the rest MPI of the ULD using P-mod software. Presence and extent of perfusion defect were analysed. Pearson’s correlation was used to compare ejection fraction (EF), end diastolic volume (EDV), and end systolic volume (ESV) between both protocols. SD revealed ischaemia in 23, scar in 3, and an equivocal finding in 1 patient, while normal findings were documented in 29 patients. ULD resulted in the following findings: ischaemia 23, scar 3, and 30 normal scans. Congruence of SD and ULD was 22/23 for ischaemia, 3/3 for scar, and 29/29 in normal patients; one patient with ischaemia in SD was classified as scar in ULD. Overall agreement of ULD with SD was 98%. The mean extent of defect was comparable between SD and ULD for the stress (10% vs. 11%, respectively, P = NS) and rest studies (5% vs. 7%, respectively, P = NS). An excellent correlation between SD and ULD was found for EF (r = 0.93), EDV (r = 0.95), and ESV (r = 0.97). Conclusion CZT cameras may enable reliable MPI scanning in patients with known or suspected coronary artery disease using protocols with about a factor 4-decrease in radiation dose exposure compared with traditional protocols. CZT gamma camera, dose reduction, myocardial perfusion imaging Introduction Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the Western countries. According to the recent guidelines on myocardial revascularization in stable CAD, proof of myocardial ischaemia is mandatory previous to revascularization.1 Myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) has been well-established as a non-invasive diagnostic tool for detection of myocardial ischaemia. As there are growing concerns regarding the radiation burden of SPECT MPI2 several strategies for dose reduction have been explored in the recent years, such as for example use of technetium tracers instead of thallium and stress only protocols avoiding the high dose of the second 1-day protocol scan. In an important proportion of patients undergoing MPI SPECT a stress induced defect is found, which renders a subsequent rest scan necessary to discriminate between scar (fixed defect) and ischaemia (reversible defect). Other dose-reduction strategies include modern image reconstruction algorithms with resolution recovery allowing half-dose acquisition protocols.3,4 Recently, a new generation of gamma cameras has been introduced with the concept of cadmium zinc telluride (CZT) semiconductor detectors. These detectors offer a linear counting-rate response characteristic, which allow accurate subtraction.5 In addition, the higher system sensitivity allows the use of doses below 200 MBq per scan, referred to as ultra low-dose (ULD) by Einstein et al.5 We tested the hypothesis that using a CZT SPECT camera allows combining both strategies by using an ULD of 99mTc-tetrofosmin equal for stress and rest. Materials and Methods Patient population and study design Fifty-six consecutive patients who underwent a standard 1-day low-dose stress/high-dose rest CZT MPI scan for suspected or known CAD were prospectively enrolled to undergo an additional 1-day CZT MPI within 2 weeks using an equal ULD for both scans. Exclusion criteria were a body mass index > 32 kg/m2 and any change in cardiovascular events, medication, or any invasive procedure between the two examinations. The study protocol was approved by the institutional ethics committee and written informed consent was obtained from each study participant (KEK 849). Standard 1-day (low-dose/high-dose) MPI protocol Patients were advised to refrain from theophylline or caffeine-containing beverages for at least 12 h prior to the study. Pharmacological stress was performed with adenosine infused at a rate of 140 µg/kg/min during 6 min, and 99mTc-tetrofosmin at a standard dose of 320 MBq was injected 3 min into the pharmacological stress. Approximately 60 min later gated stress MPI was acquired on a hybrid SPECT/computed tomography (CT) scanner (DNM/CT 570c; GE Healthcare, Milwaukee, WI, USA) integrating a CZT gamma camera and a 64-slice CT device.6,7 Thereafter, a three-fold higher dose of Tc-tetrofosmin i.e. 960 MBq according to SD protocol was injected followed by electrocardiogram (ECG) gated rest MPI acquisition.8 Each standard stress/rest (320 MBq/960 MBq) MPI scan was acquired over 5 min according to our clinical routine protocols previously established for the CZT SPECT component of the hybrid camera.9–13 Attenuation correction scans were performed on the CT part of the scanner using the following parameters: prospective ECG triggering at inspiratory breath hold; 2.5 mm slice thickness, 0.35 s gantry rotation time with 120 kV tube current, and 200–250 mA depending on patient’s size as previously reported.14,15 Ultra low-dose 1-day MPI protocol Within 2 week the 1-day MPI was repeated using 160 MBq 99mTc-tetrofosmin for stress and 160 MBq 99mTc-tetrofosmin for rest (ULD), i.e. an equal ULD for both scans as illustrated in Figure 1. Figure 1 View largeDownload slide Acquisition protocol using SD and ULD. CTAC, computed tomography attenuation correction scan; SD, standard protocol; ULD, ultra low-dose protocol. Figure 1 View largeDownload slide Acquisition protocol using SD and ULD. CTAC, computed tomography attenuation correction scan; SD, standard protocol; ULD, ultra low-dose protocol. MPI reconstruction All SPECT images were reconstructed using a commercially available dedicated software package (Myovation for Alcyone; GE Healthcare, Milwaukee, WI, USA) with a modern iterative algorithm based on integrated collimator geometry modelling, using maximum-penalized likelihood iterative reconstruction to obtain perfusion images in standard axes as previously reported.9 In brief, 40 and 50 iterations of the algorithm were used for reconstruction of the stress and rest datasets, respectively. A Butterworth post-processing filter with cut-off frequency of 0.37 cycle/cm and an order of seven was applied to the reconstructed slices. CT images were transferred to the Xeleris workstation (GE Healthcare) for attenuation correction map generation as previously reported.15 Stress–rest count subtraction For ULD, background activity was subtracted from the ULD rest examination using the commercially available PMOD software package (version 3.2; PCARD, PMOD Technologies Ltd, Zurich, Switzerland) as previously validated.7 Briefly, using the rest and stress MPI datasets, a subtraction algorithm (rest minus stress with negative regional results set to zero) was performed. The resulting data sets were transferred to the Myovation for Alcyone software for further processing and image analysis. SPECT data analysis A perfusion polar map was displayed using a 20-segment model representation of the left ventricle, and segmental uptake values (percentage of maximum uptake) as well as extent of perfusion abnormalities at stress and rest, including its reversibility were calculated. A semi-quantitative score (0–4) for severity of perfusion abnormalities was computed based on segmental uptake values: uptake >70% (score 0); 70–50% (score 1); 49–30% (score 2); 29–10% (score 3); <10% (score 4). The summed rest scores (SRS) were assessed from SD and ULD scans and were subtracted from the summed stress scores (SSS) to obtain summed difference scores (SDS). An SSS ≥ 4 was considered abnormal and an SDS ≥ 2 was considered to represent clinically relevant ischaemia.16–18 Left ventricular (LV) volumes and ejection fraction (EF) were obtained using gated data sets reconstructed at eight frames with the quantitative Gated SPECT/Quantitative Perfusion SPECT software package (Cedars QGS/QPS; Cedars-Sinai Medical Center), which also provided the defect extent in percentage of LV myocardium. No subtraction was performed for the analysis of the gated datasets. Anonymized data were presented blindly and randomly to consensual evaluation by two experienced nuclear cardiologist for image quality, perfusion findings (normal/abnormal) and the presence of ischaemia. Image quality was classified as optimal, fair and poor based on definition of the LV borders, homogeneity of the cardiac uptake and the amount of extracardiac activity. Statistical analysis The SPSS software (version 16.0.1 for Windows, SPSS Inc., Chicago, IL, USA) was used for all statistical evaluations. Categorical values were presented as proportions and percentages, and continuous variables as mean ± standard deviation or median with interquartile range where appropriate. Agreement on image quality and clinical diagnosis was evaluated using kappa-statistics. Extent of perfusion defects and perfusion scores were compared using paired t-test. Differences in perfusion scores were evaluated using the Wilcoxon’s test. Pearson’s correlation, intraclass correlation and Bland–Altman (BA) limits of agreement were used to compare EF, end diastolic volume (EDV), and end systolic volume (ESV) between SD protocol and ULD. All P-values < 0.05 were considered significant. Results All 56 patients completed the SD and ULD without complications. The baseline characteristics of the study participants are given in Table 1. Table 1 Baseline characteristics of the study population (n = 56) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) BMI, body mass index; CAD, coronary artery disease. Table 1 Baseline characteristics of the study population (n = 56) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) BMI, body mass index; CAD, coronary artery disease. Qualitative analysis Image quality SD low-dose stress scans yielded optimal image quality in 53, fair in 3, and poor in 0 patients. From SD high-dose stress the respective image quality was optimal in 55, fair in 1, and poor in 0 patients. The ULD resulted in 54 patients with optimal and 2 with fair image quality, both for stress and rest. Perfusion abnormalities SD revealed ischaemia in 23, scar in 3, and an equivocal finding in 1 patient, while normal findings were documented in 29 patients. ULD resulted in the following findings: ischaemia 23, scar 3, and 30 normal scans. Congruence of SD and ULD was 22/23 for ischaemia, 3/3 for scar, and 29/29 in normal patients. One patient presenting with a mild defect with additional reversibility (ischaemia) by SD was classified as having a mild fixed defect (no ischaemia) by ULD. Overall agreement of ULD with SD was 98% (kappa = 0.96) (Figure 2). Figure 2 View largeDownload slide Illustrative case showing comparable extent of perfusion defect using ULD and SD at stress (upper panel A) and rest (lower panel B). SD, standard protocol; ULD, ultra low-dose protocol. Figure 2 View largeDownload slide Illustrative case showing comparable extent of perfusion defect using ULD and SD at stress (upper panel A) and rest (lower panel B). SD, standard protocol; ULD, ultra low-dose protocol. Quantitative analysis Extent and severity of perfusion defect The extent of LV perfusion defect at stress, rest, and the extent of reversible defect for SD vs. ULD examination were 9.3% vs. 9.6% (P = NS), 5.1% vs. 6.3% (P = NS), and 4.3% 3.2% (P = NS), respectively (Figure 3). Figure 3 View largeDownload slide Extent of perfusion defect using SD and ULD. LV, left ventricular; SD, standard protocol; ULD, ultra low-dose protocol. Figure 3 View largeDownload slide Extent of perfusion defect using SD and ULD. LV, left ventricular; SD, standard protocol; ULD, ultra low-dose protocol. The mean SSS, SRS, and SDS for SD vs. ULD examination were 7.2 vs. 7.1, 3.6 vs. 3.9, and 3.1 vs. 2.7, respectively (all P = NS). The difference in SSS between the two protocols was within one point in 35/56 patients (62.5%) and two or more in 21/56 patients (37.5%) (P = 0.095). Similarly, the difference in SDS was within one point in 37/56 patients (66%), within two points in 48/56 patients (85%), and two or more in 19/56 patients (34%) (P = 0.731). In vascular territories, the difference in SSS between the two protocols was within one point in 42/66 (75%), 46/56 (82%), and 47/56 (83%), respectively for the left anterior descending (LAD), circumflex (Cx), and right coronary artery (RCA) territories. Also, the difference in SDS was within one point between the two protocols in 35/56 (62.5%), 43/56 (76.7%), and 46/56 (82%), respectively in the LAD, Cx, and RCA territories. When applying these quantitative criteria in a dichotomous fashion, 24 of 27 patients with normal findings by SD protocol also returned normal by ULD examination. Also 23 of 29 patients with abnormal findings by SD protocol were equally classified abnormal by ULD. This translated into an agreement rate of 83.93% [kappa 0.68, 95% confidence interval (CI) 0.49–0.87] for the finding of a normal examination. Similarly, 24 of 29 patients with SD protocol showing no ischaemia were also not classified as non-ischaemic by ULD. And 21 of 27 patients with ischaemia by SD dose were classified as ischaemic by ULD. The agreement rate for the finding of ischaemia was 80.4% (kappa 0.61, 95% CI 0.40–0.81). Ejection fraction and volumes The values of EF and LV volumes obtained from SD and ULD protocol as well as the correlation are summarized in Table 2. For stress images, the mean EF, EDV, and ESV obtained from SD and ULD examination were 51.7 ± 15.9%, 99.1 ± 40.8 mL, 52.9 ± 38.7 mL and 54.3 ± 15.7%, 105.1 ± 46.3 mL, 53.8 ± 42.4 mL, respectively (P = 0.001). Table 2 Left ventricular ejection fraction and volumes Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 BA, Bland–Altman; EDV, left ventricular end diastolic volume; EF, left ventricular ejection fraction; ESV, left ventricular end systolic volume. Table 2 Left ventricular ejection fraction and volumes Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 BA, Bland–Altman; EDV, left ventricular end diastolic volume; EF, left ventricular ejection fraction; ESV, left ventricular end systolic volume. For rest images, the mean EF, EDV, and ESV obtained from SD and ULD examination were 51.5 ± 16.59%, 91.6 ± 41.5 mL, 49.2 ± 39.5 mL and 55.6 ± 15.8%, 103.4 ± 47.6 mL, 51.5 ± 43.1 mL, respectively (P = 0.001). The correlation coefficients between SD and ULD examination at stress and rest for EF, EDV, and ESV were 0.90, 0.94, 0.97 and 0.92, 0.96, 0.97, respectively. The mean bias (BA limits of agreements) between SD and ULD examination for EF, EDV, and ESV was 2.5% (−7.4 to 12.5%), 5.9 mL (−14.0 to 25.9 mL), 0.8 mL (−19.1 to 20.8 mL) and 4.1% (−10.0 to 14.1%), 11.7 mL (−8.2 to 31.7 mL), 2.3 mL (−17.6 to 22.3 mL), respectively (Table 2 and Figure 4). Figure 4 View largeDownload slide Correlation and Bland–Altman plots of LVEF between standard dose and ultra low-dose at rest (A and B) and stress (C and D). Difference is standard minus ultra low-dose. LVEF, left ventricular ejection fraction. Figure 4 View largeDownload slide Correlation and Bland–Altman plots of LVEF between standard dose and ultra low-dose at rest (A and B) and stress (C and D). Difference is standard minus ultra low-dose. LVEF, left ventricular ejection fraction. Discussion The results of this study illustrate how the new generation of gamma camera with highly sensitive CZT detector technique may pave the way to a substantial decrease in the radiation exposure to the patient with maintained image quality. Although our protocol pushes the boundaries towards low-dose SPECT MPI, this is still on solid ground as the low-dose for stress MPI suggested in our ULD protocol is covered by the latest ASNC guidelines including reduced dose recommendations for newer technologies gamma camera.8 ULD images yielded clinical information comparable to that obtained from SD with regard to defect extent and severity, as well as volumes and function. The latter is important as the LVEF is a strong predictor of outcome and also due to the added value of wall motion and thickening information for discrimination of artefact from scar.19 Combining ULD stress and rest MP resulted in a 98% agreement with the SD for discriminating normal from abnormal scan and, thus, for detecting CAD. This compares favourably to test–retest agreement in large trials.4,20 The validity of the ULD protocol is further underlined by the fact that the differences in regional scores of ischaemic territories between SD and ULD was less or equalling one in the vast majority of patients and within two points in 85% of patients, which by the latter is considered as an appropriate cut-off value depicting clinical relevance.7,16,18 The ULD protocol enables coronary functional evaluation with radiation exposure to the patient in the range of modern non-invasive anatomic evaluation of the coronary arteries by CT,21,22 while it is lower than most values reported for CT perfusion imaging, which is currently considered an emerging tool for MPI.23 In this study an apparent drawback is the fact that the dose reduction was partly achieved at the cost of an increase in total scan time summing up to 30 min duration. However, this lies well within scan and protocol times required by other traditional MPI modalities. As the potential for increased workflow has been highlighted by the original publications of CZT equipped gamma cameras, through ultrafast acquisition protocols,9,24 to some extent this benefitted only to high through-put laboratories were camera time harboured an economic importance. Recent publication focusing on the dose reduction algorithm including this study7 offer the perspective, on top of improving patient and medical staff protection against ionizing radiations, to provide economic saves through reduced need in technetium generators regardless of their patient’s through-put. Limitations We acknowledge the following limitations. First, the fact that such protocol is somehow depending on optimal registration between the stress and rest studies. This might be problematic in restless patients in whom image subtraction might be less efficient. However, such patients would still benefit from half stress radiotracer administration, which was proved comparable to SD stress dose in this study, and conventional doubled or tripled rest radiotracer administration. Second, we compared the new MPI protocol to another established MPI study rather than choosing an anatomic standard of reference such as coronary angiography. This, however, should not be seen as major limitation as fundamental differences between physiological vs. anatomic evaluation of CAD exist.25–28 Comparison of a perfusion protocol vs. another perfusion protocol appears more meaningful and appropriate. Third, we did not measure how much of the 99mTc-tetrofosmin dose is stuck in the syringe and tube system. This may represent a minor issue when higher doses are used but makes more of an impact the lower the dose is injected while trying to maintain proportional counts. Fourth, our findings cannot be extrapolated in obese patients since they were excluded in our study. This population may represent an additional challenge for imaging with CZT gamma camera owing to the shorter field of view when compared with traditional gamma camera with potential truncation artefacts. Conclusion CZT cameras may enable reliable MPI scanning in patients with known or suspected CAD using protocols with about a factor 4-decrease in radiation dose exposure compared with traditional protocols. Acknowledgements We would like to thank Ennio Mueller, Edlira Loga, Myriam De Bloome, Sabrina Epp, and Patrick von Schultess for their excellent technical support. Funding This work was supported by a grant from the Swiss National Science Foundation (SNSF to P.A.K.). Conflict of interest: None declared. 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Google Scholar PubMed 19 Fleischmann S , Koepfli P , Namdar M , Wyss CA , Jenni R , Kaufmann PA. Gated (99m)Tc-tetrofosmin SPECT for discriminating infarct from artifact in fixed myocardial perfusion defects . J Nucl Med 2004 ; 45 : 754 – 9 . Google Scholar PubMed 20 Iskandrian AE , Bateman TM , Belardinelli L , Blackburn B , Cerqueira MD , Hendel RC et al. . Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial . J Nucl Cardiol 2007 ; 14 : 645 – 58 . Google Scholar CrossRef Search ADS PubMed 21 Buechel RR , Husmann L , Herzog BA , Pazhenkottil AP , Nkoulou R , Ghadri JR et al. . Low-dose computed tomography coronary angiography with prospective electrocardiogram triggering: feasibility in a large population . J Am Coll Cardiol 2011 ; 57 : 332 – 6 . Google Scholar CrossRef Search ADS PubMed 22 Achenbach S , Marwan M , Ropers D , Schepis T , Pflederer T , Anders K et al. . Coronary computed tomography angiography with a consistent dose below 1 mSv using prospectively electrocardiogram-triggered high-pitch spiral acquisition . Eur Heart J 2010 ; 31 : 340 – 6 . Google Scholar CrossRef Search ADS PubMed 23 Rochitte CE , George RT , Chen MY , Arbab-Zadeh A , Dewey M , Miller JM et al. . Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study . Eur Heart J 2014 ; 35 : 1120 – 30 . Google Scholar CrossRef Search ADS PubMed 24 Garcia EV , Faber TL , Esteves FP. Cardiac dedicated ultrafast SPECT cameras: new designs and clinical implications . J Nucl Med 2011 ; 52 : 210 – 7 . Google Scholar CrossRef Search ADS PubMed 25 Gaemperli O , Schepis T , Valenta I , Koepfli P , Husmann L , Scheffel H et al. . Functionally relevant coronary artery disease: comparison of 64-section CT angiography with myocardial perfusion SPECT . Radiology 2008 ; 248 : 414 – 23 . Google Scholar CrossRef Search ADS PubMed 26 White CW , Wright CB , Doty DB , Hiratza LF , Eastham CL , Harrison DG et al. . Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 1984 ; 310 : 819 – 24 . Google Scholar CrossRef Search ADS PubMed 27 Uren NG , Melin JA , De Bruyne B , Wijns W , Baudhuin T , Camici PG. Relation between myocardial blood flow and the severity of coronary-artery stenosis . N Engl J Med 1994 ; 330 : 1782 – 8 . Google Scholar CrossRef Search ADS PubMed 28 Tonino PA , Fearon WF , De Bruyne B , Oldroyd KG , Leesar MA , Ver Lee PN et al. . Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation . J Am Coll Cardiol 2010 ; 55 : 2816 – 21 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

High efficiency gamma camera enables ultra-low fixed dose stress/rest myocardial perfusion imaging

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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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Abstract

Abstract Aims We validated a 1-day myocardial perfusion imaging (MPI) protocol using an ultra low-dose(ULD) equal for stress and rest on a cadmium zinc telluride (CZT). Methods and results Fifty-six patients underwent a 1-day MPI protocol using a standard (SD) 99mTc-tetrofosmin dose at stress (320 MBq) and rest (960 MBq) with 5 min acquisition time each (SD). Within 2 weeks MPI was repeated using ULD 99mTc-tetrofosmin equal for stress and rest (160 MBq) with 15 min acquisition time each (ULD). All scans were performed on a CZT camera (DNM 570c, GE Healthcare). Background subtraction was applied on the rest MPI of the ULD using P-mod software. Presence and extent of perfusion defect were analysed. Pearson’s correlation was used to compare ejection fraction (EF), end diastolic volume (EDV), and end systolic volume (ESV) between both protocols. SD revealed ischaemia in 23, scar in 3, and an equivocal finding in 1 patient, while normal findings were documented in 29 patients. ULD resulted in the following findings: ischaemia 23, scar 3, and 30 normal scans. Congruence of SD and ULD was 22/23 for ischaemia, 3/3 for scar, and 29/29 in normal patients; one patient with ischaemia in SD was classified as scar in ULD. Overall agreement of ULD with SD was 98%. The mean extent of defect was comparable between SD and ULD for the stress (10% vs. 11%, respectively, P = NS) and rest studies (5% vs. 7%, respectively, P = NS). An excellent correlation between SD and ULD was found for EF (r = 0.93), EDV (r = 0.95), and ESV (r = 0.97). Conclusion CZT cameras may enable reliable MPI scanning in patients with known or suspected coronary artery disease using protocols with about a factor 4-decrease in radiation dose exposure compared with traditional protocols. CZT gamma camera, dose reduction, myocardial perfusion imaging Introduction Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the Western countries. According to the recent guidelines on myocardial revascularization in stable CAD, proof of myocardial ischaemia is mandatory previous to revascularization.1 Myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) has been well-established as a non-invasive diagnostic tool for detection of myocardial ischaemia. As there are growing concerns regarding the radiation burden of SPECT MPI2 several strategies for dose reduction have been explored in the recent years, such as for example use of technetium tracers instead of thallium and stress only protocols avoiding the high dose of the second 1-day protocol scan. In an important proportion of patients undergoing MPI SPECT a stress induced defect is found, which renders a subsequent rest scan necessary to discriminate between scar (fixed defect) and ischaemia (reversible defect). Other dose-reduction strategies include modern image reconstruction algorithms with resolution recovery allowing half-dose acquisition protocols.3,4 Recently, a new generation of gamma cameras has been introduced with the concept of cadmium zinc telluride (CZT) semiconductor detectors. These detectors offer a linear counting-rate response characteristic, which allow accurate subtraction.5 In addition, the higher system sensitivity allows the use of doses below 200 MBq per scan, referred to as ultra low-dose (ULD) by Einstein et al.5 We tested the hypothesis that using a CZT SPECT camera allows combining both strategies by using an ULD of 99mTc-tetrofosmin equal for stress and rest. Materials and Methods Patient population and study design Fifty-six consecutive patients who underwent a standard 1-day low-dose stress/high-dose rest CZT MPI scan for suspected or known CAD were prospectively enrolled to undergo an additional 1-day CZT MPI within 2 weeks using an equal ULD for both scans. Exclusion criteria were a body mass index > 32 kg/m2 and any change in cardiovascular events, medication, or any invasive procedure between the two examinations. The study protocol was approved by the institutional ethics committee and written informed consent was obtained from each study participant (KEK 849). Standard 1-day (low-dose/high-dose) MPI protocol Patients were advised to refrain from theophylline or caffeine-containing beverages for at least 12 h prior to the study. Pharmacological stress was performed with adenosine infused at a rate of 140 µg/kg/min during 6 min, and 99mTc-tetrofosmin at a standard dose of 320 MBq was injected 3 min into the pharmacological stress. Approximately 60 min later gated stress MPI was acquired on a hybrid SPECT/computed tomography (CT) scanner (DNM/CT 570c; GE Healthcare, Milwaukee, WI, USA) integrating a CZT gamma camera and a 64-slice CT device.6,7 Thereafter, a three-fold higher dose of Tc-tetrofosmin i.e. 960 MBq according to SD protocol was injected followed by electrocardiogram (ECG) gated rest MPI acquisition.8 Each standard stress/rest (320 MBq/960 MBq) MPI scan was acquired over 5 min according to our clinical routine protocols previously established for the CZT SPECT component of the hybrid camera.9–13 Attenuation correction scans were performed on the CT part of the scanner using the following parameters: prospective ECG triggering at inspiratory breath hold; 2.5 mm slice thickness, 0.35 s gantry rotation time with 120 kV tube current, and 200–250 mA depending on patient’s size as previously reported.14,15 Ultra low-dose 1-day MPI protocol Within 2 week the 1-day MPI was repeated using 160 MBq 99mTc-tetrofosmin for stress and 160 MBq 99mTc-tetrofosmin for rest (ULD), i.e. an equal ULD for both scans as illustrated in Figure 1. Figure 1 View largeDownload slide Acquisition protocol using SD and ULD. CTAC, computed tomography attenuation correction scan; SD, standard protocol; ULD, ultra low-dose protocol. Figure 1 View largeDownload slide Acquisition protocol using SD and ULD. CTAC, computed tomography attenuation correction scan; SD, standard protocol; ULD, ultra low-dose protocol. MPI reconstruction All SPECT images were reconstructed using a commercially available dedicated software package (Myovation for Alcyone; GE Healthcare, Milwaukee, WI, USA) with a modern iterative algorithm based on integrated collimator geometry modelling, using maximum-penalized likelihood iterative reconstruction to obtain perfusion images in standard axes as previously reported.9 In brief, 40 and 50 iterations of the algorithm were used for reconstruction of the stress and rest datasets, respectively. A Butterworth post-processing filter with cut-off frequency of 0.37 cycle/cm and an order of seven was applied to the reconstructed slices. CT images were transferred to the Xeleris workstation (GE Healthcare) for attenuation correction map generation as previously reported.15 Stress–rest count subtraction For ULD, background activity was subtracted from the ULD rest examination using the commercially available PMOD software package (version 3.2; PCARD, PMOD Technologies Ltd, Zurich, Switzerland) as previously validated.7 Briefly, using the rest and stress MPI datasets, a subtraction algorithm (rest minus stress with negative regional results set to zero) was performed. The resulting data sets were transferred to the Myovation for Alcyone software for further processing and image analysis. SPECT data analysis A perfusion polar map was displayed using a 20-segment model representation of the left ventricle, and segmental uptake values (percentage of maximum uptake) as well as extent of perfusion abnormalities at stress and rest, including its reversibility were calculated. A semi-quantitative score (0–4) for severity of perfusion abnormalities was computed based on segmental uptake values: uptake >70% (score 0); 70–50% (score 1); 49–30% (score 2); 29–10% (score 3); <10% (score 4). The summed rest scores (SRS) were assessed from SD and ULD scans and were subtracted from the summed stress scores (SSS) to obtain summed difference scores (SDS). An SSS ≥ 4 was considered abnormal and an SDS ≥ 2 was considered to represent clinically relevant ischaemia.16–18 Left ventricular (LV) volumes and ejection fraction (EF) were obtained using gated data sets reconstructed at eight frames with the quantitative Gated SPECT/Quantitative Perfusion SPECT software package (Cedars QGS/QPS; Cedars-Sinai Medical Center), which also provided the defect extent in percentage of LV myocardium. No subtraction was performed for the analysis of the gated datasets. Anonymized data were presented blindly and randomly to consensual evaluation by two experienced nuclear cardiologist for image quality, perfusion findings (normal/abnormal) and the presence of ischaemia. Image quality was classified as optimal, fair and poor based on definition of the LV borders, homogeneity of the cardiac uptake and the amount of extracardiac activity. Statistical analysis The SPSS software (version 16.0.1 for Windows, SPSS Inc., Chicago, IL, USA) was used for all statistical evaluations. Categorical values were presented as proportions and percentages, and continuous variables as mean ± standard deviation or median with interquartile range where appropriate. Agreement on image quality and clinical diagnosis was evaluated using kappa-statistics. Extent of perfusion defects and perfusion scores were compared using paired t-test. Differences in perfusion scores were evaluated using the Wilcoxon’s test. Pearson’s correlation, intraclass correlation and Bland–Altman (BA) limits of agreement were used to compare EF, end diastolic volume (EDV), and end systolic volume (ESV) between SD protocol and ULD. All P-values < 0.05 were considered significant. Results All 56 patients completed the SD and ULD without complications. The baseline characteristics of the study participants are given in Table 1. Table 1 Baseline characteristics of the study population (n = 56) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) BMI, body mass index; CAD, coronary artery disease. Table 1 Baseline characteristics of the study population (n = 56) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) Characteristics Values Age (years), mean (range) 65 (53–88) Gender male/female, n (%) 43/13 (76/24) BMI (kg/m2), mean (range) 26.1 (18–30) High blood pressure, n (%) 41 (73) Hypercholesterolaemia, n (%) 38 (68) Diabetes, n (%) 11 (20) Smoking, n (%) 21 (37) History of CAD, n (%) 12 (21) Known CAD, n (%) 34 (60) Angina (typical/atypical), n (%) 10/8 (18/14) Asymptomatic, n (%) 22 (39) BMI, body mass index; CAD, coronary artery disease. Qualitative analysis Image quality SD low-dose stress scans yielded optimal image quality in 53, fair in 3, and poor in 0 patients. From SD high-dose stress the respective image quality was optimal in 55, fair in 1, and poor in 0 patients. The ULD resulted in 54 patients with optimal and 2 with fair image quality, both for stress and rest. Perfusion abnormalities SD revealed ischaemia in 23, scar in 3, and an equivocal finding in 1 patient, while normal findings were documented in 29 patients. ULD resulted in the following findings: ischaemia 23, scar 3, and 30 normal scans. Congruence of SD and ULD was 22/23 for ischaemia, 3/3 for scar, and 29/29 in normal patients. One patient presenting with a mild defect with additional reversibility (ischaemia) by SD was classified as having a mild fixed defect (no ischaemia) by ULD. Overall agreement of ULD with SD was 98% (kappa = 0.96) (Figure 2). Figure 2 View largeDownload slide Illustrative case showing comparable extent of perfusion defect using ULD and SD at stress (upper panel A) and rest (lower panel B). SD, standard protocol; ULD, ultra low-dose protocol. Figure 2 View largeDownload slide Illustrative case showing comparable extent of perfusion defect using ULD and SD at stress (upper panel A) and rest (lower panel B). SD, standard protocol; ULD, ultra low-dose protocol. Quantitative analysis Extent and severity of perfusion defect The extent of LV perfusion defect at stress, rest, and the extent of reversible defect for SD vs. ULD examination were 9.3% vs. 9.6% (P = NS), 5.1% vs. 6.3% (P = NS), and 4.3% 3.2% (P = NS), respectively (Figure 3). Figure 3 View largeDownload slide Extent of perfusion defect using SD and ULD. LV, left ventricular; SD, standard protocol; ULD, ultra low-dose protocol. Figure 3 View largeDownload slide Extent of perfusion defect using SD and ULD. LV, left ventricular; SD, standard protocol; ULD, ultra low-dose protocol. The mean SSS, SRS, and SDS for SD vs. ULD examination were 7.2 vs. 7.1, 3.6 vs. 3.9, and 3.1 vs. 2.7, respectively (all P = NS). The difference in SSS between the two protocols was within one point in 35/56 patients (62.5%) and two or more in 21/56 patients (37.5%) (P = 0.095). Similarly, the difference in SDS was within one point in 37/56 patients (66%), within two points in 48/56 patients (85%), and two or more in 19/56 patients (34%) (P = 0.731). In vascular territories, the difference in SSS between the two protocols was within one point in 42/66 (75%), 46/56 (82%), and 47/56 (83%), respectively for the left anterior descending (LAD), circumflex (Cx), and right coronary artery (RCA) territories. Also, the difference in SDS was within one point between the two protocols in 35/56 (62.5%), 43/56 (76.7%), and 46/56 (82%), respectively in the LAD, Cx, and RCA territories. When applying these quantitative criteria in a dichotomous fashion, 24 of 27 patients with normal findings by SD protocol also returned normal by ULD examination. Also 23 of 29 patients with abnormal findings by SD protocol were equally classified abnormal by ULD. This translated into an agreement rate of 83.93% [kappa 0.68, 95% confidence interval (CI) 0.49–0.87] for the finding of a normal examination. Similarly, 24 of 29 patients with SD protocol showing no ischaemia were also not classified as non-ischaemic by ULD. And 21 of 27 patients with ischaemia by SD dose were classified as ischaemic by ULD. The agreement rate for the finding of ischaemia was 80.4% (kappa 0.61, 95% CI 0.40–0.81). Ejection fraction and volumes The values of EF and LV volumes obtained from SD and ULD protocol as well as the correlation are summarized in Table 2. For stress images, the mean EF, EDV, and ESV obtained from SD and ULD examination were 51.7 ± 15.9%, 99.1 ± 40.8 mL, 52.9 ± 38.7 mL and 54.3 ± 15.7%, 105.1 ± 46.3 mL, 53.8 ± 42.4 mL, respectively (P = 0.001). Table 2 Left ventricular ejection fraction and volumes Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 BA, Bland–Altman; EDV, left ventricular end diastolic volume; EF, left ventricular ejection fraction; ESV, left ventricular end systolic volume. Table 2 Left ventricular ejection fraction and volumes Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 Parameters Standard Ultra low-dose Correlation [r (P-value)] Intraclass correlation [k (P-value)] BA limits of agreement Stress study  EF (%) 51.7 ± 15.9 54.3 ± 15.7 0.90 (P = 0.001) 0.93 (P = 0.001) −7.4 to 12.5  EDV (mL) 99.1 ± 40.8 105.1 ± 46.3 0.94 (P = 0.001) 0.93 (P = 0.001) −14.0 to 25.9  ESV (mL) 52.9 ± 38.7 53.8 ± 42.4 0.97 (P = 0.001) 0.96 (P = 0.001) −19.1 to 20.8 Rest study  EF (%) 51.5 ± 16.59 55.6 ± 15.8 0.92 (P = 0.001) 0.91 (P = 0.001) −10.0 to 14.1  EDV (mL) 91.6 ± 41.5 103.4 ± 47.6 0.96 (P = 0.001) 0.96 (P = 0.001) −8.2 to 31.7  ESV (mL) 49.2 ± 39.5 51.5 ± 43.1 0.97 (P = 0.001) 0.97 (P = 0.001) −17.6 to 22.3 BA, Bland–Altman; EDV, left ventricular end diastolic volume; EF, left ventricular ejection fraction; ESV, left ventricular end systolic volume. For rest images, the mean EF, EDV, and ESV obtained from SD and ULD examination were 51.5 ± 16.59%, 91.6 ± 41.5 mL, 49.2 ± 39.5 mL and 55.6 ± 15.8%, 103.4 ± 47.6 mL, 51.5 ± 43.1 mL, respectively (P = 0.001). The correlation coefficients between SD and ULD examination at stress and rest for EF, EDV, and ESV were 0.90, 0.94, 0.97 and 0.92, 0.96, 0.97, respectively. The mean bias (BA limits of agreements) between SD and ULD examination for EF, EDV, and ESV was 2.5% (−7.4 to 12.5%), 5.9 mL (−14.0 to 25.9 mL), 0.8 mL (−19.1 to 20.8 mL) and 4.1% (−10.0 to 14.1%), 11.7 mL (−8.2 to 31.7 mL), 2.3 mL (−17.6 to 22.3 mL), respectively (Table 2 and Figure 4). Figure 4 View largeDownload slide Correlation and Bland–Altman plots of LVEF between standard dose and ultra low-dose at rest (A and B) and stress (C and D). Difference is standard minus ultra low-dose. LVEF, left ventricular ejection fraction. Figure 4 View largeDownload slide Correlation and Bland–Altman plots of LVEF between standard dose and ultra low-dose at rest (A and B) and stress (C and D). Difference is standard minus ultra low-dose. LVEF, left ventricular ejection fraction. Discussion The results of this study illustrate how the new generation of gamma camera with highly sensitive CZT detector technique may pave the way to a substantial decrease in the radiation exposure to the patient with maintained image quality. Although our protocol pushes the boundaries towards low-dose SPECT MPI, this is still on solid ground as the low-dose for stress MPI suggested in our ULD protocol is covered by the latest ASNC guidelines including reduced dose recommendations for newer technologies gamma camera.8 ULD images yielded clinical information comparable to that obtained from SD with regard to defect extent and severity, as well as volumes and function. The latter is important as the LVEF is a strong predictor of outcome and also due to the added value of wall motion and thickening information for discrimination of artefact from scar.19 Combining ULD stress and rest MP resulted in a 98% agreement with the SD for discriminating normal from abnormal scan and, thus, for detecting CAD. This compares favourably to test–retest agreement in large trials.4,20 The validity of the ULD protocol is further underlined by the fact that the differences in regional scores of ischaemic territories between SD and ULD was less or equalling one in the vast majority of patients and within two points in 85% of patients, which by the latter is considered as an appropriate cut-off value depicting clinical relevance.7,16,18 The ULD protocol enables coronary functional evaluation with radiation exposure to the patient in the range of modern non-invasive anatomic evaluation of the coronary arteries by CT,21,22 while it is lower than most values reported for CT perfusion imaging, which is currently considered an emerging tool for MPI.23 In this study an apparent drawback is the fact that the dose reduction was partly achieved at the cost of an increase in total scan time summing up to 30 min duration. However, this lies well within scan and protocol times required by other traditional MPI modalities. As the potential for increased workflow has been highlighted by the original publications of CZT equipped gamma cameras, through ultrafast acquisition protocols,9,24 to some extent this benefitted only to high through-put laboratories were camera time harboured an economic importance. Recent publication focusing on the dose reduction algorithm including this study7 offer the perspective, on top of improving patient and medical staff protection against ionizing radiations, to provide economic saves through reduced need in technetium generators regardless of their patient’s through-put. Limitations We acknowledge the following limitations. First, the fact that such protocol is somehow depending on optimal registration between the stress and rest studies. This might be problematic in restless patients in whom image subtraction might be less efficient. However, such patients would still benefit from half stress radiotracer administration, which was proved comparable to SD stress dose in this study, and conventional doubled or tripled rest radiotracer administration. Second, we compared the new MPI protocol to another established MPI study rather than choosing an anatomic standard of reference such as coronary angiography. This, however, should not be seen as major limitation as fundamental differences between physiological vs. anatomic evaluation of CAD exist.25–28 Comparison of a perfusion protocol vs. another perfusion protocol appears more meaningful and appropriate. Third, we did not measure how much of the 99mTc-tetrofosmin dose is stuck in the syringe and tube system. This may represent a minor issue when higher doses are used but makes more of an impact the lower the dose is injected while trying to maintain proportional counts. Fourth, our findings cannot be extrapolated in obese patients since they were excluded in our study. This population may represent an additional challenge for imaging with CZT gamma camera owing to the shorter field of view when compared with traditional gamma camera with potential truncation artefacts. Conclusion CZT cameras may enable reliable MPI scanning in patients with known or suspected CAD using protocols with about a factor 4-decrease in radiation dose exposure compared with traditional protocols. Acknowledgements We would like to thank Ennio Mueller, Edlira Loga, Myriam De Bloome, Sabrina Epp, and Patrick von Schultess for their excellent technical support. Funding This work was supported by a grant from the Swiss National Science Foundation (SNSF to P.A.K.). Conflict of interest: None declared. 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All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Jun 2, 2018

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