- Email: [email protected]
Gated myocardial perfusion imaging for the assessment of left ventricular function and volume: From SPECT to PET
EDITORIAL Gated myocardial perfusion imaging for the assessment of left ventricular function and volume: From SPECT to PET Tali Sharir, MD
See related article on p. 680 The clinical importance of left ventricular (LV) function in patients with coronary artery disease (CAD) has long been recognized. The first radionuclide method for quantitative assessment of the ejection fraction (EF) was electrocardiography (ECG)– gated planar equilibrium radionuclide angiography. Studies published in the 1980s and early 1990s, based on the database of Duke University (Durham, NC),1-3 demonstrated the powerful prognostic value of resting and exercise EF in CAD patients and showed that exercise EF provided incremental prognostic value over clinical, exercise, and angiographic data. The value of LV volume was less extensively evaluated during that period because of technical difficulties in its measurement, and therefore its prognostic power was less appreciated. White et al4 demonstrated that angiographically measured end-systolic volume (ESV) was a better predictor of survival compared with EF, end-diastolic volume (EDV), and coronary angiography data in patients after myocardial infarction. Similar results were reported by Hamer et al5 in patients with impaired LV function who were undergoing coronary artery bypass surgery. Since the early 1990s, the use of stress myocardial perfusion single photon emission computed tomography (SPECT) has been continually growing, to play a central role in both the diagnosis and risk stratification of patients with established or suspected CAD. The use of technetium 99m–labeled radiotracers and the addition of ECG gating to myocardial perfusion SPECT provided accurate and reproducible information on LV function6,7 and volume.8 In the early 2000s ECG-gated SPECT was estimated to be performed in approximately 80% of all
From the Nuclear Cardiology Unit, Procardia, Maccabi Health Services, Tel Aviv, Israel. Reprint requests: Tali Sharir, MD, Nuclear Cardiology Unit, Procardia, Maccabi Health Services, 156 Hyarkon St, Tel Aviv, Israel; [email protected]. J Nucl Cardiol 2007;14:631-3. 1071-3581/$32.00 Copyright © 2007 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2007.07.001
myocardial perfusion SPECT studies in the United States.9 The large bulk of LV function and volume data combined with perfusion data, obtained by routine gating of perfusion studies, enhanced the contribution of gated SPECT data to the diagnosis and risk stratification of patients with established or suspected CAD. Studies from the database of Cedars-Sinai Medical Center (Los Angeles, Calif) demonstrated that poststress EF and ESV, obtained by Tc-99m sestamibi gated SPECT, provided significant information over the extent and severity of perfusion defects in prediction of cardiac death.10 Furthermore, the ESV provided prognostic information over the poststress EF and improved stratification of patients into risk levels. A subsequent study by this group demonstrated that the poststress EF was the best predictor of cardiac death, whereas the amount of stress-induced ischemia was the strongest predictor of myocardial infarction.11 Thus the prognostic information incorporated in function and perfusion data is complementary. In the absence of coronary, valvular, or myocardial heart disease, LV volume correlates with body size. Moreover, LV volume in women is smaller than that in men, whereas EF is higher. Therefore ESV index and EDV index, obtained by normalizing volumes to the body surface area, are clinically more meaningful than nonindexed volumes. On the basis of the Cedars-Sinai database, the upper normal limit (mean ⫹2 SDs) of poststress ESV in individuals with a low prescan likelihood of CAD was 27 mL/m2 for women and 39 mL/m2 for men.12 The lower normal limit of the poststress EF was 51% in women and 43% in men. By use of these normal limits, poststress EF and ESV index by gated myocardial perfusion SPECT provided comparable incremental prognostic information over perfusion in women and men. In recent years the growing use of positron emission tomography (PET) cameras in oncology, as well as the advance in PET instrumentation, facilitated larger utilization of these cameras for cardiology purposes. Furthermore, the parallel advance in multislice computed tomography (CT) angiography and hybrid PET/CT systems allows noninvasive assessment of coronary anatomy and function during the same session. 631
632
Sharir Assessment of left ventricular function and volume
Few studies have evaluated the accuracy of rubidium 82 myocardial perfusion for the detection of CAD. Bateman et al13 demonstrated the superiority of gated Rb-82 myocardial perfusion PET over gated Tc-99m sestamibi SPECT in image quality, interpretive certainty, and diagnostic accuracy in 2 matched patient populations. Sampson et al14 showed high sensitivity (93%), specificity (83%), and normalcy rate (100%) for Rb-82 rest/stress myocardial perfusion PET/CT (for attenuation correction); however, these investigators did not assess the contribution of ECG gating to diagnostic accuracy. Several studies have evaluated the accuracy of automated LV function and volume by gated myocardial perfusion PET. Using the Cedars-Sinai quantitative gated SPECT (QGS) software, Schaefer et al15 demonstrated a highly linear correlation between LV EF and volume obtained by fluorine 18 fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging. These investigators found a small underestimation of EDV and overestimation of ESV, resulting in a small underestimation of EF. In a subsequent study Schaefer et al16,17 demonstrated comparable results of FDG-PET EF and volumes by 2 different automatic software programs (QGS and 4D-SPECT (University of Michigan, Ann Arbor, MI)), with some underestimation of EF by QGS compared with magnetic resonance imaging. Nitrogen 13 ammonia (NH3) has also been used in assessing LV function. Using a model-based analysis for estimation of endocardial and epicardial borders, Khorsand et al18 demonstrated excellent correlation between LV EF, EDV, ESV, and myocardial mass by N-13 NH3 PET and FDG PET. In a recent study Kanayama et al19 showed good correlation between LV EF, EDV, and ESV obtained by N-13 NH3 PET and left ventriculography, as well as good agreement of visually scored regional wall motion for the 2 methods. However, whether software developed for quantitative analysis of gated SPECT images can be applied to gated N-13 NH3 PET needs to be determined. In this issue of the Journal, Kanayama et al20 report the results of a comparison between gated N-13 NH3 PET and gated Tc-99m sestamibi SPECT for quantitative assessment of global and regional LV function, as well as LV volume, using QGS software, in 51 patients who underwent both nuclear tests. These investigators found excellent correlation between EDV, ESV, and EF by N-13 NH3 PET to the corresponding variables derived from Tc-99m sestamibi SPECT. There was some underestimation of EDV and ESV by N-13 NH3 PET, observed mainly in patients with a very large LV (EDV ⬎200 mL). No consistent underestimation or overestimation of EF was observed. They also found good correlation in quantitative segmental wall motion and thickening between the 2 imaging methods. Of note, wall thickening by N-13 NH3 PET was significantly lower than
Journal of Nuclear Cardiology September/October 2007
wall thickening by Tc-99m sestamibi SPECT in most of the segments, most likely as a result of the better spatial resolution and smaller influence of the partial-volume effect in PET imaging compared with SPECT. Therefore normal limits used for quantitative analysis of wall thickening by myocardial perfusion SPECT21 should be adjusted for PET imaging. In addition, the assessment of gender-specific normal limits of EF, ESV index, and EDV index is required for the clinical use of these indices. The future for PET imaging in cardiology is promising. The possibility to assess relative myocardial perfusion, quantitative ventricular volume and function, and myocardial flow reserve in 1 session, as well as the option for metabolic assessment (if combined with FDG), has the potential of improving the diagnosis and management of patients with CAD. Acknowledgment The author has indicated he has no financial conflicts of interest.
References 1. Lee KL, Pryor DB, Pieper KS, Harrell FE, Califf RM, Mark DB. Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables. Circulation 1990;82:1705-17. 2. Jones RH, Johnson SH, Bigelow C, Pieper KS, Coleman RE, Cobb FR, et al. Exercise radionuclide angiocardiography predicts cardiac death in patients with coronary artery disease. Circulation 1991; 84:I52-8. 3. Pryor DB, Harrell FE, Lee KL, Rosati RA, Coleman RE, Cobb FR, et al. Prognostic indicators from radionuclide angiography in medically treated patients with coronary artery disease. Am J Cardiol 1984;53:18-22. 4. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987;76:44-51. 5. Hamer AW, Takayama M, Abraham KA, Roche AH, Kerr AR, Williams BF, et al. End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Circulation 1994;90:2899-904. 6. Germano G, Kiat H, Kavanagh PB, Moriel M, Mazzanti M, Su HT, et al. Automatic quantification of ejection fraction from gated myocardial perfusion SPECT. J Nucl Med 1995;36:2138-47. 7. Johnson LL, Verdesca SA, Aude WY, Xavier RC, Nott LT, Campanella MW, et al. Postischemic stunning can affect left ventricular ejection fraction and regional wall motion on poststress gated sestamibi tomograms. J Am Coll Cardiol 1997;30: 1641-8. 8. Iskandrian AE, Germano G, VanDecker W, Ogliby JD, Wolf N, Mintz R, et al. Validation of left ventricular volume measurements by gated SPECT 99mTc-labeled sestamibi imaging. J Nucl Cardiol 1998;5:574-8. 9. Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging— executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines
Journal of Nuclear Cardiology Volume 14, Number 5;631-3
10.
11.
12.
13.
14.
15.
(ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol 2003;42:1318-33. Sharir T, Germano G, Kavanagh PB, Lai S, Cohen I, Lewin HC, et al. Incremental prognostic value of post-stress left ventricular ejection fraction and volume by gated myocardial perfusion single photon emission computed tomography. Circulation 1999;100: 1035-42. Sharir T, Germano G, Kang X, Lewin HC, Miranda R, Cohen I, et al. Prediction of myocardial infarction versus cardiac death by gated myocardial perfusion SPECT: risk stratification by the amount of stress-induced ischemia and the poststress ejection fraction. J Nucl Med 2001;42:831-7. Sharir T, Kang X, Germano G, Bax JJ, Shaw LJ, Gransar H, et al. Prognostic value of poststress left ventricular volume and ejection fraction by gated myocardial perfusion SPECT in women and men: gender-related differences in normal limits and outcomes. J Nucl Cardiol 2006;13:495-506. Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA, Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol 2006;13:24-33. Sampson UK, Dorbala S, Limaye A, Kwong R, Di Carli MF. Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. J Am Coll Cardiol 2007;49:1052-8. Schaefer WM, Lipke CS, Nowak B, Kaiser HJ, Buecker A, Krombach GA, et al. Validation of an evaluation routine for left ventricular volumes, ejection fraction and wall motion from gated
Sharir Assessment of left ventricular function and volume
16.
17.
18.
19.
20.
21.
633
cardiac FDG PET: a comparison with cardiac magnetic resonance imaging. Eur J Nucl Med Mol Imaging 2004;30:545-53. Schaefer WM, Lipke CS, Nowak B, Kaiser HJ, Reinartz P, Buecker A, et al. Validation of QGS and 4D-MSPECT for quantification of left ventricular volumes and ejection fraction from gated 18F-FDG PET: comparison with cardiac MRI. J Nucl Med 2004;45:74-9. Ficaro EP, Quaife RA, Kritzman JN, Corbett JR. Accuracy and reproducibility of 3D-MSPECT for estimating left ventricular ejection fraction in patients with severe perfusion abnormalities [abstract]. Circulation 1999;100(suppl):I26. Khorsand A, Graf S, Eidherr H, Wadsak W, Kletter K, Sochor H, et al. Gated cardiac 13N-NH3 PET for assessment of left ventricular volumes, mass, and ejection fraction: comparison with electrocardiography-gated 18F-FDG PET. J Nucl Med 2005; 46:2009-13. Kanayama S, Matsunari I, Hirayama A, Kitayama M, Matsudaira M, Yoneyama T, et al. Assessment of global and regional left ventricular function by electrocardiographic gated N-13 ammonia positron emission tomography in patients with coronary artery disease. Circ J 2005;69:177-82. Kanayama S, Matsunari I, Kajinami KComparison of gated N-13 ammonia PET and gated Tc-99m sestamibi SPECT for quantitative analysis of global and regional left ventricular function. J Nucl Cardiol 2007;14:680-7. Sharir T, Berman DS, Waechter PB, Areeda J, Kavanagh PB, Gerlach J, et al. Quantitative analysis of regional motion and thickening by gated myocardial perfusion SPECT: normal heterogeneity and criteria for abnormality. J Nucl Med 2001; 42:1630-8.
See related article on p. 680 The clinical importance of left ventricular (LV) function in patients with coronary artery disease (CAD) has long been recognized. The first radionuclide method for quantitative assessment of the ejection fraction (EF) was electrocardiography (ECG)– gated planar equilibrium radionuclide angiography. Studies published in the 1980s and early 1990s, based on the database of Duke University (Durham, NC),1-3 demonstrated the powerful prognostic value of resting and exercise EF in CAD patients and showed that exercise EF provided incremental prognostic value over clinical, exercise, and angiographic data. The value of LV volume was less extensively evaluated during that period because of technical difficulties in its measurement, and therefore its prognostic power was less appreciated. White et al4 demonstrated that angiographically measured end-systolic volume (ESV) was a better predictor of survival compared with EF, end-diastolic volume (EDV), and coronary angiography data in patients after myocardial infarction. Similar results were reported by Hamer et al5 in patients with impaired LV function who were undergoing coronary artery bypass surgery. Since the early 1990s, the use of stress myocardial perfusion single photon emission computed tomography (SPECT) has been continually growing, to play a central role in both the diagnosis and risk stratification of patients with established or suspected CAD. The use of technetium 99m–labeled radiotracers and the addition of ECG gating to myocardial perfusion SPECT provided accurate and reproducible information on LV function6,7 and volume.8 In the early 2000s ECG-gated SPECT was estimated to be performed in approximately 80% of all
From the Nuclear Cardiology Unit, Procardia, Maccabi Health Services, Tel Aviv, Israel. Reprint requests: Tali Sharir, MD, Nuclear Cardiology Unit, Procardia, Maccabi Health Services, 156 Hyarkon St, Tel Aviv, Israel; [email protected]. J Nucl Cardiol 2007;14:631-3. 1071-3581/$32.00 Copyright © 2007 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2007.07.001
myocardial perfusion SPECT studies in the United States.9 The large bulk of LV function and volume data combined with perfusion data, obtained by routine gating of perfusion studies, enhanced the contribution of gated SPECT data to the diagnosis and risk stratification of patients with established or suspected CAD. Studies from the database of Cedars-Sinai Medical Center (Los Angeles, Calif) demonstrated that poststress EF and ESV, obtained by Tc-99m sestamibi gated SPECT, provided significant information over the extent and severity of perfusion defects in prediction of cardiac death.10 Furthermore, the ESV provided prognostic information over the poststress EF and improved stratification of patients into risk levels. A subsequent study by this group demonstrated that the poststress EF was the best predictor of cardiac death, whereas the amount of stress-induced ischemia was the strongest predictor of myocardial infarction.11 Thus the prognostic information incorporated in function and perfusion data is complementary. In the absence of coronary, valvular, or myocardial heart disease, LV volume correlates with body size. Moreover, LV volume in women is smaller than that in men, whereas EF is higher. Therefore ESV index and EDV index, obtained by normalizing volumes to the body surface area, are clinically more meaningful than nonindexed volumes. On the basis of the Cedars-Sinai database, the upper normal limit (mean ⫹2 SDs) of poststress ESV in individuals with a low prescan likelihood of CAD was 27 mL/m2 for women and 39 mL/m2 for men.12 The lower normal limit of the poststress EF was 51% in women and 43% in men. By use of these normal limits, poststress EF and ESV index by gated myocardial perfusion SPECT provided comparable incremental prognostic information over perfusion in women and men. In recent years the growing use of positron emission tomography (PET) cameras in oncology, as well as the advance in PET instrumentation, facilitated larger utilization of these cameras for cardiology purposes. Furthermore, the parallel advance in multislice computed tomography (CT) angiography and hybrid PET/CT systems allows noninvasive assessment of coronary anatomy and function during the same session. 631
632
Sharir Assessment of left ventricular function and volume
Few studies have evaluated the accuracy of rubidium 82 myocardial perfusion for the detection of CAD. Bateman et al13 demonstrated the superiority of gated Rb-82 myocardial perfusion PET over gated Tc-99m sestamibi SPECT in image quality, interpretive certainty, and diagnostic accuracy in 2 matched patient populations. Sampson et al14 showed high sensitivity (93%), specificity (83%), and normalcy rate (100%) for Rb-82 rest/stress myocardial perfusion PET/CT (for attenuation correction); however, these investigators did not assess the contribution of ECG gating to diagnostic accuracy. Several studies have evaluated the accuracy of automated LV function and volume by gated myocardial perfusion PET. Using the Cedars-Sinai quantitative gated SPECT (QGS) software, Schaefer et al15 demonstrated a highly linear correlation between LV EF and volume obtained by fluorine 18 fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging. These investigators found a small underestimation of EDV and overestimation of ESV, resulting in a small underestimation of EF. In a subsequent study Schaefer et al16,17 demonstrated comparable results of FDG-PET EF and volumes by 2 different automatic software programs (QGS and 4D-SPECT (University of Michigan, Ann Arbor, MI)), with some underestimation of EF by QGS compared with magnetic resonance imaging. Nitrogen 13 ammonia (NH3) has also been used in assessing LV function. Using a model-based analysis for estimation of endocardial and epicardial borders, Khorsand et al18 demonstrated excellent correlation between LV EF, EDV, ESV, and myocardial mass by N-13 NH3 PET and FDG PET. In a recent study Kanayama et al19 showed good correlation between LV EF, EDV, and ESV obtained by N-13 NH3 PET and left ventriculography, as well as good agreement of visually scored regional wall motion for the 2 methods. However, whether software developed for quantitative analysis of gated SPECT images can be applied to gated N-13 NH3 PET needs to be determined. In this issue of the Journal, Kanayama et al20 report the results of a comparison between gated N-13 NH3 PET and gated Tc-99m sestamibi SPECT for quantitative assessment of global and regional LV function, as well as LV volume, using QGS software, in 51 patients who underwent both nuclear tests. These investigators found excellent correlation between EDV, ESV, and EF by N-13 NH3 PET to the corresponding variables derived from Tc-99m sestamibi SPECT. There was some underestimation of EDV and ESV by N-13 NH3 PET, observed mainly in patients with a very large LV (EDV ⬎200 mL). No consistent underestimation or overestimation of EF was observed. They also found good correlation in quantitative segmental wall motion and thickening between the 2 imaging methods. Of note, wall thickening by N-13 NH3 PET was significantly lower than
Journal of Nuclear Cardiology September/October 2007
wall thickening by Tc-99m sestamibi SPECT in most of the segments, most likely as a result of the better spatial resolution and smaller influence of the partial-volume effect in PET imaging compared with SPECT. Therefore normal limits used for quantitative analysis of wall thickening by myocardial perfusion SPECT21 should be adjusted for PET imaging. In addition, the assessment of gender-specific normal limits of EF, ESV index, and EDV index is required for the clinical use of these indices. The future for PET imaging in cardiology is promising. The possibility to assess relative myocardial perfusion, quantitative ventricular volume and function, and myocardial flow reserve in 1 session, as well as the option for metabolic assessment (if combined with FDG), has the potential of improving the diagnosis and management of patients with CAD. Acknowledgment The author has indicated he has no financial conflicts of interest.
References 1. Lee KL, Pryor DB, Pieper KS, Harrell FE, Califf RM, Mark DB. Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables. Circulation 1990;82:1705-17. 2. Jones RH, Johnson SH, Bigelow C, Pieper KS, Coleman RE, Cobb FR, et al. Exercise radionuclide angiocardiography predicts cardiac death in patients with coronary artery disease. Circulation 1991; 84:I52-8. 3. Pryor DB, Harrell FE, Lee KL, Rosati RA, Coleman RE, Cobb FR, et al. Prognostic indicators from radionuclide angiography in medically treated patients with coronary artery disease. Am J Cardiol 1984;53:18-22. 4. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987;76:44-51. 5. Hamer AW, Takayama M, Abraham KA, Roche AH, Kerr AR, Williams BF, et al. End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Circulation 1994;90:2899-904. 6. Germano G, Kiat H, Kavanagh PB, Moriel M, Mazzanti M, Su HT, et al. Automatic quantification of ejection fraction from gated myocardial perfusion SPECT. J Nucl Med 1995;36:2138-47. 7. Johnson LL, Verdesca SA, Aude WY, Xavier RC, Nott LT, Campanella MW, et al. Postischemic stunning can affect left ventricular ejection fraction and regional wall motion on poststress gated sestamibi tomograms. J Am Coll Cardiol 1997;30: 1641-8. 8. Iskandrian AE, Germano G, VanDecker W, Ogliby JD, Wolf N, Mintz R, et al. Validation of left ventricular volume measurements by gated SPECT 99mTc-labeled sestamibi imaging. J Nucl Cardiol 1998;5:574-8. 9. Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging— executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines
Journal of Nuclear Cardiology Volume 14, Number 5;631-3
10.
11.
12.
13.
14.
15.
(ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol 2003;42:1318-33. Sharir T, Germano G, Kavanagh PB, Lai S, Cohen I, Lewin HC, et al. Incremental prognostic value of post-stress left ventricular ejection fraction and volume by gated myocardial perfusion single photon emission computed tomography. Circulation 1999;100: 1035-42. Sharir T, Germano G, Kang X, Lewin HC, Miranda R, Cohen I, et al. Prediction of myocardial infarction versus cardiac death by gated myocardial perfusion SPECT: risk stratification by the amount of stress-induced ischemia and the poststress ejection fraction. J Nucl Med 2001;42:831-7. Sharir T, Kang X, Germano G, Bax JJ, Shaw LJ, Gransar H, et al. Prognostic value of poststress left ventricular volume and ejection fraction by gated myocardial perfusion SPECT in women and men: gender-related differences in normal limits and outcomes. J Nucl Cardiol 2006;13:495-506. Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA, Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol 2006;13:24-33. Sampson UK, Dorbala S, Limaye A, Kwong R, Di Carli MF. Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. J Am Coll Cardiol 2007;49:1052-8. Schaefer WM, Lipke CS, Nowak B, Kaiser HJ, Buecker A, Krombach GA, et al. Validation of an evaluation routine for left ventricular volumes, ejection fraction and wall motion from gated
Sharir Assessment of left ventricular function and volume
16.
17.
18.
19.
20.
21.
633
cardiac FDG PET: a comparison with cardiac magnetic resonance imaging. Eur J Nucl Med Mol Imaging 2004;30:545-53. Schaefer WM, Lipke CS, Nowak B, Kaiser HJ, Reinartz P, Buecker A, et al. Validation of QGS and 4D-MSPECT for quantification of left ventricular volumes and ejection fraction from gated 18F-FDG PET: comparison with cardiac MRI. J Nucl Med 2004;45:74-9. Ficaro EP, Quaife RA, Kritzman JN, Corbett JR. Accuracy and reproducibility of 3D-MSPECT for estimating left ventricular ejection fraction in patients with severe perfusion abnormalities [abstract]. Circulation 1999;100(suppl):I26. Khorsand A, Graf S, Eidherr H, Wadsak W, Kletter K, Sochor H, et al. Gated cardiac 13N-NH3 PET for assessment of left ventricular volumes, mass, and ejection fraction: comparison with electrocardiography-gated 18F-FDG PET. J Nucl Med 2005; 46:2009-13. Kanayama S, Matsunari I, Hirayama A, Kitayama M, Matsudaira M, Yoneyama T, et al. Assessment of global and regional left ventricular function by electrocardiographic gated N-13 ammonia positron emission tomography in patients with coronary artery disease. Circ J 2005;69:177-82. Kanayama S, Matsunari I, Kajinami KComparison of gated N-13 ammonia PET and gated Tc-99m sestamibi SPECT for quantitative analysis of global and regional left ventricular function. J Nucl Cardiol 2007;14:680-7. Sharir T, Berman DS, Waechter PB, Areeda J, Kavanagh PB, Gerlach J, et al. Quantitative analysis of regional motion and thickening by gated myocardial perfusion SPECT: normal heterogeneity and criteria for abnormality. J Nucl Med 2001; 42:1630-8.