Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552.

Evaluation of regional myocardial blood flow by conventional scintigraphic techniques is limited to the qualitative assessment of regional tracer distribution. Dynamic imaging with positron emission tomography allows the quantitative delineation of myocardial tracer kinetics and, hence, the measurement of physiologic processes such as myocardial blood flow. To test this hypothesis, positron emission tomographic imaging in combination with N-13 ammonia was performed at rest and after pharmacologically induced vasodilation in seven healthy volunteers. Myocardial and blood time-activity curves derived from regions of interest over the heart and ventricular chamber were fitted using a three compartment model for N-13 ammonia, yielding rate constants for tracer uptake and retention. Myocardial blood flow (K1) averaged 88 +/- 17 ml/min per 100 g at rest and increased to 417 +/- 112 ml/min per 100 g after dipyridamole infusion (0.56 mg/kg) and handgrip exercise. The coronary reserve averaged 4.8 +/- 1.3 and was not significantly different in the septal, anterior and lateral walls of the left ventricle. Blood flow values showed only a minor dependence on the correction for blood metabolites of N-13 ammonia. These data demonstrate that quantification of regional myocardial blood flow is feasible by dynamic positron emission tomographic imaging. The observed coronary flow reserve after dipyridamole is in close agreement with the results obtained by invasive techniques, indicating accurate flow estimates over a wide range. Thus, positron emission tomography may provide accurate and noninvasive definition of the functional significance of coronary artery disease and may allow the improved selection of patients for revascularization.

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				D. Baller, G. Notohamiprodjo, U. Gleichmann, J. Holzinger, R. Weise, and J. Lehmann Improvement in Coronary Flow Reserve Determined by Positron Emission Tomography After 6 Months of Cholesterol-Lowering Therapy in Patients With Early Stages of Coronary Atherosclerosis Circulation, June 8, 1999; 99(22): 2871 - 2875. [Abstract] [Full Text] [PDF]

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				G. Holmvang, S. Fry, H. A. Skopicki, S. A. Abraham, N. M. Alpert, A. J. Fischman, M. H. Picard, and H. Gewirtz Relation Between Coronary "Steal" and Contractile Function at Rest in Collateral-Dependent Myocardium of Humans With Ischemic Heart Disease Circulation, May 18, 1999; 99(19): 2510 - 2516. [Abstract] [Full Text] [PDF]

				O.-P. Pitkanen, P. Nuutila, O. T. Raitakari, K. Porkka, H. Iida, I. Nuotio, T. Ronnemaa, J. Viikari, M.-R. Taskinen, C. Ehnholm, et al. Coronary Flow Reserve in Young Men With Familial Combined Hyperlipidemia Circulation, April 6, 1999; 99(13): 1678 - 1684. [Abstract] [Full Text] [PDF]

				A. N. Kitsiou, S. L. Bacharach, M. L. Bartlett, G. Srinivasan, R. M. Summers, A. A. Quyyumi, and V. Dilsizian 13N-ammonia myocardial blood flow and uptake: Relation to functional outcome of asynergic regions after revascularization J. Am. Coll. Cardiol., March 1, 1999; 33(3): 678 - 686. [Abstract] [Full Text] [PDF]

				M. Guethlin, A. M. Kasel, K. Coppenrath, S. Ziegler, W. Delius, and M. Schwaiger Delayed Response of Myocardial Flow Reserve to Lipid-Lowering Therapy With Fluvastatin Circulation, February 2, 1999; 99(4): 475 - 481. [Abstract] [Full Text] [PDF]

				F. M. Bengel, M. Hauser, C. S. Duvernoy, A. Kuehn, S. I. Ziegler, J. C. Stollfuss, M. Beckmann, U. Sauer, O. Muzik, M. Schwaiger, et al. Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1955 - 1961. [Abstract] [Full Text] [PDF]

				A Al-Mohammad, I R Mahy, M Y Norton, G Hillis, J C Patel, P Mikecz, and S Walton Prevalence of hibernating myocardium in patients with severely impaired ischaemic left ventricles Heart, December 1, 1998; 80(6): 559 - 564. [Abstract] [Full Text]

				R M Quinlivan, R O Robinson, and M N Maisey Positron emission tomography in paediatric cardiology Arch. Dis. Child., December 1, 1998; 79(6): 520 - 522. [Full Text]

				M. J. Stevens, D. M. Raffel, K. C. Allman, F. Dayanikli, E. Ficaro, T. Sandford, D. M. Wieland, M. A. Pfeifer, and M. Schwaiger Cardiac Sympathetic Dysinnervation in Diabetes : Implications for Enhanced Cardiovascular Risk Circulation, September 8, 1998; 98(10): 961 - 968. [Abstract] [Full Text] [PDF]

				I. Yokoyama, T. Ohtake, S.-i. Momomura, K. Yonekura, N. Kobayakawa, T. Aoyagi, S. Sugiura, Y. Sasaki, and M. Omata Altered Myocardial Vasodilatation in Patients With Hypertriglyceridemia in Anatomically Normal Coronary Arteries Arterioscler. Thromb. Vasc. Biol., February 1, 1998; 18(2): 294 - 299. [Abstract] [Full Text] [PDF]

				J. P. Donnelly, D. M. Raffel, B. L. Shulkin, J. R. Corbett, E. L. Bove, R. S. Mosca, and T. J. Kulik Resting coronary flow and coronary flow reserve in human infants after repair or palliation of congenital heart defects as measured by positron emission tomography J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 103 - 110. [Abstract] [Full Text] [PDF]

				M.G. Niemeyer, A.F.M. Kuijper, J.G. Meeder, M.J.M. Cramer, A.J.M. Cleophas, E.E. van der Wall, and M. G. Niemeyer Comparison of Thallium Scintigraphy and Positron Emission Tomography Angiology, October 1, 1997; 48(10): 843 - 853. [Abstract] [PDF]

				H. G. Wolpers, W. Burchert, J. van den Hoff, R. Weinhardt, G.-J. Meyer, and P. R. Lichtlen Assessment of Myocardial Viability by Use of 11C-Acetate and Positron Emission Tomography : Threshold Criteria of Reversible Dysfunction Circulation, March 18, 1997; 95(6): 1417 - 1424. [Abstract] [Full Text]

				I. Yokoyama, T. Ohtake, S.-i. Momomura, J. Nishikawa, Y. Sasaki, and M. Omata Reduced Coronary Flow Reserve in Hypercholesterolemic Patients Without Overt Coronary Stenosis Circulation, December 15, 1996; 94(12): 3232 - 3238. [Abstract] [Full Text]

				D. D. Miller, T. J. Donohue, T. L. Wolford, M. J. Kern, S. R. Bergmann, C. M. Mechem, and J. J. Hartman Assessment of Blood Flow Distal to Coronary Artery Stenoses: Correlations Between Myocardial Positron Emission Tomography and Poststenotic Intracoronary Doppler Flow Reserve Circulation, November 15, 1996; 94(10): 2447 - 2454. [Abstract] [Full Text]

				H. A. Skopicki, S. A. Abraham, N. J. Weissman, A. K. Mukerjee, N. M. Alpert, A. J. Fischman, M. H. Picard, and H. Gewirtz Factors Influencing Regional Myocardial Contractile Response to Inotropic Stimulation: Analysis in Humans With Stable Ischemic Heart Disease Circulation, August 15, 1996; 94(4): 643 - 650. [Abstract] [Full Text]

				J. Czernin, R. J. Barnard, K. T. Sun, J. Krivokapich, E. Nitzsche, D. Dorsey, M. E. Phelps, and H. R. Schelbert Effect of Short-term Cardiovascular Conditioning and Low-Fat Diet on Myocardial Blood Flow and Flow Reserve Circulation, July 15, 1995; 92(2): 197 - 204. [Abstract] [Full Text]

				E. L. Fallen, C. Nahmias, A. Scheffel, G. Coates, R. Beanlands, and E. S. Garnett Redistribution of Myocardial Blood Flow With Topical Nitroglycerin in Patients With Coronary Artery Disease Circulation, March 1, 1995; 91(5): 1381 - 1388. [Abstract] [Full Text]

				N. G. Uren, J. A. Melin, B. De Bruyne, W. Wijns, T. Baudhuin, and P. G. Camici Relation between Myocardial Blood Flow and the Severity of Coronary-Artery Stenosis N. Engl. J. Med., June 23, 1994; 330(25): 1782 - 1788. [Abstract] [Full Text]

				B. L. Zaret and F. J. Wackers Nuclear Cardiology- Second of Two Parts N. Engl. J. Med., September 16, 1993; 329(12): 855 - 863. [Full Text]