A noninvasive, accurate, economical method to screen for coronary artery disease and/or assess its severity in symptomatic or asymptomatic individuals would permit therapy to reverse or slow progression of coronary atheroma and prevent acute myocardial infarction or sudden death, sixty percent of which occur with no prior symptoms. We have shown that the sensitivity and specificity for diagnosis of moderate to severe coronary artery disease by standard positron emission tomography of Rb-82 or N-13 ammonia uptake (residue function) are 98% and 100% respectively in symptomatic or asymptomatic man. However the sensitivity for detecting mild coronary artery disease in the range of 40-55% diameter narrowing is only 52%. Therefore, the specific aims of this proposal are to confirm definitively in more animal and human studies under different physiologic conditions and over a wide range of coronary flows the hypotheses that: (a) peak myocardial uptake after bolus iv injection of Rb-82 or N-13 ammonia occurs before significant venous egress of tracer from the field, thereby proving the validity of our extraction and first pass models, which are the basis of early phase myocardial perfusion imaging. (b) early phase myocardial perfusion images by positron emission tomography accurately, reproducibly, and quantitatively show relative myocardial flow distribution as measured by microspheres and electromagnetic flow meter in dogs. (c) quantitative severity of stress induced defects on early phase myocardial perfusion images by PET quantitatively relate to and accurately predict stenosis severity in man defined in terms of coronary stenosis flow reserve by automated, quantitative, arteriographic analysis taking into account all stenosis dimensions. d) early phase myocardial perfusion imaging by PET is feasible as a clinical routine and improves diagnostic sensitivity and specificity to 98% or greater for stenoses in the range of 40-55% diameter narrowing in man, comparable to the current sensitivity for moderate to severe lesions. The project will therefore result in a final, routine, quantitative, clinically validated screening method for diagnosing and quantifying severity of coronary artery disease in symptomatic or asymptomatic man for stenoses ranging down to 40-55% diameter narrowing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL026862-07
Application #
3338768
Study Section
Cardiovascular Study Section (CVA)
Project Start
1980-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Yoshida, K; Mullani, N; Gould, K L (1996) Coronary flow and flow reserve by PET simplified for clinical applications using rubidium-82 or nitrogen-13-ammonia. J Nucl Med 37:1701-12
Gould, K L (1994) Reversal of coronary atherosclerosis. Clinical promise as the basis for noninvasive management of coronary artery disease. Circulation 90:1558-71
Gould, K L; Martucci, J P; Goldberg, D I et al. (1994) Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing coronary endothelium. Circulation 89:1530-8
Fleming, R M; Harrington, G M; Gibbs, H R et al. (1994) Quantitative coronary arteriography and its assessment of atherosclerosis. Part I. Examining the independent variables. Angiology 45:829-33
Fleming, R M; Harrington, G M (1994) Quantitative coronary arteriography and its assessment of atherosclerosis. Part II. Calculating stenosis flow reserve from percent diameter stenosis. Angiology 45:835-40
Seiler, C; Kirkeeide, R L; Gould, K L (1993) Measurement from arteriograms of regional myocardial bed size distal to any point in the coronary vascular tree for assessing anatomic area at risk. J Am Coll Cardiol 21:783-97
Yoshida, K; Gould, K L (1993) Quantitative relation of myocardial infarct size and myocardial viability by positron emission tomography to left ventricular ejection fraction and 3-year mortality with and without revascularization. J Am Coll Cardiol 22:984-97
Seiler, C; Kirkeeide, R L; Gould, K L (1992) Basic structure-function relations of the epicardial coronary vascular tree. Basis of quantitative coronary arteriography for diffuse coronary artery disease. Circulation 85:1987-2003
Gould, K L; Ornish, D; Kirkeeide, R et al. (1992) Improved stenosis geometry by quantitative coronary arteriography after vigorous risk factor modification. Am J Cardiol 69:845-53
Gould, K L (1992) Quantitative analysis of coronary artery restenosis after coronary angioplasty--has the rose lost its bloom? J Am Coll Cardiol 19:946-7

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