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.
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