An accurate, rapid, automated method for regional quantitation of rest-stress cardiac PET has been developed which analyzes the size, intensity, statistical significance in comparison to normal, changes in perfusion defects and provides regional measures of both relative and absolute flow reserve for assessing regional or """"""""balanced"""""""" coronary artery stenoses, diffuse small vessel disease, and/or response to dipyridamole. To extend these basic concepts to diagnostic perfusion imaging, to validate the automated quantitative PET method experimentally, to confirm its clinical accuracy and to compare it with current standard SPECT thallium imaging, the following hypotheses would be tested true or false by the null hypothesis: 1) In dogs the severity of LCx coronary artery stenosis alone or of combined LCx and proximal LAD stenoses of disparate and """"""""balanced"""""""" severity is accurately determined by rest-dipyridamole PET using the automated quantification of relative radiotracer distribution on stress images, reflecting relative flow reserve, and absolute activity ratio of stress/rest images, reflecting absolute coronary flow reserve, as compared to flowmeter and microsphere measurements; 2) In 250 patients with rest-dipyridamole stress PET scans on file, the applicant's newly completed automated PET analysis of relative radiotracer distribution on stress images and regional absolute activity ratio of stress/rest images correlates closely with and predicts stenosis severity in retrospective, blinded comparison to quantitative coronary arteriography done in every patient; 3) In 200 patients prospectively undergoing diagnostic cardiac catherization and exercise thallium SPECT, dipyridamole stress PET provides markedly better diagnostic accuracy, localization and measures of severity in direct comparison to thallium SPECT by blinded readers, as compared to quantitative coronary arteriography; and 4) In prospective experiments, regional relative and absolute coronary flow reserve are accurately predicated respectively, from relative activity distribution on stress images and regional absolute activity ratio on stress/rest PET images using an uptake-perfusion model based on the applicant's previous experimentally observed relation between radiotracer uptake reserve and flow reserve accounting for falling myocardial extraction of perfusion tracer at high flows.
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