Improved quantitative planar and single photon emission tomographic (SPECT) imaging techniques permitting more accurate assessment of regional myocardial perfusion and viability in patients with coronary artery disease are needed. The objectives of this research proposal are, (1) to acquire further knowledge of myocardial transport kinetics of thallium-210 (Tl-210) and technetium-99m methoxy isobutyl isonitrile (MIBI) under normal conditions, during transient or sustained ischemia, after total coronary occlusion and after coronary reperfusion in both animals and humans, and (2) to develop and test more optimum imaging methods for quantitation of in vivo risk area and distinguishing viable from irreversibly injured myocardium. In the experimental protocols, the following hypotheses are to be tested: (1) quantitation of Tl-201 uptake and redistribution at rest will be more accurate for identifying viable but underperfused myocardium distal to a coronary stenosis, than MIBI uptake; (2) MIBI uptake patterns will underestimate degree of myocardial salvage during experimental infarction when administered after reperfusion in the presence of a severe residual stenosis; (3) MIBI given too early after reperfusion will reflect reperfusion flow more than viability resulting in overestimation of degree of myocardial salvage; and, (4) risk area in the distribution of an occluded coronary artery in intact animals can accurately be quantitated by SPECT MIBI imaging, and dual simultaneous imaging of MIBI risk area and Tl- 201 redistribution should enhance detection of viability. In animal experiments, regional flow is measured by radioactive microspheres, in vivo risk areas by MIBI autoradiography and anatomic risk area infarct size by histochemical techniques. Parallel clinical research protocols are designed: (1) to differentiate ischemia from scar during exercise scintigraphy using split dose injections of MIBI 2 hrs apart; (2) to develop dual simultaneous imaging techniques with Tl-201 and MIBI to better quantitate in vivo risk area and provide more reliable detection of viable but jeopardized myocardium; (3) to develop quantitative SPECT methods for MIBI imaging to critically compare with similar planar techniques for detecting and determining extent of physiologically important CAD; (4) to improve detection of myocardial viability with Tl-201 by quantitative serial assessment of early exchange kinetics and to compare this approach with 24-hr delayed redistribution imaging; and, (5) to determine the value of simultaneous quantitation of regional wall motion and systolic thickening on ECG-gated MIBI perfusion studies using Principal Components Analysis. It is expected that this research will lead to improved applications of Tl- 201 and MIBI imaging for noninvasive detection of ischemia and assessment of myocardial viability.
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