Anatomical and Functional Assessment of Coronary Artery Disease Using Whole-Heart Dynamic Computed Tomography

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PROJECT SUMMARY/ABSTRACT Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Fortunately, morbidity and mortality are significantly reduced when patients are risk stratified using computed tomography angiography (CTA) and treated appropriately with medical therapy or revascularization. Unfortunately, CTA is limited in that lesion severity is based solely on lesion morphology; hence, collateralization, calcification, and artifacts often confound diagnostic results. Visual grading of CAD also has high intra- and inter-observer variability, and often correlates poorly with myocardial ischemia, especially for intermediate severity focal disease (30-70% luminal narrowing), diffuse disease, and microvascular disease. Hence, CTA alone cannot fully characterize the true severity of CAD, and functional assessment techniques, such as dynamic computed tomography perfusion (CTP), are necessary, in conjunction with CTA, for more objective indication of CAD significance. Unfortunately, such dynamic CTP techniques systematically underestimate perfusion and deliver unacceptably high radiation doses per CAD exam, hampering their widespread clinical utility. Given the limitations of CTA and dynamic CTP, this proposal aims to validate an accurate, low-dose, CTA and dynamic CTP fusion technique based on first-pass analysis (FPA CTAP) for combined anatomical and functional assessment of CAD. The central hypothesis is that simultaneous acquisition of CTA and dynamic CTP data using a whole-heart CT scanner, two volume scans, and a single contrast injection will enable accurate, low-dose, vessel-specific myocardial perfusion measurement. Specifically, I aim to determine if vessel-specific myocardial perfusion can be accurately measured in 15 swine through retrospective implementation of the FPA CTAP technique. I also aim to determine if vessel-specific myocardial perfusion can be accurately measured in 15 more swine through low-dose prospective implementation of the FPA CTAP technique. By validating such a combined approach to CAD assessment, this research may ultimately reduce the contrast and radiation dose associated with CTA and dynamic CTP, while improving measurement accuracy, making anatomical and functional assessment of CAD more accessible and impactful to patients in need.