Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. As a risk factor, CAD and its resultant ischemic cardiomyopathy are strongly predicative of future cardiac events. While coronary computed tomography (CT) angiography is a powerful tool for assessing CAD risk, it is fundamentally limited in that it can only assess the morphological severity of segmental CAD, but cannot define the physiological severity of concurrent mutli-vessel, diffuse, and microvascular disease. Hence, guidelines recommend additional physiological assessment of CAD, in conjunction with CT angiography, for more objective indication of patient risk. The primary modalities used for physiological assessment are single-photon emission computed tomography (SPECT), stress echocardiography, cardiac magnetic resonance (CMR), static positron emission tomography (PET), and static CT. However, such modalities only provide metrics of relative perfusion; hence, they still cannot appreciate the true physiological severity of multiform CAD. Fortunately, absolute perfusion measurement with dynamic CT can overcome these limitations, where the spatial distribution of absolute rest and stress perfusion in mL/min/g combined with physiological cutoff thresholds can be used to reliably stratify patient risk and properly guide intervention. Nevertheless, current dynamic CT perfusion techniques are known to be quantitatively inaccurate and deliver unacceptably high effective radiation doses per imaging exam, precluding their widespread clinical use. As such, there is a major unmet clinical need for an accurate, low-dose CT technique for combined morphological and physiological assessment of multiform CAD.
This dissertation research addresses that unmet clinical need through the development, validation, and preliminary clinical translation of an accurate, low-dose, comprehensive cardiac CT technique based on first-pass analysis (FPA). The comprehensive technique can accurately assess vessel-specific stress and rest perfusion, while simultaneously providing cardiac functional analysis (CFA), CT angiography, and coronary flow reserve (CFR), respectively. Thus, morphological and physiological assessment of CAD is feasible using a single low-dose exam, making comprehensive CT-based assessment of multiform CAD more accurate, accessible, and impactful to patients in need.