Hyperemia is induced by pharmacological stress agents . Intravenous adenosine is widely used in a continuous dose of 140 μg/kg/min for 2 or 3 min. Regadenoson has longer plasma half time than adenosine and is administered in a single agent. Also it is a selective adenosine 2A receptor agonist and can be used in patients with asthma or airway disease. Dobutamine, a myocardial beta-1 agonist, or dipyridamole, adenosine receptor blocker, is not commonly used (Table 31.1).

Static or snap-shot perfusion CT assesses myocardial contrast distribution in a single time and doable in most CT scanners with lesser radiation exposure to dynamic perfusion CT. With sophisticated mathematical modeling, dynamic perfusion CT enables direct quantification of myocardial blood flow (MBF), myocardial blood volume, and myocardial flow reserve (Table 31.2). Regarding the diagnostic performance, static perfusion CT showed sensitivity = 0.85 (95% confidence interval = 0.70–0.93), specificity = 0.81 (0.59–0.93), area under curve = 0.90 (0.87–0.92) [7]. A recent dynamic perfusion CT showed comparable performance compared to CMR (Table 31.3) [8–20]. Also perfusion CT is better suited for quantification of myocardial blood flow than perfusion MR. Based on the nuclear perfusion studies, the nominal value of resting myocardial blood flow is known to be 0.9 ml/μg/min. The cut-off value of hemodynamically significant stenosis in perfusion CT was reportedly 0.75–0.78 ml/μg/min [16].

Like the other fluid systems, blood flow in the cardiovascular system is ruled by the physical laws of mass conservation, momentum conservation, and energy conservation. Therefore it can be calculated by mathematical models. For patient-specific coronary circulation, 3-dimensional numerical models based on computational flow dynamics which can compute complex flow patterns are preferred to zero dimensional models or lumped parameter model which is employed in large systemic vessels. Computational FFR is derived based on the regional physical geometry, the boundary condition which is the behavior and properties at the boundaries of the region, and the physical laws of fluid in the region.

FFR can be described as a pressure gradient across stenotic segment during maximal hyperemia. Anatomical stenosis, myocardial mass, and microvascular resistance constitute FFR value and can be calculated from patient-specific sophisticated coronary arterial anatomical model, vessel-specific myocardial mass, and microvascular resistance which determine the outlet boundary condition [21, 22]. CT images provide patient-specific anatomy model of local geometry, individual coronary artery morphology, volume, and myocardial mass. From these data, cardiac output and baseline coronary blood flow can be calculated by using allometric scaling laws [23–25]. This computational approach was derived from a general model that describes the transport of essential materials through space-filling fractal branched networks, and is based on a form-function relationship [26]. The diameter-flow rate relation is determined according to Murray’s law [27] and Poiseuille’s equation, which considers shear stress on the endothelial surface and remodeling to maintain homeostasis [28]. Morphometry laws are also adapted to obtain the physiological resistance to flow aroused by coronary artery branches [29]. Microvascular resistance at baseline and during maximal hyperemia, which is fundamental for FFR measurement, can be approximated using population-based data on the effect of adenosine on coronary flow [30] (Fig. 31.3).

Landmark trials including DISCOVER-FLOW [31], DeFACTO [32], and NXT [33] showed that FFR-CT, a proprietary computational FFR, showed high diagnostic performance in discriminating ischemia in patients who had intermediate coronary artery stenosis. The NXT trial reported sensitivity and negative predictive value of FFR-CT in diagnosis of ischemia (defined as invasive FFR < 0.80) in patients with intermediate stenosis severity were 80% and 92%, respectively [33]. In a recent meta-analysis of FFR-CT based on 833 patients and 1377 vessels, FFR-CT showed a moderate diagnostic performance for identification of ischemic vessel with pooled sensitivity = 84% and specificity = 76% at a per-vessel basis [34] (Table 31.4). The PLATFORM study showed that a decision-making strategy using CCTA with FFR-CT was associated with clinical outcomes comparable to using invasive FFR and a 33% cost reduction [35]. Therefore, FFR-CT can effectively rule out intermediate lesions that cause ischemia and could also reduce the unnecessary ICA and invasive FFR.