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CT Assessment of Myocardial Perfusion and Fractional Flow Reserve in Coronary Artery Disease: A Review of Current Clinical Evidence and Recent Developments

Coronary computed tomography angiography (CCTA) is routinely used for anatomical assessment of coronary artery disease (CAD). However, invasive measurement of fractional flow reserve (FFR) is the current gold standard for the diagnosis of hemodynamically significant CAD. CT-derived FFRCT and CT perfusion are two emerging techniques that can provide a functional assessment of CAD for risk stratification and clinical decision making. Several clinical studies have shown that the diagnostic performance of concomitant CCTA and functional CT assessment for detecting hemodynamically significant CAD is at least non-inferior to that of other routinely used imaging modalities. This article aims to review the current clinical evidence and recent developments in functional CT techniques.


INTRODUCTION
value and specificity of CCTA are mediocre [1,2] due to the blooming and beam-hardening artifacts emanating from calcified plaques, which make image interpretation more difficult. In addition, similar to ICA, CCTA provides morphological assessment of the coronary arteries but cannot offer functional information regarding ischemia in the downstream myocardium, which is critical for decision-making on subsequent treatments, including optimal medical therapy and invasive revascularization interventions.
Single-photon emission computed tomography (SPECT) plays an essential role in detecting myocardial ischemia and provides robust prognostic information [5,6]. However, limitations such as being qualitative and low in spatial resolution have affected the diagnostic performance of SPECT in assessing balanced ischemia and differentiating between subendocardial and transmural perfusion defects. However, the most recent cardiology guidelines consider fractional flow reserve (FFR) as the gold standard for the functional assessment of CAD [7,8]. Consequently, cardiac imagers are keen to compare non-invasive functional imaging modalities with FFR. In this paper, we review three Korean  kjronline.org functional CT techniques, including static and dynamic CT perfusion (CTP) and CT-derived FFRCT, to assess myocardial ischemia in patients with known or suspected CAD. The current clinical evidence and recent developments in each technique will also be discussed.

Gold Standard of Functional Assessment of CAD
FFR is defined as the ratio of the post-stenotic blood pressure to the pre-stenotic blood pressure in a CAD during maximal hyperemia [9]. FFR can be measured with a pressure wire during ICA to evaluate the hemodynamic significance of stenosis. An FFR value of ≤ 0.80, has excellent diagnostic accuracy (> 90%) for identifying coronary stenosis that causes myocardial ischemia. The landmark FAME (FFR vs. angiography for multivessel evaluation) study [10] revealed that in the FFR-guided percutaneous coronary intervention (PCI) group, drug-eluting stents were deployed at the ischemia-induced lesion with an FFR value of ≤ 0.8. The results revealed favorable clinical outcomes in these patients, as evidenced by a significant decrease in major adverse cardiac events (MACE). Thus, FFR-guided PCI should be the standard protocol for reducing the number of stented arteries and using fewer resources. The series of articles based on the FAME study set up a cornerstone for interventional cardiology. In cases with ambiguous results from nuclear medicine, FFR is mandatory for decision making instead of relying on angiographic findings alone. However, there are well-documented limitations of invasive FFR. For example, FFR may not be reliable in patients with LM or recent myocardial infarction [11]. However, invasive FFR plays an essential role in decision-making and prognostic evaluation. Currently, no studies with largescale comparisons of invasive and non-invasive assessments of ischemia are available [12]. Interestingly, the results of the recently published ISCHEMIA trial demonstrated no significant difference in reducing cardiovascular events in patients with moderate or severe ischemia between the initial invasive and conservative strategies [13]. This has led to ischemia-driven intervention, which has been the cornerstone of CAD management for decades, and has more recently, become a matter of debate.

Principle of CT Myocardial Perfusion
CTP has been established as a useful imaging tool for functional assessment in patients with ischemic stroke [14]. Compared to other organs, the application of CTP for functional evaluation of heart diseases has been relatively limited, partially because of the technical challenges arising from cardiac motion and beam-hardening artifacts [15].
With the improvement of gantry rotation speed, detector coverage, and image reconstruction algorithms, stateof-the-art clinical CT scanners are capable of performing CT myocardial perfusion imaging robustly to provide incremental diagnostic value to CCTA for a comprehensive anatomic and functional evaluation of CAD in a single cardiac CT test. CCTA should be performed first as a gatekeeper, and CTP should be acquired as an "add-on" scan to CCTA to detect intermediate lesions. There should be a sufficient wait time (10 minutes or longer) between the CCTA and CTP scans to ensure clearance of contrast and nitroglycerin prior to the CTP scan. Moreover, intravenous administration of a vasodilator, most commonly adenosine and dipyridamole, is necessary for CT myocardial perfusion imaging. More recently, regadenoson has been used as a vasodilator, with a shorter administration time and reduced side effects in patients with asthma or chronic obstructive pulmonary disease [16].

Static CTP
Similar to the assessment of myocardial ischemia with first-pass cardiac magnetic resonance (CMR) and SPECT [17], static CTP assesses the relative distribution of myocardial blood flow (MBF) based on the signal (X-ray attenuation) differences in different regions of the myocardium. Static CTP assesses myocardial perfusion at a single time point during the first pass of contrast in the myocardium [18]. The optimal acquisition time for static CTP is approximately 2 to 10 seconds after the time to peak enhancement of the ascending aorta determined from the test bolus scan, which is acquired prior to the static CTP scan [19]. An illustration of the clinical utility of the static CTP is shown in Figure 1.
Furthermore, both the rest-stress and stress-rest acquisition protocols have been used in clinical static CTP studies. Usually, there is a 10-15 minutes interval between two acquisitions for optimal contrast medium washout [17]. For the rest-stress protocol, the remaining CTP that also provided coronary CTA can be used to exclude patients without coronary artery stenosis and select patients for subsequent stress CTP for the evaluation of myocardial perfusion. The limitation of this protocol is that residual https://doi.org/10.3348/kjr.2020.1277 kjronline.org contrast medium in the myocardium after rest CTP and the administration of a beta-blocker may affect the assessment of reversible perfusion defects with the subsequent stress CTP. Rest-stress protocol is often used in patients with intermediate coronary stenosis, while the stress-rest protocol is often applied in patients with a high pre-test probability of CAD or post-revascularization status. Stressrest protocol could avoid the limitation of the rest-stress protocol, but may reduce the sensitivity for the detection of myocardial infarction due to the contamination of the contrast medium from stress CTP masking fixed perfusion defects in the rest CTP [17]. Table 1 shows the radiation dose and diagnostic performance of static and dynamic CTP in comparison with nuclear medicine modalities and invasive FFR.

Diagnostic Performance of Static CTP
The clinical value of static CTP for the functional assessment of CAD has been extensively investigated. To incorporate static CTP into a routine cardiac CT test, a 64-row multidetector CT (MDCT) scanner is the minimal hardware requirement to ensure sufficient temporal and spatial resolution. In 2006, George et al. [20] reported a preclinical study in which myocardial perfusion measurements via static CTP exhibited a good correlation with the reference standard microsphere technique. Before the FAME study, the diagnostic accuracy of static CTP was mainly compared to that of other non-invasive imaging modalities, including positron emission tomography (PET), SPECT, and CMR, as well as ICA. Rocha-Filho et al. [21] reported that the incremental value of static CTP to CCTA with a 64-slice first-generation dual-source CT could improve accuracy from 0.77 to 0.99 by area under the curve (AUC) in detecting significant coronary stenosis. The CORE320, a multicenter study, evaluated the diagnostic performance of static CTP combined with CTA using a widedetector CT scanner in 381 patients to detect significant coronary stenosis (> 50%) in ICA and myocardial perfusion defects defined by SPECT. In this study, the accuracy of combined static CTP and CTA results in detecting or excluding flow-limiting CAD was 0.87 (95% confidence interval [CI]: 0.84-0.91) [22]. In the sub-analysis of CORE320, when directly comparing static CTP and SPECT, the diagnostic accuracy of MDCT was greater (0.78 vs. 0.69 by AUC) [23].
Compared to the current functional study gold standard, invasive FFR, in a wide-detector CT study with 40 symptomatic patients, Ko et al. [24] reported adding static CTP, including visual assessment and transmural perfusion ratio (TPR) on coronary CTA; as a result, the specificity increased from 78% to 95%, with decreased sensitivity from 95% to 87% and 71%, respectively. In a meta-analysis of 37 studies and 2048 patients in 2015, Takx et al. [25] reported that static CTP, CMR, and PET all had excellent diagnostic accuracy in detecting flow-limiting coronary stenosis (93%, 94%, and 93%, respectively). These diagnostic accuracies were statistically higher than those of traditional modalities, including SPECT myocardial perfusion imaging and stress echocardiography (82% and 83%, respectively). Recently, using a wide-detector CT compared to invasive FFR, Pontone et al. [26] reported static combined CTP and CCTA results with higher diagnostic accuracy than CCTA   82 Coenen et al. [79] (per-vessel)   [27].

Limitation and Recent Developments of Static CTP
Static CTP based on the regular coronary CTA protocol may not acquire myocardial imaging at the optimal timing of the time-attenuation curve (TAC) with peak enhancement in only one single-phase acquisition during the first pass of the contrast medium [17]. This could lead to an underestimation of the perfusion defects. In addition, single-phase images cannot generate quantitative (absolute) MBF and blood volume maps. Artifacts related to beam hardening, breath, and high heart rate may also impose a burden on diagnostic accuracy [15].
State-of-the-art clinical CT scanners developed by major vendors are equipped with dual-energy imaging capabilities. For instance, a dual-source or dual-layer CT scanner enables the differentiation of materials with similar attenuation coefficients but different atomic numbers. By simultaneously acquiring an additional scan with a different X-ray energy spectrum, additional spectral information may allow better differentiation of tissues with similar X-ray attenuation properties at a specific X-ray energy level [28].
Moreover, in dual-energy CT, the virtual monoenergetic images generated by blending the high-and low-energy scan data for the optimal signal-to-noise ratio could reduce beam-hardening artifacts [29]. In addition, both iodine analysis (quantitative) and eyeball (qualitative) analysis can be achieved by operating a static CTP. With regard to the radiation issue, by advanced iterative reconstruction, the radiation dose of DECT is not higher than the single energy mode in dual-source CT [30]. A dual-layer detector CT system automatically generates iodine maps and virtual monoenergetic images in static CTP study. Carrascosa et al. [31] reported that the diagnostic performance of dualenergy static CTP was greater than that of single-energy static CTP in identifying perfusion defects  69-0.84]; p = 0.007). The accuracy of iodine concentration analysis of both dual-energy and duallayer CT systems has been validated in a phantom study [32]. A study comparing CMR and an iodine map generated from dual-energy static CTP demonstrated differences in the iodine concentration of the myocardium (p < 0.001) among normal (2.56 ± 0.66 mg/mL), ischemic (1.98 ± 0.36 mg/ dL), and infarcted segments (1.35 ± 0.57 mg/mL) [33]. The optimal myocardial iodine concentration threshold to differentiate between normal and pathologic myocardium was 2.1 mg/mL (sensitivity 75%, specificity 73.6%, ROC curve 0.806, and reproducibility of 0.814 [intraclass correlation coefficient]). However, some shared limitations in stress CTP are still present in DECT, including the impact of high heart rate during adenosine infusion on imaging quality and inaccurate iodine concentration measurements of the myocardium with motion artifacts.

Dynamic CTP
The technological requirement of a dynamic CTP is higher than that of a static CTP. Specifically, the entire left ventricle of the heart should be covered in one or two scanner table positions in a non-helical/non-spiral acquisition mode. This restricts dynamic CTP to the latest generation of wide-detector CT and 2nd/3rd-generation dual-source CT owing to its higher temporal resolution and wider coverage. In approximately 30 seconds, a continuous scan of the left ventricle can be performed to acquire the image dataset of the first-pass contrast medium through the left ventricle cavity, aorta, and myocardial microcirculation. The end-systolic phase is preferred over the prospective electrocardiography-gated acquisition protocol for dynamic CTP as this can reduce beam hardening and motion artifacts [34]. With the CT attenuation changes in serial images of the myocardium and aorta, the software can generate the TAC and calculate the MBF and myocardial blood volume by dividing the convoluted maximal slope of the myocardial TAC by the maximum arterial input function [35]. Colorcoded volumetric maps, polar maps, or bull's eye plots can be generated for the diagnosis of myocardial ischemia. In addition to quantitative analysis, another advantage of dynamic CTP over static CTP is the detection of balanced ischemia in patients with multivessel disease and in diabetic patients with microvascular disease, which may be https://doi.org/10.3348/kjr.2020.1277 kjronline.org missed in qualitative analysis by static CTP [36].
To combine with CCTA, theoretically, dynamic CTP should be performed before CCTA to avoid the presence of residual contrast medium in the myocardium and facilitate an optimal CTP map. However, in a clinical scenario, CCTA selected patients with intermediate and high-grade coronary stenosis for subsequent functional assessment, which avoids unnecessary radiation exposure and contrast medium administration in patients without obstructive CAD. Therefore, for suspected CAD patients, the workflow should involve immediate interpretation of CCTA, which also provides the time window for myocardial contrast medium washout. Moreover, the cardiac imager should be the key person who decides to perform dynamic CTP for the patient [37].
More recently, Pontone et al. [42] reported that the diagnostic performance of dynamic CTP was comparable to that of invasive FFR, with a sensitivity of 73%, specificity of 86%, and accuracy of 0.88. However, the cut-off values of CT-derived MBF for hemodynamic significance vary between 75 and 164 mL/min/g among studies; such discrepancies could be related to different acquisition protocols employed for dynamic CTP assessment, CT technology, and pathologic conditions such as collateral circulation [35,40,41]. This had a great influence on the diagnostic accuracy of dynamic CTP and greatly improved the accuracy of dynamic CTP to facilitate its clinical implementation for the functional assessment of CAD. A dynamic CTP study can provide visual and quantitative assessments. Li et al. [43] conducted a direct comparison of both methods in detecting functionally significant coronary stenosis, and revealed that MBF is superior to visual analysis at the per-lesion level (AUC = 0.942, 0.802, p < 0.01) in 62 patients with 95 target vessels.

Limitation and Recent Developments of Dynamic CTP
In the past, the radiation exposure of dynamic CTP was much higher than that of static CTP [44]. Nowadays, dynamic CT study using an advanced CT scanner have a similar radiation dose (mean 3.6 mSv) to that of static CTP study [45]. Table 2 shows a direct comparison of the clinical value in static and dynamic CTP, as well as the technique.
In clinical practice, beam-hardening artifacts arising from dense iodinated contrast medium in the aorta and heart chamber pose a challenge to the accurate assessment of MBF in dynamic CTP [15]. DECT is capable of virtually synthesizing monoenergetic images and reducing beamhardening artifacts [26]. In a pig dynamic perfusion study kjronline.org with a prototypic dual-layer CT system, Fahmi et al. [46] reported that virtual monoenergetic images could be used to improve the over-estimation of functional severity on the ischemic anterior wall. In this study, the functional severity was due to beam-hardening artifact-induced hypoenhancement, and was assessed by the "endo-toepi" transmural flow ratio for subendocardial ischemia in images of 120 kVp vs 70 keV. (0.29 ± 0.01 vs. 0.55 ± 0.01; p < 0.05). Furthermore, the potential incremental value of coronary CTA extracted from the stress-dynamic CTP has also been investigated. Yi et al. [47] reported that CTP-derived single-phase CTA improved the diagnostic value compared to CTP alone (AUC: 0.963 vs. 0.922; p < 0.01) using a 3rdgeneration dual-source CT. Additionally, the study team used a 70-kVp stress CTP protocol. It is possible to further reduce the radiation dose and total scan time for a real "one-stop shop" study of CAD using an advanced CT machine for future clinical practice.

Principle of FFRCT
Without direct invasive measurement, by applying computational fluid dynamics, FFRCT can perform the simultaneous calculation of pressure and flow along coronary arteries from CCTA data [48]. There are several essential principles and steps to acquire "virtual" FFR noninvasively: 1) the total coronary flow meets the myocardial demand in a state of rest, which can be calculated from the ventricular volume and mass using an anatomical model, 2) coronary microvascular resistance of the myocardium is inversely related to the epicardial coronary arteries, 3) the response of the vasodilator of coronary arteries is predictable and can be used to simulate the reduction in microvascular resistance during maximal hyperemia from images acquired at rest, and 4) the flow and pressure along the coronary vascular bed can be computed by solving the three-dimensional Navier-Stokes equation, which comprises a set of nonlinear partial differential equations (Fig. 2) [49].
To date, there have been several companies, including HeartFlow®, Siemens, Canon, KEYAMEDICAL®, AI Medic®, United Imaging Healthcare, and the EU-funded Horizon 2020 project SMARTool, that have used the computed fluid dynamics (CFD) technique in FFRCT. HeartFlow® FFRCT is currently the most popular in the United States, Europe, and Japan, and is the only technique approved by the American Food and Drug Administration. For hospitals that have a contract with HeartFlow®, the CCTA data have to be transferred to the core laboratory of HeartFlow (Redwood, CA, USA) for subsequent processing, which takes between 1 and 4 hours. A clinical example illustrating the utility of FFRCT from HeartFlow is presented in Figure 3.
All other CFD-based techniques, including cFFR (combined CFD-based method and machine learning [ML]) (Siemens), 1-D CFD (Canon Medical Systems Corporation), uCT-FFR (United-Imaging Healthcare), AI Medic® (HeartMedi), reduced-order model FFRCT (Comprehensive Cardiac Analysis, IntelliSpace, Philips Healthcare), and DEEPVESSEL FFR (combined CFD-based method and deep learning) (Keya Medical Technology), can be used "on-site." Moreover, the computer hardware requirements of these types of software are significantly less complex, and the entire process can be completed within 10 to 30 minutes [50][51][52][53][54]. It is worth mentioning that AI Medic® (HeartMedi) has been  [53]. Currently, most other techniques are used only for research purposes. Table 3 shows the diagnostic performance of FFRCT from different software companies in comparison with the invasive FFR.
Recently, the Radiological Society of North America issued recommendations for FFRCT for the interpretation and reporting of physicians. FFRCT values of > 0.80 are considered normal, indicating myocardium supply by vessels distal to the stenosis rarely under ischemic status, while values of ≤ 0.75, are considered as lesion-specific ischemia. In coronary lesions with FFRCT values between 0.76 and 0.80, additional risk stratification is recommended. This is particularly crucial because the values assessed by FFRCT are slightly lower than those of invasive FFR [55,56], although this has been considered a "gray area" in the invasive measurements. In addition, for patients with negative results or non-obstructive lesions (< 50% stenosis) of CCTA, no further FFRCT is needed. FFRCT can be useful in anatomically moderate (50%-69%) and severe (70%-99%) stenosis [57].

Diagnostic Performance of FFRCT
The diagnostic performance of FFRCT has been validated in several major studies, predominantly using the HeartFlow® technique [48,55,56,58,59]. Promising data from three major studies, including DISCOVER-FLOW, DeFACTO, and HeartFlow NXT, demonstrated that using FFRCT < 0.8 as the cutoff value for lesion-specific ischemia shows a good correlation between FFRCT and invasive FFR. In the DISCOVER-FLOW study, the results of FFRCT of 158 vessels from 103 patients showed a per-vessel sensitivity of 87.9%, a specificity of 82.2%, and an accuracy of 84.3% compared to invasive FFR. The ROC curve for detecting a functionally significant lesion defined by invasive FFR (FFR < 0.80) was significantly improved in FFRCT compared to standard CCTA (0.90 vs. 0.75, p = 0.001) [49]. In two subsequent large studies (DeFACTO and NXT), the investigators demonstrated the incremental diagnostic value of FFRCT over CCTA in detecting functionally significant stenosis defined by invasive FFR [60], as well as a good correlation between FFRCT and invasive FFR (Pearson's R = 0.82; p < 0.001) [55]. The CFD-based SmartFFR from SMARTool showed a fast processing time (25 ± 10 minutes) and a strong correlation with invasive FFR (R = 0.93, p < 0.001) [59]. In contrast, in a single-center, prospective study of 63 patients, the deeplearning-based method, DEEPVESSEL FFR, showed good correlation with invasive FFR (R = 0.686, p < 0.001), with a per-vessel sensitivity of 97.1%, specificity of 75%, and accuracy of 87.3% for detecting invasive FFR < 0.8 [54].
The diagnostic accuracy of FFRCT in patients with heavy calcified coronary burden is another important issue. In a sub-study of an NXT trial, Nørgaard et al. [61] showed no significant differences in FFRCT in detecting ischemia between moderate-high Agatston scores (121-1703) and low-mild scores (0-120). However, two studies using ML FFRCT (cFFR) showed contrasting results. Tesche et al. [62] reported that FFRCT had superior diagnostic value to CTA in vessels with high Agatston scores (> 400) (AUC: 0.71, 0.55, p = 0.04), good discriminatory power in vessels with high Agatston scores (> 400), and high performance in

Direct Comparison between CTP and FFRCT
Recently, many researchers have focused on the integration and comparison of different methodologies of cardiac CT, including static and dynamic CTP, CTA, and FFRCT, in the diagnosis of ischemic-specific CAD. Pontone et al. [42] reported that integrated CTA, FFRCT, and dynamicstress CTP performed by a whole-heart cover CT scanner in 85 symptomatic, intermediate to high-risk patients, integrated CTA, CTP, and FFRCT outperformed other methods in detecting functionally significant CAD (CTA + CTP + FFRCT: AUC: 0.919, CTA + FFRCT: 0.878, CTA + CTP: 0.876, CTA: 0.826). In the PERFECTION study, which performed a direct comparison of FFRCT, static CTP, and invasive FFR in 147 symptomatic patients, both static CTP and FFRCT were found to perform better than CTA alone per patient (accuracies of 92% and 94% vs. 82%, respectively, both p < 0.001). There was no significant difference between FFRCT + CCTA and static CTP + CCTA [64].
More recent studies have used other FFRCT techniques. In an ML-based FFRCT (cFFR) study with 86 subjects and 157 target vessels, dynamic CT MPI outperformed cFFR for the diagnosis of functionally significant coronary stenosis (diagnostic accuracy: 84% vs. 78%, p = 0.04) [45]. Traditionally, anatomical intermediate lesions of coronary CTA require further tests to detect functionally significant diseases. Several studies, including on-and off-site FFRCT software techniques, have been discussed in relation to this issue. In the NXT trial, subsequent analyses were restricted to patients with intermediate stenoses ranging from 30% to 70% (n = 235), with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 85%, 79%, 63%, 92%, and 80%, respectively [55]. In other off-site CFD-based FFRCT studies, on a pervessel basis, the AUCs were 0. 79 [51]. It is predictable that different diagnostic performances could be related to various algorithms in different study populations. Figure 4 shows the results of selected studies evaluating the diagnostic performance of static, dynamic CTP, FFRCT, and other non-invasive modalities compared to invasive FFR, the gold standard of the functional study of CAD.
In terms of prognostic value, in a dynamic CTP study with 332 patients with suspected CAD, abnormal perfusion was an independent predictor (hazard ratio: 5.7, 95% CI: 1.9-16.9, p = 0.002) of MACE, with a significant improvement in prognostic value during a median follow-up of 2.5 years [68]. In the CORE320 study, the prognostic value of the identification of MACE at the 2-year follow-up was similar (p = 0.36) for combined static CTP and CTA (AUC: 0.68; 95% CI: 62-75), and for ICA and SPECT (AUC: 0.71; 95% CI: 65-79) [69]. In a clinical utility trial, the PLATFORM study demonstrated a low adverse event rate (5 of 581 followed-up cases) in the group cared for by the FFRCT guide [70]. Another prospective multicenter registry, the ADVANCE study, enrolled 5083 patients with stable angina and showed that FFRCT increased the number of subjects referred to ICA. Moreover, patients with FFRCT < 0.8, were more likely to have anatomical significant CAD and had a much higher MACE at 90 days of follow-up [57].

Limitations and Recent Developments of FFRCT
The rejection rate of FFRCT is relatively high. Indeed, in the ADVANCE registry and a large cohort study, the rejection rates of FFRCT were 2.9% and 8.4%, respectively [71], with responsible factors including calcified blooming, inadequate contrast enhancement, image noise, misalignment, and metal artifacts [62]. Excellent image quality of CCTA is needed to avoid these artifacts for robust FFRCT analysis. In addition, FFRCT cannot be used in patients with coronary occlusion associated with collateral circulation, because such a complicated condition cannot be handled by the current FFRCT analytic algorithm [55]. Both offsite FFRCT (HeartFlow) and various on-site technologies require accurate delineation of the boundaries of coronary artery trees for subsequent fluid analysis [72]. Most commercialized software is semi-automatic and requires manual correction, especially for vessels with a heavy calcified burden [72][73][74]. Recently, Kumamaru et al. [75] reported a 3D deep-learning-based software that could fully and automatically analyze unsegmented coronary CTA data. However, as this was a retrospective study with a small sample size, future work is needed to fully and automatically analyze FFRCT to reduce time and avoid interand intra-observer variabilities.

Summary
Recently, due to improved CT scanners and technologies, cardiac CT can provide functional information using FFRCT and CTP. Combined with CCTA, cardiac CT is the only modality that can provide a "one-stop shop" service. Compared to static CTP, which is mainly observed by eye, dynamic CTP requires software to generate MBF for full quantitative assessment. Although FFRCT requires no additional scan, "on-site" or "off-site" post-processing software is required to generate the results. Based on clinical data and CCTA, radiologists should choose adequate techniques to provide valuable functional information for clinicians.

Conflicts of Interest
The authors have no potential conflicts of interest to disclose.