Coronary CTA has been one of the most important advances in the noninvasive diagnosis of CAD in the past decade. It is capable of excluding CAD with unsurpassed negative predictive value [5
]. In the setting of non-obstructive and obstructive CAD, it is capable of determining the percentage of luminal stenosis and determining the constituents of plaque. However, in its current form, it does not provide important information on the physiologic significance of coronary stenoses.
Adenosine stress CT perfusion imaging has been well validated in preclinical and clinical studies [18
]. Those previous studies were performed with mostly single- and dual-source 64-MDCT systems. In contrast, CORE320 will use a wide-area 320-MDCT system. This scanner is capable of full cardiac coverage over a single heartbeat without the need for table movement, providing several key advantages derived from the temporal uniformity of the acquisition, including the elimination of variations in contrast enhancement and the ability to target a specific portion of the contrast bolus and optimize the timing of CT perfusion imaging [23
]. In addition, very short scan acquisition times allow reductions in contrast dose and enable arterial phase imaging before contrast transit to the venous side of the coronary circulation. Finally, prospective ECG triggering can be performed using half-scan acquisition and reconstruction for slower heart rates and segmented acquisition and reconstruction for higher heart rates commonly seen during the infusion of adenosine.
There are several components of the CORE320 acquisition, reconstruction, and analysis protocol that should be discussed. The first is the order of the CTA followed by CT perfusion imaging. Although all patients in the CORE320 study will undergo CTA and CT perfusion imaging, we think that the clinical use of CTA and CT perfusion imaging will use CTA first, followed by CT perfusion imaging in patients with moderate-to-severe stenoses. Using this sequence, a future diagnostic algorithm will take advantage of the high negative predictive value of CTA and will exclude disease in most patients. Only those patients with moderate-to-severe stenoses will then require a CT perfusion imaging study. This strategy also allows us to maintain a lower heart rate during the CTA. This improves image quality and reduces radiation dose [32
]. In a pilot study using a 256-MDCT scanner, we found in 19 patients that performance of a stress CT perfusion imaging study first results in higher heart rates during the subsequent CTA. That study showed that heart rates are 7 beats/min higher, compared with baseline, when a CTA follows a recent adenosine stress CT perfusion imaging study [19
]. These higher heart rates during CTA are undesirable because they could result in motion artifacts and eliminate the ability to use single-heartbeat prospective ECG triggering and, thus, increase radiation dose.
The CORE320 CT perfusion imaging protocol targets the upslope to peak of the contrast bolus in mid-to-late diastole measured in the descending aorta. This target is supported by preclinical and clinical data from Johns Hopkins University. An analysis in preclinical models of coronary ischemia that underwent dynamic adenosine stress CT perfusion imaging revealed that, on average, the maximum attenuation density differences in ischemic versus remote territories (56.7 ± 20.2 HU) occur in the upslope of the contrast bolus 3.8 ± 2.6 seconds before peak arterial enhancement. These differences in myocardial attenuation are less marked at peak enhancement (40.4 ± 18.9 HU) and quickly disappear in the down slope of the contrast bolus [21
]. These differences were confirmed in a similar preclinical model that underwent adenosine stress helical CT perfusion imaging during the upslope of the contrast bolus [22
]. The selection of targeting mid-to-late diastole is supported by adenosine stress CT perfusion imaging studies in 75 patients. The first group of patients underwent retrospective ECG-gated adenosine stress CT perfusion imaging (n
= 43). Image datasets were reconstructed throughout systole and diastole and were examined for the best motion-free phase. The best motion-free images were noted in mid-to-end diastole in 79% of cases. When examining diastole only, the best phase, on average, was 86% of the R-R interval (range, 75–100%) [19
]. This finding was confirmed in 32 patients who underwent adenosine stress 320-MDCT perfusion imaging that used prospective ECG triggering in mid-to-late diastole. In this group of patients, the best phase was 80% on average, with a range of 56–99% [35
The CORE320 study will use a previously validated myocardial perfusion-specific reconstruction kernel that includes a beam-hardening correction algorithm described elsewhere [27
]. That study used myocardial phantoms and animal models of coronary ischemia and found that beam-hardening artifacts can be adequately corrected for and that their correction improves the measurement of myocardial perfusion [27
]. In addition, the reconstruction kernel for CORE320 CT perfusion imaging studies lacks edge enhancement. This fact is extremely important in the assessment for subendocardial perfusion deficits, because edge enhancement can artificially lower the measured attenuation in the subendocardium as it interfaces with the contrast-enhanced left ventricular blood pool and can artificially increase the measured attenuation in the subepicardium as it interfaces with the air-filled lungs. Together, these effects of edge enhancement can give the false appearance of subendocardial perfusion deficits in normal territories.
The limitations of the CORE320 study are additional iodinated contrast and radiation given for the perfusion study. In this study, we use prospective ECG triggering and have reduced x-ray exposure times to the minimum time required to maintain image quality while reducing effective radiation dose. Although, the 320-MDCT scanner allows prospective ECG triggering with segmental acquisition and reconstruction to improve temporal resolution, β-blockers are still required to maintain optimal image quality, avoid motion artifacts, and reduce radiation dose. Studies have shown that β-blockers can blunt differences between ischemic and nonischemic myocardium, and this could affect our sensitivity for myocardial ischemia [36
In summary, the CORE320 multicenter multinational study will rigorously evaluate the accuracy of CTA combined with CT perfusion imaging to diagnose obstructive atherosclerosis causing myocardial perfusion abnormalities using 320-MDCT.