Our Human Research Committee approved this retrospective analysis and waived informed patient consent. This study was conducted in compliance with the Health Insurance Portability and Accountability Act.
Data for 18 consecutive patients who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients (7 men, 3 women; age range, 61–77 years; mean age, 70 years) who underwent adenosine stress CT, and 8 patients (4 men, 4 women; age range, 55–82 years; mean age, 72 years) who underwent rest CT as controls. All patients had been clinically referred for assessment of known or suspected CAD. The entry criteria were as follows: (1) effort or rest stable angina (documented ST-T change on electrocardiogram (ECG), or relief with administration of nitroglycerin); and (2) asymptomatic patients with a high probability of coronary artery disease (i.e., multiple coronary risk factors) or abnormal findings on exercise ECG. The exclusion criteria were as follows: (1) acute myocardial infarction (within 3 months); (2) unstable angina (recent onset of angina within 1 month, severe and worsening clinical symptoms); (3) chronic atrial fibrillation; (4) poor renal function (serum creatinine >1.5 mg/dl); (5) pregnancy, hyperthyroidism, or known allergic reaction to contrast media; (6) severe left ventricular dysfunction (left ventricular ejection fraction less than 20%); (7) known history of bronchial asthma; (8) congestive heart failure (New York Heart Association class IV); and (9) greater than first-degree atrio-ventricular block.
Coronary risk factors among the patients were as follows: hypertension (14 patients), diabetes mellitus (6), dyslipidemia (7), and cigarette smoking (6).
To decide whether to perform angioplasty or bypass surgery following DE-CT studies, adenosine stress myocardial perfusion scintigraphy (MPS) was performed in 10 (7 patients in adenosine stress CT group, 3 in rest CT group) of the 18 patients. Invasive coronary angiography (ICA) was performed in 8 patients (5 in adenosine stress CT group, 3 in rest CT group).
All patients were examined using a dual-source CT system (Definition, Siemens, Forchheim, Germany) in dual-energy mode. In each patient, a single CT acquisition was obtained with the following parameters: 330 ms gantry rotation time, 32 × 2 × 0.6-mm collimation with z-flying focal spot technique  and 165 ms temporal resolution. Helical pitch was 0.2 (heart rate: <60 beats/min), 0.25 (61–70 beats/min), 0.3 (71–80 beats/min), and 0.35 (>81 beats/min). One tube of the dual-source CT system was operated at 90 mAs/rot at 140 kV and the second tube at 180 mAs/rot at 100 kV. Data were acquired in the cranio-caudal direction with simultaneous recording of the patient’s ECG signal to enable retrospective registration of the reconstructed images to the desired cardiac phase. The anatomical range extended from the level of the carina to just below the dome of the diaphragm. A single oral dose of 25–50 mg atenolol (AstraZeneca Pharmaceuticals, London, UK) was administered 4 h before cardiac CT scanning if the pre-scan heart rate exceeded 80 beats/min. No additional medication was given if the heart rate did not decrease sufficiently following this dose.
CT examinations were contrast enhanced using our routine clinical contrast medium injection protocol. The delay time before acquiring data after the start of the injection of contrast medium was determined by test-bolus injection of 15–20 ml of a non-ionic contrast medium (Iopamidol, 370 mg/ml Iopamiron, Bayer Yakuhin, Osaka, Japan) at 4 ml/s through a 20 G intravenous antecubital catheter, followed by 20 ml of saline, using a dual-syringe injector (Stellant, Medrad, Indianola, PA). The peak time of test bolus enhancement as measured by repetitive scanning at the level of the aortic root, was used as the delay time. After the test bolus, adenosine infusion was started at 140 μg/kg/min. A retrospectively gated scan was obtained 3 min after the initiation of the infusion . Actual contrast enhancement was achieved by injecting 60–70 ml of contrast medium, followed by 30 ml of saline. All injections were delivered at 4 ml/s. Throughout the infusion, patient symptoms, heart rate, blood pressure, and the electrocardiogram were monitored by a cardiologist. Immediately after the stress CT, the adenosine infusion was discontinued.
Adenosine stress scanning was performed in 10 patients; a rest scan was not performed for these patients. A rest scan was performed in eight patients in the same protocol; adenosine stress scan was not performed for these patients.
From a single dual-energy CT data acquisition, three different image reconstructions were performed, with reconstructed section width of 0.75 mm and reconstruction increments of 0.4 mm using the routine dual-energy reconstruction algorithm implemented on the scanner platform. The first set of transverse gray-scale images aimed to optimize spatial and contrast resolution by merging 70% of the 140 kV spectrum and 30% of the 100 kV spectrum. These data sets were used for clinical coronary CTA interpretation of coronary artery morphology for stenosis detection and grading; the term ‘120 kV composite image’ used in the present study refers to the 120 kV images. Another image set was based only on the low kV (100 kV) X-ray spectrum, and yet another only on the 140-kV X-ray spectrum. The iodine map was analyzed by determining the iodine content within the tissue, based on the unique X-ray absorption characteristics of this element at different kV levels [14, 15].
Coronary enhancement ratio (CER)
Coronary enhancement was determined in each patient in Hounsfield units (HU) as the mean contrast attenuation determined at regions of interest (ROIs) positioned on the aortic root, and at the right coronary artery (RCA), the left anterior descending artery (LAD), and the left circumflex artery (LCX). Each ROI was set as large as possible without including coronary wall, plaque, or calcifications, and was located at the same site on both the iodine map and the 120 kV images. ROIs were not set at points with a diameter of <3 mm or with significant stenosis. First, the coronary arteries were each divided into three portions (RCA: proximal, mid, and distal portions; LAD: left main trunk, proximal, and mid portions; LCX: left main trunk, proximal, and distal portions) on the basis of the AHA 15 segment model. Three ROIs in each portion were set at equal intervals. Next, the intra-coronary attenuation at nine different points was measured, and the mean values on both the iodine map and the 120 kV images were calculated. Coronary enhancement ratio (CER) was used as an estimate of coronary enhancement, and was calculated by dividing the mean attenuation in the coronary artery on the iodine map or the 120 kV images by the mean attenuation in the aortic root on the 120 kV images.
Analysis of coronary CT angiogram
Coronary CT angiograms were analyzed using the 120 kV data with a software (Virtual Place, AZE, Tokyo, Japan), based on a combination of transverse sections and automatically generated curved multiplanar reformatted images of the target vessels. A semi-automated vessel analysis tool was used for grading the severity of stenosis. The images were clinically interpreted by three experienced readers (two radiologists and one cardiologist) who reached consensus, using the American Heart Association 15-segment model. Significant stenosis was defined as a reduction in diameter of more than 50%.
Adenosine stress myocardial perfusion scintigraphy (MPS)
Stress/rest thallium-201 MPS was performed according to the American College of Cardiology (ACC)/American Heart Association (AHA)/American Society of Nuclear Cardiology (ASNC) guidelines for the clinical use of cardiac radionuclide imaging . For each patient, stress was induced pharmacologically through intravenous infusion of adenosine (6 min infusion of 140 μg kg−1 min−1) as described by Nishimura et al. . The patient’s standard ECG, vital signs, and general conditions were continuously monitored during the stress protocol. Three minutes after the continuous infusion of adenosine, 111 MBq thallium-201 was injected intravenously and flushed with saline. Early single photon emission tomography (SPECT) was performed 10 min after the adenosine stress test; late SPECT was performed 4 h after the early SPECT.
The SPECT images were acquired using a three-headed SPECT system (GCA 9300; Toshiba, Tokyo, Japan). Tomographic reconstruction was performed using a standard filtered back-projection technique with a ramp filter to produce a transaxial tomogram. No scatter or attenuation correction was applied. From these transaxial tomograms, the long axis of the left ventricle was identified and oblique-angled tomograms were generated (i.e., vertical long-axis, short-axis and horizontal long-axis tomograms).
The SPECT images were visually analyzed independently by one radiologist (M.N.) and one cardiologist (K.W.). The slices were displayed sequentially to assess the myocardial perfusion in each vascular territory . The presence or absence of redistribution was visually judged in the 4 h images, which were used to determine whether ischemia was present or not.
Invasive coronary angiography (ICA)
ICA was performed by standard transfemoral arterial catheterization. A minimum of 8 projections were obtained (minimum of 5 views for the left coronary artery system and minimum of 3 views for the right coronary artery system). All ICA images were interpreted by two cardiologists (K.W., H.S.). Coronary artery segments were evaluated using a 15-segment AHA coronary tree model and were visually judged as having significant stenosis at 2 levels (i.e., if >50% or >75% luminal narrowing of the coronary artery diameter was present).
The Mann–Whitney U-test was used to examine differences in CER between stenotic and non-stenotic coronary arteries, between patients with and without stenotic coronary arteries, and between ischemia and non-ischemia on the MPS. The paired t-test was used to examine the differences in CER between the findings of the iodine map and those of 120 kV images. Probability values <0.05 were considered significant.