CTA examination was performed using either a 64-row helical scanner (Aquilion 64, Toshiba Medical Systems, Toshiba Medical Systems, Otawara, Japan) or a 320-row volumetric scanner (Aquilion ONE, Toshiba Medical Systems, Otawara, Japan). If the patient’s heart rate was ≥65 beats/minute and no contra-indications existed, beta-blocking medication (metoprolol 50 or 100 mg, single oral dose, 1 hour prior to examination) was administered. Scan parameters for the 64-row contrast enhanced scan were: 400 ms gantry rotation time, collimation of 64 × 0.5 mm, tube voltage of 100-135 kV and tube current of 250-350 mA, depending on body posture. Non-ionic contrast material (Iomeron 400, Bracco, Milan, Italy or Ultravist 370, Bayer Schering Pharma AG Berlin, Germany) was administered with an amount of 80-110 mL followed by a saline flush with a flow rate of 5 mL/second. Datasets were reconstructed from the retrospectively gated raw data, the best phase was reconstructed with an interval of 0.3 mm. Using a single test slice reconstructed throughout the various phases of the heart cycle, other suitable R-R intervals were examined for additional reconstructions. Concerning the 320-row contrast enhanced scan; imaging was performed in a single volume using prospective triggering with exposure interval depending on the heart rate. If the heart rate was ≥65 beats/minute, the phase window was set 65%-85% of R-R interval, if the heart rate was stable and <60 beats/minute the phase window was set at 70%-80% of R-R interval. Scan parameters were: 350 ms gantry rotation time, 320 × 0.5 mm collimation, 100-135 kV tube voltage and a tube current of 400-580 mA, depending on body mass index (BMI). Overall, 60-90 mL contrast material (Iomeron 400, Bracco, Milan, Italy) was administered with a rate of 5-6 mL/second followed by a saline flush. Data acquisition was performed during an inspiratory breath hold of approximately 4-10 seconds. Subsequently, images were reconstructed in the best phase of the R-R interval and transferred to a remote workstation for post-processing.

CTA datasets were evaluated using dedicated software (Vitrea 2.0 or Vitrea FX 1.1 Vital images, Minnetonka, MN, USA). Analysis was performed with the use of available post-processing tools such as cross-sectional axial slices and multiplanar reconstructions. One experienced reader, blinded to the IVUS-VH results, evaluated the CTA datasets. The coronary arteries were divided into 17 segments according to the modified American Heart Association classification.16 Each segment was evaluated for the presence of any atherosclerotic plaque. Structures >1 mm² within and/or adjacent to the coronary artery lumen, which could be clearly distinguished from the vessel lumen, were defined as atherosclerotic plaque.3

Calcification patterns in plaques on CTA were classified morphologically as non-calcified, spotty calcifications or dense calcifications. Non-calcified plaques were defined as a plaque with low CT attenuation located in the vessel wall in at least two independent image planes and clearly distinguishable from the contrast-enhanced lumen and pericardial tissue without any calcification.17 Plaques with spotty calcifications were defined as follows: length (extent in the longitudinal direction of the vessel) of the calcification <3/2 of vessel diameter and width (extent of the calcification perpendicular to the longitudinal direction of the vessel) of the calcification <2/3 of vessel diameter, as previously described (Figure 1).17 Plaques with spotty calcification were further differentiated according to their length (extent of the calcification parallel to the longitudinal direction of the vessel on curved multiplanar reconstruction) into small spotty (<1 mm), intermediate spotty (1-3 mm), and large spotty calcifications (≥3 mm) as measured with caliper function (for illustration see Figure 2).18 Dense calcifications were defined as a plaque with high CT density, completely calcified and with calcifications present bilateral on cross-sectional axial slices.

Conventional invasive coronary angiography was performed according to standard protocols. IVUS examinations were acquired with a 20 MHz, 2.9 F phased-array IVUS catheter, (Eagle Eye, Volcano Corporation, Rancho Cordova, CA, USA) and a dedicated IVUS-console (Volcano Corporation, Rancho Cordova, CA, USA) after intracoronary administration of nitroglycerine. Under fluoroscopic guidance, the IVUS catheter was introduced distally in the coronary artery and a motorized automated pullback with a continuous speed of 0.5 mm/second was used until the catheter reached the guiding catheter. Images were stored on CD-ROM or DVD for off-line analysis.

IVUS-VH analysis was performed by two experienced observers blinded to baseline patient characteristics and CTA findings with the use of dedicated software (QCU-CMS, version 4.59, Medis Medical Imaging Systems, Leiden, the Netherlands). First, contour detection (lumen and media interface) was performed manually with the use of cross-sectional views to provide compositional output.19 Secondly, on a frame-by-frame basis, the four different tissue components were differentiated and labeled with four different color-codes (fibrotic tissue was labeled in dark green, fibro-fatty tissue in light green, necrotic core in red and dense calcium in white), as validated previously.10 The mean percentage of each plaque component was obtained in the full length of the lesion observed on the CTA examination. A lesion on intravascular ultrasound imaging was defined as at least three consecutive frames with a plaque burden of at least 40%.20 In addition, the presence of the thin cap fibroatheroma (TCFA) was evaluated on a per-lesion basis. TCFA was defined as a lesion with a plaque burden ≥40%, presence of >10% confluent necrotic core on three consecutive frames and necrotic core in contact with the lumen for along the lumen circumference.14,21,22 High-risk plaque characteristics on IVUS-VH were defined by % of necrotic core and presence of TCFA.

To ensure that identical plaques were assessed by CTA and IVUS-VH, coronary ostia and side branches were used as landmarks and distances from the landmarks to the target lesions were measured (Figure 3). On CTA, distances were measured using multiplanar reconstructions. On IVUS-VH, longitudinal reconstructed ECG triggered datasets were used to measure the difference between corresponding plaque and landmarks. After alignment of plaques on CTA and IVUS-VH, we identified matching slices between the two modalities and could determine the proximal and distal end of a lesion. Examples of different calcification patterns on CTA with corresponding IVUS-VH images are demonstrated in Figures 4 and 5.