From July 2006 to February 2007, 26 consecutive patients (17 men, nine women; mean age, 56 years) with coronary atherosclerotic disease underwent 64-MDCT and IVUS. Eleven patients had acute coronary syndrome and 15 patients had stable angina. All patients had abnormal ECG results. Coronary risk was assessed using the Framingham database [4]. The Framingham risk score of these patients ranged from 12 to 17 (average, 14.7). CT was performed within 3 days before or after the catheterization procedure. Patients with arrhythmias, previous bypass surgery, unstable clinical presentation, and contraindications to iodinated contrast media were excluded from enrollment. The institutional ethics committee approved the research protocols, and all patients gave informed consent.

Patients with heart rates greater than 70 beats per minute received 25–50 mg of metoprolol orally 60 minutes before MDCT (Aquilion 64, Toshiba). MDCT data were acquired using an X-ray beam collimation width of 32 mm (0.5-mm slice thickness × 64 rows) with the spatial resolution in x-, y-, and z-axes of 0.35 mm, a gantry rotation of 400 milliseconds, a pitch of 11.2–13.2, an electric current of 350–450 mAs, and a tube voltage of 120–135 kV (depending on patient size).

Contrast medium (70–85 mL, 370 mg I/mL, depending on patient size) was injected IV at 4 mL/s followed by a 40-mL saline flush at the same injection rate. The CT value of the area of interest in the ascending aorta was monitored from the start of the injection. As soon as the CT value in the ascending aorta reached 130–150 H, scanning was manually initiated, and imaging of the entire volume of the heart was acquired during one breath-hold with simultaneous recording of the ECG tracing.

Axial images (slice thickness, 0.5 mm; increment, 0.3 mm) were reconstructed using a multisector reconstruction algorithm. Using retrospective ECG gating, we routinely performed reconstructions at 75% of the R-R interval. If motion artifacts existed at these reconstructions, another, more optimal ECG phase was chosen to provide better image quality.

The baseline axial images were postprocessed and analyzed by plaque analysis software (Sure Plaque, Toshiba) at the workstation (HP XW8200, Hewlett-Packard). The software detected both plaques and vessel walls on CT images. Different CT density ranges hypothesized to represent different components of plaque were displayed with various colors. Specifically, the lipid composition (range, –100 to 29 H) was represented by red; fibrous composition (range, 30–189 H) was represented by blue; calcification (range, 350–1,000 H) was represented by yellow; lumen (range, 190–349 H) was represented by green; and vessel wall (range, 30–189 H; same range as for fibrous composition) was represented by luteous. The Hounsfield unit ranges for plaque were preset by software and could be manually altered by the operator. The ranges should be adjusted slightly to avoid the influence of lumen density and obtain more accurate quantitative measurements. The mean density in the contrast-enhanced lumen of the proximal coronary artery (American Heart Association [AHA] segments 1, 5, 6, and 11) and the Hounsfield unit range of the vessel wall, adjusted to equal the IVUS image in size, were recorded. The results of this analysis revealed that when the average intensity in the lumen of the proximal artery is > 380 H, the optimal setting to detect plaque and the outer vessel boundaries is obtained at the CT vessel wall range of 30–189 H; however, when the average intensity of the proximal lumen is < 380 H, a CT vessel wall range of 20–179 H is optimal.

For comparisons with IVUS, the target coronary arteries were divided into 10-mm segments from the ostium or onset [2, 3]. Segments with artifacts or blur images were excluded. Plaque qualitative analysis included determinations of the presence and classification of plaque in each coronary segment. Atherosclerotic plaques were considered present when the vessel wall thickness exceeded 0.5 mm. Each plaque was classified according to the color displayed by the software. Plaques displayed as red or green were classified as noncalcified plaque. Plaques with yellow present were defined as calcified plaque without considering the calcified size. Luminal cross-sectional area (CSA) (mm²), vascular CSA—that is, external elastic membrane CSA in IVUS—and plaque burden (%) (defined as external elastic membrane CSA minus the luminal CSA and then divided by the external elastic membrane CSA again) were measured in each 10-mm interval cross section. Two investigators blinded to the IVUS results who were not involved in the later comparative analysis, performed these analyses independently [5].

Five well-distributed regions of interest (ROIs), each with a 1 mm² area, were selected in each plaque. The CT density of each ROI area was measured and recorded. The mean density was calculated by averaging the density measurements. Density measurements for calcification were performed only in hyperdense parts of the calcified plaques. To obtain accurate and complete density of noncalcified plaques, entire plaques were measured instead of hypodense tissue areas only [2]. Densities of different types (soft, fibrous, and fibrous-soft plaques) of noncalcified plaques corresponding to IVUS detection were retrospectively calculated.

IVUS was performed as part of the invasive diagnostic procedure. After coronary angiography, the patients were given intracoronary administration of 0.2 mg of nitroglycerin before introduction of the IVUS catheter. A Volcano Eagle Eye IVUS catheter (20-MHz, electronic transducer, Volcano) was used. The ultrasound catheter was positioned sufficiently distal (30 mm distal) to the targeted site, and motorized pullback at a speed of 0.5 mm/s was used.

The IVUS data were stored digitally and assessed offline by the software configuration of the IVUS system. As with MDCT, 10-mm segments were analyzed. The external elastic membrane CSA, equal to the vascular CSA in CT analysis, luminal CSA, and plaque burden were calculated by software after the borders of vessel intima and adventitia were depicted manually in each detectable cross section. These quantitative measurements were performed in accordance with the IVUS interpretation recommendations of the American College of Cardiology (ACC) [1]. According to the ACC recommendations, atherosclerotic plaques were defined as lesions located between the media and the intima with a thickness of at least 0.5 mm. Calcified plaques were defined as plaque tissue containing any tissue with an echogenicity as bright as, or brighter than, the adventitia causing acoustic shadows. Noncalcified plaques were defined as plaque tissue without acoustic shadows, including soft (hypoechoic) plaques, defined as plaque tissue revealing an echogenicity lower than the adventitia, and fibrous (hyperechoic) plaques, having an echogenicity as bright as, or brighter than, the adventitia. Plaques containing more than one acoustical subtype were considered mixed plaques. Fibrous-soft plaques were defined as plaques in which hypoechoic and hyperechoic lesion occupied approximately 50% of the plaque area, respectively, Two investigators, blinded to the CT results, independently determined the presence, classification, and quantitative measurement of athero-sclerotic plaque in IVUS images.

In this study, both 64-MDCT and IVUS were performed in 40 coronary arteries with moderate (50–75%) to significant (> 75%) coronary artery stenoses on conventional angiography, including three right coronary arteries (RCA), 14 left main arteries (LMA), 20 left anterior descending arteries (LAD), and three left circumflex arteries (LCX). Coronary atherosclerotic plaques often involve a large segment or the entire coronary vessel; therefore, the target coronary trees were divided into 10-mm segments on the basis of their distance to the ostium [2, 6]. The complete distance of the target artery from the distal reference point to the coronary ostium was measured using the longitudinally reconstructed IVUS data set and multiplanar reconstructions of the CT data set. Furthermore, we selected fiduciary points, such as side branches, characteristic calcifications, or stents, to ensure that the same corresponding coronary sections were compared. Each segment was morphologically classified according to IVUS and CT criteria. Noncalcified plaques defined by CT images included the soft, fibrous, and fibrous-soft plaques in IVUS; and calcified plaques defined by CT images were equal to the ones in IVUS, including fibrous calcified plaques. The comparison between 64-MDCT and IVUS was on a segmental basis for qualitative analysis and on a site-by-site basis for quantitative analysis. A measurement discrepancy of 1 mm per vessel section was tolerated.

Sensitivity and specificity of MDCT for detection of any plaque were calculated on a segment-per-segment basis. Cohen's kappa statistic was calculated to determine interobserver agreement in detecting plaque. The interobserver variability for 64-MDCT quantitative measurements was calculated [3]. To compare the mean density values of different plaque types, the nonparametric Kruskal-Wallis test was used. For comparison of the external elastic membrane CSA, luminal CSA, and plaque burden obtained by 64-MDCT and IVUS, the Spearman's rank correlation coefficient was determined. The paired Student's t test was used to test for potential differences between those parameters obtained by both methods. A p value < 0.05 was considered statistically significant. All calculations were performed using the SPSS13 software package (SPSS).