Accuracy of 64-Slice Computed Tomography to Classify and Quantify Plaque Volumes in the Proximal Coronary System

A Comparative Study Using Intravascular Ultrasound

Patients

From August 2004 to February 2005, we performed a contrast-enhanced 64-slice MDCT investigation as part of a research protocol in 112 patients who were scheduled for coronary angiography because of suspected coronary artery disease and referral from an independent external cardiologist. In 20 of these patients (18 men, 2 women, 59 ± 9 years) IVUS was performed in one to three vessels as part of the invasive catheterization procedure to evaluate coronary vessels without angiographic evidence of a significant stenosis >50% diameter reduction. In 12 patients, no history of coronary artery disease was known. Eight patients had coronary artery disease with previous stent implantation. The MDCT was performed at least 1 day (range, 1 to 2 days) before coronary catheterization. In patients with heart rates >70 beats/min, 50 to 100 mg of metoprolol was administered orally 60 min before the CT scan. In the presence of contraindications for a beta-blocker or an unsatisfactory lowering of the heart rate, the scan was performed at even greater heart rates. Patients with atrial fibrillation, contraindications for the administration of contrast agent, or an unstable clinical condition were not enrolled. The institutional review board of the Medical University of Munich approved the research protocol, and all patients gave informed consent.

64-slice CT scanning technique

The CT angiography was performed using a Sensation 64-slice CT scanner (Sensation 64, Siemens Medical Solutions, Forchheim, Germany). A bolus of 80 ml of contrast agent (Solutrast 300, 300 mgI/ml⁻¹, Altana, Konstanz, Germany) was injected intravenously (5 ml/s⁻¹). As soon as the signal in the ascending aorta reached a predefined threshold of 100 HU, the scan started automatically and the entire volume of the heart was acquired during one breath-hold in 8 to 9 s with simultaneous recording of the electrocardiogram (ECG)-trace. Detector collimation was 32 × 0.6 mm, gantry rotation speed was 330 ms per rotation, and tube voltage was 120 kV at a current of 550 to 750 mAs (depending on patient size) during 55% of the cardiac cycle (diastole) and a reduction of the current by 80% during the remaining time of the R-R interval. Per rotation, each detector is read out twice using a wobbling X-ray beam, resulting in 64 overlapping slices per rotation. This technology (z-sharp, Siemens Medical Solutions, Forchheim, Germany) allows one to generate slices with an overlap of 0.3 mm, resulting in a reconstructed slice thickness of approximately 0.4 mm. A detailed description of the technology is given elsewhere (7). In heart rates <65 beats/min, a half scan algorithm was applied, and for heart rates >65 beats/min, a two-segment reconstruction-algorithm offering a maximal temporal resolution of 83 ms was used (7,8). Using retrospective ECG-gating, the optimal ECG-phase providing best image quality was chosen.

64-slice CT image analysis

The display setting used for lumen and plaque quantification was empirically determined in a subset of six patients (recruited from the study population). In each patient, four different coronary sites that were easy to identify because of their location next to landmarks were selected. The image display setting at each site was then manipulated so that the MDCT image equaled the IVUS image in size (external elastic membrane area) and pattern and allowed exact separation between vessel, surrounding tissue, plaque, and lumen. The values for window width and window level of the respective section were recorded and were set in relation to the mean intensity within the lumen at the corresponding site. The results of this analysis revealed that the optimal setting to detect plaque and outer vessel boundaries is obtained on average at a width representing 155% (range, 395 to 809 Hounsfield units [HU]) of the mean intensity within the lumen and at a level representing 65% of the mean intensity (range, 165 to 339 HU). By keeping the window level (65% of mean intensity within the corresponding lumen) and reducing width to 1, lumen measurements provided optimal matching with IVUS. An independent investigator who was not involved in the later comparative analysis performed those initial measurements.

To allow comparison to IVUS, the coronary artery was divided in 3-mm sections, each section was classified according to the following criteria: Any structure with a density of 130 HU or more that: 1) could be visualized separately from the contrast-enhanced coronary lumen (either because it was “embedded” within noncalcified plaque or because its density was above the contrast-enhanced lumen); 2) could be assigned to the coronary artery wall; and 3) could be identified in at least two independent planes was defined as calcified atherosclerotic plaque (4). Structures clearly assignable to the vessel wall (in at least two views) with densities less than the lumen contrast were classified as noncalcified plaque components (5,9). Plaques in which >50% of the plaque area was occupied by calcified tissue (in the respective 3-mm section) were classified as calcified, and lesions with <50% calcium as mixed and lesions without any calcium were classified as noncalcified lesions. In addition, we classified the pattern of calcified tissue as spotty (at least two calcium spots <2 mm²embedded in noncalcified plaque tissue) or wide calcification (calcified areas >2 mm²). In the next step, all sections were analyzed for the presence of hypodense spots (lipid pools) that were defined as structures >2 mm²revealing a density of at least 20 HU less than the average value of surrounding noncalcified plaque tissue. The plaque volume for each 3-mm section was determined by multiplying the maximum plaque area within this section by 3. By adding plaque volumes of all respective sections, vessel plaque burden was calculated. Two independent investigators, both blinded to the IVUS results, did the analysis.

IVUS

We used a Volcano Eagle Eye IVUS-catheter (20-MHz, electronic transducer, Volcano Inc., Rancho Cordova, California) that accords to the technical requirements for IVUS systems recommended by the American College of Cardiology (10). The tip of the IVUS catheter was placed in the coronary vessel unless a diameter <2.5 mm was present. The pullback was performed automatically with 0.5 mm/s (Volcano Track Back II). The complete investigation was stored digitally, and the data sets were assessed offline by a cardiologist blinded to the 64-slice CT results. Because one IVUS pullback contains more than 1,000 frames, our analysis was performed by subsampling intervals of 1 mm acquired at diastole. As with MDCT, 3-mm sections were analyzed. According to the American College of Cardiology recommendations, atherosclerotic plaques were defined as structures located between the media and the intima with a thickness of at least 0.5 mm (10). The plaque volume for each 3-mm section was determined by multiplying the maximum plaque area by 3. By adding plaque volumes of all respective sections, vessel plaque burden was calculated.

Calcified plaques were defined as plaque tissue containing any tissue with an echogenity as bright or brighter than the adventitia causing acoustic shadows with an arc of calcium >180° in the respective 3-mm section. Mixed plaques were defined as having an arc of calcium <180° in the respective 3-mm section. Finally, noncalcified plaques were defined as plaque tissue without acoustic shadowing. Furthermore, we defined plaques containing an echolucent zone (no signal) as lipid core plaques, and we specifically determined the pattern of calcium as either spotty (multiple small calcium spots, arc <90%) or wide (arc <90°) (11,12).

Comparison of 64-slice CT and IVUS

To ensure that the same corresponding coronary sections were always compared with IVUS and MDCT, we selected fiduciary points, such as side branches, characteristic calcifications, or stents, for the distal starting reference. The distances between the fiduciary points and the coronary ostium were measured using the longitudinal reconstructed IVUS data sets and multiplanar reconstructions of the 64-slice CT datasets to ensure that distance measurements were the same with both methods. A measurement-discrepancy of 1.5 mm per vessel was tolerated. In the case of larger discrepancies, our comparison was restricted to smaller subsections. Starting from the distal reference point the coronary vessel was analyzed in 3-mm intervals and each section was directly compared with both methods.

Statistical analysis

For comparison of plaque volumes obtained by 64-slice CT and IVUS, Bland-Altman analysis was performed. The paired Student ttest was used to test for potential differences between mean values obtained by both methods. To determine the correlation of volume measurements by both methods, Spearman’s correlation coefficient was calculated. The interobserver variability for 64-slice CT measurements was calculated by the following formula: (volume observer 1 − volume observer 2) / [(0.5 × volume observer 1) + (0.5 × volume observer 2)], by averaging the values obtained for each individual patient the average variability was determined. For the reproducibility to detect atherosclerotic lesions within the respective sections, Cohen’s kappa coefficient was calculated. A p value <0.05 was considered to be significant.

Study limitations

A potential limitation of the present study is the fact that we did not enroll consecutive patients. However, all patients in the present study were recruited from clinical routine without any additional preselection criteria (e.g., obese patients, low heart rates, older patients) that may have affected the 64-slice CT results. An important issue and limitation for all CT studies is the significant radiation exposure to the patient, which is in the range of 9 to 14 msv with the current 64-slice CT-technology. This exposure is critical, especially if this technique is considered for preventional purposes in asymptomatic patients.

To find the optimal display settings allowing for the most accurate edge definition, we empirically determined image settings in a subset of our patients. Consequently, all results are related to these settings and may vary with the use of other settings. However, it is not likely those other settings will significantly improve the performance of 64-slice CT because only an improvement in resolution will diminish partial voluming and motion artifacts.