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1
Department of Diagnostic Radiology, Ludwig-Maximilians-University, Klinikum
Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany.
2
Department of Medical Data Processing, Biometry, and Epidemiology,
Ludwig-Maximilians-University, D-81377 Munich, Germany.
3
Department of Cardiology, Ludwig-Maximilians-University, D-81377 Munich,
Germany.
Received November 23, 1998;
accepted after revision July 28, 1999.
Address correspondence to C. R. Becker.
Abstract
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SUBJECTS AND METHODS. One hundred sixty male patients underwent electron beam CT and helical CT with a pitch of 1 (n = 30) and 2 (n = 30) and using a single-slice mode with (n = 50) and without (n = 50) prospective ECG triggering. In another 50 patients, we determined reproducibility for repeated scanning using electron beam CT. For all images, we derived the calcium score according to the Agatston method. We performed regression analysis and determined mean variability. Mean variability was calculated as the ratio of the absolute difference to the mean of the corresponding calcium scores.
RESULTS. The correlation coefficients for electron beam CT and all conventional CT modes were very high (range, 0.93-0.98). The mean variability was highest in the helical mode with a pitch of 2 (61.4%) and lowest for the single-slice mode with prospective ECG triggering (25.4%). For repeated electron beam CT, the correlation coefficient and mean variability were 0.99 and 22.1%, respectively.
CONCLUSION. ECG-triggered single-slice conventional CT had the best agreement with electron beam CT calcium scores.
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For quantitative assessment of coronary calcium load, a scoring method based on electron beam CT has been developed [2]. The method predicts angiographically detected coronary artery disease with a high sensitivity and specificity. Electron beam CT offers a short acquisition time of 100 msec and prospective ECG triggering to reduce cardiac motion artifacts. Because of longer scan times and the lack of ECG triggering, conventional CT is inadequate for the quantification of coronary calcium. However, prospective ECG triggering and acquisition times as short as 500 msec have recently become available for conventional CT [3].
Although conventional CT is useful for the detection of incidental coronary calcification [4], electron beam CT is the standard for the detection and quantification of coronary calcifications [5]. We studied the precision of calcium score measurements using conventional CT in helical and single-slice scanning modes with and without prospective ECG triggering in comparison with electron beam CT in patients suspected of having coronary artery disease.
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To ensure comparable image quality using electron beam CT (C-150XP; Imatron, San Francisco, CA) and conventional CT (Somatom Plus 4A; Siemens, Forchheim, Germany), a standard CT phantom (Catphan TM; The Phantom Laboratory, New York, NY) was scanned for determination and adaptation of image noise and high contrast resolution. For the standard scanning protocol using electron beam CT, 30 H of image noise and a high contrast resolution of seven line pairs per centimeter were determined. Using the same phantom, scanning parameters for the different modes of conventional CT were determined to obtain similar image noise and high contrast resolution with electron beam CT. Scanning parameters are summarized in Table 2.
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All patients underwent electron beam CT using standard protocols with 40 consecutive 3-mm slices of the entire heart and prospective ECG triggering at 80% of the cardiac cycle. Then the patients were randomly assigned to one of five groups. Patients in groups 1 and 2 underwent helical CT with a pitch of 1 (n = 30) or 2 (n = 30). Originally we planned to examine 50 patients in each group. However, we found that scores determined using helical CT with a pitch of 1 or 2 were significantly different (Wilcoxon's signed rank test, p = 0.01 and p = 0.003, respectively) from those determined using electron beam CT. Therefore, that portion of the study was terminated after examining 30 patients.
Patients in group 3 (n = 50) underwent single-slice conventional CT using a 500-msec scanning time without ECG triggering. Patients in group 4 (n = 50) underwent ECG-triggered single-slice conventional CT at 50% of the R-R interval. The minimal interscan delay using the single-slice scan mode is 1.5 sec. Therefore, it was impossible to cover a patient's entire heart (120 mm) with 3-mm slices during one breath-hold. Two clustered-scan series consisting of 20 slices each were performed and the patients were instructed to hold their breath for the first scan cluster. Next, the patients were allowed to breathe for 30 sec and then were instructed to hold their breath again for the second scan cluster. The duration of each scan cluster ranged from 30 to 40 sec, depending on each patient's heart rate.
To investigate the reproducibility of repeated electron beam CT, patients in group 5 (n = 50) underwent repeated scanning using electron beam CT. All investigations were performed at end-inspiration without contrast material.
All electron beam CT and conventional CT scans were transferred to a separate workstation (Magic View 1000; Siemens, Erlangen, Germany) and reviewed by one reviewer. We blinded reviewers to the scanning technique by hiding image information on the workstation. Coronary calcium plaques were identified as lesions in the coronary arteries with a density of greater than 130 H. To reduce the effect of image noise, only hyperattenuating foci with an area of greater than 2 mm2 were reviewed [6]. In ambiguous cases, consensus reading was performed by two reviewers.
We determined the calcium score using the Agatston method [2]. We used the region-of-interest function with the threshold option for pixel greater than 130 H to measure the area and peak density of plaques. Depending on the peak density of the plaque, the area of every plaque was multiplied by one of the following factors: a factor of 1 for 130-199 H, a factor of 2 for 200-299 H, a factor of 3 for 300-399 H, and a factor of 4 for densities greater than 400 H. The calcium score was then manually calculated as the total of the individual lesion scores in all coronary arteries. The time necessary to transfer images to the workstation and evaluate them ranged from 30 to 45 min per patient depending on the number of calcified plaques.
For statistical analysis, the nonparametric Wilcoxon's signed rank test for paired data, correlation, and linear regression was used with the scores derived from both techniques. Variability was calculated according to the following equation: (Abs [score 1 - score 2] / 0.5 x [score 1 + score 2]). To determine the level of systematic difference (bias) and the limit of agreement, we used a procedure proposed by Bland and Altman [7]. As the mean score increased, the difference between the two scores also increased. Therefore, as a requirement of the Bland and Altman procedure, scores +1 were transformed to the natural logarithm (ln). The level of systematic difference of the measurement (bias) corresponded to the mean (d) of (ln [electron beam CT score + 1] - ln [conventional CT score + 1]). The limit of agreement was calculated using d ± 2s (s = standard deviation).
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Scores derived from electron beam CT and helical CT pitch 1 (Wilcoxon's signed rank test, p = 0.030) and pitch 2 (p = 0.001) were significantly different. No significant difference was found for scores derived from single-slice conventional CT with (p = 0.585) or without (p = 0.453) ECG triggering and electron beam CT. We found high linear correlation for all groups with regression coefficients ranging from 0.934 to 0.993 (Fig. 1). Mean variability was smallest for repeated measurements using electron beam CT (22.1%) and slightly higher for ECG-triggered single-slice conventional CT (25.4%). Variability increased to 61.4% for helical CT pitch 2. This relation was true for the systematic error and the limit of agreement according to the Bland and Altman [7] evaluation. Repeated scanning using electron beam CT and ECG-triggered single-slice conventional CT had a negligible systematic error, whereas the systematic error was significantly higher for other groups. The limit of agreement decreased from group 1 to group 5 (Fig. 2). Results are summarized in Table 3.
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For quantification of coronary calcium, our findings showed nearly identical calcium scores for each patient, whether assessed by ECG-triggered single-slice conventional CT or electron beam CT. The small variability among measurements using electron beam CT and single-slice conventional CT is within the reported range of variability for repeated measurements using electron beam CT. The mean variability of scores for repeated scanning using electron beam CT was reported to be 29% [10], 37.2% [11], and 49% [12]; the systematic error to be -0.015 ± 0.46; and the limit of agreement to be from 0.91 to -0.94 [13]. The protocol used for these studies was based on scanning only 20 slices instead of 40 slices as was performed in our study. Only the newest version of the electron beam CT scanner can obtain 40 slices during one breath-hold, thus increasing reproducibility.
Research shows that the interobserver and intraobserver reliability for quantification using the Agatston method is high [14]. However, the interexamination reproducibility of scores by repeated electron beam CT is limited by many different factors. The most important factors that affect reproducibility are cardiac and respiratory motion artifacts [15], ECG misregistration [16], partial volume effects [13], image noise [6], field inhomogeneity [17], and the lack of calibration [18].
Cardiac Motion Artifacts
For images free of cardiac motion artifacts, acquisition times of less than
41.8 msec are necessary [19];
however, acquisition times this short are impossible to obtain using electron
beam CT or conventional CT. Because of relatively slow myocardial motion in
the diastolic phase, artifacts in electron beam CT are reduced, and
reproducibility increased with prospective ECG triggering at 80% of the R-R
interval (Figs. 3A and
3C). Because of the longer
exposure time of single-slice conventional CT, an interval of 50% was chosen
to ensure image acquisition just before significant motion artifacts arise
from systolic cardiac movement (Figs.
3B and
3D). To a certain degree, ECG
triggering also ensures scanning of the entire heart without gaps or overlap
caused by axial movement of the heart during a cardiac cycle. The important of
ECG triggering is proven by the low systematic error illustrated when using
electron beam CT and ECG-triggered single-slice conventional CT in comparison
with the high systematic error with other CT modes.
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Research shows that in helical CT reconstruction, the 180° linear
interpolation algorithm is superior to the 360° linear interpolation
algorithm for reducing motion artifacts in the ascending aorta
[20]. The 180° linear
interpolation algorithm, widely available in helical CT scanners, involves a
data range of 2 x (180° +
), with a fan beam angle
of
52°. Therefore, the temporal resolution of a 750-msec helical CT scan is
approximately 1 sec [21], two
times longer than that of a 240° partial view single-slice scan (500
msec). Longer scan time may have caused the wide-ranging values for the limit
of agreement for helical CT with pitch 1 and pitch 2. Additionally, fast table
movement in the helical mode seems to lead to pitch artifacts that increase
cardiac motion artifacts and thereby reduce the accuracy of the score
measurement using helical CT pitch 2 compared with helical CT pitch 1.
Respiratory Motion Artifacts
Using single-slice conventional CT, a minimal delay of 1.5 sec between two
slices requires the acquisition of two clustered scan series consisting of 20
slices each. This may lead to gaps or overlaps because of varying levels of
respiratory suspension for the two scan clusters. An approach using
spirometrically controlled CT
[22] may improve
reproducibility, especially for extensive calcifications in which
atherosclerosis extends to the distal part of the coronary arteries.
ECG Misregistration
ECG misregistration will result in scanning during a suboptimal phase of
the cardiac cycle. Misregistration will cause inconsistencies in slice
acquisition and result in gaps or overlaps between slices. Because the heart
rate changes during the scanning period in respiratory suspension, it is
essential to quickly adapt the ECG triggering to coincide with the changed
heart rate [23]. With electron
beam CT, prospective ECG triggering is performed by calculating the median of
the last seven R-R intervals. In single-slice conventional CT, the mean of the
last three R-R intervals is used to estimate the next R-R interval. With the
present software configuration in conventional CT, the timing of the trigger
signals during the scanning process is not recorded. The influence of a
changing heart rate, arrhythmia, and different trigger modes on the assessment
of coronary calcium thus remains unknown.
Partial Volume Effects
Partial volume effects of calcified plaques are not considered because of a
threshold, proposed by the Agatston scoring method, of 130 H for coronary
calcifications. Although streak artifacts may be seen because of longer
exposure times in conventional CT, these artifacts do not influence the
measurement of plaque (Fig. 4A,
4B). New scoring methods, such
as the continuous volume score, have been introduced to increase the
reproducibility of the coronary calcium measurements
[24]. The continuous volume
score is also based on a threshold of 130 H for the quantification of the
volume of calcified plaques.
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Image Noise
Image noise in CT is related to a low radiation dose that might hinder the
detection of small calcified plaques
[6]. Although it is impossible
to change the scanning parameters of electron beam CT, conventional CT allows
users to increase the tube current to reduce image noise. This option may be
helpful in detecting coronary calcifications in obese patients or in patients
with small amounts of coronary calcium.
Although the National Board of Radiation Protection did not allow us to examine patients younger than 50 years, our study group represented the complete range of possible calcium scores (0-6047). In a similar study on the reliability of scores using repetitive electron beam CT, a sample group of 50 patients was found to be sufficient for determining reliability [1].
Reproducibility of calcium score measurements using ECG-triggered single-slice conventional CT may be lower than using repeated electron beam CT because of the longer exposure time and the cluster scan technique used in conventional CT. However, no coronary calcium plaque for the diagnosis of coronary artery disease was overlooked using this technique. For electron beam CT, the reproducibility is insufficient to allow serial quantification earlier than 2 years after an initial scan [10]. The reproducibility of repeated scanning using conventional CT has not been established. Future studies should investigate the reproducibility of repeated scanning using conventional CT. This type of study could determine a reasonable interval for follow-up investigations using conventional CT.
Recently, helical CT has been applied to determine the quantification of coronary calcium [25]; however, its reliability in comparison with electron beam CT has not been determined. Helical CT may be preferable to electron beam CT and single-slice conventional CT for the continuous scanning of a certain volume. The advantage of helical CT is the short acquisition time without the necessity of cluster scanning. In combination with retrospective cardiac gating, a helical acquisition mode may be available for calcium scoring in the near future [26]. For single-detector scanning systems, changes of the heart rate during the scan will result in nonequidistant reconstruction increments. Multidetector row CT systems in combination with retrospective cardiac gating will allow shorter acquisition times and equidistant diastolic reconstruction at any table position [21].
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