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Coronary Artery Calcium Quantification at Multi–Detector Row CT: Influence of Heart Rate and Measurement Methods on Interacquisition Variability—Initial Experience¹

¹ From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, CB 8131, St Louis, MO 63110. Received June 7, 2002; revision requested August 9; final revision received November 18; accepted November 20. Address correspondence to K.T.B. (e-mail: baet@mir.wustl.edu).

	ABSTRACT

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PURPOSE: To assess the effect of heart rate on interacquisition variability in different coronary calcium quantification methods at multi–detector row computed tomography (CT).

MATERIALS AND METHODS: Fifty consecutive adults (39 men and 11 women; mean age, 57 years ± 13 [SD]) with various heart rates were examined with two prospectively electrocardiographically triggered multi–detector row CT acquisitions in succession for detection and quantification of coronary artery calcification. Calcium score, volume, and mass were measured for each acquisition. Interacquisition variability was evaluated in association with heart rate and quantification method in subjects and individual coronary vessels by using t tests and analysis of variance.

RESULTS: In 37 subjects with detected calcium, interacquisition variability in mass measurement (10.4%) was significantly lower than that in score (23.9%) and volume (15.7%) measurements (P < .02). The interacquisition variability in all quantification methods was well correlated with heart rate and was considerably greater when heart rates were higher than 70 beats per minute (bpm) than when heart rates were 70 bpm or lower (P < .002). There was a clear tendency for interacquisition variability to vary by vessel (P < .01). The correlation of interacquisition variability with heart rate and a significant difference in interacquisition variability between the group with heart rates of 70 bpm or lower and the group with rates higher than 70 bpm (P < .02) were found for the left main and left anterior descending arteries but not for the circumflex and right coronary arteries.

CONCLUSION: Interacquisition variability in coronary calcium measurements at multi–detector row CT is significantly less at lower heart rates. The coronary calcium mass measurement is more reproducible than are score and volume measurements.

© RSNA, 2003

Index terms: Computed tomography (CT), quantitative • Coronary vessels, calcification, 548.812 • Coronary vessels, CT, 548.1211

	INTRODUCTION

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The presence of calcium deposits in the coronary arteries is a surrogate marker of intimal atherosclerosis. The total calcium burden has been linked to severity of coronary artery disease (1), risk for future cardiac events (2), and progression of atherosclerosis during therapy (3); a semiquantitative calcium scoring system introduced by Agatston et al (4) is used to address these relationships. In the past decade, electron-beam computed tomography (CT) has become a standard modality for the detection and quantification of coronary calcification (5). In recent years, however, marked technical advances in spiral CT have sparked a great interest in the cardiac applications of conventional CT, especially multi–detector row CT. Strong correlation has been reported between spiral CT and electron-beam CT findings in the quantification of coronary calcium (6,7).

When one is monitoring the serial changes in calcium burden or assessing responses of atherosclerotic processes to therapy, a high level of reproducibility in coronary calcium measurements is crucial. One of the main problems affecting the reproducibility of coronary calcium measurement is cardiac motion artifact. For images completely free of motion artifacts, an acquisition time of 41.8 msec would be necessary (8). Such a short acquisition time is not currently possible with either electron-beam or multi–detector row CT technology. Therefore, several attempts have been made to determine optimal data acquisition timing (9,10).

However, changes in heart rate or cardiac rhythm may alter the duration or location of the components in the cardiac cycle, and, thus, acquisition may be disturbed by systole or atrial contraction. Results of previous studies have shown that both electron-beam CT and multi–detector row CT yield limited coronary image quality at high heart rates (11,12), and this limitation is more critical in multi–detector row CT because of its longer acquisition time. To our knowledge, results of no study regarding the effect of heart rate variability on the reproducibility of coronary calcium measurements at multi–detector row CT have been published.

The other source of reduced reproducibility is related to the quantification method itself. Because arbitrary scaling cofactors are used in the calculation of Agatston scores, such score values are easily and greatly affected by differences in peak CT attenuation of calcified plaques between acquisitions. A wide range of interacquisition variability of calcium scores has been reported (13,14). Alternative methods such as calcium volume (15) and mass (16) measurements have been proposed and have shown improved interacquisition reproducibility. Therefore, the purpose of this study was to assess the effect of heart rate on interacquisition variability in different coronary calcium quantification methods at multi–detector row CT.

	MATERIALS AND METHODS

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Subjects
This study was approved by the clinical study review board of our institution, and informed consent was obtained. The study group consisted of 50 consecutive adult subjects (39 men and 11 women; age range, 34–78 years; mean, 57 years ± 13 [SD]) who were referred for the detection and quantification of coronary artery calcification. The exclusion criteria included known cardiac disease, cardiac-related symptoms, and prior cardiac surgery or interventional procedures.

Imaging and Evaluation
CT scanning of the heart was performed with a multi–detector row CT scanner (VolumeZoom; Siemens, Forchheim, Germany). Each subject was imaged with two scanning passes in succession and did not change position between scanning passes. Subjects were placed in the supine position on the CT table, and electrocardiographic (ECG) leads were attached to the thorax. Each scanning pass was performed in sequential mode and within a single breath hold from 1 cm below the carina to the apex of the heart. Image data were acquired with 4 x 2.5-mm collimation, 120 kVp, 100 mA, 250-msec effective exposure time, and prospective ECG triggering. In each case, the triggering time point was determined by a radiology technologist trained in cardiac imaging, who observed tentative scanning time points projected in the ECG tracing and selected an optimal point, typically in the range of 50%–60% of the R-R interval. The optimal trigger time point was defined as that which ensured that data acquisition would occur completely or mostly within the diastolic phase. During scanning, the ECG tracing data and heart rate of subjects were monitored and recorded.

Two sets of images for each subject were transferred to a dedicated workstation (NetraMD; ScImage, Los Altos, Calif). One experienced radiologist (C.H.), who was blinded to subject information and to their heart rates, measured calcium score, volume, and mass at the workstation by manually positioning a cursor over each highlighted landmark on the left main (LM) artery, left anterior descending (LAD) artery, circumflex artery, and right coronary artery (RCA). A CT attenuation threshold of 130 HU was used for differentiating calcium lesions in the coronary arteries from soft tissues. In addition, the SD of CT attenuation in the aortic root lumen as measured within a circular region of interest (154 mm² ± 5 [SD]) was used as a measurement of image noise. The calcium score was determined according to the algorithm suggested by Agatston et al (4), in which area of a calcified lesion is defined as two or more contiguous pixels with attenuation of 130 HU or greater. Calcium volume was calculated by using the isotropic interpolation algorithm (15), while calcium mass was calculated by means of a calibration factor, which was determined from a calibration phantom scan (16).

Data Analysis
Interacquisition variability of coronary artery calcium score, volume, and mass was defined as the percentage difference in measurement values between initial and repeat acquisitions in each subject. Percentage difference was calculated as the mean of |V_i - V_r|/[0.5 x (V_i + V_r)], where V_i is the initial value and V_r is the repeat value, for all subjects and for individual coronary vessels. Relationships between interacquisition variability and heart rate were illustrated with scatterplots and were evaluated. We separated the subjects into the following groups: those with a low heart rate (≤70 beats per minute [bpm]) and those with a high heart rate (>70 bpm) (12,17) and those with a low Agatston score (≤100) and those with a high Agatston score (>100) (18). Interacquisition variability was compared between different groups and between different categories (ie, individual vessels and quantification methods) by calculating mean values. Differences between means were tested for statistical significance with paired t tests in the case of repeated calcium measurements. When the means of two different groups were compared, independent sample t tests were used. When more than two groups were compared, analysis of variance (ANOVA) was used to test for a difference among the means. P < .05 was considered to indicate a statistically significant difference.

	RESULTS

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Thirteen subjects had no detectable calcium at the 130 HU threshold, and their results were excluded from further statistical analysis. The remaining 37 subjects had a positive calcium score at both acquisitions: Three subjects had a score of 10 or lower, 15 had a score higher than 10 but less than or equal to 100, 11 had a score higher than 100 but less than or equal to 400, and eight had a score higher than 400. The medians, means, and SDs of calcium score, volume, and mass measurements are listed in Table 1. Image noise ranged from 10.0 HU to 24.5 HU, with a mean value of 15.2 HU ± 3.2 [SD].

The interacquisition variability in calcium score, volume, and mass measurements for all subjects is summarized in Table 2. Calcium score had the largest mean interacquisition variability (23.9%), followed by volume (15.7%) and mass (10.4%) measurements. The differences among the interacquisition variability values for the measurement methods were statistically significant (P < .02, paired t test). The interacquisition variability in each method correlated with that in other methods (r > 0.56, P < .001). The interacquisition variability in all methods correlated with image noise in that it tended to increase with increasing image noise. The differences in correlation with noise between the methods were small: r = 0.43, P = .008 for volume; r = 0.52, P = .001 for mass; and r = 0.56, P = .003 for score.

View larger version (32K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Scatterplot illustrates relationship between interacquisition (Interscan) variability and the heart rate of subjects. There is a clear tendency for interacquisition variability to increase as heart rate increases for volume (r = 0.55, P < .001), score (r = 0.63, P < .001), and mass (r = 0.67, P < .001) calcium quantification methods. Gray dots = score, white dots = volume, black dots = mass.

View larger version (23K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Bar graph illustrates interacquisition variability in the group of subjects with heart rates of 70 bpm or lower and in the group of subjects with heart rates higher than 70 bpm. For all measurement methods, interacquisition variability was considerably larger in the high heart rate group than in the low heart rate group (P < .002). Interacquisition variability was relatively small and uniform in all measurement methods in the group with heart rates of 70 bpm or lower; a statistically significant difference was seen only between score and mass measurement methods (P = .03, paired t test). In contrast, interacquisition variability was larger and more variable among the measurement methods when heart rates were higher than 70 bpm; statistically significant differences were observed among all measurement methods (P ≤ .01, paired t tests). Gray bar = score, white bar = volume, black bar = mass. Error bars represent 95% CIs.

View larger version (63K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Coronary artery calcium quantification with serial multi-detector row CT acquisitions in (a) a 47-year-old man with a mean heart rate of 43 bpm and (b) a 65-year-old man with a mean heart rate of 84 bpm. In a, a calcified plaque (arrows) in the proximal portion of the LAD artery is shown on two consecutive transverse images. The images are free of misregistration or motion artifact. Calcium measurements for the plaque with each of the two scans were very similar: score, volume, and mass measurements, respectively, were 76.3, 25.3 mm3, and 4.8 mg with the left image and 78.8, 25.8 mm3, and 4.8 mg with the right image. In b, two calcified plaques (arrows) in the proximal portion of the middle of the RCA are shown on two consecutive transverse images. The images are degraded by motion artifacts, and calcium measurements for the plaques with each of the two scans differed considerably: score, volume, and mass measurements, respectively, were 333.7, 313.4 mm3, and 57.4 mg with the left image and 445.8, 410.2 mm3, and 69.8 mg with the right image. Note that variation was least with mass measurement in both cases.

View larger version (75K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Coronary artery calcium quantification with serial multi-detector row CT acquisitions in (a) a 47-year-old man with a mean heart rate of 43 bpm and (b) a 65-year-old man with a mean heart rate of 84 bpm. In a, a calcified plaque (arrows) in the proximal portion of the LAD artery is shown on two consecutive transverse images. The images are free of misregistration or motion artifact. Calcium measurements for the plaque with each of the two scans were very similar: score, volume, and mass measurements, respectively, were 76.3, 25.3 mm3, and 4.8 mg with the left image and 78.8, 25.8 mm3, and 4.8 mg with the right image. In b, two calcified plaques (arrows) in the proximal portion of the middle of the RCA are shown on two consecutive transverse images. The images are degraded by motion artifacts, and calcium measurements for the plaques with each of the two scans differed considerably: score, volume, and mass measurements, respectively, were 333.7, 313.4 mm3, and 57.4 mg with the left image and 445.8, 410.2 mm3, and 69.8 mg with the right image. Note that variation was least with mass measurement in both cases.

Interacquisition variability clearly correlated with heart rate only in the LM and LAD arteries (r > 0.58, P < .001). There was a weak tendency for interacquisition variability to increase as heart rate increased in the circumflex artery (r < .25, P = .38) and the RCA (r < .27, P = .29), but this did not approach statistical significance. For all measurement methods, interacquisition variability in the LM and LAD arteries differed significantly between low and high heart rate groups (P < .02, t test). In contrast, interacquisition variability in the circumflex artery or in the RCA was not statistically different in any of the measurement methods (P > .35, t test) (Table 4).

	DISCUSSION

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Our results may be explained by the fact that coronary motion artifacts tend to increase on CT images obtained in patients with increased heart rates, thereby resulting in higher variability between acquisitions. In a previous study, Lu et al (11) measured coronary motion and found that the rest periods in the cardiac cycle for the LAD artery, circumflex artery, and RCA were 439.4–1,060.4 msec, 101.9–258.8 msec, and 87.2–167.7 msec, respectively, at heart rates lower than 70 bpm. Consequently, when heart rates are higher than 70 bpm, 250-msec temporal resolution at multi–detector row CT is probably insufficient for imaging the circumflex artery and RCA completely within the reduced cardiac rest period. In addition, heart rate acceleration increases the systolic component of the cardiac cycle (relative to diastole) (19). These increased systolic and diastolic variations cause motion artifacts and misregistration during CT data acquisition. Moreover, an increase in heart rate not only reduces the duration of diastole but also changes the location of the rest period in the cardiac cycle, which varies with heart rate and in individual vessels (9,11).

It is common practice to set ECG triggers at a fixed time point in the cardiac cycle for a prospective CT acquisition. Mao et al (10), in a report of a study of electron-beam CT, proposed an ECG trigger of 40% of the R-R interval, with which the reproducibility of coronary calcium scoring could be significantly improved. However, the heart rate variation discussed in the previous paragraph has not been considered. Because heart rate changes during suspension of respiration at CT, rapid adaptation of ECG triggers to heart rate is essential (20). It might be necessary to use an ECG trigger that is set individually according to heart rate or to a particular vessel rather than a specified trigger. Nevertheless, even such prospective ECG triggering may be inconsistent with rapid changes in heart rate or absolute arrhythmia, because the cardiac cycle varies unpredictably in such situations, thereby resulting in serious artifacts on images.

Unlike with electron-beam CT, with multi–detector row CT for coronary artery calcium measurement, a retrospective ECG gating technique is available for data acquisition. Because retrospective ECG gating does not rely on prospective estimations of the duration of the R-R interval, image reconstruction can be performed at a specific phase of the cardiac cycle, thereby effectively reducing motion artifacts. In this respect, retrospective ECG gating has potential advantages over prospective ECG triggering in patients with variable heart rates and even in patients with irregular heart rates or fibrillation. With advanced software and a retrospective ECG gating technique, cardiac time points corresponding to minimum motion artifacts can be automatically selected to sufficiently optimize image reconstruction timing, regardless of changes in heart rate during scanning (21).

Spiral CT facilitates high-spatial-resolution image data acquisition with small reconstruction intervals that reduce the partial volume averaging effect and prevent section gaps or overlaps owing to axial movement from heartbeats. This benefit may be advantageous in patients with a low coronary calcium burden. However, a trade-off for improving reproducibility with retrospectively gated spiral CT scanning is increased radiation exposure to patients, which may not be desirable in a screening study. Radiation exposure can be reduced with the use of ECG-controlled tube current modulation (22). Another option for lessening motion artifacts is to directly lower the heart rate by means of pharmacologic treatment, such as the adminstration of ß-blockers. But routine acceptance of this approach remains controversial.

Interacquisition reproducibility of measurements, in addition to benefitting from low patient heart rates, could be efficiently improved by the application of accurate and reproducible quantification methods. Our results demonstrated that, among the three methods of calcium quantification at serial multi–detector row CT, mass measurements had the best reproducibility for all subjects and for all individual vessels, in spite of the effects of heart rate and image noise. The use of a standard phantom for calibrating CT attenuation values will become increasingly important in the generation of reproducible calcium measurements, as indicated in previous reports (16,23) and in the present report. In our study, even in the group of subjects with heart rates of higher than 70 bpm and in the group of subjects with Agatston scores of 100 or less, the interacquisition variability of the mass method was significantly lower than that of conventional Agatston scoring (14,24) and was comparable with that of the optimized triggering (10) and volume algorithm (15) methods evaluated in studies of electron-beam CT in the general population.

However, in this study, the interacquisition variability in the circumflex artery and the RCA was relatively high, without a correlation with heart rate. Because 11 of 15 circumflex arteries and 12 of 18 RCAs were assigned an Agatston score below 100 and represented a large proportion of the vessels with a small amount of coronary calcification in this study, interacquisition variability was a problem primarily in these vessels, in which small differences in absolute values caused by partial volume effects or ECG misregistration may yield large percentage differences in measurements between acquisitions. In addition, because of their different anatomic courses, the RCA and circumflex artery show more extensive motion related to atrial contraction than does the LAD artery, resulting in larger variations.

In conclusion, heart rate has a significant effect on the interacquisition variability of coronary calcium measurements obtained with the current multi–detector row CT protocol (prospective ECG triggering, 4 x 2.5-mm collimation, 100 mA, 120 kVp, and 250-msec temporal resolution). The results of the present study demonstrate that higher reproducibility can be achieved at lower heart rates (≤70 bpm). The mass measurement was more reproducible than the calcium score or volume measurement. With increasing use of conventional CT, including multi–detector row CT, volume scanning for the detection of coronary calcium is becoming more readily available, and three-dimensional quantification algorithms such as determination of plaque volume and mass may replace the conventional two-dimension–based Agatston score.

	FOOTNOTES

 
Abbreviations: ANOVA = analysis of variance, ECG = electrocardiographic, LAD = left anterior descending, LM = left main, RCA = right coronary artery

Author contributions: Guarantors of integrity of entire study, C.H., K.T.B.; study concepts, C.H., K.T.B.; study design, C.H.; literature research, C.H., F.Z.; clinical studies, C.H., K.T.B.; data acquisition, C.H., T.K.P., F.Z.; data analysis/interpretation, C.H., T.K.P.; statistical analysis, T.K.P.; manuscript preparation, C.H., K.T.B., F.Z.; manuscript definition of intellectual content, C.H., K.T.B.; manuscript editing, C.H., F.Z.; manuscript revision/review, all authors; manuscript final version approval, C.H., K.T.B.

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This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hong, C. Articles by Zhu, F. Search for Related Content PubMed PubMed Citation Articles by Hong, C. Articles by Zhu, F.