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Cardiac Imaging |
1 From the Div of Cardiology, Los Angeles Biomedical Research Inst, 1124 W Carson St, Bldg E-5, Torrance, CA 90502 (R.C.D.); Dept of Biostatistics, Univ of Washington, Center for Health Studies, Group Health Cooperative, Seattle, Wash (M.A., J.N.); Dept of Medicine, Univ of California, Irvine (N.D.W.); Dept of Radiology, Wake Forest School of Medicine, Winston-Salem, NC (J.J.C.); David Geffen School of Medicine at UCLA, Los Angeles, Calif (M.M.G.); and Div of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (D.E.B.). Supported by contracts N01-HC-95159-95165 and N01-HC-95159-95169 from the National Heart, Lung, and Blood Institute. Received March 23, 2004; revision requested June 1; revision received August 30; accepted October 15. Address correspondence to R.C.D. (e-mail: rdetrano{at}labiomed.org).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: This investigation was approved by the institutional review boards of each study site and by the Institutional Review Board of the Los Angeles Biomedical Research Institute. Informed consent for scanning and participation was obtained from all participants. The study was Health Insurance Portability and Accountability Act compliant. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter observational study of 6814 participants undergoing demographic, risk factor, and subclinical disease evaluations. Coronary artery calcium was measured by using duplicate CT scans. Three study centers used electron-beam computed tomography (CT), and three used multi–detector row CT. Coronary artery calcium was detected in 3355 participants. Three calcium measurement methods—Agatston score, calcium volume, and interpolated volume score—were evaluated. Mean absolute differences between calcium measures on scans 1 and 2, excluding cases for which both scans had a measure of zero, was modeled by using linear regression to compare reproducibility between scanner types. A repeated measures analysis of variance test was used to compare reproducibility across calcium measures, with mean percentage absolute difference as the outcome measure. Rescan reproducibility in relation to misregistrations, noise, and motion artifacts was also examined. Variables were log transformed to create a more normal distribution.
RESULTS: Concordance for presence of calcium between duplicate scans was high and similar for both electron-beam and multi–detector row CT (96%, 
= 0.92). Mean absolute difference between calcium scores for the two scans was 15.8 for electron-beam and 16.9 for multi–detector row CT scanners (P = .06). Mean relative differences were 20.1 for Agatston score, 18.3 for calcium volume, and 18.3 for interpolated volume score (P < .01). Reproducibility was lower for scans with versus those without image misregistrations or motion artifacts (P < .01 for both).
CONCLUSION: Electron-beam and multi–detector row CT scanners have equivalent reproducibility for measuring coronary artery calcium. Calcium volumes and interpolated volume scores are slightly more reproducible than Agatston scores. Reproducibility is lower for scans with misregistrations or motion artifacts.
© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based multicenter observational study that includes the computed tomographic (CT) measurement of coronary calcium to further our understanding of the progression and prognosis of subclinical coronary atherosclerosis (1). In the MESA, 6814 volunteer participants were scanned, 52.8% of whom were women. The cohort had a high representation of American ethnic minorities: 27.9% black, 21.9% Hispanic, and 11.8% Asian (Chinese). Three of the six sites used electron-beam CT, and the remaining three sites used multi–detector row CT, which was performed with scanners manufactured by two vendors (Siemens and GE Medical Systems). Agatston scores, calcium volumes, and interpolated volume scores were calculated as described in the literature (2,3). The latter two measures offer theoretic advantages for reducing measurement error. Unlike Agatston scores, calcium volumes and interpolated volume scores are not dependent on multiple maximum lesion attenuation values and are therefore expected to be more stable and reproducible. The interpolated volume score offers the additional theoretic advantage of interpolative smoothing between image sections, which reduces the effect of image noise and might reduce measurement error. Thus, the purpose of our study was to evaluate the effect of scanner type (electron-beam vs multi–detector row CT scanners) and method of calcium measurement (Agatston scores, calcium volumes, and interpolated volume scores) on the reproducibility of calcium measurements.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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CT Technical Factors
Three MESA scanning sites used a C150 electron-beam CT scanner (GE Imatron, Milwaukee, Wis), one site used a LightSpeed Plus multi–detector row CT scanner (GE Medical Systems, Milwaukee, Wis), and two sites used a Volume Zoom multi–detector row CT scanner (Sensation 4; Siemens, Erlangen, Germany). Image acquisition was triggered by electrocardiograpic gating in all participants, and scans were reconstructed with a 35-cm field of view. Electron-beam CT systems operated with an image acquisition time of 100 msec. The scanner generated x-rays with a peak voltage of 130 kVp and a maximum current of 630 mA. Both multi–detector row CT systems operated with a 0.5-second gantry rotation, resulting in an effective temporal resolution of 0.33 second for the LightSpeed Plus scanner and 0.36 second for the Volume Zoom scanner, which used partial scan reconstruction algorithms. Tube current (107 mAs for Lightspeed Plus and 50 mAs for Volume Zoom) and tube voltage (120 kVp for Lightspeed Plus and 140 kVp for Volume Zoom) were user selectable and were fixed on the basis of the protocol recommended at the time of the initiation of the MESA.
For large subjects (defined as those weighing more than 220 lb [100 kg]) who were scanned with multi–detector row CT scanners, the tube current was increased 25% to reduce the anticipated increase in image noise. Current was increased on multi–detector row CT scanners only, because electron-beam CT systems do not have the capability to adjust tube current. A committee of cardiologists, epidemiologists, radiologists, and physicists decided the technical factors that were relevant to rescan variability (Table 1). Carr et al (4) provide further detail on the technical factors and estimates of effective radiation dose (5–7) for the three scanning systems.
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Quality Assessment
After the completion of scan reading, the reader subjectively evaluated the quality of the scan for the presence of (a) excessive motion artifacts (defined as a right coronary artery that appeared at least twice its expected diameter as the result of a comma-shaped motion artifact), (b) excessive misregistrations (defined as a gross irregularity in the heart border on reconstructed projection images or as an anatomic discontinuity involving at least three image section interfaces), and (c) excessive noise (defined as at least 30 false-positive lesions that were identified by the scoring computer software on or near the expected course of the coronary arteries). The reader used a dichotomous scale of excellent versus not excellent for each of these categories. In addition to these subjective assessments of image quality, the computer measured image noise as the mean (averaged over all image sections) of the standard deviation of attenuation. Measurements were obtained in a region of the calibration phantom where the hydroxyapatite had a physical density of 100 mg/cm3.
Statistical Analysis
Coronary calcium measurements were obtained at CT in all MESA participants (n = 6814). Participants who had fewer than two scans (n = 68) or who were missing one or more of the calcium measures (n = 5) were excluded from analyses, yielding an analytic sample of 6741 participants. The 3551 participants scanned with electron-beam CT were similar in sex (53.1% [1886 of 3551] female) and age distribution (62.8 years ± 10.3 [standard deviation]) to the 3190 participants (sex, 52.5% [1675 of 3190] female; mean age, 62.6 years ± 10.2) scanned with multi–detector row CT. Several methods were employed to assess differences in the rescan variability of calcium measures according to scanner type. First, the presence of calcium (Agatston score > 0) on scan 1 versus the presence of calcium on scan 2 was tabulated for all participants. Observed and chance-corrected ( statistic) agreement for the presence of calcium between the two scans were computed according to scanner type.
In addition, the absolute difference between scan 1 and scan 2 for each of the three calcium measures (Agatston score, calcium volume, and interpolated volume score) was modeled. We refer to this difference as the absolute rescan difference. A separate linear regression model was fit for the absolute rescan difference of each calcium measure, and the importance of scanner type as a predictor of rescan difference was assessed by using a Wald test. Absolute differences were highly skewed and, thus, were transformed with a natural logarithm (ie, ln[x + 1]) to normalize the distribution. Models were adjusted for body mass index and for the extent of calcium, as measured according to the mean (natural log transformed) Agatston score. No statistically significant differences were found for interactions between scanner type and the covariates (ie, body mass index and natural log transformed Agatston score). Models were fit for two subsets of participants—those with any calcium (Agatston score > 0) detected on at least one scan (n = 3355) and those with a small amount of calcium (Agatston score < 20 on both scans) detected on both scans (n = 678). The covariate-adjusted mean absolute differences in calcium measure were computed according to scanner type by exponentiating the estimated model means.
To further investigate the rescan variability of each calcium measure, multivariate linear models identical to those described previously were used to assess the effects of three dichotomous categories of image quality (motion artifacts, noise, and misregistrations), as assessed by the CT reader. If the reader rated both scans as excellent, the participant was said to have a scan pair with excellent image quality. Models were fit for all participants who had calcium (Agatston score > 0) detected on at least one scan and for those participants whose scans were graded by the primary MESA CT reader (n = 1038). Participants whose quality assessments were made by other CT readers were excluded to avoid the complicating effects of reader variability. Covariate-adjusted mean absolute differences in calcium measure were computed according to quality assurance ratings (categorized as excellent or not excellent) by exponentiating the estimated model means. No interactions between scanner type and image quality were found. A similar model fit the association between objective noise (measured continuously) and absolute rescan variability, with a partial correlation obtained and adjusted for the extent of calcium (natural log of Agatston score) and body mass index (in kilograms per square meter).
To compare the reproducibility of the three coronary calcium measures, we used methods described by Bland and Altman (12). Specifically, for each calcium measure, we plotted and linearly modeled the (arithmetic) rescan difference in calcium measures by using the mean calcium measure to test for systematic bias between scans 1 and 2. After no bias was found, we modeled the absolute rescan difference as a linear function of the mean calcium measure; the regression line was forced through the origin because the rescan difference is defined as zero when the mean calcium measure is zero. By using this regression equation and the assumption that the absolute differences follow a half-normal distribution, we computed a coefficient of reproducibility by multiplying the estimated regression line slope by 2.46—that is, 1.96 · 
(
/2) (12). By multiplying this coefficient by a participant's mean calcium measure, one can then obtain the 95% confidence interval for that participant's rescan difference. Thus, a smaller coefficient indicates better reproducibility.
To statistically test for differences in rescan variability between calcium measures, relative rescan differences (defined as the absolute rescan difference divided by the mean calcium measure of the two scans, multiplied by 100) were computed so that rescan variability of the calcium measures could be evaluated on a comparable scale. A repeated measures analysis of variance approach with log-transformed relative differences as the outcome was used to test for differences according to calcium measure. Pairwise t tests were used for post hoc comparison between each pair of calcium measures.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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statistic, was high and was the same for multi–detector row and electron-beam CT scanners ( = 0.92). For scans 1 and 2, the mean of the absolute rescan difference for each of the three calcium measures according to scanner type was adjusted for body mass index and the extent of calcium, and 95% confidence intervals were calculated (Table 2). In Table 2, the scanners are categorized according to vendor. The top half of the table presents data for all participants who had some calcification (Agatston score > 0) detected on at least one of the two scans. The mean absolute rescan difference in Agatston score was 16.9 for both multi–detector row CT scanners combined and 15.8 for electron-beam CT scanners. Similarly, no significant rescan differences were observed for calcium volume or interpolated volume score according to scanner type.
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Rescan differences were of similar magnitude for the two types of multi–detector row CT scanners (LightSpeed Plus vs Volume Zoom) for all scans and for the subset of participants with small amounts of calcium (Agatston scores < 20).
Effects of Image Quality on Rescan Variability
To further examine rescan variability, the adjusted mean absolute rescan differences were computed according to subjective assessments of the presence or absence of motion artifacts, noise, and misregistrations. The mean absolute rescan differences for all calcium measures were consistently and significantly larger for scans in which motion artifacts or misregistrations were judged as present (P 
.01 for all measures) (Table 3). There were, however, no differences in rescan variability for scans with versus those without subjectively assessed image noise (P > .5). Likewise, no differences in rescan variability were noted when noise was objectively assessed (partial correlations adjusted for the extent of calcium and body mass index were –0.13 for Agatston score [P = .46], 0.025 for the calcium volume [P = .15], and 0.034 for the interpolated volume score [P = .051]). Scans obtained at multi–detector row CT were judged to have more motion artifacts than those obtained at electron-beam CT (28.2% [900 of 3190 scans] vs 11.8% [419 of 3551 scans], respectively) (P < .05), and scans obtained at electron-beam CT were judged to have more image noise than those obtained at multi–detector row CT (11.5% [408 of 3551 scans] vs 2.1% [67 of 3190 scans], respectively) (P < .01). Adjustment for these specific image quality differences further reduced the significance of scanner type on rescan variability (P > .06 for all calcium measures).
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Comparison of Calcium Measures
The scatter diagrams of the rescan differences plotted against the means from scans 1 and 2 for each calcium measure show that the reproducibility of calcium measures evaluated in this way decreases with the extent of calcium (Fig 2). The lines on each diagram represent the limits of reproducibility, and the vertical distance between these lines can be interpreted as the range within which the absolute rescan differences will fall 95% of the time for a given level of calcium. The slopes of the lines are the coefficients of reproducibility (Table 4). The coefficient for Agatston score is 0.226, which means that 95% of the time we expect the absolute rescan difference in Agatston scores to be 226 mm3 or less for participants with a mean Agatston score of 1000. Similarly, the coefficient of reproducibility for this volume score is 0.209, which means that 95% of the time we expect rescan variability to be within 209 mm3 for a participant with a mean volume score of 1000. Note that these coefficients are descriptive and are not directly comparable because calcium measures are on different scales.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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There have been numerous assessments of rescan variability by using CT scanning. Table 5 shows most of these reports. Such reports suggest that the rescan variability of coronary calcium scanning is high and that there may be specific steps that would lead to increased reproducibility (13–23). Because these steps (eg, overlapping image section averaging, thicker image sections, and shorter triggering intervals for electron-beam CT) were not applied in the MESA, it is worthwhile to comment on them and to speculate on their potential effect on measurement reproducibility by using different scanner types.
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Mid-diastolic triggering may help to reduce rescan variability. Mao et al (18) used an electron-beam CT scanner to compare 40% RR triggering with the 80% RR triggering used in the MESA. They found significant improvement in reproducibility with the mid-diastolic 40% trigger compared with the more commonly used late diastolic 80% trigger. Though the work of Mao et al (18) requires duplication, the mid-diastolic trigger has clear theoretic advantages (24) that would strongly suggest the application of this technique in future research. Our results show that the presence of cardiac motion and misregistration artifacts is related to considerably greater rescan variability. Careful instruction in breath-hold techniques, as given in the MESA protocol, can help to minimize the likelihood of misregistrations. Motion artifact may be reduced by using a mid-diastolic trigger and by using higher temporal resolution.
Finally, Callister et al (3) found a 40% improvement in reproducibility by using the interpolated volume score in a relatively small group of subjects. In the MESA, we found that the calcium volume and interpolated volume score provided minimal improvement in reproducibility.
Our study was not a head-to-head comparison of the two types of CT scanning in the same subjects by using the same technologists. To our knowledge, only a few researchers have conducted such comparisons (25,26), and these comparisons were made by using technologies that are now outdated. Because such studies require that two scans be obtained in each subject with each scanner, at least four scans per subject would be required.
Our study was not designed to discern systematic technology-related biases toward the higher sensitivity of one type of scanner. Even with older technologies, however, such differences were difficult to elucidate (25,26).
The results reported here suggest that CT coronary calcium assessments can be performed with equivalent reproducibility by using electron-beam and multi–detector row CT scanners when careful attention is given to the standardization of scanning and reading protocols. Efforts to minimize misregistrations and motion artifacts are important because the presence of misregistrations and motion artifacts appear to reduce reproducibility in coronary artery calcium assessments. Volume-based scores appear to be slightly more reproducible than the Agatston score when either type of technology is used.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Abbreviations: MESA = Multi-Ethnic Study of Atherosclerosis
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, R.C.D.; study concepts, R.C.D., N.D.W., J.J.C., D.E.B., M.M.G.; study design, D.E.B., R.C.D., J.N., N.D.W., M.M.G., M.A.; literature research, R.C.D., N.D.W.; clinical studies, D.E.B., R.C.D., N.D.W., J.J.C., J.N.; data acquisition, D.E.B., R.C.D., N.D.W., J.J.C., M.A., J.N.; data analysis/interpretation, M.A., J.N., R.C.D.; statistical analysis, M.A., J.N., R.C.D.; manuscript preparation, R.C.D., M.A., J.N., J.J.C.; manuscript definition of intellectual content, R.C.D., M.A., J.N., J.J.C., D.E.B.; manuscript editing, revision/review, and final version approval, all authors
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References |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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