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Coronary Artery Calcium Measurement

Agreement of Multirow Detector and Electron Beam CT

¹ Department of Clinical Radiology, Ludwig-Maximilians-University Munich, Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany.
² Department of Medical Data Processing, Biometry, and Epidemiology, Ludwig-Maximilians-University Munich, Grosshadern, D-81377 Munich, Germany.
³ Department of Internal Medicine—Cardiology, Ludwig-Maximilians-University Munich, Grosshadern, D-81377 Munich, Germany.
⁴ Neolmagery Technologies, 17700 Castleton St., City of Industry, CA 91748.

Received June 1, 2000; accepted after revision October 30, 2000.

 
Address correspondence to C. R. Becker.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. The purpose of our study was to establish the most suitable algorithm to compare coronary artery calcium measurements performed with electron beam CT and multirow detector CT for the assessment of coronary artery disease.

SUBJECTS AND METHODS. Coronary artery screening was performed in 100 patients with both electron beam and multirow detector CT. The images were transferred to a dedicated workstation for determination of the calcium score, volume, mass, density, and number of lesions. In addition to the traditional threshold of 130 H, the score of multirow detector CT studies was reevaluated at a threshold of 90 H. Fifty-nine of the patients underwent conventional coronary catheterization. Receiver operating characteristic curve analysis of the different scoring algorithms for detection of significant coronary artery stenosis was performed.

RESULTS. The correlation between electron beam CT and multirow detector CT was high for every quantification algorithm. Determination of the score and the number of lesions with multirow detector CT revealed a systematic error of the measurement compared with electron beam CT. The areas under the curve in the receiver operating characteristic curve analyses for electron beam and multirow detector CT were similar for the score, volume, and mass, whereas they were lower for the density. No significant difference was found for the areas under the curve between scores using a 130-H and those using a 90-H threshold.

CONCLUSION. Volume and mass indexes are superior to the traditional score, density, and number of lesions for comparing the results of electron beam and multirow detector CT and for determining significant coronary artery disease.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Coronary artery calcification is a constituent of atherosclerosis [1]. Electron beam CT has been shown to be the most sensitive tool for detecting coronary calcification [2]. Detection of coronary calcification has been used to determine the presence of coronary artery disease in symptomatic patients with atypical chest pain [3].

Detecting coronary calcium alone would lead to an overestimation of coronary artery disease and of the risk for a coronary event, especially in young asymptomatic subjects [4]. Quantitative assessment of coronary calcium was developed by Agatston et al. [2] to overcome this limitation. The amount of coronary calcium was semiquantitatively determined using a scoring method based on a slice-by-slice analysis of electron beam CT images. The score was used to determine the amount of coronary calcium in patients with and without clinical coronary artery disease. This method of quantification also showed good correlation with the histomorphometric assessment of coronary calcium [5].

One recent study found that the total calcium load can be more accurately estimated on the basis of calcium plaque volume than on the established scoring method [6]. This group of researchers was able to follow the volume of calcified plaques in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [7]. New postprocessing workstations semiautomatically evaluate the traditional score as well as the volume, mass, and density of the coronary calcium plaque burden.

The detection and quantification of coronary calcium was also performed with dual helical CT scanners [8]. The comparison of score values obtained with electron beam CT and single-detector CT scanners showed high correlation [9]. New generation multirow detector CT scanners have recently become available that are capable of short exposure times (250 msec) and simultaneous acquisition of four slices with one ECG synchronized scan.

The first objective of our study was to determine the agreement of coronary calcium measurements with electron beam CT and multirow detector CT. Therefore, different quantification algorithms (score, volume, mass, and density) were compared. The second aim was to investigate the accuracy of the techniques and quantification algorithms in assessing significant coronary artery disease determined by selective coronary angiography.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
This comparative study was approved by the federal and institutional review boards. As a requirement of the federal board of radiation protection, only male patients could be included to avoid high effective radiation exposure of breast tissue during coronary screening in women [4]. Patient informed consent was obtained after the procedure had been fully explained. One hundred patients (age range, 27-87 years old; mean age, 63 ± 15 years) who were referred to our department because of a suspicion of coronary artery disease either because of clinical symptoms or because of the presence of cardiovascular risk factors were included in this study.

Detection and quantification of coronary calcium was performed with both electron beam CT (C150XP; Imatron, San Francisco, CA) and multirow detector CT (Somatom VolumeZoom; Siemens, Forchheim, Germany) within a maximum time interval of half an hour. For electron beam CT, we used a protocol with 3-mm slice thickness, 100-msec exposure time, 130 kV, 63 mAs, and prospective ECG triggering at 70% of the R-R interval. With multirow detector CT, slices were acquired with simultaneous acquisition of four 2.5-mm-thick slices, 140 kV, 100 mAs, 250-msec exposure time, and prospective ECG triggering at 450 msec before the next R wave. The entire heart (120 mm) was covered with both techniques in a single breath-hold (20-30 sec).

All images from electron beam CT and multirow detector CT were transferred to a dedicated workstation (InSight; NeoImagery Technologies, City of Industry, CA). With this workstation, the score according to the algorithm suggested by Agatston et al. [2] (area x cofactor; 1 = 130 - 199 H, 2 = 200 - 299 H, 3 = 300 - 399 H, 4 400 H), volume (area x slice increment), mass mass ([area x slice increment x mean CT density] / 250), and density (mass / volume) were determined by one radiologist. The same multirow detector CT image data were also used to determine a second score, for which a threshold of 90 H (score 90) was used for calculation instead of the commonly used 130 H (score 130).

For comparison of the score, volume, mass, and density, statistical analysis was performed calculating the linear regression and correlation coefficient between electron beam CT and multirow detector CT. The percentage of variability (v) was calculated as the mean of [absolute (value₁ - value₂) / (value₁ + value₂) / 2]. The systematic error (bias = d) and the limit of agreement (d ± 2s where s = standard deviation) of the two measurements were determined according to Bland and Altman [10] as the mean of [natural logarithm (value₁ + 1) - natural logarithm (value₂ + 1)]. Because the coronary calcium quantity values are not normally distributed, the values plus 1 have to be transformed for this procedure using the natural logarithm.

Fifty-nine of the patients examined with electron beam CT and multirow detector CT underwent selective coronary angiography. Selective coronary angiography was performed using a transfemoral Judkins approach with a minimum of three biplane standard projections. Cine angiograms documented on CD-ROM were displayed on an NT workstation (Acom PC V2.1; Siemens Medical Systems, Erlangen, Germany). The presence of coronary artery disease was assumed by a cardiologist (who was unaware of the results of the electron beam CT and multirow detector CT in a patient) when any significant coronary artery stenosis with more than 50% lumen reduction was present on selective coronary angiography. Receiver operating characteristic curve analysis [11] was performed in this subgroup of patients with dedicated software (MedCalc 5; MedCalc Software, Mariakerke, Belgium) to determine the area under the curve with standard error [12], sensitivity, and specificity. Comparison of the receiver operating characteristic curves from electron beam CT and multirow detector CT included calculation of the difference between the area under the curve and the p value [13].

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Using scores with the traditional 130-H threshold, we found that eight patients did not show any coronary calcium either on electron beam CT or on multirow detector CT images. In four patients, coronary calcium was revealed either on multirow detector CT (n = 3) or on electron beam CT (n = 1) but not on both techniques (Fig. 1A,1B). These four patients were excluded from further statistical analysis because inclusion of these data (with one test result negative and the other positive) would degrade the study because of the error of 100%. In the remaining 88 patients with positive findings on calcium scanning, an electron beam CT score of less than 10, 10-100, 100-400, and greater than 400 was determined in seven, 17, 21, and 43 patients, respectively. The median, mean, standard deviation, and maximum electron beam CT scores were 268, 793, 1183, and 5871, respectively.

View larger version (90K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —50-year-old man with suspected coronary artery disease. Electron beam CT image shows no calcium in artery (arrow).

View larger version (90K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —50-year-old man with suspected coronary artery disease. Multirow detector CT scan shows minute calcification (arrow) in distal part of left anterior descending coronary artery.

When we used score 90 in multirow detector CT, only six patients had negative coronary calcium findings with both electron beam CT and multirow detector CT. Five patients had negative findings on electron beam CT and positive findings on multirow detector CT, whereas three patients had negative findings with score 130 and positive findings with score 90 on multirow detector CT scans.

The correlation coefficient between electron beam CT and multirow detector CT was high for all quantification algorithms tested (r = 0.993-0.901). Linear regression used the following equations: Multirow detector CT score = 28.8 + 1.26 electron beam CT score (r = 0.987), and multirow detector CT volume = 20.9 + 1.05 electron beam CT volume (r = 0.986). The percentage variability was highest for the score (v = 32.2%) and lowest for the density (v = 8.4%). Determination of the score and the number of lesions with multirow detector CT showed a significant error of the measurement compared with electron beam CT (d = -0.206 and 0.158, respectively). The agreement of the measurement was best for the density (0.105 to -0.107), followed by the mass and the volume (0.578 to -0.61 and 0.554 to -0.598, respectively), and was worst for the number of lesions and the score (0.898 to -0.582 and 0.454 to -0.866, respectively).

Forty-five of the 59 patients showed at least one significant stenosis on selective coronary angiography. In the receiver operating characteristic curve analysis, the optimal cutpoints for predicting the presence of significant stenoses on the basis of calcium score values derived from electron beam CT and multirow detector CT were 198 and 291, respectively. The cut points for the volume were similar for electron beam CT and multirow detector CT (214 and 210, respectively). The area under the curve was higher for multirow detector CT than for electron beam CT for the score (0.845 and 0.834, respectively, Fig. 2), volume (0.843 and 0.841, respectively), mass (0.845 and 0.841, respectively), and number of lesions (0.819 and 0.781, respectively). For scores 130 and 90 in multirow detector CT, the areas under the curve for the score (Fig. 3), sensitivity, and specificity were the same (0.845, 79.5%, and 85.7%, respectively).

View larger version (13K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2. —Diagram shows receiver operating characteristic curves for electron beam CT (solid line) and multirow detector CT (dotted line). Difference of areas under receiver operating characteristic curves did not achieve statistical significance.

View larger version (14K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3. —Diagram compares receiver operating characteristic curves of multirow detector CT scores reevaluated with thresholds of 130 (solid line) and 90 (dotted line) H. Area under curve, sensitivity, and specificity are same for both quantification algorithms.

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Agatston et al. [2] were the first to describe a quantification method for coronary calcium from electron beam CT images. Using the area of the calcified lesion and a step-wise cofactor depending on the peak density of every plaque, a score is calculated that can be used to differentiate between patients with and those without coronary artery disease. However, the C-100 electron beam CT scanner used in the study by Agatston was able to acquire only a limited z-axis range (60 mm) of the entire coronary tree because of the limited number of scans (20 slices) that can be acquired in one breath-hold.

This method has been criticized because of the limited reproducibility of the score values. Hernigou et al. [14] suggested using only the first 12 of the 20 slices from the origin of the left main coronary artery to improve reproducibility. Wang et al. [15] found that covering the entire heart with 6-mm slice thickness is superior to the formerly used 3-mm protocol in terms of reproducibility. The newest version (C150) of electron beam CT scanners can image the entire heart with 3-mm slices in a single breath-hold. This method has yielded the highest sensitivity and negative predictive value for the detection of coronary artery calcium and the exclusion of coronary artery disease compared with partial scanning of the heart [16]. A recent study aimed at developing normograms for risk stratification summarized coronary calcium scores in 9728 patients. These data were collected regardless of the type of electron beam CT scanner (C-100 and C-150) and number of slices used for patient investigation [17].

Because of scanner specifications, multirow detector CT investigations of the heart need to be performed with 2.5-mm instead of 3 mm slice thickness. Nevertheless, calcified plaque is more often detected in the thinner multirow detector CT slices because of decreased partial volume. This higher sensitivity necessarily leads to a systematic error and poor agreement when comparing the score and number of lesions found using both techniques.

Three-dimensional quantification algorithms that are used to determine the plaque volume, mass, and density may be able to overcome this limitation. Detrano et al. [18] concluded that an estimate of the relative calcium mass in human heart specimens using electron beam CT is as accurate as the currently used calcium scores and reliably reflects the actual mass of precipitated calcium phosphate in diseased coronary arteries.

With the scan parameters proposed in this study, images from multirow detector CT scanners had a higher signal-to-noise ratio than electron beam CT images. Because of the better signal-to-noise ratio of mechanical scanners, the threshold for the score was reduced from 130 to 90 H using dual-slice CT scanners [19] to enable earlier detection of coronary calcifications. Despite the higher sensitivity with score 90, the area under the curve, sensitivity, and specificity were the same for scores 90 and 130, respectively.

For repeated scanning with electron beam CT, Yoon et al. [20] found a percentage variability of 37.2%, 28.2%, and 28.4% for the score, volume, and mass algorithms. These data are comparable to our results for agreement between electron beam CT and multirow detector CT. Yoon et al. concluded that the variability of the score may be decreased by adopting a continuous weighting function rather than the step function inherent in the current quantification technique. Such an approach is also supported by Shemesh et al. [19] for use with the dual-slice CT scanner. Furthermore, Yoon et al. stated that a quantification algorithm based solely on the volume of calcification performs equally well as one based on a continuous weighting function. According to our results, these statements seem to be true for the agreement between electron beam CT and multirow detector CT as well.

In addition, our results indicate that excellent agreement can also be achieved for multirow detector CT and electron beam CT density values. Plaque density seems to be a stable parameter, so that the use of a calibration phantom does not improve the reproducibility of the measurement [21]. Nevertheless, it seems that density is a poor predictor for significant coronary artery stenosis (areas under the curve for electron beam CT and multirow detector CT, 0.791 and 0.772, respectively). A threshold of 130 H corresponds to about 100 mg/dL of hydroxyapatite, indicating a lesion of the same density as spongy bone [22]. The diameter of coronary arteries and calcified plaques may vary between 4 and less than 1 mm in size. A number of calcified plaques will be smaller than the slice thickness used. In these plaques, the density on CT images depends more on the partial volume effect than on the true density of the calcified lesion. Therefore, these tiny plaques will be more accurately detected by using a smaller slice thickness.

With slice-by-slice acquisition, it remains difficult to reproduce minute calcified plaques with electron beam and with multirow detector CT. In a best-case scenario, a calcified plaque of 3-mm diameter may be exactly within a slice and thus be accurately depicted, whereas in the worst case it may be cut in half between two slices and may not be detected because of partial volume effects.

Helical multirow detector CT scanning with retrospective ECG gating is an alternative method of image acquisition that allows significantly shorter scanning time (15 sec) for 3- or 1.25-mm slice acquisition in a reasonable breath-holding time. In addition, a helical CT data set enables us to reconstruct the images at any desired slice position. Whether the number of missed plaques may be reduced with retrospective ECG gating, small incremental reconstruction, and thinner slices—and thus reduced volume averaging—needs to be investigated.

Unfortunately, retrospective ECG gating requires a larger radiation dose than prospective ECG triggering because scanning is performed during the entire cardiac cycle. Because electron beam CT has been proposed as a useful technique for assessing the progression or regression of coronary artery disease in response to treatment of risk factors such as hypercholesterolemia [7], future studies need to determine the reproducibility of the different multirow detector CT scanning techniques. In our patient population, electron beam CT and multirow detector CT showed similar accuracy in the determination of significant coronary artery disease compared with selective coronary angiography. Unfortunately, the quantity of coronary calcium is limited in the prediction of luminal narrowing because of the remodeling phenomenon of diseased coronary vessels [23].

In addition to the diagnostic implications, coronary calcium is considered to have a prognostic value in asymptomatic patients with cardiovascular risk factors [1]. In a recent meta-analysis of published literature on this topic, the summary risk ratio for coronary calcium predicting events such as nonfatal myocardial infarction and death was 4.2 [24]. The authors concluded that further studies are needed on the incremental value of electron beam CT over conventional risk prediction. However, the quality of the electron beam CT studies and the patient populations were significantly heterogeneous.

Because the agreement of the coronary artery calcium measurement between electron beam CT and multirow detector CT is high, multirow detector CT may also be considered a screening tool for coronary artery disease. However, larger and longer prospective cohort studies of non-self-referred screening subjects are needed, particularly in younger ages than those in previous studies of both electron beam and multirow detector CT.

References

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