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Sensitivity of Two Electron Beam Tomography Protocols for the Detection and Quantification of Coronary Artery Calcium

¹ EBT Research Foundation, 64 Valleybrook Dr., Hendersonville, TN 37075.
² Miami Cardiac and Vascular Institute, 8900 N. Kendall Dr., Miami, FL 33176.
³ Cardiology Section, SL 48, Tulane University School of Medicine, 14 Tulane Ave., New Orleans, LA 70112.

Received February 29, 2000; accepted after revision May 17, 2000.

 
Presented at the annual meeting of the American Roentgen Ray Society, Washington, DC, May 2000.

Address correspondence to P. Raggi.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. The purpose of this study was to compare the sensitivity of two electron beam tomography protocols for detection and quantification of coronary artery calcium.

SUBJECTS AND METHODS. We selected 101 patients (57% men, mean age 53 ± 10 years) to undergo two consecutive electron beam tomography and acquired imaging with both a 6-mm and a 3-mm slicing protocol. Three pixels (area, 1.03 mm²) and a minimal density of 130 H were used for definition of calcified plaque.

RESULTS. We found coronary artery calcifications in 46 patients when we used a 6-mm protocol and in 61 patients when we used a 3-mm protocol (p < 0.001). The average total calcium score was 77 (±140) with a 6-mm protocol and 251 (±395) with a 3-mm protocol (p < 0.005). The average number of calcified lesions per patient was 1.7 for a 6-mm protocol and 3.7 for a 3-mm protocol (p < 0.01). Of 179 individual lesions seen using a 3-mm protocol, 103 (58%) were missed using a 6-mm protocol, and only 27% of the lesions with a calcium score less than or equal to 40 seen with a 3-mm protocol were detected with 6-mm slicing (p < 0.001). The mean lesion attenuation with a 6-mm protocol was 160 (±42) H, compared with 218 (±44) H with a 3-mm protocol (p < 0.001), indicating a significantly greater partial volume averaging with the former protocol.

CONCLUSION. A 6-mm slicing protocol is significantly less sensitive than a 3-mm protocol for the detection and quantification of coronary artery calcium. Since one third of coronary events occur in patients with low calcium scores, a 6-mm protocol might be unreliable for risk assessment because of substantial loss of information in this calcium score range.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The severity of coronary artery calcification discovered on electron beam tomography has traditionally been measured using the score introduced by Agatston et al. [1]. This score bears a close correlation to the underlying atherosclerotic plaque burden [2, 3]. However, its reproducibility is poor because its calculation involves the multiplication of the area of a calcified plaque by an arbitrary coefficient based on peak plaque attenuation [4,5,6]. The original description of the score calculation assumed a slice thickness of 3 mm, a minimal area of 1 mm², and an attenuation greater than or equal to 130 H for a calcified lesion to be included in the final score [1]. Several imaging protocols have been developed to improve the reproducibility of the coronary artery calcium score calculated on electron beam tomography imaging. We recently introduced a new volumetric method based on the principle of isotropic interpolation that was shown to give more reproducible score measurements [7]. That study compared traditional and volumetric calcium scores, both obtained with a 3-mm slicing protocol. Other investigators focused on improving the traditional calcium score and showed that using a thicker 6-mm image slicing protocol renders the score more reproducible [8]. However, when the scores derived with this algorithm were applied to outcome research studies, the prognostic value of coronary artery calcification was not significantly different from that of traditional risk factors for coronary artery disease [9, 10]. This was in contrast with the results of other studies that used the traditional 3-mm imaging protocol [11, 12]. It is plausible that, even though it is more reproducible than the original 3-mm protocol, the 6-mm approach may cause significant loss of information. This would weaken the prognostic value of coronary artery calcification because cardiac events may occur in patients with low as well as high absolute calcium scores [13, 14]. The purpose of this study was to examine the sensitivity of a 3-mm and a 6-mm imaging protocol in a cohort of patients who underwent two consecutive electron beam tomography procedures. Furthermore, comparisons were made between our findings in a cohort of patients who suffered an acute myocardial infarction and those of other investigators who showed that coronary calcification does not hold a prognostic value superior to that of traditional risk factors.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The internal review board at our institution approved the protocol before study inception. The 101 patients who constitute this study were referred to our center by primary care physicians for screening electron beam tomography (57% men; mean age, 53 ± 10 years). All patients gave informed consent to undergo double electron beam tomography scanning (C-100; Imatron, San Francisco, CA). Imaging was performed using a 100-msec scanning time and either a 3-mm single-slice thickness with a total of 36 slices obtained during two breath-holding periods or a 6-mm single-slice thickness during one breath-holding period and a total of 18 slices. Imaging spanned from the carina to the diaphragm. Scanning was electrocardiographically triggered to 80% of the R-R wave interval. Images were obtained on a 30-cm² field of view (pixel size, 0.586 mm). All areas of calcification within the borders of a coronary artery with a minimal CT attenuation of 130 H were analyzed, and a minimum of 3 pixels (area, 1.03 mm²) was considered necessary for a calcified lesion to be included in the final count.

Offline image analysis was performed on a workstation (NetraMD; ScImage, Los Altos, CA). The calcium score was calculated according to the method described by Agatston et al. [1], which is briefly described here. The computer software measures the plaque area and the maximal CT attenuation within each region of interest. A score is then calculated by multiplying the measured areas by an attenuation coefficient based on the peak CT number (1, peak = 131-200; 2, peak = 201-300; 3, peak = 301-400; 4, peak > 401). The sum of all the individual scores measured within the borders of each coronary artery is used to compute the final total calcium score. Plaques visualized with either protocol were counted, and calcium scores per patient and per individual lesion were calculated. The mean attenuation of 76 pairs of calcific lesions seen on both protocols was compared.

We also measured the transverse coronary artery diameter on images obtained with a 3-mm protocol in 119 arteries, and the measurements were made at levels containing one or more calcific lesions.

A few prior studies that used a 6-mm slicing protocol [9, 10] showed a limited predictive value of coronary artery calcification for hard cardiac events (myocardial infarction and cardiac death). Of note, these studies included only older male patients (mean age, 66 ± 8 years) with several risk factors for coronary artery disease [10]. To assess whether a 6-mm imaging protocol might have influenced the results of those investigations, we further analyzed a subset of patient data reported in part in a prior publication [13]. In brief, 98 male patients (age range, 50-76 years; mean, 58 ± 6 years) without known coronary artery disease underwent electron beam tomography with a 3-mm protocol within 6 weeks of surviving a first myocardial infarction. The prevalence of coronary artery calcium and range of calcium scores were compared with those of 9899 asymptomatic men matched for age and risk factors for coronary artery disease. This comparison was conducted to estimate the prevalence of coronary artery calcification detected with a 3-mm slicing protocol in an apparently healthy population (9899 individuals) and in a cohort of patients who had recently suffered a major cardiac event (98 patients). Patients in both groups were men and in an age range similar to that of patients in studies that reported a limited predictive value for coronary artery calcium. A higher prevalence of coronary artery calcifications and frequent occurrence of calcium scores below a level detectable by a 6-mm protocol would therefore suggest the inadequacy of the imaging protocols used in such studies. Significance testing was conducted with the paired and unpaired t test for continuous variables and with the chi-square test on proportions for categoric variables. Values are expressed as mean plus or minus two standard deviations. All reported statistical values are two-tailed, and a p value of less than 0.05 was considered necessary to achieve statistical significance.

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patient Findings
Coronary artery calcifications were revealed in 61 patients with a 3-mm protocol and in 46 patients with a 6-mm protocol (p < 0.001, Table 1). Of the 15 patients with coronary artery calcifications on the 3-mm but not on the 6-mm images, 12 were men and three were women. Fourteen of these 15 patients had a total calcium score less than or equal to 40 (mean calcium score, 30 ± 8) on a 3-mm imaging protocol. Furthermore, of 22 patients with a total calcium score less than or equal to 40 seen on a 3-mm protocol, only six (27%) had coronary artery calcium on 6-mm studies. The highest score on a 3-mm study with a score of 0 on the 6-mm study was 89. On average, the total score for patients with coronary artery calcium deposits seen with both protocols was 69% lower on the 6-mm than on the 3-mm studies (77 ± 140 versus 251 ± 395, p < 0.005). In no instance were coronary artery calcifications seen on a 6-mm but not on a 3-mm study. Figure 1A,1B presents an example of discrepancy between a 3-mm and a 6-mm protocol for detection of coronary artery calcifications. The calcified area seen on the 3-mm images in the mid portion of the left anterior descending coronary artery disappears when scanning is repeated applying a 6-mm slicing protocol.

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —62-year-old woman with calcified coronary artery plaques. Axial electron beam tomography image obtained with 3-mm collimation protocol shows two distinct calcified areas at level of proximal (arrowhead) and mid (arrow) portions of the left anterior descending coronary artery.

View larger version (72K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —62-year-old woman with calcified coronary artery plaques. Axial electron beam tomography image with 6-mm collimation protocol obtained in same patient as in A. With this protocol, the proximal lesion appears much smaller, and the plaque in middle portion of vessel is undetectable. A greater degree of partial volume averaging causes smoothing and softening of image.

Individual Lesions
The total number of calcified lesions detected with a 3-mm protocol was statistically greater than that detected with a 6-mm protocol (179 versus 76, p < 0.001, Table 1). Consequently, the mean number of per-patient lesions detected with a 3-mm protocol was statistically greater than that detected with a 6-mm protocol (3.7 versus 1.7, p < 0.01). All 103 calcified areas missed on a 6-mm protocol but seen with a 3-mm protocol had a calcium score less than or equal to 40. Only 39 (27%) of 142 individual lesions seen on a 3-mm protocol with a calcium score less than or equal to 40 were identified when scanning was repeated with a 6-mm protocol (p < 0.001). The mean attenuation of 76 pairs of calcified coronary lesions detected on both protocols was 160 (±42 H) with a 6-mm and 218 ± 44 H with a 3-mm protocol (p < 0.001), indicating a significantly greater partial volume averaging with the former protocol. The transverse diameter of 119 coronary arteries segments was measured at the level of calcified lesions seen on 3-mm images. The average diameter was estimated to be 4.0 plus or minus 1 mm (4.3 ± 1 mm for men, 3.6 ± 0.9 mm for women, p < 0.001).

Patients After First Myocardial Infarction
The mean age of our 98 patients who survived a first myocardial infarction was 56 (±8). They all had coronary artery calcifications, with a mean calcium score of 495 ± 607 (range, 2-640; median, 268). For 14% of the patients, the calculated total score was less than or equal to 40. In comparison, age-matched men in the asymptomatic database showed a prevalence of coronary artery calcification of 83% and a mean calcium score of 239 ± 483 (range, 0-7623; median, 51). Of the database individuals with calcific coronary artery deposits, 35% had a score less than or equal to 40. We recall that in the prospective portion of the current study, 73% of the patients with a total calcium score less than or equal to 40 and 73% of the individual lesions seen on a 3-mm protocol with a score less than or equal to 40 were missed on a 6-mm imaging protocol. In a recent publication, Detrano et al. [10] reported using a 6-mm protocol in a study of 1196 men with a mean age of 66 years (±8 years). In contrast with the population in our database, the prevalence of coronary artery calcification in their study cohort was only 68% (83% versus 68%, p < 0.001), and the median calcium score was 44. This strongly suggests that there is a significant loss of information when electron beam tomography screening for presence of calcified coronary artery plaques is conducted using a 6-mm slicing protocol.

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
In this study, we compared a 3-mm and a 6-mm slicing protocol for the detection of coronary artery calcification in a cohort of 101 patients exposed to two consecutive electron beam tomography procedures. With a 3-mm protocol we detected significantly more calcified plaques, especially plaques of small dimension, and the calculated total calcium score was on the average approximately 70% larger than that obtained with a 6-mm protocol. Because of the demonstrable loss of information, it is probable that the predictive power of coronary artery calcium for events would be diminished if imaging were to be performed with the latter method. Some investigators used a 6-mm protocol for electron beam tomography screening in an attempt to create a more reproducible and reliable scoring method [8]. It is likely that the better interscan reproducibility of a 6-mm over a 3-mm protocol is due to two mechanisms: a shorter study acquisition time that allows reduction of motion artifacts and greater volume averaging. However, as our study suggests, the greater partial volume averaging associated with a 6-mm slicing protocol compared with that of a 3-mm protocol results in a loss of vital information. In an attempt to correct such weakness, Secci et al. [9] multiplied the calcium score measured on 6-mm images by a factor of 2. Nonetheless, we have shown in this study that the calcium score obtained with 3-mm imaging protocols is on the average 70% greater than that obtained with 6-mm protocols, and that several patients imaged with the latter protocol did not appear to have any coronary artery calcium. Therefore, the inherent limitations of a 6-mm slicing protocol could not be amended with such a simple mathematic correction.

In our uniform database of calcium scores collected in 9899 men 50-76 years old (mean age, 58 ± 6 years), the prevalence of coronary artery calcification was 83%. Strikingly, Detrano et al. [10] found only a 68% prevalence of coronary artery calcification in a cohort of older men selected because of high risk for coronary artery disease. This indicates a notable loss of sensitivity of a 6-mm protocol for detection of coronary artery calcium. The loss of sensitivity of a 6-mm protocol is particularly biased against small low-density lesions. This deficiency may be even more relevant for women, who notoriously have smaller calcium scores than men. In fact, among the women in our group of patients who survived a first myocardial infarction, 37% of the events happened in patients with a total calcium score of less than 40 (data not shown). It has been shown that small lesions as well as larger ones can be the substrate for acute coronary events [13, 14], possibly because small lesions represent more recently formed atherosclerotic lesions, and as such they may reflect the presence of vulnerable plaques [15].

The poor predictive value for events of an imaging protocol that has low sensitivity for small lesions implicitly supports this hypothesis. Indeed, the accuracy of CT scanners used for coronary and cardiac imaging may be drastically improved with the introduction of thinner slicing protocols, which would substantially limit partial volume effects. The newer multislice helical CT scanners can reduce the partial volume effect by reducing the slice thickness and can eliminate interslice gaps by acquiring a true volume of contiguous data. However, little information is available on reproducibility of calcium scores derived from the retrospective combination of data obtained during several heartbeats, although evidence is accumulating [16, 17].

Electron beam tomography has previously been shown to provide accurate measurements of coronary artery diameters [18, 19]. Our findings that the average size of a coronary artery at the level of a calcified lesion is approximately 4 mm again provide support for the arguement against using a protocol that averages data from slices of myocardium 6-mm thick. Further research is needed to improve time and spatial resolution of CT technologies applied to cardiac imaging. Until these technologic improvements are made, electron beam tomography screening should be performed using 3-mm imaging protocols to avoid loss of vital diagnostic and prognostic information.

References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

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