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DOI: 10.1148/radiol.2281012035
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(Radiology 2003;228:101-106.)
© RSNA, 2003

Cardiac Imaging

Quantification of Coronary Artery Calcium with Multi–Detector row CT: Assessing Interscan Variability with Different Tube Currents—Pilot Study1

Naoki Takahashi, MD2 and Kyongtae T. Bae, MD, PhD

1 From the Mallinckrodt Institute of Radiology, Washington University, School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110. From the 2001 RSNA Scientific Assembly. Received December 13, 2001; revision requested February 18, 2002; final revision received October 30; accepted November 11. Address correspondence to K.T.B. (e-mail: baet@mir.wustl.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To assess the interscan variability of coronary artery calcium as measured with different tube currents and quantification methods in prospective electrocardiography (ECG)-gated multi–detector row CT.

MATERIALS AND METHODS: Thirty-three subjects who were asymptomatic for coronary heart disease underwent prospective ECG-gated, subsecond multi–detector row CT of the heart. Each subject underwent two consecutive CT examinations, the first with a dose of either 40 mAs (n = 18) or 80 mAs (n = 15) and the second with a dose of 150 mAs. Calcium volume and calcium score were calculated. Pearson correlation coefficient was computed between the calcium scores of high- and low-dose examinations. Interscan variability in these measurements (ie, the absolute percentage difference) was compared between the examinations with 40–150 mAs and those with 80–150 mAs by using an independent sample t test. In addition, the interscan variabilities of calcium scores between vessels were evaluated with repeated measures of analysis of variance. The interscan variabilities between calcium score and volume measurement were also compared with paired t tests.

RESULTS: Twenty-seven of 33 subjects had coronary artery calcium deposits on both CT scans. Five subjects had no calcium deposit on either scan. One subject had calcium deposits on only one scan. The total calcium score between the high- and low-dose scans was highly correlated (r = 0.98) and was not significantly different (P = .58). The interscan variability of calcium score showed no significant difference with respect to subject (P = .25) or vessel (P = .84). The interscan variability of the calcium volume measurement was significantly lower than that of the calcium score with respect to both the subject (P < .01) and the vessel (P < .01).

CONCLUSION: A dose of 40 mAs appears adequate for quantifying coronary artery calcium at multi–detector row CT. Interscan variability of multi–detector row CT is substantially reduced by using the calcium volume method.

© RSNA, 2003

Index terms: Computed tomography (CT), multi–detector row • Coronary vessels, calcification, 54.76 • Coronary vessels, CT, 949.1291, 54.12119


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The presence of calcium deposits in coronary arteries has been well recognized as a marker of atherosclerotic coronary artery disease (1). Electron-beam computed tomography (CT) has been used successfully to quantify coronary artery calcium, which helps predict the presence of coronary artery disease (2–8), and has been reported to be useful in assessing the future risk of cardiac events (9–12).

The recent introduction of multi–detector row CT, with four simultaneously examined sections and half-second rotation time, provides a new modality for use in coronary artery imaging. Although the imaging time (temporal resolution) of multi–detector row CT is still longer than that of electron-beam CT, partial view acquisition and electrocardiographically (ECG)-gated reconstruction allow for fast image acquisition in the diastolic phase of the cardiac cycle (13). Multi–detector row CT has several advantages over electron-beam CT, including a higher signal-to-noise ratio because of a larger photon count (14,15), thinner section thickness, and simultaneous acquisition of four sections, which may reduce misregistration artifacts. The calcium score as measured with helical CT was shown in a 2000 study (16) to correlate well with that measured with electron-beam CT, although a later study demonstrated the presence of systematic differences between calcium scores measured with single–detector row helical CT and those measured with electron-beam CT (17).

CT examinations deliver a substantial amount of ionizing radiation, and the number of clinical applications of CT is continually increasing (18). Exposure to radiation is a concern, especially in subjects in the screening population, because many subjects undergo repeated examinations. Although the CT radiation dose may be relatively low per subject, the added risk to the population is substantive, with unknown long-term effects. Thus, attempts should be made to reduce the radiation dose. A reduction in radiation dose, however, may affect the image quality and quantification of coronary artery calcium deposits.

The objective of our study was to assess the interscan variability of coronary artery calcium, as measured with different tube currents and quantification methods, in prospective ECG-gated multi–detector row CT.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
This study was approved by our institutional clinical study review board, and all subjects gave their informed consent. During approximately 1 year, 33 consecutive subjects (20 men and 13 women; age range, 45–83 years; mean age, 63.0 years; standard deviation, 9.4 years) underwent CT during a single visit. Some subjects participated in the study in response to our advertisement for coronary calcium measurement research, while others were recruited at the radiology department during their clinical CT examination. None of the subjects had acute chest pain or other cardiac-related symptoms. Subjects with coronary stents, a cardiac pacemaker, or a history of cardiac surgery were excluded from the study.

Image Acquisition
CT examinations of the heart were performed by using a four–detector row CT scanner (Somatom Plus 4 Volume Zoom; Siemens Medical Systems, Iselin, NJ). Each subject underwent two consecutive CT examinations. The first examination was performed with either 40 mAs (n = 18) or 80 mAs (n = 15) and the second with 150 mAs. Other CT parameters used were ECG-triggered sequential scan mode, 4 x 2.5-mm collimation, and 140 kVp. Subjects remained stationary on the CT gantry table during both examinations. The examination was performed during a single breath hold from approximately 1 cm below the carina to the inferior margin of the heart. CT image acquisition at each sequential table position was triggered at a fixed scan delay of the R-R interval recorded in the monitoring ECG signal linked to the CT scanner. The scan delay from the previous R-R interval was determined from the subject’s heart rate, with a scan delay of 60% for a heart rate of 70 beats per minute or lower, 50% for a heart rate of 70–79 beats per minute, and 45% for a heart rate of 80 beats per minute or higher. This scan delay was recommended in the cardiac imaging protocol provided by the manufacturer of the CT scanner. At each trigger, four sections were simultaneously acquired with a gantry rotation time of 500 msec and a temporal resolution of 330 msec (a half-scan plus additional scan coverage for fan-beam width). One rotation covered 10 mm (4 x 2.5 mm) in the direction of the z axis. The scan duration, which was dependent on heart rate, typically lasted 20 seconds for 120 mm of coverage. The images were reconstructed with a standard soft-tissue reconstruction kernel in a small field of view (typically 200–280 mm) that encompassed the entire heart. This field of view resulted in 0.4–0.5 mm/pixel resolution in a 512 x 512 matrix CT image.

Data Measurement and Analysis
CT images were transferred to a workstation (Virtuoso; Siemens Medical Systems) with dedicated cardiac analysis software. Calcium score was calculated by a radiologist (N.T.) with the Agatston algorithm (19). With this algorithm, a calcified lesion was defined as two or more contiguous pixels with CT attenuation equal to or greater than 130 HU in each section. An attenuation factor was determined on the basis of the maximal CT attenuation of the lesion as follows: factor 1 = 130–199 HU, factor 2 = 200–299 HU, factor 3 = 300–399 HU, and factor 4 = 400 HU or greater. A calcium score was calculated by multiplying the area of calcified plaque by an attenuation factor. The total calcium score was determined by summing the lesion scores for all sections. Calcium score for each coronary vessel (left main, left anterior descending, left circumflex, and right coronary arteries) was also calculated. In addition, the total calcium volume was calculated by multiplying the area of the calcified lesion (measured in square millimeters) by section thickness (2.5 mm). The calcium volume for each coronary vessel was computed by summing the volumes of the lesions in that vessel for all sections. Finally, the total volume from all the vessels became the calcium volume for a subject.

Calcium score and volume at high- and low-dose scanning were calculated separately in different sessions. Measurements at high and low dose were compared according to vessel and according to total for each subject by using a paired t test. Correlation of the calcium score was measured with the Pearson correlation coefficient. Since the calcium score data were highly skewed in raw form, they were log-transformed (log10 [1 + score]) and became more suitable for correlation analysis.

The absolute percentage differences between high- and low-dose scans were calculated for calcium scores and calcium volume measurements. Absolute percentage difference was defined as

where A1 is the calcium score or volume measurement from the high-dose scan, and A2 is the calcium score or volume from the low-dose scan. The absolute percentage differences of calcium score were compared between vessels by using repeated measures of analysis of variance (ANOVA). When the results of ANOVA were statistically significant, differences between individual pairs were tested by using paired t tests. The absolute percentage differences of calcium score were also compared between the subject group that underwent 40-mAs and 150-mAs scanning and the subject group that underwent 80-mAs and 150-mAs scanning according to vessel and according to total for subjects with an independent sample t test. The absolute percentage differences of calcium score and calcium volume measurements were also compared with paired t tests. A P value of .05 was considered to indicate a statistically significant difference for a single comparison, and a P value of .01 was considered to indicate a statistically significant difference for multiple comparisons. Two-sided tests were used in all pairwise comparisons. All statistical analyses were performed by using computer software (JMP; SAS Institute, Cary, NC).

Each subject was assigned a clinical cardiovascular risk based on his or her calcium score by using the guideline proposed by Rumberger et al (20). According to this guideline, a calcium score of 0 is categorized as normal, 1–10 as minimal, 11–100 as mild, 101–400 as moderate, and more than 401 as high risk. The guideline recommends a treatment and intervention plan based on this calcium score and other risk factors. Since each subject underwent two consecutive CT examinations, separate risk categories were calculated by using the calcium score obtained for each examination.

Noise level of each image was calculated from the standard deviation of the CT attenuation in the 1-cm2 circular region of interest placed by a radiologist (N.T.) over the lumen of the ascending aorta at the level of the main pulmonary artery.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Twenty-seven of 33 subjects had coronary artery calcium deposits at both CT examinations, five subjects had no calcium deposit at either examination, and one subject had a calcium deposit at only one of two examinations. Figure 1 demonstrates multi–detector row CT images obtained with high and low doses in two subjects. The mean total calcium score was 326.2 (range, 0–2,500). No significant difference between the high-dose scan and the low-dose scan was found in total calcium score (paired t test, P = .58). The log-transformed total calcium scores of the high-dose scan and low-dose scan were highly correlated (r = 0.98).



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  		Figure 1. A and B, Two consecutive transverse CT scans obtained with (A) 150 mAs and (B) 40 mAs in one subject. C and D, Two consecutive transverse CT scans obtained with (C) 150 mAs and (D) 80 mAs in another subject. All four scans show calcium deposits (arrows in A and C) in the left anterior descending artery. Increases in noise with lower dose values are apparent in these images.

 
Of 132 individual vessels studied, 81 had a calcified plaque on at least one scan (left main, 11; left anterior descending, 25; circumflex, 25; right coronary, 20), and 51 vessels had no calcified plaque on either scan. A calcified plaque was detected on only one of two scans in eight vessels (left main, two; left anterior descending, none; circumflex, three; right coronary, three). Of these, six were detected only on the high-dose scan, and two were detected only on the low-dose scan; however, no significant difference between the high-dose scan and low-dose scan was observed in the calcium score of individual vessels (paired t test, P = .65). There was a strong correlation (r = 0.98) between the scores of high-dose scans and low-dose scans by vessel (Fig 2).



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  		Figure 2. The log-transformed calcium scores of low-dose scans and high-dose scans according to vessel are highly correlated (r = 0.98). {diamond} = left main coronary artery, {square} = left anterior descending coronary artery, {triangleup} = circumflex coronary artery, x = right coronary artery. In this logarithm calcium score scale, 0-1, 1-2, and 2-3 ranges correspond to minimal-, moderate-, and high-risk categories, respectively.

 
The means and standard deviations of the absolute percentage differences for calcium score are presented in Table 1. The absolute percentage differences were calculated with respect to total calcium score of the subject and calcium score of the individual vessel. A significant difference was observed between vessels (repeated measures ANOVA, P = .01). When the vessels were compared in a pairwise fashion, the circumflex vessel differed significantly from the left anterior descending vessel (P < .001) and the left main vessel (P = .01), but it did not differ significantly from the right coronary vessel (P = .06). No other differences were statistically significant (P > .3). Since the interscan variability is affected by the prevalence of calcium deposit in the individual coronary arteries, the absolute percentage differences were also calculated for subjects or vessels in which calcium was noted after at least one examination (Table 1). For comparison, the data obtained with electron-beam CT by Yoon et al (21) are included in Table 1.


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  		TABLE 1. Absolute Percentage Differences for Calcium Score, according to Modality

 
The absolute percentage differences for calcium score between the subject group that underwent 40-mAs and 150-mAs examinations and the subject group that underwent 80-mAs and 150-mAs examinations are shown in Figure 3 and Table 2. No significant difference between the two groups was observed with respect to the total calcium score of the subject (independent samples t test, P = .25) or the vessel (independent samples t test, P = .84).



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  		Figure 3. The absolute percentage differences for calcium score by vessel between the subject group that underwent 40-mAs and 150-mAs examinations ({diamondsuit}) versus the subject group that underwent 80-mAs and 150-mAs examinations ({square}). There was no significant difference between the two groups with respect to total score of the subject (independent samples t test, P = .25) or the vessel (independent samples t test, P = .84).

 

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  		TABLE 2. Absolute Percentage Differences for Calcium Score according to Radiation Dose

 
The absolute percentage differences for calcium score and calcium volume were compared with paired t tests and are summarized in Table 3. The interscan variability was significantly lower in calcium volume compared to calcium score, with respect to the subject (P < .01) and vessel (P < .01).


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  		TABLE 3. Absolute Percentage Differences (ie, Interscan Variability) for Calcium Score and Volume Measurements

 
The numbers of scans classified at each risk category according to high- and low-dose imaging protocols are shown in Table 4. In six subjects, the risk category changed by one level when going from the low- to high-dose imaging protocols. In two subjects, the risk category was upgraded by one, while in four subjects, the risk category was downgraded by one.


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  		TABLE 4. Classification of Risk Categories Based on Calcium Scores, according to High- and Low-Dose Examinations

 
The mean noise level measured in the aortic lumen was 9.6 ± 3.0, 11.8 ± 3.2, and 19.0 ± 6.4 (mean ± standard deviation) in scans obtained with a dose of 150, 80, and 40 mAs, respectively.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
The calcium score between the high-dose and the low-dose scans was highly correlated with respect to the subject and vessel. As expected, the absolute percentage difference was larger in the subjects or vessels with a lower calcium load. Fifteen of 16 subjects with a total calcium score above 100 had interscan variability below 50%.

The absolute percentage difference of 31.9% in the total calcium score in our study is comparable to that in previous studies that used electron-beam CT, in which the absolute percentage differences of total calcium score ranged from 22.1% to 44.5% (16,21–24). The absolute percentage difference in calcium score by vessel was also similar to the result obtained with electron-beam CT (21). The high correlation between two consecutive scans in our study was also comparable to the high correlation (r = 0.96–0.99) reported for previous studies that used electron-beam CT (16,21,25). In a study that compared coronary calcium scores calculated from single– and multi–detector row CT and electron-beam CT data, Becker et al (16) observed that the absolute percentage differences between helical CT and electron-beam CT were 25.4% and 28.8% for single– and multi–detector row CT, respectively.

The causes of interscan variability include observer error, cardiac motion artifact, volume averaging, misregistration artifact, breathing motion artifact, and inherent image noise. Intraobserver or interobserver variability play very little role relative to these other issues (15,26). Cardiac motion cannot always be avoided by using multi–detector row CT with temporal resolution of 330 msec and may be a major source of interscan variability. Cardiac motion artifact is known to artificially raise the calcium score (27). Electron-beam CT is superior to multi–detector row CT in reducing this artifact because of the higher temporal resolution of electron-beam CT. On the other hand, the advantages of multi–detector row CT over electron-beam CT are less quantum noise, thinner section thickness, and simultaneous acquisition of four sections, which reduces misregistration artifact.

Subject population will affect the interscan variability when comparing two subject groups. Subjects without coronary artery calcium or with heavy calcium load have a favorable effect on the interscan variability. To reduce this bias, the absolute percentage differences were calculated for subjects in whom calcium was detected on at least one scan. The percentage differences were higher than expected, but our results were similar to those of Yoon et al (21).

Rumberger et al (20) proposed a clinical cardiovascular risk stratification scheme for subject care on the basis of a subject’s calcium score. In our study, despite a relatively large interscan variability, the risk stratification changed between two consecutive examinations by one level in six subjects. The calcium scores of these subjects were near the threshold values of the risk stratification levels; thus, a small change in scores between the scans resulted in different risk levels. This finding suggests that interscan variability may have little bearing on cardiovascular risk assessment and the subsequent care of the subject.

Previous studies have shown that the average increase in calcium score was 24%–33% per year (28,29). The interscan variability of CT for calcium score is probably too large to make monitoring annual change meaningful on an individual basis. Several attempts have been made to reduce interscan variability, including use of larger section thickness (23), lower CT attenuation number threshold (15) or larger pixel size threshold (30) as a definition of calcium lesion, and calcium volume measurement (24, 30). It has been shown that interscan variability decreases with use of calcium volume measurement (24, 30). It is thought that this reduction occurs because the attenuation scale factors used in the calcium score calculation are kept constant for calcium volume measurement. Finally, another approach to reduce the interscan variability is to perform two consecutive examinations and average the calcium scores (21).

Our results confirm that interscan variability decreases from 31.9% to 22.4% for the subject and from 37.1% to 33.4% for the vessel when changing from calcium score to calcium volume. This is compatible with the results published in previous studies (24,30), in which interscan variability decreased from 37%–40% for calcium score to 25%–28% for calcium volume. Callister et al (24) also noted that interscan variability improved from 29% to 18% with respect to subject and from 35% to 22% with respect to vessel by combining the section interpolation technique with calcium volume measurement. The section interpolation technique was not incorporated in our study. Despite its higher interscan variability, calcium score has been more widely used than calcium volume because extensive clinical databases have been accrued and are available on calcium score, as correlated with clinical cardiovascular risk and atherosclerotic disease.

The estimated radiation dose from a 150-mAs multi–detector row CT examination in this study is 0.6 mSv, with breast glandular tissue being the critical organ in women. Reducing the radiation in the examination has a proportional effect on reducing the radiation dose to the subject. Although the noise level of 40-mAs scans is approximately 50% higher than that of 80 mAs scans, the interscan variability of 40-mAs scans was comparable to that of 80-mAs scans. This result may be interpreted so that the noise factor is smaller than other sources (heart rate variation, partial volume averaging, and calcium attenuation threshold), contributing to the overall interscan variability, which we did not evaluate in this study.

One of the limitations of our study is that we used a dose of 40 mAs or 80 mAs for the first examination and a dose of 150 mAs for the second examination. The overall interscan variability of multi–detector row CT, which we compared with that of electron-beam CT, was calculated from examinations performed with three different doses. The interscan variability we used to compare 40-mAs and 80-mAs examinations was obtained from the scans of subjects who underwent 40-mAs and 150-mAs examinations and those who underwent 80-mAs and 150-mAs examinations. This does not truly represent interscan variability of 40-mAs or 80-mAs examinations, since no subject underwent a 40-mAs examination followed by an 80-mAs examination. In the current study, 150 mAs was chosen for the high dose examination on the basis of the protocol recommended by the vendor at the time the study was begun.

Another limitation is that we did not test doses lower than 40 mAs. The threshold of 130 HU for calcified lesions was determined as 2 standard deviations above the average CT attenuation number of blood by using electron-beam CT (31). In our study, the mean noise levels, as defined by the 1 standard deviation of the CT attenuation number measurement of the blood in the ascending aorta, were 19.0 HU ± 6.4, 11.8 HU ± 3.2, and 9.6 HU ± 3.0 (mean ± standard deviation) for scans obtained with doses of 40 mAs, 80 mAs, and 150 mAs, respectively. If the noise level is assumed to be inversely proportional to the square root of the dose (measured in milliampere-second), a scan obtained with a dose of 30 mAs would give a noise level of approximately 24 HU ± 8. In most subjects, the noise level would be below 40 HU. The CT attenuation number of blood (42 HU) plus twice the noise level (2 x 40 HU) would still be lower than the threshold of 130 HU for calcium lesions. Further study may be useful to test if a dose lower than 40 mAs could provide scans of adequate quality for calcium scoring. It has been shown that for lung cancer screening with helical CT, the tube current can be lowered to 25 mAs, without substantially decreasing diagnostic accuracy (32).

In conclusion, use of 40 mAs appears adequate for quantifying coronary artery calcium with multi–detector row CT. The large interscan variability remains the major drawback of the calcium quantification with CT. We confirm that the interscan variability of multi–detector row CT is similar to that of electron-beam CT. The interscan variability was significantly smaller with calcium volume than with calcium score. An alternative practical approach for reducing interscan variability may be to repeat an examination and average the results of the examinations in the subset of subjects who have a minimal to mild calcium score on the initial scan.


   ACKNOWLEDGMENTS
 
The authors thank Thomas K. Pilgram, PhD, for his help with statistical analysis.


   FOOTNOTES
 
2 Current address: Department of Radiology, International Medical Center of Japan, Tokyo. Back

Abbreviations: ECG = electrocardiography, ANOVA = analysis of variance

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


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

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