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AJR 2005; 184:1917-1923
© American Roentgen Ray Society

Variability of Repeated Coronary Artery Calcium Measurements by 16-MDCT with Retrospective Reconstruction

Jun Horiguchi1, Hideya Yamamoto2, Yuji Akiyama1, Nobuhiko Hirai1, Kazushi Marukawa3, Hiroshi Fukuda1 and Katsuhide Ito3

1 Department of Clinical Radiology, Hiroshima University Hospital, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551, Japan.
2 Department of Molecular and Internal Medicine, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
3 Department of Radiology, Division of Medical Intelligence and Informatics, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima Univerisity, Hiroshima, Japan.

Received June 25, 2004; accepted after revision September 22, 2004.

 
Address correspondence to J. Horiguchi (horiguch{at}hiroshima-u.ac.jp).


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. High reproducibility on coronary calcium scoring is an important factor in monitoring the progression of coronary atherosclerosis. The purposes of this study were, using a 16-MDCT scanner with retrospective reconstruction, to compare the effects of thin-slice images and overlapping image reconstruction on the reproducibility of coronary calcium scoring and to compare 16-MDCT with electron beam CT (EBCT).

MATERIALS AND METHODS. Fifty patients underwent two sequential examinations using both EBCT and MDCT. For MDCT, images were reconstructed from the same raw data using the following thicknesses and increments (thickness/increment): 1.25 mm/1.25 mm, 2.5 mm/2.5 mm, and 2.5 mm/1.25 mm. The Agatston, volume, and mass scores were calculated on four pairs of image sets. Statistical analysis was performed to determine significant differences in interscan variability among image acquisition protocols and among measurement algorithms.

RESULTS. Overlapping reconstructed images (thickness/increment, 2.5 mm/1.25 mm) obtained on a 16-MDCT scanner showed the lowest variability (mean, 13%; median, 10%) when compared with the Agatston score.

CONCLUSION. The use of 16-MDCT with overlapping reconstruction by retrospective reconstruction, yielding low variability of coronary artery calcium measurement on two sequential scans, has an advantage over EBCT in monitoring the progression of atherosclerosis.


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Electron beam CT (EBCT) is a noninvasive tool for detection and quantification of coronary artery calcium. The amount of coronary artery calcium is related to the risk of myocardial infarction and sudden cardiac death [1, 2]. Monitoring coronary artery calcium using EBCT may enable the assessment of the progression and regression of coronary atherosclerosis, risk factors, and medical interventions [3, 4]. For this purpose, high reproducibility and accuracy of coronary artery calcium measurements are essential. However, the variability using EBCT [5] yields 20-37% [6-9] interexamination variability. According to previous articles, the causes of interscan variability are multifactorial. These include partial volume effect [10], the use of the step function in the Agatston method to quantify calcium [7], coronary artery motion [11], image noise [12], field inhomogeneity [13], lack of calibration [14], total amount of coronary artery calcium [9], and many other factors.

To reduce interscan variability in coronary artery calcium scoring, some authors have suggested the use of thin-slice images to decrease partial volume effect [7, 15, 16]. Moreover, overlapping image reconstruction has been found to improve reproducibility in coronary artery calcium scoring [17-20].

Recently, new-generation 16-MDCT scanners equipped with retrospectively ECG-gated reconstruction software for cardiac study have become available. With these scanners, the collection of volume data consisting of thin-slice collimation has become feasible for a short breath-hold time. The purposes of this study on the reproducibility of coronary artery calcium scoring using a 16-MDCT scanner were to compare the effects of thin-slice images and overlapping image reconstruction and to compare 16-MDCT with EBCT.


Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This study was approved by our institutional review committee. Informed consent was received from all patients involved after the nature of the procedure had been fully explained. For 6 months, 61 consecutive subjects (47 men and 14 women; mean age, 66 ± 10 [SD] years; age range, 44-84 years) who were asymptomatic with at least one cardiac risk (n = 32) or complaints of chest pain (n = 29) were included. Two sequential CT scans were obtained using an EBCT scanner (C-150 XL, Imatron) and a 16-MDCT scanner (LightSpeed Ultrafast 16, GE Healthcare). For both EBCT and MDCT scanners, the second scan was obtained with no change in subject positioning immediately after the first scan. The time between EBCT and MDCT scanning was less than 15 min.

EBCT Protocol
The standard EBCT protocol used was as follows: 100-msec acquisition time, 35-40 continuous gapless slices of 3 mm thickness, 130 kV, and 625 mA. The single-section mode images were obtained with the ECG triggered to 70% of the R-R interval. Image reconstruction was performed with a 512 x 512 pixel matrix using a sharp reconstruction filter. A display field of 26 cm was sufficient and yielded a pixel size of approximately 0.5 mm.

16-MDCT Protocol
Volumetric data of the entire heart were obtained using the helical mode with scanning parameters of a 1.25-mm collimation width x 16 detectors, a gantry rotation speed of 0.5 sec/rotation, 120 kV, and 100 mA. The pitch was set to 0.275, enabling multisector reconstruction, where pitch is defined as table feed per gantry; rotation divided by the total X-ray beam width (N x T); N is the number of active data-acquisition system (DAS) channels, and T is the single DAS channel width. Multisector reconstruction uses a retrospective ECG-gated image reconstruction algorithm. With this algorithm, combining some (n = 2-4, depending on the heart rate) adjacent cardiac cycles (segments) improves temporal resolution while maintaining image quality [21]. Three reconstructions—2.5-mm-thickness images with a 2.5-mm increment, 1.25-mm-thickness images with a 1.25-mm increment, and 2.5-mm-thickness images with a 1.25-mm increment—were reconstructed from the same raw data. Accordingly, a total of six data sets from two scans were created and were used for the analysis. The center of the temporal window was set to 70% of the R-R interval. The matrix size and field of view were the same as for the EBCT protocol, and the reconstruction filter was standard.

Calcium Scoring
Calcium score, volume, and mass were determined on a commercially available external workstation (Advantage Windows version 4.1, GE Healthcare) using software for coronary artery calcium scoring (Smartscore version 3.5) both with EBCT and MDCT. According to the Agatston method [5], we defined the regions of interest by vessel and slice with the threshold option for pixels greater than 130 H to measure the area and peak density of plaques. Depending on the peak density of the plaque, an area of at least 0.52 mm2 (2 pixels) was multiplied by one of the following cofactors: a factor of 1 for 130-199 H, a factor of 2 for 200-299 H, a factor of 3 for 300-399 H, and a factor of 4 for densities greater than 400 H. The total calcium score was calculated as the sum of the individual lesion scores in all coronary arteries.

The Agatston score was calculated using the following formula:

The different quantification algorithms—calcium, volume, and mass—were calculated. The equation for volume was as follows:

The following equation was used to calculate mass:

A radiologist, who had 4 years' experience with coronary artery calcium measurements, scored both the EBCT and MDCT scans to avoid interobserver variability.

Statistical Analysis
Values are reported as mean ± SD (median). The percentage of variability was calculated as the mean of

For statistical analysis, repeated-measures of analysis of variance were used to determine differences in scores and variability between CT scanners, among scoring algorithms, and among image reconstructions. The Student's t test was also performed to determine differences between individual pairs. A p value of less than 0.05 was considered to identify significant differences.


Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
All patients were able to hold their breath on both EBCT and MDCT. On MDCT, the median heart rate was 63 ± 11 (SD) beats per minute (bpm) (range, 42-83 bpm) on scan 1 and 64 ± 12 bpm (range, 47-90 bpm) on scan 2. The change in heart rate was 6 ± 12 bpm during scan 1 and 8 ± 17 bpm during scan 2. The number of segments used in the multisector reconstruction was 2-4. The number depended on the heart rate and variability and thus varied even during one scan. Almost all MDCT images had a temporal resolution of 100-250 msec, determined according to patient heart rate and the number of segments used for reconstruction.

Eight patients did not show coronary artery calcium on either EBCT or MDCT, and three patients had scores of both nonzero and zero on eight image sets (EBCT and MDCT). These 11 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 an error value of 100% [21, 22].

The mean of the two scoring values of the two sequential scans by different scoring algorithms on EBCT and MDCT are summarized in Table 1. There were no statistical differences on the Agatston, volume, and mass scores (repeated-measures analysis of variance, p = 0.990 for Agatston, p = 0.979 for volume, p = 0.996 for mass).


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  		TABLE 1 Mean of the Two Scoring Values on Two Sequential Scans

 

A plot of the Agatston scores of the scan 1 versus the scan 2 scans for the EBCT and the three MDCT data sets are shown in Figures 1A, 1B, 1C, and 1D. The strongest relationship was observed on 2.5 mm/1.25 mm MDCT (thickness/increment).



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  		Fig. 1A. —Scatterplots of Agatston scores for scans 1 and 2 for electron beam CT (EBCT) and for three MDCT protocols. Scatterplot of Agatston scores for EBCT shows linear correlation follows an equation: scan 2 = 51.3 + 0.86 x scan 1 (r2 = 0.961).

 


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  		Fig. 1B. —Scatterplots of Agatston scores for scans 1 and 2 for electron beam CT (EBCT) and for three MDCT protocols. Scatterplot of Agatston scores for 1.25-mm MDCT shows linear correlation follows an equation: scan 2 = -3.0 + 1.05 x scan 1 (r2 = 0.966).

 


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  		Fig. 1C. —Scatterplots of Agatston scores for scans 1 and 2 for electron beam CT (EBCT) and for three MDCT protocols. Scatterplot of Agatston scores for 2.5 mm/2.5 mm MDCT shows linear correlation follows an equation: scan 2 = -0.8 + 1.06 x scan 1 (r2 = 0.981).

 


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  		Fig. 1D. —Scatterplots of Agatston scores for scans 1 and 2 for electron beam CT (EBCT) and for three MDCT protocols. Scatterplot of Agatston scores for 2.5 mm/1.25 mm MDCT shows linear correlation follows an equation: scan 2 = -22.1 + 1.08 x scan 1 (r2 = 0.991).

 
The variability of the values on the two sequential scans is summarized in Table 2. When compared among the CT protocols, a significant difference was observed for the Agatston scores (p < 0.01) but was not seen for the volume (p = 0.223) and mass (p = 0.447) scores (repeated-measures analysis of variance). On pairwise fashion by Student's t test, the variability of the Agatston scores on 2.5 mm/1.25 mm MDCT was the lowest compared with EBCT (p = 0.02), 1.25 mm/1.25 mm MDCT (p = 0.02), and 2.5 mm/2.5 mm MDCT (p < 0.01). The variability of Agatston scores on 1.25 mm/1.25 mm MDCT was lower than that on EBCT (p < 0.01) and 2.5 mm/2.5 mm MDCT (p = 0.05).


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  		TABLE 2 Variability of the Values on Two Sequential Scans

 

When compared among coronary artery calcium scoring algorithms, there were no statistically significant levels using the repeated-measures analysis of variance (EBCT, p = 0.543; 1.25 mm/1.25 mm, p = 0.936; 2.5 mm/2.5 mm, p = 0.368; 2.5 mm/1.25 mm, p = 0.716). However, when the Student's t test was used, the variability of the calcium volume scores was lower than that of the Agatston score on EBCT (p = 0.02) and 2.5 mm/2.5 mm MDCT (p = 0.04). In contrast to this, there was no significance between the two scores on 1.25 mm/1.25 mm and on 2.5 mm/1.25 mm MDCT. The variability of calcium mass on 2.5 mm/1.25 mm MDCT was the lowest, and a statistical difference was observed between that and the variability on EBCT (p = 0.02).



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  		Fig. 2A. —44-year-old asymptomatic man (heart rate, 68 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), first 1.25-mm-thickness MDCT (B), and first 2.5-mm-thickness MDCT show heart. Calcium is not detected on EBCT and 2.5-mm-thickness MDCT. Calcium in left main coronary artery is detected on 1.25-mm-thickness MDCT.

 



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  		Fig. 2B. —44-year-old asymptomatic man (heart rate, 68 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), first 1.25-mm-thickness MDCT (B), and first 2.5-mm-thickness MDCT show heart. Calcium is not detected on EBCT and 2.5-mm-thickness MDCT. Calcium in left main coronary artery is detected on 1.25-mm-thickness MDCT.

 



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  		Fig. 2C. —44-year-old asymptomatic man (heart rate, 68 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), first 1.25-mm-thickness MDCT (B), and first 2.5-mm-thickness MDCT show heart. Calcium is not detected on EBCT and 2.5-mm-thickness MDCT. Calcium in left main coronary artery is detected on 1.25-mm-thickness MDCT.

 
The variability for the Agatston score was compared among subgroups divided on the basis of the amount of coronary artery calcium burden. For each protocol, 50 cases were assigned to four cardiovascular risk subgroups according to the mean Agatston scores for the two sequential scans. The results show that variability was high in the low coronary artery calcium score subgroups on both EBCT and MDCT. The variability improvement from EBCT to 2.5 mm/1.25 mm MDCT is greatest in the subgroups with lower Agatston scores (Table 3).


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  		TABLE 3 Comparison of Variability for the Agatston Score Depending on Amount of Calcification

 

Finally, systematic error and the limit of agreement between EBCT (first scan) and 2.5 mm/1.25 mm MDCT (first scan) on Agatston scores were determined according to the Bland-Altman procedure as the mean of [natural logarithm (EBCT value + 1) - natural logarithm (MDCT value + 1)] to reduce skewness. For this analysis only, the 11 patients who had been excluded were included. The systematic error and the limits of agreement were 0.04 and 0.26 to -0.19, respectively, for the two scores.


Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
High reproducibility is a key requirement for coronary artery calcium scoring because the application has been suggested to monitor the progression of atherosclerotic plaque burden. However, the interexamination variability of coronary artery calcium scoring using EBCT (13-38%) is too much considering the normal progression of coronary artery calcium scores per year (range, 14-27%; average, 24%) [23] or the acceleration of up to 33-48% seen with significant coronary disease [24, 25].

MDCT, with its improved temporal resolution, has been shown to have good correlations with EBCT in coronary artery calcium measurement [21, 22]. Possible high reproducibility in coronary artery calcium measurement, which has not been achieved on EBCT and may be achieved on MDCT with the reduction of partial volume effect by virtue of its thin-slice volume data, is now a great concern for this technology. With the conventional Agatston method, however, high levels of interscan variability between two consecutive scans have been reported—that is, 38.6% [26] on 2-MDCT and 23% [19], 43.1% [27] and 45.5% [20] on 4-MDCT. The variability in the current study yields 25% on EBCT and 22% on 16-MDCT with nonoverlapping 2.5 mm thickness, with neither being satisfactory.



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  		Fig. 3A. —69-year-old man complaining of anterior chest pain (heart rate, 55 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), second EBCT (B), first 1.25-mm-thickness MDCT (C), second 1.25-mm-thickness MDCT (D), first 2.5-mm-thickness MDCT (E), and second 2.5-mm-thickness MDCT (F) show heart. Calcium in right coronary artery is most clearly seen on 1.25-mm-thickness MDCT. On EBCT, calcium is detected on first scan and is not detected on second scan.

 



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  		Fig. 3B. —69-year-old man complaining of anterior chest pain (heart rate, 55 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), second EBCT (B), first 1.25-mm-thickness MDCT (C), second 1.25-mm-thickness MDCT (D), first 2.5-mm-thickness MDCT (E), and second 2.5-mm-thickness MDCT (F) show heart. Calcium in right coronary artery is most clearly seen on 1.25-mm-thickness MDCT. On EBCT, calcium is detected on first scan and is not detected on second scan.

 



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  		Fig. 3C. —69-year-old man complaining of anterior chest pain (heart rate, 55 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), second EBCT (B), first 1.25-mm-thickness MDCT (C), second 1.25-mm-thickness MDCT (D), first 2.5-mm-thickness MDCT (E), and second 2.5-mm-thickness MDCT (F) show heart. Calcium in right coronary artery is most clearly seen on 1.25-mm-thickness MDCT. On EBCT, calcium is detected on first scan and is not detected on second scan.

 



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  		Fig. 3D. —69-year-old man complaining of anterior chest pain (heart rate, 55 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), second EBCT (B), first 1.25-mm-thickness MDCT (C), second 1.25-mm-thickness MDCT (D), first 2.5-mm-thickness MDCT (E), and second 2.5-mm-thickness MDCT (F) show heart. Calcium in right coronary artery is most clearly seen on 1.25-mm-thickness MDCT. On EBCT, calcium is detected on first scan and is not detected on second scan.

 



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  		Fig. 3E. —69-year-old man complaining of anterior chest pain (heart rate, 55 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), second EBCT (B), first 1.25-mm-thickness MDCT (C), second 1.25-mm-thickness MDCT (D), first 2.5-mm-thickness MDCT (E), and second 2.5-mm-thickness MDCT (F) show heart. Calcium in right coronary artery is most clearly seen on 1.25-mm-thickness MDCT. On EBCT, calcium is detected on first scan and is not detected on second scan.

 



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  		Fig. 3F. —69-year-old man complaining of anterior chest pain (heart rate, 55 beats per minute). Transaxial images from first electron beam CT (EBCT) (A), second EBCT (B), first 1.25-mm-thickness MDCT (C), second 1.25-mm-thickness MDCT (D), first 2.5-mm-thickness MDCT (E), and second 2.5-mm-thickness MDCT (F) show heart. Calcium in right coronary artery is most clearly seen on 1.25-mm-thickness MDCT. On EBCT, calcium is detected on first scan and is not detected on second scan.

 
Partial volume effect is a major factor that influences variability on coronary artery calcium measurement. Vliegenthart et al. [16] have shown that, on a static phantom scan using EBCT, a 1.5-mm-thickness protocol yields more accurate estimates of calcified volume than a conventional 3.0-mm-thickness protocol. Overlapping reconstruction has been shown to improve reproducibility by previous studies on a static phantom with EBCT [17], a beating phantom with EBCT and 4-MDCT [18], and 50 patients [19] and 75 patients [20] with 4-MDCT. Ohnesorge et al. [19] explored the effect of overlapping increments of 1.0, 1.5, and 2.0 mm in 3-mm-thickness images. Interestingly, the results showed that overlapping increment had an impact on the reduction of variability; however, no substantial difference could be observed among the three increments. This seems to suggest a reconstruction pitch of almost half of the slice thickness is enough to reduce variability.

On 16-MDCT, 1.25-mm-collimation volume data of the heart can be obtained in a breath-hold of approximately 10 sec. The characteristic of our study is that three image sets were reconstructed from the same raw scan data, thereby comparison of the reconstruction algorithms themselves became possible. Both thin-slice reconstruction (1.25 mm/1.25 mm) and overlapping image reconstruction (2.5 mm/1.25 mm) have shown improved reproducibility of coronary artery calcium measurement, and the latter reached a statistical level.

The presence or absence of calcium is one clear-cut point that has been suggested to have clinical usefulness. Vliegenthart et al. [16] have investigated the accuracy of a 1.5-mm-slice protocol for EBCT. Their results showed that almost half of the small calcifications detectable on 1.5-mm scans were missed on the 3.0-mm scans, which is similar to our findings (Figs. 2A, 2B, and 2C). Thin-slice images are also considered advantageous in the agreement of detection or no detection of coronary artery calcium on two sequential scans (Figs. 3A, 3B, 3C, 3D, 3E, and 3F).



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  		Fig. 4A. —69-year-old obese man complaining of anterior chest pain (heart rate, 60 beats per minute). Transaxial electron beam CT (EBCT) image (A), transaxial 1.25-mm-thickness MDCT image (B), and transaxial 2.5-mm-thickness MDCT image (C) show heart. SDs of CT values in region of interest placed in aortic root were measured as 39, 42, and 30 H on EBCT and 1.25- and 2.5-mm-thickness MDCT, respectively. No apparent calcium is found in left coronary artery region. However, hyperdense noise exceeds CT value of 130 H on EBCT and 1.25-mm-thickness MDCT.

 



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  		Fig. 4B. —69-year-old obese man complaining of anterior chest pain (heart rate, 60 beats per minute). Transaxial electron beam CT (EBCT) image (A), transaxial 1.25-mm-thickness MDCT image (B), and transaxial 2.5-mm-thickness MDCT image (C) show heart. SDs of CT values in region of interest placed in aortic root were measured as 39, 42, and 30 H on EBCT and 1.25- and 2.5-mm-thickness MDCT, respectively. No apparent calcium is found in left coronary artery region. However, hyperdense noise exceeds CT value of 130 H on EBCT and 1.25-mm-thickness MDCT.

 



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  		Fig. 4C. —69-year-old obese man complaining of anterior chest pain (heart rate, 60 beats per minute). Transaxial electron beam CT (EBCT) image (A), transaxial 1.25-mm-thickness MDCT image (B), and transaxial 2.5-mm-thickness MDCT image (C) show heart. SDs of CT values in region of interest placed in aortic root were measured as 39, 42, and 30 H on EBCT and 1.25- and 2.5-mm-thickness MDCT, respectively. No apparent calcium is found in left coronary artery region. However, hyperdense noise exceeds CT value of 130 H on EBCT and 1.25-mm-thickness MDCT.

 
Noise often shows hyperattenuation (CT value > 130 H) that is difficult to distinguish from calcification [12], thus having a considerable effect on coronary artery calcium measurement (Figs. 4A, 4B, and 4C). Achenbach et al. [9] on sequential EBCT scans have shown that the variability in measurements for images with low noise was lower than that in images with high noise. Volume data of 0.65 mm thickness covering the entire heart can be obtained on 16-MDCT, and 16-MDCT is expected to reduce variability caused by partial volume averaging. Thin sections, however, are dominated by image noise. The direction that advances in MDCT need to go is toward obtaining thin sections and many of them at the same time and then reconstruct to various section thicknesses depending on the user's requirement for high spatial resolution or improved image noise.

The volumetric approach has been shown to improve the reproducibility of coronary artery calcium measurement on either EBCT [6, 7, 9] or MDCT [18, 19]. According to our study, interexamination variability of the calcium volume measurements was reduced more than the Agatston score on EBCT and 2.5 mm/2.5 mm MDCT but was not reduced on 1.25 mm/1.25 mm MDCT and 2.5 mm/1.25 mm MDCT. We consider this to be because the partial volume effect on thin-slice images and the overlapping image reconstruction are reduced, thereby the volumetric quantification algorithm does not have much effect.

We have options on how to use cardiac volume data for retrospective image reconstruction: a fixed cardiac phase—for example, late diastolic or other multicardiac phases. In the former, a concept of ECG-controlled modulation, enabling 45-48% reduction of radiation [28], is considered preferable. The latter is also promising because the cardiac phase during which motion artifacts are least differs considerably among coronary arteries and among individuals [29]. The variability of coronary artery calcium measurements caused by motion artifacts may be reduced by selecting the optimal image-reconstruction window on individual calcified plaques [30]. In conclusion, 16-MDCT with overlapping reconstruction by retrospective reconstruction, yielding low variability of coronary artery calcium measurement on two sequential scans, has an advantage over EBCT in monitoring the progression of atherosclerosis.


References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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