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Cardiopulmonary Imaging
Original Research
OBJECTIVE. The purpose of this article is to evaluate to what extent Agatston scores
may be derived from CT coronary angiography (CTA) examinations, compared with traditional unenhanced CT calcium scores.
MATERIALS AND METHODS. Fifty patients with a CT calcium scoreAgatston
score of zero and 50 patients with a CT calcium scoreAgatston score of 1 or greater whose
CT calcium scores had been calculated and who had undergone CTA using volumetric 320MDCT were included. Agatston scores were obtained at 3.0-mm slices for CT calcium score
and CTA. Method agreement, interobserver agreement, and diagnostic performance of CTA
for detecting coronary calcium were evaluated.
RESULTS. Of 50 patients with a positive CT calcium scoreAgatston score, coronary
artery calcium was detected with CTA in 43 patients by observer 1 (mean CTA score, 102
202; mean CT calcium score, 254 501) and in 46 patients by observer 2 (mean CTA score,
94 147; mean CT calcium score, 272 531). Of the 50 patients with a CT calcium score
Agatston score of zero, 49 (98%, observer 1) and 50 (100%, observer 2) had a zero score
with CTA as well. An intraclass correlation of 0.78 and 0.62 was found between CT calcium
score and CTA (p < 0.01), whereas higher Agatston scores were underestimated with CTA.
For observer 1, the sensitivity, specificity, positive predictive value, negative predictive value,
and diagnostic accuracy for detection of coronary calcium with CTA were 86%, 98%, 98%,
88%, and 92%, respectively, and the corresponding values for observer 2 were 92%, 100%,
100%, 93%, and 96%, respectively. Interobserver agreement was 0.996 for CT calcium score
and 0.93 for CTA.
CONCLUSION. Coronary artery calcium can be detected on CTA images with high accuracy. The Agatston calcium score derived from CTA images shows good correlation with
unenhanced CT calcium score and is highly reproducible. However, higher Agatston scores
are systematically underestimated when derived from CTA images.
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CT Protocol
All examinations were performed with a 320MDCT scanner (Aquilion ONE, Toshiba). The
patients had undergone prospectively ECG-gated
unenhanced volumetric CT (to calculate CT calcium score) for scoring the amount of coronary
calcium according to Agatston et al. [3] during the
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same session, followed by a prospectively ECGgated contrast-enhanced volumetric CTA for coronary artery evaluation, with (n = 68) or without
(n = 32) functional analysis. To lower the heart
rate, 25100 mg of oral metoprolol was administered to patients with a cardiac frequency exceeding 60 beats per minute, if no contraindications
were present. Mean ( SD) heart rate during scanning was 54 7 beats per minute.
The scan range was planned between the carina
and cardiac apex. Depending on the expected scan
range, a 320 0.5 mm or 280 0.5 mm detector
configuration was used. Immediately before image acquisition, an optimal reconstruction phase
was determined during a breath-hold exercise with
ECG recording. Full cardiac CT calcium score acquisition was performed within a single heart beat
during breath-hold at inspiration. Scan parameters
were 120 kV tube voltage and 200400 mA tube
current (mean, 320 49 mA), depending on patient size and shape (200 mA for small or thin patients, 250 mA for average size patients, and 300
400 mA for large or obese patients). Rotation time
was 0.35 second. Effective radiation dose estimation was based on the doselength product provided by the scanner for each patient and by using the
correction factor 0.017 for chest imaging in adults
[26]. The estimated dose was 1.9 0.3 mSv.
CTA was performed after bolus injection of
5070 mL of iodinated contrast agent (400 mg/mL
iomeprol; Iomeron, Bracco) via antecubital vein
injection with a flow rate of 5.0 mL/s followed by a
20 mL mix of 50% contrast agent and 50% saline,
followed by a 25-mL saline flush using an automatic injector (Stellant CT, MedRad). Bolus tracking was performed by placing a region of interest
in the left ventricle. Image acquisition was automatically started 7 seconds after reaching a predefined threshold difference of 100 HU. Scan parameters dependent on body mass index (BMI)
were as follows: 100 kV and 450550 mA for BMI
1723 (15 patients); 120 kV and 400580 mA for
BMI 2330 (65 patients); and 135 kV and 510 mA
for BMI greater than 30 (20 patients). Mean BMI
was 26 4. Rotation time was 0.35 second. The
scan range for CTA had been planned with the aid
of the CT calcium score scan; care was taken to include the full range of the coronary arteries. Full
cardiac CTA acquisition was performed within a
single heartbeat during breath-hold at inspiration,
with or without functional analysis, including dose
modulation throughout the cardiac cycle. Estimated effective radiation dose was 10.7 5.9 mSv.
Image Reconstruction
Standard reconstruction kernel filters were
used for image reconstruction: FC12 for CT calcium score and FC43 for CTA. For CT calcium
score, nonoverlapping 3.0-mm data sets were reconstructed, which is the standard method used in
clinical practice based on electron-beam CT [3].
Similarly, for CTA, data sets of nonoverlapping
3.0-mm slices were reconstructed for evaluation
of coronary calcium. An additional 0.5-mm CTA
data set, with 0.25-mm increments, that is used
for CTA evaluation in clinical practice was reconstructed. The reconstructions were transferred to
a workstation for analysis.
Analysis
Analysis of coronary artery calcium was performed on a postprocessing workstation (Vitrea
FX, version 1.0, Vital Images) using dedicated
CT calcium score analysis software (VScore, Vital Images). Coronary calcium was defined as an
area of at least three face-connected voxels in
the axial plane in the course of a coronary artery,
with an attenuation threshold value of 130 HU or
greater. Three in-axial-plane face-connected voxels correspond to a minimum lesion area greater
than 1 mm 2, which is used as a reference value in
calcium scoring [6]. Calcium scores of each investigation were calculated and expressed as Agatston scores for standard of reference CT calcium
score and for CTA reconstructions.
Contour drawing was performed by two investigators with 2 years (observer 1) and 4 years (observer 2) of experience in cardiac CT; observer 1
was supervised by a radiologist with 7 years of
experience in cardiac CT. Observers were aware
that patients had been selected on the basis of the
presence (n = 50) or absence (n = 50) of coronary
calcium but were not aware of medical history
of individual patients. Examinations were presented in random order. For CTA, calcifications
that were visually identified in the course of the
coronary arteries were marked by the investigator. The investigator was allowed to compare the
3.0-mm CTA data set with the 0.5-mm CTA data
set. Marking was done on the 3.0-mm data set by
precise contour drawing of visually identified calcium spots after zooming in on the focus, allowing visual identification of individual pixels. Automatic recognition of pixels of 130 HU or greater
was switched off because the design of the coronary calcium analysis program is dedicated for
unenhanced CT. After manual contour drawing,
calcium scores were automatically calculated on
the basis of the 130 HU threshold value. After obtaining the calcium scores in the CTA data sets of
all patients, the calcium scores were obtained in
CT calcium score data sets. With automatic recognition of 130 HU or more, pixels exceeding this
threshold value are colored purple by the postprocessing tool. In each slice (depending on scan
range, 47 or 53 slices), these areas were manually
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applied to determine a statistically significant difference between the calcium scores obtained with
CT calcium score and CTA. The intraclass correlation coefficient (ICC) was calculated to evaluate method agreement between CT calcium score
and CTA investigations and to assess interobserver
agreement. An ICC less than 0.4 indicated poor reproducibility, an ICC of 0.40.75 indicated fair to
good reproducibility, and an ICC greater than 0.75
indicated excellent reproducibility [30]. The method described by Bland and Altman [31] was used
to study limits of agreement and systematic error
between the two methods and between the two observers, respectively. A p value of less than 0.05
was considered statistically significant.
No. of
Patients
CT
Calcium
Score
CT
Angiography
0.3 1.6
NS
47
31 20
50
0 0
110
11
3 3
11100
15
42 31
101400
16
188 91
95 53
1158 792
391 401
> 400
Observer 2
CT
Calcium
Score
CT
Angiography
0 0
0.1 0.8
NS
NS
3 4
NS
45 26
1243 818
44
NS
29 15
0.02
100 56
< 0.001
339 236
0.01
NoteData are the mean SD Agatston score for 3.0 mm CT calcium score and 3.0 mm CT angiography
reconstructions. NS = not significant.
encircled when present in the course of each coronary artery. Calcium scores were automatically
calculated. A time interval of at least 2 weeks between scoring the CTA and the CT calcium score
was used to prevent recognition bias. Patients
were classified according to Agatston risk groups
as defined by Rumberger et al. [27]. Although this
risk stratification scheme is based on absolute Agatston scores and does not account for patient age,
sex, and race, recent studies have shown that absolute calcium scores may predict cardiovascular
events better than adjusted percentiles [28, 29].
Statistical Analysis
Statistical analysis was performed using SPSS
for Windows (version 16.0, SPSS). The diagnostic
performance of CTA in the detection of coronary
artery calcium is presented as sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy; CT calcium score was
used as the standard of reference. The mean and
median calcium scores and SDs were calculated for
CT calcium score and for CTA for the whole group
and for the Agatston risk groups [27]. The Wilcoxons signed rank test for two related samples was
Results
Positive Calcium Score ( 1)
For observer 1, the mean calcium score of
the 50 patients with a positive CT calcium
score was 254 501 (median, 82). At CTA,
coronary calcium was detected in 43 (86%)
of 50 patients, with a mean calcium score of
102 202 (median, 40). Seven patients had
a false-negative calcium score at CTA, with
scores of 1 (n = 4 patients), 2 (n = 1 patient),
4 (n = 1 patient), and 8 (n = 1 patient). Figure 1 shows a comparison of coronary artery
calcium visualization with CT calcium score
and CTA.
For observer 2, the mean calcium score of
the 50 patients with a positive CT calcium
score was 272 531 (median, 82). Coronary
artery calcium was detected in 46 (92%) of
these 50 patients at CTA, with a mean calcium
score of 94 147 (median, 45). Four patients
had a false-negative calcium score, with scores
of 1 (n = 2 patients) and 8 (n = 2 patients).
The distribution of patients within different
Agatston risk groups, as defined by Rumberger et al. [27], is shown in Table 1. No statistically significant difference was found between
CT calcium score and CTA-derived calcium
scores for patients with low calcium scores
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2,000
1,000
1,000
1,000
1,000
1
2,000
10
1,000
100
10,000
10
100
1,000
10,000
Fig. 2Bland-Altman analysis showing limits of agreement and systematic errors for both observers. Results for Agatston calcium scores obtained with CT calcium
score (CTCS) and CT angiography (CTA) are shown for observer 1 (A) and for observer 2 (B). Dashed lines show upper and lower limits of agreement 1.96 SD and 95% CI.
Note that good agreement can be observed for low calcium scores, whereas highest Agatston scores above upper limit of calcium score exceeding 544 (observer 1) and
686 (observer 2) contain systematic error.
Observer 1
Observer 2
No. of
Patients
Shift Up
Shift Down
Total Shift
50
Total Shift
110
11
11100
15
101400
16
10
10
> 400
Total
100
23
27
19
20
NoteData the number of patients shifting between Agatston score risk groups. Dashes indicate that no risk
group-shift occurred.
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ity, 98% (95% CI, 88100%); positive predictive value, 98% (95% CI, 86100%); negative
predictive value, 88% (95% CI, 7594%);
and diagnostic accuracy, 92%. For observer 2, the values were as follows: sensitivity,
92% (95% CI, 8097%); specificity, 100%
(95% CI, 91100%); positive predictive value, 100% (95% CI, 90100%); negative predictive value, 93% (95% CI, 8198%); and
diagnostic accuracy, 96%.
The change in classification according
to risk groups for the whole patient population for CTA-derived Agatston scores, compared with the standard of reference CT calcium score, for the two observers is shown
in Table 2. Classification in another risk
group occurred for 27% of patients by using
CTA-derived calcium scores; for observer 1,
downgrading of the Agatston risk group
occurred in 23% of cases, and upgrading of
Agatston risk group occurred in 4% of cases.
For observer 2, classification in another risk
group occurred for 20% of patients by using
CTA-derived calcium scores, whereas downgrading of the Agatston risk group occurred
in 19% of cases, and upgrading of Agatston
risk group occurred in 1% of cases.
Interobserver Variability
Interobserver agreement was excellent for
both the CT calcium scoreAgatston scores
(ICC, 0.997; p < 0.001) as well as the CTAderived Agatston scores (ICC, 0.94; p < 0.001)
for the total group. Also, for the groups with
a positive CT calcium scoreAgatston score,
500
Difference CTA Agatston Score
(Observer 1 Observer 2)
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500
250
250
500
250
500
250
10
100
1,000
10
100
1,000
Fig. 3Bland-Altman analysis showing interobserver agreement, limits of agreement, and systematic errors for Agatston calcium score calculated by both CT calcium
score (CTCS) (A) and CT angiography (CTA) (B). Dashed lines show upper and lower limits of agreement 1.96 SD and 95% CI. Excellent agreement can be observed for
both CTCS as well as CTA-derived calcium scores between two observers (p < 0.001).
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