DOI:10.2214/AJR.05.0052
AJR 2006; 187:W1-W6
© American Roentgen Ray Society
Variability of Repeated Coronary Artery Calcium Measurements on Low-Dose ECG-Gated 16-MDCT
Jun Horiguchi1,
Hideya Yamamoto2,
Nobuhiko Hirai1,
Yuji Akiyama1,
Chikako Fujioka1,
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 University, Hiroshima, Japan.
Received January 10, 2005;
accepted after revision May 3, 2005.
Address correspondence to J. Horiguchi
(horiguch{at}hiroshima-u.ac.jp).
WEB
This is a Web exclusive article.
Abstract
OBJECTIVE. High reproducibility on coronary artery calcium (CAC)
scoring is a key requirement in monitoring the progression of coronary
atherosclerosis. Retrospective ECG-gated helical CT has been shown to be
superior to prospective gating helical CT in the reproducibility of CAC
measurements. However, it brings with it a high level of radiation exposure.
The purpose of this study was to compare low- and standard-dose protocols in
the variability of CAC scores and in image quality, thereby assessing the
feasibility of low-dose retrospective ECG-gated helical CT in CAC
measurements.
SUBJECTS AND METHODS. Eighty-six patients with CAC were scanned
using a tube current setting of 100 mA once and then a tube current setting
equivalent to the patient's body weight twice. CAC scores (Agatston and
volume) and interscan variability were evaluated. The mean and SD of the CT
attenuation values in regions of interest in the aorta were measured, and the
value (mean + 2 x SD) was obtained.
RESULTS. A high correlation of log10 (Agatston score + 1)
was observed between sequential helical CT scans (r = 0.998). The
variability in CAC measurements ranged from 11% to 12% for both the Agatston
and volume scores. With the tube current equivalent to body weight, the value
(mean + 2 x SD) did not exceed a CT attenuation value of 130 H.
CONCLUSION. Low-dose retrospective ECG-gated helical
CTyielding low variability and achieving the level of image quality
needed to measure CACcan be used to monitor patients with coronary
atherosclerosis.
Keywords: atherosclerosis cardiac imaging coronary artery disease MDCT
Introduction
Electron beam CT is an accepted standard for the detection and
quantification of coronary artery calcium (CAC)
[1]. The amount of CAC is
related to the risk of myocardial infarction and sudden cardiac death
[2]. Monitoring CAC is
suggested to assess the progression and regression of coronary
atherosclerosis, thereby documenting risk factors and response to
lipid-lowering pharmacologic therapy
[3]. For this purpose, low
interscan variability in CAC measurements is mandatory. The normal progression
of a patient's CAC score per year is reported to be 14-27% (average, 24%)
[4], whereas it is accelerated
up to 33-48% in patients with significant coronary disease
[5,
6]. However, in previous
studies, the variability of Agatston scores
[1] using electron beam CT has
ranged from 20% to 37%
[7-10],
which jeopardizes the detection of any changes in this range. Therefore,
serial use of electron beam CT to monitor the response of coronary artery
lesions to medical interventions designed to cause regression of disease has
not been recommended by the American College of Cardiology-American Heart
Association expert committee
[2].
Interscan variability of CAC measurements using helical CT has also been
examined. By using the conventional Agatston method on nonoverlapping
reconstructions, however, high levels of interscan variability between two
consecutive scans have been reported: 23%
[11], 27%
[12], 43.1%
[13], 45.5%
[14] on 4-MDCT, and 22%
[15] on 16-MDCT. In contrast
to this, with the use of overlapping reconstructions, a considerable reduction
in interscan variability can be achieved: from 23% to 12%
[11] and from 22% to 13%
[15].
An obvious trade-off of the retrospective ECG-gated helical CT technique
enabling overlapping reconstructions is the considerably increased radiation
exposure compared with ECG-triggering scan protocols with helical CT or
electron beam CT [11]. The
purpose of this study was to compare low and standard doses and to compare
first and second low doses in helical CT, thus assessing the feasibility of
low-dose ECG-gated helical CT for measuring CAC.

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Fig. 1A Placement of region of interest (ROI, circles) in
64-year-old man complaining of chest pain (heart rate, 68 beats per minute;
body weight, 62 kg). Transaxial helical CT images of heart obtained using
100-mA (A), first 60-mA (B), and second 60-mA (C)
protocols. Mean and SD CT attenuation values (Hounsfield units) in ROIs set in
aorta at level of left coronary artery were 49 ± 14, 47 ± 19,
and 45 ± 19 H, respectively. Value means + 2 x SD were 76, 85,
and 83 H, respectively. Calcium in left main coronary and anterior descending
arteries is well shown on all helical CT scans.
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Fig. 1B Placement of region of interest (ROI, circles) in
64-year-old man complaining of chest pain (heart rate, 68 beats per minute;
body weight, 62 kg). Transaxial helical CT images of heart obtained using
100-mA (A), first 60-mA (B), and second 60-mA (C)
protocols. Mean and SD CT attenuation values (Hounsfield units) in ROIs set in
aorta at level of left coronary artery were 49 ± 14, 47 ± 19,
and 45 ± 19 H, respectively. Value means + 2 x SD were 76, 85,
and 83 H, respectively. Calcium in left main coronary and anterior descending
arteries is well shown on all helical CT scans.
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Fig. 1C Placement of region of interest (ROI, circles) in
64-year-old man complaining of chest pain (heart rate, 68 beats per minute;
body weight, 62 kg). Transaxial helical CT images of heart obtained using
100-mA (A), first 60-mA (B), and second 60-mA (C)
protocols. Mean and SD CT attenuation values (Hounsfield units) in ROIs set in
aorta at level of left coronary artery were 49 ± 14, 47 ± 19,
and 45 ± 19 H, respectively. Value means + 2 x SD were 76, 85,
and 83 H, respectively. Calcium in left main coronary and anterior descending
arteries is well shown on all helical CT scans.
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Subjects and Methods
The 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 10 months, 105 consecutive subjects
(72 men and 33 women; mean age ± SD, 68 ± 9 years; range, 37-85
years) who were asymptomatic with at least one cardiac risk factor (n
= 74) or complaints of chest pain (n = 31) were included. Three
sequential CT scans were obtained using a 16-MDCT scanner (LightSpeed
Ultrafast 16, GE Healthcare) with no change in subject positioning. The table
was advanced 1 mm each time during the three sequential scans.
Volumetric data of the heart were obtained by helical mode with a 1.25-mm
collimation width x 16 detectors. The gantry rotation speed was 0.5
s/rotation, and the tube voltage was 120 kV. The tube current was 100 mA for
the first scan; for the second and third scans, the tube current was set to
almost equivalent to the patient body weightfor example, 60 mA for a
patient weighing 62 kg, 65 mA for a patient weighing 63 kg because the tube
current could be set in 5-mA steps. We did not use any other dose modulation
methods, such as topogram-based z-axis modulation or modulation
within a slice.
CT pitch factors were variable by the heart rate and were set according to
the manufacturer's recommendations for coronary CT angiography
protocolsthat is, 0.275 for patients with a heart rate of less than 45
beats per minute (bpm), 0.3 for 45-49 bpm, 0.325 for 50-59 bpm, 0.3 for 60-75
bpm, and 0.275 for more than 76 bpm (where pitch is defined as table feed per
gantry rotation divided by the total X-ray beam width [N x
T], where N is the number of active data-acquisition system
[DAS] channels and T is the single DAS channel width).
Images of 2.5-mm thickness with the center of the temporal window
corresponding to 70% of the R-R interval were retrospectively reconstructed
with 1.25-mm spacing. In image reconstruction, single-sector reconstruction,
which is derived from approximately 240° of one 360° gantry rotation
data, was used when the heart rate was less than 60 bpm. Multisector
reconstruction was applied when the heart rate was 60 bpm or more. With this
algorithm, by combining some (n = 2-4, depending on the heart rate)
adjacent cardiac cycles (segments), temporal resolution is improved while
maintaining image quality
[16]. Image reconstruction was
performed with a 512 x 512 pixel matrix using a standard kernel. A
display field of view of 26 cm was sufficient and yielded a pixel size of
approximately 0.5 mm.
Calcium Scoring
Agatston and volume scores were determined on a commercially available
external workstation (Advantage Windows [version 4.1], GE Healthcare) using
CAC-scoring software (SmartScore [version 3.5], GE Healthcare). In accordance
with the Agatston method [1],
we defined the regions of interest (ROIs) 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 cofactor of 1 for ROIs that were 130-199 H; a cofactor of 2,
200-299 H; a cofactor of 3, 300-399 H; and a cofactor of 4, for densities 400
H or greater. 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 calcium volume [7] was
calculated using the following formula:
The calcium mass was not calculated because no calibration phantom was
available. To avoid interobserver variability, all CT scans were scored by a
radiologist with 5 years' experience measuring CAC.
Statistical Analysis
The Agatston and volume scores were compared among protocols: 100-mA versus
first low-dose, 100-mA versus second low-dose, and first versus second
low-dose protocols. Correlation was performed in a form of log10
transformation (Agatston score + 1) to reduce skewness.
The percentage of variability in Agatston and volume scores was calculated
as follows:
This variability was compared between 100-mA and first low-dose, 100-mA and
second low-dose, and first and second low-dose protocols. Whether volume
quantification algorithms reduce the variability more than the Agatston
approach was also tested. Furthermore, the variability was compared between
the single-sector (heart rate
60 bpm) and multisector (heart rate > 61
bpm) reconstruction groups.
The mean and SD of CT attenuation values in ROIs set in the aorta at the
level of the left coronary artery were measured and then the value mean + 2
x SD and signal-to-noise ratio (defined as the value mean divided by SD)
were calculated (Figs. 1A,
1B, and
1C). These values were compared
between the 100-mA and low-dose protocols.
For statistical analysis, repeated-measures analysis of variance,
Mann-Whitney U test, and Student's t tests were used to
determine differences; p values of < 0.05 were considered to
identify significant differences.
Results
All patients were able to hold their breath on the three sequential CT
scans. The median heart rate during the 100-mA CT scan was 61 ± 11 (SD)
bpm. The mean change in heart rate during the scan was 6 ± 8 bpm.
Almost all helical CT images had a temporal resolution of 100-250 msec,
although the temporal resolution achieved by multisector reconstructions
differed according to the heart rate and the number of cardiac cycles used for
image reconstruction. The mean body weight of the patients was 60 ± 10
kg (range, 37-105 kg); therefore, the tube current used as the
"low-dose" setting was 60 ± 11 mA (range, 35-105 mA).
Eighty-six of the 105 patients had CAC deposits detected on the three
sequential CT scans, and the remaining 19 patients had no CAC deposit seen on
any of the scans. There were no patients showing both positive and negative
CAC measurements on the three scans.
The Agatston and volume scores on the three scans are summarized in
Table 1. There was no
statistical significance between the three scans (repeated-measures analysis
of variance: Agatston score, p = 0.993; volume score, p >
0.999). The log10 transformed scores (Agatston score + 1) of the
100-mA scans versus the first low-dose scans, 100-mA versus second low-dose,
and first versus second low-dose were highly correlated (r = 0.998)
(Figs. 2,
3, and
4).

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Fig. 2 Graph shows that log10 transformed scores
(Agatston scores + 1) of 100-mA scans versus first low-dose scans are highly
correlated (r = 0.998). In this logarithm calcium scale, 0, 1,
2, 2.6, and > 2.6 ranges almost correspond to normal, minimal,
mild, moderate, and high-risk categories, respectively.
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Fig. 3 Graph shows that log10 transformed scores
(Agatston scores + 1) of 100-mA scans and second low-dose scans are highly
correlated (r = 0.998). In this logarithm calcium scale, 0, 1,
2, 2.6, and > 2.6 ranges almost correspond to normal, minimal,
mild, moderate, and high-risk categories, respectively.
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Fig. 4 Graph shows that log10 transformed scores
(Agatston scores + 1) of first low-dose scans and second low-dose scans are
highly correlated (r = 0.998). In this logarithm calcium scale, 0,
1, 2, 2.6, and > 2.6 ranges almost correspond to normal,
minimal, mild, moderate, and high-risk categories, respectively.
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The percentage variability in the CAC scores is summarized in
Table 2. Low variability was
obtained even using low-dose protocols without significant differences
(repeated-measures analysis of variance: Agatston score, p = 0.994;
volume score, p = 0.923). The variability was not significantly
different between the Agatston and volume algorithms (repeated-measures
analysis of variance, p = 0.667, 0.949, and 0.760). The variability
in both Agatston and volume scores was not significantly different between the
single-sector (heart rate
60 bpm) and multisector (heart rate > 61
bpm) groups (Mann-Whitney U test, p = 0.218-0.958)
(Table 3).
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TABLE 3: Single-Sector vs Multisector Reconstruction in the Percentage of
Variability in the Coronary Artery Calcium Scores
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The mean, SD, mean + 2 x SD, and signal-to-noise ratio of the CT
attenuation values in the ROIs are summarized in
Table 4. On repeated-measures
analysis of variance, there was no significant difference in the mean value
(p = 0.981); however, there was a significant difference in both the
SD (p < 0.01) and signal-to-noise ratio (p < 0.01). On
pair-wise comparison using the Student's t test, the SD on the 100-mA
scans was lower than those on the first low-dose (p < 0.01) and
second low-dose (p < 0.01) scans. The signal-to-noise ratio on the
100-mA scans was higher than those on the first low-dose (p <
0.01) and second low-dose (p < 0.01) scans. In contrast, the SD
(p = 0.110) and signal-to-noise ratio (p = 0.559) were not
statistically different between the first low-dose and second low-dose scans.
With the tube current setting equivalent to the patient's body weight, the
value (mean + 2 x SD) did not exceed a CT attenuation of 130 H, whereas
the value was 135 H for a patient weighing 105 kg on a scan obtained using a
tube current of 100 mA.
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TABLE 4: Mean and SD of CT Attenuation Values in Regions of Interest Set in the
Aorta at the Level of the Left Coronary Artery
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Discussion
Factors influencing interscan variability are partial volume effect
[17], the use of the step
function in the Agatston method to quantitate calcium
[8], coronary artery motion
[18], image noise
[10,
19], field inhomogeneity
[20], lack of calibration
[21], total amount of CAC
[10], and so on. Among these,
a major contributor is partial volume effect. To reduce this, the use of
thin-slice images [5,
22,
23] or overlapping image
reconstructions [11,
14,
24,
25] has been suggested. In a
recent study [15] using
thin-collimation volume data on helical CT, both thin-slice images and
overlapping reconstruction images were shown to be superior to electron beam
CT in terms of the variability of CAC measurements. The tube current used in
the study was 100 mA; therefore, image quality was satisfactory even in
thin-slice images. To reduce radiation exposure, however, overlapping
reconstructions seem preferable to thin-slice images because image noise is
also an important factor in variability.
The German Cardiac Society recommends a tube current of 100 mA for CAC
measurement on MDCT [26]. For
most MDCT scanners, a 100-mA tube current is used to achieve sufficient
signal-to-noise levels for detection of small calcified lesions. The tube
current may be increased for obese patients (e.g., to 150 mA) to maintain a
diagnostic signal-to-noise level at the expense of increased radiation
exposure [27]. In comparison
with prospectively ECG-triggered acquisition using electron beam CT (effective
dose, 0.7 mSv) and helical CT (effective dose, 1 mSv), however, CT acquisition
using retrospective ECG gating is associated with a higher effective radiation
dose (range, 2.6-4.1 mSv)
[28]. A retrospective
ECG-gated protocol, using standard 100 mA in the current study, yields an
effective dose of 3.2-3.7 mSv (varies according to pitch chosen).
Takahashi and Bae [29],
with prospectively ECG-gated 4-MDCT, showed that variability in CAC scores was
not significantly different between the 40-mA versus 150-mA (23.7%) groups and
the 80-mA versus 150-mA (41.8%) groups. The two-group all-over variability of
31.9% in Agatston score was reduced to 22.4% by using the volume score. The
variability level, however, does not seem to be satisfactory for monitoring
normal or accelerated CAC progression. This is probably due to the use of the
prospective ECG-triggering approach. Mahnken et al.
[30] proposed individual body
weight-adapted tube current settings (body weight in kilograms + 33
mAseff) and showed that no significant changes in CAC score were
seen and that there was a relevant increase of noise in comparison with the
standard dose (133 mAseff). The variability of CAC scores between
the two protocols was not tested in this study.
The mean tube current used as a low-dose protocol in the current study was
60 mA. Although the dose was reduced to 1.9-2.2 mA (by 40%), it was still
higher than prospectively ECG-triggered acquisitions with electron beam CT and
helical CT. Combined with ECG-controlled modulation, which would enable a
45-48% reduction of radiation
[31], an almost 70% reduction
in radiation exposure would theoretically be possible using the low-dose
protocol. This would result in an effective dose of almost 1 mSv. This dose is
comparable to that associated with the prospectively ECG-triggered
technique.
Although the optimum definition of a threshold for the detection of CAC is
not known, a CT attenuation value of 130 H was selected because that level is
more than 2 x SDs above the average attenuation of blood
[19]. On the low-dose scan in
the current study, this calculation value does not exceed 130 H. Therefore,
the images were considered sufficient to maintain the signal-to-noise ratio
needed. It remains unresolved as to what level we can reduce the milliampere
setting. Takahashi and Bae
[29] stated that, in most
subjects, a dose of 30 mA (140 kVp) would give a mean noise level of 24
± 8 H, which is of practical use. This may be true; however, individual
dose setting is considered more rational.
The volumetric approach proposed by Callister et al.
[7] has been shown to improve
the reproducibility of CAC measurement on both electron beam CT
[8,
10] and helical CT
[11,
25]. Interestingly, reduction
of the variability by using the volume scoring algorithm was not effective in
our current study. Similar results were experienced through clinical research
using retrospective ECG-gated helical CT with overlapping reconstructions
[15]. The trend is moving
toward obtaining a mass or volume score because of its high reproducibility in
CAC measurement. Patient management at this time, however, is difficult
because of the paucity of representative data about CAC distribution
[32]. In this respect, the
high reproducibility of CAC measurements using the Agatston score in a wide
range of heart rates is considered advantageous.
In conclusion, low-dose retrospective ECG-gated helical CT, yielding low
variability and achieving image quality needed for CAC measurement, can be
used to monitor patients with coronary atherosclerosis.
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2(5):
548 - 555.
[Abstract]
[Full Text]
[PDF]
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