Download Assessment of calcium scoring performance in cardiac computed

Eur Radiol (2003) 13:484–497
DOI 10.1007/s00330-002-1746-y
Stefan Ulzheimer
Willi A. Kalender
Received: 19 June 2002
Revised: 30 September 2002
Accepted: 10 October 2002
Published online: 4 December 2002
© Springer-Verlag 2002
S. Ulzheimer (✉) · W. A. Kalender
Institute of Medical Physics,
University of Erlangen-Nürnberg,
Krankenhausstrasse 12,
91054 Erlangen, Germany
e-mail:
[email protected]
Tel.: +49-9131-8526268
Fax: +49-9131-8522824
CARDIAC
Assessment of calcium scoring performance
in cardiac computed tomography
Abstract Electron beam tomography (EBT) has been used for cardiac
diagnosis and the quantitative assessment of coronary calcium since
the late 1980s. The introduction of
mechanical multi-slice spiral CT
(MSCT) scanners with shorter rotation times opened new possibilities
of cardiac imaging with conventional
CT scanners. The purpose of this
work was to qualitatively and quantitatively evaluate the performance for
EBT and MSCT for the task of coronary artery calcium imaging as a
function of acquisition protocol,
heart rate, spiral reconstruction algorithm (where applicable) and calcium scoring method. A cardiac CT
semi-anthropomorphic phantom was
designed and manufactured for the
investigation of all relevant image
quality parameters in cardiac CT.
This phantom includes various test
objects, some of which can be
moved within the anthropomorphic
phantom in a manner that mimics realistic heart motion. These tools
were used to qualitatively and quantitatively demonstrate the accuracy
of coronary calcium imaging using
typical protocols for an electron
beam (Evolution C-150XP, Imatron,
South San Francisco, Calif.) and a
0.5-s four-slice spiral CT scanner
(Sensation 4, Siemens, Erlangen,
Germany). A special focus was put
on the method of quantifying coronary calcium, and three scoring systems were evaluated (Agatston, vol-
ume, and mass scoring). Good reproducibility in coronary calcium scoring is always the result of a combination of high temporal and spatial
resolution; consequently, thin-slice
protocols in combination with retrospective gating on MSCT scanners
yielded the best results. The Agatston score was found to be the least
reproducible scoring method. The
hydroxyapatite mass, being better reproducible and comparable on different scanners and being a physical
quantitative measure, appears to be
the method of choice for future clinical studies. The hydroxyapatite mass
is highly correlated to the Agatston
score. The introduced phantoms can
be used to quantitatively assess the
performance characteristics of, for
example, different scanners, reconstruction algorithms, and quantification methods in cardiac CT. This is
especially important for quantitative
tasks, such as the determination of
the amount of calcium in the coronary arteries, to achieve high and
constant quality in this field.
Keywords Computed tomography ·
Cardiac imaging · Quality
assurance · Coronary calcium ·
Heart · Cardiac phantom
485
Introduction
According to a recent World Health Report by the World
Health Organization (WHO) the leading cause of mortality in the world, amounting to 13.7%, is coronary artery
disease (CAD). Due to higher risk factors and a lower
number of infectious diseases, the percentage in industrialized countries is dramatically higher, e.g., 25.5% in
Europe [1].
Conventional X-ray coronary angiography and intravascular ultrasound (IVUS) are considered to be the gold
standards for the assessment of artherosclerotic changes
of the coronary arteries, the cause of CAD. As these
quite expensive procedures are highly invasive having a
small but not negligible risk of mortality (0.15%) and
morbidity (1.5%) [2], alternative methods for the assessment of coronary artery wall irregularities are desirable.
Moreover, since possibly as many as half of the coronary
events occur in previously asymptomatic persons [3] an
early and easy diagnosis of CAD – possibly feasible as a
screening procedure – is urgently needed.
Early changes in the walls of the coronary arteries that
cannot be assessed with coronary angiographies determine
the risk for coronary events [4, 5]. Since calcium in the
form of hydroxyapatite (HA) {Ca [Ca3 (PO4)2]3}2+·2OH−
in the coronary arteries is a known marker for the presence of artherosclerotic lesions of the coronary arteries,
the screening for it has been suggested as an early indication for CAD. It has been shown that the risk for coronary
events is associated with the amount of coronary calcium
[6, 7]. The absence of coronary calcium does almost certainly imply the absence of CAD [8]. Calcium strongly attenuates X-rays due to its relatively high atomic number;
therefore, X-ray techniques are suitable methods for detecting coronary calcifications. Plain chest radiographs
and fluoroscopy were used to detect coronary calcifications, but they are both not very sensitive and it is not possible to quantify the amount of calcium [9].
The first group that used electron beam tomography
(EBT) images for the quantification of coronary calcium
were Agatston et al. in 1990 [10]. They introduced a
scoring method later called “Agatston score” which has
been used for more than a decade. The reproducibility in
the quantification of coronary calcium with EBT and the
Agatston score is not known exactly, although individual
papers addressed this issue in patient studies [11, 12, 13,
14, 15, 16, 17]. Yoon et al. determined a reproducibility
of around 30% [18]. This means that according to the “3
σ criterion,” a measured change has to surpass 90% in
order to be accepted as a statistically significant change.
Consequently, Wang et al. even judged the method as being “... not sufficiently reproducible to allow serial quantification of coronary calcium in individual patients over
relatively short periods (<2 years) [17]. Modifications
for the Agatston score were suggested to improve its reproducibility [19] or sensitivity [20]. Calibration phan-
toms for EBT were introduced to reduce variability in
coronary calcium scoring [21] and some groups started
to use mass scoring in parallel to the Agatston score but
all efforts were not consistent and have not led to better,
widely accepted standards.
Despite their comparatively long scan times, even
conventional CT scanners with rotation times of up to
1.5 s were used to quantify coronary calcium without
making special arrangements to reduce motion artifacts
[20, 22, 23, 24, 25, 26]. Compared with the known high
interscan variability of calcium scores for EBT and the
Agatston score, these conventional approaches yielded
similar results. For example, the intermodality variability
in a recent study which compared conventional 0.75-s
sequential scans without ECG triggering to EBT was
42% [22].
The present technology offers new potential. The new
widely available multi-slice spiral computed tomography
(MSCT) scanners of the latest generation offer the possibility of cardiac imaging with similar or even better image quality than EBT. They offer rotation times of down
to 420 ms and can acquire up to 16 slices with nearly
isotropic resolution by using slice collimations of down
to 0.5 mm.
Since the rotation times of the present scanners can
still be long compared with the duration of one complete
cardiac cycle, special techniques for cardiac imaging
with sequential (prospective triggering) and spiral CT
(retrospective gating) [27] were developed at the Institute of Medical Physics (IMP) at the University of Erlangen Nürnberg. They use the recorded ECG signal for image acquisition and reconstruction and aim at reducing
effective scan times. These techniques were already introduced in 1997 for single-slice scanners [28, 29, 30,
31] and showed impressive results; however, only their
generalizations to multi-slice scanners which allow the
depiction of the whole heart with high spatial and temporal resolution from one MSCT scan in a single breathhold led to a breakthrough for cardiac CT [32, 33, 34,
35, 36, 37]. Presently, all CT manufacturers implemented variations of these algorithms in their scanners.
Especially for follow-up studies high reproducibility
is mandatory to be able to detect changes in the observed
parameters, i.e., the progress of the disease or the response to a certain medication. The accurate assessment
of reproducibility and measurement errors which has
been neglected up to now for coronary calcium scoring
is very important for the determination of significant
changes in the state of the disease.
This article closely describes tools and concepts for
quality assurance in cardiac CT especially in the field of
quantifying the amount of calcium in the coronary arteries. These tools were first introduced in scientific exhibitions at the European Congress of Radiology in 1999
and 2000 [38, 39]. Their performance is demonstrated
here in a systematic fashion for two exemplary systems.
486
Fig. 1 a Sketch and b photo
of the anthropomorphic phantom body. It can hold different
inserts at the position of the
heart. c The sketch of a solid
insert that allows the static assessment of calcium scoring
performance and the determination of calibration factors
Further details on the assessment of image-quality parameters for two scanners and several protocols in cardiac CT are presented in a recent PhD thesis [40].
Materials and methods
Tools for quality assurance
Anthropomorphic phantoms consisting of tissue-, water-, and
bone-equivalent materials have been developed that allow the assessment of all important image quality parameters in cardiac CT
in general and especially quality assurance in coronary calcium
scoring. We thereby continued the concepts successfully established for bone mineral density (BMD) and lung density measurements. The semi-anthropomorphic European Spine Phantom [41]
constitutes an internationally accepted calibration standard for Xray based osteoporosis assessment. The Pulmo Phantom is established in the Siemens Pulmo CT option; its semi-anthropomorphic
geometry was derived as an average of a reference population consisting of young male adults used for determination of normal
lung density value in 1994. All phantom materials are based on
epoxy resin. Several additives, such as calcium carbonate CaCO
3, magnesium oxide MgO, hydroxyapatite and microspheres were
added to obtain solid water, soft tissue, and lung and bone equivalent materials for X-ray photons in an energy range from 30 to
150 keV [41, 42]. The manufacturer of the phantoms and phantom
materials used here (QRM Quality Assurance in Radiology and
Medicine GmbH, Möhrendorf, Germany) takes special care in the
manufacturing and testing to ensure that materials and phantoms
can be used as calibration standards for HA. Since coronary calci-
fications consist of HA [8], we can use this material directly for
the simulation of calcifications.
To be able to achieve maximum flexibility in the assessment of
different image parameters a modular concept was chosen.
Anthropomorphic environment
To be able to offer a reproducible and realistic environment for the
assessment of image quality, an anthropomorphic phantom body
was developed consisting of a cross section of the human thorax
with artificial lungs and a spine insert surrounded by tissue-equivalent material (Fig. 1). As a model we used the Pulmo Phantom.
At the position of the heart we placed an empty hole that can hold
different kinds of inserts for various purposes.
Inserts for the assessment of image-quality parameters
With the described phantom body, principally all objects that are
suitable for the investigation of image-quality parameters in cardiac CT can be scanned in an anthropomorphic and reproducible environment. This can be achieved by putting the respective objects
(e.g., wires, discs, hole or bar patterns, water-equivalent materials
as well as low- and high-contrast structures), which are well
known from the determination of image-quality parameters in
non-anthropomorphic environments [27], in a water-filled tank
that fits into the hole of the cardiac phantom body.
In this paper we concentrate on the assessment of calcium scoring performance in cardiac CT. For this purpose, small, exactly defined cylinders of different hydroxyapatite densities were manufactured and immersed in water-equivalent rods to simulate varying
sizes and densities of coronary calcifications. Cylinders with diam-
487
Fig. 2a–c The motion phantom. A robot setup was developed for
moving arbitrary 3D objects inside a water tank on realistic trajectories to simulate cardiac motion. The setup also produces a corresponding ECG signal. c A pseudo-4D plot of a realistic motion
function obtained from angiography data in correspondence to the
ECG signal. An animated sequence of this plot can be accessed on
http://www.imp.uni-erlangen.de/e/research/cardio/
eters of 1, 2, 3, and 5 mm were produced, whereby the length of
the cylinders always equals its diameter. Each calcification exists
in three different HA densities of 200, 400, and 800 mg/cm3. In addition, to these 12 artificial calcified inserts, we obtained a calcified coronary artery specimen which was also immersed in waterequivalent plastic. All these inserts were manufactured in a way so
that they can be moved dynamically in the phantom.
We also composed solid, stationary inserts for the quick and
easy assessment of image-quality parameters. One of these inserts
is shown in Fig. 1c). This solid cylinder that fits in the hole of the
phantom body contains nine small calcifications of varying size
and HA density. Moreover, we included two larger calibration in-
serts (solid water and 200 mg HA/cm3) for the determination of
calibration factors.
Setup for the simulation of cardiac motion
Since the influence of cardiac motion is of decisive interest in cardiac CT, a primary focus of the phantom developments was the creation of assemblies that allow the examination of the effect of realistic cardiac motion on image quality; therefore, a setup was constructed to allow the movement of different objects for quality assurance in a water tank inside the anthropomorphic environment.
Realistic motion functions were obtained from cineangiography. For all investigations, we used the typical motion of a left anterior descending (LAD) coronary artery obtained from a patient
with a heart rate of 58 bpm. The maximum contraction and therefore a maximum of the motion function is at 29% (systole), and
the minimum at 96% of R-R interval (end diastole). The amplitude
from the maximum to the minimum of this motion curve is approximately 7.5 mm. During diastole from 55 to 85% of R-R is a
phase of relatively little movement (Fig. 2c).
488
It is clear that this motion function can only be an example for
the movement of structures in the heart, as there are big differences for varying positions on the heart walls, different heart rates,
and above all between different individuals. Especially for the
right coronary artery, the amplitudes and velocities are much higher. This specific function was chosen as it includes all details
needed for comparing different imaging methods in a sufficient
manner, above all realistic phases of fast and slow motion. This
motion function was scaled for different heart rates by simply decreasing the time for the R-R cycle. This is not in accordance with
the physiologic behavior as the motion function significantly
changes with increasing heart rate. Nevertheless, this method of
scaling to other heart rates appears sufficient for our purpose: the
time of slow motion decreases and the velocities increase which
corresponds to the physiologic tendency. To really find the motion
function for higher heart rates for the specific individual was not
the goal in this proof of concept, as the variation between individuals are very high anyway. Nevertheless, for future studies any desired motion function can be used in this setup.
A commercially available set of linear translation tables (iselautomation, Eiterfeld, Germany) were used which were mounted
perpendicular to each other in order to reach all points in 3D
space. A system of metal rods that reaches into a water tank was
attached to one of the translation tables. Water-equivalent rods
containing the respective test objects were attached to the end of
the metal rod. Each linear table can be accessed independently
with a control unit and a software library. This library was used in
the implementation of a C++ program that allows the comfortable
input and execution of arbitrary 3D motion functions with a precision of 1/100 mm. The only limitations in the present implementation are the achievable velocity of approximately 150 mm/s and
the cruising radius of approximately 200 mm. The control unit for
the linear tables can be programmed to generate 12-V signals that
correspond to the desired motion. These signals are converted to a
corresponding ECG signal of approximately 2 mV with a selfbuilt voltage divider. This signal can be fed directly into the ECG
monitor used for triggering and gating techniques. Figure 2 shows
a drawing of the setup and a photo of the complete setup inside the
gantry of a CT scanner.
Image acquisition
CT scanners
For all measurements concerning EBT, the EBT Scanner Evolution C150XP (Imatron, South San Francisco, Calif.) with software
version 12.4 was used. As an example of a modern MSCT scanner, we used the Sensation 4 (Siemens, Erlangen, Germany). It
provides the simultaneous acquisition of up to four slices and rotation times of down to 0.5 s. For cardiac applications the slice collimations of 4×1 and 4×2.5 mm are relevant.
Scan protocols
Scan protocols have in common that they allow the coverage of
the complete heart (typically approximately 120 mm) during one
breathhold (typically <20–40 s) with the respective modality.
For coronary calcium screening with EBT, usually a singleslice mode with 3-mm collimation, a scan time of 100 ms per
slice, a table increment d of 3 mm per slice, and prospective triggering are used because this allows the coverage of the whole
heart (N=40 slices) during one breathhold and keeps noise within
a reasonable range. The tube current and voltage are fixed to
I=630 mA and U=130 kV on this EBT scanner. This protocol is
commonly accepted [43].
For calcium scoring with MSCT scanners, two principally different image acquisition methods are possible: prospective trigger-
ing in sequential mode and retrospective gating in spiral mode. We
used the protocol suggested by the manufacturer for coronary calcium scoring with prospective triggering (S=4×2.5 mm, d=10 mm,
N=10, I=100 mA, U=120 kV and rotation time trot=500 ms) and a
consensus protocol proposed by German Sensation 4 users for coronary calcium scoring with spiral CT (S=4×2.5 mm, pitch
p=0.375, number of rotations N=32, I=100 mA, U=120 kV and trot
=500 ms). Moreover, some MSCT scans with thinner slice collimations (4×1 mm) were carried out to investigate the influence of
thinner slice collimations on the quantification of coronary calcium.
Image reconstruction
For EBT image reconstructions were carried out only with the
scanner’s software with the prescribed sharp reconstruction kernel
and a field of view of 250 mm.
For MSCT two options were used to reconstruct images from
the scanner’s attenuation raw data:
Firstly, we used the Siemens software Somaris/5 (version
VA20Q) with a special option for cardiac imaging which allows
prospective ECG triggering and retrospective ECG gating. The exact implementation of the retrospective gating algorithm on the
scanner has not been published. Nevertheless, publications by Siemens engineers give some hints [44, 45, 46]: above a certain heart
rate, the algorithm switches from a partial scan approach with an
effective scan time of 250 ms to an interpolation approach called
multiphasic or biphasic reconstruction with a fixed effective scan
time of 125 ms.
Secondly, to be able to reconstruct images with our own reconstruction software and the well-described and evaluated cardiac
reconstruction algorithms 180° multi-slice cardiac delta (MCD)
and 180°multislice cardiac interpolation (MCI) [36, 37] the raw
data and the ECG information was exported to a special image reconstruction station (ImpactIR, VAMP, Möhrendorf, Germany).
The software runs on any standard PC. Currently, a reconstruction
time of below 1.5 s per 512×512 image is achieved with a 1-GHz
dual Pentium III processor and 1 GB of memory.
For comparison purposes we also reconstructed images with
standard reconstruction algorithms 180° multi-slice filtered interpolation (MFI) and 180° multi-slice linear interpolation (MLI)
[27] that do not utilize ECG information for image reconstruction.
In all cases MSCT images were reconstructed with a field of view
of 220 mm and the recommended Siemens kernel B35f. All reconstructed images were exported in Digital Imaging and Communications in Medicine (DICOM) format to CD or network drives and
evaluated with self-developed software tools.
Measurements and data evaluation
All 12 artificial calcifications and the specimen were scanned
three times with the three different protocols at rest and for at least
two different heart rates to allow the assessment of measurement
errors. Additionally, to investigate the influence of the heart rate
more closely one of the artificial calcifications (3 mm, 400 mg
HA/cm3) was scanned three times for seven more heart rates with
all protocols.
For prospective triggering techniques data sets for at least five
different positions in the R-R interval were acquired to be able to
determine the influence of heart phase on image quality. These
measurements resulted in more than 450 raw data sets. For the retrospective gating technique images were reconstructed for ten different positions in the R-R cycle and evaluated with the three
quantification methods defined below.
The images of each method which contained the least motion
artifacts were taken for further evaluation. Shaded-surface dis-
489
plays (SSDs) of the calcifications were rendered with a threshold
of 130 HU to allow an easy 3D inspection.
To be able to estimate the detection limits for the different systems and protocols the mean CT value above the threshold of the
calcification is plotted against the size (see Fig. 4). The detection
limit, i.e., the size where the maximum CT value falls below the
threshold of 130 HU, can be determined by a linear extrapolation
of the curves to zero. This yields rough estimates for which sizes
of calcifications are just visible in CT images.
For all quantitative measurements the mean absolute error
or the relative error
of the determined mean value of
a quantity x is shown either as an error bar in diagrams or in the
form of a table. Most test series conducted contain only a small
number of measured values and so
itself is subject to a significant error. For such small measurement series
has
tobe calculated from the standard deviation s, the number of measured values N, and a so-called t -factor that corrects for the small
number of measured values [47]. t depends on the number of measured values N and the probability p that a measured value
lies within the interval
.
We used p=95% (significance) and mostly N=3 which yields
t=4.3 and
.
We determined the measurement errors
for all artificial and
real calcifications for different scan protocols and scoring methods. The implementation of the different quantification methods is
based on the definitions given below.
Quantification methods
Agatston score. The Agatston score in its original form is determined from 20 contiguous EBT slices of the heart (3-mm slice
thickness, no interslice gaps, 100-ms data acquisition time per
slice during breath holding). It was implemented as described in
the original publication [10].
In each of the 20 images, calcifications are determined by setting a threshold of 130 HU and ignoring structures with sizes below 1 mm2 to exclude noise from evaluation. Then, one region of
interest (ROI) is placed around lesion j of coronary artery i in each
of the 20 images and the area Aij in mm2 and the maximum CT
numbers
in HU of the ROI are determined. The score Sij
of lesion j in coronary artery i is calculated by multiplying the area
of the lesion with a weighting factor wij that depends on the maximum CT number in the lesions for each image:
(1)
with
used by Agatston. If arbitrary spacing of the images with, for instance, reconstruction increments RI or table feeds smaller than
the slice thickness, i.e., RI<S, are allowed and the score in each
image is determined as before, RI0/RI more slices per volume are
evaluated. Then the determined Agatston score had to be multiplied with the factor RI/RI 0 to keep it invariant with respect to
these parameters and to be able to compare the obtained scores
with the ones obtained with EBT. For 2.5-mm slices the determined score was multiplied with
to obtain a comparable Agatston score.
Moreover, the fact that different systems and protocols yield
different absolute CT numbers for the same structure does not only
influence the segmentation threshold but also the threshold of the
weighting function for the Agatston score. The reconstruction kernels also severely affect CT numbers of small calcifications and
consequently the Agatston score, an effect that cannot be easily
corrected for. Here we corrected the Agatston scores only for the
different slice thicknesses. All other parameters were neglected.
Volume scores. Volume scores are simply calculated as the number
of voxels Nvoxel in the volume data set that belong to the calcification multiplied by the volume of one voxel Vvoxel
(4)
One has to be aware that V does not necessarily represent the real
volume of the calcification as it strongly depends on the threshold
used. This is obviously a drawback of this scoring method as it
also does not correspond to a real physical measure. The observed
size of a segmented homogeneous structure strongly depends on
the position of the threshold compared with the maximum CT value of the structure [40]. Generally, if the threshold is set to
CT#max/2, V approaches the real volume of the calcification. At a
fixed threshold of 130 HU, V overestimates the volume of very
dense calcifications and underestimates the volume of less dense
calcifications. Only the volume of calcifications with mean CT
numbers of approximately 260 HU is close to the real volume.
This is the reason why these scores are called “volume scores” and
not simply the volume of the calcification. Additionally, when using slice thicknesses that are relatively large compared with the
size of the calcification, this quantification method can lead to
large deviations from the true diameters of the calcification due to
the fact that objects much smaller than one voxel but with high
density nevertheless contribute to the score with the complete voxel volume (linear partial-volume effect).
Hydroxyapatite mass. The best and easiest quantification method
might be to use the calcium mass as a measure for the amount of
calcium as it corresponds to a real physical measure, automatically
corrects for linear partial-volume effects, and is invariant with respect to most scan parameters when using appropriate calibration.
The density of a homogeneous calcification is defined as
ρHA=m/V. This means that the mass is given as m =ρHA·V or for
the general case of calcifications with heterogeneous density
(5)
(2)
The total calcium score (Stot or TCS) is determined by summing
up the scores of the lesions for all arteries in all images:
(3)
The Agatston score was designed for a special modality and protocol; therefore, the score is not invariant with respect to image parameters such as slice thickness, slice spacing, absolute CT numbers, and reconstruction kernels.
For example the images used for calcium scoring with new
scanners and protocols will not necessarily have a slice thickness
of S0=3 mm and a spacing of RI0=3 mm such as in the protocol
If we assume that the HA density is directly proportional to the
CT numbers
(6)
with cHA as calibration constant, and if we consider the case of
discrete voxels, we get
(7)
If we now take into account that
we get
(8)
490
i.e., the mean CT number
of each calcification multiplied by
the volume score V of the calcification is directly proportional to
the calcium massm.
To obtain absolute values for the calcium mass, a calibration
measurement of a sufficiently large calcification with known HA
density ρHA has to be carried out and the calibration factor cHA has
to be determined. The calibration factor cHA is calculated as
(9)
Equation 9 assumes that the CT number of water
is 0 according to definitions. If an exact CT value for water is available
from the same calibration measurement, and if it is not equal to 0,
this can be taken into account by subtracting the CT value for water from the CT number of the calcification (baseline correction):
Table 1 Calibration factors for determination of the hydroxyapatite (HA) mass for all tube voltages of the Siemens Sensation 4
and the Imatron Evolution C–150XP
Scanner
Evolution C–150XP
130 kV
200
261.7
10.2
0.795
Sensation 4
80 kV
200
120 kV
200
140 kV
200
384.7
268.9
240.2
1.1
3.7
3.6
0.521
0.754
0.845
(10)
In practical cases the CT number of water always has to be
checked and taken into account.
As the CT number of all materials, except water, depends on
the X-ray spectrum used, the calibration factor has to be determined for all scanners and protocols.
Of course, the determined HA mass can only be the mass
above the threshold used for segmentation. The lower the threshold can be chosen, the more exactly the HA mass can be determined. Nevertheless, it must be ensured that the calcification is
safely separated from the background with the threshold chosen;
therefore, if no other errors are involved, it can be expected that
the real mass is always underestimated by a certain amount. Apart
from effects that are due to the fact that calcifications may contain
non-calcium components, the calcium mass automatically corrects
for linear partial-volume effects, however, as objects smaller than
the slice thickness are displayed with accordingly decreased mean
CT numbers.
Results
Determination of calibration factors for the HA mass
Table 1 shows the result of a calibration for the
C–150XP and the Sensation 4 for all tube voltages based
on the 0- and 200-mg HA/cm3 regions of the calibration
insert (Fig. 1c). Apparently, a voltage setting of 120 kV
with the Sensation 4 yields approximately similar absolute CT values as the EBT scanner. This is important
when comparing the Agatston score which uses absolute
CT values for different scanners. Using tube voltages
other than 120 kV would yield significantly different
Agatston scores without additional corrections. Such
corrections would affect both the weighting function and
the threshold for segmentation.
Performance assessment in calcium scoring
Figure 3 shows a qualitative comparison of the different
methods at different heart rates for an artificial calcification and the calcified specimen.
The standard reconstruction algorithms 180°MFI and
180°MLI without ECG correlation are only able to de-
pict the calcifications with strong motion artifacts. A
180°MFI tends to smear the calcification due to its very
low temporal resolution, and 180°MLI tends to provide
sharper displays but ruptures the calcification apart due
to its better temporal resolution. For the low heart rate all
other methods yield good results, although the higher
spatial resolution of the 4×1-mm collimation is clearly
visible. For the high heart rate, especially methods with
low temporal resolution run into more or less severe
problems. For the small and less dense HA cylinder the
interpolation algorithm 180°MCI performs still very
well, whereas the partial scan algorithm 180°MCD and
the prospective triggering technique with MSCT clearly
show artifacts. For the large and quite dense calcification
(Fig. 3b) we get a different picture. Here, also the interpolation algorithm 180°MCI increasingly runs into problems with the depiction of the calcification. Although it
performs still better than 180°MCD, small calcium pieces turn up in the vicinity of the calcification. The reason
for this effect is star-shaped artifacts in the axial images
for high heart rates that are above the threshold for dense
and large calcifications but below the threshold for
smaller and less dense calcifications.
Detection limits
When the HA mass was introduced in the previous section we assumed that the HA density of a calcification is
directly proportional to its CT number (ρHA∝CT#). If it
were that easy, the determination of detection limits
would not be a big problem. It would be enough to determine the HA concentration which leads to values above
the threshold. For the protocols and scanners examined
here this would be a HA density of approximately
100 mg/cm3 (Table 1) which corresponds to a threshold
of 130 HU. This assumption is only true for large objects
where partial-volume effects do not occur. For small objects the maximum CT value and with it the mean CT
value of the calcification are decreased. For calcifications their maximum CT value in the image is important
491
Fig. 3a, b The artificial calcification (diameter: 3 mm; length:
3 mm; hydroxypapatite (HA)
density: 400 mg HA/cm3) and
the calcified specimen (diameter 5 mm, length 15 mm)
scanned at rest (0 bpm) and at
different heart rates depicted as
shaded-surface display. The
top row indicates the different
reconstruction or scan methods
and the slice collimations used
for scanning. Seq stands for
sequential conventional CT
with prospective triggering.
Always the data sets that contained least motion artifacts
are shown. MFI multi-slice filtered interpolation, MLI multislice linear interpolation,
MCD multi-slice cardiac delta,
MCI multi-slice cardiac interpolation, EBT electron beam
tomography
as this parameter determines if the calcification is detected above a given threshold, in our case 130 HU; thus, the
detectability of calcifications also depends on their size
and not only on their density.
Figure 4 exemplarily illustrates this effect for resting
calcifications consisting of different HA density for the
three different protocols. Table 2 shows an overview of
the detection limits determined for the three protocols, different HA densities of calcifications, and heart rates. The
different protocols and scanners yield different results
mainly due to their different effective slice thicknesses
and in-plane resolution. Thinner slices yield a lower detection limit of calcifications over the threshold of
130 HU due to decreased linear partial-volume effects;
therefore, the detection limit for calcifications at rest is
best with MSCT and prospective triggering (effective slice
width Seff=2.5 mm) and worst with retrospectively gated
MSCT with four times 2.5-mm slice collimation due to its
relatively large effective slice width of Seff=3.3 mm. For
resting objects EBT (Seff=3.0 mm) shows a slightly worse
detection limit compared with prospective triggering due
to its slightly larger effective slice width. The large effective slice width for retrospective gating is due to the fact
that we also used cardiac reconstruction algorithms with a
simulated ECG signal for resting calcifications.
The detection limits for moving objects are affected
by motion according to the temporal resolution of the
scanning method.
492
Measurement errors and reproducibility
Fig. 4 Determination of detection limits for calcifications in coronary calcium scoring at rest. The mean CT number of the calcification above the threshold is plotted against the calcification’s
size. An extrapolation to zero yields an estimate for the size where
the maximum CT number of the calcification falls below the
threshold. Calcifications with smaller sizes cannot be detected using the given threshold. MSCT multi-slice spiral computed tomography
Table 2 Detection limits at a threshold of 130 HU in coronary
calcium scoring. EBT electron beam tomography, MSCT multislice spiral CT, HA hydroxyapatite
mg HA/cm3
0 bpm
(mm)
60 bpm
(mm)
100 bpm
(mm)
EBT
200
400
800
1.7
1.3
1.0
1.8
1.5
1.1
2.0
1.7
1.2
MSCT, prospective
triggering
200
400
800
1.6
1.2
0.9
2.0
1.4
1.0
2.9
1.8
1.2
MSCT, retrospective
gating
200
400
800
3.0
1.6
1.0
3.7
1.7
1.2
3.7
1.8
1.4
Table 3 Variation of Agatston
scores and HA mass for the
different methods and varying
heart rate shown in Fig. 5. The
mean values for the different
heart rates, the standard deviation σ, and the coefficient of
variation CV=σ/Mean are calculated for the different methods. IMP Institute of Medical
Physics
Agatston score
Mean
σ
CV (%)
HA mass
Mean (mg)
σ (mg)
CV (%)
The measurement errors for all three protocols and all
calcifications have been assessed for all resting and
moving calcifications. Additionally, the influence of the
heart frequency was examined more closely for a typical
medium size calcification with average density (length:
3 mm; density: 400 mg HA/cm3). Figure 5a shows the
Agatston score’s dependence on the heart rate for different protocols. We also examined the influence of different slice thicknesses and reconstruction methods; therefore, in addition to the standard calcium scoring protocols, retrospectively gated MSCT with a thin-slice collimation of 4×1 mm was used and the acquired data for
the 4×2.5-mm collimation were reconstructed with the
manufacturer’s image reconstruction algorithm and the
IMP algorithm 180° MCI.
Table 3 shows the evaluation of quantitative measures
for the different methods from Fig. 5. The mean values,
the standard deviation σ, and the coefficient of variation
CV=σ/mean of the different methods for varying heart
rate, were calculated.
Firstly we can note that the 4×1-mm collimation in
combination with retrospective gating on the MSCT
scanner definitely yields the best results with respect to
reproducibility (CV=5.9%). As expected, the methods
are influenced by motion to a degree according to their
temporal resolution. Retrospective gating techniques
show improved reproducibility because overlapping slices are reconstructed. Nevertheless, the scores decrease
with increasing heart rate due to increased blurring. The
IMP implementation of the reconstruction algorithm
180° MCI appears more robust as the score decreases to
a lesser extent than for the manufacturer’s implementation.
The same applies when calculating the calcium mass
(Fig. 5b), but generally, compared with the Agatston
score, the measurement errors are clearly decreased,
which can be seen when looking at the error bars in the
diagrams. The quality of the scoring method is not ex-
EBT
prospective
triggering,
3 mm,
Imatron
MSCT,
prospective
triggering,
4×2.5 mm,
Siemens
MSCT,
retrospective
gating,
4×2.5 mm,
Siemens
MSCT,
retrospective
gating,
4×2.5 mm,
IMP
MSCT,
retrospective
gating,
4×1.0 mm,
IMP
35.5
3.3
9.3
20.8
5.8
27.9
21.6
6.1
28.3
24.1
4.8
19.8
28.0
1.6
5.9
6.3
0.3
5.3
3.9
0.9
22.2
4.2
1.0
23.9
4.8
0.8
16.1
4.9
0.2
4.1
493
By evaluating the measurements for all calcifications
from 1 to 5 mm and for different densities, we found that
the volume score and the HA mass are clearly advantageous compared with the Agatston score in terms of reproducibility. The calcification’s mass above the threshold is another key factor for good reproducibility. For
high HA densities and large calcifications measurement
errors are low. Even large calcifications but with low
densities are highly affected by motion.
Accuracy and comparability
Fig. 5a, b Reproducibility of the Agatston score and the HA mass
for a moving calcification (length: 3 mm; diameter: 3 mm; density: 400 mg HA/cm3) for different scanning methods. Retrospective
gating with thin slice collimation yields best, prospective triggering with MSCT worst reproducibility. Generally, b the calcium
mass is better reproducible than a the Agatston score
pected to be mainly a function of heart rate and therefore
the calculated CVs are not dramatically decreased for the
calcium mass compared with the Agatston score. Nevertheless, also here the lower CVs indicate that mass scoring is more robust.
As for the Agatston score, the thin-slice collimation
yields the best results and the mean values for the manufacturer’s reconstruction algorithm decrease more
strongly than those determined from the images reconstructed with 180° MCI. Especially, the IMP algorithm
180° MCI can clearly deal better with heart rates over 70
compared with the manufacturer’s implementation
(p<0.00116, Wilcoxon test).
In this section the accuracy of the methods, i.e., how
good the measured values correspond to the true ones, is
evaluated. For the Agatston score no physically true values exist; therefore, we here use the Agatston score determined with EBT as reference to which we compare
the Agatston scores determined with the other scanner.
In Fig. 6 the Agatston scores of all calcifications measured with MSCT are plotted against the ones determined with EBT. The comparison yields a reasonable
correlation, although especially low scores seem to be
underestimated with MSCT compared with EBT. For
prospectively triggered MSCT and scores below 50, deviations of approximately 50% occur. Retrospectively
gated MSCT with a slice collimation of 4×2.5 mm underestimates the scores more severely due to its larger
effective slice width of 3.3 mm; therefore, many of the
small and low-density calcifications are missed even
though they are depicted above the threshold with EBT.
It has been pointed out before that the Agatston score
has many disadvantages; nevertheless, the extensive data
acquired with it should not be lost when switching to a
new score. The Agatston score does not increase linearly
with the density but at least the steps of the weighting
function are in equal distance; therefore, it is of interest
to investigate if it is possible to estimate the calcium
mass from the Agatston score, and vice versa, with a reasonable error. This was tried for EBT and all measured
values in Fig. 7. Apparently, the calcium mass is closely
correlated to the Agatston score (R2=0.9733). The calcium mass can be calculated quite accurately from the total calcium score (Agatston) by multiplying with a factor
τ:
(11)
where in this case τ=0.1922 mg. For prospectively triggered MSCT and retrospectively gated MSCT the correlation of HA mass and Agatston score is quite good also.
The respective values are given in Table 4.
Nine measured values in Fig. 7 with HA masses
above 80 mg have been excluded from the regression.
They are too dense and therefore yield too high CT numbers to still yield an approximately linear relationship
with the Agatston score. These are the measured values
494
Fig. 7 Relation of the HA mass vs the Agatston score. Nine measured values with HA masses above 80 mg were not included in
the linear regression. They were too dense and therefore yield too
high CT numbers to still yield an approximately linear relationship
with the Agatston score (see text)
Discussion and conclusion
Fig. 6 Comparison of Agatston scores determined with a prospectively triggered MSCT and b retrospectively gated MSCT with
EBT. Due to its relatively large effective slice width of 3.3 mm
with the given protocol, retrospective gating yields zero scores for
small calcifications that can be detected with EBT using the
threshold of 130 HU
Table 4 Conversion factors from Agatston score to HA mass for
different techniques and protocols
Protocol
τ/mg
R2
EBT
Prospective triggering
Retrospective gating
0.1922
0.1752
0.1771
0.9733
0.9734
0.9709
for the 5-mm, 800-HA calcification at rest and for two
different heart rates. The 5-mm, 800-HA calcification is
probably not physiologically relevant due to its large size
combined with very high density.
Using a custom-designed anthropomorphic cardiac phantom, we have qualitatively and quantitatively evaluated
the performance of coronary calcium imaging as a function of scanner type, heart rate, reconstruction algorithm,
and quantification system.
The new MSCT scanners offer the possibility of highquality cardiac imaging with good reproducibility in
quantitative studies. Prospective triggering with MSCT
scanners is most severely affected by motion, and EBT is
least severely affected by motion. Although retrospective
gating is affected by motion to a lesser extent, due to
shorter effective scan times and the possibility of reconstructing overlapping images, its relatively high effective
slice thickness of 3.3 mm with the 4×2.5-mm slice collimation yields the worst detection limits. This also leads
to the worst reproducibility in many cases as the amount
of calcium above the threshold is a key factor for good
reproducibility.
Good performance in the assessment of quantitative
parameters is always the result of high temporal and high
spatial resolution. Thin-slice protocols in combination
with retrospective gating have the potential to improve
the performance of MSCT scanners significantly. These
protocols are already used in CT angiography applications for coronary imaging, but they are avoided for
screening procedures such as calcium scoring due to the
higher patient dose of 4–8 mSv applied [40, 48]. Patient
dose values of the present standard protocols for the
quantification of coronary calcium are in the range of approximately 0.5 to 2 mSv [40]. Probably methods for
495
dose reduction in spiral CT [27, 40, 46] will help to decrease patient dose values to an extent that they can be
used for the quantification of coronary calcium.
Not only the scanners have a big influence on the reproducibility of scoring results, but also the quantification methods themselves. The Agatston score with its
many limitations has been used since 1990. The most obvious drawbacks are its complexity, its dependence on
CT number levels and on the number of slices per scan
length, its non-linearity, and its strong dependence on
small variations due to noise and motion as it uses maximum CT numbers. Furthermore, as the score does not
correspond to a physical measure, it cannot be easily
compared with true values for exactly defined calcifications and cannot be used in an intuitive manner. The
large amount of data acquired with the Agatston score
and the risk tables derived therefrom for coronary events
[6, 7] are the only reason to keep it. Epidemiologic data
has been derived from these measurements and many
physicians are used to this score.
Nevertheless, it appears mandatory to switch to a new
quantification method that can be compared for different
scanners and that is robust with respect to modifications
of scanners, protocols, and segmentation approaches.
Here the HA mass measured in milligrams of hydroxyapatite above a certain threshold is clearly superior. It
can be determined easily with a simple calibration measurement that has to be carried out only once for each
scanner and protocol used, and it is a physical measure
which can be validated. It offers significantly improved
reproducibility and even correlates – with certain limitations – to the Agatston score. This might be important
for those who thus far have doubted the clinical relevance of the HA mass compared with the Agatston
score. The cutoff points for risk groups determined in epidemiologic studies can be converted in good approximation from Agatston score to HA mass. Thereby these
data will not be lost and all investigations can be continued with the HA mass instead of the Agatston score.
Also the segmentation methods leave much room for
improvement. They can be considered to lower the
threshold for modern scanners as they allow to reduce
noise significantly by increasing the tube current. The
only reason for the traditionally relatively high threshold
of 130 HU for EBT is the high noise in EBT images. We
suggest to switch from a CT number threshold in HU to
an HA density threshold (e.g., 80 mg HA/cm3) that is independent of the scanner in future studies. Moreover,
non-threshold-based segmentation approaches have to be
considered.
Progression studies that aim at already detecting
small changes of calcium in a short time should always
be carried out with the same scanner, with the same
scanning technique, and with the same evaluation method because only this ensures highest reproducibility.
There is a clear analogy to other quantitative methods,
such as BMD measurements, in osteoporosis [27]. Although it is possible to correct for certain effects with the
introduced quality assurance tools, some errors will still
remain for which there is no compensation. For scanners
that are not as stable as the current MSCT scanners, it
can be considered to scan a reference phantom with each
scan to be able to correct individually for variations in
tube voltage, etc.
Generally, future clinical studies will require standardized methods for image evaluation that have to be
compiled to assure high quality of the assessment of
quantitative parameters with different scanners. Performance characteristics of scanners have to be evaluated
and scan protocols and evaluation procedures have to be
optimized in order to achieve high reproducibility and
comparability of data acquired at different clinical sites.
Initiatives in Europe and in the U.S. are already working
on this ambitious subject. Only then will it be possible to
obtain reliable results in the field of coronary calcium
scoring.
Modifications to the described phantoms already implemented by the authors offer the possibility of inserting ionization chambers at different positions for the assessment of dose values, and extension rings allow simulation of different patient sizes with the introduced quality-assurance tools. Respective measurements and the assessment of physical parameters, such as slice-sensitivity
profiles, modulation transfer functions, contrast and
noise, and patient dose, including the new generation of
8- and 16-slice scanners, are presently in progress.
Acknowledgements We thank our colleagues from the Department of Cardiology, especially S. Achenbach and D. Ropers, and
from the Department of Diagnostic Radiology, for a good and
pleasant collaboration. S. Achenbach supplied us with the cardiac
4D motion functions determined from angiography data. Parts of
this work were supported by grants from the Bayerische Forschungsstiftung (AZ 262/98 and AZ 322/99). We also thank the
reviewers for their constructive comments which helped to improve the manuscript.
496
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