Detection and Quantification of CalcifiedCoronary Plaque With Multidetector-Row CT 11

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Detection and Quantification of Calcified

Coronary Plaque With Multidetector-Row CT

J. J EFFREY C ARR , MD , MSCE

INTRODUCTION

Multidetector-row computed tomography (MDCT) has rap- idly developed into a powerful tool for noninvasive measure- ment of calcified plaque in the coronary arteries over the past decade. Identification and quantification of coronary artery calcifications (CAC) with X-ray devices is well established in the literature with chest radiographs, fluoroscopy, computed tomography (CT without electrocardiogram [ECG] gating) and cardiac CT (electron beam CT [EBCT], helical CT , and MDCT with cardiac gating) (1–6). Calcified plaque is an established component of coronary atherosclerosis, and radiographic tech- niques are highly sensitive to calcified atherosclerotic plaque (1,7). The presence of calcified plaque documents the presence of subclinical atherosclerosis in the coronary artery. Calcified plaque is an active and regulated process occurring in the vessel wall, with pathways similar to those of bone metabolism (8,9).

As of 2003, two consensus documents (1,10) concerning car- diac CT and the recommendations of the Prevention V Confer- ence (11) are available to guide clinical application. The results of several large epidemiological studies, as well as pharmaceu- tical trials, will become available during the next five years and will provide new information to guide the medical community and society at large as to the appropriate utilization of CAC screening in the population.

Cardiac CT is rapidly transitioning from a research tool with modest clinical application to a diagnostic test integral in our management of cardiovascular disease. There is increasing evidence that cardiac CT applied to measuring CAC will be effective in the risk stratification of individuals asymptomatic for cardiovascular disease (CVD), as will be discussed later in this chapter. The rapid development of the cardiac-gated MDCT techniques was made possible through the pioneering work performed with EBCT in the 1980s and 1990s. Technological advances in engineering, manufacturing, and computer sci- ences made possible the current-generation MDCT systems.

The strengths of cardiac CT and, specifically, MDCT, are detailed in the technical chapters, but are based on high spatial resolution, volumetric coverage, high temporal resolution, rapid scan times, high patient productivity, robust protocols,

consistent results, and high patient acceptance. In this chapter we will review the history of MDCT for the measurement of CAC, discuss the technical aspects and various implementa- tions of MDCT protocols for measuring CAC, and review sci- entific results published and in-progress with cardiac CT and MDCT specifically.

EVOLUTION OF HELICAL CT TO CARDIAC-GATED MDCT

The ability to identify the heart and calcifications related to the coronary arteries was noted even with early-generation CT scanners, despite insufficient temporal resolution to stop car- diac motion (12,13). The motion of the heart blurred anatomic detail related to the coronary arteries and cardiac chambers.

The development of slip-ring CT technology, which enabled spiral or helical CT scanning, dramatically improved the tem- poral resolution of mechanical CT systems. Increased gantry speed provided improved temporal resolution and greater scan coverage per unit time, which facilitated protocols incorporat- ing suspended respiration (14). When CT gantries capable of 1 s were possible, the nongated ECG scans through the chest clearly demonstrated improved cardiac and coronary morphol- ogy, and strategies for quantifying CAC were developed (2,15,16). Cardiac gating of helical CT exams using a helical acquisition was first coupled with low-pitch overlapping recon- struction algorithms designed to maximize temporal resolution and create multilevel, multiphase images of the entire coronary circulation. (17). Synchronized recording of the ECG tracing during the scan acquisition allowed the images to be aligned with the ECG tracing of cardiac activity. This retrospective ECG gating was performed after the scan was acquired (i.e., postexam processing) on a computer workstation, and allowed the user or computer algorithm to select the appropriate dias- tolic phase image for measuring CAC (Fig. 1). The introduc- tion of the 0.8-s gantry rotation and higher heat unit X-ray tubes made possible a more clinically feasible study with further improved image quality. The 0.8-s gantry rotation resulted in cardiac imaging with a temporal resolution of 520 ms per im- age, and the high heat unit tube meant that the scans could be obtained in clinical practice without extended wait periods for tube cooling. This first-generation cardiac-gated helical CT technique allowed scanning the entire heart in a single breath- hold ranging from 30 to 50 s, depending on heart rate, which determined the helical pitch (4).

11

From: Contemporary Cardiology: CT of the Heart:

Principles and Applications

Edited by: U. Joseph Schoepf © Humana Press, Inc., Totowa, NJ

Fig. 1. Retrospective gating with a single-slice helical CT system. The image is from a retrospectively gated helical scan performed in June

of 1999 (General Electric Medical Systems)—CTi, with 0.8-s gantry, SmartScore calcium scoring package on the Advantage Windows

workstation). Overlapping images are reconstructed throughout each cardiac cycle, represented by the gray diamonds. An automated selection

algorithm picks the diastolic phase image at a preprogrammed percentage of the cardiac cycle (red diamond) and is displayed in the image

window below the electrocardiogram (ECG) tracing. As discussed in the text, images are obtained throughout the cardiac cycle, resulting in

significantly higher exposure than in a prospectively triggered sequential protocol. Modern multidetector-row CT systems obtain multiple

channels of data simultaneously (4, 8, 12, or 16, depending on model). However, like the single-slice helical CT system, the helical reconstruc-

tion algorithm requires data throughout the scan, and thus the X-ray tube is on continuously. ECG dose modulation is available and reduces

tube current during systole to improve the dose profile of the study. However, even with tube modulation, prospective triggering results in the

lowest dose profile while maintaining comparable image-quality factors. Calcified plaques are demonstrated in the left anterior descending

coronary artery.

The studies comparing the single-slice scanners with ECG gating demonstrated high correlation and good agreement between calcium scores obtained with that generation of EBCT systems (C150) and the single-slice helical CT systems (3,4,18–20). This new capability for helical CT came with limitations. First, the overlapping reconstructions resulted in a large number of images—typically 450–600 images per scan series. The large number of images required significant com- putational resources to reconstruct the images, and this pro- cess would often have to be completed offline to reduce impact on patient throughput on the CT scanner. The scans also tended to result in relatively long breath-holds, ranging from 35 to 50 s. With the single-slice helical CT, the breath-hold time was dependent upon the patient’s heart rate, which was used to set the speed of the CT couch as it moved the patient through the scanner. The single-slice helical CT exam was dose-ineffi- cient in that the patient was irradiated for the entire cardiac cycle, but only a few cardiac phases at most were utilized for calcium scoring. Prospective ECG triggering was developed and tested on these systems, but the application was limited by long scan times, which required multiple breath-holds to image the entire heart (3). Nonetheless, single-slice helical CT systems operating with effective temporal resolutions of 520 ms demonstrated the capability of mechanical CT scanners to accurately and reproducibly measure CAC with comparable measurement error to EBCT. Direct comparison of helical CT and EBCT with individuals receiving paired scans on each system demonstrated no statistically significant difference in the interexam or intraobserver variability when using the stan- dard 130-Hounsfield unit (HU) threshold (21). The foundation developed for single-slice helical CT was critical for develop- ing cardiac applications, reconstruction algorithms, ECG and non-ECG gating strategies, and postprocessing for the revolu- tion in CT—the introduction of multislice scanners.

MDCT SYSTEMS—APPLICATION

TO CORONARY CALCIUM MEASUREMENT The introduction of the four-channel MDCT systems created new possibilities for cardiac imaging. The ability to acquire four 2.5-mm slices results in covering 10 mm along the z axis with each heart beat. The entire heart, typically 120 mm in z axis length, could be imaged with only 12 movements of the CT couch. For the first time the entire heart could be covered with prospective ECG gating in a clinically acceptable breath-hold time. The initial release of the four-channel MDCT systems had gantry rotations of 0.8 s, although this was followed by systems with gantry rotation speeds of 0.5, 0.42, and 0.4 s, resulting in temporal resolutions ranging from 520 to 240 ms when scanning in the cardiac mode (i.e., partial scan recon- struction). The MDCT scanner is operated in the sequential scan mode (on some systems this is called axial or cine scan mode), resulting in significantly less radiation exposure than the helical approach utilizing retrospective ECG gating. This approach is fundamentally identical to calcium screening pro- tocols implemented with EBCT systems that also utilize a “step- and-shoot” sequential scan technique.

The basic operation of a MDCT system for sequential CAC study with prospective ECG gating is the same whether it is 4, 8, or 16 slices. The operator prescribes the start and end loca- tions based on the scout image of the thorax. The MDCT scan- ner moves the CT couch so that the first block of 4, 8, or 16 images is appropriately positioned inside the gantry. The scan sequence is started by the breathing instructions, and the first block of images is obtained at the prescribed offset from the R wave on the ECG. In the sequential mode, the X-ray beam is on for only a very brief exposure at each level. For a 0.5-s gantry system this time is slightly more than the number of views required to reconstruct an image, and is typically in the range of 330–360 ms, depending upon manufacturer. For a General Electric LightSpeed™ 8 or 16 MDCT with a 0.5-s gantry, the X-ray exposure time is only 2 s for the entire scan. During the majority of the 10–20-s scan time, the X-ray tube is off because the CT couch is moving to the next location or the CT is waiting for the appropriate cardiac phase. Upon completion of the first set of images, the CT couch then moves the patient to the next block of scans along the z axis. This movement occurs during the second cardiac cycle, which then allows the second block of slices to be obtained during the third cardiac cycle of the breath hold. This sequence of acquiring and skip- ping a heartbeat continues until all the prescribed scan loca- tions have been completed.

As of 2003, MDCT systems use various detector arrays with a length along the z axis of 20 mm. For the MDCT(4) systems, a 4 × 2.5-mm slice protocol uses the center 10 mm of the detector. The introduction of the MDCT(8) and MDCT(16) systems allowed scans for coronary calcium using an 8 × 2.5-mm configuration, thus utilizing the entire 20-mm width of the detector array. A comparison of MDCT systems is presented in Table 1. The direct benefits of this for coronary calcium scan- ning are the reduction in reduced breath-hold time to 10–20 s as opposed to 20–40 with MDCT(4). Only six CT couch trans- lations and thus only 6 cardiac cycles—as opposed to 12 with MDCT(4)—are needed to image the entire heart, which improves the image quality by reduced variability related to cardiac beat-to-beat variations, improved slice registration along the z axis, and reduced patient dose through improved dose efficiency.

One way to conceptualize prospective ECG gating with

MDCT is to mentally construct the “ideal” CT device, in which

a detector covers the entire heart. This system might have 48

channels or rows (i.e., capable of 2.5-mm slices × 48 levels =

128-mm detector) through the use of either a panel or dramati-

cally expanded matrix array detector (22,23). To measure coro-

nary calcium with a similar protocol to today’s CT systems, the

hypothetical “MDCT(48)” scanner would operate in the

sequential mode and acquire 48 slices, each 2.5 mm thick,

within a single heart beat. If we assume no further improvement

in gantry rotation speeds beyond 0.4 s and utilize the current

partial scan reconstruction algorithm, then scan acquisition and

breath-hold time would be 250 ms! The entire coronary arterial

tree would be acquired within a 250-ms phase of a single car-

diac cycle, and no movement of the patient by the CT couch

would be required. “Sequential” would be a misnomer, since only one block or set of 48 images would be obtained. By acquiring all levels or slices of the coronary tree in a single heartbeat, slice misregistration related to beat-to-beat coronary motion, breath-holding, and voluntary patient motion would be eliminated. A more likely scenario is that this enhanced imag- ing capability would be coupled with more sophisticated recon- struction algorithms, providing either enhanced temporal resolution or increased coverage of cardiac motion (multiphase imaging) or both to varying degrees.

MDCT systems will continue to rapidly develop new capa- bilities focused on cardiac imaging, based in large part on the intense global competition between CT manufacturers. Based on the rapid developments with CT of the past decade, it is foolhardy to speculate what capabilities may be available to cardiac imagers even in the near future from the descendents of today’s MDCT systems. It is clear that future MDCT systems will incorporate enhanced resolution both temporal and spatial, greater coverage of the heart, new methods for cardiac motion compensation, dose reduction techniques, scan reconstruction and postprocessing applications specifically designed for cardiac imaging. What remains unknown is when, and what impact these advances in cardiac imaging with CT will have on clinical management.

MEASURING CALCIFIED CORONARY PLAQUE WITH CARDIAC CT

In quantifying the amount of calcified plaque in the coro- nary arteries, the CT system is acting as a measurement device.

Something common to all measurement techniques is the pres- ence of measurement error. Comparison of two measurements will by definition incorporate the combined errors of the two measurements. The problems associated with comparing a new technique to an established technique are well documented in medical and statistical literature (24,25). Accuracy is defined as how well the instrument is calibrated to the true value of the object being measured. Precision indicates the degree of refine-

ment of the reported value. Thus a measurement can have high precision (alternatively, highly reproducible or refined), pro- viding nearly the same value on multiple measurements but biased from the true value. Likewise a device can be well cali- brated but have significant variability, resulting in decreased precision. Most importantly, the degree of accuracy and preci- sion must be appropriate for the desired task. Fortunately, car- diac CT can measure plaque burden with high accuracy and good precision in the range of values for which clinical deci- sions are likely to be made, based on existing outcomes data.

Specifically, EBCT and MDCT have extremely good measure- ment characteristics for plaque burden above Agatston scores of 50. More problematic, as will be discussed later, are the low scores, where detection and image noise issues have been shown to negatively impact the ability to measure calcified plaques. Likewise, changes in calcium scores over short time intervals can easily be shown in groups of patients, with reason- able statistical power; however, tracking change in CAC in an individual over a year requires significantly greater precision and accuracy.

CT was developed as a medical imaging device, with less emphasis on quantification of the X-ray attenuation values (a.k.a. CT numbers or HU). The CT attenuation values extend from –1000 to +4000. CT number 0 is calibrated to water, –1000 to air, +1000 to dense bone, and >1000 to metal objects. Limi- tations in the CT scanners’ ability to measure small calcified objects were established early in the history of CT, during attempts to quantify calcification in pulmonary nodules. Since this effort, there has been significant improvement in the CT system stability and quality control over the past decade (26).

When comparing CT devices (EBCT vs EBCT, MDCT vs MDCT, or EBCT vs MDCT) an understanding of the influ- ences of accuracy and precision are important to understand any observed differences. Significant variability in the mea- surement of coronary calcium between EBCT systems at the same site maintained and calibrated by the same engineers has been reported with the 130 HU threshold varying between 77.1 Table 1

Comparison of MDCT Multislice Capability

on Scan Time—Sequential Scan Mode With Prospective ECG Gating

Multislice Slice thickness Slab thickness Slabs per 120 mm Scan time

capability (mm) (mm) coverage (s)

1 2.5 2.5 48 80–160

4 2.5 10 12 20–40

8 2.5 20 6 10–20

8 or 16 2.5 or 1.25 20

20 6 10–20

48 2.5 120 1 0.24

Slab thickness roughly corresponds to beam collimation; however, the beam must be slightly wider than the nominal detector configuration. Current 16-channel systems are limited in their z axis coverage by the 20-mm width of the detector. These systems can typically acquire in either an 8-slice mode (8 × 2.5 mm) or 16-slice (16 × 1.25 mm) with increased spatial resolution in the slice direction (z axis). The hypothetical 48-slice MDCT system is provided as an example of how the increasing size of the detector along the z axis will impact future cardiac CT protocols.

Numerous technical challenges remain to be solved before this type of system or some variant is ready for clinical

applications.

and 136.4 mg/cm

of calcium hydroxyapatite (27). Likewise, when replicate calcium determinations are performed using EBCT, significant measurement error has been documented.

Mean interscan variability using the Agatston scoring method has ranged from 18 to 43%, and there remains debate about the impact of a 40% vs 80% phase for image acquisition (28–32).

The nature of the calcium score and the range of values from 0 to greater than 10,000 requires an understanding that the mea- surement error changes based on the amount of calcified plaque;

a more detailed analysis using methods proposed by Bland to determine limits of agreement is indicated and has been performed by some researchers (24,33). Comparable degrees of measurement error, as will be discussed later, have been documented for MDCT. It must be remembered that if one measurement device is labeled the “gold standard,” all com- parison instruments will have the error inherent in the gold standard included and in some cases erroneously attributed as error related to the comparison device. The measurement error is related to the physiology of the heart and the size of the calcified plaques we are measuring with the CT systems. Spe- cifically, we are asking the CT system to measure relatively small calcified plaques located on 3-mm or smaller coronary arteries using a slice collimation of 2.5–3 mm, depending on CT system. This results in partial volume averaging of the plaque within or between two slices, which can dramatically alter the CT numbers of the plaque. In addition, motion blurring is present with EBCT and to a greater extent with MDCT. Blur- ring of the plaque secondary to coronary motion is most com- mon in the right coronary artery, and alters the values of the picture elements (pixels) within a given image. Lastly, detec- tion of calcified plaques is determined by the presence of more signal (information about the plaque and surrounding struc- tures) than noise. Image noise is random by definition and obscures information or signal. The noise in the CT images creates false-positive plaques that cannot be differentiated from true calcified plaques. The impact of image noise on small- lesion detection has been documented with EBCT (34). A limi- tation of EBCT is the fixed mAs (approx 60). With mAs fixed, image noise increases with thoracic size and degrades image quality in larger patients. The established relation between body size and image noise will creates an erroneous relationship between obesity and CAC (35,36). Since both obesity and CAC are associated with CVD, this results in confounding the true relationship. The ability to alter technique and maintain a con- stant image quality (i.e., an acceptable level of image noise) is a critical benefit of MDCT techniques for CAC (37,38). There is by definition a trade-off between improved image quality (i.e., less image noise means more signal and more X-ray pho- tons) and increased dose. Thus, image quality should be selected based on the clinical application of the results. Current and likely future clinical recommendations indicate changes in management using significant levels of plaque burden corre- sponding to Agatston scores ranging from 100 to 400. How- ever, if a percentile approach or progression rates are to be utilized in clinical practice, then these issues become critical and further research into the optimal level of image quality is required.

STUDIES EVALUATING CALCIFIED PLAQUE MEASUREMENT WITH CARDIAC CT

In the studies to date, extremely high correlations have been seen between CT devices for both the amount of calcified plaque and the rank ordering of patients’ calcium burdens. In the initial comparisons of EBCT to single-slice helical CT with ECG gat- ing, the correlation between scores performed on the same indi- viduals was near perfect (R > 0.97), and mean interscan variability was 25% (3,4). In addition, the more conservative nonparametric Spearman’s test of rank order was shown to be extremely high (0.96), and agreement at grouping patients based on Agatston scores of 100, 200, and 400 was 97%, 92%, and 94%

respectively. The study by Goldin et al. is the only study to date in which a direct comparison of interscan variability between EBCT and helical CT/MDCT has been performed. In this study, participants had paired scans and calcium measurements on an EBCT (C150) and a GE helical CT system with cardiac gating (0.8-s gantry), and no statistically significant difference in interscan or interobserver variability was found when using the 130 CT threshold and Agatston scoring method. Differences in risk stratification were observed between the two methods. The documented high correlations for both amount of calcium and ordering of calcified plaque burden in these studies indicates that differences in agreement could be improved through cali- bration of calcium plaque measured by CT to an external stan- dard (4,27). This calibration would reduce systematic bias related to the CT system and further improve agreement.

The National Heart, Lung and Blood Institute of the National

Institutes of Health is funding the Multi-Ethnic Study of Ath-

erosclerosis (MESA), in which 6800 individuals asymptomatic

for CVD have received an extensive CVD exam, including

cardiac CT measurement of CAC. MESA exams are performed

at six field centers across the United States (39). The partici-

pants had replicated measures of coronary calcium made dur-

ing the baseline CT visit in order to measure interscan

variability and to improve the ability to track progression of

calcified plaque in subsequent planned exams of the cohort. In

MESA, three field centers utilized EBCT (C150) and three

MDCT (4-slice). Findings from the baseline exam on cardiac

CT interscan variability were presented at the American Heart

Association Scientific Session in 2002 (40). After adjusting for

mean calcium score and body mass index, there was no signifi-

cant difference between median interscan variability using the

Agatston score (EBCT 22.7 vs MDCT 24.7, p = 0.15) or volume

score (EBCT 11.0 vs MDCT 11.9, p = 0.84). The median

interscan percentage differences using the Agatston score were

18.1 % (EBCT) and 18.7% (MDCT), and are consistent with

the range of interscan variability published for EBCT of

18–43% as well as the result published with MDCT(4) demon-

strating interscan variability of 20.4%, 13.9%, and 9.3% for

Agatston score, volume, and mass respectively (41). The con-

clusions we can draw from these data is that the measurement

precision of EBCT and MDCT(4) are very similar. The compo-

nent of the overall observed variability attributable to the CT

systems (EBCT vs EBCT, MDCT vs MDCT, EBCT vs MDCT)

is small relative to the intrinsic variability present in measuring

CAC with existing cardiac CT technology.

MDCT—CARDIAC-GATED HELICAL ACQUISITIONS FOR CAC

MDCT systems can scan in a helical mode and can recon- struct images compensated for cardiac motion using either ECG waveform or the inherent motion of the heart (42–44). These techniques are detailed in other chapters, but evolved directly from the single-slice helical CT retrospective gating described previously (Fig. 1). Although currently used and developed for MDCT coronary angiography, it is clear that these advances in coronary imaging can be applied to measuring calcified plaque in the coronary arteries during a non-contrast-enhanced study.

Specifically, the improved spatial and temporal resolution pos- sible with these techniques has already been shown to reduce inter-exam variability from 35% with EBCT using the standard sequential technique and 3-mm slices to 4% with volumetric MDCT using a helical scan with overlapping 2.5-mm slices in controlled testing with a motion phantom of the coronary arter- ies (45,46). These methods hold significant potential. The increased radiation exposure and limited clinical experience has limited their application to date. Lower-dose methods incorporating mA modulation and low-kV imaging are avail- able, and initial reports have demonstrated promising results (47–49). At this time, prospective ECG gating with a sequential scan acquisition is the preferred standard for clinical use, based on the lower radiation exposure and more extensive clinical and research experience to date. The future application of the helical technique to coronary calcium imaging, although prom- ising, remains to be fully defined and validated for clinical practice.

IMAGE NOISE AND CARDIAC CT

Atherosclerosis begins as early as the second decade of life, and includes the formation of small calcified lesions (50).

Detection of calcified plaques in the walls of the coronary arteries requires increasing image quality as the size of the plaque becomes smaller. In essence, with CT (EBCT or MDCT) the device is measuring those calcified plaques above the pre- defined threshold and size criteria configured in the scoring software. These factors are determined not by the pathobiology of atherosclerosis but by the imaging specifications of the CT devices. Individuals with a calcium score of zero represent a range of calcified coronary plaque not measurable by existing CT technologies. Previous authors have suggested lowering the threshold for CT-measurable calcified plaque from 130 to 90 CT units (16). This effectively increases the sensitivity of the CT test for earlier plaque. For helical CT and MDCT sys- tems, this is possible through the ability to maintain sufficient image quality by adjusting the mA or tube current to maintain the signal-to-noise ratio (SNR) at an acceptable level. Without maintaining the SNR, the image quality is degraded to the point that image noise obscures the small, calcified plaques. With EBCT, mAs is fixed. Individuals with increasing thoracic girth have increasing image noise. Image noise can vary on MDCT systems depending upon the technique employed, but typically range between 8 and 16 noise/HU, compared to 24 noise/HU for EBCT. Image noise can be scored as CAC resulting in false- positive results and inflate the size of true lesions. This relation

between patient size and image noise with EBCT has been demonstrated to confound the true relation between CAC and obesity (35). Cardiac imaging requires all aspects of image quality (SNR, temporal resolution, contrast-to-noise, and spatial resolution) to be balanced appropriately for the desired task. In the specific case of detecting and quantifying small calcified plaques in the coronary arteries, the critical influence of image noise was established early in the literature with EBCT (34). The epidemic of obesity in industrialized societies and the elevated risk of CVD seen in individuals with the metabolic syndrome (which includes obesity) means that any device that will be used for screening the general population for CVD must be able to handle individuals weighing greater than 100 kg (220 lb) without creating false-positive calcium scores. Main- taining a consistent level of image quality across various patient sizes will significantly improve image quality and the measure- ment of CAC.

IMPROVED SPATIAL RESOLUTION

The continued technological advancement of MDCT sys- tems will allow imaging with increasing spatial resolution in the slice or z direction. Current MDCT-16 systems can pro- vide 1.25-mm slices by 16 levels simultaneously with proto- cols reconstructing 2.5 mm × 8 levels at no increased dose or exposure to patient. With increasing spatial resolution, issues related to dose and SNR become increasingly important. Fun- damentally, improved spatial resolution will allow more accurate measurement of small coronary plaques (Fig. 2). If the CT technique and radiation exposure is held constant, by definition greater image noise will be present on the thinner 1.25-mm images, when compared to the 2.5-mm images reconstructed from the same scan data. These improvements in measurement capability may be particularly important in measuring the change in plaque burden over time, and this is an area of extremely active research. Rapid progression of coronary atherosclerosis and thus potentially calcified plaque may be a key predictor of future clinical events.

STANDARDIZED SCANNING PROTOCOL FOR MDCT

The continued technological change in MDCT makes stan- dardization problematic. For measuring CAC, by far the great- est experience is using prospective ECG gating (also called triggering) and scanning in a sequential scan mode. Gantry speeds of 0.5 s or greater should be used for cardiac applica- tions. 120 kVp with mAs ranging from 50 to 100 are consis- tently used in research and clinical applications. The tradeoff between 50 and 100 mAs is between dose (effective dose ranges between 1 and 2 mSv, respectively) and image noise.

Note that increasing mAs with patient size is desirable to

maintain image quality. In the MESA CT protocol, mA was

increased by 25% for those individuals weighing greater than

100 kg (220 lb). Slice collimation is relatively standardized at

2.5 mm for MDCT systems when operating in the sequential

mode. MDCT scans should be performed at the maximum

multislice capability (i.e., widest nominal beam width) pos-

sible in order to reduce variability related to coronary and

Fig. 2. Improvement in spatial resolution using 1.25-mm slice collimation. Images A and B are from the same cardiac-gated scan through the heart performed on a multidetector-row CT(16) system (General Electric LightSpeed Pro) using 0.4-s gantry rotation and segmented recon- struction algorithm. (A) The direct axial slice reconstructed with 2.5-mm slice thickness; (B) the same data reconstructed at 1.25-mm slice thickness. Note how there is increased image noise apparent in the 1.25 slice by the more “textured” appearance of the homogenous blood in the ascending aorta and main pulmonary artery. (C,D) Oblique reconstructions positioned to create a cross-section through the left anterior descending coronary artery using the 2.5-mm and 1.25-mm data respectively. Note how the calcifications in the wall of the left anterior descending artery demonstrate more detail secondary to the improved spatial resolution with the 1.25-mm dataset. These sets of images demonstrate how improved technique will be required as slice thickness is reduced if the level of noise is to remain constant.

patient motion. The wider beam will also reduce extraneous scatter radiation and increase dose efficiency while reducing patient exposure.

CALIBRATED CALCIUM MASS

Calibration of any measurement device is central to improv- ing accuracy. The Agatston score is a quantitative scoring sys- tem with limitations related to the discrete weighting factors that increase variability, and it has no straightforward means of calibration (41,51,52). The various volume-scoring methods allow calculation of the volume of calcified plaque in S.I. units such as milliliters. Volume methods are strongly influenced by the threshold of “CT measurable calcium,” typically set at 130 HU. It has already been demonstrated that there is variability between patient and CT system in the determination of this threshold (27). Plaque volume does not account for plaque

density, which may provide important information in relation-

ship to CVD risk assessment. There are several methods of

determining a calibrated mass, which include calibrating the

CT scanner to an external standard as well as including a cali-

bration phantom within the scan field of view for each scan

(Fig. 3). The calibrated calcium mass in milligrams has several

advantages. Based on imaging principles, it is more robust to

the effect of partial volume averaging than either a volume

score or Agatston score. Data with MDCT in both phantom

studies and with human research participants have demon-

strated less variability with a calibrated mass measurement than

either volume or Agatston methods (41,52). Lastly, the cali-

brated mass can be reported in milligrams of calcium and will

allow for standardization of measurements across CT systems

and techniques as well as for currently undiscovered future

techniques.

Fig. 3. Calibration phantom for calcium mass. One slice from a research study in which a calcium calibration phantom is used. These phantoms were originally designed for measurement of trabecular bone mineral density with CT, also known as quantitative computed tomography (QCT). The phantom is positioned underneath the participant during the scan and contains four cylinders with the following concentrations of calcium hydroxyapatite: 0 mg/mL, 50 mg/mL, 100 mg/mL, and 200 mg/mL. These known quantities of calcium are then used to calibrate the CT numbers such that the resulting mass determination is reported in mg of calcium hydoxyapatite. Calibration of each patient’s scan provides the greatest gain in accuracy.

STUDIES IMPACTING THE CLINICAL APPLICATION OF CAC

Increasing evidence supports the use of CAC as a tool for better quantifying coronary heart disease risk among asymp- tomatic individuals. The Saint Francis Heart Study has recently reported data with 4.3 yr on average of follow-up of asymptom- atic individuals aged 50–70 yr using EBCT (53). In this study, participants with CAC scores >100 had a 10-fold increase in relative risk for CVD events. The calcium score had signifi- cantly better prognostic ability for coronary events than the Framingham Risk Index. The National Heart, Lung and Blood Institute’s MESA is following an asymptomatic cohort of 6800

individuals whose coronary calcium was measured by either EBCT or MDCT between 2000 and 2002 (39). The results from MESA will provide data on both prevalence and the predictive ability of CAC for CVD events in men and women as well as four ethnic groups.

CONCLUSION

Accumulating evidence supports the use of the calcified

plaque as measured by cardiac CT (EBCT or MDCT) as a valu-

able predictor of future CVD risk. Ongoing population-based

research and clinical trials will provide additional information

to determine the appropriate clinical role. Calibration of car-

diac CT measurements of coronary calcified plaque burden to mass of calcium will improve accuracy and reduce variability.

As both EBCT and MDCT systems continue to improve in terms of image quality, tracking the progression of plaque bur- den and greater understanding of calcified plaque morphology will provide important new information on coronary heart dis- ease. Based on preliminary data, it is likely that coronary cal- cium provides additive information to traditional CVD risk factors. The specific results of ongoing epidemiological stud- ies will help determine the appropriate at-risk population for CVD screening with cardiac CT for coronary calcium. Cardiac CT with MDCT is well positioned to make screening for sub- clinical coronary atherosclerosis a viable and cost-effective option for identifying the individual at elevated CVD risk. Once these individuals are identified, proven interventions for CVD prevention are currently available and can be employed to reduce the tremendous burden of CVD on the population.

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