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Calcified Coronary Artery Plaque Measurement with Cardiac CT in Population-based Studies: Standardized Protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) Study¹

¹ From the Departments of Radiology and Public Health Sciences, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157 (J.J.C.); Department of Biostatistics, University of Washington Center for Health Studies, Group Health Cooperative, Seattle, Wash (J.C.N.); Heart Disease Prevention Program, University of California, Irvine, Calif (N.D.W.); Department of Radiology, School of Medicine, University of California, Los Angeles, Calif (M.M.G.); Department of Clinical Medicine, Columbia University, New York, NY (Y.A.); Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minn (D.R.J.); Kaiser Permanente Research Division, Oakland, Calif (S.S.); Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (D.E.B.); Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Ala (O.D.W.); and Harbor-UCLA Research and Education Institute, Los Angeles, Calif (R.C.D.). Received March 5, 2004; revision requested May 13; revision received June 1; accepted June 18. Supported by contracts N01-HC-95159 through N01-HC-95169, as well as N01-HC-48047 through N01-HC-48050 and N01-HC-95095, with the National Heart, Lung, and Blood Institute. Additional support was provided by General Clinical Research Center, Wake Forest University Health Sciences, grant M01-RR07122. Address correspondence to J.J.C.

	ABSTRACT

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Calcified coronary artery plaque, measured at cardiac computed tomography (CT), is a predictor of cardiovascular disease and may play an increasing role in cardiovascular disease risk assessment. The Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study of the National Heart, Lung, and Blood Institute are population-based studies in which calcified coronary artery plaque was measured with electron-beam and multi–detector row CT and a standardized protocol in 6814 (MESA) and 3044 (CARDIA study) participants. The studies were approved by the appropriate institutional review board from the study site or agency, and written informed consent was obtained from each participant. Participation in the CT examination was high, image quality was good, and agreement for the presence of calcified plaque was high ( = 0.92, MESA; = 0.77, CARDIA study). Extremely high agreement was observed between and within CT image analysts for the presence ( > 0.90, all) and amount (intraclass correlation coefficients, >0.99) of calcified plaque. Measurement of calcified coronary artery plaque with cardiac CT is well accepted by participants and can be implemented with consistently high-quality results with a standardized protocol and trained personnel. If predictive value of calcified coronary artery plaque for cardiovascular events proves sufficient to justify screening a segment of the population, then a standardized cardiac CT protocol is feasible and will provide reproducible results for health care providers and the public.

© RSNA, 2005

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Subclinical coronary artery atherosclerosis is highly prevalent among adults in industrialized societies and precedes the occurrence of clinical cardiovascular disease. Calcified coronary artery plaques are a component of atherosclerosis that can be quantified by using cardiac computed tomography (CT). The medical and scientific community has requested scientific validation of the importance of coronary artery calcium quantification (1,2). The Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study are population-based cohort studies that include the CT measurement of calcified coronary artery plaque as a means of furthering our understanding of the factors that influence cardiovascular disease and its outcomes (3,4). The CARDIAstudy began in 1986 with black and white men and women who were 18–30 years old and who were 33–45 years old at the time of examination (between May 2000 and September 2001). The MESA began in 2000 with Asian (Chinese), black, Hispanic, and white men and women who were 45–84 years old at the time of examination (between July 2000 and July 2002). Standardized data collection protocols were used to obtain cardiac CT scans at six MESA communities (Baltimore, Md; Chicago, Ill; Los Angeles, Calif; Minneapolis, Minn; New York, NY; and Winston-Salem, NC) and at four CARDIA study communities (Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; South San Francisco, Calif). At a central CT reading center at Harbor-UCLA Research and Education Institute, Los Angeles, Calif, all activities were coordinated and measurements of calcified coronary artery plaque were performed for both studies. In this article, we describe in detail the method of measurement used and its application to the cardiac CT examination in these two studies.

	PROTOCOL DEVELOPMENT

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
The steering committees for MESA and the CARDIA study established a joint MESA–CARDIA Study Committee composed of experts in cardiac CT at each of the scanning sites, statisticians from the coordinating centers, and epidemiologists from various sites and from the National Heart, Lung, and Blood Institute, Bethesda, Md, project offices for both the CARDIA study and MESA. This committee evaluated the existing literature and in consensus made decisions and recommendations related to the cardiac CT examination. The studies were approved by the appropriate institutional review board from the study site or agency, and written informed consent was obtained from each participant.

	PARTICIPANT PREPARATION

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Designing the CT examination to be efficient and simple for the participant and the CT technologist reduced participant burden, enhanced protocol standardization across scanning sites, and made possible the integration of the participants’ research study scans into busy clinical scanning schedules. The examination involved obtaining two consecutive scans per participant and was designed to require less than 15 minutes of CT room time. For this examination, scanning in participants was performed without administration of oral or intravenous contrast agents. The two sequential cardiac scans were obtained by using a single breath hold at end inspiration. This approach helped to reduce motion artifacts from breathing and improved image quality in the distal coronary artery circulation by depressing the diaphragm and liver, thereby leading to a reduction in beam attenuation. Participants were instructed about breath holding and its importance to the CT examination.

	CT EQUIPMENT

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Electron-beam CT and four–detector row CT were used in both studies. At two of four CARDIA study sites and three of six MESA sites, CT examinations were performed with electron-beam CT (Table 1). At electron-beam CT, x-rays are created with an electron gun to sweep a stream of electrons onto stationary tungsten rings that partially encircle the patient. The x-rays then pass through the patient in a 216° arc for each imaging level and are used to generate a CT image with a partial scan reconstruction algorithm. At four–detector row CT, an x-ray tube that is mounted on a rotating gantry is used to produce x-rays. The x-rays produced by the tube pass through the patient and are reconstructed by using a partial-scan reconstruction algorithm, but with 220° of data. For both technologies, the images are acquired in an axial scan mode, which is alternatively termed sequential or step-and-shoot mode. Prospective electrocardiographic (ECG) triggering, in which the x-ray beam is turned on and off according to the ECG signal, was used at all sites except one, a CARDIA study site where retrospective ECG gating was used with an axial scan mode. In this mode, the x-ray beam is turned on for two full rotations (1.6 seconds) around the patient. Then the data are retrospectively sorted according to the ECG signal recorded during the x-ray exposure to create an image during the desired phase of the cardiac cycle. With either approach, the four–detector row CT scanners acquired four image sections simultaneously. The four–detector row CT gantry rotation period was 0.5 second for all systems except the system that used retrospective gating; the gantry rotation period for that system was 0.8 second. The similarities and differences between electron-beam CT and multi–detector row CT have been detailed previously (5,6).

	CT TECHNICAL FACTORS

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

Image quality is related to the photon flux of x-rays through the anatomy being imaged and ultimately recorded by the CT detectors. The energy and number of x-ray photons are determined by the x-ray beam energy (tube voltage expressed in peak kilovolts) and the product of the tube current (expressed in milliamperes) multiplied by time (expressed in seconds), which is expressed in milliampere-seconds. These factors also determine radiation exposure. For the electron-beam CT systems, these factors are fixed. The four–detector row CT systems allow users to adjust the tube current and thus the flux of x-rays and subsequent patient dose as appropriate for the imaging task. This capability makes it possible to increase the tube current with patient size to maintain image quality. For the MESA–CARDIA study protocol for four–detector row CT, a two-level setting of tube current that was based on body weight was used. Individuals who weighed 100 kg (220 lb) or less underwent CT with the standard tube current setting, and those who weighed more than 100 kg underwent CT with a tube current setting that was 25% higher than the standard setting (Table 1).

The images were reconstructed into a display field of view of 350 mm (35 cm) to include a calibration phantom, which was positioned under the thorax of each participant. Reconstruction algorithms were specified to be standard nonenhanced algorithms (ie, Imatron C150, normal; LightSpeed QXi and LightSpeed Plus, standard; Volume Zoom, B30f). The nominal section thickness was 3.0 mm for electron-beam CT and 2.5 mm for four–detector row CT. Spatial resolution can be described by the smallest volume element, or voxel, for the protocol for each system and was 1.15 mm³ for four–detector row CT (0.68 x 0.68 x 2.50 mm) and 1.38 mm³ for electron-beam CT (0.68 x 0.68 x 3.00 mm).

	CARDIAC ECG GATING METHOD

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Cardiac ECG gating reduces errors of measurement of calcified coronary artery plaque by synchronizing the time of image acquisition for each level of the scan to a specific phase of the cardiac cycle. The instantaneous velocity of the coronary arteries varies throughout the cardiac cycle, and it varies according to vessel and vessel segment and among individuals (7,8). The ECG triggering was set at 80% of the R-R interval for electron-beam CT and at 50% of the R-R interval for four–detector row CT (Fig 1). The four–detector row CT systems acquired four images per cardiac cycle, and the electron-beam CT systems acquired one image per cardiac cycle. In the CARDIA study, the 0.8-second LightSpeed QXi system used retrospective cardiac gating, and the image corresponding to 50% of the R-R interval was selected by using an automated program designed for this purpose (SmartScore; GE Medical Systems) in a postprocessing step.

View larger version (20K): [in this window] [in a new window] [Download PPT slide]   Figure 1. ECG obtained during a cardiac CT examination illustrates ECG triggering points and temporal resolution of CT systems. In this example, heart rate (60 beats per minute) results in the cardiac cycle (R-R interval) of 1000 msec. For four-detector row CT (MDCT) systems, image acquisition began after 50% of the R-R interval with a temporal window of approximately 250-300 msec for all systems except for those at one scanning site in CARDIA study; the temporal window for systems at that center was approximately 520 msec. For electron-beam CT (EBCT) systems, image acquisition began at 80% of the R-R interval with a temporal window of 100 msec.

	RADIATION DOSIMETRY

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

	MEASUREMENT OF CALCIFIED CORONARY ARTERY PLAQUE

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
During the CT examinations at the CT reading center, two consecutive scans (scans 1 and 2) of the heart were obtained; these scans were independently analyzed for calcified coronary artery plaque and were assessed for quality by CT image analysts (or observers). The CT reading center investigators (R.C.D. and N.D.W.) supervised the initial training and quality control of the CT image analysts and the reading process. The image analysts were dedicated research personnel (graduates of non-U.S. medical schools) who were selected on the basis of their prior experience and training and who were trained by the two investigators just indicated in the technical aspects of using the software and measuring calcified plaque. To reduce between–image analyst (observer) variability, only two individuals served as image analysts in each study.

At the CT reading center, custom software was developed to measure calcified plaque specifically for these studies; the custom software was based on software used during the year 10 examination in 1994–1995 of the CARDIA study (15). Key aspects of the software and reading process include the blinding of CT image analysts to any clinical information about study participants and to the calculated results (eg, Agatston score). In the reading process, batches of up to 250 scans on an electronic work list were randomized, thereby reducing the probability that the CT image analysts would sequentially process the two scans of a participant. The software automatically checks the technical parameters (eg, tube voltage expressed in peak kilovolts, tube current expressed in milliamperes, and field of view) used to obtain the scan and notifies the image analyst if values are outside those specified in the protocol. On the CT images, the software automatically locates the four calibration phantom standards and measures the CT attenuation of each calibration phantom by computing the mean CT number for pixels contained within each of the four 15-mm-diameter regions of interest on the image. These data are used to calibrate the image to a standardized level across all study sites.

The image analysts identify the anatomic course of the coronary arteries on the CT images by assigning waypoints along the length of the major arteries. The waypoints are used by the software, along with image data, to define a line corresponding to the trajectory of the coronary artery across the surface of the heart. The program calculates and then displays the three-dimensional course of each coronary artery trajectory in the image data. The image analysts review the coronary artery trajectories determined by the program and adjust the computer-generated trajectory if it deviates from the observed course of the coronary artery. The coronary artery trajectories allow quantification and location of calcified plaque within the coronary arteries and are saved to facilitate future analysis. By using the coronary artery trajectories, the software automatically identifies candidate calcified plaques on the basis of predefined minimum criteria for CT attenuation (130 HU), minimum calcified plaque size (4.6 mm³, four–detector row CT; 5.5 mm³, electron-beam CT), and distance from the coronary artery trajectory (location within an 8-mm radius of the trajectory). The image analyst systematically reviews each candidate calcified plaque and either accepts or rejects its inclusion as calcified coronary artery plaque. Image analysts are trained to reject calcification outside the anatomic boundary of the arteries or false-positive artifacts related to lymph nodes, pericardium, or motion. The review of candidate plaques by the image analyst is immediately repeated after image calibrations with the phantom data are performed. The software computes several measures of calcified coronary artery plaque, and these measures include the Agatston score (by using the standard 130-HU threshold, modified to adjust for section thickness), calcified plaque volume, and interpolated calcified plaque volume along the section direction. After image calibration, the measures of calcified plaque were recalculated to provide phantom-adjusted Agatston score, volume, and interpolated volume measures. The image analyst then completes a quality control assessment of quality in several categories: motion artifact, misregistration artifact, noise artifact, phantom placement, and coverage of the heart.

	DATA TRANSMISSION AND ARCHIVING

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
The CT image data from the scanning sites were transferred electronically to the CT reading center by means of the Digital Imaging and Communication in Medicine (version 3.0) standard without data compression. Results of the analyses were electronically transferred from the central CT reading center to their respective data coordinating centers on a weekly basis. Coordinating centers monitored data flow to and from all sites and implemented computerized data tracking procedures to ensure timely, accurate, and complete data transmission. Image data and results were archived to compact disc and stored by the CT reading center. Backup copies were made and sent to the coordinating centers for off-site storage.

	DATA QUALITY

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Numerous procedures were designed and implemented to ensure high levels of CT image and data quality, facilitate protocol standardization across scanning sites, and reduce measurement error. Manuals in which the CT procedures, as well as the other examination components, are documented are publicly available and can be accessed through the Internet at www.cardia.dopm.uab.edu/ (CARDIA study) and www.mesa-nhlbi.org (MESA).

	CT SCAN ACQUISITION QUALITY

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Lead technologists at each imaging site participated in a 2-day training course that included didactic material, hands-on training, supervised training, and testing of proficiency. Full certification of a CT technologist was provided by the CT reading center only after successful completion and review of a series of pilot examinations. To confirm that technicians were obtaining scans in accordance with the protocol, the technical scanning parameters (tube voltage expressed in kilovolts, tube current–time product expressed in milliampere-seconds, etc) were extracted from the image headers by using an automated computer program for each participant’s scan. CT scans that deviated from the protocol were flagged for review by CT reading center personnel and communicated to the CT technologist and other scanning site personnel as appropriate.

After the image analyst analyzed each scan for calcified plaque, he or she completed a subjective assessment of image and scan acquisition quality in the following categories: motion artifact (defined as right coronary artery appearance as comma-shaped and twice its expected diameter or greater), misregistration artifact (defined as inconsistency in the anatomic borders of the heart displayed on sagittal or coronal reformatted images or between images of at least three transverse sections), noise artifact (defined as at least 30 false-positive lesions identified by scoring software on or near the coronary arteries), phantom placement (defined as cropping of portions of the calibration phantom from the image), and coverage of the heart (defined as failure to include portions of the coronary arteries). Images were rated as excellent or unacceptable in each category. Image quality scores for each CT technologist were reported regularly to the technologists and scanning site investigators to provide performance feedback, identify image quality problems, and direct additional training as necessary.

Acquisition of two consecutive CT scans in each MESA and CARDIA study participant yielded sequential measures of calcified coronary artery plaque for each participant. The rationale for obtaining replicate measures was to provide an improved point estimate of true calcified plaque burden, assess measurement error, and provide the opportunity for the CT technologist to correct any potential errors identified on the first scan (16–18). A physician investigator (R.C.D.) reviewed scans with the largest differences between the first and second scans to determine the reasons for the discrepancies (eg, misregistration) and correct obvious data errors.

	QUALITY CONTROL OF CALCIFIED PLAQUE MEASUREMENT

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
To assess performance of the CT image analysts in the measurement of calcified coronary artery plaque, scans were randomly selected each quarter by the respective coordinating centers for inter- and intraobserver quality control reading (n = 806, MESA; n = 850, CARDIA study). A stratified sampling scheme that was based on the calcium score was used to select the scans for quality control readings, and target values at 70% (MESA) or 50% (CARDIA) of selected scans had a positive Agatston calcium score (a score > 0) for inter- and intraobserver analysis. The quality control examinations were selected during the performance of the examination, resulting in statistical fluctuations, with the actual values as follows: MESA—intraobserver reading, 240 (68%) of 351, and interobserver reading, 338 (74%) of 455; CARDIA—intraobserver reading, 230 (50%) of 460, and interobserver reading, 195 (50%) of 390. The initial image analyst reread half of the selected scans, and a different image analyst reread the other half to provide measures of intraobserver (within–image analyst) and interobserver (between–image analyst) variability. In addition, a fixed set of images was selected and reread at several time points throughout the examination period to assess temporal drift (change over time). The same physician investigator as mentioned previously reviewed the results of the quality control readings to determine potential reasons for observed discrepancies as part of the quality control process.

	QUALITY CONTROL PHANTOM DATA

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
To monitor temporal drift within each CT system and to assess the comparability of the CT systems between scanning sites, a biweekly quality control scan was obtained. At each site, a standard torso insert positioned on the calibration phantom (Fig 2) was scanned, the torso and calibration phantom CT numbers were recorded, and these data were sent to the CT reading center. Calibrated torso values were calculated by linearly regressing the observed CT attenuation values (in Hounsfield units) from each of the calibration phantom regions on the image with the established values of calcium hydroxyapatite (0, 50, 100, and 200 mg/mL) contained in the phantom.

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Phantom used in MESA and the CARDIA study. The torso phantom is positioned on top of the quality control phantom containing the four cylinders with 0, 50, 100, and 200 mg/mL of calcium hydroxyapatite as part of the quality control procedures to track how the CT systems measure calcium with standardized conditions.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Cardiac CT scan obtained in a study participant with quality control phantom in the transverse plane. The CT image demonstrates the quality control phantom positioned posteriorly to the supine participant during the cardiac CT examination. Four cylinders inside the phantom contain stable calcium concentrations of 0, 50, 100, and 200 mg/mL (from left to right) and were used to calibrate the CT numbers (Hounsfield units) for each scan. Note that the cylinder with 0 mg/mL of calcium is located on the far left and cannot be distinguished from the base material of the phantom.

	CT EXAMINATION PARTICIPATION

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

	CT IMAGE QUALITY

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
CT image quality was rated qualitatively by the image analysts during the reading process and was high for all sites and all CT technologies. Less than 1.0% of scans were rated as unacceptable with regard to streak artifact, phantom placement, and scan centering. Section registration or scan coverage was unacceptable for less than 5%. Image noise was rated as unacceptable in 6.2% and 11.7% of scans for MESA and the CARDIA study, respectively. Unacceptable image noise was higher for electron-beam CT than it was for four–detector row CT systems (8.3% vs 2.0% in MESA and 18.8% vs 4.3% in the CARDIA study, respectively). Unacceptable artifact secondary to motion was present in 7.7% of scans (measured in MESA only), and a higher percentage of unacceptable ratings was observed for four–detector row CT scanners than it was for electron-beam CT scanners (14.1% vs 4.5%).

	STATISTICAL ANALYSES

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
Statistical analyses were performed as part of the quality control procedures. We specifically evaluated possible change over time (temporal drift) in the ability of the CT systems to measure calcium and how the image analysts compared in their performance of measuring calcified plaque with the CT scans and software at the central CT reading center (ie, intra- and interobserver agreement). Image analyst performance was measured in terms of agreement about the presence or absence of calcified plaque, as well as agreement about the amount of calcified plaque present.

	CT SCANNER COMPARABILITY OVER TIME

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 
The mean torso phantom values over time at each scanning site are presented in Table 2. All mean torso phantom values were within 2.7% of each other, and differences between scanning sites were not significant (P > .05). The variation in torso phantom values across time was less than 3% (standard deviation) for all sites, and the absence of a significant trend for any site over time (at the P = .05 level) indicated that the CT measurement of calcium was very stable over time at all sites in these studies.

	AGREEMENT ABOUT PRESENCE OF CALCIFIED CORONARY ARTERY PLAQUE BETWEEN CONSECUTIVE CT SCANS

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

	AGREEMENT BETWEEN CT IMAGE ANALYSTS ABOUT PRESENCE OF CALCIFIED CORONARY ARTERY PLAQUE

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

Interobserver and intraobserver reproducibility for the CT image analysts with the continuous calcified coronary artery plaque measures among those participants with a positive calcium score in MESA are reported in Table 4. The intraclass correlation coefficients for the Agatston score, volume, and volume score for readings performed by the same or by different CT image analysts indicate very high agreement (all intraclass correlation coefficients, >0.99).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

CT measurement of calcified coronary artery plaque has largely been performed without calibration to an external standard, and therefore its use as a measure of atherosclerosis for both research and clinical practice is limited. The inclusion of a standardized calibration phantom in each participant’s CT examination, coupled with dedicated software, allowed calibration of scan attenuation between CT scanning sites and CT systems. The phantom calibration provides a means of standardizing the CT attenuation (alternatively called CT number, Hounsfield unit, or degree of brightness) between CT sites and across participants. The results demonstrate that with current-generation CT systems variation is less than 3% in measured CT numbers over time, given the presence of a quality control process to monitor CT system calibration. In addition, the calibration phantom will be useful in the evaluation of factors such as changes in body mass index of participants, in scanning technique, or in CT equipment, which might influence the measurement of calcified plaque over time.

Measures of scan quality in both MESA and the CARDIA study showed a preponderance of excellent ratings for key quality characteristics, which included phantom placement, arterial coverage, lack of misregistration, noise, and motion artifact. The higher level of image noise with electron-beam CT and increased presence of motion artifacts for four–detector row CT are consistent with the physical limitations of these technologies. Categories related to motion and section registration had similar high ratings with each technology.

The measurement of the amount of calcified coronary artery plaque by means of CT, whether by using the Agatston or volume scores, in these studies was highly reproducible, both between and within CT image analysts (observers); that is, intraclass correlation coefficients approached unity. Likewise, agreement between and within CT image analysts (observers) was high with regard to the presence or absence of measurable calcified plaque.

Although every effort is made to minimize radiation exposure through protocol design, research studies involving CT are limited by availability of equipment at sites during the time of the study. Prospective ECG gating with multi–detector row CT scanners had been introduced only recently when the examination period for one of the studies began. Subsequently, prospective ECG gating has become the clearly preferred method for the measurement of calcified coronary artery plaque. In addition, the research CT protocol of MESA and the CARDIA study included two sequential scans obtained through the heart. The paired scans and subsequent paired measurements of calcified plaque were obtained to aid in the assessment of calcified plaque progression through a better understanding of the measurement error and as part of the quality control procedures of the study. Research is ongoing to assess the utility of repeated scans for risk assessment and determination of calcified plaque progression.

A Food and Drug Administration report on whole-body screening with CT states that "for any one person the risk of radiation-induced cancer is much smaller than the natural risk of cancer" (9). This Food and Drug Administration report estimates that a 10-mSv CT exposure may result in "an increase in the possibility of fatal cancer of approximately 1 chance in 2000" and further recommends that this possibility should be compared with "the natural incidence of fatal cancer in the U.S. population, about 1 chance in 5." Even though the potential risk is minimal, research protocols should routinely be reassessed to further reduce radiation exposure where possible.

Calcified plaque in the coronary arteries is a component of subclinical atherosclerosis that can be successfully measured with cardiac-gated CT in multisite population-based cohort studies in which both electron-beam CT and four–detector row CT technologies are used. The results from the CARDIA study and MESA will provide additional insight into the relationship between calcified coronary artery plaque and other traditional and novel markers of cardiovascular disease. This protocol will be used to determine the reliability of cardiac CT–measured calcified coronary artery plaque as a predictor of future cardiovascular events in a population-based sample of asymptomatic individuals classified by sex, ethnic background, and age strata and located in the United States. Results of the CARDIA study will provide data on factors in early adulthood that can be used to predict the development of calcified coronary artery plaque later in life.

Screening for subclinical disease in asymptomatic populations requires a robust diagnostic test that can be widely and consistently implemented. The experience with the cardiac CT examination in MESA and the CARDIA study demonstrates that cardiac CT can be successfully implemented with consistent results at multiple sites with the use of existing clinical CT systems and a standardized protocol. If the predictive value of calcified coronary artery plaque measured with cardiac CT proves sufficient to justify screening a segment of the population, a standardized protocol is feasible and will provide reproducible results for health care providers and the public.

	ACKNOWLEDGMENTS

 
The authors thank the staff and participants in the CARDIA study and MESA for their important contributions.

	FOOTNOTES

 
Abbreviations: ECG = electrocardiographic, CARDIA = Coronary Artery Risk Development in Young Adults, MESA = Multi-Ethnic Study of Atherosclerosis

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, J.J.C., R.C.D., D.E.B.; study concepts, J.J.C., R.C.D., D.E.B., J.C.N., N.D.W., M.M.G.; study design, all authors; literature research, J.J.C., R.C.D., D.E.B.; data acquisition and analysis/interpretation, all authors; statistical analysis, J.J.C., R.C.D., D.E.B., O.D.W., J.C.N., M.M.G.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, all authors

	REFERENCES

TOP ABSTRACT INTRODUCTION PROTOCOL DEVELOPMENT PARTICIPANT PREPARATION CT EQUIPMENT CT TECHNICAL FACTORS CARDIAC ECG GATING METHOD RADIATION DOSIMETRY MEASUREMENT OF CALCIFIED... DATA TRANSMISSION AND ARCHIVING DATA QUALITY CT SCAN ACQUISITION QUALITY QUALITY CONTROL OF CALCIFIED... QUALITY CONTROL PHANTOM DATA CT EXAMINATION PARTICIPATION CT IMAGE QUALITY STATISTICAL ANALYSES CT SCANNER COMPARABILITY OVER... AGREEMENT ABOUT PRESENCE OF... AGREEMENT BETWEEN CT IMAGE... DISCUSSION REFERENCES

 

1. Committee on Advanced Cardiac Imaging and Technology, Council on Clinical Cardiology, and Committee on Newer Imaging Modalities, Council on Cardiovascular Radiology, American Heart Association. Potential value of ultrafast computed tomography to screen for coronary artery disease. Circulation 1993; 87:2071.[Free Full Text]
2. Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications: a statement for health professionals from the American Heart Association—Writing Group. Circulation 1996; 94:1175-1192.[Free Full Text]
3. Bild DE, Bluemke DA, Burke GL, et al. Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol 2002; 156:871-881.[Abstract/Free Full Text]
4. Cutter GR, Burke GL, Dyer AR, et al. Cardiovascular risk factors in young adults: the CARDIA baseline monograph. Control Clin Trials 1991; 12(suppl 1):1S-77S.[CrossRef][Medline]
5. Detrano R, Carr JJ. Computed tomography of the heart. In: Topol EJ, eds. Textbook of cardiovascular medicine. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2002; 1281-1296.
6. Carr JJ. Coronary calcium: the case for helical computed tomography. J Thorac Imaging 2001; 16:16-24.[CrossRef][Medline]
7. Hofman MB, Wickline SA, Lorenz CH. Quantification of in-plane motion of the coronary arteries during the cardiac cycle: implications for acquisition window duration for MR flow quantification. J Magn Reson Imaging 1998; 8:568-576.[Medline]
8. Achenbach S, Ropers D, Holle J, Muschiol G, Daniel WG, Moshage W. In-plane coronary arterial motion velocity: measurement with electron-beam CT. Radiology 2000; 216:457-463.[Abstract/Free Full Text]
9. U.S. Food and Drug Administration. Whole body scanning using computed tomography (CT). Available at: www.fda.gov/cdrh/ct/rqu.html. Accessed March 4 2004.
10. Protection ICoR: 1990 recommendations of the International Commission on Radiological Protection Oxford, England: Pergamon, 1991.
11. McCollough CH, Schueler BA. Calculation of effective dose. Med Phys 2000; 27:828-837.[CrossRef][Medline]
12. Morin RL, Gerber TC, McCollough CH. Radiation dose in computed tomography of the heart. Circulation 2003; 107:917-922.[Free Full Text]
13. McNitt-Gray MF. Radiation issues in computed tomography screening. Semin Roentgenol 2003; 38:87-99.[CrossRef][Medline]
14. McNitt-Gray MF. AAPM/RSNA physics tutorial for residents: topics in CT—radiation dose in CT. RadioGraphics 2002; 22:1541-1553.[Abstract/Free Full Text]
15. Yaghoubi S, Tang W, Wang S, et al. Offline assessment of atherosclerotic coronary calcium from electron beam tomograms. Am J Card Imaging 1995; 9:231-236.[Medline]
16. Bielak LF, Kaufmann RB, Moll PP, McCollough CH, Schwartz RS, Sheedy PF, 2nd. Small lesions in the heart identified at electron beam CT: calcification or noise? Radiology 1994; 192:631-636.[Abstract/Free Full Text]
17. Becker CR, Jakobs TF, Aydemir S, et al. Helical and single-slice conventional CT versus electron beam CT for the quantification of coronary artery calcification. AJR Am J Roentgenol 2000; 174:543-547.[Abstract/Free Full Text]
18. Carr JJ, Crouse JR, 3rd, Goff DC, Jr, D’Agostino RB, Jr, Peterson NP, Burke GL. Evaluation of subsecond gated helical CT for quantification of coronary artery calcium and comparison with electron beam CT. AJR Am J Roentgenol 2000; 174:915-921.[Abstract/Free Full Text]

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				A. B. Lehtinen, K. P. Burdon, J. P. Lewis, C. D. Langefeld, J. T. Ziegler, S. S. Rich, T. C. Register, J. J. Carr, B. I. Freedman, and D. W. Bowden Association of {alpha}2-Heremans-Schmid Glycoprotein Polymorphisms with Subclinical Atherosclerosis J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 345 - 352. [Abstract] [Full Text] [PDF]

				M. J. Budoff, S. Achenbach, R. S. Blumenthal, J. J. Carr, J. G. Goldin, P. Greenland, A. D. Guerci, J. A.C. Lima, D. J. Rader, G. D. Rubin, et al. Assessment of Coronary Artery Disease by Cardiac Computed Tomography: A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology Circulation, October 17, 2006; 114(16): 1761 - 1791. [Full Text] [PDF]

				M. J. Pletcher, B. J. Hulley, T. Houston, C. I. Kiefe, N. Benowitz, and S. Sidney Menthol Cigarettes, Smoking Cessation, Atherosclerosis, and Pulmonary Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Arch Intern Med, September 25, 2006; 166(17): 1915 - 1922. [Abstract] [Full Text] [PDF]

				L. Wang, M. Jerosch-Herold, D. R. Jacobs Jr, E. Shahar, R. Detrano, A. R. Folsom, and for the MESA Study Investigators Coronary Artery Calcification and Myocardial Perfusion in Asymptomatic Adults: The MESA (Multi-Ethnic Study of Atherosclerosis) J. Am. Coll. Cardiol., September 5, 2006; 48(5): 1018 - 1026. [Abstract] [Full Text] [PDF]

				K. Matthews, J. Schwartz, S. Cohen, and T. Seeman Diurnal Cortisol Decline is Related to Coronary Calcification: CARDIA Study. Psychosom Med, September 1, 2006; 68(5): 657 - 661. [Abstract] [Full Text] [PDF]

				D. W. Bowden, M. Rudock, J. Ziegler, A. B. Lehtinen, J. Xu, L. E. Wagenknecht, D. Herrington, S. S. Rich, B. I. Freedman, J. J. Carr, et al. Coincident linkage of type 2 diabetes, metabolic syndrome, and measures of cardiovascular disease in a genome scan of the diabetes heart study. Diabetes, July 1, 2006; 55(7): 1985 - 1994. [Abstract] [Full Text] [PDF]

				A. V. Diez Roux, N. Ranjit, L. Powell, S. Jackson, T. T. Lewis, S. Shea, and C. Wu Psychosocial factors and coronary calcium in adults without clinical cardiovascular disease. Ann Intern Med, June 6, 2006; 144(11): 822 - 831. [Abstract] [Full Text] [PDF]

				J. C. Nelson, X.-C. Jiang, I. Tabas, A. Tall, and S. Shea Plasma Sphingomyelin and Subclinical Atherosclerosis: Findings from the Multi-Ethnic Study of Atherosclerosis Am. J. Epidemiol., May 15, 2006; 163(10): 903 - 912. [Abstract] [Full Text] [PDF]

				R. Katz, N. D. Wong, R. Kronmal, J. Takasu, D. M. Shavelle, J. L. Probstfield, A. G. Bertoni, M. J. Budoff, and K. D. O'Brien Features of the Metabolic Syndrome and Diabetes Mellitus as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis Circulation, May 2, 2006; 113(17): 2113 - 2119. [Abstract] [Full Text] [PDF]

				L. L. Yan, K. Liu, M. L. Daviglus, L. A. Colangelo, C. I. Kiefe, S. Sidney, K. A. Matthews, and P. Greenland Education, 15-year risk factor progression, and coronary artery calcium in young adulthood and early middle age: the Coronary Artery Risk Development in Young Adults study. JAMA, April 19, 2006; 295(15): 1793 - 1800. [Abstract] [Full Text] [PDF]

				K. A. Matthews, S. Zhu, D. C. Tucker, and M. A. Whooley Blood Pressure Reactivity to Psychological Stress and Coronary Calcification in the Coronary Artery Risk Development in Young Adults Study Hypertension, March 1, 2006; 47(3): 391 - 395. [Abstract] [Full Text] [PDF]

				M. E. Clouse, J. Chen, H. M. Krumholz, M. E. Clouse, J. Chen, and H. M. Krumholz Noninvasive Screening for Coronary Artery Disease With Computed Tomography Is Useful Circulation, January 3, 2006; 113(1): 125 - 146. [Full Text] [PDF]

				R. L. McClelland, H. Chung, R. Detrano, W. Post, and R. A. Kronmal Distribution of Coronary Artery Calcium by Race, Gender, and Age: Results from the Multi-Ethnic Study of Atherosclerosis (MESA) Circulation, January 3, 2006; 113(1): 30 - 37. [Abstract] [Full Text] [PDF]

				T. Edvardsen, R. Detrano, B. D. Rosen, J. J. Carr, K. Liu, S. Lai, S. Shea, L. Pan, D. A. Bluemke, and J. A.C. Lima Coronary Artery Atherosclerosis Is Related to Reduced Regional Left Ventricular Function in Individuals Without History of Clinical Cardiovascular Disease: The Multiethnic Study of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 206 - 211. [Abstract] [Full Text] [PDF]

				A. V. Diez Roux, R. Detrano, S. Jackson, D. R. Jacobs Jr, P. J. Schreiner, S. Shea, and M. Szklo Acculturation and Socioeconomic Position as Predictors of Coronary Calcification in a Multiethnic Sample Circulation, September 13, 2005; 112(11): 1557 - 1565. [Abstract] [Full Text] [PDF]

				R. C. Detrano, M. Anderson, J. Nelson, N. D. Wong, J. J. Carr, M. McNitt-Gray, and D. E. Bild Coronary Calcium Measurements: Effect of CT Scanner Type and Calcium Measure on Rescan Reproducibility--MESA Study Radiology, August 1, 2005; 236(2): 477 - 484. [Abstract] [Full Text] [PDF]

				M. M. McDermott, K. Liu, M. H. Criqui, K. Ruth, D. Goff, M. F. Saad, C. Wu, S. Homma, and A. R. Sharrett Ankle-Brachial Index and Subclinical Cardiac and Carotid Disease: The Multi-Ethnic Study of Atherosclerosis Am. J. Epidemiol., July 1, 2005; 162(1): 33 - 41. [Abstract] [Full Text] [PDF]

				B. I. Freedman, C. D. Langefeld, K. K. Lohman, D. W. Bowden, J. J. Carr, S. S. Rich, and L. E. Wagenknecht Relationship between Albuminuria and Cardiovascular Disease in Type 2 Diabetes J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2156 - 2161. [Abstract] [Full Text] [PDF]

				H. Kramer, D. R. Jacobs Jr, D. Bild, W. Post, M. F. Saad, R. Detrano, R. Tracy, R. Cooper, and K. Liu Urine Albumin Excretion and Subclinical Cardiovascular Disease Hypertension, July 1, 2005; 46(1): 38 - 43. [Abstract] [Full Text] [PDF]

				J. C. Nelson, R. A. Kronmal, J. J. Carr, M. F. McNitt-Gray, N. D. Wong, C. M. Loria, J. G. Goldin, O. D. Williams, and R. Detrano Measuring Coronary Calcium on CT Images Adjusted for Attenuation Differences Radiology, May 1, 2005; 235(2): 403 - 414. [Abstract] [Full Text] [PDF]

				D. E. Bild, R. Detrano, D. Peterson, A. Guerci, K. Liu, E. Shahar, P. Ouyang, S. Jackson, and M. F. Saad Ethnic Differences in Coronary Calcification: The Multi-Ethnic Study of Atherosclerosis (MESA) Circulation, March 15, 2005; 111(10): 1313 - 1320. [Abstract] [Full Text] [PDF]

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