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1 Department of Diagnostic Radiology, Eberhard-Karls-University Tuebingen,
Hoppe-Seyler-Strasse 3, Tuebingen 72076, Germany.
2 Department of Cardiology, University Hospital, Tuebingen, Germany.
3 Department of Radiology, Mayo Clinic, Jacksonville, FL.
Received March 21, 2004;
accepted after revision September 9, 2004.
Address correspondence to M. Heuschmid
(martin.heuschmid{at}med.uni-tuebingen.de).
Abstract
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MATERIALS AND METHODS. Thirty-seven patients (28 men, nine women) underwent unenhanced helical CT and MDCT angiography of the coronary arteries. After patients received oral ß-blocker medication, CT scans were obtained during a single breath-hold with a 16-MDCT scanner using ECG-gating (0.75-mm collimation, 2.8-mm table feed/rotation, 0.42-sec rotation time). The image quality was assessed in terms of artifacts and segment visibility by two reviewers. Stenosis severity was compared with the results of conventional invasive coronary angiography.
RESULTS. The data evaluation of the image quality was based on a total of 488 segments, of which 380 segments were considered to have diagnostic image quality. One hundred eight segments (22.1%) could not be sufficiently evaluated because of severe calcifications (35 segments) and motion artifacts (73 segments). The mean calcium score (Agatston score equivalent [ASE]) was 524.3 ± 807.6. Twenty-eight (75.7%) of the 37 patients had an ASE of less than 1,000 (mean ASE, 90.8 ± 152.3 [SD]), and nine (24.3%) patients had an ASE of 1,000 or greater (mean ASE, 1,761.0 ± 637.6). For detecting lesions 50% or greater (without any exclusion criteria), the overall sensitivity, specificity, positive predictive value, and negative predictive value were 59%, 87%, 61%, and 87%, respectively. When limiting the number of patients to those with a calcium score of less than 1,000 ASE, the threshold-corrected sensitivity for lesions 50% or greater was 93%; specificity, 94%; positive predictive value, 68%; and negative predictive value, 99%.
CONCLUSION. In patients with no or moderate coronary calcification, MDCT of coronary arteries using 16-MDCT technology allows the reliable detection of coronary artery stenoses with high diagnostic accuracy. Obtaining an initial unenhanced scan was found to be mandatory to avoid performing useless examinations in patients with severe calcifications.
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With the new generation of MDCT systems offering simultaneous acquisition of up to 16-submillimeter slices and gantry rotation times of 420 msec, both spatial and temporal resolution can be improved further, and examination times are now considerably reduced [6]. According to the initial clinical results showing improved image quality, new 16-MDCT technology might have the potential to overcome the limitations of 4-MDCT systems [7–11].
The aim of our study was to investigate image quality and diagnostic accuracy in detecting coronary artery lesions using a 16-MDCT scanner.
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MDCT Examination
All CT examinations were performed with a 16-MDCT scanner (Sensation 16,
Siemens Medical Solutions) with patients in the supine position. In all
patients, an unenhanced scan was obtained to determine the total calcium
burden of the coronary arteries (1.5-mm collimation, maximum of 133 mAs
[modulated dose reduction] at 120-kV tube voltage). For MDCT angiography, the
individual circulation time was determined in the lumen of the ascending aorta
using a test bolus of 20 mL of IV-administered contrast medium (400 mg I/mL
iomeprol [Imeron 400, Altana]) at a flow rate of 4 mL/sec and a chaser bolus
of 20 mL of normal saline. For MDCT angiography, the following scanning
protocol was used: 12 x 0.75 mm collimation (cardiac mode), 2.8-mm table
feed/rotation, 420-msec gantry rotation time, and 120-kV tube voltage. The
tube current was ECG-controlled, modulated, and reduced during the systolic
phases, while maintained at 500 mAs during the diastolic phase centered around
60% of the cardiac cycle (when best image quality is required). Eighty
milliliters of contrast medium (Imeron 400) was injected IV in two phases: 50
mL was injected at a flow rate of 4 mL/sec and 30 mL was injected at a flow
rate of 2.5 mL/sec. In patients with coronary bypass grafts, 100 mL of
contrast medium was administered: 50 mL was injected at a flow rate of 4
mL/sec and 50 mL was injected at a flow rate of 2.5 mL/sec.
In all patients, the standard built-in reconstruction algorithm was used for image reconstruction. For all unenhanced images, the standard reconstruction window was set at 60% of the R-R interval. For the contrast-enhanced scan, the reconstruction interval with the fewest motion artifacts was determined by reconstructing a slice at the level of the middle of the left ventricle in 2% steps from 35% to 75% of the R-R interval. The time point with the least motion arti-fact in the right and left coronary arteries was used to reconstruct the CT angiography images for diagnostic interpretation. In cases with different optimal time points for the right and left coronary arteries, two different image sets were reconstructed for the whole examination. The effective slice thickness of CT angiography images was 1 mm using a reconstruction increment of 0.5 mm.
On an offline workstation (Leonardo, Siemens Medical Solutions), vessel wall calcifications were assessed visually and determined quantitatively on the basis of a standard built-in algorithm. For MDCT, the adapted Agatston score equivalent (ASE) and the total calcium mass in milligrams of calcium hydroxyapatite were measured.
Two experienced reviewers who were not aware of clinical information or the coronary angiographic findings evaluated all MDCT images jointly. In addition to the original 1-mm axial slices, sliding thinslab maximum-intensity-projection [12] and other postprocessing techniques, such as multiplanar reconstruction and 3D volume rendering, were used, depending on the individual case.
Image quality was graded in terms of artifacts and visibility as follows: 1, excellent; 2, good; 3, diagnostic; 4, diagnostically limited due to heavy calcifications; and 5, diagnostically limited due to motion artifacts. Only lesions with a diameter reduction of 50% or greater were included in the analysis. All coronary vessel segments were documented separately using a modified American Heart Association classification system (right coronary artery: 1 = proximal, 2 = middle, 3 = distal, and 4 = combined posterior descending and posterolateral branches; 5 = left mainstem artery; left anterior descending artery: 6 = proximal, 7 = middle, 8 = distal, 9 = first diagonal, 10 = second diagonal; left circumflex artery: 11 = proximal, 12 = distal, 13 = first marginal branch) [13].
Quantitative Coronary Angiography
Conventional invasive coronary angiograms were obtained within 1–5
days after MDCT examination using 4-French catheters. All angiograms were
evaluated by quantitative coronary analysis with automated vessel contour
detection by an independent, experienced interventional cardiologist. The
angiography catheter was used for calibration for the quantitative coronary
analysis. Lesions with a diameter reduction of 50% or more were considered to
be significant lesions. All coronary vessel segments were included in the
statistical analysis. Coronary angiography was considered as the reference
standard for detection of relevant vascular stenoses. In coronary segments
with more than one lesion, the lesion with the most severe diameter reduction
determined the diagnostic accuracy.
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The total calcium burden of the coronary arteries was determined in all
patients. The mean calcium score (ASE) was 524.3 ± 807.6 (SD), and the
mean calcium mass was 80.9 ± 136.1 (SD) mg calcium hydroxyapatite. We
divided all patients into two groups according to their ASE (ASE < 1,000 vs
ASE 
1,000): 28 (75.7%) of the 37 patients had an ASE of less than 1,000
(mean ASE, 90.8 ± 152.3; mean calcium mass, 16.4 ± 26.1 mg
calcium hydroxyapatite), whereas nine (24.3%) of the 37 patients had an ASE of
1,000 or greater (mean ASE, 1,761.0 ± 637.6; mean calcium mass, 318.8
± 143.3 mg calcium hydroxyapatite)
(Table 2).
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The analysis of image quality was based on a total of 488 vessel segments (481 segments of the coronary tree and seven bypasses). In summary, images of 77.9% (380 segments) of the segments were of acceptable quality, whereas the vessel lumen of the coronary segments could not be assessed sufficiently on images of 22.1% (108 segments) (Table 2). Image quality was graded as excellent for 127 coronary segments and as good for 130 coronary segments. Images of 123 segments were considered to be of diagnostic quality. The imaging assessment of 35 segments was not possible because of severe calcifications. Furthermore, motion artifacts affected the diagnostic evaluation of 73 segments. Fifty-two (71.2%) of the 73 segments affected by motion artifacts were distal segments or side branches (segment 4, n = 16; 8, n = 1; 9, n = 6; 10, n = 10; 12, n = 9; 13, n = 10). When the distal segments and side branches (segments 4, 9, 10, 12, and 13) are excluded from the analysis, the percentage of segments for which the image quality is acceptable rises from 77.9% (380/488 segments) to 85.1% (258/303 segments).
Thirty-seven lesions with a diameter reduction of 50% or greater were found on conventional invasive coronary angiography (Figs. 1A, 1B, 1C and 2A, 2B, 2C, 2D). MDCT correctly detected 22 of the 37 lesions with a diameter reduction of 50% or greater. Fifteen lesions were missed or overlooked or incorrectly estimated on MDCT because of insufficient image quality caused by calcifications and motion artifacts. Fourteen lesions with a stenosis that was 50% of the diameter or greater were detected on MDCT only (right coronary artery, n = 3; left mainstem, n = 1; left anterior descending, n = 5; left circumflex, n = 5). These lesions were not confirmed by conventional coronary angiography and were thus considered as false-positives. The overall sensitivity was 59%; specificity, 87%; the positive predictive value, 61%; and the negative predictive value, 87%.
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Nine of the 37 patients had severe calcifications with an ASE of 1,000 or greater. When the 28 patients with an ASE threshold of less than 1,000 (n = 28) were evaluated separately, a total of 14 lesions with a diameter reduction of 50% or greater were detected using conventional coronary angiography (right coronary artery, n = 6; left mainstem, n = 0; left anterior descending, n = 6; left circumflex, n = 2). MDCT angiography correctly assessed 13 of the 14 lesions with a diameter reduction of 50% or greater. One lesion was missed in a side branch (segment 9) of the left anterior descending artery. Six lesions with a diameter reduction of 50% or greater (right coronary artery, n = 1; left mainstem, n = 0; left anterior descending, n = 3; left circumflex, n = 2) were overestimated by the MDCT angiography investigators and were counted as false-positive findings. Sensitivity for the detection of lesions in this subgroup was 93%; specificity, 94%; positive predictive value, 68%; and negative predictive value, 99% (Table 3).
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In 36 (97.3%) of the 37 patient studies, the correct clinical diagnosis (at
least one lesion 50%) was correctly determined using 16-MDCT. In one
patient with severe calcifications, a vascular stenosis with diameter
reduction of 50% or greater was not sufficiently shown. In one patient, MDCT
overestimated a left main stenosis that could not be confirmed by coronary
angiography.
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Our results show that recently introduced 16-MDCT is a promising tool for the detection of coronary artery stenoses. However, severe coronary artery calcifications and motion artifacts still remain limitations. Specific thresholds seem to be useful to raise the diagnostic accuracy of 16-MDCT. Using the same technique, comparable results were found by Nieman et al. [9] and Ropers et al. [10]. Nieman et al. [9] were excluding vessels with a diameter of less than 2 mm from their data evaluation. To raise diagnostic accuracy, Ropers et al. focused their data analysis on patients with heart rates below 60 bpm.
Assessment of the coronary artery lumen on CT is difficult when severely calcified lesions are present. The poor differentiation between contrast-enhanced vessel lumen and high-density calcified plaques may lead to misinterpretation of stenotic lesions and may make some vascular segments unassessable, as has been described by several groups [5, 22]. Therefore, we focused on patients without excessive coronary calcifications and defined a threshold of less than 1,000 ASE. Other exclusion criteria such as heart rate and vascular diameter were not used in our data evaluation.
The diagnostic accuracy was higher in the below-threshold group with fewer calcified plaques (sensitivity, 93%; specificity, 94%) than for the group overall (overall sensitivity, 59%; overall specificity, 87%). The negative predictive value was 87% for all patients and 99% for patients with an ASE of less than 1,000. The positive predictive value was 61% and 68%, respectively. Overestimation of the grade of stenoses leads to these low numbers for the positive predictive value. Overestimation of vascular stenoses is often caused by cardiac motion artifacts and by vascular wall calcifications. Even smaller soft plaque lesions of the vascular wall that cause vascular wall irregularities may lead to the overestimation of vascular stenoses.
The influence of higher heart rates on motion artifacts using 4-MDCT has been described by several groups [21, 23, 24]. One reason for that can be seen in the limited temporal resolution of 4-MDCT. The 16-MDCT systems have a gantry rotation time of 420 msec that results in improved temporal resolution of 210 and 105 msec in patients with a heart rate of more than 70 bpm (biphasic reconstruction algorithm) compared with 4-MDCT scanners with a 0.5-sec rotation time [6]. In our study, the mean heart rate of 64.5 ± 13.3 bpm was achieved through oral ß-blocker administration. Comparable heart rates were found by Ropers et al. [10] using 50 mg of atenolol.
The use of retrospective ECG-gating and of helical data acquisition allows image reconstruction at any time position within the cardiac cycle (R-R interval). The need to optimize the reconstruction window was described by Kopp et al. [25]. Because of the high interindividual variations among patients, test series are recommended to look at each of the three major coronary arteries. In our patients, test series of the CT angiography data sets were performed, and the images were evaluated to determine the time point with minimum motion artifact to avoid loss of image quality.
Similar to conventional angiography, MDCT angiography requires the injection of iodinated contrast medium. Especially in patients with diminished kidney function, lower amounts of contrast medium may help reduce the risk of kidney failure. Sophisticated CT technology with data acquisition of up to 16 slices (12 slices in the cardiac mode for Siemens scanners) per rotation enables scanning times to be less than 20 sec. This means that the amount of contrast agent can be reduced from 140–160 mL in 4-MDCT systems [20] to 80–100 mL in 16-MDCT scanners. In addition, biphasic injection protocols can be used to obtain optimized vascular enhancement while lowering the amount of contrast medium administered. In CT angiography of the abdominal aorta and iliac arteries, Fleischmann et al. [26] showed the advantages of biphasic contrast medium injection. This biphasic injection technique leads to superior uniform enhancement in comparison with standard uniphasic injections and allows optimal visualization of vessels. For that reason, a biphasic injection protocol was used in all patients. No effects of flow limitations from proximal critical stenoses on distal visualization of the coronary arteries were found in our contrast-enhanced series. On all cardiac scans, filling of the coronary venous system was found, and even in high-grade stenoses, contrast enhancement of distal parts was seen.
One major limitation of the application of MDCT in the diagnosis of coronary artery disease is radiation exposure. In conventional coronary angiography, dosage levels depend to a large extent on the examiner and are approximately 3 mSv [16]. Radiation exposure in cardiac CT is influenced by the scanning protocols and parameters used [27]. In 4-MDCT angiography of the coronary arteries, the effective doses of 10.4 mSv in men and 12.7 mSv in women have to be expected (scan length, 13 cm) [28]. Newly developed scanner software for dose saving is provided by the manufacturers and allows tube current modulation according to each patient's ECG findings, referred to as "ECG-pulsing." In 16-MDCT, Trabold et al. [29] found an estimated effective dose (using an Alderson-Rando phantom) for the helical scan obtained to determine the calcium score to be 2.9 mSv in men and 3.6 mSv in women without ECG-pulsing and 1.6 and 2.0 mSv, respectively, with ECG-pulsing. For coronary CT angiography without and with ECG-controlled tube current modulation, the effective dose was 8.1 and 4.3 mSv, respectively, in men and 10.9 and 5.6 mSv, respectively, in women.
The number of patients investigated in this study is relatively small and does not allow a satisfying statistical analysis of all the different aspects of coronary MDCT angiography. In all patients, the total calcium burden of the coronary arteries was determined using an unenhanced helical scan. The decision of when to obtain a contrast-enhanced helical scan of the heart is influenced by different factors, such as heart rate, heart rhythm, and body weight. The threshold of 1,000 ASE was chosen arbitrarily and cannot be seen as a definitive threshold. However, it shows the influence of severe coronary calcifications on the diagnostic accuracy of MDCT of the heart. All patients were in sinus rhythm and received an oral ß-blocker medication before CT examination. Thus, further studies are needed to investigate the influence of arrhythmias and increased heart rates on 16-MDCT coronary angiography. In comparison with quantitative coronary analysis, the grade of stenoses on MDCT was estimated visually. All MDCT studies were evaluated by two radiologists in a joint review manner. A separate data evaluation would have allowed an investigation of the interobserver variability.
In conclusion, in patients with no to moderate coronary calcium burden, MDCT angiography of the coronary arteries is a suitable technique to diagnose vascular stenoses. Severe coronary calcifications and motion artifacts may still affect the diagnostic accuracy of 16-MDCT coronary angiography, and an initial unenhanced scan was found to be mandatory to avoid useless examinations in patients with severe calcifications. However, in comparison with 4-MDCT systems, 16-MDCT scanners with submillimeter data acquisition and faster gantry rotation speed offer considerable improvements in coronary artery visualization and stenosis detection.
Acknowledgments
We wish to thank the radiographers Ayser Birinci, Henriette Heners, and
Nicole Sachse for their excellent assistance.
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