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DOI:10.2214/AJR.07.2987
AJR 2008; 190:W242-W246
© American Roentgen Ray Society


Original Research

Measuring Noncalcified Coronary Atherosclerotic Plaque Using Voxel Analysis with MDCT Angiography: Phantom Validation

Adeel Sabir1, Chun-Shan Yam1, Norihiko Yoshimura1, Jacqueline L. Buros2, Alec M. De Grand3, Vassilios Raptopoulos1 and Melvin E. Clouse1

1 Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, One Deaconess Rd., WCC-302, Boston, MA 02215.
2 PERFUSE Core Laboratory and Data Coordinating Center, Harvard Medical School, Boston, MA.
3 Small Animal Imaging Facility, Harvard Medical School, Boston, MA.

Received October 23, 2006; accepted after revision October 12, 2007.

 
Address correspondence to M. E. Clouse (mclouse{at}bidmc.harvard.edu).

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Abstract
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
OBJECTIVE. This purpose of this study was to evaluate the accuracy and reproducibility of a voxel analysis technique for measuring noncalcified plaque in the coronary arteries.

MATERIALS AND METHODS. Polyethylene phantoms representing noncalcified plaque were scanned in both MDCT and micro-CT scanners and inter- and intrareader variability of volume calculation was performed.

RESULTS. Volume measurements by both MDCT and micro-CT were comparable to the true volume as measured by micrometry (< 3%, p = 0.05).

CONCLUSION. There appears to be no significant difference (< 3%) between MDCT and micro-CT measurements.

Keywords: aorta • CT angiography • coronary imaging • MDCT • micro-CT • voxel analysis


Introduction
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
MDCT angiography can assess non calcified intraluminal plaque to estimate total plaque burden noninvasively [17]. However, the usual approach of manually drawing lines around vessels on the computer screen to determine wall thickness and subsequent luminal diameter is difficult and time-consuming. To overcome this problem, we developed a semiautomatic computer application based on the gradient change in Hounsfield units across coronary artery regions (epicardial fat, arterial wall, noncalcified plaque, and lumen). We implemented this voxel analysis technique using Analyze 6 (Analyze Direct), commercially available software for 3D volume rendering [8]. The purpose of this study was to validate this technique using a phantom.


Materials and Methods
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
Scanning
Stationary phantoms were made from laboratory-grade polyethylene tubing (LDPE, Cole-Palmer Instrument Co.) having a 4.80-mm outer diameter, 2.80-mm inner diameter as measured by a pin gauge micrometer, and 1.0-mm wall thickness as measured by a digital micrometer. Initially, a tube was filled with a 1:60 mixture of Optiray 320 (ioversol, Mallinckrodt) and gelatin to simulate the contrast density in blood vessels. This was satisfactory for measure ments determining wall thickness and luminal diameter; however, the contrast was not sufficient to measure intraluminal particulate material (represented in this study by a mixture of soybean oil, glycerin and phospholipids, butter fat, and canola oil). There fore, small polyethylene particles of tubing— 9.50 mm3, 4.07 mm3, and 3.6 mm3 (measured by a micrometer [Model 230, Starrett Precision Tools]—accuracy to 0.001 mm) were placed inside a host length of polyethylene tubing and were used to simulate noncalcified plaque deposited in or on the endo thelium, with air serving as contrast material. The tubing containing the three polyethylene particles was scanned in the axial mode on a micro-CT scanner (RS80, GE Healthcare) with a 50-µ focal spot at 80 kV, 450 mA, and an exposure time of 400 milliseconds with a step-and-shoot gantry rotation. The detec tors were 10 x 10 µm cesium iodide crystals fiberoptically connected to a high-efficiency charge-coupled device with 45-µm resolution. MicroView software (GE Health care) was used to reconstruct cross-sectional images into 100-µ isotropic voxels.

To compare the micro-CT measurements with those of clinical scanner studies, the same tubing containing the polyethylene particles was scanned in a standard 16-cm Lucite Head Phantom (Model 76–414, Cardinal Health) using an MDCT Aquilion 64 scanner (Toshiba America Medical Systems) with the following parameters: focal spot size, 1.4 x 1.6 mm; slice thickness, 0.5 mm; overlap, 0.2-mm; gantry rotation, 400 milliseconds; 135 peak kVp; 350 mA; field of view, 32 cm; image matrix, 512 x 512; pixel size, 0.39 mm2; continuous helical scanning; pitch, 0.2–0.3; without ECG input. Cross-sectional images were reconstructed using 400-µ voxels on the Analyze 6 workstation. Volume measurements were evaluated by three independent readers.

Volume Measurements
The reconstructed images from both micro-CT and MDCT were sent to a stand-alone image processing workstation for volume measurement using our voxel analysis technique: Step 1, representative cross-sectional images were viewed by the readers and one image was selected containing all three regions (particle, lumen, and wall). Step 2, Hounsfield density profiles were manually plotted to encompass only the wall and lumen. Step 3, Hounsfield unit values at these two boundaries (H1, inner wall and lumen; H2, outer wall and epicardial fat) were determined by the computer on the basis of the gradient changes. This step was repeated four times to obtain an average. Step 4, a 3D intraluminal volume model was created based on the two Hounsfield values obtained in Step 3. This model represents the sum of these pixels that exceed the defined Hounsfield unit limits. Step 5, the wall of the 3D model was peeled away, leaving only the Hounsfield density (volume) of the particle (Figs. 1A, 1B, 1C, 1D, 2A, 2B, 2C, and 2D).


Figure 1
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Fig. 1A Voxel analysis using micro-CT. Cross-sectional micro-CT image of 4.07 mm3 phantom shows line drawn manually by reader. For this particular case, line was drawn across right side of phantom wall. A–B = phantom edges.

 

Figure 2
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Fig. 1B Voxel analysis using micro-CT. Voxel (H) plot of phantom image shows locations of two boundaries (H1, inner wall and lumen; H2, outer wall and epicardial fat) determined by gradient changes. A–B = phantom edges.

 

Figure 3
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Fig. 1C Voxel analysis using micro-CT. Color-coded 3D model of phantom shows three regions at these two boundaries representing arterial wall, lumen, and noncalcified plaque, as in clinical cases.

 

Figure 4
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Fig. 1D Voxel analysis using micro-CT. Three-dimensional model shows final noncalcified plaque volume after removing (peeling off) arterial wall and lumen. Measured volume was 4.05 mm3.

 

Figure 5
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Fig. 2A Voxel analysis using MDCT. Cross-sectional MDCT image of 4.07 mm3 phantom shows line drawn manually by reader. For this particular case, line was drawn across right side of phantom wall. A–B = phantom edges.

 

Figure 6
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Fig. 2B Voxel analysis using MDCT. Voxel (H) plot of phantom image shows locations of two boundaries (H1, inner wall and lumen; H2, outer wall and epicardial fat) determined by gradient changes. A–B = phantom edges.

 

Figure 7
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Fig. 2C Voxel analysis using MDCT. Color-coded 3D model of phantom shows three regions at these two boundaries representing arterial wall, lumen, and noncalcified plaque, as in clinical cases.

 

Figure 8
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Fig. 2D Voxel analysis using MDCT. Three-dimensional model shows final noncalcified plaque volume after removing (peeling off) arterial wall and lumen. Measured volume was 3.71 mm3.

 
Statistical Methods
Three independent analysts measured the volume of the three intraluminal polyethylene particles twice by each of the two scanning methods (MDCT and micro-CT). A total of 36 volume measurements were performed, with six measurements per particle per method and two measurements per particle per method per analyst. All measurements were included in the analysis irrespective of quality.

The true volumes of the intraluminal polyethylene particles were 9.50, 4.07, and 3.71 mm3 as measured by the micrometer. The accuracy of each measurement method was calculated as the aver age percentage of difference between measured volume and true volume, and the precision was similarly calculated as the average percentage of difference between the first and second volume measurements performed by the same person on the same particle by the same method. All percentages are calculated relative to the true volume of the particle. Accuracy and precision estimates for each scanning method are summarized per particle and across all polyethylene particles as mean and 95% CIs.

For each measurement method, the correlation of true particle size with either measurement accuracy or measurement precision was determined using a rank sum Kruskal-Wallis test for association. Tests for differences of accuracy or precision between methods were evaluated using Wilcoxon's rank sum test for association and the Student's t test for the difference between two means. The intraand interreader variability results are reported as the within-reader and between-reader SDs. The overall reliability of each measurement method is summarized as the concordance correlation coefficient [9, 10], which incorporates both within- and between-reader reliabilities. All analyses were conducted using Stata version 9.2 software (Stata Statistical Software).


Results
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
All 36 volume measurements are listed in Table 1. The average measured volume of the 9.50 mm3 particle was 9.45 mm3 (range, 9.22–9.61 mm3) by micro-CT, whereas the average measured volume by MDCT was 9.88 mm3 (range, 8.58–10.62 mm3). The average measured volume of the 4.07 mm3 particle by micro-CT was 4.04 mm3 (range, 3.91–4.12 mm3), whereas that by MDCT was 3.65 mm3 (range, 3.58–3.71 mm3). The average measured volume of the 3.60 mm3 particle by micro-CT was 3.53 mm3 (range, 3.44–3.63 mm3), whereas that by MDCT was 3.72 mm3 (range, 3.33–4.16 mm3) (Table 1).


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TABLE 1: Volume Measurements

 

The accuracy and precision errors of polyethylene particle volume measurements are summarized in Table 2. Overall volume measurements by each method (micro-CT and MDCT) were 2.05% less than the true volume after averaging over all the three particle sizes. The difference in accuracy between the two scanners was 0.00% (95% CI, –5.3% to 5.3%), with a p value (p = 0.25) for comparing the accuracy of micro-CT with that of MDCT. The magnitude of accuracy errors (as a percentage of true particle volume) did vary according to the particle volume for micro-CT (p = 0.03), whereas that with MDCT showed a weak trend (p = 0.14) (Table 2).


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TABLE 2: Accuracy and Precision Errors According to Scanning Technique and According to True Particle Volume

 

The precision error of volume measurements with micro-CT was 0.88% and with MDCT was 2.17%, so that overall precision error with MDCT was 1.29% greater than with micro-CT (95% CI, –4.0% to 6.6%). There was a possible trend for different precision errors over the range of true volumes when measured by micro-CT (p = 0.19), but there was otherwise little indication of any association between precision error and either the measurement method or the true volume (Table 2).

The intra- and interreader variabilities are summarized in Table 3. Intrareader SD was 0.098 mm [3] (range, 0.061–0.155 mm3) for micro-CT and 0.190 mm3 (0.119–0.301 mm3) for MDCT. Interreader SD was 0.038 mm3 (0.002–0.655 mm3) for micro-CT and 0.67 mm3 (0.377–1.223 mm3) for MDCT. The concordance correlation coefficient between intra- and interreader reliability was 0.999 (range, 0.997–1,000) for micro-CT and 0.972 (range, 0.948–0.995) for MDCT (Table 3).


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TABLE 3: Intra- and Interreader Reliability of Volume Measurements According to Scanning Technique

 


Discussion
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
Our voxel analysis technique for measuring noncalcified plaque was validated with a phantom experiment. The phantom contained three polyethylene particles of known size to simulate endothelial plaque and was scanned using both micro-CT and 64-MDCT. The dimensions of the tubing were comparable to the sizes of the midsections of human adult coronary arteries [11] and to the wall thickness of 0.75–1.05 mm reported by others [1216]. Micrometry was performed to calculate true volume as the gold standard for volume measurement.

Excellent concordance of volume measurements was seen in terms of intra- and interreader reliability for both micro-CT (concordance correlation coefficient = 0.999) and MDCT (concordance correlation coefficient = 0.972) (Table 3). In addition, the micro-CT and MDCT measurements were accurate relative to true volume measurements. Overall accuracy error was 2.05% (range, –10.44% to 4.00%) less than true volume for the three averaged polyethylene particles for both scanners. Although the individual accuracy errors varied, we found no significant difference between micro-CT (p = 0.025) and MDCT (p = 0.135). This is not unexpected because measurement using larger voxels could cause larger variations when measuring smaller particles due to volume averaging; thus, an individual voxel accounts for a larger percentage of the volume of a smaller particle. It may indeed be more accurate to measure all polyethylene particles with 100-µ rather than 400-µ voxels with the clinical scanner. For example, for the 4.07 mm3 polyethylene phantom particle, one voxel accounted for a volume error of 8.89% (Table 1).

Volume measurements by both micro-CT and MDCT were similarly precise (0.88% vs 2.17%), with a difference in precision error of 1.29% (95% CI, –4.0% to 6.6%). A possible trend was seen for difference in precision estimates over the range in particle size for micro-CT (p = 0.19), but there was otherwise little indication of any associated difference between precision, scanners, or true particle volume (p = 0.505) (Table 2). These findings, however promising, must be further evaluated with different voxel sizes for both scanners.

Our voxel analysis technique using Analyze 6 software for measuring noncalcified plaque has been shown by micrometry and micro-CT to be accurate. Apparently no significant difference exists in terms of volume measurements between micro-CT and MDCT using our technique. Both scanners appear able to image the particle sizes with excellent agreements: accuracy error, –2.05% (micro-CT and MDCT) and precision error, 0.88% (micro-CT) versus 2.17% (MDCT). Overall precision error between the two scanners was 1.29%. Similar to the volume measurement findings given earlier, the process requires further substantiation with a larger sample size.

Accuracy error for true volume (2.05% greater or less than the measured number) appears accurate and appropriate in the clinical setting. MDCT did underestimate true volume by 2.05% but, more important, MDCT was not different from micro-CT in the sample (mean, 0.0%). Thus, if the accuracy of the two methods were different, it is not likely to be significant (95% CI, –5.3% to 5.3%).

The precision error is also important. The average precision error for MDCT was 2.2%, which was not very different from that for micro-CT (mean difference, 1.3%; 95% CI, –4.0% to 6.7%). We doubt that a precision error of this amount would be significant in the context of measuring plaque in the clinical setting.

In addition to the previously mentioned accuracy in volume validation, another significant advantage of our voxel analysis technique is that it uses Hounsfield unit gradient changes, rather than fixed Hounsfield unit values, to determine the boundaries of the inner wall and lumen and of the outer wall and epicardial fat, which allows this technique to be patient-specific (i.e., adaptable to patient size).

On the basis of our phantom experiments, the results suggest that our technique is adequate for measuring the volume of noncalcified plaque in coronary arteries. These findings have allowed us to perform a pilot study measuring plaque in a small number of coronary arteries using 100-µ voxels in an institutional review board–approved study. The weakness of the study is that it was performed using a phantom model rather than histopathologic specimens, necessitating the use of air as contrast material outside and inside the tubes. In addition, the use of 100-µ voxels in clinical studies may improve the accuracy for volume and precision measurements.


References
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 

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