- Email: [email protected]
Coronary calcium scores are systematically underestimated at a large chest size: A multivendor phantom study
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 4 1 5 e4 2 1
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofCardiovascularCT.com
Original Research Article
Coronary calcium scores are systematically underestimated at a large chest size: A multivendor phantom study Martin J. Willemink MDa,*, Bronislaw Abramiuc MScb, Annemarie M. den Harder MDa, Niels R. van der Werf BScb, Pim A. de Jong MD, PhDa, Ricardo P.J. Budde MD, PhDa,c, Joachim E. Wildberger MD, PhDd, Rozemarijn Vliegenthart MD, PhDb,e, Tineke P. Willems MD, PhDb, Marcel J.W. Greuter PhDb, Tim Leiner MD, PhDa a
Department of Radiology, University Medical Center Utrecht, P.O. Box 85500, E01.132, Utrecht 3508 GA, The Netherlands b Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands c Department of Radiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands d Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands e Center for Medical Imaging North East Netherlands, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
article info
abstract
Article history:
Objective: To evaluate the effect of chest size on coronary calcium score (CCS) as assessed
Received 22 December 2014
with new-generation CT systems from 4 major vendors.
Received in revised form
Methods: An anthropomorphic, small-sized (300 200 mm) chest phantom containing 100
11 March 2015
small calcifications (diameters, 0.5e2.0 mm) was evaluated with and without an extension
Accepted 30 March 2015
ring on state-of-the-art CT systems from 4 vendors. The extension ring was used to mimic
Available online 2 April 2015
a patient with a large chest size (400 300 mm). Image acquisition was repeated 5 times with small translations and/or rotations. Routine clinical acquisition and reconstruction
Keywords:
protocols for small and large patients were used. CCS was quantified as Agatston and mass
Coronary calcium score
scores with vendor software.
Agatston score
Results: The small-sized phantom resulted in median (interquartiles) Agatston scores of 10
Computed tomography
(9e35), 136 (123e146), 34 (30e37), and 87 (85e89) for Philips, GE, Siemens, and Toshiba,
Chest size
respectively. Mass scores were 4 mg (3e9 mg), 23 mg (21e27 mg), 8 mg (8e9 mg), and 20 mg (20e20 mg), respectively. Adding the extension ring resulted in reduced Agatston scores for all vendors (17%e48%) and mass scores for 2 vendors (11%e49%). Median Agatston scores decreased to 9 (5e10), 79 (60e80), 27 (24e32), and 45 (29e53) units, and median mass scores
Conflict of interest: The Department of Radiology, Utrecht University Medical Center received research support from Philips Healthcare. The Department of Radiology, Maastricht University Medical Center received research support from Siemens Healthcare. * Corresponding author. E-mail address: [email protected] (M.J. Willemink). 1934-5925/$ e see front matter ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2015.03.010
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remained similar for Philips at 4 mg (4e6 mg) and Siemens at 8 mg (7e8 mg) and decreased for the other vendors to 13 mg (11e14 mg) and 10 mg (8e13 mg), respectively. Conclusion: This multivendor phantom study showed that CCS can be underestimated up to 50% (49%e66%) for Agatston scores and 49% (36%e59%) for mass scores at a larger chest size, which may be relevant for women and large patients. However, CCS underestimation by chest size differs considerably by vendor. ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
1.
Introduction
Coronary calcification is a strong predictor for future cardiovascular events.1e3 Therefore, CT is commonly used for assessing the coronary calcium score (CCS) as part of individual risk evaluation. The number of CCS examinations is expanding rapidly and it is already the most common type of CT screening in the United States.4 Recent American Heart Association guidelines recommend CCS for asymptomatic individuals at low-to-intermediate and intermediate cardiovascular risk.5 It is expected that this recommendation will result in a further increase in the number of CCS examinations. Previous studies have shown that obesity is associated with higher CCS,6e8 and increased body weight is also associated with poorer CT image quality.9e11 This might influence calcium scoring as body weight is positively correlated with chest size.12,13 Furthermore, women have relatively more thoracic fat and breast tissue. With the expanding prevalence of obesity and growing number of CCS examinations, it is essential to assess whether the CCS derived in patients with a large chest size is accurate. Because the tube voltage of CCS acquisition protocols is fixed at 120 kV, raised CCS could be caused by either overestimation due to poor image quality at an increased body size or due to actually increased amount of coronary calcification in obese individuals. However, the effect of chest size has not been evaluated yet on routinely used protocols of current state-of-the-art CT systems. The purpose of the present study is to evaluate the effect of chest size on CCS as assessed with new-generation CT systems from the 4 major vendors.
2.
Methods
2.1.
Phantom
An anthropomorphic chest phantom (QRM Thorax, QRM GmbH, Mo¨hrendorf, Germany) was used that consisted of artificial lungs, a spine, and a cylindrical recess. A cardiac phantom was placed within this cylindrical recess, which contained 100 small cylindrical calcifications varying in size and density.14 Calcification diameters ranged from 0.5 to 2.0 mm and densities ranged from 90 to 540 mg hydroxyapatite per cm3. Image acquisition was performed without and with an extension ring (QRM Thorax; Fig. 1). The phantom dimensions without extension ring were 300 mm 200 mm and with extension ring 400 mm 300 mm, respectively. The density of the extension ring was comparable to fat density (approximately 100 Hounsfield units). The phantom without extension ring was used to mimic a patient with a small chest
size and the extension ring was used to mimic a patient with a large chest size. Retrospective analysis of clinically acquired cardiac CT data found that these dimensions match true patient chest sizes. In 26 patients who underwent a cardiac CT examination, the lateral dimensions ranged from 340.1 mm in a patient weighing 67 kg to 522.1 mm in a patient weighing 120 kg.
2.2.
CT protocol
Image acquisition was performed using state-of-the-art CT systems from 4 major vendors (Brilliance iCT, Philips Healthcare, Best, the Netherlands; Discovery CT 750 HD, GE Healthcare, Waukesha, WI; SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany; and Aquilion ONE Vision, Toshiba Medical Systems, Otawara, Japan). Routine acquisition protocols for small patients were used for the phantom without extension ring, and routine acquisition protocols for large patients were used for the phantom with extension ring (Table 1). Vendor-recommended protocols were used with a fixed tube voltage of 120 kV and different tube currents based on body size. For 2 vendors, preset mAs values were used (Philips and GE), and for the other 2 vendors, mAs modulation was applied (Siemens and Toshiba). Prospectively electrocardiography-triggered sequential modes were used with a simulated heart rate of 60 beats/min. Image acquisition was repeated 5 times with small translations of approximately 2 mm and/or rotations of approximately 2 to assess the effects of interscan variation. CCS was quantified as Agatston and mass scores with semiautomatic software from the same manufacturer as the CT system. Size-specific calcium calibration factors as provided by the software were used for mass scoring. Images were reconstructed with vendor-recommended filtered back projection kernels.
2.3.
Reference scores
Measured scores were compared with previously reported reference scores as obtained by scanning the phantom multiple times with an electron beam tomography system.14 The reference Agatston score was 92.1 36.7, and the reference mass score was 20.6 6.5 mg. The physical mass of all calcifications in the phantom is 50.2 mg.
2.4.
Noise measurements
Noise levels were measured in all reconstructions using regions of interest of the same size at the same location within every reconstruction. Standard deviations of the regions of interest were used as a measure of noise. These
J o u r n a l o f C a r d i o v a s c u l a r C o m p u t e d T o m o g r a p h y 9 ( 2 0 1 5 ) 4 1 5 e4 2 1
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Fig. 1 e Phantom with calcification inserts. measurements were performed to evaluate whether different noise levels cause potential differences in CCS.
2.5.
Statistical analysis
Statistical analysis was performed using SPSS (version 20.0 for Microsoft Windows, SPSS Inc, Chicago, Il). The Shapiro-Wilk test was used to identify normally distributed data. To evaluate whether median values differed statistically significantly, data were compared using the Wilcoxon signed rank test. A P value less than 0.05 was considered statistically significant. CCS values are given as medians of the 5 measurements with interquartile ranges.
3.
Results
3.1.
Agatston scores
systems from different vendors. Agatston scores decreased with the extension ring to median scores ranging from 8.6 (5.0e10.0) to 79.0 (60.0e80.0) for CT systems from different vendors. However, the decrease was statistically significant (P ¼ .043) only for 1 vendor (Toshiba), with Agatston scores decreasing from 87.0 (85.0e89.0) to 45.0 (29.0e53.0). Example images of the phantom without and with the extension ring are displayed in Fig. 2. Agatston and mass scores for the smalland the large-sized phantom are displayed in Fig. 3. These figures indicate that rescan variability differs between vendors, and variability was largest in GE and Toshiba scans. Compared to the reference Agatston score of 92.1 36.7, one vendor (GE) had higher scores for the small-sized phantom, one vendor (Toshiba) had similar scores for the smallsized phantom, and all other scans resulted in lower scores.
3.2.
Median Agatston scores for the phantom without extension ring varied from 10.3 (8.6e34.8) to 136.0 (123.0e146.0) for CT
Calcium mass
Median calcium mass for the phantom without extension ring varied from 3.6 mg (2.5e8.9 mg) to 23.4 mg (21.1e27.3 mg) for CT systems from different vendors. Mass scores decreased
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Table 1 e Acquisition and reconstruction parameters. Parameter Acquisition parameters Acquisition mode Tube voltage (kV) Tube current time productdsmall/heavy (mAs) Volumetric CT dose index (mGy) Rotation time (s) Collimation (mm) Reconstruction parameters Slice thickness (mm) Increment (mm) Field of view (mm) Reconstruction kernel
Philips
GE
Siemens
Toshiba
Sequential 120 50/60 4.1/4.9 0.27 128 0.625
Sequential 120 175/193 10.0/10.6 0.35 64 0.625
Sequential 120 22/70 0.8/2.4 0.28 32 1.2
Sequential 120 13/53 1.6/6.4 0.35 240 0.5
3.0 3.0 250 XCA
2.5 2.5 250 Standard
3.0 1.5 250 B35f
3.0 3.0 250 FC12
with the extension ring to median scores ranging from 4.4 mg (4.2e5.5 mg) to 10.3 mg (7.8e13.1 mg) for CT systems from different vendors. Differences were statistically significant for only 1 vendor (Toshiba; P ¼ .04), with mass scores decreasing from 20.0 mg (19.7e20.2 mg) to 10.3 mg (7.8e13.1 mg). Compared to the physical mass of the calcifications (50.2 mg), all vendors underestimated the scores for both the small-sized and the large-sized phantom. However, comparison with the reference mass score derived from the electron beam tomography system (20.6 6.5 mg) gave similar results as the Agatston scores. One vendor (GE) had higher scores for the small-sized phantom, one vendor (Toshiba) had similar scores for the small-sized phantom, and all other scans resulted in lower scores.
3.3.
Noise measurements
Adding the extension ring resulted in increased median noise values for all vendors from 10.6 to 16.3 (Philips), from 11.7 to
24.3 (GE), from 20.2 to 29.5 (Siemens), and from 23.4 to 26.0 (Toshiba).
4.
Discussion
This multivendor phantom study found that Agatston scores and calcium mass decreased for all major vendors by adding an extension ring, even with routinely used weight-adjusted acquisition protocols. Compared with reference scores, all large phantom scans resulted in underestimated calcium scores, and for 2 vendors, the small-sized phantom resulted also in underestimated calcium scores. This implicates that Agatston scores and calcium mass are underestimated in patients with large chest size when compared to those with small chest size. Depending on the vendor, this underestimation can be up to 50% for CCS. Prior studies found that obesity is associated with raised CCS6e8 and CT image quality deteriorates with increased body
Fig. 2 e Example images.
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Fig. 3 e Effect of body size on Agatston scores (A) and mass scores (B). Red lines indicate reference scores. Significant differences are indicated with P values. Other values do not differ significantly.
weight.9e11 Both of these factors might influence the absolute CCS. On the other hand, obese patients often have multiple elevated risk factors for cardiovascular disease, which might also explain raised CCS.15 Our study sought to answer the question to what extent variations in chest size are responsible for variations in CCS. Our study showed that the CCS is underestimated at a larger chest size, even with weightadapted CT acquisition protocols for all major vendors. These results suggest that the association between obesity and raised CCS is even stronger and thus that the future risk of cardiovascular events may be underestimated in individuals with a larger chest size. For the present study, an extension ring with fat density was added to simulate an individual with a large chest size. However, besides a heavy individual this extension ring can also be used to simulate breast tissue. Therefore, our results also suggest that CCS can be underestimated in women. Part of the observed difference between women and men, especially in the premenopausal age group,16 may be attributable to underestimated calcium scores. Agatston scores are influenced by the threshold above which a lesion is classified as a calcification, by the size of the calcification and by the highest Hounsfield unit value of a calcification.17 The threshold used for the Agatston score is 130 Hounsfield units. Therefore, attenuation values have an influence on Agatston scores. Attenuation values may differ between body sizes and CT hardware. Nelson et al10 found that differences in attenuation values up to 15% occur depending on scanner type and body size. Furthermore, they found lower attenuation values in patients with a higher body mass index. Stanford et al11 and Raggi et al18 also found that a higher body mass index is associated with a lower mean density, which can result in lower calcium scores. A solution for this problem might be the use of calcium calibrations or the use of a different threshold for the assessment of coronary
calcifications in patients with a large chest size.18,19 An individual threshold based on the calcium density will probably be more accurate; however, this should be evaluated with future research.17,18,20 Another alternative method for quantifying coronary calcium without using a fixed threshold has been proposed by Liang et al, 21 which deserves further attention. Calcium mass scores are strongly influenced by the density of calcifications, whereby an increase in density leads to a higher score. One would thus expect that an increased density would result in an increased risk of a cardiovascular event. However, the relationship between a higher density of coronary calcifications and an increased risk of a cardiovascular event is controversial because the risk of cardiovascular disease is higher in patients with noncalcified plaques compared to those with calcified plaques.22 Recently, a large multicenter prospective study by Criqui et al23 found that higher calcium density is inversely related to the risk of future cardiovascular disease, suggesting that the mass score may not be the optimal assessment tool for the risk of a future cardiovascular event. Another reason for the decrease in Agatston score and calcium mass in heavy patients is the generally diminished image quality in patients with increased body size9,24,25 caused by an increase in image noise and radiation scatter in heavy patients.18 The effect of noise can be reduced by using iterative reconstruction techniques.26 A previous multivendor study showed that iterative reconstruction algorithms from 4 vendors did not affect CCS in a small-sized phantom indicating that iterative reconstruction can be used for small-sized patients.27 The application of iterative reconstruction algorithms for CCS in heavy patients remains to be evaluated. The present study showed that despite using weight-dependent scan protocols, noise levels increased for all vendors by adding an extension ring. CCS decreased after adding the extension ring; this indicates that the CCS is
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influenced by noise levels. Besides noise, other factors such as volume of calcifications and beam hardening may also play a role in affecting calcium scores. Our study also found that state-of-the-art CT systems from the 4 largest CT vendors result in different Agatston scores, and in some cases, a wide variation between the 5 scans. The effect of older CT systems from different vendors on CCS has been investigated by McCollough et al.28 They found differences in Agatston scores and calcium mass scores of 4.0% and 4.7%, respectively. In the present study, large differences in Agatston scores and calcium mass scores were found, similar to the results from Willemink et al.29 We applied routinely used protocols for every vendor and found large intervendor differences in calcium scores and in volumetric CT dose index (CTDIvol) values. However, for the previous study from Willemink et al,29 CTDIvol values were similar between vendors. This indicates that even with similar CTDIvol values, calcium scores differ substantially between vendors. These results indicate that calcium quantification should be validated not only for body size but also for CT system and software. Variability of the 5 scans was substantial for some vendors. This was probably caused by the different protocols between the vendors. One would expect that higher noise levels result in increased variability. However, no correlation between dose level and interscan variability was found in the present study. Furthermore, the wide interquartile ranges (and thus the large variability) may have contributed to the finding that decreased Agatston and mass scores were only significant for 1 vendor. The large variability between vendors may also be caused by these small calcifications. Not all vendors detected the same calcifications. The present study has limitations. First, it concerns an in vitro study. Because it is not possible to evaluate the same individual with different chest sizes, an in vivo design was not feasible. Second, only small uniform nonanthropomorphic calcifications were inserted in the phantom. Therefore, it could be possible that results differ for larger calcifications. However, small calcifications are more interesting, as relevant reclassification of individuals is more likely at low CCS. Third, a nondynamic phantom was used. The influence of cardiac motion could therefore not be taken into account. In conclusion, this multivendor phantom study showed that Agatston scores and calcium mass decrease when using an extension ring suggesting a systematic underestimation of Agatston scores and calcium mass in patients with larger chest sizes.
references
1. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010;56:e50ee103. 2. Mohlenkamp S, Behrenbeck TR, Pump H, et al. Reproducibility of two coronary calcium quantification algorithms in patients with different degrees of calcification. Int J Cardiovasc Imaging. 2001;17:133e142.
3. Wolk MJ, Bailey SR, Doherty JU, et al. ACCF/AHA/ASE/ASNC/ HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2014;63:380e406. 4. Burger IM, Kass NE, Sunshine JH, Siegelman SS. The use of CT for screening: a national survey of radiologists’ activities and attitudes. Radiology. 2008;248:160e168. 5. Goff Jr DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;129(25 Suppl 2):S49eS73. 6. Allison MA, Wright CM. A comparison of HDL and LDL cholesterol for prevalent coronary calcification. Int J Cardiol. 2004;95:55e60. 7. Kramer CK, von MD, Gross JL, Barrett-Connor E. A prospective study of abdominal obesity and coronary artery calcium progression in older adults. J Clin Endocrinol Metab. 2009;94:5039e5044. 8. Sabour S, Grobbee DE, Prokop M, van der Schouw YT, Bots ML. Change in abdominal obesity and risk of coronary calcification. J Epidemiol Community Health. 2011;65:287e288. 9. Dewey M, Vavere AL, Arbab-Zadeh A, et al. Patient characteristics as predictors of image quality and diagnostic accuracy of MDCT compared with conventional coronary angiography for detecting coronary artery stenoses: CORE-64 multicenter international trial. AJR Am J Roentgenol. 2010;194:93e102. 10. Nelson JC, Kronmal RA, Carr JJ, et al. Measuring coronary calcium on CT images adjusted for attenuation differences. Radiology. 2005;235:403e414. 11. Stanford W, Burns TL, Thompson BH, Witt JD, Lauer RM, Mahoney LT. Influence of body size and section level on calcium phantom measurements at coronary artery calcium CT scanning. Radiology. 2004;230:198e205. 12. Menke J. Comparison of different body size parameters for individual dose adaptation in body CT of adults. Radiology. 2005;236:565e571. 13. Parmenter DC, Gray H. Chest measurement as a gage of body weight. JAMA. 1922;79:2159. 14. Groen JM, Kofoed KF, Zacho M, Vliegenthart R, Willems TP, Greuter MJ. Calcium score of small coronary calcifications on multidetector computed tomography: results from a static phantom study. Eur J Radiol. 2013;82:e58ee63. 15. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53:1925e1932. 16. Kuller LH, Matthews KA, Edmundowicz D, Chang Y. Incident coronary artery calcium among postmenopausal women. Atherosclerosis. 2008;200:278e285. 17. Hong C, Bae KT, Pilgram TK, Suh J, Bradley D. Coronary artery calcium measurement with multi-detector row CT: in vitro assessment of effect of radiation dose. Radiology. 2002;225:901e906. 18. Raggi P, Callister TQ, Cooil B. Calcium scoring of the coronary artery by electron beam CT: how to apply an individual attenuation threshold. AJR Am J Roentgenol. 2002;178:497e502. 19. Ferencik M, Ferullo A, Achenbach S, et al. Coronary calcium quantification using various calibration phantoms and scoring thresholds. Invest Radiol. 2003;38:559e566.
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20. Groen JM, Dijkstra H, Greuter MJ, Oudkerk M. Threshold adjusted calcium scoring using CT is less susceptible to cardiac motion and more accurate. Med Phys. 2009;36:438e446. 21. Liang CJ, Budoff MJ, Kaufman JD, Kronmal RA, Brown ER. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA). BMC Med Imaging. 2012;12:14. 22. Hou ZH, Lu B, Gao Y, et al. Prognostic value of coronary CT angiography and calcium score for major adverse cardiac events in outpatients. JACC Cardiovasc Imaging. 2012;5:990e999. 23. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA. 2013;311(3):271e278. 24. Hall EF. Commentary: use of EBCT in epidemiological studies: the effect of noise and body size on coronary calcium scores. Int J Epidemiol. 2005;34:179e180. 25. Yoneyama K, Vavere AL, Cerci R, et al. Influence of image acquisition settings on radiation dose and image quality in
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coronary angiography by 320-detector volume computed tomography: the CORE320 pilot experience. Heart Int. 2012;7(2):e11. Willemink MJ, Leiner T, de Jong PA, et al. Iterative reconstruction techniques for computed tomography part 2: initial results in dose reduction and image quality. Eur Radiol. 2013;23:1632e1642. Willemink MJ, Takx RAP, de Jong PA, et al. The impact of CT radiation dose reduction and iterative reconstruction algorithms from four different vendors on coronary calcium scoring. Eur Radiol. 2014;24(9):2201e2212. McCollough CH, Ulzheimer S, Halliburton SS, Shanneik K, White RD, Kalender WA. Coronary artery calcium: a multi-institutional, multimanufacturer international standard for quantification at cardiac CT. Radiology. 2007;243:527e538. Willemink MJ, Vliegenthart R, Takx RAP, et al. Coronary artery calcification scoring with state-of-the-art CT scanners from different vendors has substantial effect on risk classifications. Radiology. 2014;273(3):695e702.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofCardiovascularCT.com
Original Research Article
Coronary calcium scores are systematically underestimated at a large chest size: A multivendor phantom study Martin J. Willemink MDa,*, Bronislaw Abramiuc MScb, Annemarie M. den Harder MDa, Niels R. van der Werf BScb, Pim A. de Jong MD, PhDa, Ricardo P.J. Budde MD, PhDa,c, Joachim E. Wildberger MD, PhDd, Rozemarijn Vliegenthart MD, PhDb,e, Tineke P. Willems MD, PhDb, Marcel J.W. Greuter PhDb, Tim Leiner MD, PhDa a
Department of Radiology, University Medical Center Utrecht, P.O. Box 85500, E01.132, Utrecht 3508 GA, The Netherlands b Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands c Department of Radiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands d Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands e Center for Medical Imaging North East Netherlands, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
article info
abstract
Article history:
Objective: To evaluate the effect of chest size on coronary calcium score (CCS) as assessed
Received 22 December 2014
with new-generation CT systems from 4 major vendors.
Received in revised form
Methods: An anthropomorphic, small-sized (300 200 mm) chest phantom containing 100
11 March 2015
small calcifications (diameters, 0.5e2.0 mm) was evaluated with and without an extension
Accepted 30 March 2015
ring on state-of-the-art CT systems from 4 vendors. The extension ring was used to mimic
Available online 2 April 2015
a patient with a large chest size (400 300 mm). Image acquisition was repeated 5 times with small translations and/or rotations. Routine clinical acquisition and reconstruction
Keywords:
protocols for small and large patients were used. CCS was quantified as Agatston and mass
Coronary calcium score
scores with vendor software.
Agatston score
Results: The small-sized phantom resulted in median (interquartiles) Agatston scores of 10
Computed tomography
(9e35), 136 (123e146), 34 (30e37), and 87 (85e89) for Philips, GE, Siemens, and Toshiba,
Chest size
respectively. Mass scores were 4 mg (3e9 mg), 23 mg (21e27 mg), 8 mg (8e9 mg), and 20 mg (20e20 mg), respectively. Adding the extension ring resulted in reduced Agatston scores for all vendors (17%e48%) and mass scores for 2 vendors (11%e49%). Median Agatston scores decreased to 9 (5e10), 79 (60e80), 27 (24e32), and 45 (29e53) units, and median mass scores
Conflict of interest: The Department of Radiology, Utrecht University Medical Center received research support from Philips Healthcare. The Department of Radiology, Maastricht University Medical Center received research support from Siemens Healthcare. * Corresponding author. E-mail address: [email protected] (M.J. Willemink). 1934-5925/$ e see front matter ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved. http://dx.doi.org/10.1016/j.jcct.2015.03.010
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remained similar for Philips at 4 mg (4e6 mg) and Siemens at 8 mg (7e8 mg) and decreased for the other vendors to 13 mg (11e14 mg) and 10 mg (8e13 mg), respectively. Conclusion: This multivendor phantom study showed that CCS can be underestimated up to 50% (49%e66%) for Agatston scores and 49% (36%e59%) for mass scores at a larger chest size, which may be relevant for women and large patients. However, CCS underestimation by chest size differs considerably by vendor. ª 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
1.
Introduction
Coronary calcification is a strong predictor for future cardiovascular events.1e3 Therefore, CT is commonly used for assessing the coronary calcium score (CCS) as part of individual risk evaluation. The number of CCS examinations is expanding rapidly and it is already the most common type of CT screening in the United States.4 Recent American Heart Association guidelines recommend CCS for asymptomatic individuals at low-to-intermediate and intermediate cardiovascular risk.5 It is expected that this recommendation will result in a further increase in the number of CCS examinations. Previous studies have shown that obesity is associated with higher CCS,6e8 and increased body weight is also associated with poorer CT image quality.9e11 This might influence calcium scoring as body weight is positively correlated with chest size.12,13 Furthermore, women have relatively more thoracic fat and breast tissue. With the expanding prevalence of obesity and growing number of CCS examinations, it is essential to assess whether the CCS derived in patients with a large chest size is accurate. Because the tube voltage of CCS acquisition protocols is fixed at 120 kV, raised CCS could be caused by either overestimation due to poor image quality at an increased body size or due to actually increased amount of coronary calcification in obese individuals. However, the effect of chest size has not been evaluated yet on routinely used protocols of current state-of-the-art CT systems. The purpose of the present study is to evaluate the effect of chest size on CCS as assessed with new-generation CT systems from the 4 major vendors.
2.
Methods
2.1.
Phantom
An anthropomorphic chest phantom (QRM Thorax, QRM GmbH, Mo¨hrendorf, Germany) was used that consisted of artificial lungs, a spine, and a cylindrical recess. A cardiac phantom was placed within this cylindrical recess, which contained 100 small cylindrical calcifications varying in size and density.14 Calcification diameters ranged from 0.5 to 2.0 mm and densities ranged from 90 to 540 mg hydroxyapatite per cm3. Image acquisition was performed without and with an extension ring (QRM Thorax; Fig. 1). The phantom dimensions without extension ring were 300 mm 200 mm and with extension ring 400 mm 300 mm, respectively. The density of the extension ring was comparable to fat density (approximately 100 Hounsfield units). The phantom without extension ring was used to mimic a patient with a small chest
size and the extension ring was used to mimic a patient with a large chest size. Retrospective analysis of clinically acquired cardiac CT data found that these dimensions match true patient chest sizes. In 26 patients who underwent a cardiac CT examination, the lateral dimensions ranged from 340.1 mm in a patient weighing 67 kg to 522.1 mm in a patient weighing 120 kg.
2.2.
CT protocol
Image acquisition was performed using state-of-the-art CT systems from 4 major vendors (Brilliance iCT, Philips Healthcare, Best, the Netherlands; Discovery CT 750 HD, GE Healthcare, Waukesha, WI; SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany; and Aquilion ONE Vision, Toshiba Medical Systems, Otawara, Japan). Routine acquisition protocols for small patients were used for the phantom without extension ring, and routine acquisition protocols for large patients were used for the phantom with extension ring (Table 1). Vendor-recommended protocols were used with a fixed tube voltage of 120 kV and different tube currents based on body size. For 2 vendors, preset mAs values were used (Philips and GE), and for the other 2 vendors, mAs modulation was applied (Siemens and Toshiba). Prospectively electrocardiography-triggered sequential modes were used with a simulated heart rate of 60 beats/min. Image acquisition was repeated 5 times with small translations of approximately 2 mm and/or rotations of approximately 2 to assess the effects of interscan variation. CCS was quantified as Agatston and mass scores with semiautomatic software from the same manufacturer as the CT system. Size-specific calcium calibration factors as provided by the software were used for mass scoring. Images were reconstructed with vendor-recommended filtered back projection kernels.
2.3.
Reference scores
Measured scores were compared with previously reported reference scores as obtained by scanning the phantom multiple times with an electron beam tomography system.14 The reference Agatston score was 92.1 36.7, and the reference mass score was 20.6 6.5 mg. The physical mass of all calcifications in the phantom is 50.2 mg.
2.4.
Noise measurements
Noise levels were measured in all reconstructions using regions of interest of the same size at the same location within every reconstruction. Standard deviations of the regions of interest were used as a measure of noise. These
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Fig. 1 e Phantom with calcification inserts. measurements were performed to evaluate whether different noise levels cause potential differences in CCS.
2.5.
Statistical analysis
Statistical analysis was performed using SPSS (version 20.0 for Microsoft Windows, SPSS Inc, Chicago, Il). The Shapiro-Wilk test was used to identify normally distributed data. To evaluate whether median values differed statistically significantly, data were compared using the Wilcoxon signed rank test. A P value less than 0.05 was considered statistically significant. CCS values are given as medians of the 5 measurements with interquartile ranges.
3.
Results
3.1.
Agatston scores
systems from different vendors. Agatston scores decreased with the extension ring to median scores ranging from 8.6 (5.0e10.0) to 79.0 (60.0e80.0) for CT systems from different vendors. However, the decrease was statistically significant (P ¼ .043) only for 1 vendor (Toshiba), with Agatston scores decreasing from 87.0 (85.0e89.0) to 45.0 (29.0e53.0). Example images of the phantom without and with the extension ring are displayed in Fig. 2. Agatston and mass scores for the smalland the large-sized phantom are displayed in Fig. 3. These figures indicate that rescan variability differs between vendors, and variability was largest in GE and Toshiba scans. Compared to the reference Agatston score of 92.1 36.7, one vendor (GE) had higher scores for the small-sized phantom, one vendor (Toshiba) had similar scores for the smallsized phantom, and all other scans resulted in lower scores.
3.2.
Median Agatston scores for the phantom without extension ring varied from 10.3 (8.6e34.8) to 136.0 (123.0e146.0) for CT
Calcium mass
Median calcium mass for the phantom without extension ring varied from 3.6 mg (2.5e8.9 mg) to 23.4 mg (21.1e27.3 mg) for CT systems from different vendors. Mass scores decreased
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Table 1 e Acquisition and reconstruction parameters. Parameter Acquisition parameters Acquisition mode Tube voltage (kV) Tube current time productdsmall/heavy (mAs) Volumetric CT dose index (mGy) Rotation time (s) Collimation (mm) Reconstruction parameters Slice thickness (mm) Increment (mm) Field of view (mm) Reconstruction kernel
Philips
GE
Siemens
Toshiba
Sequential 120 50/60 4.1/4.9 0.27 128 0.625
Sequential 120 175/193 10.0/10.6 0.35 64 0.625
Sequential 120 22/70 0.8/2.4 0.28 32 1.2
Sequential 120 13/53 1.6/6.4 0.35 240 0.5
3.0 3.0 250 XCA
2.5 2.5 250 Standard
3.0 1.5 250 B35f
3.0 3.0 250 FC12
with the extension ring to median scores ranging from 4.4 mg (4.2e5.5 mg) to 10.3 mg (7.8e13.1 mg) for CT systems from different vendors. Differences were statistically significant for only 1 vendor (Toshiba; P ¼ .04), with mass scores decreasing from 20.0 mg (19.7e20.2 mg) to 10.3 mg (7.8e13.1 mg). Compared to the physical mass of the calcifications (50.2 mg), all vendors underestimated the scores for both the small-sized and the large-sized phantom. However, comparison with the reference mass score derived from the electron beam tomography system (20.6 6.5 mg) gave similar results as the Agatston scores. One vendor (GE) had higher scores for the small-sized phantom, one vendor (Toshiba) had similar scores for the small-sized phantom, and all other scans resulted in lower scores.
3.3.
Noise measurements
Adding the extension ring resulted in increased median noise values for all vendors from 10.6 to 16.3 (Philips), from 11.7 to
24.3 (GE), from 20.2 to 29.5 (Siemens), and from 23.4 to 26.0 (Toshiba).
4.
Discussion
This multivendor phantom study found that Agatston scores and calcium mass decreased for all major vendors by adding an extension ring, even with routinely used weight-adjusted acquisition protocols. Compared with reference scores, all large phantom scans resulted in underestimated calcium scores, and for 2 vendors, the small-sized phantom resulted also in underestimated calcium scores. This implicates that Agatston scores and calcium mass are underestimated in patients with large chest size when compared to those with small chest size. Depending on the vendor, this underestimation can be up to 50% for CCS. Prior studies found that obesity is associated with raised CCS6e8 and CT image quality deteriorates with increased body
Fig. 2 e Example images.
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Fig. 3 e Effect of body size on Agatston scores (A) and mass scores (B). Red lines indicate reference scores. Significant differences are indicated with P values. Other values do not differ significantly.
weight.9e11 Both of these factors might influence the absolute CCS. On the other hand, obese patients often have multiple elevated risk factors for cardiovascular disease, which might also explain raised CCS.15 Our study sought to answer the question to what extent variations in chest size are responsible for variations in CCS. Our study showed that the CCS is underestimated at a larger chest size, even with weightadapted CT acquisition protocols for all major vendors. These results suggest that the association between obesity and raised CCS is even stronger and thus that the future risk of cardiovascular events may be underestimated in individuals with a larger chest size. For the present study, an extension ring with fat density was added to simulate an individual with a large chest size. However, besides a heavy individual this extension ring can also be used to simulate breast tissue. Therefore, our results also suggest that CCS can be underestimated in women. Part of the observed difference between women and men, especially in the premenopausal age group,16 may be attributable to underestimated calcium scores. Agatston scores are influenced by the threshold above which a lesion is classified as a calcification, by the size of the calcification and by the highest Hounsfield unit value of a calcification.17 The threshold used for the Agatston score is 130 Hounsfield units. Therefore, attenuation values have an influence on Agatston scores. Attenuation values may differ between body sizes and CT hardware. Nelson et al10 found that differences in attenuation values up to 15% occur depending on scanner type and body size. Furthermore, they found lower attenuation values in patients with a higher body mass index. Stanford et al11 and Raggi et al18 also found that a higher body mass index is associated with a lower mean density, which can result in lower calcium scores. A solution for this problem might be the use of calcium calibrations or the use of a different threshold for the assessment of coronary
calcifications in patients with a large chest size.18,19 An individual threshold based on the calcium density will probably be more accurate; however, this should be evaluated with future research.17,18,20 Another alternative method for quantifying coronary calcium without using a fixed threshold has been proposed by Liang et al, 21 which deserves further attention. Calcium mass scores are strongly influenced by the density of calcifications, whereby an increase in density leads to a higher score. One would thus expect that an increased density would result in an increased risk of a cardiovascular event. However, the relationship between a higher density of coronary calcifications and an increased risk of a cardiovascular event is controversial because the risk of cardiovascular disease is higher in patients with noncalcified plaques compared to those with calcified plaques.22 Recently, a large multicenter prospective study by Criqui et al23 found that higher calcium density is inversely related to the risk of future cardiovascular disease, suggesting that the mass score may not be the optimal assessment tool for the risk of a future cardiovascular event. Another reason for the decrease in Agatston score and calcium mass in heavy patients is the generally diminished image quality in patients with increased body size9,24,25 caused by an increase in image noise and radiation scatter in heavy patients.18 The effect of noise can be reduced by using iterative reconstruction techniques.26 A previous multivendor study showed that iterative reconstruction algorithms from 4 vendors did not affect CCS in a small-sized phantom indicating that iterative reconstruction can be used for small-sized patients.27 The application of iterative reconstruction algorithms for CCS in heavy patients remains to be evaluated. The present study showed that despite using weight-dependent scan protocols, noise levels increased for all vendors by adding an extension ring. CCS decreased after adding the extension ring; this indicates that the CCS is
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influenced by noise levels. Besides noise, other factors such as volume of calcifications and beam hardening may also play a role in affecting calcium scores. Our study also found that state-of-the-art CT systems from the 4 largest CT vendors result in different Agatston scores, and in some cases, a wide variation between the 5 scans. The effect of older CT systems from different vendors on CCS has been investigated by McCollough et al.28 They found differences in Agatston scores and calcium mass scores of 4.0% and 4.7%, respectively. In the present study, large differences in Agatston scores and calcium mass scores were found, similar to the results from Willemink et al.29 We applied routinely used protocols for every vendor and found large intervendor differences in calcium scores and in volumetric CT dose index (CTDIvol) values. However, for the previous study from Willemink et al,29 CTDIvol values were similar between vendors. This indicates that even with similar CTDIvol values, calcium scores differ substantially between vendors. These results indicate that calcium quantification should be validated not only for body size but also for CT system and software. Variability of the 5 scans was substantial for some vendors. This was probably caused by the different protocols between the vendors. One would expect that higher noise levels result in increased variability. However, no correlation between dose level and interscan variability was found in the present study. Furthermore, the wide interquartile ranges (and thus the large variability) may have contributed to the finding that decreased Agatston and mass scores were only significant for 1 vendor. The large variability between vendors may also be caused by these small calcifications. Not all vendors detected the same calcifications. The present study has limitations. First, it concerns an in vitro study. Because it is not possible to evaluate the same individual with different chest sizes, an in vivo design was not feasible. Second, only small uniform nonanthropomorphic calcifications were inserted in the phantom. Therefore, it could be possible that results differ for larger calcifications. However, small calcifications are more interesting, as relevant reclassification of individuals is more likely at low CCS. Third, a nondynamic phantom was used. The influence of cardiac motion could therefore not be taken into account. In conclusion, this multivendor phantom study showed that Agatston scores and calcium mass decrease when using an extension ring suggesting a systematic underestimation of Agatston scores and calcium mass in patients with larger chest sizes.
references
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