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Techniques for quantifying coronary artery calcification
Techniques for Quantifying Coronary Artery Calcification Jeffrey Girshman and Steven D. Wolff Coronary calcium scoring is increasingly used as a screening test for coronary artery disease. Widespread agreement exists that coronary artery calcium (CAC) is a population marker for intimal atherosclerosis, However, the numerical significance of an individual's calcium score and what impact that score should have on future patient management is subject to disagreement. Questions also exist with regard to the interpretation of serial changes in CAC score. The answers to these questions heavily depend on an accurate and reproducible method of quantifying CAC. The purpose of this article is to review the alogrithms and techniques used in CAC quantification, and to identify those variables that may significantly affect its derivation.
Copyright 2003, Elsevier Science (USA). A l l rights reserved.
p
hysicians and their patients are increasingly using coronary calcium scoring as a screening test for coronary artery disease. While there is widespread agreement that coronary artery calcium (CAC) is a population marker for the presence of intimal atherosclerosis, 1-4 there is controversy regarding the numerical significance of an individual's calcium score and what impact that score should have on future patient management. 1'5"7 Questions also exist with regard to the interpretation of any serial changes in the score of the same patient, with or without therapeutic intervention. 8 The answers to these questions, first and foremost, depend on an accurate and reproducible method of quantifying CAC. The purpose of this article is to review the alogrithms and techniques used in quantifying CAC and to identify those variables that may significantly affect its derivation. In the late 1980s, electron beam computed tomography (EBCT) emerged as a method of accurate, noninvasive visualization of the coronary arterial tree and underlying CAC. In EBCT, X-rays are generated by electromagenetically steering a high intensity electron beam on stationary tungsten targets positioned as a 210 ° anode array around the patient. Emitted X-rays are collimated and subsequently detected by scintillation crystal tings positioned 240 ° above the patient. The acquisition of approximately forty contiguous 3 ram-thick transverse slices is required to scan the entire coronary arterial system, and this can usually be accomplished within a single 30-second breath hold. Sub-second temporal resolution is critical when acquiring data in the setting of cardiac motion, because blurring and streak artifacts can decrease the accuracy of the final calculated CAC score. Because EBCT does not rely on a mechanically moving gantry, this system can produce images
rapidly with a temporal resolution of - 1 0 0 ms per image. Agatston and his group 9 used the results from EBCT to develop the first standardized method of CAC quantification, as a way to assess the extent of atherosclerotic disease. This quantification algorithm is still commonly used and has been incorporated into a number of post-processing workstation software applications. In a further attempt to limit the blurring effects of cardiac motion, Agatston et al obtained serial tomographic images during the cardiac cycle's quiescent period. This task was accomplished by synchronizing the patient's electrocardiogram to trigger data acquisition at 80% of the R-R interval or mid-diastole. With the Agatston system (Figs 1 and 2; Table 1), an operator manually designates specific regions of calcification, following data compilation. The application software subsequently calculates the area, mean density, and peak density of the calcification for each segmental lesion. A region of calcification within a coronary vessel is arbitrarily defined as four contiguous pixels (ie, pixel size of 0.25 mm) with an attenuation threshold of at least 130 HU (three times that of soft tissue attenuation). The Agatston method applies a density weighting factor to each lesion defined by the peak plaque densities; that is, a factor of 1 for peak plaque densities measuring 130 to 199 HU, 2 for 200 to 299, 3 for 300 to 399, and 4 for ->400 HU. The total calcium score is then derived as the sum of
From the Cardiovascular Research Foundation and Lenox Hill Hospital New York, NY. Address reprint requests to Steven Wolff, 62 East 88th Street, New York, N Y 1012& e-mail: [email protected] Copyright 2003, Elsevier Science (USA). All rights reserved. 0887-2171/03/2401-167530.00/0 doi :10.1053/sult.2003.S0887- 2171 (03)00003-9
Seminars in Ultrasound, CT, and MRI, Vol 24, No 1 (February), 2003: pp 33-38
33
34
GIRSHMAN AND WOLFF
Fig 1.
Axial tomogram depicting a heavily calcified left anterior descending coronary artery.
the coronary calcium score of the left main, left circumflex, left anterior descending, and fight coronary artery. Patient risk stratification is subsequently performed by ranking an individual's total calcium score against a percentile database of gender and age-matched cohorts. One of the larger compiled calcium score nomograms derived its percentile data from studying 35,246 subjects, while another was compiled from 9728 subjects, lo-12
More recently, multidetector computed tomography (MDCT) has been utilized to evaluate and quantify CAC. MDCT systems require rotation of a heavy x-ray tube around the patient to generate an image, which effectively limits temporal resolution to --250 ms, significantly worse than the --100 ms temporal resolution attained by EBCT. As with EBCT workstations, images are typically acquired with prospective gating, such that data is gathered during diastole, at the nadir of cardiac activity. Commercially available MDCT systems can presently acquire 4 to16 slices simultaneously, a number that is likely to increase in the near
future. The simultaneous image acquisition of MDCT helps compensate for its lower temporal resolution, enabling relatively motion-free tomographic imaging of the entire heart within a 20 to 25 second breath hold. The use of prospective gating techniques with ECG synchronization has since been improved upon. Greater reproducibility in obtaining calcium scores has been achieved by tailoring the ECG trigger to scan at intervals determined by the individual's specific heart rate, rather than relying on a set 80% R-R interval derived from the immediately preceding cardiac cycles, a3 Unfortunately, the prospective gating technique is limited in the setting of patients with cardiac arrhythmias as well as idiosyncratic beat-to-beat variation of the cardiac cycle, a4 Retrospectively gated-cardiac scans can overcome this limitation and yield even greater uniformity in scoring. The downside of retrospective gating is greater radiation exposure to the patient as a result of continuous and redundant scanning. The retrospective technique acquires images while tracking the heart rate and performs
TECHNIQUES IN QUANTIFYING CAC
35
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Fig 2. (A) Calcified lesion in the proximal left anterior descending coronary artery. (B) Raw image data from this artery. The area of each pixel is 0.25 mm 2, The Agatston Score for this calcification is (0.25 mm x 27 pixels) x (4) = 27 (see Table I for methodology).
image reconstructions during the most optimal windows of the individual cardiac cycle, as determined by the interpreter. Essentially, both the individually tailored, prospective and retrospective
ECG gated methods have yielded greater reproducibility in calcium scoring by limiting the impact of cardiac motion artifact on calcium scoring. 9'13-15 Some early criticisms levied against both EBCT
36
GIRSHMAN AND WOLFF
Table 1. Agatston Method of Calcium Scoring Lesion PeakDensityin HU
Density Weighting Factor
<130 130-199 200-299 300-399 z4O0
O 1 2 3 4
Agatston Score = (area in mm 2) x (weighting factor) Total Calcium Score = ~, left main + left circumflex + left anterior descending + right coronary artery
and MDCT have revolved around issues of calcium score inter-test variability. Several investigators have addressed this issue by employing alternative methods of image analysis and acquisition. Callister et 3.] 15 introduced a volumetric method for calculating the calcium score. According to this method, the volume of calcified plaque is estimated based on isotropic interpolation in which volume element dimensions of height, width, and depth are equal. Calculating the volume of calcified regions of interest is performed irrespective of plaque area or plaque density; therefore, the derived calcium score is not affected by the scaling factor used in the Agatston method. For example, a slight change in density attenuation of a calcified plaque may substantially affect the overall calcium score, as the Agatston weighting factor may easily change from 3 to 4 at the border limits of the arbitrarily set attenuation categories. The calcium score generated by the volumetric method has shown greater reproducibility in CAC scoring on serial examinations, as relatively small changes in plaque area or density no longer produce substantial variations in the calcium score. 15 Becker et 0.116 demonstrated the relative equality of EBCT and MDCT in determining significant CAD when utilizing a volume index rather than the traditional Agatston score. When comparing the two technologies as they relate to calcium scoring, a few advantages of MDCT over EBCT have surfaced. For example, image slice thickness of MDCT is typically thinner than EBCT. Most MDCT protocols acquire 2.5 mm-thick slices, while others can attain 1.25 ram, in comparison to the 3ram-thick slices acquired by EBCT. The advantage of acquiring thinner slices is that MDCT may be less sensitive to partial volume averaging effects. The higher signal-to-noise ratios of MDCT over EBCT equate to a more accurate depiction of smaller and lower density calcifica-
tions. This is accomplished by reducing the definable lesion size to 2 pixels with MDCT as opposed to 4 pixels with EBCT. Consequently, small, low density calcified lesions can be included in the final analysis, rather than discarded secondary to an inability to differentiate calcified plaque from imaging noise. The inclusion of such lesions into the data set may be important in the identification of early atherosclerotic plaque formation. The inherently improved signal-to-noise ratios possible with MDCT permits the lowering of the minimum attenuation threshold defining calcified plaque from 130 HU to 90 HU, 17 although altering this threshold has not affected the high correlation found between EBCT and MDCT calcium scoring. 18'19 Another advantage of MDCT is that it is less prone to spatial misregistration between slices, as multiple contiguous slices are acquired simultaneously during the same heartbeat. With EBCT, adjacent images are always acquired on consecutive heartbeats that may vary owing to variations in cardiac and respiratory motion. CLINICAL APPLICATIONS
The application of coronary artery calcium scoring in clinical practice is gaining greater acceptance as ongoing research demonstrates its prognostic value. Traditionally utilized stress tests, such as pharmacologically stressed or exercise stressed treadmill testing with radionuclide imaging, rely on the presence of flow-limiting lesions to reflect the extent of atherosclerotic disease. EBCT and MDCT technology offer the ability to assess nonobstructive, preclinical CAD, as reflected by overall CAC. The importance of some type of subclinical assessment relates to the fact that many acute coronary events occur in patients with negative stress tests or in patients categorized as "low risk" according traditional risk stratification schemes. Unfortunately the extent of CAC is not a perfect predictor of which individual will have an acute coronary event. It is widely held that the rupture of "soft" plaques (composed of a high core lipid content and a thin fibrous cap) and subsequent thrombus formation is the immediate precursor for coronary events. Although soft plaques are, by definition, devoid of a significant amount of calcium, it is felt that the aggregate CAC generally reflects the underlying total plaque burden, and as such indirectly estimates the presence, though not
TECHNIQUES IN QUANTIFYING CAC
37
necessarily the location, o f soft, vulnerable plaque. 2° Various authors h a v e supported this c l a i m by correlating the increased risk o f a coronary e v e n t with an increase in a m a s s e d C A C . 4't°'21-23 Interestingly, total C A C has b e e n f o u n d to be a stronger predictor of future m y o c a r dial events than the w e l l k n o w n traditional risk factors o f hyperlipidemia, hypertension, smoking, diabetes, and age. Furthermore, C A C can independently predict the risk o f obstructive disease, irrespective o f other k n o w n risk factors. 1°'24 T h e d e v e l o p m e n t o f n e w diagnostic modalifies that seek to i m p r o v e patient risk stratification in
C A D p r e v e n t i o n and treatment is vital. E a r l y and a g g r e s s i v e alteration of k n o w n and n e w l y identifiable risk factors, c o u p l e d with t i m e l y intervention in the progression o f C A D , m a y l o w e r the substantial i m p a c t o f c a r d i o v a s c u l a r disease. N e w generation M D C T scanners are entering the m a r k e t p l a c e and h a v e the potential to build on the technical i m p r o v e m e n t s already established by earlier m o d els w i t h regard to scan accuracy, reproducibility, and i m a g i n g speed. A s these scanners penetrate the marketplace, their u n p r e c e d e n t e d versatility in m u l t i - o r g a n i m a g i n g opens the d o o r to an unparalleled expansion o f C A C applications.
REFERENCES 1. 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 94:1175-1192, 1996 2. Janowitz WR: CT imaging of coronary artery calcium as an indicator of atherosclerotic disease: An overview. J Thoracic Imaging 16:2-7, 2001 3. Agatston AS, Janowitz WR, Kaplan G, Gasso J, Hildnet F, Viamonte M: Ultrafast computed tomography detected coronary calcium refects the angiographic extent of coronary artery atherosclerosis. Am J Cardiol 74:1272-1274, 1994 4. Detrano RC, Wong ND, Tang W, et al: Prognostic significance of cardiac cinefluoroscopy for coronary calcific deposits in asymptomatic high risk subjects. J Am Coll Cardiol 24:354358, 1994 5. Greenland P, Abrams J, Aurigemma GP, et al: Prevention Conference V: Beyond secondary prevention: Identifying the high risk patient for primary prevention: Noninvasive tests for atherosclerotic burden. Writing group III. Circulation 101:e16e22, 2000 6. Conti CR: Clinical usefulness of electron beam computed tomography to detect coronary artery calcification. Clin Cardiol 24:755-756, 2001 7. O'Malley PG, Taylor AJ, Jackson JL, Doherty TM, Detrano RC: Prognostic value of coronary electron beam computed tomography for coronary heart disease events in asymptomatic populations. Am J Cardiol 85:945-948, 2000 8. Callister TQ, Raggi P, Cooli B, et al: Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med 339:19721978, 1998 9. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827-832, 1990 10. Raggi P, Callister TQ, Cooil B, et al: Identification of patients at increased risk of first unheralded acute myocardial infarction by electron beam computed tomography. Circulation 101:850-855, 2000
11. Hoff JA et al: Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35, 246 adults. Am J Cardiology 87:13351339, 2001 12. Raggi P, Cooil B, Callister TQ: Use of electron beam tomography data to develop models for prediction of hard coronary events. Am Heart J 141:375-382, 2001 13. Man S, Budoff MJ, Bakhsheshi H, Liu S: Improved reproducibility of coronary artery calcium scoring by electron beam tomography with a new electrographic trigger method. Invest Radiol 36:363-367, 2001 14. Becker CR, Schoepf UJ, Reiser MF: Methods for quantification of coronary artery calcifications with electron beam and conventional CT and pushing the spiral CT envelope: New cardiac applications. Int J Cardiovasc Imaging 17:203-211, 2001 15. Callister TQ, Cooil B, Raya SP, Lippolis NJ, Russo DJ, Raggi P: Coronary artery disease: Improved reproducibility of calcium scoring with an electron beam CT volumetric method. Radiology 208:807-814, 1998 16. Becker CR, Kleffel T, Crispin A, et al: Coronary artery calcium measurement: Agreement of mnltirow detector and electron beam CT. AJR 176:1295-1298, 2001 17. Broderick LS, Shemesh J, Wilensky RL, et al: Measurement of coronary artery calcium with dual-slice helical CT compared with coronary angiography: Evaluation of CT scoring methods, interobserver variations, and reproducibility. AJR 167:439-444, 1996 18. Becker CR, Jakobs TF, Aydemir S, et al: Helical and single-slice conventional CT versus electron beam CT for quantification of coronary artery calcification. AIR 174:543547, 2000 19. Carr JJ, Crouse JR, Burke GL, et al: Evaluation of subsecond-gated helical computed tomography for quantification of coronary artery calcium and comparison with electron beam computed tomography. AJR 174:915-921, 2000 20. Rumberger JA, Simons B, Fitzpatrick LA, et al: Coronary artery calcium area by electron beam computed tomography and coronary atherosclerotic plaque area: A histopathologic correlative study. Circulation 92:2157-2162, 1995
38
21. Arad Y, Spadaro LA, Goodman K, et al: Predictive value of electron beam computed tomography of the coronary arteries: 19 month follow-up of 1173 asymptomatic subjects. Circulation 93:1951-1953, 1996 22. He Z, Hedrick TD, Pratt CM, et al: Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial 'ischemia. Circulation 101:244-251, 2000
GIRSHMAN AND WOLFF
23. Rumberger, JA, Sheedy PF, Breen JF, Schwartz RS: Electron Beam computed tomographic calcium score cut-points and severity of associated angiographic lumen stenosis. J Am Coll Cardiol 29:1542-1548, 1997 24. Guerci AD, Spadaro LA, Goodman KJ, et al: Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease. J Am Coil Cardiol 32:673-679, 1998
Copyright 2003, Elsevier Science (USA). A l l rights reserved.
p
hysicians and their patients are increasingly using coronary calcium scoring as a screening test for coronary artery disease. While there is widespread agreement that coronary artery calcium (CAC) is a population marker for the presence of intimal atherosclerosis, 1-4 there is controversy regarding the numerical significance of an individual's calcium score and what impact that score should have on future patient management. 1'5"7 Questions also exist with regard to the interpretation of any serial changes in the score of the same patient, with or without therapeutic intervention. 8 The answers to these questions, first and foremost, depend on an accurate and reproducible method of quantifying CAC. The purpose of this article is to review the alogrithms and techniques used in quantifying CAC and to identify those variables that may significantly affect its derivation. In the late 1980s, electron beam computed tomography (EBCT) emerged as a method of accurate, noninvasive visualization of the coronary arterial tree and underlying CAC. In EBCT, X-rays are generated by electromagenetically steering a high intensity electron beam on stationary tungsten targets positioned as a 210 ° anode array around the patient. Emitted X-rays are collimated and subsequently detected by scintillation crystal tings positioned 240 ° above the patient. The acquisition of approximately forty contiguous 3 ram-thick transverse slices is required to scan the entire coronary arterial system, and this can usually be accomplished within a single 30-second breath hold. Sub-second temporal resolution is critical when acquiring data in the setting of cardiac motion, because blurring and streak artifacts can decrease the accuracy of the final calculated CAC score. Because EBCT does not rely on a mechanically moving gantry, this system can produce images
rapidly with a temporal resolution of - 1 0 0 ms per image. Agatston and his group 9 used the results from EBCT to develop the first standardized method of CAC quantification, as a way to assess the extent of atherosclerotic disease. This quantification algorithm is still commonly used and has been incorporated into a number of post-processing workstation software applications. In a further attempt to limit the blurring effects of cardiac motion, Agatston et al obtained serial tomographic images during the cardiac cycle's quiescent period. This task was accomplished by synchronizing the patient's electrocardiogram to trigger data acquisition at 80% of the R-R interval or mid-diastole. With the Agatston system (Figs 1 and 2; Table 1), an operator manually designates specific regions of calcification, following data compilation. The application software subsequently calculates the area, mean density, and peak density of the calcification for each segmental lesion. A region of calcification within a coronary vessel is arbitrarily defined as four contiguous pixels (ie, pixel size of 0.25 mm) with an attenuation threshold of at least 130 HU (three times that of soft tissue attenuation). The Agatston method applies a density weighting factor to each lesion defined by the peak plaque densities; that is, a factor of 1 for peak plaque densities measuring 130 to 199 HU, 2 for 200 to 299, 3 for 300 to 399, and 4 for ->400 HU. The total calcium score is then derived as the sum of
From the Cardiovascular Research Foundation and Lenox Hill Hospital New York, NY. Address reprint requests to Steven Wolff, 62 East 88th Street, New York, N Y 1012& e-mail: [email protected] Copyright 2003, Elsevier Science (USA). All rights reserved. 0887-2171/03/2401-167530.00/0 doi :10.1053/sult.2003.S0887- 2171 (03)00003-9
Seminars in Ultrasound, CT, and MRI, Vol 24, No 1 (February), 2003: pp 33-38
33
34
GIRSHMAN AND WOLFF
Fig 1.
Axial tomogram depicting a heavily calcified left anterior descending coronary artery.
the coronary calcium score of the left main, left circumflex, left anterior descending, and fight coronary artery. Patient risk stratification is subsequently performed by ranking an individual's total calcium score against a percentile database of gender and age-matched cohorts. One of the larger compiled calcium score nomograms derived its percentile data from studying 35,246 subjects, while another was compiled from 9728 subjects, lo-12
More recently, multidetector computed tomography (MDCT) has been utilized to evaluate and quantify CAC. MDCT systems require rotation of a heavy x-ray tube around the patient to generate an image, which effectively limits temporal resolution to --250 ms, significantly worse than the --100 ms temporal resolution attained by EBCT. As with EBCT workstations, images are typically acquired with prospective gating, such that data is gathered during diastole, at the nadir of cardiac activity. Commercially available MDCT systems can presently acquire 4 to16 slices simultaneously, a number that is likely to increase in the near
future. The simultaneous image acquisition of MDCT helps compensate for its lower temporal resolution, enabling relatively motion-free tomographic imaging of the entire heart within a 20 to 25 second breath hold. The use of prospective gating techniques with ECG synchronization has since been improved upon. Greater reproducibility in obtaining calcium scores has been achieved by tailoring the ECG trigger to scan at intervals determined by the individual's specific heart rate, rather than relying on a set 80% R-R interval derived from the immediately preceding cardiac cycles, a3 Unfortunately, the prospective gating technique is limited in the setting of patients with cardiac arrhythmias as well as idiosyncratic beat-to-beat variation of the cardiac cycle, a4 Retrospectively gated-cardiac scans can overcome this limitation and yield even greater uniformity in scoring. The downside of retrospective gating is greater radiation exposure to the patient as a result of continuous and redundant scanning. The retrospective technique acquires images while tracking the heart rate and performs
TECHNIQUES IN QUANTIFYING CAC
35
B -gf
-68
-11
29
35
57
gI
I05
g5
88
80
-43
-tl
42
, 64
79
~06
t22
t2
1If
t03
9t
-2
38
65
70
59
50
190 288
163 202
130 13'2
82
67
193 284
tf5
37
f28 t61
&q
47'
fO0
86
45
57
199
369
382
245
f fO
47
20
f42
104
87'
149
282
408
392
232
82
f5
-5
f03
06
124
228
-19
-50
89
176
286 142
48
3t
347 207
166
22
316 ~7
63
0
-49
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32
75
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72
28
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-77
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4
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-59
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-82
Fig 2. (A) Calcified lesion in the proximal left anterior descending coronary artery. (B) Raw image data from this artery. The area of each pixel is 0.25 mm 2, The Agatston Score for this calcification is (0.25 mm x 27 pixels) x (4) = 27 (see Table I for methodology).
image reconstructions during the most optimal windows of the individual cardiac cycle, as determined by the interpreter. Essentially, both the individually tailored, prospective and retrospective
ECG gated methods have yielded greater reproducibility in calcium scoring by limiting the impact of cardiac motion artifact on calcium scoring. 9'13-15 Some early criticisms levied against both EBCT
36
GIRSHMAN AND WOLFF
Table 1. Agatston Method of Calcium Scoring Lesion PeakDensityin HU
Density Weighting Factor
<130 130-199 200-299 300-399 z4O0
O 1 2 3 4
Agatston Score = (area in mm 2) x (weighting factor) Total Calcium Score = ~, left main + left circumflex + left anterior descending + right coronary artery
and MDCT have revolved around issues of calcium score inter-test variability. Several investigators have addressed this issue by employing alternative methods of image analysis and acquisition. Callister et 3.] 15 introduced a volumetric method for calculating the calcium score. According to this method, the volume of calcified plaque is estimated based on isotropic interpolation in which volume element dimensions of height, width, and depth are equal. Calculating the volume of calcified regions of interest is performed irrespective of plaque area or plaque density; therefore, the derived calcium score is not affected by the scaling factor used in the Agatston method. For example, a slight change in density attenuation of a calcified plaque may substantially affect the overall calcium score, as the Agatston weighting factor may easily change from 3 to 4 at the border limits of the arbitrarily set attenuation categories. The calcium score generated by the volumetric method has shown greater reproducibility in CAC scoring on serial examinations, as relatively small changes in plaque area or density no longer produce substantial variations in the calcium score. 15 Becker et 0.116 demonstrated the relative equality of EBCT and MDCT in determining significant CAD when utilizing a volume index rather than the traditional Agatston score. When comparing the two technologies as they relate to calcium scoring, a few advantages of MDCT over EBCT have surfaced. For example, image slice thickness of MDCT is typically thinner than EBCT. Most MDCT protocols acquire 2.5 mm-thick slices, while others can attain 1.25 ram, in comparison to the 3ram-thick slices acquired by EBCT. The advantage of acquiring thinner slices is that MDCT may be less sensitive to partial volume averaging effects. The higher signal-to-noise ratios of MDCT over EBCT equate to a more accurate depiction of smaller and lower density calcifica-
tions. This is accomplished by reducing the definable lesion size to 2 pixels with MDCT as opposed to 4 pixels with EBCT. Consequently, small, low density calcified lesions can be included in the final analysis, rather than discarded secondary to an inability to differentiate calcified plaque from imaging noise. The inclusion of such lesions into the data set may be important in the identification of early atherosclerotic plaque formation. The inherently improved signal-to-noise ratios possible with MDCT permits the lowering of the minimum attenuation threshold defining calcified plaque from 130 HU to 90 HU, 17 although altering this threshold has not affected the high correlation found between EBCT and MDCT calcium scoring. 18'19 Another advantage of MDCT is that it is less prone to spatial misregistration between slices, as multiple contiguous slices are acquired simultaneously during the same heartbeat. With EBCT, adjacent images are always acquired on consecutive heartbeats that may vary owing to variations in cardiac and respiratory motion. CLINICAL APPLICATIONS
The application of coronary artery calcium scoring in clinical practice is gaining greater acceptance as ongoing research demonstrates its prognostic value. Traditionally utilized stress tests, such as pharmacologically stressed or exercise stressed treadmill testing with radionuclide imaging, rely on the presence of flow-limiting lesions to reflect the extent of atherosclerotic disease. EBCT and MDCT technology offer the ability to assess nonobstructive, preclinical CAD, as reflected by overall CAC. The importance of some type of subclinical assessment relates to the fact that many acute coronary events occur in patients with negative stress tests or in patients categorized as "low risk" according traditional risk stratification schemes. Unfortunately the extent of CAC is not a perfect predictor of which individual will have an acute coronary event. It is widely held that the rupture of "soft" plaques (composed of a high core lipid content and a thin fibrous cap) and subsequent thrombus formation is the immediate precursor for coronary events. Although soft plaques are, by definition, devoid of a significant amount of calcium, it is felt that the aggregate CAC generally reflects the underlying total plaque burden, and as such indirectly estimates the presence, though not
TECHNIQUES IN QUANTIFYING CAC
37
necessarily the location, o f soft, vulnerable plaque. 2° Various authors h a v e supported this c l a i m by correlating the increased risk o f a coronary e v e n t with an increase in a m a s s e d C A C . 4't°'21-23 Interestingly, total C A C has b e e n f o u n d to be a stronger predictor of future m y o c a r dial events than the w e l l k n o w n traditional risk factors o f hyperlipidemia, hypertension, smoking, diabetes, and age. Furthermore, C A C can independently predict the risk o f obstructive disease, irrespective o f other k n o w n risk factors. 1°'24 T h e d e v e l o p m e n t o f n e w diagnostic modalifies that seek to i m p r o v e patient risk stratification in
C A D p r e v e n t i o n and treatment is vital. E a r l y and a g g r e s s i v e alteration of k n o w n and n e w l y identifiable risk factors, c o u p l e d with t i m e l y intervention in the progression o f C A D , m a y l o w e r the substantial i m p a c t o f c a r d i o v a s c u l a r disease. N e w generation M D C T scanners are entering the m a r k e t p l a c e and h a v e the potential to build on the technical i m p r o v e m e n t s already established by earlier m o d els w i t h regard to scan accuracy, reproducibility, and i m a g i n g speed. A s these scanners penetrate the marketplace, their u n p r e c e d e n t e d versatility in m u l t i - o r g a n i m a g i n g opens the d o o r to an unparalleled expansion o f C A C applications.
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