Physicians have long sought a noninvasive test that would both assess cardiovascular risk (by measuring atherosclerosis) and investigate the lumen of the coronary artery for stenosis. Both electron-beam tomography and multidetector CT have strengths and weaknesses in these applications.

The data on coronary artery calcification (CC), as measured by CT, go back to the mid-1980s. EBT has been shown to be a specific marker of atherosclerosis, and calcium scores can be related to extent and severity of disease.1 EBT has been used clinically as a method to directly assess atherosclerosis by visualizing the calcified plaque in the coronary artery. The greater the calcium score (a sum of all the calcified plaque in the coronary arteries), the greater the atherosclerotic burden and risk.

The National Cholesterol Education Panel,2 Prevention V Guidelines,3 and others4 have endorsed the approach of using the presence of significant CC to increase antiatherosclerotic therapy. Recent studies have validated that coronary calcium measurement adds independent and incremental prognostic information to traditional risk factors, supporting its use for risk stratification.1,5

The St. Francis Heart Study, the largest prospective study of CC, further supports the use of EBT for the asymptomatic population. In the 5585 subjects, aged 59 plus/minus 5 years, a calcium score greater than or equal to 100 predicted all atherosclerotic cardiovascular disease events, all coronary events, and the sum of nonfatal myocardial infarction and coronary death events with relative risks of 9.5 to 10.7 at 4.3 years.5 The calcium score also predicted events independently of, and more accurately than, measured risk factors. The area under the receiver operating characteristic curve for event prediction with risk factors alone was 0.71, increasing to 0.81 with EBT testing (p < 0.001).

DIFFERENT CT MODALITIES

For years, EBT was the only CT technique fast enough to visualize the coronary arteries. It can acquire high-resolution images of the heart in 100 msec and gate to the cardiac cycle, taking advantage of the diastolic imaging phase when cardiac motion is slightest. This modality, however, is more expensive and less available than conventional MDCT. CT scanners were previously unable to gate the electrocardiogram and had acquisition times > 1 second, far too slow to "freeze" cardiac motion.

MDCT scanners have undergone considerable evolution in the last three to five years, with increases in both detectors and temporal resolution. The current generation of MDCT systems is capable of acquiring four, eight, or 16 (and potentially 32) levels of the heart simultaneously with ECG gating in either a prospective or retrospective mode. MDCT scanners differ from single-slice spiral CT systems principally in the design of the detector arrays and data acquisition systems, which allows the detector arrays to be configured electronically to acquire multiple levels of various slice thickness simultaneously. Thus, in the current 16-channel MDCT systems, 16 slices that are 0.75 to 1.25 mm thick or eight slices that are 2.5 to 3 mm thick can be acquired. (Siemens' 16-slice scanner uses 12 rather than all 16 channels for cardiac studies.)

Most MDCT systems now have gantry speeds of 420 to 750 msec and temporal resolution of 220 to 500 msec per image when used for measuring CC or for noninvasive angiography, as compared with 100 msec for EBT and 50 msec for the new GE Imatron e-Speed.6 Using more detectors (i.e., two- versus four- versus eight- versus 16-detector/channel systems) does not improve the temporal resolution of the images but reduces scan time (i.e., breath-hold time) and slice misregistration.

Partial imaging, in which multiple images are combined to form a single image, is a new method that manufacturers claim will decrease image acquisition time. It requires certain heart rates and a steady rhythm, and it has a very limited clinical success rate, and thus is probably more a theoretical possibility than a true patient application. Slowing the heart rate to < 60 beats per minute remains a necessity when performing noninvasive coronary angiography with MDCT, and it is beneficial for decreasing motion artifacts in CC scanning (Figure 1).

The accompanying table provides a comparison of MDCT and EBT, and several studies have been published that compare the two for CC measurement. The overall correlation between the two modalities is fair to good, but some innate differences exist in the acquisition of images for measurement of CC. Becker et al compared MDCT with EBT in 100 patients and reported a high correlation between the two modalities.7 The percentage variability between the two was 32% for calcium scoring. Moreover, the level of individual precision was limited, and the scores < 100 appeared to have more deviation with MDCT as compared with EBT.

In a recent study, MDCT with a retrospective ECG-gating algorithm showed a high correlation with coronary calcium scores determined using EBT in 20 normal volunteers.8 The total radiation dose for EBT was 3.67 mGy, increasing to 49.42 mGy for four-slice retrospective MDCT imaging. Use of retrospective gating is probably not practical as a screening tool, as this study estimated a 13-fold increased radiation dose with MDCT for measuring CC. More studies are needed comparing EBT and MDCT scans in the same patients, especially with calcium scores < 100. The newer 16-slice scanners have yet to be compared with EBT for CC but certainly have promise for improved correlations.

REPRODUCIBILITY

These technologies promise to accurately and noninvasively measure atherosclerosis burden and to track changes over time, allowing the clinician to assess efficacy of therapy.9 A score that is increasing rapidly may indicate increasing plaque burden, although this hypothesis needs further validation. This ability to assess progression of CC depends on the reproducibility of the technologies. EBT interscan reproducibility has been shown to be approximately 11% to 18%, with inter-reader variability approximately 3% and intrareader variability < 1%.10,11

Interscan variability has been substantially more problematic with MDCT. In several early studies, it was 32% to 40%,12,13 which led the authors to conclude that "helical CT is not sufficiently reproducible to allow serial quantification of total calcium score over time." A more recent study of 537 patients undergoing two studies on four-slice MDCT with cardiac gating demonstrated a mean variability of 36% for volume scoring and 43% for Agatston scoring.14 The reproducibility of 16-slice scanners or the e-Speed has not been reported.

RADIATION

The higher tube currents available with MDCT devices generally result in images with somewhat better signal-to-noise ratio and higher spatial resolution compared with EBT. While the latter has only a prospective mode for analysis, MDCT can acquire data in either a retrospective mode (taking multiple images and retrospectively correlating with the ECG tracing to find optimal images) or a prospective mode (acquiring data at only the optimal point in the cardiac cycle). Of note, radiation exposure from prospectively gated studies is much less than from retrospectively gated studies. In a radiation study comparing EBT and four-level MDCT, EBT for CC measurement yielded effective doses of 1 and 1.3 mSv for men and women, while MDCT yielded doses of 1.5 to 5.2 mSv for men and 1.8 to 6.2 mSv for women.15

NONINVASIVE ANGIOGRAPHY

CC scores correlate well with the total atherosclerotic burden16 and strongly predict future cardiac events,17,18 yet the amount of CC does not correlate well with the stenosis severity of a given lesion.19 As a result, high calcium scores impart an approximate 10-fold increased risk of future cardiac event but do not always indicate a tight stenosis. Visualizing the lumen becomes necessary to predict the need for angioplasty or bypass surgery.

Given the high costs and invasiveness of coronary angiography, interest is increasing in noninvasive CT coronary angiography, which has made great strides as a clinically useful tool to augment conventional coronary angiography. The ability to visualize the lumen of the coronary artery has been at the forefront of these advances. Selective cardiac catheterization, the reference standard for visualization of coronary artery stenosis, is an invasive procedure with a significant cost and a small but measurable procedure-related morbidity and mortality. An alternative, less expensive, and noninvasive test for use as a diagnostic tool before possible intervention could have a major impact on healthcare practice and cost containment.

Noninvasive coronary angiography is challenging, due to rapid coronary motion, limited arterial size, and tortuous course. Advances in imaging techniques, hardware, and workstations, however, have allowed noninvasive imaging with promising success rates. With EBT, electrocardiographic triggering is employed, so that each image is obtained at the same point in diastole. With MDCT, retrospective application of the ECG tracing is used to identify times when coronary motion is limited. For both techniques, iodinated contrast is administered through an antecubital or jugular vein. Volumes of contrast vary from 80 to 160 mL with different techniques and patient characteristics. Sequential cross-sectional images are obtained, and 3D reconstructions are performed. The study is completed in a single breath-hold, usually in 25 to 40 seconds. The entire protocol is completed within 15 to 20 minutes. The test is easy to perform, and interpretation can be made in minutes.

The lumen of the coronary artery can be determined with both MDCT and EBT with intravenous contrast (Figure 2). EBT has been shown to be 89% to 93% accurate as compared with coronary angiography,20,21 with diagnostic success rates of 75% to 93%. Although four-level MDCT is able to obtain images when heart rates are low, in one study it demonstrated only a 30% diagnostic rate (all four major coronary arteries being evaluable), with a sensitivity for stenosis of significant lesions of only 58%.22 Use of the new 16-slice scanners shows much greater promise to accurately visualize the lumen, however. These scanners, with 420-msec rotation time and 12 x 0.75-mm collimation, allow faster and thinner imaging than four-slice scanners.

Two studies have reported improved accuracy using 16-slice scanners compared with prior reports on four-slice scanners. Both achieved sensitivity of 73% to 95% and specificity of 86% to 93%.23,24 The two studies conclude that MDCT with beta blocker premedication permits detection of coronary artery disease with high accuracy and suggest that noninvasive angiography with MDCT should be limited to experienced centers with 16-slice scanners.

Unfortunately, performing noninvasive angiography with MDCT requires using the retrospective mode. Since radiation is continuously applied while only a fraction of the acquired data is used, higher radiation doses of 6 to 13 rad/study limit the clinical applicability of this modality. Thinner slice imaging, possible with 16-slice scanners, will further raise the radiation dose, as more images are required to cover the same anatomy.

A study of CT radiation dose demonstrated electron-beam angiography doses of 1.5 to 2 mSv, MDCT angiography 8.1 to 13 mSv, and coronary angiography 2.1 to 2.3 mSv.25 Another study reported EBA doses of 1.1 mSv and MDCT doses of 9.3 to 11.3 mSv.15 As 360 degrees of imaging is not necessary to create a cardiac image, it is likely that radiation doses with MDCT will be reduced as new strategies are instituted, such as rapidly turning off the beam when it passes behind the subject (dose modulation). Reduced radiation doses and improved rotation times will make MDCT a more clinically useful modality.

FUTURE DIRECTIONS

With the introduction of the e-Speed scanner, EBT enables multiphase imaging and even faster imaging times. This advancement allows for scanning at times as low as 33 msec, promising even less cardiac motion and improved visualization of smaller vessels. The challenge with EBT is spatial resolution and slice thickness, which is better with MDCT.

MDCT with 16-level scanners, and potentially going to 32 slices, promises even thinner slices, as well as better and more reliable visualization of the vessel wall. The challenge with MDCT is the continued need for improved temporal resolution. MDCT studies evaluating progression, reproducibility, plaque burden with intravascular ultrasound or autopsy, and outcomes are needed to fully evaluate the modality's potential to measure and track atherosclerosis prior to widespread implementation.

Given the high negative predictive values, use of noninvasive angiography in patients with lower probabilities of obstructive disease could potentially allow physicians to exclude obstructive coronary artery disease in proximal and midvessels. The negative predictive values have ranged from 95%

to 99% in different studies. EBA is minimally invasive, has an extremely short acquisition time of 15 minutes, and has a markedly lower radiation dose than invasive angiography.26

While it is unlikely that any CT modality will be able to visualize "vulnerable" plaque (the thickness of the fibrous cap is measured in microns, not millimeters), it is possible for these modalities to see "soft" plaque (Figure 3). Several investigators have begun to evaluate the plaque composition.27 This requires contrast enhancement, but potentially will be better able to visualize the plaque composition and identify other components of atherosclerosis, in addition to visualizing the calcified plaque and the lumen.

Selective use of noninvasive CT angiography might prove cost-effective and provide a method that is safer and less invasive for patients. These noninvasive techniques have the potential to assess perfusion and coronary flow in addition to coronary anatomy and thus may provide a comprehensive cardiac evaluation. The most common clinical application of EBA or CTA is to evaluate patients with symptoms following coronary artery bypass graft surgery and coronary angioplasty evaluation, assessment of congenital heart disease and coronary anomalies,28 and measurement of wall motion, myocardial mass, and right and left ejection fractions.29

Accurate measurement of subclinical coronary atherosclerosis should significantly improve the accuracy of global cardiovascular risk prediction and allow for tracking of atherosclerosis burden and better prediction of future cardiovascular events. Successful development of a noninvasive angiogram with consistently high sensitivity and specificity for obstructive CAD would greatly reduce the cost and the morbidity and mortality associated with conventional coronary arteriography.

Replacement of these invasive procedures by noninvasive means is very desirable. Potential uses include follow-up after a nondiagnostic stress test, in patients with intermediate likelihood of CAD (where the step to coronary angiography might be premature), in symptomatic persons post-coronary angioplasty and possibly poststent, evaluation of graft patency post-CABG, and early detection of obstructive CAD in a high-risk person.30

The three most prominent differences between EBT and MDCT are speed of acquisition (EBT acquiring images at 50 to 100 msec and MDCT at 250 to 330 msec), radiation dose (for CC, EBT dose is 0.7 to 1.1 mSv and MDCT dose is 1.5 to 2.4 mSv; for noninvasive angiography, EBT dose is 1.1 to 2 mSv and MDCT dose is 8 to 13 mSv), and interscan variability of measurement when using cardiac gating (11% to 15% for EBT and 25% to 36% for MDCT).

All published studies report that the coronary calcium score predicts coronary disease events independently of standard risk factors. Several recent large studies demonstrate incremental prognostic ability over risk factors alone. Given the current utility of these techniques, we can expect a rapid growth in both the knowledge and experience with CT noninvasive angiography, leading to a much wider clinical use of these new techniques in visualizing the coronary lumens to evaluate obstructive coronary disease.

References

1. Budoff MJ. Prognostic value of coronary artery calcification. J Clin Out Manag 2001;8:42-48.

2. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.

3. Smith SC, Greenland P, Grundy SM. AHA conference proceedings: Prevention Conference V: beyond secondary prevention: identifying the high-risk patient for primary prevention: executive summary: American Heart Association. Circulation 2000;101:111-116.

4. Greenland P, Smith SC Jr, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation 2001;104(15):1863-1867.

5. Arad Y, Roth M, Newstein D, et al. Coronary calcification, coronary risk factors, and atherosclerotic cardiovascular disease events. The St. Francis Heart Study. J Am Coll Cardiol 2003;41:6.

6. Budoff MJ, Mao SS, Zalace CP, et al. Comparison of spiral and electron beam tomography in the evaluation of coronary calcification in asymptomatic persons. Int J Cardiol 2001;77:181-188.

7. Becker CR, Kleffel T, Crispin A, et al. Coronary artery calcium measurement: agreement of multirow detector and electron beam CT. AJR 2001;176:1295-1298.

8. Horiguchi J, Nakanishi T, Ito K. Quantification of coronary artery calcium using multidetector CT and a retrospective ECG-gating reconstruction algorithm. AJR 2001;177:1429-1435.

9. Budoff MJ, Raggi P. Coronary artery disease progression assessed by electron-beam computed tomography. Am J Cardiol 2001;88(suppl):46E-50E.

10. Mao SS, Bakhsheshi H, Lu B, et al. Effect of ECG triggering on reproducibility of coronary artery calcium scoring. Radiology 2001;220(3):707-7111.

11. Lu B, Mao SS, Zhuang N, et al. Coronary artery motion during the cardiac cycle and optimal ECG triggering for coronary artery imaging. Invest Radiol 2001;36:250-256.

12. Shemesh J, Tenenbaum A, Kopecky KK, et al. Coronary calcium measurements by double helical computed tomography. Using the average instead of peak density algorithm improves reproducibility. Invest Radiol 1997 Sept;32(9):503-506.

13. Qanadli SD, Mesurolle B, Aegerter P, et al. Volumetric quantification of coronary artery calcifications using dual-slice spiral CT scanner: improved reproducibility of measurements with 180 degrees linear interpolation algorithm. JCAT 2001;25(2):278-286.

14. Daniell, AL, Wong ND, Friedman JD, et al. Reproducibility of coronary calcium measurements from multidetector computed tomography. J Am Coll Cardiol 2003;41:456-457.

15. Hunold P, Vogt FM, Schmermund A, et al. Radiation exposure during cardiac CT: effective doses at multi-detector row CT and electron-beam CT. Radiology 2003;226:145-152.

16. Agatston AS, Janowitz WR, Kaplan G, et al. Ultrafast computed tomography detected coronary calcium reflects the angiography extent of coronary arterial atherosclerosis. Am J Cardiol 1994;74:1272-1274.

17. Arad Y, Sparado LA, Goodman K, et al. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000;36:1253-1260.

18. 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 2000;101:850-855.

19. Mautner SL, Mautner GC, Froenlich J, et al. Coronary artery calcification assessment with electron beam CT and histomorphometric correlation. Radiology 1994;192:619-623.

20. Achenbach S, Moshage W, Ropers D, et al. Value of electron-beam computed tomography for the noninvasive detection of high-grade coronary artery stenoses and occlusions. NEJM 1998;339:1964-1671.

21. Budoff MJ, Oudiz RJ, Zalace CP, et al. Intravenous three-dimensional coronary angiography using contrast enhanced electron beam computed tomography. Am J Cardiol 1999;83:840-845.

22. Achenbach S, Giesler T, Ropers D, et al. Detection of coronary artery stenoses by contrast-enhanced, retrospectively electrocardiographically-gated, multislice computed tomography. Circulation 2001;103:2535-2538.

23. Ropers D, Baum U, Pohle K, et al. Detection of coronary artery stenosis with thin-slice multi-detector row spiral computed tomography and multiplanar reconstruction. Circulation 2003;107:664-666.

24. Nieman K, Cademartiri F, Lemos PA, et al. Reliable noninvasive coronary angiography with fast submillimeter multislice computed tomography. Circulation 2002;106:2051-2054.

25. Morin RL, Gerber TC, McCollough CH. Radiation dose in computed tomography of the heart. Circulation 2003;107:917-922.

26. Becker C, Schatzl M, Feist H, et al. Assessment of the effective dose for routine protocols in conventional CT, electron beam CT and coronary angiography. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1999;170:99-104.

27. Nieman K, van der Lugt A, Pattynama PM, de Feyter PJ. Noninvasive visualization of atherosclerotic plaque with electron beam and multislice spiral computed tomography. J Interv Cardiol 2003 April;16(2):123-128.

28. Ropers D, Moshage W, Daniel WG, et al. Visualization of coronary artery anomalies and their anatomic course by contrast-enhanced electron-beam tomography and 3-dimensional reconstruction. Am J Cardiol 2001;87:193-197.

29. Baik HK, Budoff MJ, Lane KL, et al. Accurate measures of ejection fraction using electron beam tomography, radionuclide angiography, and catheterization angiography. Int J Cardiac Imaging 2000;16:391-398.

30. Budoff MJ, Achenbach S, Duerinckx A. Clinical utility of CT and MR techniques for noninvasive coronary angiography. JACC 2003: in press.

DR. BUDOFF is director of cardiac CT at Saint John's Cardiovascular Research Center at Harbor-UCLA Medical Center Research and Education Institute in Torrance, CA. He is a member of GE Medical Systems' speakers bureau.

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COMPARISON OF EBT AND MDCT

EBT

Manufacturer: GE Imatron

Cost of scanner: $1.3 million to $1.8 million

No x-ray tubes (uses electrons)

True speed: 50 to 100 msec

Central image resolution: 33 to 86 msec

Radiation exposure: calcium scan, 0.7 to 1.1 mSv; noninvasive angiogram, 1.1 to 2 mSv

Calcium scoring reproducibility: 11% to 18% (interscan variability)

Resolution: up to 10 line pairs/cm

Minimal slice thickness: 1.5 mm

Angiography: maximum heart rate, 120 beats per minute

MDCT

Manufacturers: GE, Philips, Siemens, Toshiba

Cost of scanner: $0.8 million to $1.2 million

Uses x-ray tubes (speed limited by centrifugal force)

True speed: 420 to 800 msec

Central image resolution: 220 to 330 msec

Radiation exposure: calcium scan, 1.5 to 2.4 mSv; noninvasive angiogram, 8.1 to 13 mSv (with dose modulation, 5 to 6 mSv)

Calcium scoring reproducibility: 32% to 40% (interscan variability)

Resolution: up to 13 line pairs/cm

Minimal slice thickness: 0.75 mm

Angiography: maximum heart rate, 65 beats per minute