- Email: [email protected]
Beyond perfusion with ultrafast computed tomography
Beyond Perfusion with Ultrafast Computed Tomography Bruce H. Brundage,
MD
Ultrafast computed tomography (CT) has been available for the clinician for nearly 10 years. Although cost, as well as availability of competing technologies, have limited its application, seveml investigative groups have demonstmted the feasibility of measuring regional myocardial blood flow by this method. Ultmfast CT provides accumte measurements when myocardial blood flow is normal or reduced. However, when flow is increased (e.g., by pharmacologic vasodilation), the technique underestimates flow. (This can apparently be corrected by using a complex curve-fitting technique.) Direct injection of contmst medium into the aorta distinguishes differences in endocardial and epicardial blood flow. Although imaging of myocardial perfusion has proven clinical value, there is a need for
new noninvasive approaches for detecting silent coronary atherosclerosis before coronary events occur. Here it is possible to make use of the close association between coronary atherosclerosis and coronary intimal calcium, recognized over 35 years ago. Even though the amount of coronary calcium is a function of age, individuals with coronary artery disease usually have greater amounts, and the greater the number of coronary vessels with calcium, the greater the likelihood of obstructive coronary disease. Ultmfast CT has proven value for visualizing coronary calcium. No contmst medium is required and mdiation exposure is approximately 425 mmds. (Am J Cardioll995;75:69D-730)
ltrafast computed tomography (CT) technology has been clinically available for nearly 10 years. Cost and competing technologies have limited its wide application in the diagnosis of cardiovascular disease. However, growing experience with this imaging modality, both in this country and abroad, has stimulated a renewed interest. Ultrafast CT is a form of x-ray transmission CT and differs from conventional x-ray CT only by the speed with which images are acquired. The unique electron beam technology can create images in as little as 50 msec. This high-speed image acquisition prevents motion artifact caused by cardiac contraction, as is seen with conventional scanners. A powerful electron beam is generated proximal to the head of the supine patient. The beam passes through a magnetic coil, which permits focusing, angulating, and steering the beam across a series of 4 tungsten targets (Figure 1). As the beam sweeps each target, it creates a 210” “fan” beam of x-rays that traverse the patient and then are recorded by an opposing array of detectors for digitization and reconstruction by usual CT algorithms. The x-ray beam emanating from the tungsten targets is split
into 2 adjacent collimated beams so that each sweep of the target produces 2 adjacent slices of anatomy. Slice thickness ranges from 1.5-S mm. In sequence, the 4 targets can be swept by the electron beam to produce 8 adjacent slices of anatomy. In the multilevel mode, slice thickness is limited to 8 mm at the present time. The multilevel mode is often used to evaluate myocardial perfusion. When more precise definition of cardiac anatomy is desired, a single slice imaging protocol is used that permits slices as thin as 1.5 mm. Adjacent anatomy is imaged by moving the patient couch precise distances, usually equivalent to the slice thickness. Several investigative groups have demonstrated the feasibility of measuring regional myocardial blood flow by ultrafast CT.ld The most common method uses a bolus injection of intravenous contrast medium and records the time-concentration curves created in the myocardium and aorta (Figure 2). The flow in any region of myocardium is proportional to the height of the time-concentration curve divided by the area under the aortic time-concentration curve:
U
From the Departments of Medicine and Radiological Sciences, University of California at Los Angeles, School of Medicine, Los Angeles; Division of Cardiology, Harbor-University of California at Los Angeles, Medical Center, Los Angeles; and St. John’s Cardiovascular Research Center, Torrence, California. Address for reprints: Bruce H. Brundage, MD, Harbor-UCLA Medical Center, Division of Cardiology, 1 124 W. Carson Street, RB2, Torrence, California 90502-2052.
flow /volume
of myocardium =
height of myocardial curve area under aortic curve
Computations based on this simple formula provide accurate estimations of myocardial blood flow A SYMPOSIUM:
CARDIAC
IMAGING
690
FIGURE 1. A cutaway diagmm of the uhrafast CT scanner depicts the path of the electron beam from the cathode (GUN) to anode targets. DAS = digital acquisition system.
when flow is normal or reduced. However, when myocardial flow is significantly increased, such as with pharmacologic vasodilation, the technique significantly underestimates the flow1 (Figure 3). Recently reported work suggests that with a complex curve-fitting technique, the underestimation can be corrected.5 Further work is necessary to corroborate these promising findings. A more invasive technique that requires direct injection of contrast medium into the aorta has reported accurate measurements of myocardial blood flow at all degrees of flo~.~ By using this technique, coupled with single thin (3 mm) slice scanning, it is possible to distinguish differences in endocardial and epicardial blood flo~.~ In well-controlled experimental models, good estimates of myocardial blood flow are possible. In the clinical setting reproducible results have been more difficult to achieve. In part, this is due to problems with the reconstruction algorithm created by beam hardening and Compton scatter. Improvement in the reconstruction algorithm should be able to overcome this difficulty. Although assessment of myocardial perfusion is a worthwhile goal in clinical medicine, physicians are increasingly aware that in the evaluation of coronary artery disease, demonstration of normal perfusion does not always predict freedom from future coronary events. In the past decade there has been recognition that coronary atherosclerosis is a dynamic process and that plaque rupture can reduce a previously adequate coronary lumen in minutes to produce acute myocardial infarction or even sudden death. Previously conventional clinical wisdom led us to believe that most if not all coronary events were preceded by gradual narrow-
FIGURE 2. Top, Tim-oncentration curve from descending aorta for region of interest outlined by cursor. Area under this curve is determined by fitting a gamma variate function. Bottom, Tim+concentration curve from the lateral wall of mid-left ventricle as outlined by cursor. Height is measured from baseline to peak and = 28 Hounsfield units (HU).
700
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
75
APRIL 13, 1995
ing of the coronary artery lumen and that diagnostic tests that evaluated adequacy of myocardial perfusion, particularly during some form of stress, would identify most people at risk. A growing understanding of the pathogenesis of acute coronary syndromes has resulted in a rethinking of the paradigm. Clinicians have realized for a long time that stress testing of asymptomatic individuals, even with consideration of risk factors for coronary artery disease, may not identify those at risk for future coronary events. As a result, there has long been controversy over the value of exercise electrocardiography in this group.6 Recently, even the value of stress testing with thallium myocardial scintigraphy has been questioned in asymptomatic individuals.7 Therefore, although myocardial perfusion imaging has proven clinical value, there is a need for new noninvasive approaches for detecting silent coronary atherosclerosis before coronary events occur. In addition, the recognition that diet, lipid-lowering drugs, and other methods to control risk factors can retard, arrest, or even reverse the atherosclerotic process makes the development of such diagnostic tests even more necessary. Nearly 35 years ago, David Blakenhorn recognized the close association between coronary atherosclerosis and coronary intimal calcium.8 Clinicians quickly recognized the potential value of Blakenhorn’s observation and began to use fluoroscopy to identify coronary calcium.9 However, the time-consuming nature of fluoroscopy and its relative insensitivity for detecting small amounts of coronary calcium prevented its widespread use as a
2.5
R= .93 N=72 SEE=.21 0
” 1
” ” 2 3 Microsphere
” 4 Flow
’ “‘I’ 5 6 MIIMinlCm
7
’ 8
FIGURE 3. Ultrafast computed tomography (CT)-determined regional myocardial blood flows compared to simultaneous microsphere measurements demonstrate the underestimation of uhrafast computed tomography measurements at high flow rates. The uhrafast computed tomography measurements at flows <2 ml/min/gm correlate well. (Reprinted with permission from Circulation.l)
screening test. The use of ultrafast CT to detect coronary calcium was first reported in 1986lO (Figure 4). Advantages of ultrafast CT compared with fluoroscopy are an increased sensitivity to detect coronary calcium, the ability to distinguish coronary calcium easily from valvular and aortic wall calcium, and a method to quantitate it. Further, the test can be performed in < 10 minutes by a CT technician without a physician present. No contrast medium is required and the radiation exposure is approximately 425 mrad. Since this method for detecting coronary calcium was first reported, numerous studies have documented the strong corre-
FIGURE 4. The ultraf& computed tomogmphy scan of the proximal left coronary artery demonstrates typical calcium deposits.
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IMAGING
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600
600 ? 0 400
200 0 0
T 4th
T
T
5th
6th
7th
DECADE
FIGURE 5. This gmph shows that patients with known coronary altery disease have significantly higher calcium scores at any age compared with asymptomatic indiiduals. CT# = cakium score; S.E. = standard error of the mean. (Adapted from J Am Cdl CatdioL1z)
lation between calcium and coronary atherosclerosis and disease.“-l4 Agatston and colleagues12 were the first to demonstrate that the greater the amount of coronary calcium, the higher the likelihood for obstructive disease. They demonstrated that, even though the amount of coronary calcium is also a function of age, individuals with known coronary artery disease usually had greater amounts of coronary calcium than asymptomatic individuals of the same age (Figure 5). Investigators at the Mayo Clinic demonstrated in a study of cadaver hearts that regions of the coronary artery free of calcium, as determined by ultrafast CT, rarely had obstructive atherosclerosis (2.5%) in the same region.15 In another study at the Mayo Clinic, patients with angiographically significant coronary artery disease always had coronary calcium detected by ultrafast CT.i3 In a multicenter study of 710 patients having both coronary angiography and ultrafast CT, only 1 individual > 50 years old had significant coronary disease and no coronary calcium. l6 Further analysis of these patients demonstrated that the amount of calcium in the coronary arteries was predictive of multivesse1 coronary artery disease.17 Patients with very high scores (> 1,000 by the Agatson scoring method) had > 75% probability of having multivesse1 disease regardless of age. Additional analysis of these data also indicates that the greater the number of coronary vessels with calcium, the greater the likelihood of obstructive coronary artery disease. Therefore, these studies indicate that the presence of any coronary calcium is very sensitive for detecting coronary disease and atherosclerosis. Further, the amount of calcium and the number of vessels with calcium are quite specific for obstructive coronary disease. 72D
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
75
One recent report suggests that coronary disease may be present in younger individuals, especially under the age of 40 years, without coronary calcium detected by ultrafast CT.14 However, the multicenter study indicates that the majority ( > 80%) of younger people ( < 50 years) without detectable coronary calcium and angiographic obstruction have single-vessel disease.16 The major limitation of the studies reviewed is that they all involve predominantly symptomatic populations who entered the medical system for diagnostic evaluation. However, 2 prospective studies of asymptomatic populations also indicate that the presence of coronary calcium predicts future coronary events. One study is following > 1,400 subjects for 5 years. Entry criteria from the study required a calculated Framingham risk for coronary events of > 1% per year based on traditional coronary risk factors. Evaluation for the presence of coronary calcium was done by digital fluoroscopy. After only 1 year of follow-up, individuals with detectable coronary calcium by this technique have a statistically significant higher incidence of coronary events than those without calcium.is A second study is following 124 asymptomatic individuals who were determined by ultrafast CT to have unusually large amounts of coronary calcium. After only 6 months of follow-up, 19.7% had had a spontaneous coronary event or had undergone revascularization.19 Ultrafast CT may prove to be a useful tool for assessing myocardial perfusion, particularly when excellent spatial resolution is required, such as evaluating subendocardial blood flow. However, further improvements in the reconstruction algorithms are necessary to eliminate artifacts secondary to beam hardening and Compton scatter. Moreover, growth in our understanding of the pathogenesis of acute coronary syndromes has created a need for diagnostic methods that can detect silent coronary atherosclerosis before highgrade fixed obstruction occurs, as well as those asymptomatic individuals who have silent coronary artery disease and are candidates to become one of the 75,000 people whose first symptom is sudden death or one of the 300,000 people whose first symptom is acute myocardial infarction. Therefore, a method other than the assessment of myocardial perfusion is required. The detection of coronary calcium by ultrafast CT appears to be the significant breakthrough needed for this new approach to the assessment of coronary atherosclerosis. APRIL 13. 1995
1. Wolfkiel CT, Ferguson JL, Chomka EV, Law WL, Labii IN, Tenser ML, Booker M, Brundage BH. Measurement of myocardii blood flow by ultrafast computed tomography. Circnl&on 1987;76:1262-1273. 2. Rumberger JA, Feiring AJ, Lipton MJ, H&ens CB, El1 SR, Marcus ML. Use of ultrafast computed tomography to quantitate regional myocardial perfusion: a preliminary report. JAm Co11 Car&l 1987959-69. 3. Weiss RM, Hajduczok X, Marcus ML A new tine CT algorithm for quantitation of myocardiai perfusion. (Abstr.) CLrulation 1988,78:11-398. 4. Canty JM, Brady A, Klocke FJ. Quantitative assessment of reductions in subendocardial and full-thickness regional flow reserve during progressive corenaty stenosis using ultrafast computed tomography. (Abstr.) J Am CoU Can&l 1990,15:161A. 5. Wohkiel CJ, Brundage, BH. Transfer function analysis of UFCI myocardiai time density curves by time varying recursive least squares analysis. IEEE Tram Rio Eng 1994;41:69-76.
6. Epstein SE, Quyyumi AA, Bonow RO. Sudden cardiac death without warning. N Engl J Med 1989;321:32&324. 7. Schwartz RS, Jackson WG, Celia PV, Richardson LA, Hickman JR. Accuracy of exercise 2OlTI myocardial scintigraphy in asymptomatic young men. Circulation 1993;87:165172. 8. Blankenhom DH, Stem D. Calcification of the coronary arteries. Am J Roetgml1959;81:772-777.
9. Margolis JR, Chen JT, Kong Y, Peter RH, Behar VS, Kiss10 JA. The diagnostic and prognostic signiticance of coronaty artery calcitication: a report of 800 cases. Dingn RadioI 1980;137:60!%616. 10. Tanenbaum SR, Kondos GT, Chomka EV, Brundage BH. Ultrafast cornputed tomography in the detection of coronary artery calcification: correlation with selective coronary arteriography. World Congress of Cardiology Scientific Sessions, Abstract Book, Washington, DC, 19%:6. 11. Tanenbaum SR, Kondos GT, Vesehk KE, Pendergast MR, Brundage BH, Chomka EV. Detection of calcific deposits in coronary arteries by ultrafast
computed tomography and correlation with angiography. Am J CamW 1989;63: 87&871. 12. Agatston AS, Janowitz WE, HiIdner FJ, Zusmer NR, Viamonte M, Detrano R. Quanititication of coronary artery calcium using ultrafast computed tomography. JAm CoU Ca&11990,15:827~32. 13. Breen JF, Sheedy PF, Schwartz RS, Stanson AW, Kaufmann RB, Mall PP, Rumberger JA. Coronary artery calcification detected with ultrafast CT as an indication of coronary artery disease. Radio&v 1992,185:435439. 14. Fallavollita JA, Brady AS, Bunnell IL Ktnnar K, Canty JM. Fast cotnputed tomography detection of coronary calcification in the diagnosis of coronary artery disease: comparison with angiography in patients <50 years old. circulalion 1994;89%5-290. 15. Simons DB, Schwartz RS, Edwards WD, Sheedy PF, Breen JF, Rumberger JA. Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: a quantitative pathologic comparison study. JAm CoU Ca&11992;20:11111126. 16. Georgiou D, Budoff M, Kennedy JM, Bleiweis MS, Wolfkiel C, Bnxly AS, Stanford W, Shields P, Brundage BH. The value of ultrafast CT coronary calcification in predicting significant coronary artery disease compared to angiography: a multicenter study. (Abstr.) Cirnrlarion 1993;88:1-639. 17. Georgiou D, Kennedy JM, Brady AS, Lewis RJ, Wohkiel C, Agatston AS, Janowitz WR, Stanford W, Shields P, Brundage BH. Probability of multivessel coronary artery disease in 531 patients based upon ultrafast CT (UFCI) coronary calcification: a multicenter study. (Abstr.) J Am Coil Cardiol 1994;23: 179A. 18. Detrano R, Wang N, Tang W, French W, Georgiou D, Brezden 0, Narahara K, Doherty T, Brundage B. Coronary calcium predicts mronary heart disease in high risk asymptomatic adults. (Abstr.) JAm Cofl Cm&l 1994; 24354-358. 19. Brundage BH, Rich S, Rassman W, Wolfkiel C, Georgiou D, Friedman B, Nickerson S. Follow-up of asymptomatic individuals with high coronary calcium scores on UFCT scans. (Abstr.) J Am Co17 Candid 1994;23:419A.
A SYMPOSIUM:
CARDIAC
IMAGING
73D
MD
Ultrafast computed tomography (CT) has been available for the clinician for nearly 10 years. Although cost, as well as availability of competing technologies, have limited its application, seveml investigative groups have demonstmted the feasibility of measuring regional myocardial blood flow by this method. Ultmfast CT provides accumte measurements when myocardial blood flow is normal or reduced. However, when flow is increased (e.g., by pharmacologic vasodilation), the technique underestimates flow. (This can apparently be corrected by using a complex curve-fitting technique.) Direct injection of contmst medium into the aorta distinguishes differences in endocardial and epicardial blood flow. Although imaging of myocardial perfusion has proven clinical value, there is a need for
new noninvasive approaches for detecting silent coronary atherosclerosis before coronary events occur. Here it is possible to make use of the close association between coronary atherosclerosis and coronary intimal calcium, recognized over 35 years ago. Even though the amount of coronary calcium is a function of age, individuals with coronary artery disease usually have greater amounts, and the greater the number of coronary vessels with calcium, the greater the likelihood of obstructive coronary disease. Ultmfast CT has proven value for visualizing coronary calcium. No contmst medium is required and mdiation exposure is approximately 425 mmds. (Am J Cardioll995;75:69D-730)
ltrafast computed tomography (CT) technology has been clinically available for nearly 10 years. Cost and competing technologies have limited its wide application in the diagnosis of cardiovascular disease. However, growing experience with this imaging modality, both in this country and abroad, has stimulated a renewed interest. Ultrafast CT is a form of x-ray transmission CT and differs from conventional x-ray CT only by the speed with which images are acquired. The unique electron beam technology can create images in as little as 50 msec. This high-speed image acquisition prevents motion artifact caused by cardiac contraction, as is seen with conventional scanners. A powerful electron beam is generated proximal to the head of the supine patient. The beam passes through a magnetic coil, which permits focusing, angulating, and steering the beam across a series of 4 tungsten targets (Figure 1). As the beam sweeps each target, it creates a 210” “fan” beam of x-rays that traverse the patient and then are recorded by an opposing array of detectors for digitization and reconstruction by usual CT algorithms. The x-ray beam emanating from the tungsten targets is split
into 2 adjacent collimated beams so that each sweep of the target produces 2 adjacent slices of anatomy. Slice thickness ranges from 1.5-S mm. In sequence, the 4 targets can be swept by the electron beam to produce 8 adjacent slices of anatomy. In the multilevel mode, slice thickness is limited to 8 mm at the present time. The multilevel mode is often used to evaluate myocardial perfusion. When more precise definition of cardiac anatomy is desired, a single slice imaging protocol is used that permits slices as thin as 1.5 mm. Adjacent anatomy is imaged by moving the patient couch precise distances, usually equivalent to the slice thickness. Several investigative groups have demonstrated the feasibility of measuring regional myocardial blood flow by ultrafast CT.ld The most common method uses a bolus injection of intravenous contrast medium and records the time-concentration curves created in the myocardium and aorta (Figure 2). The flow in any region of myocardium is proportional to the height of the time-concentration curve divided by the area under the aortic time-concentration curve:
U
From the Departments of Medicine and Radiological Sciences, University of California at Los Angeles, School of Medicine, Los Angeles; Division of Cardiology, Harbor-University of California at Los Angeles, Medical Center, Los Angeles; and St. John’s Cardiovascular Research Center, Torrence, California. Address for reprints: Bruce H. Brundage, MD, Harbor-UCLA Medical Center, Division of Cardiology, 1 124 W. Carson Street, RB2, Torrence, California 90502-2052.
flow /volume
of myocardium =
height of myocardial curve area under aortic curve
Computations based on this simple formula provide accurate estimations of myocardial blood flow A SYMPOSIUM:
CARDIAC
IMAGING
690
FIGURE 1. A cutaway diagmm of the uhrafast CT scanner depicts the path of the electron beam from the cathode (GUN) to anode targets. DAS = digital acquisition system.
when flow is normal or reduced. However, when myocardial flow is significantly increased, such as with pharmacologic vasodilation, the technique significantly underestimates the flow1 (Figure 3). Recently reported work suggests that with a complex curve-fitting technique, the underestimation can be corrected.5 Further work is necessary to corroborate these promising findings. A more invasive technique that requires direct injection of contrast medium into the aorta has reported accurate measurements of myocardial blood flow at all degrees of flo~.~ By using this technique, coupled with single thin (3 mm) slice scanning, it is possible to distinguish differences in endocardial and epicardial blood flo~.~ In well-controlled experimental models, good estimates of myocardial blood flow are possible. In the clinical setting reproducible results have been more difficult to achieve. In part, this is due to problems with the reconstruction algorithm created by beam hardening and Compton scatter. Improvement in the reconstruction algorithm should be able to overcome this difficulty. Although assessment of myocardial perfusion is a worthwhile goal in clinical medicine, physicians are increasingly aware that in the evaluation of coronary artery disease, demonstration of normal perfusion does not always predict freedom from future coronary events. In the past decade there has been recognition that coronary atherosclerosis is a dynamic process and that plaque rupture can reduce a previously adequate coronary lumen in minutes to produce acute myocardial infarction or even sudden death. Previously conventional clinical wisdom led us to believe that most if not all coronary events were preceded by gradual narrow-
FIGURE 2. Top, Tim-oncentration curve from descending aorta for region of interest outlined by cursor. Area under this curve is determined by fitting a gamma variate function. Bottom, Tim+concentration curve from the lateral wall of mid-left ventricle as outlined by cursor. Height is measured from baseline to peak and = 28 Hounsfield units (HU).
700
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
75
APRIL 13, 1995
ing of the coronary artery lumen and that diagnostic tests that evaluated adequacy of myocardial perfusion, particularly during some form of stress, would identify most people at risk. A growing understanding of the pathogenesis of acute coronary syndromes has resulted in a rethinking of the paradigm. Clinicians have realized for a long time that stress testing of asymptomatic individuals, even with consideration of risk factors for coronary artery disease, may not identify those at risk for future coronary events. As a result, there has long been controversy over the value of exercise electrocardiography in this group.6 Recently, even the value of stress testing with thallium myocardial scintigraphy has been questioned in asymptomatic individuals.7 Therefore, although myocardial perfusion imaging has proven clinical value, there is a need for new noninvasive approaches for detecting silent coronary atherosclerosis before coronary events occur. In addition, the recognition that diet, lipid-lowering drugs, and other methods to control risk factors can retard, arrest, or even reverse the atherosclerotic process makes the development of such diagnostic tests even more necessary. Nearly 35 years ago, David Blakenhorn recognized the close association between coronary atherosclerosis and coronary intimal calcium.8 Clinicians quickly recognized the potential value of Blakenhorn’s observation and began to use fluoroscopy to identify coronary calcium.9 However, the time-consuming nature of fluoroscopy and its relative insensitivity for detecting small amounts of coronary calcium prevented its widespread use as a
2.5
R= .93 N=72 SEE=.21 0
” 1
” ” 2 3 Microsphere
” 4 Flow
’ “‘I’ 5 6 MIIMinlCm
7
’ 8
FIGURE 3. Ultrafast computed tomography (CT)-determined regional myocardial blood flows compared to simultaneous microsphere measurements demonstrate the underestimation of uhrafast computed tomography measurements at high flow rates. The uhrafast computed tomography measurements at flows <2 ml/min/gm correlate well. (Reprinted with permission from Circulation.l)
screening test. The use of ultrafast CT to detect coronary calcium was first reported in 1986lO (Figure 4). Advantages of ultrafast CT compared with fluoroscopy are an increased sensitivity to detect coronary calcium, the ability to distinguish coronary calcium easily from valvular and aortic wall calcium, and a method to quantitate it. Further, the test can be performed in < 10 minutes by a CT technician without a physician present. No contrast medium is required and the radiation exposure is approximately 425 mrad. Since this method for detecting coronary calcium was first reported, numerous studies have documented the strong corre-
FIGURE 4. The ultraf& computed tomogmphy scan of the proximal left coronary artery demonstrates typical calcium deposits.
A SYMPOSIUM:
CARDIAC
IMAGING
71 D
600
600 ? 0 400
200 0 0
T 4th
T
T
5th
6th
7th
DECADE
FIGURE 5. This gmph shows that patients with known coronary altery disease have significantly higher calcium scores at any age compared with asymptomatic indiiduals. CT# = cakium score; S.E. = standard error of the mean. (Adapted from J Am Cdl CatdioL1z)
lation between calcium and coronary atherosclerosis and disease.“-l4 Agatston and colleagues12 were the first to demonstrate that the greater the amount of coronary calcium, the higher the likelihood for obstructive disease. They demonstrated that, even though the amount of coronary calcium is also a function of age, individuals with known coronary artery disease usually had greater amounts of coronary calcium than asymptomatic individuals of the same age (Figure 5). Investigators at the Mayo Clinic demonstrated in a study of cadaver hearts that regions of the coronary artery free of calcium, as determined by ultrafast CT, rarely had obstructive atherosclerosis (2.5%) in the same region.15 In another study at the Mayo Clinic, patients with angiographically significant coronary artery disease always had coronary calcium detected by ultrafast CT.i3 In a multicenter study of 710 patients having both coronary angiography and ultrafast CT, only 1 individual > 50 years old had significant coronary disease and no coronary calcium. l6 Further analysis of these patients demonstrated that the amount of calcium in the coronary arteries was predictive of multivesse1 coronary artery disease.17 Patients with very high scores (> 1,000 by the Agatson scoring method) had > 75% probability of having multivesse1 disease regardless of age. Additional analysis of these data also indicates that the greater the number of coronary vessels with calcium, the greater the likelihood of obstructive coronary artery disease. Therefore, these studies indicate that the presence of any coronary calcium is very sensitive for detecting coronary disease and atherosclerosis. Further, the amount of calcium and the number of vessels with calcium are quite specific for obstructive coronary disease. 72D
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
75
One recent report suggests that coronary disease may be present in younger individuals, especially under the age of 40 years, without coronary calcium detected by ultrafast CT.14 However, the multicenter study indicates that the majority ( > 80%) of younger people ( < 50 years) without detectable coronary calcium and angiographic obstruction have single-vessel disease.16 The major limitation of the studies reviewed is that they all involve predominantly symptomatic populations who entered the medical system for diagnostic evaluation. However, 2 prospective studies of asymptomatic populations also indicate that the presence of coronary calcium predicts future coronary events. One study is following > 1,400 subjects for 5 years. Entry criteria from the study required a calculated Framingham risk for coronary events of > 1% per year based on traditional coronary risk factors. Evaluation for the presence of coronary calcium was done by digital fluoroscopy. After only 1 year of follow-up, individuals with detectable coronary calcium by this technique have a statistically significant higher incidence of coronary events than those without calcium.is A second study is following 124 asymptomatic individuals who were determined by ultrafast CT to have unusually large amounts of coronary calcium. After only 6 months of follow-up, 19.7% had had a spontaneous coronary event or had undergone revascularization.19 Ultrafast CT may prove to be a useful tool for assessing myocardial perfusion, particularly when excellent spatial resolution is required, such as evaluating subendocardial blood flow. However, further improvements in the reconstruction algorithms are necessary to eliminate artifacts secondary to beam hardening and Compton scatter. Moreover, growth in our understanding of the pathogenesis of acute coronary syndromes has created a need for diagnostic methods that can detect silent coronary atherosclerosis before highgrade fixed obstruction occurs, as well as those asymptomatic individuals who have silent coronary artery disease and are candidates to become one of the 75,000 people whose first symptom is sudden death or one of the 300,000 people whose first symptom is acute myocardial infarction. Therefore, a method other than the assessment of myocardial perfusion is required. The detection of coronary calcium by ultrafast CT appears to be the significant breakthrough needed for this new approach to the assessment of coronary atherosclerosis. APRIL 13. 1995
1. Wolfkiel CT, Ferguson JL, Chomka EV, Law WL, Labii IN, Tenser ML, Booker M, Brundage BH. Measurement of myocardii blood flow by ultrafast computed tomography. Circnl&on 1987;76:1262-1273. 2. Rumberger JA, Feiring AJ, Lipton MJ, H&ens CB, El1 SR, Marcus ML. Use of ultrafast computed tomography to quantitate regional myocardial perfusion: a preliminary report. JAm Co11 Car&l 1987959-69. 3. Weiss RM, Hajduczok X, Marcus ML A new tine CT algorithm for quantitation of myocardiai perfusion. (Abstr.) CLrulation 1988,78:11-398. 4. Canty JM, Brady A, Klocke FJ. Quantitative assessment of reductions in subendocardial and full-thickness regional flow reserve during progressive corenaty stenosis using ultrafast computed tomography. (Abstr.) J Am CoU Can&l 1990,15:161A. 5. Wohkiel CJ, Brundage, BH. Transfer function analysis of UFCI myocardiai time density curves by time varying recursive least squares analysis. IEEE Tram Rio Eng 1994;41:69-76.
6. Epstein SE, Quyyumi AA, Bonow RO. Sudden cardiac death without warning. N Engl J Med 1989;321:32&324. 7. Schwartz RS, Jackson WG, Celia PV, Richardson LA, Hickman JR. Accuracy of exercise 2OlTI myocardial scintigraphy in asymptomatic young men. Circulation 1993;87:165172. 8. Blankenhom DH, Stem D. Calcification of the coronary arteries. Am J Roetgml1959;81:772-777.
9. Margolis JR, Chen JT, Kong Y, Peter RH, Behar VS, Kiss10 JA. The diagnostic and prognostic signiticance of coronaty artery calcitication: a report of 800 cases. Dingn RadioI 1980;137:60!%616. 10. Tanenbaum SR, Kondos GT, Chomka EV, Brundage BH. Ultrafast cornputed tomography in the detection of coronary artery calcification: correlation with selective coronary arteriography. World Congress of Cardiology Scientific Sessions, Abstract Book, Washington, DC, 19%:6. 11. Tanenbaum SR, Kondos GT, Vesehk KE, Pendergast MR, Brundage BH, Chomka EV. Detection of calcific deposits in coronary arteries by ultrafast
computed tomography and correlation with angiography. Am J CamW 1989;63: 87&871. 12. Agatston AS, Janowitz WE, HiIdner FJ, Zusmer NR, Viamonte M, Detrano R. Quanititication of coronary artery calcium using ultrafast computed tomography. JAm CoU Ca&11990,15:827~32. 13. Breen JF, Sheedy PF, Schwartz RS, Stanson AW, Kaufmann RB, Mall PP, Rumberger JA. Coronary artery calcification detected with ultrafast CT as an indication of coronary artery disease. Radio&v 1992,185:435439. 14. Fallavollita JA, Brady AS, Bunnell IL Ktnnar K, Canty JM. Fast cotnputed tomography detection of coronary calcification in the diagnosis of coronary artery disease: comparison with angiography in patients <50 years old. circulalion 1994;89%5-290. 15. Simons DB, Schwartz RS, Edwards WD, Sheedy PF, Breen JF, Rumberger JA. Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: a quantitative pathologic comparison study. JAm CoU Ca&11992;20:11111126. 16. Georgiou D, Budoff M, Kennedy JM, Bleiweis MS, Wolfkiel C, Bnxly AS, Stanford W, Shields P, Brundage BH. The value of ultrafast CT coronary calcification in predicting significant coronary artery disease compared to angiography: a multicenter study. (Abstr.) Cirnrlarion 1993;88:1-639. 17. Georgiou D, Kennedy JM, Brady AS, Lewis RJ, Wohkiel C, Agatston AS, Janowitz WR, Stanford W, Shields P, Brundage BH. Probability of multivessel coronary artery disease in 531 patients based upon ultrafast CT (UFCI) coronary calcification: a multicenter study. (Abstr.) J Am Coil Cardiol 1994;23: 179A. 18. Detrano R, Wang N, Tang W, French W, Georgiou D, Brezden 0, Narahara K, Doherty T, Brundage B. Coronary calcium predicts mronary heart disease in high risk asymptomatic adults. (Abstr.) JAm Cofl Cm&l 1994; 24354-358. 19. Brundage BH, Rich S, Rassman W, Wolfkiel C, Georgiou D, Friedman B, Nickerson S. Follow-up of asymptomatic individuals with high coronary calcium scores on UFCT scans. (Abstr.) J Am Co17 Candid 1994;23:419A.
A SYMPOSIUM:
CARDIAC
IMAGING
73D