Past, Present, and Future Perspective of Cardiac Computed Tomography

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1 JOURNAL OF MAGNETIC RESONANCE IMAGING 19: (2004) Invited Review Past, Present, and Future Perspective of Cardiac Computed Tomography Christoph R. Becker, MD,* and Andreas Knez, MD In the United States, more than 1 million diagnostic invasive coronary angiograms are performed annually, and in about 50% the investigation is followed by an interventional procedure. The remaining symptomatic patients after angiography are treated conservatively or by bypass graft surgery. In recent decades coronary angiography has advanced to a fast and safe investigation. Nevertheless, in particular, patients are well aware of the small but not negligible risk of complications and the discomfort of the invasive procedure. In addition to electrocardiogram (EKG) or ultrasound stress test and thallium scintigraphy, there is further need for another noninvasive method that displays the morphology of the coronary arteries in a way that would allow the triage of patients with suspicion of coronary artery disease (CAD) for a conservative, interventional, or surgical treatment. Key Words: computed tomography; coronary atherosclerosis; coronary artery disease; myocardial infarction; contrast media J. Magn. Reson. Imaging 2004;19: Wiley-Liss, Inc.. INITIALLY, COMPUTED TOMOGRAPHY (CT) of the heart was performed by electron beam CT (EBCT) without contrast media to assess coronary calcifications. In EBCT, electrons are accelerated with an electron gun at 130 kv and 630 ma and focused on target rings that are mounted underneath the patient table. By deceleration of the electrons in the target rings, x-rays are produced that penetrate through the patient. A stationary detector ring above the patient then detects these x-rays. Because of lack of any moving items, the scan time in EBCT can be as short as 100 msec, or even less. To avoid cardiac motion artifacts, scan acquisition is triggered by the electrocardiogram (EKG) signal at the middiastolic phase of the cardiac cycle, typically 40% to 80% of the RR interval. Department of Clinical Radiology and Cardiology, Klinikum Gro hadern, Munich, Germany. *Address reprint requests to: C.R.B., Department of Clinical Radiology and Cardiology, Klinikum Gro hadern, Marchioninistr. 15, Munich, Germany. christoph.becker@ikra.med.uni-muenchen.de Received September 9, 2003; Accepted February 12, DOI /jmri Published online in Wiley InterScience ( ASSESSMENT OF CORONARY CALCIFICATIONS WITH EBCT Agatston et al (1) was the first to report that scanning the coronary arteries without contrast media by EBCT is significantly more sensitive to detect coronary calcifications than conventional fluoroscopy. Scoring the amount of calcifications, they found that symptomatic patients with CAD had a significantly higher score than patients without CAD. Laudon et al (2) found that in patients with chest pain referred to the emergency department, the absence of coronary calcifications was found to be highly predictive (98%) for a negative coronary angiogram. The morphology of calcifications may already give a hint of the likelihood of a stenosis. Kajinami et al (3) reported that the positive predictive values for significant stenosis ( 75%) in none, spotty, and long calcifications were 4%, 18%, and 32%, respectively. Wide and diffuse calcifications may have positive predictive values of 40% and 56%, respectively. In conclusion, only if small calcifications in the coronary arteries are present does a significant stenosis appear to be rather unlikely. However, in case of extensive coronary calcifications, a significant stenosis can be neither determined nor ruled out. Coronary calcifications are currently more understood as a surrogate marker for preclinical coronary atherosclerosis. As part of the entire plaque burden in coronary atherosclerosis, coronary calcifications may be associated with vulnerable plaques. These vulnerable plaques may be prone to rupture, leading then to sudden thrombosis, occluding the coronary artery, and may therefore lead to an acute cardiac event with myocardial infarction. Numerous attempts have been made to determine the predictive value of coronary calcifications for cardiac events. Based on the available literature, there appears to be a moderate association between hard coronary events, such as myocardial infarction and death, and coronary calcifications. However, all of these studies suffer from not having enrolled a large prospective cohort of a non-self-referred screening population (4). Currently, the PACC (5), RECALL (6), and NIH-MESA (7) trials are ongoing and designed to determine the dependent or independent predictive value of coronary calcium for hard coronary events. The results from these trials may become available at the end of this decade. It 2004 Wiley-Liss, Inc. 676

2 Past, Present, and Future of Cardiac CT 677 Table 1 Cardiac MDCT Scan Protocols (e.g., Siemens Sensation 4/16, Forchheim, Germany)* Coronary screening Coronary CTA Bypass graft CTA Pulmonary CT venography Collimation (mm) Gantry rotation (msec) Feed per rot (mm) 3 2 1, EKG gating Yes Yes Yes Yes Yes Yes No No Slice thickness (mm) Increment (mm) Effective mas kvp Scan range (mm) Scan time (second) Scan delay (second) Iodine concentration (mg/ml) Contrast (ml) Flow (ml/second) Radiation exposure 1 msv 1 msv 4 msv 5 msv 5 msv 6 msv 2 msv 2 msv *The use of a dual injector is recommended in particular for the 16-detector-row CT scanner. can be assumed that asymptomatic patients with an intermediate risk, as determined by conventional risk factor assessment, may benefit from coronary calcium screening for the decision of a more or less aggressive risk factor modification. DETECTION OF CORONARY ARTERY STENOSES WITH EBCT Coronary EBCT with contrast enhancement showed promising results for detecting coronary artery stenoses. Achenbach et al (8) reported a sensitivity and specificity for contrast-enhanced EBCT angiography compared to cardiac catheter of 92% and 94%, respectively. Unfortunately, EBCT images suffer from low spatial resolution (1.2-mm in-plane resolution, 3-mm slice thickness) and high image noise. Therefore, reliable assessment of coronary artery stenoses is restricted to the proximal part of the coronary artery tree only. As one of the limitations, Schmermund et al (9) reported that small vessel diameter may lead to false positive findings for coronary artery stenosis. Furthermore, extensive calcifications might interfere with the detection of coronary artery stenoses, resulting in false negative results compared to selective coronary angiography. A reason for this observation may be that standard CT soft tissue reconstruction kernels dense material, such as coronary calcifications or stents, are exaggerated in their size compared to soft tissue structures. This phenomenon is called blooming artifact and may obscure the vessel lumen and wall changes of small structures such as coronary arteries. MULTIDETECTOR ROW CT ACQUISITION TECHNIQUE EBCT and conventional rotating-gantry CT were originally designed as cardiac and all-purpose scanner, respectively. Conventional CT scanners have now improved to acquire cardiac structures as well. The combination of fast gantry rotation, slow table movement, and multislice helical acquisition now allows for acquiring a high number of x-ray projection data. The EKG is recorded simultaneously, and retrospectively CT images are reconstructed from the slow motion diastole phase of the heart. Depending on the clinical question, we are using different scan protocols for coronary calcium screening, coronary CT angiography, bypass graft CT angiography and pulmonary CT venography. These protocols differ in respect to scan range, length, slice collimation, x-ray tube current and voltage, contrast media quantity, and peripheral venous injection flow rate. A summary of the proposed protocols for a 4- and 16-detector row CT scanner is given in Table 1. The exposure time in multidetector row CT (MDCT) with retrospective EKG gating may be considerably longer ( 200 msec with 370-msec gantry rotation) and the radiation exposure higher ( 5 10 msv) than in EBCT ( 2 msv). However, image quality is superior in MDCT than in EBCT with respect to higher spatial resolution (isotropic in-plane resolution and slice thickness of 0.8 mm) and lower image noise (10). In MDCT, attempts have been made to further improve temporal resolution by multisector reconstruction. For this technique, x-ray projections of more than one heartbeat are used to reconstruct an image. This technique requires absolute consistent data from at least two consecutive heartbeats for successful image reconstruction. Unfortunately, the rhythm of the human heart may change rapidly, in particular under special conditions such as breath holding and Valsalva maneuver. For this reason, this technique does not guarantee consistently good image quality under general clinical conditions. The redundant radiation occurring during the radiation exposure in the systole can substantially be reduced by a technique called prospective EKG tube current modulation. On the basis of the EKG signal, the x-ray tube current is switched to its nominal value during the diastole phase and is reduced by 80% during the systole phase of the heart. This technique reduces the dose by 30% to 50% depending on heart rate, but is most effective in patients with low heart rate. For in-

3 678 Becker and Knez stance, in a patient with a heart rate around 60 beats/ minute the radiation exposure will be reduced by approximately 50% (11). By coronary MDCT, patients are exposed to radiation comparable to that of a typical diagnostic coronary catheter procedure ( 5 msv) (12). Image reconstruction always begins with a careful analysis of the EKG trace recorded with the helical scan. The reconstruction interval is best placed in between the T- and P-waves of the EKG corresponding to the mid-diastole interval. The point of time for the least coronary motion may be different for every coronary artery. Least motion artifacts may result for reconstructing the right, left anterior descending, and left circumflex coronary arteries at 50%, 55%, and 60% of the RR interval, respectively. Individual adaptation of the point of time for reconstruction seems to further improve image quality. However, the lower the heart rate, the easier it is to find the single best interval for all three major branches of the coronary artery tree (13). The patient room time is between 15 and 30 minutes, and image reconstruction and postprocessing can be performed within approximately another 15 minutes. In addition, retrospective EKG gating allows for reconstruction of images at any time within the cardiac cycle. Setting the images together that are reconstructed, every 10% of the RR interval allows visualization of the cardiac function. The functional CT data can be evaluated by software in a fashion similar to that for MR images for global and regional wall motions (14). However, reconstruction of functional CT data currently requires at least 20 minutes postprocessing time and the currently available 200-msec exposure time may not be sufficient to reliably assess the cardiac function in the systole phase of the cardiac cycle. Similar to EBCT, coronary calcifications can be detected with a low-dose ( 2 msv) MDCT performed without contrast media (11). With MDCT, detection and quantification of coronary calcium are as sensitive and accurate as with EBCT (15). Scoring of coronary calcifications according to the proprietary EBCT Agatston algorithm turned out to be problematic with MDCT. MDCT images allow for standardized absolute quantification of the mass of coronary calcium and may improve reproducibility of the measurement for follow-up investigations (16,17). PATIENT PREPARATION For morphological assessment of the coronary arteries with around 200-msec exposure time, low heart rate during the scan is a prerequisite to achieve consistently high image quality in every patient (13). Therefore, patients should avoid caffeine or any drug like atropine or nitroglycerin that increases the heart rate prior to a cardiac CT angiography (CTA) investigation. Instead, the use of beta-blocker may become necessary for patient preparation, aiming at a heart rate of 60 beats/ minute or less. To consider beta-blocker for patient preparation, contraindications (bronchial asthma, AV block, severe congestive heart failure, aortic stenosis, etc. (18)) have to be ruled out and informed consent must be obtained from the patient. In case the heart rate of a patient is significantly above 60 beats/minute, mg of metoprolol tartrate can be administered orally minutes prior to the investigation. Alternatively, 5 20 mg of metoprolol tartrate divided in four doses can be administered intravenously (18) immediately prior to scanning. Monitoring of vital functions, heart rate, and blood pressure is essential during this approach. Indeed, the positive effect of beta-blockers on cardiac MDCT scanning is fourfold: The sedating effect of betablockers results in better patient compliance and less movement during scanning. The patient is exposed to less radiation because with lower heart rate, EKG tube current modulation is working more effectively. Cardiac motion artifacts are substantially reduced and because of the lower cardiac output with a beta-blocker, the contrast enhancement will increase. CONTRAST ADMINISTRATION A timely, accurate, and homogenous vascular lumen enhancement is essential for full diagnostic capability of coronary MDCT angiography studies. Higher contrast enhancement is superior to identify small vessels in MDCT. However, dense contrast material in the right atrium cavity may cause streak artifacts arising from the right atrium that may interfere with the right coronary artery. In addition, high enhancement of the coronary arteries may interfere with coronary calcifications and may therefore hinder the delineation of the residual lumen. A peripheral venous iodine flow rate of 1 g/second will result in an enhancement of approximately Hounsfield units (HU) in the majority of patients (19) and still allows for delineation of coronary calcification. The final vessel enhancement will depend not only on the iodine flow rate but also on the cardiac output of the patient. In patients with low cardiac output, e.g., under beta-blocker medication, the contrast media will accumulate in the cardiac chambers and lead to a higher enhancement than in patients with high cardiac output, where the contrast agent will be diluted faster by nonenhanced blood (20). The circulation time can be determined by a test bolusof5gofiodine injected with 1 g/second iodine flow rate and followed by a saline chaser bolus. A series of scans is acquired at the level of the ascending aorta every other second. The arrival time of the test bolus can be determined by taking the delay time between start of the contrast injection and peak enhancement of the ascending aorta into account. The appropriate time to scan after contrast injection depends on the acquisition time of the CT scanner used. In a four-detector row CT with a 40-second acquisition time, scan acquisition may start directly at the time of the predetermined peak enhancement of the test bolus. Scanning with a 16-detector row CT with a 20- second acquisition time requires an additional delay time to allow the contrast media to reach the left ventricular system and coronary arteries. In our current experience, another six seconds should be added to the peak enhancement of the test bolus to allow for complete enhancement of the left ventricular system in a

4 Past, Present, and Future of Cardiac CT 679 seconds has to be added in a 4- and 16-detector row CT, respectively, to allow for a timely, adequate contrast enhancement. The patients should be instructed not to press while taking a deep breath in to avoid the Valsalva maneuver. The Valsalva maneuver increases the intrathoracic pressure, preventing the influx of contrast media through the superior vena cava into the right atrium. Nonenhanced blood from the inferior vena cava entering the right atrium leads to an inhomogeneous enhancement of the cardiac volume during the CTA scan. Figure 1. Peripheral venous injection of 1 g/second iodine leads to a homogenous enhancement of approximately 250 HU. With adequate timing and a dual component injection of contrast media and saline, a kind of CT levocardiogram can be achieved with bright enhancement of the left ventricular system (LV) and coronary arteries and washout in the right ventricular system (RV). 16-detector row CT with a 20-second acquisition time. The contrast media has to be injected for the duration of the scan plus the delay time, and therefore has to be maintained for 40 and 26 seconds in a 4- and 16- detector row CT, respectively. With the use of a dual injector with sequential peripheral venous injection of contrast media and saline, the bolus of contrast media with a high viscosity will be kept compact (20), the total amount of contrast media may be reduced (21,22), and a central venous enhancement profile can be achieved (23). Reducing the amount and use of iso-osmolar contrast media may reduce the risk of contrast-induced nephropathy (24). In addition, changes of heart rate have been observed less frequently during the injection of iso-osmolar contrast agent (25). In a 16-detector row CT the sequential injection of contrast media and saline allows for selective enhancement of the left ventricular cavity (CT levocardiogram) with washout of dense contrast media in the right atrium, helping to avoid artifacts (Fig. 1). Alternatively, the beginning of the CT scan can be triggered automatically by the arrival of the contrast bolus. A prescan is taken at the level of the aortic root and a region of interest is placed into the ascending aorta. When contrast injection starts, repeated scanning at the same level is performed every second. If the density in the ascending aorta reaches 100 HU, a countdown begins until the acquisition starts. Right in front of the CT scan acquisition the patient is instructed to hold his breath. An additional delay time of 4 and 10 POSTPROCESSING The primary axial slices are best suited to rule out CAD. However, the detection of coronary artery stenoses in axial CT images may be problematic since every slice displays only a small part of the entire coronary artery. Multiplanar reformatting, volume rendering, virtual coronary endoscopy, and shaded surface display have been tested for reconstruction of CTA images to detect coronary artery stenosis. None of these postprocessing techniques proved to be superior to axial slices for this task (26). Maximum intensity projections (MIPs) postprocessing of CTA images were found to be helpful for following the course of the coronary arteries and for creating angiographic-like projections that may allow for better detection of coronary artery stenoses. Standardized thin-slab MIP reconstruction may be performed with 5-mm slab thickness and 2.5-mm increment in three different planes, similar to standard cardiac catheter projections (27). MIPs along the interand atria-ventricular groove create images in similar planes as the right and left anterior oblique angiographic projections, respectively (Fig. 2). The 30 right anterior projection is suited to demonstrate the course of the left anterior descending coronary artery, whereas the 45 left anterior projection best displays the course of the right and left circumflex coronary arteries (Fig. 3). In addition, similar to coronary angiography, a projec- Figure 2. MIPs in the right anterior oblique (RAO) plane are best suited to display the course and detect atherosclerosis in the left anterior descending coronary artery (arrow).

5 680 Becker and Knez tion with 45 left anterior oblique and 30 cranial angulations can be reconstructed following the long axis of the heart. This projection plane spreads the branches of the left anterior descending coronary artery and is therefore called the spider view. The spider view is designed to demonstrate the proximal part of all three major coronary arteries (Fig. 4). EVALUATION OF CORONARY CT For the first run, MIP images may help to identify coronary artery stenosis. Volume rendering was found to be helpful for demonstrating the course in case of coiling and kinking of the coronary arteries, i.e., in hypertensive heart disease, in a coronary fistula, or in case of suspicion of any other coronary anomaly. However, every finding from postprocessed images has to be confirmed in the original axial CT slices. Image analysis begins with identification of the coronary artery segments in the axial CT slices. Coronary segments can be numbered according to the model suggested by the American Heart Association (28). A lumen-narrowing scoring system according to Schmermund et al (9) may be used to describe different grades of coronary artery stenosis in the proximal and middle coronary artery segments: A angiographically normal segment (0% stenosis), B nonobstructive disease (1% to 49% lumen diameter stenosis), C significant (50% to 74%) stenosis, D high-grade (75% to 99%) stenosis, and E total occlusion (100% stenosis). The patency of the distal coronary artery segments should be reported as well. CLINICAL APPLICATION OF CORONARY CTA Because of the limited spatial resolution in CTA and the blooming of calcifications, the definite assessment of Figure 3. For the same purpose, left anterior oblique (LAO) projections are best suited to display the course of the right and circumflex coronary arteries (arrow). Figure 4. The so-called spider (left anterior oblique (LAO) is a typical angiographic projection plane displaying the course of the left anterior coronary artery and the diagonal branches (arrows) by a steep caudal angulation. Similar reconstruction can be performed with MDCT images accordingly. the degree of coronary artery stenoses remains problematic. Therefore, coronary CTA is currently not suited to determine the progression in patients with known CAD, typical angina, or obvious myocardial ischemia on exercise testing. These patients are better approached by cardiac catheter examination with the option to perform percutaneous coronary interventions in the same session (29). It should be considered when interpreting coronary CTA that details like collateral vessels, contrast runoff, and direction of filling of coronary arteries are not visualized by CTA. Finally, the hemodynamic relevance of coronary artery stenoses may not reliably be determined without wall motion analysis or myocardium perfusion data under rest and exercise. Further limitations have been seen in patients with a body mass index above 30 (26) and absolute arrhythmia (30), leading to a degradation of image quality in CTA by severe image noise and cardiac motion artifacts. The real strength of CTA is to display wall changes of the coronary arteries. Coronary calcifications can easily be assessed even without contrast media and represent an advanced stage of atherosclerosis. However, as different stages of coronary atherosclerosis may be present simultaneously, calcifications may also be associated with more early stages of coronary atherosclerosis. Therefore, the entire extent of coronary atherosclerosis will be underestimated by assessing coronary calcifications alone (31). With contrast enhancement, calcified as well as noncalcified lesions can completely be assessed by MDCT simultaneously. In patients with an acute coronary syndrome we have observed noncalcified plaques with irregular border and nonhomogeneous but low (20 40) Hounsfield

6 Past, Present, and Future of Cardiac CT 681 Figure 5. A: In patients with acute coronary syndrome, irregular, noncalcified plaques (arrow) may correspond to thrombus formation. B: Frequently, coronary stenosis (arrow) is seen at this particular region in catheter angiography. units (32). These soft tissue plaques in the coronary artery most likely correspond to intracoronary thrombus formation and will appear as stenosis in conventional angiography (Fig. 5). In asymptomatic patients and patients dying for other than cardiac reasons, well-defined noncalcified lesions are frequently observed in the coronary artery wall. The density of these plaques may vary in between 50 and 90 HU and may correspond to lipid and fibrous rich plaques, respectively (33) (Fig. 6). Commonly, spotty calcified lesions may be present in MDCT angiography studies that may correlate to minor wall changes in conventional coronary angiography only (3) (Fig. 7). However, it is known from pathologic studies that such calcified nodules may also be the source of unheralded plaque rupture and consecutive thrombosis and may lead to sudden coronary death in very rare cases (34). In patients with chronic and stable angina, calcified and noncalcified plaques are commonly found next to each other (35). Even in contrast-enhanced studies coronary calcifications can easily be detected and quantified because the density of calcium ( 350 HU) is beyond the density of contrast media in the coronary artery lumen ( HU) (16). However, because of partial-volume effects and the relation to the myocardium, it is difficult to quantify noncalcified plaques. Therefore, the optimal quantification algorithm for the assessment of atherosclerosis determined by contrast-enhanced MDCT is still under development. In patients with extensive coronary calcifications, noncalcified plaques are uncommon in coronary CTA, most likely because the previously described blooming artifact prevents their assessment. Therefore, and because the coronary artery stenosis cannot be reliably assessed (3), contrast-enhanced MDCT cannot be recommended in patients presenting with extensive coronary calcifications. SIGNS OF MYOCARDIAL INFARCTION Figure 6. The combination of extensive coronary calcifications and noncalcified plaques (arrow) may be the result of an ongoing plaque rupture and healing and may be found in patients with chronic and stable angina. However, the degree of stenosis is difficult to assess because of the exaggeration of calcium and the limitation in spatial resolution. In patients with known history of CAD, subendocardial or transmural myocardial infarction scars can frequently be identified as hypodense areas. Every region of the myocardium can be assigned to the territory of the coronary vessel supplying it. The left anterior descending coronary artery is supplying the anterior left ventricular wall with the roof of the left ventricle, the apex, the superior part of the septum, and the anterior papillary muscle. The posterior left ventricular wall and

7 682 Becker and Knez Figure 7. Significant coronary artery stenoses are highly unlikely if only spotty calcifications without noncalcified plaques are present (arrows). the posterior papillary muscle are supplied by the left circumflex coronary artery. The inferior left ventricular wall and the inferior part of the septum finally are supplied by the right coronary artery. Below the mitral valve all three territories can be identified in one axial slice. Later development of a subendocardial or transmural myocardial infarction may lead to a thinning of the myocardial wall or myocardial aneurysm, respectively. Due to myocardial dysfunction or atrial fibrillation, thrombus formation is likely to develop in the cardiac chambers and can be detected by CTA more superiorly than by transthoracic ultrasound (36). A late uptake of contrast media after first pass in the myocardium of patients after infarction has already been observed in CT, similar to MRI nearly two decades ago (36). To observe this contrast pattern of the myocardium, the optimal point of time for scanning may be between 10 and 40 minutes after first pass of the contrast media (37). It is rather likely that this kind of myocardial enhancement may correspond to interstitial uptake of contrast media within necrotic myocytes, six weeks to three months after onset. However, it is currently unclear if enhancing myocardium in CT corresponds to nonviable tissue like in MRI. Furthermore, para-cardial findings may frequently be observed in CTA studies and have to be reported. These findings may include lymph node enlargement, pulmonary nodules, infiltrates, and tumors (38), or even, quite commonly, esophageal hernias. These incidental findings should trigger an additional reconstruction with a larger field of view, or a more dedicated (CT) investigation should then be recommended. In patients with paroxysmal atrial fibrillation, radio frequency ablation of ectopic foci is a common interventional procedure. One possible complication of this intervention may be development of a stenosis of the pulmonary vein. The presence, morphology, scarring, and stenosing of the pulmonary veins can easily be assessed by CT (39). COMPARISON WITH ALTERNATIVE INVESTIGATION METHODS Coronary MDCT has been compared by cardiac catheter by a number of research groups (40 44). In summary, coronary MDCT angiography has mean sensitivity, specificity, and positive and negative predictive values for detecting significant coronary artery stenoses of 87%, 89%, 77%, and 97%, respectively (Table 2). Unfortunately, the findings of a significant stenosis detected by MDCT are neither specific for the site nor the degree of the stenosis, compared to cardiac catheter. However, all authors agreed upon the high negative predictive value of MDCT to rule out CAD. The current limitation of all the current studies is that MDCT has been tested so far in a heterogeneous group of patients with suspicion of CAD and established CAD with recurrent symptoms (high pretest probability of CAD). Because of the high negative value, coronary MDCT seems Table 2 Comparison Between MDCT Angiography and Cardiac Catheter for Detection Significant Coronary Artery Stenosis Reference Channels Number of patients Sensitivity Specificity Positive predictive value Negative predictive value Not assessable Nieman et al. (41) % 90% 81% 97% 30% Achenbach et al. (42) % 76% 59% 98% 32% Knez et al. (44) % 98% 85% 96% 6% Nieman et al. (40) % 86% 80% 97% 0% Ropers et al. (43) % 93% 79% 97% 12% Mean 87% 89% 77% 97% 18% Sum 278

8 Past, Present, and Future of Cardiac CT 683 Table 3 Pretest Likelihood of CAD in Percent in Symptomatic Patients According to Age and Sex (45) Non angina Age chest pain Atypical angina Typical angina Men Women Men Women Men Women Figure 8. Noncalcified lesions (arrow) may also be found in patients without any symptoms. From intracoronary ultrasound and pathological studies, these lesions may raise the suspicion of a coronary atheroma. However, the vulnerability of such plaques to rupture and to develop subsequent coronary thrombosis is currently unclear. to be ideally suited to rule out CAD, and therefore further studies are required to determine the accuracy in a patient cohort with an unknown history of CAD and ambiguous coronary symptoms or stress tests (low to moderate pretest probability of CAD, Table 3) (45). Cardiac catheter seems not to be suited to assess the entire extent of coronary atherosclerosis completely. Histological and intravascular ultrasound (IVUS) studies have shown that high atherosclerotic plaque burden can be found even in the absence of high-grade coronary stenoses on conventional coronary angiography. From the clinical standpoint, the correlation between acute cardiac events and high-grade coronary artery stenoses is only poor. It has been reported that 68% of the patients who received coronary angiography by incidence prior to their acute cardiac event did not show any significant coronary artery stenoses (46). In early stages of coronary atherosclerosis, the coronary arteries may undergo a process of positive remodeling that compensates for the coronary wall thickening and keeps the inner lumen of the vessel rather unchanged (47). The pathomechanism of this phenomenon is still unknown, but the underlying type of CAD may be a fibrous cap atheroma with accumulation of cholesterol. In case of inflammatory processes, the fibrous cap of an atheroma may become thinned, putting the plaque at risk for rupture and consecutive thrombosis (34) (Fig. 8). The current gold standard to assess coronary atherosclerosis in vivo is intracoronary ultrasound. Schroeder et al (48) reported that coronary lesions classified as soft, intermediate, and dense in intracoronary ultrasound correspond to coronary artery wall plaques with a density of 14 26, 91 21, and HU in MDCT, respectively. In general, patients after coronary intervention are difficult to follow by MDCT. Because of their disease, many of these patients have severe calcification, and coronary stents commonly implanted after angioplasty appear like highly dense calcified plaque that hinder the detection of in-stent stenoses. Recently, it has been reported in one case that measuring the contrast density curve behind a stent may allow demonstration of the success of a reintervention (49). For the morphological assessment of bypass graft patency with MDCT compared to cardiac catheter, Ropers et al (50) reported a sensitivity and specificity of 97% and 98%, respectively (Fig. 9). For the detection of bypass graft stenosis, the sensitivity and specificity were significantly lower, with 75% and 92%, respectively. Sequential scanning and administration of a small contrast bolus have already been shown to allow determination of a spiral CT flow index with a single-detector CT. This index agreed with angiographically determined Figure 9. Volume-rendering image of a bypass graft CT angiography. The left internal mammary artery (LIMA) to the left anterior descending coronary artery, the arterial bypass graft (A) to the circumflex coronary artery, and the venous bypass graft (V) to the diagonal branch are patent.

9 684 Becker and Knez coronary bypass flow in 85% of the grafts investigated (51). CONCLUSION AND FUTURE ASPECT The newest generation of MDCT now allows for consistently good image quality if regular sinus rhythm is present and the heart rate is in the range of beats/minute. Extensive calcifications and coronary stents may hinder the assessment of the coronary artery lumen and noncalcified atherosclerosis. In asymptomatic patients with intermediate risk of future cardiac events, nonenhanced low-dose MDCT scans may be performed to initiate therapeutic strategies for risk factor modification. However, the predictive value of calcified and noncalcified lesions for cardiac events as detected by MDCT angiography is currently unknown and requires further prospective cohort studies. Because of the high negative predictive value, coronary CTA may be justified in symptomatic patients with low to moderate pretest probability for CAD. In these patients, coronary macroangiopathy in the proximal and middle coronary artery segments can reliably be ruled out, and unnecessary cardiac catheter procedures may be avoided. In patients with an acute coronary syndrome, MDCT may be able to demonstrate the location and extent of a coronary thrombus and may be used in the future to guide coronary interventions. To overcome the current limitations of MDCT, there is need for improved temporal and spatial resolution. Currently, the temporal resolution is two times less than that in EBCT and the spatial resolution is five times less than that in cardiac catheter. The next generation of MDCT scanner may be available with higher temporal resolution and area detectors that would allow for imaging the heart with a quality close to that of the cardiac catheter. 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