Stephan Achenbach, MD

Plaque rupture is the main cause of acute coronary syndromes, which are associated with high mortality and morbidity. The prevalence of plaque rupture in acute coronary syndrome is more than 70%.1 Rupture-prone plaques are characterized by a large core of extracellular lipid with a thin fibrous cap (Figure 1). Inflammation, particularly in the plaque shoulder, causes the fibrous cap to thin and results in disruption of the atherosclerotic plaque. When the fibrous cap ruptures, thrombogenic substances are exposed to the blood. The developing thrombus, which consists of platelet aggregates, leukocytes, fibrin, and red blood cells, obstructs the vessel, causing myocardial infarction or stroke.

Plaque rupture is seen as a morphologic lumen abnormality on many different imaging modalities. Intravascular ultrasound,2 angioscopy,3 and optical coherence tomography (OCT)4 are all popular tools for detecting plaque rupture. Early detection of vulnerable plaque, including rupture-prone plaque, is necessary to identify vulnerable patients. Both IVUS and angioscopy have detected multiple plaque rupture in patients with acute coronary syndrome.2,3 The development of virtual histology IVUS and integrated backscatter IVUS has improved plaque characterization significantly,5,6 as has the advent of techniques such as thermography, palpography, and elastography.

Multislice CT and MRI have been shown to visualize the coronary vasculature with high accuracy compared with invasive angiography.7,8 MSCT is also able to perform plaque characterization.7,9,10 The spatial resolution of MSCT was previously poor compared with other invasive plaque imaging devices, but the latest generation of equipment, including dual-source CT, has changed this. The spatial resolution of DSCT can reach 0.3 to 0.4 mm.11

Both noninvasive and invasive modalities can consequently be used to detect plaque rupture and to monitor the healing process of ruptured plaques.

Coronary angiography, which is essentially luminography, can give only limited information on vessel wall pathology. A retrospective analysis of angiography showed that two-thirds of patients with acute myocardial infarction had a previous stenosis ( < 50% occlusion) at the site of the culprit lesion before plaque rupture.12 When the plaque is ruptured without occlusion, coronary angiography depicts the culprit lesion as ulceration. Angiography cannot identify these sites as vulnerable, however, or monitor the healing process.

Gray-scale IVUS can detect major features of ruptured plaque, such as ulceration, cavity, intimal flap, thrombus, and aneurysm (Figure 2).13 It can also partially detect the fibrous cap.13 Plaques identified on IVUS as having a larger echolucent area or thinner fibrous plaque appear to be prone to rupture.14

Spectral analysis of the radiofrequency component of backscatter IVUS, or virtual histology IVUS, has been developed for real-time in vivo plaque classification.5 This technique classifies fibrofatty plaque, fibrous plaque, necrotic core, and dense core from histologic data (Figure 3A). Which component contributes most to the plaque's vulnerability remains controversial. Thin-cap fibroatheroma lesions are the most prevalent substrate of plaque rupture. Research has shown that the percentage volume of atheroma and the mean percentage of necrotic core in stable patients and in patients with acute coronary syndrome are no different.15

Integrated backscatter IVUS is another new technique based on RF data analysis that is able to evaluate a lipid core accurately and quantitatively (Figure 3C).5,6 Integrated backscatter values for plaque components have been described as follows:16

intimal hyperplasia or lipid core: > -73 and lesser than or equal to -63

fibrous tissue: > -63 and lesser than or equal to -55

mixed lesions: > -55 and lesser than or equal to -30

calcification: > -30 and lesser than or equal to -23

When using either virtual histology or integrated backscatter IVUS, the lumen border should be assessed on gray-scale images (3B and 3D).

Lesions causing acute coronary syndrome are typically seen on angioscopy as yellow plaque with an irregular surface covered by a thrombus.3,10 The yellow color represents the lipid-rich core and thin fibrous cap, and the intensity of yellow color reflects vulnerability (Figure 4).10 Asakura et al found the prevalence of yellow plaques and thrombus in lesions causing acute coronary syndrome to be 90% and 81%, respectively.3 Patients with acute coronary syndrome had widespread disease in all three major coronary arteries and multiple yellow intact plaques.3

OCT is a high-resolution imaging method with 10-nm spatial resolution.4 There is good correlation between OCT and histologic measurements of the fibrous cap.17 OCT can identify mural and luminal morphologies, including lumen dimensions, plaques, thrombi, dissections, and tissue flaps.4 It can also detect ruptured plaque.18 The limited penetration of OCT (1 to 2 mm) might make it difficult to image an entire vulnerable plaque using this technique.

MSCT can detect coronary stenosis with high accuracy when compared with invasive coronary angiography.7 One of the main strengths of MSCT is its extremely high negative predictive value.7 A major weakness, however, is the difficulty of interpreting plaque characteristics and distribution from gray-scale CT. CT number (defined as water = 0 and air = -1000) can be used for tissue characterization, but region of interest or profile curve was not comprehensive for the analysis. To counter this, we developed a new method of plaque color mapping (Plaque Map) that is based on CT number (Figure 5).9,10

MSCT is regarded as a valuable tool for detecting acute coronary syndrome in the emergency room.10 Limitations include the use of contrast media and exposure to ionizing radiation.

The advent of DSCT may provide a more precise noninvasive way of examining coronary plaque.11 Current DSCT systems are equipped with two x-ray tubes mounted at 90 degrees to one another. Beta blockers are not required to control heart rate, given the improved temporal resolution (83 msec). Spatial resolution of DSCT is 0.3 to 0.4 mm, while that of 64-slice MSCT is 0.5 mm at best. DSCT can demonstrate ruptured plaque with lipid pool.19 The benefits of a dual-energy setup for detecting plaque should be the subject of future study.

Noninvasive detection of coronary stenosis by MR coronary angiography is also possible. A patient-based analysis performed by Sakuma et al found the sensitivity, specificity, positive predictive values, and negative predictive values compared with x-ray coronary angiography to be 82%, 90%, 88%, and 86%, respectively.8 Diagnostic accuracy in the individual segments were 78%, 96%, 69%, and 98%, respectively.8 MR coronary angiography can detect morphologic abnormalities of silent plaque rupture, such as double lumen and positive remodeling (Figure 6).20 MRA can potentially depict atherothrombotic plaque components, including lipid, fibrous tissue, calcium, and thrombus. Further improvements to temporal and spatial resolution are needed, though, before MRA can be used to detect coronary artery plaque.

Sudden coronary occlusion leading to acute coronary syndrome is often preceded by a period of plaque instability and thrombus formation. This may start days or weeks before symptomatic onset.21 We have devised a strategy for detecting coronary artery plaque ruptures in high-risk patients using DSCT. The culprit lesion itself should be treated invasively. Ruptured plaque at nonculprit lesions should be treated with a plaque stabilization therapy such as statin drugs, clopidogrel, or aspirin. Follow-up should be performed on DSCT (Figure 7).22

Rioufol et al treated 14 patients with statin and antiplatelet agents for 28 lesions of spontaneous coronary plaque rupture without significant stenosis detected by IVUS. They found that half of the lesions were healed or the grade of stenosis was diminished for two-year follow-up. Spontaneous coronary plaque rupture without significant stenosis, detected on first acute coronary syndrome diagnosis, healed without significant plaque modification in 50% of cases with medication.23

A two-year follow-up period was used for this study.

The combination of noninvasive and invasive imaging devices may provide the optimal strategy for studying the pathogenesis of acute coronary syndrome and applying the best therapy to patients.

Assisting in the preparation of this manuscript were Dr. Christoph D. Garlichs, Dr. Dieter Ropers, Dr. Alexander Kuhlmann, Dr. Ulrike Ropers, and Prof. Dr. Werner G. Daniel from the department of cardiology, University of Erlangen-Nuernberg; Dr. Tilman Rau, Dr. David Lukas Wachter, and Dr. Valentina Campean from the department of pathology, University of Erlangen-Nuernberg; Dr. Atsushi Hirayama and Dr. Kazuhisa Kodama from the cardiovascular division, Osaka Police Hospital; and Prof. Masatsugu Hori from the department of cardiovascular medicine, Osaka University Graduate School of Medicine, Suita.

Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003;108(14):1664-1672.

Hong MK, Mintz GS, Lee CW, et al. The site of plaque rupture in native coronary arteries; a three-vessel intravascular ultrasound analysis. J Am College Cardiol 2005;46(2):261-265.

Asakura M, Ueda Y, Yamaguchi O, et al. Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. J Am College Cardiol 2001;37(5):1284-1288.

Gerckens U, Buellesfeld L, McNamara E, Grube E. Optical coherence tomography (OCT). Potential of a new high-resolution intracoronary imaging technique. Herz 2003;28(6):496-500.

Nair A, Kuban BD, Tuzcu EM, et al. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002;106(17):2200-2206.

Komiyama N, Berry GJ, Kolz ML, et al. Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries. Am Heart J 2000;140(4):565-574.

Achenbach S. Computed tomography coronary angiography. J Am College Cardiol 2006;48(10):1919-1928.

Sakuma H, Ichikawa Y, Chino S, et al. Detection of coronary artery stenosis with whole-heart coronary magnetic resonance angiography. J Am College Cardiol 2006;48(10):1946-1950.

Komatsu S, Hirayama A, Omori Y, et al. Detection of coronary plaque by computed tomography with the novel plaque analysis system, 'Plaque Map,' and comparison with intravascular ultrasound and angioscopy. Circ J 2005;69(1):72-77.

Komatsu S, Ueda Y, Omori Y, et al. Diagnosis of vulnerable plaque and vulnerable patient by coronary angioscopy and multi-detector row computed tomography-from invasive to non-invasive plaque imaging. Vascular Disease Prevention 2006;3(4):319-325.

Achenbach S, Ropers D, Kuettner A, et al. Contrast-enhanced coronary artery visualization by dual-source computed tomography-initial experience. Europ J Radiol 2006;57(3):331-335.

Ambrose JA, Winters SL, Stern A, et al. Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am College Cardiol 1985;5(3):609-616.

Jensen LO, Mintz GS, Carlier SG, et al. Intravascular ultrasound assessment of fibrous cap remnants after coronary plaque rupture. Am Heart J 2006;152(2):327-332.

Ge J, Chirillo F, Schwedtmann J, et al. Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound. Heart 1999;81(6):621-627.

Rodriguez-Granillo GA, Garcia-Garcia HM, McFadden EP, et al. In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis. J Am College Cardiol 2005;46(11):2038-2042.

Kawasaki M, Takatsu H, Noda T, et al. In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings. Circulation 2002;105(21):2487-2492.

Kume T, Akasaka T, Kawamoto T, et al. Measurement of the thickness of the fibrous cap by optical coherence tomography. Am Heart J 2006;152(4):755.e1-4.

MacNeill BD, Jang IK, Bouma BE, et al. Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. J Am College Cardiol 2004;44(5):972-979.

Komatsu S, Daniel WG, Achenbach S. Demonstration of clinically silent plaque rupture by dual-source computed tomography. Eur Heart J 2007; February 6 [E-pub ahead of print].

Komatsu S, Murakawa T, Shinohe T, et al. Detection of silently ruptured plaque by coronary magnetic resonance. Int J Cardiol 2006;113(3):430-431.

Rittersma SZ, van der Wal AC, Koch KT, et al. Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: a pathological thrombectomy study in primary percutaneous coonary intervention. Circulation 2005;111(9):1160-1165.

Articles

Plaque rupture is the main cause of acute coronary syndromes, which are associated with high mortality and morbidity. The prevalence of plaque rupture in acute coronary syndrome is more than 70%.1 Rupture-prone plaques are characterized by a large core of extracellular lipid with a thin fibrous cap (Figure 1). Inflammation, particularly in the plaque shoulder, causes the fibrous cap to thin and results in disruption of the atherosclerotic plaque.

Vessel imagers focus on plaque characterization

Acute coronary syndromes, especially acute myocardial infarction and sudden cardiac death, are most often caused by the rupture or erosion of coronary atherosclerotic plaques.1 The plaque itself does not have to be associated with lumen narrowing. Coronary blood flow may be obstructed by a thrombus forming at the site of plaque rupture. In fact, the majority of lesions that cause acute coronary syndromes are not stenotic before the event occurs.

Patients are frequently entirely asymptomatic up to their first coronary artery disease event, which may be sudden death. Identification of patients at risk of acute coronary syndromes is consequently difficult. Atherosclerotic risk factors such as hypertension, family history, diabetes, elevated cholesterol, and smoking have been used to identify patients at risk, but their predictive accuracy is limited.

The continuous improvement of invasive and noninvasive imaging technology has made it possible to visualize coronary atherosclerotic plaques directly. Imaging-led detection, quantification, and characterization of coronary atherosclerotic plaque may potentially be an accurate way of detecting high-risk patients requiring pharmacological intervention. Imaging may also be able to single out individual atherosclerotic plaques that pose a very high risk (vulnerable plaques) and may be amenable to local treatment.

Invasive methods for visualizing coronary atherosclerotic plaque include intravascular ultrasound, optical coherence tomography, and angioscopy (Figure 1). Their invasiveness and high cost and the potential risk of complications should restrict these methods to selected patient groups. MRI has demonstrated its potential to visualize, quantify, and characterize atherosclerotic plaque in some of the larger arteries, such as the aorta and carotids. Limited spatial resolution, however, makes coronary MRI extremely challenging, and the modality is currently unable to visualize coronary artery plaque reliably.2

Limited spatial and temporal resolution precluded CT imaging of the coronary arteries for many years. The only exception was coronary artery calcification assessment (Figure 2) using electron-beam CT. EBCT scanners were designed specifically for cardiac imaging, providing a temporal resolution of 100 msec. The presence and amount of coronary calcification, as assessed by EBCT, has been shown to be a very strong predictor of future cardiovascular disease events.3

Several prospective studies have also demonstrated convincing evidence that coronary calcium has stronger predictive power than the assessment of cardiovascular risk factors. Not all coronary atherosclerotic plaques contain calcium, though, and the extent of calcification is not related to plaque stability or vulnerability. EBCT's relatively low spatial resolution and high image noise make the modality unsuitable for reliable assessment of noncalcified plaque components.

The introduction of multislice CT scanners offering considerably better temporal resolution than early-generation spiral CT technology has made it possible to perform cardiac CT. The coronary arteries can be visualized reliably with 16- and especially 64-slice CT, given certain prerequisites: Patients need to have a regular and preferably low heart rate (below 65 bpm), they should not be too obese, and they need to cope with breath-hold acquisitions of approximately 10 to 20 seconds duration.

The initial focus of coronary imaging using 16- and 64-slice CT has been contrast-enhanced detection of coronary artery stenoses. This proved to be reasonably accurate with sufficient image quality. Initial investigators also recognized the potential of MSCT to visualize coronary atherosclerotic lesions in these contrast-enhanced scans, whether or not they were associated with significant stenosis.4,5 MSCT can detect calcified and noncalcified plaque components (Figure 3). The potential of this information for risk stratification has sparked intense interest in plaque imaging to identify patients at high risk of a coronary event.

Several studies have evaluated the accuracy of 16- and 64-slice CT to detect the presence of nonstenotic coronary atherosclerotic plaque. These investigations validated MSCT against intracoronary ultrasound and assessed the ability of MSCT to detect plaque in certain coronary artery segments. Detection of single coronary plaques was not considered.

Schoenhagen et al reported an accuracy of 80% for the detection of noncalcified plaque with 16-slice CT.6 Achenbach et al found a sensitivity of 82% and specificity of 88% in 22 patients, though this high sensitivity was driven by the detection of calcified plaque. Segments with entirely noncalcified plaque were identified with a sensitivity of only 53%.7 Leber et al reported a sensitivity and specificity of 84% and 91%, respectively, for the detection of nonobstructive plaque by 16-slice CT in comparison to intravascular ultrasound.8 This same group also studied 19 patients on 64-slice CT and found sensitivities of 83% for the detection of noncalcified plaque, 94% for the detection of mixed plaque, and 95% for the detection of calcified plaque. Specificity was 95%.9

Van Mieghem et al demonstrated the influence of plaque size on sensitivity using 64-slice CT. They reported 76% sensitivity for the detection of lesions greater than 2 mm and 60% sensitivity for lesions smaller than 1 mm. Overall, MSCT yielded a sensitivity of 86% in this analysis of 67 coronary arteries and a specificity of 69%.10

The reported accuracies certainly sound impressive. It is important to note, however, that these results were obtained by experienced investigators in selected groups of patients, all of whom had coronary vessels large enough for study by the relatively bulky intravascular ultrasound catheters used as a reference standard. The true accuracy of MSCT in everyday scans is difficult to assess, but it is likely to be lower than that reported in the scientific studies. For example, motion artifacts mimicking the appearance of noncalcified plaque can lead to false-positive diagnoses. On the other hand, improvements in CT technology, such as the introduction of dual-source scanners, should make plaque detection more reliable in the future.11

The small size of coronary arteries means that CT-based plaque measurements are challenging. Moselewski et al found a relatively poor correlation coefficient of r2 = 0.55 for the measurement of cross-sectional areas of noncalcified coronary plaque by 16-slice MSCT compared with intravascular ultrasound.12

For plaque volumes, Achenbach et al reported a moderately high correlation coefficient of r2 = 0.8 when comparing plaque volume per coronary segment between 16-slice MSCT and intravascular ultrasound.7 In a study performed using 64-slice CT, Leber et al found a significant and moderately close correlation for plaque volumes per 3-mm coronary artery section, with a correlation coefficient of r2 = 0.83. But CT significantly underestimated plaque burden in this study. The mean interobserver variability for measuring plaque volumes was 37%, illustrating the difficulty of measuring these tiny structures with CT.9

Several factors are assumed to influence the vulnerability of a coronary atherosclerotic plaque. These include macrophage content and the thickness of the protective fibrous cap. Fibrous caps thinner than 65 micron are assumed to imply increased risk of plaque rupture, but dimensions in this range cannot be measured by coronary CT.

The lipid content of atherosclerotic lesions is also believed to be associated with their risk of rupturing. Several investigators have explored the ability of MSCT to differentiate lipid-rich from fibrous lesions by measuring CT attenuation values within the plaque. It has consistently been shown that plaques with a lipid-rich appearance on intravascular ultrasound have lower CT attenuation values than plaques with a fibrous appearance (see table).13-18

CT attenuation values vary widely from one study to the next, however. Significant variation is also observed within plaques of a similar type in the same study.18 So while mean attenuation values may differ between plaque types in a large sample, characterization of a single plaque based on measured CT attenuation alone does not seem possible. It has additionally been shown that external factors, such as contrast concentration in the coronary artery lumen, have a strong influence on CT attenuation values measured within coronary atherosclerotic plaques.19,20 This further complicates CT-based plaque characterization. The necessary standardization of acquisition parameters will be extremely difficult to achieve.

Despite the tremendous wealth of data on the prognostic significance of coronary calcium, information on the clinical meaning of noncalcified, nonobstructive plaque detected by CT is not available. Three retrospective studies in small patient groups (23 to 42 patients) have shown that noncalcified plaque is more prevalent in patients with acute coronary syndromes than in patients with stable coronary artery disease.21-23

No prospective trials have been conducted yet, and the predictive power of noncalcified plaque regarding the occurrence of future cardiac events is unknown. Noncalcified plaques are, in fact, detected frequently in contrast-enhanced data sets acquired for coronary CT angiography.24 It would be easy to assume that an individual whose CT data show the presence of noncalcified coronary plaque is at an increased risk for future coronary events. Yet the exact meaning of this finding is not currently known. The less-than-perfect sensitivity and specificity of MSCT, especially in data sets of suboptimal image quality, also needs to be taken into account.

So what are the current clinical implications of noncalcified plaque imaging by MSCT? The relative paucity of hard data means that any conclusion-including this one-will be subject to personal opinion. It is clearly not justifiable to perform CT coronary angiography in asymptomatic individuals for the mere purpose of risk stratification. This investigation requires the use of a contrast agent and substantial exposure to ionizing radiation. The accuracy of plaque detection is also insufficient for screening purposes, and prognostic data providing guidance on the consequences of a positive scan are also unavailable.

It is much more difficult to recommend what should happen when nonobstructive plaque is detected as an incidental finding during scheduled CT coronary angiography of a symptomatic patient. The plaque's presence should probably be reported, along with a measure of confidence of this finding.

Decisions on the administration of lipid-lowering drugs must be made on a case-by-case basis, taking account of clinical circumstances. Recommendations on the management of patients with a high clinical risk profile, but no plaque detectable on CT, also cannot be taken out of their clinical context.

Prospective data on the significance of these findings are not currently available.

PROF. DR. ACHENBACH is a senior consultant in the department of internal medicine II (cardiology) at the University of Erlangen-Nuremberg in Germany.

Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (I). NEJM 1992;326(4):242-250.

Fayad ZA, Fuster V, Nikolaou K, Becker C. Computed tomography and magnetic resonance imaging for noninvasive coronary angiography and plaque imaging: current and potential future concepts. Circulation 2002;106(15):2026-2034.

Bellasi A, Raggi P. Diagnostic and prognostic value of coronary artery calcium screening. Curr Opin Cardiol 2005;20(5):375-380.

Schroeder S, Kopp AF, Baumbach A, et al. Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. J Am College Cardiol 2001;37(5):1430-1435.

Becker CR, Knez A, Ohnesorge B, et al. Imaging of noncalcified coronary plaques using helical CT with retrospective ECG gating. AJR 2000;175(2):423-424.

Schoenhagen P, Tuzcu EM, Stillman AE, et al. Non-invasive assessment of plaque morphology and remodeling in mildly stenotic coronary artery segments: comparison of 16-slice computed tomography and intravascular ultrasound. Coron Artery Dis 2003;14(6):459-462.

Achenbach S, Moselewski F, Ropers D, et al. Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography: a segment-based comparison with intravascular ultrasound. Circulation 2004;109(1):14-17.

Leber AW, Knez A, von Ziegler F, et al. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am College Cardiol 2005;46(1):147-154.

Leber AW, Becker A, Knez A, et al. Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound. J Am College Cardiol 2006;47:672-677.

Van Mieghem CA, McFadden EP, de Feyter PJ, et al. Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS). J Am College Cardiol 2006;47(6):1134-1142.

Achenbach S, Ropers D, Kuettner A, et al. Contrast enhanced coronary artery visualization by dual-source computed tomography - initial experience. Europ J Radiol 2006;57(3):331-335.

Moselewski F, Ropers D, Pohle K, et al. Comparison of measurement of cross-sectional coronary atherosclerotic plaque and vessel areas by 16-slice multidetector computed tomography versus intravascular ultrasound. Am J Cardiol 2004;94(10):1294-1297.

Estes JM, Quist WC, Lo Gerfo FW, Costello P. Noninvasive characterization of plaque morphology using helical computed tomography. J Cardiovasc Surg (Torino) 1998;39(5):527-534.

Schroeder S, Kuettner A, Leitritz M, et al. Reliability of differentiating human coronary plaque morphology using contrast-enhanced multislice spiral computed tomography: a comparison with histology. JCAT 2004;28(4):449-454.

Becker CR, Nikolaou K, Muders M, et al. Ex vivo coronary atherosclerotic plaque characterization with multi-detector-row CT. Europ Radiol 2003;13(9):2094-2098.

Leber AW, Knez A, Becker A, et al. Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am College Cardiol 2004;43(7):1241-1247.

Carrascosa PM, Capunay CM, Garcia-Merletti P, et al. Characterization of coronary atherosclerotic plaques by multidetector computed tomography. Am J Cardiol 2006;97(5):598-602.

Pohle K, Achenbach S, MacNeill B, et al. Characterization of noncalcified coronary atherosclerotic plaque by multi-detector row CT: Comparison to IVUS. Atherosclerosis 2007;190(1):174-180.

Schroeder S, Flohr T, Kopp AF, et al. Accuracy of density measurements within plaques located in artificial coronary arteries by X-ray multislice CT: results of a phantom study. JCAT 2001;25(6):900-906.

Cademartiri F, Mollet NR, Runza G, et al. Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography. Europ Radiol 2005;15(7):1426-1431.

Leber AW, Knez A, White CW, et al. Composition of coronary atherosclerotic plaques in patients with acute myocardial infarction and stable angina pectoris determined by contrast-enhanced multislice computed tomography. Am J Cardiol 2003;91(6):714-718.

Inoue F, Sato Y, Matsumoto N, et al. Evaluation of plaque texture by means of multislice computed tomography in patients with acute coronary syndrome and stable angina. Circ J 2004;68(9):840-844.

Hoffmann U, Moselewski F, Nieman K, et al. Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am College Cardiol 2006;47(8):1655-1662.

Hausleiter J, Meyer T, Hadamitzky M, et al. Prevalence of noncalcified coronary plaques by 64-slice computed tomography in patients with an intermediate risk for significant coronary artery disease. J Am College Cardiol 2006;48(2):312-318.

Acute coronary syndromes, especially acute myocardial infarction and sudden cardiac death, are most often caused by the rupture or erosion of coronary atherosclerotic plaques. The plaque itself does not have to be associated with lumen narrowing.

Multislice CT bolsters coronary plaque analysis

I have been performing CT angiography of the coronary arteries since 1993, mainly at the University of Erlangen-Nuremberg. Collaboration with radiologists has been good from the start. I know of several other hospitals in Germany where cardiac CTA works similarly well, but I also know of many where it does not. Why the difference?

Turf battles over cardiac CTA have been caused by two main issues. The first is ownership. Put simply, radiologists have the equipment and cardiologists have the patients. Cardiologists may be unwilling to send their patients to radiology for a diagnostic examination. They may have concerns over scan quality, especially if the practitioner is not thoroughly trained in cardiac CT. They may also want to keep the business for themselves, which they can do by performing cardiac catheterization. But cardiologists may not be able to justify buying a high-end CT scanner themselves.

The second issue, relevant in many countries, is the question of who may legally operate a CT scanner. A radiology qualification or CT certification may be necessary. Dedicated licenses-for example, for radiation protection-may be required as well. Cardiologists may have experience in x-ray-based imaging, but their licenses may not include CT.

A third issue is emerging as well. If you reconstruct the data from cardiac CT a little differently, you can also see parts of the lung. Some say that if you can see the lung, then you should check for asymptomatic pathology. This is a reasonable point of view. Of course, cardiologists are not trained to read the lung, so radiologists then say that they should be doing the cardiac CTA because they are better trained to spot these incidental findings.

This matter is unresolved at the moment. It is likely to increase in importance as cardiac CTA enters routine clinical practice. Some debate remains about the need for practitioners to look at the lung when performing a cardiac scan. After all, cardiologists use ultrasound to examine the heart all the time. In theory, if they angled the transducer a little differently, they could see the liver. No one is asking cardiologists to specifically look at the liver during an echocardiography examination.

We have managed to avoid starting a turf war over cardiac CTA at Erlangen. Cardiology and radiology each have their own CT scanners, which eases the ownership problem. Although cardiology paid for its own CT equipment, and the scanner is operated by cardiologists, the license is held by the chief of radiology. If a patient walks into the radiology department and wants a cardiac CT, he or she can get cardiac CT from the radiology department. If the patient walks into the cardiology department, he or she can get that scan from us. If the radiologist looking at the heart has a problem, I can look at the scan too. The radiologists look at the scans with us to analyze incidental findings.

I have observed that the turf war over cardiac CT has died down a bit in many centers over the past few years. Centers setting up programs now are thinking more about the practical and economic aspects and realizing that it is better to collaborate from the beginning. Radiologists and cardiologists now often visit Erlangen together to see how we are using our CT scanner for cardiac work. We are also seeing large cardiology groups that want to buy a scanner themselves and then hire a radiologist.

Any group setting up a cardiac CT program needs to bring cardiologists and radiologists together somehow. Staff should be trained properly from the outset. Radiologists should be willing to learn more about the heart, and cardiologists should be willing to learn about tomographic imaging, contrast, and radiation protection. Attending specialty meetings such as the European Society of Cardiology's annual meeting, the European Congress of Radiology, or dedicated cardiac CT courses is a good way to do this. I don't think it makes a great deal of difference where you start, but you have to be willing to make this investment in learning.

Cardiac CTA calls for close collaboration from day one

The first announcements came at the 2003 RSNA meeting, informing the radiology community that 64-slice CT would soon be available for clinical practice. Initial site installations by Siemens Medical Solutions and GE Healthcare began shortly after, in late spring and early summer of 2004. The introduction of this new technology came as a surprise to many, since 16-slice CT had been widely available only since 2002.

Radiologists began to wonder if this new generation of scanners would be truly revolutionary or simply evolutionary. Our early experiences have encouraged us to examine the directions we think 64-slice CT will take in the near term. Although all the major CT vendors-GE, Philips, Siemens, and Toshiba-have installed at least one 64-slice CT scanner, we have used only the Siemens Sensation 64 scanner, and our discussion of technical features will focus on that system. Our review of the clinical potential and applications of 64-slice CT technology, however, is not vendor-specific.

The introduction of 16-slice CT addressed many of the challenges and limitations present in quadslice CT scanning. Sixteen-slice CT provided for routine subsecond scan rotation times (usually around 0.5 sec), routine submillimeter slice acquisition parameters (usually 0.5 to 0.75 mm), and true isotropic data sets. Combining these scanning parameters with the ability to reduce long acquisition times and problems with tube heating meant that multislice CT had met most of the challenges of true CT volume imaging. Not surprisingly, clinical applications also evolved to take advantage of these technical advancements in three main areas:

- Classic applications such as evaluation of the liver, pancreas, and kidneys could be done with improved scan protocols, leading to better detection of disease, more accurate staging, and improved patient management.

- Vascular applications commonly referred to as CT angiography could be expanded now that true isotropic volume acquisitions were possible, overcoming the limitations of quadslice CT.

- New applications such as coronary CT angiography and peripheral runoff studies, although attempted at select institutions with quadslice CT, became practical routine applications.

Although 16-slice CT soon became the accepted gold standard for CT imaging, the ability to combine fast acquisition with properly timed injection rates and isotropic resolution still faced certain inherent limitations, especially with applications such as coronary angiography or functional imaging. Thus, researchers immediately began to look to the next generation of scanners, which could improve on experience with 16-slice CT.

In times of rapid changes in scanner technology, it is not surprising that each manufacturer regards its product as a superior one that will provide the user with the optimal scanning environment. Two of the leading CT scanning vendors for the past two decades, GE and Siemens, have introduced and installed 64-slice scanners for clinical use in the U.S. and, in Siemens' case, Europe and Japan. Although both machines are defined in the generic sense as 64-slice scanners, the vendors point out some important differences that they consider key differentiators.

Since the number of installations is small and the winner or winners cannot be determined, we asked both vendors to define the attributes of their product from a technical perspective. We will not try to compare claims of superiority, but hope to clarify the performance of each system and let the test of time show the advantages. As noted, these parameters are provided by the manufacturers and not the authors.

The Siemens Sensation 64 scanner, through its new z-sampling technology, delivers < 0.4-mm isotropic resolution for pitch values up to 1.5 in routine studies, even at isocenter, without spiral artifacts. This is achievable at a coverage speed of up to 87 mm/sec. This speed is calculated using the best resolution, which is 0.4 mm, and by setting pitch to 1.5 and the feed/second at 0.33-sec, rotation time = 1.5 x 19.2/0.33 = 87 mm/sec. The 19.2 mm is calculated by a feed per rotation of 32 x 0.6 mm. Although the Siemens 64-slice system has 32 detector elements in the center of the assembly, it has a 64-slice data acquisition system behind those detectors. The new z-sampling scheme and this detector assembly enable the simultaneous readout of two projections. The detector readout of two times 32 slices for every viewing angle enables full 64-slice acquisition. The scanner has a rotation speed of 0.33 sec, which provides unique protocol possibilities that will have an impact across a range of applications.

The GE LightSpeed VCT scanner has 64 rows of 0.625-mm detectors. At a pitch of just under 1 (63/64 = 0.984), with 40 mm of full-resolution coverage, it will scan 39.38 mm per rotation with the same or better z-axis resolution as the LightSpeed 16, 0.36 mm as measured by IMPACT. The GE detector elements are essentially square (0.625 x 0.6 mm) at isocenter, and the scanner is intrinsically isotropic. LightSpeed VCT will have an optional 0.35-sec rotation. GE also claims that in cardiac-gated mode, the scanner can do a 12 to 15-cm cardiac acquisition in five to six seconds. On the LightSpeed VCT, in high-resolution mode (64 x 0.625 mm), the anatomic coverage is 40 mm per rotation. At 1:1 pitch and 0.37-sec rotation, this corresponds to 108 mm/sec.

Now that we have obtained these amazing scan parameters, the question becomes what the impact will be in clinical practice. We all experienced the revolutionary changes of 16-slice CT over quadslice but wonder whether 64-slice CT will spark a similar revolution. Although we are very early in the game, the answer is a resounding yes, no, and maybe. The path of 16-slice CT offers insight into the possible path of 64-slice CT.

There is little doubt that 16-slice CT is an impressive piece of technology. Even though it was developed and introduced into clinical practice only two years ago, most institutions have seen a double-digit growth of body CT scanning because of its capabilities.

At Johns Hopkins, our body CT scan volume increased over 20% in the last fiscal year, but the 3D/CTA volumes increased more than 40%. These numbers are not surprising to anyone who has witnessed CT's transformation into the physical examination of the 21st century. CT has replaced a range of other studies and is rapidly becoming the primary noninvasive vascular imaging study. But we recognize that as good as 16-slice CT is, definite limitations persist. These include speed of acquisition, image resolution, and image noise and artifact for select applications. This is where 64 will become the de facto standard. Yet most institutions will likely use a combination of 16- and 64-slice scanners in their clinical practice.

No doubt, the most exciting application for 64-slice CT is coronary artery and cardiac imaging. With 16-slice CT, we began doing coronary CTA. But even with the use of beta blockers, the study success rate was adequate in only 80% of patients. The problems related to a combination of acquisition time and slice thickness, or what might be described as temporal and spatial resolution. With 64-slice CT, we are able to use cardiac gating and acquire a data set in as little as five to seven seconds, or a few heartbeats.

The ability to visualize the coronary arteries in unprecedented detail without motion artifact is the promise that 64-slice CT brings. Acquisition of 4D data provides studies of cardiac motion, cardiac function, and valve function. The use of fast scanning also allows sequential imaging of the myocardium to look for perfusion changes of early myocardial infarction. Many centers are beginning to develop protocols to look at acute coronary syndrome with 64-slice CT as the initial, and potentially only, exam. If successful, this approach will revolutionize care in the emergency room and lead to changes in the management algorithm for millions of ER patients every year.

Vascular imaging beyond the heart and coronary arteries will also benefit from 64-slice technology. Two specific applications are evaluation of the carotid artery and peripheral runoff studies. Both have faced limitations with prior technologies. Carotid imaging-when done from the aortic arch through the base of the skull or even through the circle of Willis-was often degraded by rapid venous contamination. Although the use of editing tools, clip planes, and volume rendering made these studies possible, 64-slice technology will allow an acquisition fast enough to avoid venous contamination.

In peripheral studies, two issues are the timing of the bolus transit and whether this should be done at the aorta or popliteal vessels. Both strategies have faced limitations. With the 64-slice scanner, the scan can be monitored until contrast appears in the lower legs, triggering acquisition. This will potentially limit venous contamination caused by scanning too late or inadequate enhancement due to scanning too early.

Similarly, a 64-slice system with higher spatial and temporal resolution will no doubt provide better data sets for routine imaging, ranging from evaluation of suspected liver metastases and staging of renal tumors to detection of pulmonary embolism. Yet 16-slice CT is so good that improvement in sensitivity and specificity might be limited if a traditional approach accompanies the shift to 64-slice imaging. We expect 64-slice CT to result in a new paradigm. We will move from purely structural imaging of normal anatomy and pathology to a more functional approach. Functional or physiologic imaging not only detects discrete lesions per se but also recognizes increases or decreases in vascular flow.

To date, most functional CT imaging has targeted the brain, with varying success. In some institutions, it is a critical part of stroke imaging. But organ enhancement often is a result of a range of factors that go far beyond the presence of a discrete lesion or vascular invasion by a mass. Rather, functional flow changes may occur on a microscopic level where no detectable tumor mass is seen. Early changes on a vascular level due to tumor may result in changes in perfusion that could suggest the presence of early disease. Previously, articles have suggested that changes in liver perfusion may be a good indicator of future metastatic disease. In addition, flow-related changes in a kidney or liver mass may help define the degree of angiogenesis in a tumor and guide surgical management. We also think that perfusion may be a way to look for early pulmonary embolism, taking advantage of both visualization of the pulmonary arteries and lung perfusion, thereby matching some of the attributes of traditional lung perfusion scanning with nuclear medicine studies.

With development of new agents for PET scanning or even with current agents, a combination of perfusion mapping may go a long way to support continuing understanding of tumor activity and recurrence patterns using PET.

The introduction of 64-slice CT could suggest that all of our limitations with CT have been solved, and, as Charles H. Duell, U.S. commissioner of patents in 1899, said, "Everything that can be invented has been invented." In fact, nothing is further from the truth. Sixty-four-slice CT is but one step leading to area detectors, with which a scan of the heart or liver might be done in less than a heartbeat. The era of 64-slice CT creates new issues, reminding us of a combination of Richard Nixon's "Solutions are not the answer" and Eric Sevareid's "The chief cause of problems is solutions."

Radiologists are already concerned about network transfers, archiving, and retrieving of 16-slice CT data sets, which run in the 400 to 1200-slice range for most CTAs. What will they do with two to three times that number of slices from 64-slice CT? That challenge must be addressed. In addition, workstations have been upgraded in recent years with special processing boards to interactively render 1000 or more slices. But can they handle 3000 to 5000-slice data sets? What about the load time for these data sets on a workstation?

Radiologists and referring physicians are now becoming comfortable with volume visualization as a primary reading and review mode. But they are not willing-nor should they be willing-to wait 10 to 15 minutes for a data set to load. Storage of data on central servers as well as retrieval of data will become enterprise-wide issues that require solutions. Success in solving the backbone issues will go a long way toward ensuring the success of 64-slice CT. Surmounting the challenges to efficient workflow is critical if 64-slice CT is to reach its full potential.

We are confident that these problems and others will be overcome through careful collaboration between industry and academia. This approach should include radiologists, technologists, referring physicians, computer scientists, and design specialists. New models will evolve, and the radiologist must lead, rather than react to, this change.

The advent of 64-slice CT will probably lead to the implementation of an imaging workflow that truly incorporates volume visualization into routine practice. It has taken almost 20 years to get to this point. We are anxious to see what the next two years will bring.

Dr. Fishman is a professor of radiology and director of diagnostic radiology and body CT, and Dr. Horton is an associate professor of radiology, both at Johns Hopkins Hospital in Baltimore; Dr. Anders is a radiology resident, and Dr. Achenbach is an assistant professor of radiolgy, both at the University of Erlangen in Erlangen, Germany.

Clinicians weigh 64-slice CT's revolutionary potential

The first announcements came at RSNA 2003, informing the radiology community that 64-slice CT would soon be available for clinical practice. Initial site installations by Siemens Medical Solutions and GE Healthcare began shortly after, in late spring and early summer of 2004. The introduction of this new technology came as a surprise to many, since 16-slice CT had been widely available only since 2002.

The Siemens Sensation 64 scanner, through its new z-sampling technology, delivers  