Over the last few years, noninvasive imaging of atherosclerosis has increasingly been used in clinical practice. In some cases, guidelines have been produced that recommend screening all healthy adults for atherosclerosis. It is appalling to realize, however, that there is a lack of data regarding the impact of such screening. In a recent systematic review by Rodondi et al, the authors assessed whether atherosclerosis screening with noninvasive imaging (eg, carotid ultrasound, coronary calcification) improves cardiovascular risk factors, cardiovascular events, or mortality in adults without cardiovascular disease. They identified 4 randomized controlled trials (n-709) and 8 nonrandomized studies comparing participants with evidence of atherosclerosis on screening with those who showed no evidence (n-2994). In the randomized controlled trial, atherosclerosis screening did not improve cardiovascular risk factors, but in one randomized controlled trial, smoking cessation rates increased (18% versus 6%; F-0.03). In the nonrandomized studies, the authors found improvements in several Intermediate outcomes such as increased motivation to change lifestyle and increased perception of cardiovascular risk. However, the data were conflicting and were limited by the lack of a randomized control group. No studies examined the impact of screening on cardiovascular events or mortality, Heterogeneity in screening methods and studied outcomes did not permit pooling of results. The authors of the systematic review concluded that it is available. evidence regarding atherosclerosis screening is limited, with mixed results regarding cardiovascular risk factor control; increased smoking cessation in one randomized controlled trial, and no date on cardiovascular events. Such screening should obviously be validated through large clinical trials before its widespread use.

In another study, Hackam et al analyzed 7 randomized trials that compared the use of different imaging modalities(CT, magnetic resonance imaging [MRI], and echocardiography. positron emission tomography [PET], arterial ultrasonography, nuclear myocardial perfusion imaging. exercise electrocardiography, and radionuclide angiography) with usual care and report any of the following outcomes in a primary prevention setting medication prescribing, lifestyle modification (including diet, exercise, or smoking cessation), angiography, or revascularization. 4 In this analysis, imaging had no effect on medication prescribing overall or on the provision of lipid-modifying drugs, or antihypertensive drugs. or antiplatelet agents. Similarly, no effect was seen on dietary improvement, physical activity, or smoking cessation. Imaging was not associated with invasive ease at baseline and followed them for a median time of 12.2 years. They studied the ability to measure intima-media thickness in the common carotid artery on top of Framingham risk factors to better classify people into categories of low (<10%), intermediate (10%- 20%), and high (>20%) 10-year risk of hard coronary heart disease (CHD) and stroke compared with models based only on Framingham risk factors. They found a sex difference: in older men, the addition of CIMT to Framingham risk factors did not improve the prediction of hard CHD or stroke. In older women, the addition of CIMT to Framingham risk factors significantly improved risk classification. Reclassification was most substantial in women at intermediate risk. The authors concluded that CIMT had some additional value beyond traditional risk factors in the cardiovascular risk stratification of older women, but not of
older men. Figure 1 is an example.

The authors therefore concluded that limited evidence suggests that noninvasive cardiovascular imaging alters primary prevention efforts. However, they also concluded that given the imprecision of these results, further high-quality studies are needed. In fact, one of the conclusions that we may draw at this time concerns the lack of robust, large studies that look at a scientifically sound way at the potential advantages of using imaging to help direct prevention more efficiently and in a more cost-effective way.

Caroline intima-media thickness (CIMT) assessed by ultrasound has proven to be a noninvasive biomarker of early atherosclerosis, and a positive association between CIMT and the risk of subsequent cardiovascular never been shown. 10 Thus, it may improve global cardiova risk prediction. However, several recently published studies have in some instances shown contradictory results. Eliss-Smole et al in the Rotterdam Study looked at whether the intima-media thickness of the common carouartery in addition to traditional risk factors improves classification in a general population of older people.

In the recently published PROG-IMT collaborative project (carotid intima-media thickness progression to predict cardiovascular events in the general population), the association between changes in CIMT and cardiovascular risk which is frequently assumed, but has rarely been reported was rested 3 The authors identified general population studies that assessed CIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The association between CIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study was determined. Of21 eligible studies. 16 were included with a total of 36 984 participants and a mean. follow-up period of 7.0 years. An interesting finding in this study was that although no associations with CIMT progression were detected in sensitivity analyses, the mean CIMT of the 2 ultrasound scans was positively and robustly associated with cardiovascular risk. In 3 studies including 3439 participants who had 4 ultra-sound acans. CIMT progression did not correlate between occasions. The variability in measurement/lack of evidence for its use in clinical risk prediction has been one of the main limitations regarding CIMT vae in a clinical setting. 14 Based on these results, the FROG-IMT authors concluded that the association between CIMT progression, as assessed from 2 ultra-sound scans, and cardiovascular risk in the general population remains improved and, therefore, no conclusion can be derived regarding the use of CIMT progression as a surrogate in clinical trials.

In a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Nicolaides et al determined the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery stenosis is Hazard ratios for internal carotid artery stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORT) events were calculated using proportional hazards models A total of 1121 patients with 50%-99% asymptomatic internal carotid artery stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for a mean of 48 months. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks or stroke, low gray-sole median, increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas without acoustic shadowing were associated with increased risk. The press under the receiver operating characteristic curves for a model of stenosis alone, a model of stenosis cum-bined with clinical features, and a model of stenosis combined. with clinical and plaque features were 0.59 (95% confidence interval [CT], 0.54-0.64), 0.66 (95% CI, 0.62-0.72), and 0.82 (95% CI, 0.78-0.86), respectively. In the last model, stenosis, history of contralateral transient ischemic attacks or stroke, gray-scale median, plaque areas, and discrete white areas were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. The authors concluded that cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. 

It seems clear that there is an independent association between CIMT and cardiovascular events.16-19 However, there are data showing that it improves measures of predictive performance.20 Despite the fact that it has already been used as a surrogate end point in randomized clinical trials of new cardiovascular drugs, there is still a need for a a standardized approach that will allow widespread clinical screening. 

The detection of coronary artery calcium (CAC) by elec tron beam CT or multidetector CT has gained some relevance due to the documented association between coronary calcium scores and risk of cardiovascular events 21.32 An increase in CAC scores over time (CAC progression) improves prediction of CHD events. In a recent shady, Okwuosa et al determined whether novel markers not involving ionizing radiation could predict CAC progression in a population of 2620 individuals classified as being at low risk of CHD events (Framing-ham risk score 10%) and who underwent follow-up CAC measurement 23 In addition to traditional risk factors, various combinations of novel marker models were selected on the basis of data-driven, clinical, or backward stepwise selection techniques. It was shown that after a mean follow-up period of 2.5 years, CAC progression occurred in 574 participants (22% overall: 214 of 1830 with baseline CAC= 0 and 360 of 790 with baseline CAC-0). The addition of various combinations of novel markers to the base model revealed improvements in discrimination of approximately only 0.005 each for the best-fit models. All three best-fit novel marker models calibrated well, but they were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared with the lowest probability quartile groups (39.2% to 40.3% versus 6.4% το 7.1%1).

The authors concluded that in individuals at low predicted risk according to the Framingham risk score, traditional risk factors predicted CAC progression in the short term with good discrimination and calibration. In addition, prediction improved minimally when various novel markers were added to the model. Figure 2 shows electron beam CT images at different scan planes illustrating extended CAC Centile distribution (25th, 50th, 75th. 90th centiles) of men aged between 45-75 years are also illustrated based on the results of the Heinz Nixdorf Recall study.24,25 

In another study, Owens et al teated whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary prevention population 26 Anrtic scleroses is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. It is also unknown whether this association extends to younger individuals. A prospective analysis of 6685 participants in the subclinical atherosclerosis. However, despite these results, the association between AVC and excess cardiovascular mortality beyond coronary atherosclerotic risk merits further investigation.

Another area of research has been the use of CT angiography to determine the prognostic value of the absence or presence of coronary artery disease (CAD). Abdulla Et al carried out a meta-analysis to determine the prognostic value of 64-slice CT angiography by quantifying the risk of major adverse cardiac events in different <50% of luminal narrowing or obstructive (stenosis 250% of luminal narrowing) CAD was compared with those who had normal angiography without CAD. Numbers of major adverse cardino events (cardiac death. nonfatal myocardial infarction, and revascularization) were used to calculate odds ratios (OR) with a 95% CI in each group. The cumulative rate of major adverse cardiac events over 21 months was 0.5% in patients with normal CT angiography. 3.5% Figure 2. Electron beam computed tomographic Imoges at different scan planes illustrating extended coronary nullification (Agatston man who, since his youth, sportsman 638) in an active Cenisis distribution (23rd. 50sh. 73nk 900k censies of som aged between 45-75 years breed on the results of the of the Heinz Nixdorf Recall study are else intrared After reference 24: Erbelal. Heart 2007,93.1620-1629 2007, HA Publishing Group Lnd and the British Cardiovascular Society.

In a very extensive document, Waugh er al assessed the clinical effectiveness and cost-effectiveness of CT screening for asymptomatic CAD. They also sought to establish whether CAC predicts coronary events and adds anything to risk factor scores, and whether measuring CAC changes treatment 20 They carried out a search using the main electronic databases for literature published up to 2005, with a MEDLINE update in February 2006, and carried out a systematic review screening studies and economic evaluations. Studies were included in the review if screening for CHD was the principal theme of the study, and if data were provided that allowed comparison of CT screening with current practice, which was taken to be risk factor screening. Mismatches between CAC scores and risk factor scoring were of particular interest. A review of the case for screening against the criteria used by the National Screening Committee for assessing screening programs was also undertaken. The authors found no randomized controlled trials that assessed the value of CT screening in reducing cardiac events. Seven studies including 30 599 individuals were identified that assessed the association between CAC scores on CT and cardiac outcomes in asymptomatic people. Six of the studies used electron-beam CT. The relative risk of a cardiac event was 4,4日 CAC was present compared with no CAC being present. Aa the CAC score increased, so did the risk of carding event The correlation between CAC and cardiac risk was consistent across students. There was evidence that CAC scores differed among the same Framingham risk factor scores and that within the same Framingham bands, people with higher CAC scores had significantly higher cardiac event rates. This applied mainly when the CAC scores exceeded 300. There was little difference in event rates among the groups with no CAC and scores of 1-100 and 101-300. In one study, the CAC score was a better predictor of cardiac events than the Framingham risk scores. No studies were found that showed whether the addition of CAC scores to standard risk factor assessment would improve outcomes. There were reports from 2 observational studies that lowered low-density lipoprotein cholesterol by about 3 mmol/l. or below with statin treatment modestly reduced CAC scores, but this was not confirmed in 2 randomized controlled trials. In 3 studies examining whether knowledge of CAC scores would affect compliance with lifestyle measures, perception of risk was affected, but it did not improve smoking cessation rates, although it did increase anxiety. There were few economic studies of CT screening for heart disease, which provided useful data on the costs of scans, other investigations, and treatment, but they relied on a number of assumptions and were unable to provide definitive answers. One modeling study estimated that adding CT screening to risk factor scoring and only giving statins to those with a CAC score of 100 would be money, based on a cost per CT screen of US$400 and statin costs of US$1000 per annum per patient However, the arrival of generic statins has reduced the price of this drug dramatically, and these savings no longer apply. In this important systematic review, Clexamination of the coronary arteries was able to detect calcification indicative of arterial disease in asymptomatic people, any of whom would be at low risk when assessed by traditional risk factors. The higher the CAC score, the higher the risk. Treatment with statins can reduce that risk. However, CT screening would miss many of the most dangerous patches of arterial disease, because they are not yet calcified, and so there would be false-negative results: normal CT followed by a heart attack. There would also be false-positive results in that many calcified arteries will have normal blood flow and will not be affected by clinically apparent thrombosis: abnormal CT not followed by a heart attack For CT screening to be cost-effective, it has to add value over risk factor scoring by producing sufficient additional information to change treatment, and hence cardiac outcomes, at an affordable cost per quality-adjusted life-year. There was insufficient evidence to support this. Most of the National Screening Committee criteria were either not met or only partially met. Ir would be useful to have more data on the distributions of risk scores and CAC scores in asymptomatic people, the level of concordance between risk factor and CAC scores, the risk of cardiac events per annum according to CAC score and risk factor cores, information on the acceptability of CT screening, information about the radiation doses used, and a randomized controlled trial of addition of CT screening to current risk factor-based practice.

The magnitude of age-related public health problems such as atrial fibrillation and heart failure is enormous and escalating despite the conventional strategies for clinical risk factor assessment and management. Therefore, new paradigms for risk stratification need to be considered. Of all the currently available imaging technologies, echocardiography is likely the one with a wider margin of patient safety and that is also mature enough to be used in prevention. Alongside its unique characteristics of portability, availability at the population level, and relatively low cost, echocardiography is well-positioned for use in preventive strategies. The ability to detect subclinical abnormalities early in the natural history of a disease may potentially allow treatment within the window of opportunity, interrupting the cascade of events that lead to adverse outcomes. The important contribution of echocardiography in prognostication and its role in risk stratification has been shown in different studies. This shows that echocardiography has evolved from being solely a tool for confirming diagnosis to one that will also guide the prevention of public health problems.

Carerj et al in the DAVES trial (Disfunzione Asintomalica VEntricolare Sinistra) carried out an echocardiographic examination of subjects with stage A heart failure, cardiovascular risk factors, and normal electrocardiogram and clinical examination results to (i) define whether stage A subjects with risk factors are really free of functional or structural cardiac abnormalities, and assess the impact of the presence of risk factors and the incremental value of echocardiographic parameters in the prediction of progression of heart failure or development. of cardiovascular events 30 In this study, a total of 1097 asymptomatic participants underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors Left ventricular (LV) dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated according to standard criteria.

The participants were divided according to different criteria: the presence of 1 or more risk factors, the presence or absence of LV systolic dysfunction, and the presence or absence of LV diastolic dysfunction. A follow-up period of 26+11 months was undertaken, with observation of primary (cardiac death, myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, acute pulmonary edema, stroke, and transient ischemic attack) and secondary (cardiologist-made diagnosis of heart failure and heart failure hospitalization) endpoints. The multivariate analysis for independent predictors of combined endpoints showed that only age, gender, obesity, and systolic dysfunction represented the significant predictors. Echocardiography showed a high incremental value in the detection of systolic LV dysfunction and the prediction of cardiovascular events during follow-up in participants with at least 2 risk factors Importantly, this study demonstrated that preclinical functional or structural myocardial abnormalities could be detected by echocardiography in asymptomatic individuals with 2 or more cardiovascular risk factors and without electrocardiogram abnormalities (stage A of heart failure classification). Moreover, the presence or absence of LV systolic dysfunction or LV diastolic dysfunction, as demonstrated by echocardiography, has incremental value to cardiovascular risk factors in predicting both the evolution toward more severe stage Cheart failure and the occurrence of cardiovascular events. 

The incremental value of left atrial (LA) deformation analysis by speckle tracking echocardiography compared with LA volume or LA ejection fraction as a cardiovascular risk marker has recently been evaluated. In a recent study by Cameli et al, LA function by speckle tracking echocardiography was compared with other conventional LA parameters for prediction of adverse cardiovascular outcomes a1 This prospective study included 312 adults (mean age 71+6 years: 56% men) in sinus rhythm who were followed for the development of first atrial fibrillation, congestive heart failure, stroke, transient ischemic attack, myocardial infarction, coronary revascularization, and cardiovascular death. Globalpeak atrial longitudinal strain (PALS) by speckle tracking echocardiography was measured in all individuals averaging all atrial segments (see Figure 4). The left atrium was assessed using biplane LA volume, ejection fraction, 4-chamber LA area, and M-mode dimension. All patients were followed for the development of new outcome events (eg, atrial fibrillation, stroke, transient ischemic attack, myocardial infarction, coronary revascularization, congestive heart failure, and cardiovascular death). Of the 312 participants at baseline, 43 had 61 new events during a mean follow-up period of 3.1+1 4 years. All LA parameters were independently predictive of combined outcomes (P<0.0001 for all comparisons). Overall performance for prediction of cardiovascular events was greatest for global PALS (area under receiver operator characteristic curve: global PALS. 0.83. indexed LA volume, 0.71; LA ejection fraction, 0.69; LA area, 0.64, LA diameter, 0.59). 

A graded association between the degree of LA enlargement and risk of cardiovascular events was evident only for global PALS and indeed LA volume. Importantly, it was found in this study that global PALS is a strong and independent predictor of cardiovascular events and appears to be superior to conventional parameters of LA analysis.

In summary, we agree with the conclusions of Tsang at the Feigenbaum lecture 2008:

The magnitude of age-related public health problems, such as atrial fibrillation and heart failure, is enormous and is expected to increase foreseeable future. Echocanliography is safe and effective for the early detection of subclinical normalities, segmenting clinical prediction of first cardiovascular events. At this same, relatively little is known regarding the impact of reversing LA remodeling and dias online dysfunction on outcomes, and studies that can provide a greater understanding of the cost-effectiveness of population screening and monitoring are warranted. Echocardiography continues to rapidly evolve beyond in established role as a noninvasive diagnostic tool to one that will assume as integral role in the prediction and prevention of age-related cardiovascular outcomes.

CT coronary angiography (CTCA) and myocardial perfusion imaging techniques are established noninvasive modalities for the diagnosis of CAD.13-36 Cardiac hybrid imaging consists of the combination (or "fusion") of both modalities and allows complementary morphological (coronary anatomy, stenoses) and function-al (myocardial perfusion) information to be obtained Furthermore, integration of the detailed specialized cardiac centers, the ongoing efforts to reduce radiation exposure and the increasing clinical in-there will. further, paving the way for increasing the use of cardiac hybrid imaging in clinical practice 33 Figure shows image fusion of a myocardial perfusion SPECT bull's-eye plot and CTCA.

Pazhenkottil et al carried out a study aimed at assessing the impact of cardiac hybrid imaging on the choice of a treatment strategy for CAD in 318 consecutive patients who underwent a 1-day stress/rest (v9mTc)-tetrofosmin SPECT and a CTCA on a separate scanner for evaluation of CAD.16 Patients were divided into one of the following 3 groups according to findings in the hybrid images obtained by fusing SPECT and CTCA images: (i) matched finding of stenosis on CTCA and corresponding reversible SPECT defect; (ii) unmatchedCTCA and SPECT finding; and (in) normal finding on both CTCA and SPECT. Follow-up was confined to the first 60 days after hybrid imaging, as this best allows assessment of treatment strategy decisions. Including revascularization procedures, triggered by the findings of hybrid imaging. Hybrid images revealed. matched, unmatched, and normal findings in 51. 74, and 193 patients, respectively. The revascularization rate within 60 days was 41%, 11%, and 0% for matched, unmatched, and normal findings, respectively (P<0.001 for all intergroup comparisons). The authors concluded that cardiac hybrid imaging with SPECT and CTCA provides added. clinical value for decision-making with regard to treatment strategies for CAD.

A recent study by Johnson et al sought to understand the physiological integration of data obtained from different imaging techniques.34 The authors proposed two-dimensional scatter plots of stress flow and coronary flow reserve with superimposed thresholds for normal flow, reduced flow without ischemia, definite ischemia, and transmural infarction to allow for automatic and objective classification. Application of this schema to 1500 studies demonstrated that flow capacity is inversely related to risk
factors and atherosclerotic burden. For broad application in all patients, interpretation of stress flow for clinical decision- making requires rest flow or coronary flow reserve. Although relative uptake images alone are adequate in some patients, in many individuals, they can lead to either underestimation or over-estimation of flow capacity. In conclusion, a standardized framework could prompt future studies and lead to a trial of revascularization guided by absolute flow measurements.

Cardiovascular imaging has played a major role in the identification and characterization of the so-called "vulnerable plaque. A major goal in particular over the past years has been the possibility of identifying individuals at risk of plaque rupture and therefore developing an acute coronary syndrome. This early identification of atherosclerotic plaques that are more likely to rupture could lead to the development of pharmacological and interventional strategies aimed at reducing clue coronary events and their dreadful consequences.

The morphological characteristics of atherosclerotic plaques may be targeted by noninvasive and invasive imaging modalities such as angiography, and intravascular ultrasonography, optical coherence tomography, CT., and MRI. In addition, molecular imaging offers the possibility of better discriminating the individual components of plaque. Thus, in order to globally assess vulnerable plaque, imaging modalities should target plaque morphology and structure and plaque inflammation. apoptosis, and thrombosis, and provide information regarding flow and wall stress. 

Intravascular ultrasonography has been used to try to identify high-risk plaques. Plaque features shown to be related to acute coronary syndromes art positive re-modeling.sa plaque rupture Jy and hypoechoic plaque.sa Attenuated plaques are also frequently found in patients with acute coronary syndromes. These are defined as being hypoechoic with deep ultrasound attenuation, in the absence of calcification. Histopathology studies have shown microcalcification, cholesterol crystals, and importantly, thrombus in these plaques. Moreover, the burden of attenuated plaque correlates with the no-reflow phenomenon in ST-segment elevation myocardial infarction.45 However, recognition of the existence of non-culprit attenuated plaques that remain stable during follow-up brings into question their usefulness in predicting acute coronary syndromes.

Although in vivo coronary arterial histology is not feu-sible, radiofrequency intravascular ultrasonography analysis provides a characterization of vessel wall components with high accuracy 42 The images obtained are usually color-coded to discriminate dense calcium, the necrotic core, fibrofatty tissue, and fibrotic tissue as According to the relative amounts of the components, lesions may be classified as thin-cap fibroatheroma, thick-cap fibroatheroma, pathologic intimal thickening, fibrotic plaque, and fibrocalcific plaque. Figure 6 shows an example of the automatic characterization of athero-sclerotic plaque by virtual histology.

 In the PROSPECT trial (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), events unrelated to previous culprit lesions typically occurred at sites that were classified as thin-cap fibro-atheroma Although promising and pioneering in terms of in vivo detection of vulnerable plaque, these observations lack specificity. In fact, the simultaneous presence of the 3 independent determinants of cardiac events (thin-cap fibroadenoma, minimal luminal area $4.0 mm2, and plaque burden of 270% at the minimal luminal areal only predicted events in 18% of such plaques after 3 years. Thus, this stunning modality is not suitable for prompt utilization in the clinical detection of vulnerable plaques. However, PROSPECT is a good example of how these new imaging modalities should be tested.

 Optical coherence tomography is an imaging modality that uses light instead of ultrasound for generating intravascular images Spatial resolution is about 10 times higher than with intravascular ultrasonography, but due to the limited depth of penetration, imaging of the vessel wall and plaque burden is often problematic. However, this imaging modality may provide characterization of plaque components, particularly the differentiation of fibrous. fibrocalcific, and calcific plaques es In addition, in patients with acute coronary syndromes, optical coherence tomography identifies fibrous cap disruption, fibrous cap erosion, intracoronary thrombus, and thin-cap fibroatheroma more frequently than does intravascular ultrasonography, making it an attractive imaging method for the identification of the vulnerable plaque 4s New and emerging optics coherence tomography modalities like polarization-sensitive optical coherence tomography, which provides an assessment of plaque collagen content, new way emerging optical coherence tomography modalities like polarization-sensitive optical coherence tomography, which provides an assessment of plaque collagen content,47 may expand the future capabilities of this intravascular imaging technique. However, large prospective studies in this area are currently lacking. 

Angioscopy is an intravascular imaging modality that allows direct visualization of the plaque surface and luminal thrombus. Patients with yellow plaques more frequently develop acute coronary syndromes.48 Yellow plaques are usually thin-capped, exhibit positive remodeling, have high lipid content, and often present intraluminal thrombi.46,48,49 However, there are considerable limitations that impair further use of this technique; namely, the need for blood displacement and the subjectivity of the assessment of plaque color. 

Other invasive imaging modalities currently under development that show promise for the morphologic detection of vulnerable plaques include near-infrared spectroscopy and intravascular magnetic resonance. In the future, these modalities may be able to provide chemical characterization of plaque components,50,51 but their relevance still needs to be prospectively tested. 

There are specific advantages and hurdles associated with each modality for imaging the vulnerable atherosclerotic plaque in the coronary arteries. There are certain technical and patient-security challenges associated with molecular imaging modalities that need to be overcome in order for them to become clinical tools. These imaging techniques should therefore be tested in clinical trials to assess their utility in real-life prediction of coronary events. Although all of these imaging modalities are very promising, ultimately, their ability to identify and differentiate patients who will benefit from intense medical therapy, local intravascular therapy, or preventive coronary bypass surgery will dictate their success. 

Multimodal imaging integrating coronary morphology, wall composition, and characterization, in addition to coronary wall stress assessment, may provide a highly accurate and predictive assessment of the vulnerable plaque. In providing this integrated individual risk profile, invasive imaging modalities currently present several advantages over MRI and CT. They provide higher anatomical detail, have tissue characterization capabilities, and, in the case of intravascular ultra- sonography, may assess inflammation and thrombo- sis through molecular imaging and localize high wall stress areas. 

There is ample evidence to support a strong relationship between plaque morphology and patient outcome. However, molecular imaging may add significant relevant information concerning tissue inflammation and subclinical thrombosis. Additionally, identification of arterial wall exposed to high-shear stress may further identify rupture-prone arterial segments. These new modalities may thus contribute to lowering the individual, social, and economic burden of cardiovascular disease.

Thus, much of the effort in the development of the new imaging modalities has come from the basic sciences. An integrative clinical translation of this work will be crucial to the future success of vulnerable plaque imaging for prediction of individual cardiovascu- lar risk and development of pharmacological and interventional strategies to reduce acute coronary events.

Evaluation of myocardial perfusion and the structures of coronary arteries using advanced technologies, such as MRI, advanced echocardiography, spiral CT, and a broad spectrum of nuclear cardiology techniques, is gaining more and more importance in the diagnosis and management of CHD. Detection of coronary atherosclerosis and evaluation of early signs of myocardial hypoperfusion may significantly impact the selection of an effective treatment modality and may also provide risk stratification value. Nuclear cardiac studies are frequently being used in this field, and importantly, outstanding results are being achieved by PET and combined acquisitions involving PET/CT and SPECT/CT hybrid systems. CTCA and myocardial perfusion imaging provide additional complementary information to these techniques regarding vascular structure and myocardial perfusion. Spiral CT, which can reveal calcium deposits in blood vessels, has an important role in the detection of the severity and extent of atherosclerotic lesions. Shortly, use of multislice CT could potentially replace use of coronary angiography, particularly for assessment of the degree of stenosis and patency of grafts. 

MRI has also had noticeable success in this field. Cardiac MRI clearly has potential and has already emerged as a robust
method for assessing ventricular function, myocardial mass, and myocardial viability, and this approach is increasingly being used for clinical rest and stress perfusion measurements. While cardiac MRI angiography holds great promise as a radiation-free method, further improvement is needed regarding equipment and methodological approaches involving use of novel contrast agents to achieve the accuracy of CT angiography in noninvasive coronary angiography. In patients with CAD, the ideal approach would be to embrace multimodal applications that cover both morphological and functional assessment to achieve early diagnosis and allow early planning of therapeutic strategies. Moreover, in the field of ultrasonography, recent developments have enabled objective quantification of global and regional ventricular function, and real-time evaluation of coronary walls and lesions. Although more knowledge about atherosclerotic lesions is gained through use of intravascular ultrasound, tissue Doppler and strain imaging have emerged as being able to provide a more objective assessment of myocardial function. In addition, three-dimensional quantification of carotid plaque by ultrasound may be a stronger predictor of atherosclerotic cardiovascular disease than the current two-dimensional approach. However, the predictive value of this novel approach will remain unknown until further prospective outcome data are obtained. Ultrasound and other imaging techniques that measure both anatomy and function provide well-validated surrogate markers for atherosclerosis that are incremental to the Framingham heart study score. Of course, as with any diagnostic test, careful use of pretest probability assessment to determine individuals
most likely to benefit from an imaging modality (ie, those at intermediate risk), and individual interpretation and treatment on the basis of test results, are imperative. 

AVC has been shown to serve as a marker of subclinical atherosclerosis severity. Whether AVC adds to cardiovascular risk prediction beyond the Framingham risk categorization merits additional investigation. 

These new developments in imaging represent an economical and effective method of screening for CHD risk and for informing clinical management decisions. In summary, atherosclerosis is systemic, silent, and deadly. Primary risk reduction is effective; however, cost-effective risk modification relies on accurate and individualized risk stratification. Traditional risk factor–based assessments fail to account for individual progression along the pathophysiologic continuum. The incremental use of imaging as a reliable additional tool to help in preventing the development of heart disease is a reality and will certainly be an area of intense research in the near future. This research will document whether these approaches are clinically effective and have a positive cost/benefit ratio in the management and risk assessment of heart disease.