Address for Correspondence:  Yun Zhang， M.D， Ph.D， Shandong University Qilu Hospital， Jinan， No.107， Wen Hua Xi Road， Jinan ， Shandong， 250012， P.R.China， E-mail:zhangyun @ sdu.edu.cn
 
Cardiovascular disease has been the number one killer only in the developed countries but also in the developing countries such as China. According to the medical statistics published in 2003， there was one cardiovascular death every 34 seconds in the United States but only every 16 seconds in China (1). Most of these patients died suddenly without prior warning symptoms. Recent studies have proved that most acute coronary events including acute myocardial infarction and sudden cardiac death are caused by plaque rupture and the most common type of plaques vulnerable to rupture is known as thin-cap fibroatheroma (TCFA)(2). Therefore， development of imaging technology that is able to detect vulnerable plaques may greatly reduce the incidence of acute coronary events. This brief overview will focus on the latest development of imaging techniques for detection of vulnerable plaques. 

   Non-invasive imaging techniques

   Among non-invasive imaging techniques for detecting vulnerable plaques， high frequency vascular ultrasound imaging has been by far the most commonly used technique which is able to measure the intima-media thickness (IMT) of the carotid and the femoral arteries. Our study demonstrated that the normal value of the carotid IMT in a Chinese population involving subjects is 0.63±0.15 mm (3). Randomized clinical trials have proved that carotid IMT is a reliable surrogate end-point for assessing the anti-atherosclerotic effects of a variety of drugs (4). Using high frequency vascular ultrasound and intravascular ultrasound (IVUS)， we found that an increased IMT was an independent predictor of coronary plaque rupture in patients with unstable angina (5). A major problem in the clinical application of the carotid IMT is the lack of standardization and automation in measurement since a small error in the measurement may lead to a great variation in derived values. 

Multiplane transesophageal echocardiography (MTEE) is a semi-noninvasive technique with a higher spatial resolution than transthoracic echocardiography which allows visualization of the plaques located in the ascending and descending thoracic aorta. Our study indicates that MTEE is a useful technique to assess the vulnerability of the aortic plaques and prevent plaque rupture induced by aortic clamping during coronary artery bypass grafting surgery. There is also a good correlation between thoracic aortic plaque rupture detected by MTEE and cerebral and peripheral embolism. The major limitation of MTEE lies in its semi-noninvasive nature although MTEE is more likely to be accepted by patients than IVUS as an imaging technique for assessment of plaque regression and stabilization therapy.

   Multidetector row computed tomography angiography (MDCTA) with 64-detector rows has a high sensitivity and specificity in measuring the degree of coronary artery stenosis and recent studies have found this technique promising for displaying coronary plaque morphology and composition. MDCTA has a good correlation with both IVUS and histopathology for discrimination between soft， intermediate and calcified plaques， and also for measurement of plaque area， plaque volume and vascular remodeling (6). Further technical refinement， however， is required to increase both spatial and spatial resolution of MDCTA and the prognostic significance of the classification of non-calcified plaques by MDCTA should be evaluated in prospective clinical studies. With increased number of detector rows， faster rotating gantries and more sophisticated image reconstruction algorithms， MDCTA will probably become the technique of choice in detecting coronary vulnerable plaques in the near future.  

   Magnetic resonance imaging allows for three-dimensional evaluation of coronary arteries and depiction of plaque components such as lipid， fibrous tissues， calcium and thrombus formation. A potentially important application of MRI is to combine contrast with cellular and molecular targets to display active inflammation within the vulnerable plaques. At the present time， MRI is limited by the low signal-to-noise ratio of images， relatively thick slices and the small size and motion of coronary arteries， and technical improvement is required before MRI before MRI can be routinely used to assess vulnerable plaques (7). 

Positron emission tomography and single-photon emission computed tomography hold promise in imaging vulnerable plaques in large arteries. Nuclear tracers for assessing activities of macrophages， foam cells and matrix metalloproteinase have been developed and tested in the carotid and peripheral circulation (8). It remains difficult， however， for these techniques to display inflamed lesions within the coronary circulation due to small plaque size， cardiac and respiratory motion.

Invasive imaging techniques

   Intravascular ultrasound (IVUS) is currently the most useful technique in clinical practice for detecting plaque rupture and thrombosis， differentiating between lipids， fibrous tissues and calcium within the plaques as well as measuring plaque size， plaque eccentricity and vascular remodeling. Our study demonstrated that most coronary plaque ruptures occurred at a single site with a big plaque burden and positive vascular remodeling pattern. In a group of patients with stable and unstable angina， we identified that the carotid IMT， coronary remodeling index and high sensitive C-reactive were the three independent predictors of coronary plaque rupture detected by IVUS(5). The major problem with IVUS is that a quantitative assessment of plaque components is not available in most instruments and prospective clinical studies in a large cohort of patients are still lacking for validating the predictive value of IVUS parameters.  

New development of IVUS techniques such as integrated backscatter， wavelet analysis and virtual histology has focused on mathematic transformation of the radiofrequency signals from the reflected ultrasound waves to a color-coded display of plaque components(9). These images have been validated against histopathological sections in both animal and autopsy samples. Another exciting development of IVUS technology is intravascular palpography which assesses the local elasticity in the plaque and surrounding tissues. Experimental studies showed higher strain in fatty plaques than in fibrous plaques and high strain at the lumen has 88% sensitivity and 89% specificity for identifying vulnerable plaques (10). Our recent study demonstrated that carotid plaques with a higher strain during the cardiac cycle were closely associated with the occurrence of ischemic stroke.

   Optical coherence tomography(OCT) has the highest spatial resolution (10-20μm) in all commercially available imaging modalities which allows for a clear visualization of fibrous cap and necrotic core in vulnerable plaques and thus a reliable identification of TCFA can be achieved using OCT (11). The major limitation of this technique is the need for temporary balloon occlusion of the proximal coronary artery to avoid beam attenuation by blood and this may provoke chest pain and ST segment elevation in patients with coronary artery disease. Another limitation is a low beam penetration and thus an inability to visualize the entire vessel wall. In the future， a combination of OCT and IVUS may provide an ideal technique for “looking near and far” in the coronary arteries.

In conclusion，development of imaging techn