Cardiovascular disease is the most common cause of death not only in developed countries, but also in developing countries such as China. According to medical statistics published in 2003, there was one cardiovascular death every 16 seconds in China compared with one only every 34 seconds in the US.1 Most of these patients died suddenly without any warning symptoms. Recent studies have proved that most acute coronary events, including acute myocardial infarctions and sudden cardiac deaths, are caused by plaque rupture. The most common type of plaque vulnerable to rupture is known as a 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 article will focus on the latest developments of imaging techniques for the detection of vulnerable plaques.
Non-invasive Imaging Techniques
Among the non-invasive imaging techniques for detecting vulnerable plaques, high-frequency vascular ultrasound imaging has been by far the most commonly used technique that is able to measure the intima-media thickness (IMT) of the carotid and femoral arteries. Our study demonstrated that the normal value of the carotid IMT in a Chinese population involving subjects aged 20–65 years is 0.63±0.15mm.3 Randomised clinical trials have proved that carotid IMT is a reliable surrogate end-point for assessing the antiatherosclerotic 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 standardisation and automation in measurement, as a small error in the measurement may lead to a great variation in derived values. Multiplane trans-oesophageal echocardiography (MTOE) provides a semi-non-invasive technique with a higher spatial resolution than transthoracic echocardiography that allows visualisation of the plaques located in the ascending and descending thoracic aorta. Our study indicates that MTOE 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 MTOE and cerebral and peripheral embolism. The major limitation of MTOE lies in its semi-non-invasive nature. However, it is more likely to be chosen by patients than IVUS as an imaging technique for assessment of plaque regression and stabilisation 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 remodelling.6 However, further technical refinement is required to increase both spatial and temporal resolution of MDCTA, and the prognostic significance of the classification of non-calcified plaques by MDCTA should be evaluated in prospective clinical studies. With an increased number of detector rows, more quickly rotating gantries and more sophisticated image reconstruction algorithms, MDCTA will probably become the technique of choice in detecting vulnerable coronary plaques in the near future.
Magnetic resonance imaging (MRI) allows for 3D evaluation of coronary arteries and depiction of plaque components such as lipids, fibrous tissues, calcium and thrombus formations. A potentially important application of MRI is to combine contrast with cellular and molecular targets to display active inflammation within the vulnerable plaques. Currently, 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 can be routinely used to assess vulnerable plaques.7 Positron emission tomography (PET) and single-photon emission CT (SPECT) 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 However, it remains difficult for these techniques to display inflamed lesions within the coronary circulation due to several factors, including small plaque size and cardiac and respiratory motion.
Invasive Imaging Techniques
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 remodelling. Our study demonstrated that most coronary plaque ruptures occurred at a single site with a large plaque burden and positive vascular remodelling pattern.
In a group of patients with stable and unstable angina we identified that the carotid IMT, coronary remodelling index and highly sensitive C-reactive protein 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 developments of IVUS techniques such as integrated backscatter, wavelet analysis and virtual histology have focused on mathematical transformation of the radiofrequency signals from the reflected ultrasound waves to a colour-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 fibrous plaques and high strain at the lumen revealed by intravascular palpography 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 ischaemic stroke.
Optical coherence tomography (OCT) has the highest spatial resolution (10–20μm) in all commercially available imaging modalities, which allows for a clear visualisation of fibrous cap and necrotic core in vulnerable plaques. 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; this may provoke chest pain and ST segment elevation in patients with coronary artery disease. Another limitation is a low beam penetration, resulting in an inability to visualise the entire vessel wall. In the future, a combination of OCT and IVUS may provide an ideal technique for looking near and far into the coronary arteries.
In conclusion, the development of imaging technology for detection of vulnerable plaques is of huge clinical importance. Invasive imaging techniques such as IVUS and OCT still play a major role in the detection of some features of vulnerable plaques, and long-term follow-up studies in patients with coronary artery disease are required to validate prognostic parameters derived from these techniques. However, with further technological developments, non-invasive techniques such as MDCTA will eventually surpass invasive techniques and become the method of choice in identifying vulnerable plaques in patients with sub-clinical atherosclerosis.
- Chinese Ministry of Health, A statistical report of the development of Chinese public health in 2003. Accessed at www.moh.gov.cn
- Virmani R, Burke AP, Farb A, Kolodgie FD, Pathology of the vulnerable plaques, J Am Coll Cardiol, 2006;47:C13–18.
- Zhang M, Zhang Y, Zhang W, et al., A study of the diagnostic criteria of intima-media thickening of and effects of drugs on peripheral arteries, Natl Med J China, 2004;84:1252–5.
- Mancini GBJ, Dahlof B, Diez J, Surrogate Markers for Cardiovascular Disease: Structural Markers, Circulation, 2004;109:22–30.
- Chen WQ, Zhang M, Ji XP, et al., Prediction of plaque rupture in patients with angina pectoris with high frequency vascular ultrasound imaging and serum inflammatory markers, in press.
- Hoffmann U, Shi H, Schmitz BL, et al., Non-invasive coronary angiography with multislice computed tomography, JAMA, 2005;293:2471–8.
- Wilensky RL, Song HK, Ferrari VA, Role of magnetic resonance and intravascular magnetic resonance in the detection of vulnerable plaques, J Am Coll Cardiol, 2006;47:C48–56.
- Davies JR, Rubb JHF, Weissberg PL, Narula J, Radionuclide imaging for the detection of inflammation in vulnerable plaques, J Am Coll Cardiol, 2006;47:C57–68.
- Nair A, Kuban BD, Tuzcu EM, et al., Coronary plaque classification with intravascular ultrasound radiofrequency data analysis, Circulation, 2002;106:2200–06.
- Schaar JA, Regar E, Mastik F, et al., Incidence of high strain patterns in human coronary arteries: assessment with 3D intravascular palpography and correlation with clinical presentation, Circulation, 2004;109:2716–19.
- Yabushita H, Bouma BE, Houser SL, et al., Characterisation of human atherosclerosis by OCT, Circulation, 2002;106:1640–45.