Rapidly accumulating clinical data suggest that a search to identify a single vulnerable plaque to guide local therapy may seriously underestimate the complexity of the challenge. Indeed, this issue is further complicated by the fact that coronary plaque erosion without any rupture of a lipid core is a frequent cause of coronary thrombosis and sudden coronary death. Although topographic correlation has been shown between the presence of an inflammatory infiltrate and the site of plaque rupture and thrombosis, different pathological observations support the concept that plaque vulnerability and adverse outcome are not only related to a localised vascular accident but a reflection of a more generalised pathophysiologic process of diffuse involvement of the entire coronary tree. Patients whose burden of disease includes flow-limiting stenoses usually harbour diffuse but angiographically unseen disease along the length of their arteries. The concept of 'patient vulnerability' in ACS is suggested by numerous clinical studies showing increased acute-phase reactants in the serum of patients with unstable angina and those at risk of future myocardial infarction (MI). The major predictors of plaque progression have been recognised to be multivessel disease, prior PCI and age less than 65 years.

Although these observations underscore the need for identifying those multiple dangerous plaques in high-risk-profile patients who will benefit from early prophylactic intervention, the question remains how this evidence should improve practice. Clearly, early invasive management, including local intervention on the culprit lesion in conjunction with contemporary systemic therapy can improve outcomes of many patients affected by ACS. Still, recurrent cardiovascular events in this population remain unacceptably high. Therefore, in addition to angiography, ready-available, high-resolution imaging modalities are needed to improve the search and recognition of high-risk plaques.

VH-IVUS and Other Modalities for Vulnerable Plaque Imaging
Various imaging techniques are currently under investigation by extensive clinical testing to identify which could become the most sensible and specific modality for vulnerable plaque detection. Non-invasive imaging, such as computed tomography (CT), is overcoming motion artefacts with the use of multi-detector rows, ultra-thin slices and increased gantry speeds. CT has shown limited success using ex vivo histology of peripheral arteries in identifying high-risk plaques such thincap atheroma (TCFA), and is of limited use in calcified arteries, which is a significant drawback. Magnetic resonance imaging (MRI) holds promise as recent advances in hardware and pulse sequences have improved signal-to-noise ratio, allowing resolution of ≤400mm. However, the distance between the coil and the coronary vasculature, tortuosity of vessels and motion effects limit usefulness to the major epicardial arteries.

The emerging technologies with the greatest resolution are indeed catheter-based and many intravascular modalities have been developed for identification of TCFA. Optical coherence tomography (OCT) offers resolution as fine as 10μm. Furthermore, acquisition rates are high, and there are no transducers within the catheters. However, attenuation by blood and surface foam cells and lack of penetration of deeper regions of plaque remain obstacles to the current utilisation of OCT as a diagnostic tool.