calcium deposits accurately, superior to IVUS [137]. Additionally, a great ability to detect calcified nodules have been reported with a sensitivity of 96% and specificity of 97% [138]. Recently, striking images showing a close correlation between pathological and OCT findings in a human coronary artery were reported [139]. However, more recent studies have raised an important issue with regard to the visualization of intense dorsal shadowing generated by protruding red thrombus and protruding bony calcified spicules [140,141]. Further investigation is required to clarify whether protruding luminal red thrombus emerged directly, or small bony calcified nodules generated intense dorsal shadowing.
OCT‐derived Vulnerable Plaques
OCT‐ derived TCFA
With the high resolution of OCT, this modality might be the best for its reliability as a tool to measure the fibrous cap thickness in vivo. A histology study examined 38 human cadavers and showed a good correlation of the fibrous cap thickness between OCT and histology (r=0.90; p<0.001) [142]. In the clinical setting, OCT‐TCFA was reported to be more frequently observed in the culprit lesion in patients with STEMI compared with those with stable coronary artery disease [143], and NSTEMI [122]. In addition, its distribution in the coronary tree was similar to that in the previous pathological observation demonstrating that TCFAs were more commonly found in the proximal distribution of the coronary artery [88, 144]. Subsequently, serial OCT imaging has been employed to assess the natural history and the impact of lipid modification on atherosclerotic coronary plaques. OCT‐TCFA has been shown to be a predictor of subsequent plaque progression and acute coronary events [145]. An early clinical study reported that in patients with AMI, the use of statins for nine months significantly increased fibrous cap thickness compared with placebo control,146 indicating that its effects of stabilization on vulnerable atherosclerotic coronary plaques. Subsequently, the effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque assessed by optical coherence tomography (EASY‐FIT) trial compared the efficacy of 20 mg and 5 mg atorvastatin on plaque microstructures acquired from OCT in 70 patients with unstable angina pectoris. The increase in fibrous cap thickness was significantly greater with the higher dose of atorvastatin (69% vs 17%, p<0.001), along with more favourable changes in lipid arc (–27% vs –8%, p<0.001) and macrophage grade (–38% vs –24%, p<0.001) [147].
Macrophage infiltration
Pathophysiologically, macrophages play a very important role in the development of atherosclerosis and are the predominant inflammatory cell population within the fibrous cap of vulnerable plaques [79]. TCFA manifested by the infiltration of macrophages (average size 20 to 50 μm) has been recognized as contributing to weakening structural integrity of the cap [148–150] and predispose plaques to rupture. They are more frequently found in coronary artery specimens obtained from patients with ACS compared to stable CAD.150 The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. OCT visualizes macrophages as signal‐rich, distinct or confluent punctuate regions with heterogeneous backward shadows (Figure 1.5,). Tearney, et al. demonstrated that the OCT‐derived macrophage density of plaque fibrous caps correlated strongly (r=0.84, p<0.0001) with macrophage density quantified histolomorphometrically by CD68 immunoperoxidase staining in the corresponding histological samples [151]. They also showed that macrophage density in the fibrous caps correlated with the circulating white blood cell count, which is used in clinical practice as a marker of systemic inflammation and has been shown to be an independent predictor of cardiovascular events, and presence of TCFA [152]. Thus, OCT has been employed to identify and quantify macrophage infiltration.
Cholesterol crystal (CCs)
CCs are formed very early in the process of atherogenesis and activate the proinflammatory cytokines interleukin‐1‐beta (IL‐1β) and IL‐18 via activating inflammasomes in neutrophils and monocytes/macrophages [153], which has been postulated to contribute to CC‐mediated plaque destabilization. These findings are supported by the fact that demonstrated CCs are often seen abundantly within atheromatous plaques and at sites of plaque disruption [154]. Cholesterol crystallization in plaque is an important trigger for core expansion, leading to intimal injury [155]. Therefore, CCs have been thought to be one of the factors leading to disruption of the plaque cap and overlying intima. With OCT, cholesterol crystals (CCs) are defined as linear, highly backscattering structures within the plaque (Figure 1.5). Preliminary, Kataoka, et al. demonstrated that plaques containing CCs exhibited distinct OCT‐derived microstructures associated with plaque vulnerability [156]. Recently, in a study that investigated the relationship between CCs and culprit lesion vulnerability in patients with ACS, the frequency of CCs was significantly higher in patients with STEMI compared to NSTEMI (50.8% vs 34.7%, p=0.032). Moreover, culprit lesions with CCs had higher prevalence of macrophage accumulation (77.8% vs 40.0%, p<0.001), microchannels (67.9% vs 24.8%, p<0.001), plaque rupture (58.0% vs 36.0%, p=0.001), thrombosis (66.7% vs 49.6%, p=0.016) and spotty calcification (35.8% vs 10.4%, p<0.001), suggesting that CCs may increase plaque vulnerability and trigger plaque rupture in patients with ACS [157].
Neovascularization
In atherosclerotic plaques, neovascularization proliferates from the adventitia into the arterial wall in order to supply nutrition and inflammatory cell accumulation to the lesion. Also, micro‐vessels play a role in plaque haemorrhage associated with lipid core expansion through the accumulation of free cholesterol from erythrocyte membranes [89]. Therefore, pathological neovascularization of the artery wall is a consistent feature of atherosclerotic plaque development and progression of disease. In addition, it has also been recognized as a common feature of plaque vulnerability [89]. Some previous reports showed that micro‐vessels are increased in coronary lesions from patients with acute myocardial infarction [158, 159]. Micro‐channels are characterized using OCT as black holes with a diameter of 50–300 μm within plaque that are present on at least three consecutive frames (Figure 1.5). According to a study that examined 63 patients with CAD, micro‐channels detected by OCT evaluation were associated with a higher incidence of concomitant TCFAs and increased high‐sensitivity C‐reactive protein levels, which indicates the importance of intraplaque micro‐channels as a marker for plaque vulnerability [160].
Neoatherosclerosis
It is seen as diffusely bordered, signal‐poor regions with overlying signal‐rich bands, while calcific neointima shows well‐delineated, signal‐poor regions with sharp borders (Figure 1.1).
Near infrared spectroscopy (NIRS)
Advances in catheter‐based spectroscopy enables generation of a chemical fingerprint of atherosclerotic plaque. Near infrared spectroscopy (NIRS) is a technique that has been used for decades in the physical sciences to characterize chemical composition for substances [161]. This method could be ideal for identification of lipid‐rich and potentially vulnerable atherosclerotic plaques. The initial catheter‐based system was LipiscanTM (InfraRedx Inc., Burlington, MA, USA). Subsequently, since NIRS imaging did not provide any volumetric data of plaques, the NIRS/intravascular ultrasound (IVUS) catheter (TVC Imaging SystemTM, InfraRedx Inc., Burlington, MA, USA) was developed. NIRS generates a color map that displays the lipid content of the arterial wall as a “chemogram”. Every pixel represents the probability of lipid presence at the given location on a colour scale in which low probabilities of lipids are depicted as red, and high probabilities of lipids are shown as yellow (Figure 1.6). The “block chemogram” is a semiquantitative summary of the results for each
