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Intravascular imaging (IVUS)
The combination of high‐frequency ultrasound placed within close proximity to the artery wall generates a high resolution, cross‐sectional image of the full thickness of the artery wall. This enables us to visualize the full circumference of the vessel wall and atherosclerotic plaque, to examine arterial remodeling and to measure the area of plaque within each cross‐sectional image with quantitative techniques. A series of cross‐sectional images throughout a length of the artery is acquired with continuous imaging during catheter withdrawal, extending the quantitation of plaque burden to a volumetric measure. Additionally, intravascular ultrasound (IVUS) provides a unique opportunity to characterize the plaque morphology in the atherosclerotic coronary artery. Although identification of atherosclerotic plaque components is limited, several IVUS signatures have been suggested to be associated with either clinically unstable or a high risk for cardiovascular events in patients with coronary artery disease undergoing percutaneous coronary intervention [106–111]. Indeed, a preliminary pathological study has enhanced these findings with the relationship of the vulnerable IVUS characteristics with lipid contents and necrotic core [112]. These characteristics include atherosclerotic plaques with plaque attenuation characterized by a hypoechoic area with deep ultrasonic attenuation despite the absence of bright calcium (attenuated plaque) (Figure 1.2a), plaque echolucency characterized by an intraplaque zone of absent or low echogenicity (echolucent plaque) (Figure 1.2b), and spotty calcification characterized by the presence of lesions 1 to 4 mm in length containing an arc of calcification of <90° (Figure 1.2c). These coronary plaque characteristics associated with atherosclerotic vulnerability, inherent to IVUS imaging, offer potential advantages in the evaluation of coronary artery disease. Subsequently, IVUS has provided a valuable tool to study the vascular biology of coronary atherosclerosis in vivo.
Backscattered radio‐frequency (RF) IVUS
Beyond the IVUS, there is considerable interest in the ability to distinguish individual plaque components. Spectral analysis of IVUS radiofrequency backscattered signals, known as virtual histology IVUS (VH‐IVUS, Volcano Therapeutics, Inc., Roncho Cordova, Calfornia) or integrated backscatter IVUS (IB‐IVUS, TERUMO, Japan), was developed to reconstruct a color‐coded tissue map of plaque composition that distinguishes between fibrous, fibrofatty, necrotic core and dense calcific material (Figure 1.3) and provide detailed quantitative information of these individual components. Indeed, it has been shown that the RF IVUS has a 80% to 92% in vitro accuracy when used to identify the four different types of atherosclerotic plaques [113]. Additionally, according to the relative amount of these components, the pathological analysis is conducted to classify as pathological intimal plaque (PIT), thin‐cap fibroatheroma (TCFA), thick‐cap fibroatheroma (ThFA), fibrotic plaque and fibrocalcific plaque. Anatomical characteristics of vulnerable plaques which are prone to rupture were identified by the histological studies to have fibrous caps that are thin and rich in macrophages overlying a lipid pools [114]. Subsequent studies defined TCFA fibrous cap thickness as <65 μm [80] and showed that the majority of TCFAs had >10% of the plaque area occupied by a lipid‐rich NC [115]. Given that the resolution of VH‐IVUS is insufficient to directly image a thin fibrous cap, TCFA acquired from VH‐IVUS, VH‐TCFA, has been defined as the presence of >10% necrotic core volume without obvious overlying fibrous tissue and a total plaque burden of >40% observed within three consecutive VH‐IVUS frames. In the clinical settings, it has been shown by a three‐vessel VH‐IVUS study that patients with ACS have a greater incidence of VH‐TCFA than those with stable coronary artery disease [116]. Prospective analyses found that the baseline presence of VH‐TCFA was independently predictive of future coronary events in patients admitted with an ACS [117,118]. The Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study assessed 700 patients with ACS to identify the impact of baseline plaque composition on future coronary events [117], which demonstrated that the highest risk plaque type for recurrent cardiac events was TCFA derived by VH‐IVUS with small luminal area and large plaque burden. Furthermore, the European Collaborative Project in Inflammation and Vascular Wall Remodeling in Athersclerosis‐Intravascular Ultrasound (ATHEROREMO‐IVUS) study that demonstrated that the predictive value of TCFA derived by VH‐IVUS in a non‐culprit coronary artery for the occurrence of acute cardiac events, particularly of death and ACS was even stronger [119]. Thus, a color‐coded mapping method using IVUS radiofrequency is a promising research tool to identify plaque characteristics across a range of patient populations that may predict adverse outcomes.
Figure 1.2 IVUS features of vulnerable plaques. (a) Attenuated plaque (red arrows): a hypoechoic area with deep ultrasonic attenuation despite the absence of bright calcium. (b) Echolucent plaque (red arrows): plaque echolucency characterized by an intraplaque zone of absent or low echogenicity. (c) Spotty calcification: the presence of lesions 1 to 4 mm in length containing an arc of calcification of <90°.
Figure 1.3 VH‐IVUS imaging. Red –
