Clinical applications of optical coherence tomography

Rupture of vulnerable plaque (VP) is responsible for most coronary events. Optical coherence tomography (OCT) is a high-resolution imaging method that allows excellent characterization of atherosclerotic plaque. While this technique is limited by the need to interrupt blood flow and a shallow depth of penetration, its resolution is an order of magnitude greater than possible with intravascular ultrasound (IVUS), and it has demonstrated better sensitivity and specificity for accurately determining plaque composition. Early in vitro and in vivo experiences have affirmed the excellent quality of these images making it an attractive technology for the analysis of VP. Its high resolution likely renders it the best imaging modality currently available for the evaluation of proper stent deployment and of intracoronary pathology in the setting of percutaneous coronary interventions (PCI). Our institution is currently involved in a multicenter trial to evaluate the effectiveness of OCT when compared to IVUS in this setting. Ongoing technological improvements aim to permit rapid scanning which should alleviate its current major limitation of needing to scan in a blood-free space. OCT is a promising new technology in the evaluation of atherosclerotic plaque and coronary microstructure.     

Optical coherence tomography and coronary revascularization: from indication to procedural optimization

Angiography alone is the most commonly used imaging modality for guidance of percutaneous coronary interventions. Angiography is limited, however, by several factors, including that it only portrays a low resolution, two-dimensional outline of the lumen and does not inform on plaque composition and functional stenosis severity. Optical coherence tomography (OCT) is an intracoronary imaging technique that has superior spatial resolution compared to all other imaging modalities. High-resolution imaging of the vascular wall enables precise measurement of vessel wall and luminal dimensions, more accurately informing about the anatomic severity of epicardial stenoses, and also provides input for computational models to assess functional severity. The very high-resolution images also permit plaque characterization that may be informative for prognostication. Moreover, periprocedural imaging provides valuable information to guide lesion preparation, stent implantation and to evaluate acute stent complications for which iterative treatment might reduce the occurrence of major adverse stent events. As such, OCT represent a potential future all-in-one tool that provides the data necessary to establish the indications, procedural planning and optimization, and final evaluation of percutaneous coronary revascularization.     

光学相干断层成像在检测易损斑块中的应用价值

冠状动脉粥样硬化斑块易发斑块破裂,导致急性冠状动脉综合征,引起急性心肌梗死。有效的评价斑块的结构及成份特点,监测其演变过程,对选择治疗时机和治疗方案有重要意义。光学相干断层成像是一种新型的生物医学成像技术,它可以对易损斑块准确识别。现就光学相干断层成像在检测易损斑块中的应用价值作一综述。     

Intracoronary Imaging in the Detection of Vulnerable Plaques

Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging.     

Optical coherence tomography and its use in detection of vulnerable plaque

Acute coronary syndromes and their associated complications related to coronary ischemia continue to be the leading cause of morbidity and mortality in the world. The most commonly encountered pathophysiologic cascade of events resulting in this picture is initiated by formation of a vulnerable plaque. Despite the widespread use of a variety of imaging technologies, high-resolution detection of the vulnerable plaque and designing a method to correlate the results of the imaging modality with disease severity and prognosis have proven to be an arduous task. The recent introduction of optical coherence tomography has proven to be an innovative contribution to the diagnostic armamentarium for the cardiologist. This article presents an overview of vulnerable plaque and methods for its imaging. It focuses on how optical coherence tomography comes into play and how it compares with other modalities in regard to plaque characterization.     

Usefulness of multidetector computed tomography for noninvasive evaluation of coronary arteries in asymptomatic patients

This editorial addresses the capabilities, limitations, and potential of multidetector computed tomography (MDCT) for the noninvasive evaluation of coronary arteries in asymptomatic patients. The quantification of coronary calcium with MDCT correlates highly with that obtained by electron-beam computed tomography, but to date, neither has the capability of assessing the distribution of various morphologic patterns of calcium and their relation to other "soft" plaque components. Although MDCT can assess the thickness of the atherosclerotic wall and can readily identify calcific deposits, further plaque characterization (e.g., lipid pools and fibrous tissue), a prerequisite for the identification of most vulnerable lesions, is not yet a workable reality, even with the 64-slice machines in their current configuration. The noninvasive identification by MDCT of plaque components subtending vulnerable lesions will require additional improvement in the primary instrumentation, the use of hybrid constructs (e.g., with positron emission tomography and magnetic resonance imaging), the development of novel methods of post-acquisitional analysis to extract latent images of plaque components (e.g., signal analysis based on 3-dimensional wavelets), or the adaptation of molecular imaging techniques at the cell and gene levels to computed tomography. Such unique approaches may soon contribute a long list of additional parameters that could be evaluated on a noninvasive basis as predictors of acute coronary syndromes and overall patient vulnerability.     

Vulnerable plaque imaging and acute coronary syndrome

The term vulnerable plaque has been established to describe an atherosclerotic lesion with a high probability of causing a future coronary event [1], [2]. The identification and stabilization of the lesion before its rupture may reduce the morbidity and mortality caused by coronary artery disease. Modern imaging modalities such as computer tomography coronary angiography, intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy have a potential in finding these vulnerable plaques. This raises opportunities in the primary and secondary prevention of coronary artery disease. This review summarizes the current knowledge with an emphasis put on the research advances in the field of near-infrared spectroscopy a modality that has been intentionally developed for the detection of lipid-core plaques.     

Italian Chapter of the International Society of Cardiovascular Ultrasound expert consensus document on coronary computed tomography angiography: overview and new insights

Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three‐dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image‐guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography.     

The comparison between optical coherence tomography and intravascular ultrasound

Coronary angiography, despite its long history, has well recognized limitations, arising in part from the inability to image a three dimensional structure in a single plane. Furthermore the angiographic image of the arterial lumen conceals atherosclerotic processes that occur within the arterial wall. Alternative imaging techniques have evolved as an adjunct to angiography in an attempt to overcome these limitations. Two such invasive techniques are intravascular ultrasound and optical coherence tomography. Intravascular ultrasound allows tomographic imaging of long segments of the coronary tree, highlighting the arterial lumen as well as the arterial wall. Over the last 13 years intravascular ultrasound has enhanced our understanding of the pathophysiology of atherosclerosis, and the mechanisms involved in coronary intervention. Optical coherence tomography is an optical analogue of intravascular ultrasound that has recently reached coronary application. Its superior resolution results in improved diagnostic potential, particularly for vulnerable plaque in which the thin fibrous cap often measures 10-50 mm. The similarities, contrasts and applications of these two imaging techniques in terms of design, image interpretation, and future directions forms the subject of this review.     

New developments in the detection of vulnerable plaque

Failure of coronary angiography (luminography) in prediction of future acute coronary syndromes has cast a shadow of doubt over the value of this old gold-standard technique. The fact that angiographically invisible or nonsignificant lesions cause the majority of acute coronary syndromes has driven scientists to develop new diagnostic methods. In this article, we review the ongoing worldwide research on both invasive techniques (such as intravascular angioscopy and colorimetry, ultrasound, thermography, optical coherence tomography, near infrared spectroscopy, Raman spectroscopy, fluorescence emission spectroscopy, elastography, magnetic resonance imaging [MRI] and spectroscopy, nuclear immunoscintigraphy, electrical impedance imaging, vascular tissue doppler, and shear stress imaging) and noninvasive techniques (such as MRI, contrast-enhanced MRI with and without immunolabeled agents, electron beam computed tomography, multi-slice spiral / helical computed tomography, and nuclear imaging, including positron emission tomography). Each of these techniques and their potential combination holds promise for characterization of plaques responsible for acute coronary syndromes, namely vulnerable plaque.     

Diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of atherosclerotic plaque composition in ex-vivo coronary specimens: a comparison with histology

BACKGROUND: Both intravascular ultrasound and optical coherence tomography have been purported to accurately detect and characterize coronary atherosclerotic plaque composition. The aim of our study was to directly compare the reproducibility and diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of coronary plaque composition ex vivo as compared with histology. METHODS AND RESULTS: Intravascular ultrasound (20 MHz) and optical coherence tomography imaging was performed in eight heart specimens using motorized pullback. Standard histology using hematoxylin-eosin and van Gieson staining was performed on 4 mum thick slices. Each slice was divided into quadrants and accurately matched cross-sections were analyzed for the presence of fibrous, lipid-rich, and calcified coronary plaque using standard definitions for both intravascular ultrasound and optical coherence tomography and correlated with histology. After exclusion of 145/468 quadrants, we analyzed the remaining 323 quadrants with excellent image quality in each procedure. Optical coherence tomography demonstrated a sensitivity and specificity of 91/88% for normal wall, 64/88% for fibrous plaque, 77/94% for lipid-rich plaque, and 67/97% for calcified plaque as compared with histology. Intravascular ultrasound demonstrated a sensitivity and specificity of 55/79% for normal wall, 63/59% for fibrous plaque, 10/96% for lipid-rich plaque, and 76/98% for calcified plaque. Both intravascular ultrasound and optical coherence tomography demonstrated excellent intraobserver and interobserver agreement (optical coherence tomography: kappa=0.90, kappa=0.82; intravascular ultrasound: kappa=0.87, kappa=0.86). CONCLUSION: Optical coherence tomography is superior to intravascular ultrasound for the detection and characterization of coronary atherosclerotic plaque composition, specifically for the differentiation of noncalcified, lipid-rich, or fibrous plaque.     

Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound

OBJECTIVES: The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND: Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS: The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS: Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS: Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.     

Molecular imaging of plaques in coronary arteries with PET and SPECT

Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography （PET） and single photon emission computed tomography （SPECT） has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.     

Imaging of coronary atherosclerosis using computed tomography: Current status and future directions

Computed tomography (CT) imaging of the coronary arteries, using either electron beam tomography (EBT) or multidetector row CT (MDCT), offers two possibilities to assess coronary atherosclerosis. Without injection of contrast agent, coronary calcifications can be detected and quantified. Their presence and extent correlates to the presence and amount of coronary atherosclerotic plaque. Prospective studies have demonstrated a high predictive value concerning the occurrence of coronary artery disease events and overall mortality. An emerging consensus seems to indicate that calcium imaging may be clinically useful in patients at intermediate risk for coronary artery disease events as determined based on traditional risk factors. In addition, recent studies have shown that after injection of contrast agent and using high-resolution scan protocols, the visualization of noncalcified plaque is also possible with CT techniques. However, data on the accuracy of plaque detection, quantification of plaque volume, and characterization of plaque (eg, lipid-rich vs fibrous) is currently limited, and the prognostic significance of noncalcifed coronary atherosclerotic plaque detection is unclear.     

动脉粥样硬化易损斑块的动物模型和检测技术

动脉粥样硬化易损斑块破裂、血栓形成是急性冠状动脉综合征的发病机制已成为共识。由于缺乏理想的易损斑块的动物模型,对斑块破裂前的血清学及影像学特征研究较少,尚缺乏能够早期识别易损斑块及预防斑块破裂的最佳方法。本实验室已成功构建家兔和Apo E-/-小鼠的易损斑块模型。易损斑块的检测技术主要包括非侵入性及侵入性的影像学检测及功能学检测技术。对易损斑块的早期准确识别以便及时干预具有十分重要的临床意义。     

Vulnerable plaque: the challenge to identify and treat it

In order to understand, treat, and prevent acute coronary syndromes we need to improve our ability to identify the rupture-prone, vulnerable atherosclerotic coronary plaque. The diagnostic modalities that are currently available to clinical practice have not fulfilled this expectation, and newer diagnostic techniques based on the recently identified features of the vulnerable plaque are quite promising. Coronary angiography, intravascular ultrasound, and angioscopy have been used in the clinical arena of interventional cardiology with several limitations regarding the identification of the vulnerable plaque. Thermography, optical coherence tomography, elastography, Raman spectroscopy, and infrared spectroscopy are used in clinical trials and the results are encouraging. Ultrafast computed tomography and magnetic resonance imaging have the advantage of being noninvasive. With our progress in the identification of the rupture-prone vulnerable coronary plaque, we will be able to identify patients that are at high risk and will benefit from a more aggressive therapeutic approach.     

Intravascular modalities for detection of vulnerable plaque: current status

Progress in the diagnosis, treatment, and prevention of atherosclerotic coronary artery disease is dependent on a greater understanding of the mechanisms of coronary plaque progression. Autopsy studies have characterized a subgroup of high-risk, or vulnerable, plaques that result in acute coronary syndromes or sudden cardiac death. These angiographically modest plaques share certain pathologic characteristics: a thin, fibrous cap, lipid-rich core, and macrophage activity. Diagnostic techniques for vulnerable-plaque detection, including serologic markers and noninvasive and invasive techniques, are needed. Recent advances in intravascular imaging have significantly improved the ability to detect high-risk, or vulnerable, plaque in vivo by using various features of plaque vulnerability as methods of identification. The characteristic anatomy of a thin, fibrous cap overlying a lipid pool has promoted high-resolution imaging, such as intravascular ultrasound, optical coherence tomography, and intracoronary magnetic resonance. The lipid-rich core is identifiable by angioscopically detected color changes on the plaque surface or by its unique absorption of energy, or "Raman shift," of its cholesterol core, driving coronary spectroscopy. Finally, temperature heterogeneity arising at foci of plaque inflammation has prompted the development of intracoronary thermography. In this review, we will discuss these techniques, their relative advantages and limitations, and their potential clinical application.     

What are the most useful and trustworthy noninvasive anatomic markers of existing vascular disease?

Cardiovascular disease is the leading cause of mortality and morbidity in developed countries. Evidence challenges the notion that the severity of lesions on angiography is a predictor of future cardiac events. With the recognition that subclinical coronary artery stenoses are responsible for myocardial infarcts and sudden death, it may be important to identify patients with plaque characteristics that may place them at increased risk. Intravascular ultrasound, though invasive, remains the current imaging gold standard. Computed tomography, cardiac magnetic resonance, and single-photon emission CT positron emission tomography are evolving and promising modalities. Functional studies reflecting plaque temperature and molecular imaging reflecting plaque constituents are being developed. We review the pathology of the vulnerable atherosclerotic plaque and recent innovations in imaging modalities to assess plaque complication risk.     

Current status of vulnerable plaque detection

Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes (ACS) and sudden cardiac death. Autopsy studies have identified a subgroup of high‐risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and noninvasive imaging techniques have shown the potential to identify these high‐risk plaques. The anatomical characteristics of the vulnerable plaque such as thin cap fibroatheroma and lipid pool can be identified with angioscopy, high frequency intravascular ultrasound, intravascular MRI, and optical coherence tomography. Efforts have also been made to recognize active inflammation in high‐risk plaques using intravascular thermography. Plaque chemical composition by measuring electromagnetic radiation using spectroscopy is also an emerging technology to detect vulnerable plaques. Noninvasive imaging with MRI, CT, and PET also holds the potential to differentiate between low and high‐risk plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque neither has been shown to definitively predict outcome. Nevertheless in contrast, there has been a parallel development in the physiological assessment of advanced atherosclerotic coronary artery disease. Thus recent trials using fractional flow reserve in patients with modest non flow‐limiting stenoses have shown that deferral of PCI with optimal medical therapy in these patients is superior to coronary intervention. Further trials are needed to provide more information regarding the natural history of high‐risk but non flow‐limiting plaque to establish patient‐specific targeted therapy and to refine plaque stabilizing strategies in the future. © 2009 Wiley‐Liss, Inc.