Complementary value of cardiac FDG PET and CT for the characterization of atherosclerotic disease

For decades, the identification of significant luminal narrowing has been the hallmark to characterize the presence and extent of coronary artery disease. However, it is now known that characterizations of systemic atherosclerosis burden and inflammation, as well as the local quality of plaque composition and morphology, allow better characterization of coronary artery disease and thus may allow improved prediction of adverse cardiovascular events. Plaque characterized histologically as a thin-cap fibroatheroma (ie, an atheroma with a thin fibrous cap, an underlying lipid-rich necrotic core, and inflammatory activity) has been recognized as representing vulnerable or high-risk plaque. Positron emission tomography (PET) and cardiac computed tomography (CT) are noninvasive modalities that provide metabolic (PET) and morphologic (CT) information about atherosclerotic plaque. PET allows the quantification of the uptake of fluorine 18 fluorodeoxyglucose (FDG) within the arterial wall, which provides a measure of macrophage activity within atheromatous plaque. Coronary CT allows the depiction of plaque morphology and composition. Thus, integrated imaging with PET and CT (PET/CT) permits coregistration of FDG activity with the presence and morphology of plaque and may lead to improved characterization of vulnerable plaque or vulnerable patients, or both. This review details the methods and principles of cardiac FDG PET and coronary CT and provides an overview of the research, with an emphasis on the identification and characterization of vulnerable plaque.     

心脑血管粥样易损斑块的诊断及研究进展

动脉粥样硬化易损斑块是指稳定性差及存在血栓形成倾向的斑块,急性心脑血管缺血事件主要是由易损斑块的破裂和继发血栓形成所致。研究表明,冠状动脉粥样硬化常与头颈动脉粥样硬化密切相关且常同时发生,一些炎症因子在发病早期即可在外周血中被检测到。诊断易损斑块的临床手段有很多,笔者就冠状动脉、头颈部血管粥样易损斑块的影像学诊断及相关血清炎症因子的研究现状与前景进行综述。     

Methods of plaque quantification and characterization by cardiac computed tomography

The pathologic evolution of coronary artery atherosclerosis occurs slowly over decades, which may provide an opportunity for diagnostic imaging to identify patients before clinical events evolve. Cardiac computed tomography (CT) is an emerging noninvasive imaging tool, which can visualize the entire coronary tree with submillimeter resolution. We reviewed the current status of cardiac CT to qualitatively and quantitatively determine coronary plaque dimensions and composition, and its potential to improve our understanding of the natural history of coronary artery disease as well as prevention of cardiovascular events.     

Targeting the vulnerable plaque: The evolving role of nuclear imaging

The majority of acute ischemic events relating to atherosclerosis are caused by plaque rupture and ensuing thrombosis. The risk of plaque rupture is dictated in part by plaque morphology, which in turn is influenced by pathophysiologic mechanisms at the cellular and molecular level. Anatomic imaging modalities such as intravascular ultrasound, high-resolution magnetic resonance imaging, and multislice computed tomography can identify morphologic features of the vulnerable plaque, such as a large lipid core and thin fibrous cap, but give little or no information regarding molecular and cellular mechanisms, such as endothelial function, macrophage activation, lipid transport and metabolism, and cell death. Recent studies suggest that nuclear imaging may be able to provide images of sufficient quality to identify and quantify some of these molecular and cellular pathophysiologic processes. In the future this could allow for the early identification and noninvasive monitoring of vulnerable plaque.     

正电子示踪剂在动脉粥样硬化易损斑块评价中的应用研究

动脉粥样硬化（AS）易损斑块糜烂及破裂是引起急性心脑血管疾病的主要原因之一,早期发现对于有效预防和管理心肌梗死和脑卒中等危及生命的心血管事件至关重要。正电子发射体层成像（PET）可无创地监测与AS相关的生物过程,放射性示踪剂能够从炎症、微钙化、缺氧、新生血管生成、淀粉样变、趋化因子受体等多方面反映病变发生机制,对诊断斑块性质有很好的应用前景。就各类新型正电子放射性示踪剂用于PET探测AS易损斑块的作用及价值予以综述。     

ISCHEMIA trial – Failed intervention or failed stratification?

Treatment of stable ischemic heart disease remains controversial due to lack of proper measures to identify the vulnerable patient who will suffer acute coronary events. Imaging modalities can identify rupture-prone coronary plaques but studies have found that most plaque ruptures without causing clinical events (1). High risk plaques identified by CT Angiogram (CTA) was found to be predictive of acute coronary events (ACS) in a large cohort study but the extent of atherosclerotic burden was a confounder (2). As such, numerous studies have suggested total atherosclerotic plaque burden as the main determinant of adverse patient outcomes (3,4). Coronary artery calcium (CAC) is a highly specific surrogate for coronary atherosclerosis burden and is the most predictive single cardiovascular risk marker in asymptomatic persons (5). The greater the atherosclerotic plaque burden, the more likely plaque ruptures will occur and the greater the probability that one of them triggers vascular thrombosis and a clinical event (6).     

PET-CT在冠心病诊断中的临床应用及新进展

PET-CT对冠心病的诊断、治疗方案的选择及预后的判断等具有重要意义,可无创性诊断冠心病、评估动脉粥样硬化斑块性质、指导冠心病治疗方法的选择与疗效监测、判断预后等.该文介绍PET-CT在冠心病中的临床应用及新进展.     

CT-based calcium scoring to screen for coronary artery disease: why aren't we there yet?

OBJECTIVE: The purpose of this article is to examine the value of coronary artery calcium scoring as a screening tool for identifying individuals at risk of experiencing a catastrophic coronary event. CONCLUSION: Because of the noninvasive nature of CT and the large societal burden of coronary atherosclerosis, there is great interest in developing CT-based techniques for detection of coronary artery calcium, a known marker of underlying atherosclerosis. However, important questions remain including the role of calcium in the process of acute plaque rupture, the utility of this technique in the asymptomatic population, and the statistical distribution of calcium scores and hard cardiac events in the general population.     

Role of inflammation in atherosclerosis.

Inflammation plays a major role in all phases of atherosclerosis. Stable plaques are characterized by a chronic inflammatory infiltrate, whereas vulnerable and ruptured plaques are characterized by an "active" inflammation involved in the thinning of the fibrous cap, predisposing the plaque to rupture. Although a single vulnerable atherosclerotic plaque rupture may cause the event, there are many other types of plaques, several of which are vulnerable. The existence of multiple types of vulnerable plaques suggests that atherosclerosis is a diffuse inflammatory process. A current challenge is to identify morphologic and molecular markers able to discriminate stable plaques from vulnerable ones, allowing the stratification of patients at high risk for acute cardiovascular and cerebrovascular events before clinical syndromes develop. With that aim in mind, this article summarizes the natural history of atherosclerotic plaques, focusing on molecular mechanisms affecting plaque progression and serum markers correlated with plaque inflammation.     

MR imaging of atherosclerotic plaque

MRI is a powerful noninvasive imaging tool with high spatial resolution that continues to prove its value in determining atherosclerotic plaque size, volume, and tissue components. Multispectral MRI sequences have been validated to characterize atherosclerotic plaque components in animals; they have recently been applied to human aorta and carotid artery and are being used to identify the vulnerable plaque. The ability to measure wall thickness in human coronary artery wall has been realized. Future developments may allow plaque characterization in the coronary arteries with surface coil imaging, but intravascular MRI may play an important role in this regard. Novel contrast agents for identifying inflammation and thrombus within atherosclerotic plaque will aid in the identification of higher-risk atherosclerotic disease. Lastly, MRI has progressed to the point where it can be used in serial studies of atherosclerotic plaque progression and regression in the face of therapeutic intervention. MRI will continue to evolve an important role in imaging of atherosclerotic plaque.     

Coronary artery calcium score: has anything changed?

Calcium deposition along the coronary artery walls is a surrogate biomarker for atherosclerosis, and its presence in the coronary arteries could reflect the severity of coronary artery disease (CAD) High coronary artery calcium score (CACS) correlates with advanced disease and a higher likelihood of coronary stenoses. Many studies have supported the role of CACS as a screening tool for CAD. Historically, CACS was introduced with electron beam computed tomography (EBCT), but in the last 30 years, many changes have occurred in CT, where the development of multidetector spiral technology has made reliable the noninvasive study of the heart and coronary arteries. Correlation studies with intravascular ultrasound (IVUS) and histology have demonstrated the capability of multidetector CT (MDCT) to provide information useful for characterising atherosclerotic plaque in a noninvasive manner. This has shifted the interest from heavily calcified deposits to plaque with a low-density core and small, superficial calcified nodules, features more frequently present in atherosclerotic plaque prone to rupture and responsible for acute coronary events (culprit lesions). The purpose of this review article is to summarise the recent evolution and revolution in the field of CT, strengthen the importance of a coronary CT study not limited to CACS evaluation and CAD grading but also used to obtain information about plaque composition, and to improve stratification of the patient at risk for acute coronary events.     

MRI of atherosclerosis

The emergence of high-resolution, rapid imaging methods has enabled MRI to noninvasively image the fine internal structure of atherosclerotic artery walls. This capability has, in turn, captured the interest of clinicians, who see it as an opportunity to assess disease severity based on the characteristics of atherosclerotic lesions themselves, rather than only their effects on the vessel lumen. MRI of atherosclerosis thus has the potential to be used in medical treatment decisions or to assess the effects of experimental treatment options. Given this potential, a number of research groups have been investigating MRI of atherosclerosis in an effort to establish the ability of MRI to determine atherosclerotic plaque burden, detect plaque composition, and ultimately identify vulnerable plaque before it leads to a clinical event. In this review, the current state of the art is summarized for the three primary vessel targets: the carotid artery, the aorta, and the coronary arteries.     

The clinical utility of hybrid imaging for the identification of vulnerable plaque and vulnerable patients

Despite decades of research and major innovations in technology, cardiovascular disease remains the leading cause of death globally. Our understanding of major cardiovascular events and their prevention is centred around the atherosclerotic plaque and the processes that ultimately lead to acute plaque rupture. Recent advances in hybrid imaging technology allow the combination of high spatial resolution and anatomical detail with molecular assessments of disease activity. This provides the ability to identify vulnerable plaque characteristics and differentiate active and quiescent disease, with the potential to improve patient risk stratification. Combined positron emission tomography and computed tomography is the prototypical non-invasive hybrid imaging technique for coronary artery plaque assessment. In this review we discuss the current state of play in the field of hybrid coronary atherosclerosis imaging.     

16层螺旋CT对冠状动脉粥样斑块的研究

目的探讨16层螺旋CT对冠状动脉斑块诊断的价值。方法35例临床诊断为冠心病患者按危险度分为2组:急性冠状动脉综合征(ACS)组(包括急性心肌梗塞,不稳定型心绞痛)和稳定型心绞痛组。行16层螺旋CT冠状动脉成像及图像后处理,对检出的斑块进行定性分析,并对各种性质斑块所引起的管腔狭窄程度进行分析。结果35例中,ACS组27例,软斑块19个,中间斑块11个,钙化斑块7个;8例稳定型心绞痛组中软斑块3个,中间斑块3个,钙化斑块11个,经统计学卡方检验P<0.05有统计学意义,表明中间斑块和软斑块(尤其是软斑块)与冠心病危险性程度成显著的正相关;非钙化斑块导致管腔狭窄程度:轻度狭窄8处,中度狭窄9处,重度狭窄22处,而钙化斑块:轻度狭窄10处,中度狭窄5处,重度狭窄5处,经统计学卡方检验P<0.05有统计学意义,表明不同性质斑块与其导致管腔狭窄间有显著差别。结论16层螺旋CT冠状动脉造影成像是一种有效、无创、简便、优良的诊断方法,可作为诊断冠心病的可靠手段用于临床。     

高频CDFI超声在颈动脉粥样硬化病变中的检测价值

 目的探讨高频彩色多普勒血流显像(CDFI)超声对高血压、冠心病、脑梗死及糖尿病患者颈动脉粥样硬化病变的检测价值.方法应用高频CDFI超声检查高血压、冠心病、脑梗死及糖尿病患者的颈动脉,测量其管腔内径,内膜中膜的厚度(Intima-media thickness,IMT),并观察斑块的有无及血流动力学变化,并与正常对照组相比较.结果高血压、冠心病、脑梗死及糖尿病患者中的颈动脉粥样硬化、斑块形成,管腔内膜中膜均有不同程度的增厚,并伴有管腔狭窄等情况,其异常超声检出率与对照组比较有显著性差异(P＜0.05).结论高频CDFI超声检查对高血压、冠心病、脑梗死及糖尿病患者颈动脉病变的诊断有一定的临床价值,相对于动脉造影来说,是一种无创性检查和发现、筛选心脑血管疾病高危患者的首选方法,能为临床了解及监测病情及对预后的判断提供较丰富的影像学依据.     

How accurate is atherosclerosis imaging by coronary computed tomography angiography?

Invasive coronary plaque imaging such as intravascular ultrasound and optical coherence tomography has been widely used to observe culprit or non-culprit coronary atherosclerosis, as well as optimize stent sizing, apposition and deployment. Coronary computed tomographic angiography (CTA) is non-invasively available to assess coronary artery disease (CAD) and has become an appropriate strategy to evaluate patients with suspected CAD. Given recent technologies, semi-automated plaque software is available to identify coronary plaque stenosis, volume and characteristics and potentially allows to be used for the assessment of more details of plaque information, progression and future risk as a surrogate tool of the invasive imaging modalities. This review article aims to focus on various evidence in coronary plaque imaging by coronary CTA and describes how accurate coronary CTA can classify coronary atherosclerosis.     

Cardiovascular magnetic resonance imaging of coronary atherothrombosis

Summary  Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombus formation, is the major cause of acute coronary syndromes and cardiovascular death. CMR imaging of coronary atherothrombosis is challenging because of the small caliber of the vessels combined with respiratory and cardiac motion. Freebreathing 3D CMR coronary vessel wall imaging has enabled in vivo quantification of coronary plaque burden and remodeling as a marker of subclinical CAD. Molecular imaging via novel target-specific contrast agents such as fibrin-binding agents to detect arterial thrombus shows great promise as the new frontier in noninvasive imaging. Advances in molecular imaging and CMR techniques offer the potential for direct imaging of coronary thrombosis and in-stent thrombosis by use of novel fibrin-binding molecular MR contrast agents. Although the current role of noninvasive CMR imaging of atherothrombosis remains investigational, these techniques should enhance our understanding of the natural history of acute coronary syndromes and thereby facilitate strategies to prevent acute coronary syndromes and cardiovascular death in vulnerable patients.     

粥样硬化易损斑块传统影像与分子影像检测与评价现状

易损斑块引发的心脑血管急性事件是威胁人类生命健康的主要原因之一,检测与评价斑块的易损性尤为重要.传统影像学技术多从形态结构方面评价粥样斑块,目前的扫描技术有一定进步,但在早期发现和评估斑块方面有其局限性.分子影像学方法在核素显像、MRI、超声和光学成像中均有应用,对易损斑块的显像靶点涉及斑块组成、炎症、血栓形成、新生血管、凋亡等方面,能反映斑块形态结构和功能代谢的改变.多模式分子影像综合了各单一显像模式的优势,将会为易损斑块的早期检测与评估提供帮助.该文就传统影像与分子影像在粥样硬化易损斑块检测与评价中的现状进行综述.     

Computed tomography coronary calcium screening and myocardial perfusion imaging

Cardiac computed tomography (CT) has seen an exponential increase in interest as applications expanded from identification of coronary artery calcification to noninvasive coronary angiography and, more recently, identification of soft and noncalcified plaques. The interest arises from the well-known fact that cardiovascular disease remains the most prevalent cause of death in the Western hemisphere and the fact that in a large proportion of patients the initial event is either sudden death or a disabling myocardial infarction or stroke. Although traditional risk factors are extremely helpful in determining risk in a population, the prognostic ability of risk factors alone in the individual patient is limited. Hence, researchers have turned their attention to noninvasive modalities to image the atherosclerotic plaque in its preclinical stages, hoping to better address this ailment at its inception and change the natural history of the disease. Measurements of coronary artery calcium (CAC) serve as a quantitative reflection of the severity of coronary artery atherosclerosis, and greater calcium burdens correlate with more advanced disease. Indeed, CAC has been shown to add prognostic value to traditional risk factors in patients at intermediate risk, and in this group of patients, it is most cost-effective. Furthermore, CAC measurements providing an assessment of coronary atherosclerotic plaque burden appear to be complementary to myocardial perfusion single photon emission computed tomography that offers information regarding inducible ischemia. In this manner, a better assessment of risk in a patient suspected of harboring preclinical or early coronary artery disease can be achieved. In this article we review the most relevant literature regarding the utilization of CAC testing as a tool to refine risk assessment and use several case studies to exemplify the combination of CT imaging and functional myocardial perfusion studies, which may provide a better identification of patients in need of aggressive medical therapy and those needing invasive assessment for possible coronary revascularization.     

Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries

Atherosclerosis is a dynamic inflammatory disorder. The biological composition and inflammatory state of an atherosclerotic plaque, rather than the degree of stenosis or its size are the major determinants of acute clinical events. A noninvasive technique to detect vulnerable atherosclerotic plaque is critically needed. FDG-PET/CT, a combined functional and structural whole-body imaging modality, holds great potential for this purpose. FDG uptake in large arteries has been frequently observed and is associated with cardiovascular risk factors. FDG accumulates in plaque macrophages and uptake is correlated with macrophage density. It is known that vascular FDG uptake and calcification do not overlap significantly and changes of FDG uptake are common, suggesting that FDG uptake may represent a dynamic inflammatory process. It has been reported that vascular FDG uptake can be attenuated by simvastatin in patients, and by the antiinflammatory drug probucol in rabbits. Vascular FDG uptake has been linked to cardiovascular events in some preliminary studies. Data from basic sciences, and animal and clinical studies support the emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries in humans.