MRI of atherosclerosis: diagnosis and monitoring therapy

Atherosclerosis is a prevalent disease affecting millions of Americans. Despite our advances in diagnosis and treatment, atherosclerosis is the leading cause of death in America. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading noninvasive imaging modality for atherosclerotic disease. Atherosclerosis of the arterial wall of the human carotid, aortic, peripheral and coronary arteries have all been successfully evaluated. In addition, the power of magnetic resonance imaging to differentiate the major components of atherosclerotic plaque has been validated. The ability to image the vessel wall and risk stratify atherosclerotic plaque will create management decisions not previously faced, and has the potential to change the way atherosclerosis is treated.     

磁共振评估冠状动脉粥样硬化斑块的研究进展

冠状动脉粥样硬化性心脏病(coronary atherosclerosis heart disease,CHD)是人类主要死亡原因之一,其中急性冠脉综合征(acute coronary syndromes,ACS)是导致患者预后不良和发生猝死的主要原因。尸检病理结果发现,ACS发病的主要原因为动脉粥样硬化易损斑块破裂或内皮表面糜烂导致冠脉内血栓形成。磁共振成像(magnetic resonance imaging,MRI)作为一种无创、可重复性强、组织分辨率高的检查方法,多对比成像序列经过20余年的研发在颈动脉粥样硬化斑块中的应用已得到广泛证实,并在临床上及病理对照上得到进一步的验证。但冠状动脉管壁成像由于成像技术复杂,目前尚处于研究阶段。本文就磁共振成像评估冠状动脉粥样硬化斑块的研究进展进行综述。     

Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

Atherosclerosis is the primary underlying cause of cardiovascular disease (CVD). It is the leading cause of morbidity and mortality in the Western world today and is set to become the prevailing disease and major cause of death worldwide by 2020. In the 1950s surgical intervention was introduced to treat symptomatic patients with high‐grade carotid artery stenosis due to atherosclerosis – a procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic plaque from the affected carotid artery of these patients, CEA is beneficial by preventing subsequent ipsilateral ischemic stroke. However, it is known that patients with low to intermediate artery stenosis may still experience ischemic events, leading clinicians to consider plaque composition as an important feature of atherosclerosis. Today molecular imaging can be used for characterization, visualization and quantification of cellular and subcellular physiological processes as they take place in vivo; using this technology we can obtain valuable information on atherosclerostic plaque composition. Applying molecular imaging clinically to atherosclerotic disease therefore has the potential to identify atherosclerotic plaques vulnerable to rupture. This could prove to be an important tool for the selection of patients for CEA surgery in a health system increasingly focused on individualized treatment. This review focuses on current advances and future developments of in vivo atherosclerosis PET imaging in man.     

MRI对易损斑块的临床研究进展

动脉粥样硬化斑块破裂和血栓形成是诱发心脑血管疾病的直接原因。及时识别斑块的易损性逐渐成为近年的研究热点。影像学技术能直观易损斑块相关特征,提供相应治疗策略。核磁共振作为一项无创检查手段,可以对斑块的形态和功能进行综合评价。本文就核磁共振对颈动脉斑块的形态功能学检查做一简要综述。     

Current Development of Molecular Coronary Plaque Imaging using Magnetic Resonance Imaging towards Clinical Application

Cardiovascular disease (CVD) remains the leading cause of death in Western countries despite improvements in prevention, diagnosis and treatment. Atherosclerosis is a chronic inflammatory disease that remains clinically silent for many decades. Sudden rupture of “high-risk/vulnerable” plaques has been shown to be responsible for the majority of acute cardiovascular events, including myocardial infarction and stroke. Therefore, early detection of biological processes associated with atherosclerosis progression and plaque instability may improve diagnosis and treatment and help to better monitor the effectiveness of therapeutic interventions. Molecular magnetic resonance imaging (MRI) is a promising tool to detect molecular and cellular changes in the carotid, aortic and coronary vessel wall including endothelial dysfunction, inflammation, vascular remodelling, enzymatic activity, intraplaque haemorrhage and fibrin deposition and thus may allow early detection of unstable lesions and improve the prediction of future coronary events. Evaluation of atherosclerosis at both, the preclinical and clinical level includes non-contrast-enhanced (NCE) and contrast-enhanced (CE) MRI with and without the use of MR contrast agents. To increase the biological information obtained by MRI a variety of targeted-specific molecular probes have been developed for the non-invasive visualization of particular biological processes at the molecular and cellular level. This review will discuss the recent advances in molecular MRI of atherosclerosis, covering both pulse sequence development and also the design of novel contrast agents, for imaging atherosclerotic disease in vivo.     

Imaging of the vulnerable plaque: new modalities

Atherosclerosis is currently considered to be an inflammatory and thus a systemic disease affecting multiple arterial beds. Recent advances in intravascular imaging have shown multiple sites of atherosclerotic changes in coronary arterial wall. Traditionally, angiography has been used to detect and characterize atherosclerotic plaque in coronary arteries, but recently it has been found that plaques that are not significantly stenotic on angiography cause acute myocardial infarction. As a result, newer imaging and diagnostic modalities are required to predict which of the atherosclerotic plaque are prone to rupture and hence distinguish "stable" and "vulnerable" plaques. Intravascular ultrasound can identify multiple plaques that are not seen on coronary angiography. Thermography has shown much promise and is based on the concept that the inflammatory plaques are associated with increased temperature and can also identify "vulnerable patients." Of all these newer modalities, magnetic resonance imaging has shown the most promise in identification and characterization of vulnerable plaques. In this article, we review the newer coronary artery imaging modalities and discuss the limitations of traditional coronary angiography.     

Magnetic Resonance Imaging of Carotid Atherosclerosis and the Risk of Stroke

Stroke attributable to carotid atherosclerosis is a leading cause of mortality and morbidity. The clinical management of carotid atherosclerosis presently relies on the degree of stenosis determined by angiography. Degree of stenosis is limited in stratifying patients’ risk of stroke. Advances in magnetic resonance imaging have resulted in the ability to directly assess atherosclerotic plaque components, morphology, and biomechanical stress levels. Components of atherosclerosis, including lipid-rich necrotic core, fibrous cap thickness/disruption, and intraplaque hemorrhage, are promising emerging indicators of stroke. Information beyond luminal stenosis from magnetic resonance imaging may allow for improved detection of patients at risk of stroke from carotid atherosclerosis. We review the recent literature on the relationship of magnetic resonance imaging detected plaque components and cerebrovascular events. Clinical applications of magnetic resonance imaging of carotid plaque components are discussed.     

Plaque progression and regression in atherothrombosis

Summary.  Atherosclerotic disease is a pathological process characterized by the deposition of lipid and other blood-borne material within the arterial wall. The deposition of these materials and the subsequent thickening of the wall may significantly compromise the vessel lumen. Atherosclerosis is a diffuse disease with focal clinical manifestations that are the consequence of thrombotic complications on disrupted atherosclerotic lesions. Until recently, atherosclerosis development was envisaged as an incessant progressing process; however, new evidence has shown that atherosclerotic plaque homeostasis is not necessarily a constantly progressing process. There are many data showing that atherosclerotic plaque formation can be slowed, stopped or even reversed. Comprehension of the underlying mechanisms involved in the homeostasis of atherosclerotic plaque (progression/regression) should allow the development of interventions enhancing the regression pathway. Novel imaging technology has allowed the accurate evaluation of plaque progression, vital in the assessment of the efficacy of interventions. In this review we discuss the processes involved in the formation and progression of atherosclerotic lesions, the triggers for plaque disruption, as well as new therapies. We also deal with the potential pathways of plaque regression, as well as tools for accurate serial atherosclerotic quantification.     

ARFI imaging for noninvasive material characterization of atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death in the United States, with 70% of CVD mortalities the result of sequelae of atherosclerosis. An urgent need for enhanced delineation of vulnerable plaques has catalyzed the development of novel atherosclerosis imaging strategies that use X-ray computed tomography, magnetic resonance and ultrasound modalities. As suggested by the pathophysiology of plaque development and progression to vulnerability, insight to the focal material, i.e., mechanical, properties of arterial walls and plaques may enhance atherosclerosis characterization. We present acoustic radiation force impulse (ARFI) ultrasound in application to mechanically characterizing a raised focal atherosclerotic plaque in an iliac artery extracted from a relevant pig model. ARFI results are correlated to matched immunohistochemistry, indicating elastin and collagen composition. In regions of degraded elastin, slower recovery rates from peak ARFI-induced displacements were observed. In regions of collagen deposition, lower ARFI-induced displacements were achieved. This work demonstrates ARFI for characterizing the material nature of an atherosclerotic plaque.     

Subclinical atherosclerosis: what it is, what it means and what we can do about it

Atherosclerosis is a chronic, progressive, inflammatory disease with a long asymptomatic phase. Disease progression can lead eventually to the occurrence of acute cardiovascular events such as myocardial infarction, unstable angina pectoris and sudden cardiac death. While the disease is still in a subclinical stage, however, the presence of atherosclerosis can be identified by several methods, including coronary angiography, intravascular ultrasonography, B-mode ultrasonography, computed tomography and magnetic resonance imaging. Based on the results of imaging studies, statin therapy can slow, halt or even reverse the progression of atherosclerotic disease, depending on the intensity of treatment. Whether to screen and treat patients for subclinical atherosclerosis remains controversial. Although atheromatous plaque burden reduction has not yet been definitively correlated with significant decreases in risk for acute coronary events in asymptomatic patients, statin therapy contributes significantly to the risk reduction observed in clinical trials in patients with and without overt coronary disease.     

Noninvasive imaging of atherosclerotic vessels by MRI for clinical assessment of the effectiveness of therapy

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized countries. Despite advances in our understanding of the mechanisms of pathogenesis and new treatment modalities, the absence of an adequate noninvasive method for early detection limits prevention or treatment of patients with various degrees and localizations of atherothrombotic disease. The ideal clinical imaging modality for atherosclerosis should be safe, inexpensive, noninvasive or minimally invasive, accurate, and reproducible, thus allowing longitudinal studies in the same patients. Additionally, the results should correlate with the extent of atherosclerotic disease and have high predictive values for clinical events. In vivo, high-resolution magnetic resonance imaging (MRI) has recently emerged as one of the most promising techniques for the noninvasive study of atherothrombotic disease in several vascular beds such as the aorta, the carotid arteries, and the coronary arteries. Most importantly MRI can be used to characterize plaque composition as it allows the discrimination of lipid core, fibrosis, calcification, and intra-plaque hemorrhage deposits. MRI findings have been extensively validated against pathology in ex vivo studies of carotid, aortic, and coronary artery specimens obtained at autopsy and using experimental models of atherosclerosis. In vivo MRI of carotid arteries of patients referred for endarterectomy has shown a high correlation with pathology and with previous ex vivo results. A recent study in patients with plaques in the thoracic aorta showed that compared with transesophageal echocardiography plaque composition and size are more accurately characterized and measured using in vivo MRI. The composition of the plaque rather than the degree of stenosis determines the patient outcome. Therefore, a reliable noninvasive imaging tool able to detect early atherosclerotic disease in the various regions and identify the plaque composition is clinically desirable. MRI has potential in the detection arterial thrombi and in the definition of thrombus age. MRI has been used to monitor plaque progression and regression in several animal model of atherosclerosis and more recently in human. Advances in diagnosis prosper when they march hand-in-hand with advances in treatment. We stand at the threshold of accurate noninvasive assessment of atherosclerosis. Thus, MRI opens new strategies ranging from screening of high-risk patients for early detection and treatment as well as monitoring the target areas for pharmacological intervention.     

The assessment of the vulnerable atherosclerotic plaque using MR imaging: a brief review

The study of atherosclerotic disease during its natural history and after therapeutic intervention may enhance our understanding of the progression and regression of this disease and will aid in selecting the appropriate medical treatments or surgical interventions. Several invasive and non-invasive imaging techniques are available to assess atherosclerotic disease vessels. Most of these techniques are strong in identifying the morphological features of the disease such as lumenal diameter and stenosis or wall thickness, and in some cases provide an assessment of the relative risk associated with the atherosclerotic disease. However, none of these techniques can fully characterize the composition of the atherosclerotic plaque in the vessel wall and therefore are incapable of identifying the vulnerable plaques. High-resolution, multi-contrast, magnetic resonance (MR) can non-invasively image vulnerable plaques and characterize plaques in terms of lipid and fibrous content and identify the presence of thrombus or calcium. Application of MR imaging opens up whole new areas for diagnosis, prevention, and treatment of atherosclerosis.     

Intravascular Photoacoustic Imaging: A New Tool for Vulnerable Plaque Identification

The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to be the most prominent type of vulnerable plaque. No clinically available imaging technique can characterize atherosclerotic lesions to the extent needed to determine plaque vulnerability prognostically. Intravascular photoacoustic imaging (IVPA) has the potential to take a significant step in that direction by imaging both plaque structure and composition. IVPA is a natural extension of intravascular ultrasound that adds tissue type specificity to the images. IVPA utilizes the optical contrast provided by the differences in the absorption spectra of plaque components to image composition. Its capability to image lipids in human coronary atherosclerosis has been shown extensively ex vivo and has recently been translated to an in vivo animal model. Other disease markers that have been successfully targeted are calcium and inflammatory markers, such as macrophages and matrix metalloproteinase; the latter two through application of exogenous contrast agents. By simultaneously displaying plaque morphology and composition, IVPA can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention.     

Optimization of ex vivo CT- and MR- Imaging of Atherosclerotic Vessel Wall Changes

OBJECTIVE: To optimize a methodology for ex vivo imaging of atherosclerotic vessel wall changes using multidetector-row computed tomography (MDCT) and multi-contrast magnetic resonance imaging (MRI). METHODS: In phantom studies and studies on intact ex vivo porcine and human hearts, various filling mixtures of MDCT and MRI contrast agents have been evaluated, to enable filling and distension of the coronary arteries for optimal visualization of atherosclerotic vessel wall changes with both techniques. Various proportions of methyl cellulose, iodine-containing CT contrast agent and paramagnetic MR contrast agent containing iron-oxide particles have been tested. Imaging parameters have been optimized for high resolution plaque imaging using a four detector-row CT scanner and a 1.5 T MR system. RESULTS: Phantom studies and studies on ex vivo porcine and human hearts demonstrated optimal proportion of methyl cellulose and CT contrast agent to be 98% vs. 2%, and 75% vs. 25% of methyl cellulose vs. MR contrast agent, respectively. These proportions provided optimal opacification of the vessel lumen in the MDCT images with 250 Hounsfield Units, and good signal suppression within the vessel lumen in the MR images, resembling in vivo imaging techniques. After retrospective matching with histopathology, atherosclerotic lesions of the human ex vivo specimens could be identified on MRI and MDCT images. CONCLUSION: Using an optimized mixture of methyl cellulose, MDCT and MRI contrast agents, visualization of atherosclerotic vessel wall changes is feasible, and applicable to various ex vivo models.     

动脉粥样硬化易损斑块的影像学诊断进展

动脉粥样硬化导致心脑血管疾病是影响人类健康的主要原因,斑块破裂导致的血栓和栓塞约占心脑血管事件的70%。早期发现易引发缺血事件的易损斑块并及时给予治疗,对于预防和减少心脑血管事件的发生意义重大。本文综述近年来各种影像诊断技术检测易损斑块的研究进展,旨在为临床正确应用影像新技术检测易损斑块、预防和降低心脑血管事件的发生提供帮助。     

Aortic plaque imaging and monitoring atherosclerotic plaque interventions

The atherosclerotic process that results in coronary artery disease (CAD) is recognized to be a generalized process that may involve the entire vasculature. The association between CAD and atherosclerotic plaques in the thoracic aorta has often been reported using transesophageal echocardiography. An autopsy study showed plaques in the abdominal aorta, but not in the thoracic aorta, to be severe in patients with cardiac events. However, studies evaluating an association between abdominal aortic plaques and CAD are scarce. Recently, magnetic resonance imaging (MRI) has become a useful tool for the noninvasive evaluation of atherosclerotic plaques in both the thoracic and abdominal aortas. Plaques in the thoracic and abdominal aortas were found to be characteristically associated with hypercholesterolemia and smoking, respectively, suggesting different susceptibilities to risk factors. Because patients have various risk factors, it seems to be preferable to evaluate atherosclerosis in multiple vascular beds than in just 1 bed. Magnetic resonance imaging can evaluate atherosclerosis in multiple vascular beds in the same examination session. Complex aortic plaques, especially in the abdominal aorta, were found to be associated with myocardial infarction and complex coronary lesions, suggesting a link between aortic and coronary plaque instability. Aortic MRI may thus be useful for identifying vulnerable patients. Moreover, MRI is a powerful tool to serially evaluate plaque progression and regression. Intensive lipid-lowering therapy can regress aortic plaques, but the susceptibility to lipid lowering and the process of plaque regression may differ between the thoracic and abdominal aortic plaques.     

冠状动脉旁脂肪促进冠状动脉粥样硬化的研究进展

近年来随着对全身脂肪、循环脂质水平升高与冠心病发病关系的临床证据和基础研究的深入,越来越充分的证据表明脂肪组织通过旁分泌、自分泌炎症因子加重全身血管炎症状态、介导胰岛素抵抗、促进血液高凝等途径直接导致冠心病等血管性疾病的发病率大幅增加。传统的冠状动脉粥样硬化理论认为冠状动脉粥样硬化起始于高血压、高血脂、高血糖和其他血管内危险因素导致的血管内皮损伤,继而引起内皮功能紊乱、内膜增生、炎症细胞趋化、脂质累积,最终这些"由内而外"的因素导致动脉粥样硬化斑块的形成,新近的研究渐渐把这种"由外而内"的发病机制和传统的由血管内因素(血浆脂质)异常到内皮功能损害、内膜增殖、脂质斑块形成联系起来,最近的证据表明新生滋养血管与血管壁重构是冠状动脉旁脂肪促进动脉粥样硬化斑块易损的两个重要机制。本文基于现有临床和实验方面的最新证据,阐明冠状动脉旁脂肪组织参与整个动脉粥样硬化的时间和空间过程。     

F-18-FDG Imaging for Atherosclerotic Plaque Characterization

Atherosclerosis is a dynamic inflammatory disease of the arterial vessel wall which is still the “number one killer” in Western civilization. It turned out recently that the molecular composition and the metabolic state of atherosclerotic plaques rather than their size or degree of stenosis is of crucial importance to predict the fate of individual plaques. Thus, an imaging modality noninvasively characterizing plaques is needed. In this context, FDG-PET has great potential since FDG accumulates in plaque macrophages and uptake is correlated with macrophage density which is high in highly inflammatory atherosclerotic plaques. FDG uptake in atherosclerosis of large arteries is observed frequently, is associated with cardiovascular risk factors on the one hand, and is probably correlated with the occurrence of cardiovascular events. Moreover, it is reported that vascular FDG uptake can be attenuated by cholesterol-lowering therapies and therefore could also serve as a tool of therapy monitoring. Despite some positive results of preliminary studies, imaging of rupture-prone atherosclerotic plaques with FDG-PET still remains a challenge and is not yet established. The following article provides the biological basis of FDG imaging of atherosclerotic plaques, an overview of preclinical studies, important clinical studies and approaches of coronary artery imaging.     

Segmentation of wall and plaque in in vitro vascular MR images

Atherosclerosis leads to heart attack and stroke, which are major killers in the western world. These cardiovascular events frequently result from local rupture of vulnerable atherosclerotic plaque. Non-invasive assessment of plaque vulnerability would dramatically change the way in which atherosclerotic disease is diagnosed, monitored, and treated. In this paper, we report a computerized method for segmentation of arterial wall layers and plaque from high-resolution volumetric MR images. The method uses dynamic programming to detect optimal borders in each MRI frame. The accuracy of the results was tested in 62 T1-weighted MR images from six vessel specimens in comparison to borders manually determined by an expert observer. The mean signed border positioning errors for the lumen, internal elastic lamina, and external elastic lamina borders were –0.1 ± 0.1, 0.0 ± 0.1, and –0.1 ± 0.1 mm, respectively. The presented wall layer segmentation approach is one of the first steps towards non-invasive assessment of plaque vulnerability in atherosclerotic subjects.     

A focus on inflammation as a major risk factor for atherosclerotic cardiovascular diseases

Atherosclerosis is a dynamic, pathogenic process in the artery wall, with potential adverse outcome for the host. Acute events such as myocardial infarction and ischemic stroke often result from rupture of unstable atherosclerotic lesions. Understanding the underlying pathology of such lesions and why and when they rupture, is therefore of great interest for the development of new diagnostics and treatment. Inflammation is one of the key drivers of atherosclerotic plaque development and the interplay between inflammation and lipids constitutes the hallmark of atherosclerotic disease. This review summarizes the role of inflammation in atherosclerosis and presents some of the latest discoveries as well as unmet needs regarding the role of inflammation as major risk factor in atherosclerotic disease.