Imaging Atherosclerosis and Vulnerable Plaque (original) (raw)
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In vivo Detection of Vulnerable Atherosclerotic Plaque by MRI in a Rabbit Model
Circulation: Cardiovascular Imaging, 2010
Background-The ability to identify atherosclerotic plaques with a high risk for sudden disruption before stroke or myocardial infarction would be of great utility. We used a rabbit model of controlled atherothrombosis to test whether in vivo MRI can noninvasively distinguish between plaques that disrupt after pharmacological triggering (vulnerable) and those that do not (stable). Methods and Results-Atherosclerosis was induced in male New Zealand White (nϭ17) rabbits by cholesterol diet and endothelial denudation of the abdominal aorta. After baseline (pretrigger) MRI with and without gadolinium contrast, the rabbits underwent 2 pharmacological triggerings to induce atherothrombosis, followed by another MRI 48 hours later (post-triggering). Atherosclerosis was identified by the pretriggered images in all rabbits, and thrombosis was identified in 9 of 17 animals (53%) by post-trigger MRI. After the animals were euthanized, 95 plaques were analyzed; 28 (29.5%) had thrombi (vulnerable) and 67 did not (70.5%). Pretriggered MRI revealed comparable stenosis in stable and vulnerable plaques, but vulnerable plaques had a larger plaque area (4.8Ϯ1.6 versus 3.0Ϯ1.0 mm 2 ; Pϭ0.01), vessel area (9.2Ϯ3.0 versus. 15.8Ϯ4.9 mm 2 ; Pϭ0.01), and higher remodeling ratio (1.16Ϯ0.2 versus 0.93Ϯ0.2; Pϭ0.01) compared with stable plaques. Furthermore, vulnerable plaques more frequently exhibited (1) positive remodeling (67.8% versus 22.3%; Pϭ0.01), in which the plaque is hidden within the vessel wall instead of occluding the lumen; and (2) enhanced gadolinium uptake (78.6% versus 20.9%; Pϭ0.01) associated with histological findings of neovascularization, inflammation, and tissue necrosis. Conclusions-We demonstrate that in vivo MRI at 3.0 T detects features of vulnerable plaques in an animal model of controlled atherothrombosis. These findings suggest that MRI may be used as a noninvasive modality for localization of plaques that are prone to disruption. (Circ Cardiovasc Imaging. 2010;3:323-332.) The online-only Data Supplement is available at http://circimaging.ahajournals.org/cgi/content/full/CIRCIMAGING.109.918524./DC1.
Molecular Imaging to Identify the Vulnerable Plaque—From Basic Research to Clinical Practice
Molecular Imaging and Biology, 2012
Cardiovascular disease (CVD) is still the leading cause of death in the Western World. Adverse outcomes of CVD include stroke, myocardial infarction, and heart failure. Atherosclerosis is considered to be the major cause of CVD and is estimated to cause half of all deaths in developed countries. Atherosclerotic lesions of the vessel wall may obstruct blood flow mechanically through stenosis, but rupture of atherosclerotic plaques causing formation of occlusive thrombi is far more prevalent. Unfortunately, conventional diagnostic tools fail to assess whether a plaque is vulnerable to rupture. Research over the past decade identified the biological processes that are implicated in the course towards plaque rupture, like cell death and inflammation. Knowledge about plaque biology propelled the development of imaging techniques that target biologic processes in order to predict the vulnerable plaque. This paper discusses novel and existing molecular imaging targets and addresses advantages and disadvantages of these targets and respective imaging techniques in respect of clinical application and socio-economic impact.
International Journal of Molecular Sciences
Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different inv...
The International Journal of Cardiovascular Imaging, 2010
Atherosclerotic plaque disruption accounts for the major part of cardiovascular mortality and the risk of disruption appears to depend on plaque composition. Carotid plaques in patients, scheduled for endarterectomy, have been successfully characterised with MRI. MRI has the advantage of combining information about morphology and function. Unfortunately, the tortuosity and size of the coronary arteries, and the respiratory and cardiac motion hinder the in vivo characterisation of human coronary plaque. In addition to plaque composition several molecular markers of the different processes involved in atherosclerosis, such as integrins, matrix metalloproteinases and fibrin seem to correlate with risk of plaque rupture and clinical outcome. These molecular markers can be targeted with antibodies coupled to carriers, which are loaded with gadolinium for detection (molecular MRI). Several cellular/molecular MRI studies in animal models and some in human patients have been conducted with varying levels of success. The advent of clinical high field magnets, the development of contrast agent carriers with high relaxivity and the development of relatively new MR contrast techniques are promising in the field of plaque imaging. Future MRI studies will have to focus on the molecular target of the atherosclerotic process, which has the highest prognostic value with regard to acute coronary syndromes and on the most suitable contrast agent to visualize that target.
Molecular Imaging of Inflammation in Atherosclerosis
Theranostics, 2013
Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic.
Clinical Molecular Imaging for Atherosclerotic Plaque
Journal of Imaging, 2021
Atherosclerosis is a well-known disease leading to cardiovascular events, including myocardial infarction and ischemic stroke. These conditions lead to a high mortality rate, which explains the interest in their prevention, early detection, and treatment. Molecular imaging is able to shed light on the basic pathophysiological processes, such as inflammation, that cause the progression and instability of plaque. The most common radiotracers used in clinical practice can detect increased energy metabolism (FDG), macrophage number (somatostatin receptor imaging), the intensity of cell proliferation in the area (labeled choline), and microcalcifications (fluoride imaging). These radiopharmaceuticals, especially FDG and labeled sodium fluoride, can predict cardiovascular events. The limitations of molecular imaging in atherosclerosis include low uptake of highly specific tracers, possible overlap with other diseases of the vessel wall, and specific features of certain tracers’ physiologi...
Vulnerable atherosclerotic plaque - a review of current concepts and advanced imaging
Biomedical Papers
Atherosclerosis is the most common cause of both carotid and coronary steno-occlusive disease. Rupture of an atherosclerotic plaque may lead to the formation of an overlying thrombosis resulting in complete arterial occlusion or downstream embolism. Clinically, this may manifest as a stroke or acute myocardial infarction, the overall leading causes of mortality and disability in developed countries. In this article, we summarize current concepts of the development of vulnerable plaque and provide an overview of commonly used imaging methods that may suggest/indicate atherosclerotic plaque vulnerability.
Radiolabelled probes for imaging of atherosclerotic plaques
American journal of nuclear medicine and molecular imaging, 2012
Cardiovascular disease is the leading cause of death worldwide. Unstable atherosclerotic plaques are prone to rupture followed by thrombus formation, vessel stenosis, and occlusion and frequently lead to acute myocardial infarction and brain infarction. As such, unstable plaques represent an important diagnostic target in clinical settings and the specific diagnosis of unstable plaques would enable preventive treatments for cardiovascular disease. To date, various imaging methods such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and intravascular ultrasound (IVUS) have been widely used clinically. Although these methods have advantages in terms of spatial resolution and the ability to make detailed identification of morphological alterations such as calcifications and vessel stenosis, these techniques require skill or expertise to discriminate plaque instability, which is essential for early diagnosis and treatment and can present difficulties for ...
Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque
Radiology Research and Practice, 2015
Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.