Advances in Molecular Imaging: Innervation Imaging

Cardiac autonomic nervous system plays a major role in maintaining hemodynamic and electrophysiological stability to changing demands. There is increasing evidence showing that imaging cardiac autonomic nervous system can evaluate patients with different cardiac conditions, including ischemic heart disease, arrhythmias and heart failure (HF), with high prognostic value, thus providing a potential tool for improving patient management. Excellent reviews on cardiac autonomic imaging with SPECT and PET tracers have been recently published. This review is aimed to bring the reader up-to-date on the subject with particular emphasis on the major findings of recent years.     

Magnetic Resonance Molecular Imaging of Plaque Angiogenesis

Neovascular expansion of the vasa vasorum is an early pathological biomarker of atherosclerosis, preceding endothelial dysfunction. Plaque angiogenesis accompanies intraplaque hemorrhage and plaque rupture, precursors of myocardial infarction and stroke. Molecular imaging of angiogenesis aims to map the expression of neovascular biomarkers on a cellular scale, often utilizing paramagnetic or superparamagnetic MRI contrast agents in order to generate sufficient image enhancement. Both clinically approved extracellular contrast agents and experimental targeted nanoparticles have demonstrated MRI signal enhancement that is proportional to the neovascular density in the vessel wall. Furthermore, targeted contrast agents formulated with anti-angiogenic drugs can be used to quantify drug deposition within the plaque and predict subsequent therapeutic effects. Molecular imaging of plaque angiogenesis has shown promise for interrogating the pathophysiology of atherosclerotic lesions rather than just their physical characteristics, with the ultimate goal of identifying the high-risk plaques that are most likely to cause cardiovascular events.     

Advances in Molecular Imaging: Cardiac Regeneration

In addition to the standard cardiovascular pharmacological treatment and catheter-based and surgical procedures, cardiac restorative therapy was recently introduced. Despite the encouraging results obtained in pre-clinical research, cardiac regenerative therapy is still not used in clinical practice, because of the modest effect on cardiac function. To improve cardiac regenerative strategies, the identification of non-invasive powerful tools is required. Due to availability of various radiotracers and acquisition protocols nuclear imaging is the most promising and can be used both in gene and in cell therapy. This review summarizes current status and future role of nuclear imaging in the area of myocardial regeneration.     

Imaging the Coronary Artery Plaque: Approaches,Advances, and Challenges

Purpose of Review

Atherosclerosis is a major cause of morbidity and mortality in the world, largely due to the disruption of high-risk plaques (HRP). Understanding how best to identify HRP, using imaging, has the potential to improve assessment of cardiovascular disease (CVD) risk and facilitate better targeting of care to patients.

Recent Findings

Technological advances have been made across several imaging modalities, which provide opportunities to image HRP. Advances in computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS) target multiple features of HRP.

Summary

A growing number of studies have demonstrated their utility in assessing risk and guiding therapeutic interventions. While opportunities exist today to employ HRP imaging, further studies are needed to assess the value of imaging HRP to refine CVD risk and target therapeutics.

     

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.     

Coronary Artery CT Angiography for Plaque Imaging

Cardiac CT is becoming a mainstream and integral part of many cardiology practices based on a vast base of literature supporting and validating its clinical utility. As the technology continues to advance, coronary imaging has improved in stride. In the next several years, cardiac CT may become the “gatekeeper” of cardiac testing, surpassing the more common and widespread nuclear testing as the initial strategy in evaluating ischemia. Unfortunately, in spite of an arsenal of tests available to detect clinically significant stable coronary artery disease, many people continue to suffer acute myocardial infarction and other acute coronary syndromes, leading to significant morbidity and mortality due to unstable coronary artery disease. These unstable, “vulnerable” plaques continue to plague cardiologists across the globe. The ability to identify vulnerable plaque is a step in the right direction toward therapy. It is in this particular arena that advancements in cardiac CT technology may bear the most fruit. A growing body of evidence supporting the utility of cardiac CT in plaque imaging has emerged and has demonstrated that potentially unstable coronary artery disease is able to be identified accurately and noninvasively.     

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.     

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.     

Imaging of the Small Bowel: Challenges and Advances in Imaging Techniques

This article reviews the diagnostic imaging modalities currently available that are used to evaluate pathologies affecting the small bowel. The small bowel has been a challenging part of the body to investigate because of its length of approximately 6 m, compounded by the small area within the abdominal cavity in which it is constrained. The costs, patient preferences, strengths, and potential weaknesses of each diagnostic imaging modality will be discussed, including examples of pathologies that are best suited to each modality. In addition, new frontiers in small bowel imaging will be introduced. These innovative imaging technologies, such as magnetic resonance imaging and positron emission tomography scanning, as well as updated computed tomography hardware and novel scanning protocols, may improve sensitivity and specificity of detecting abnormalities of the small bowel.     

Molecular Imaging in Synthetic Biology,and Synthetic Biology in Molecular Imaging

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.     

Contrast-Enhanced Ultrasound Imaging of Carotid Plaque Neo-vascularization: Accuracy of Visual Analysis

The aim of our study was to evaluate whether neo-vascularization of the carotid plaque can be accurately assessed by visual analysis of contrast-enhanced ultrasound images and whether these findings correlate with intensity-over-time curve analysis (ITC) and histopathology. Patients with ≥50% symptomatic or ≥60% asymptomatic stenosis according to European Carotid Surgery Trial criteria were included. Four investigators evaluated contrast enhancement visually (three grades), with positive agreement when three or more investigators were unanimous. ITC analysis of contrast enhancement was performed in the plaque and in the lumen. Histopathology (microvessel density with CD34 + staining) was completed when endarterectomy was performed. Visual grading (33 patients, inter-observer agreement = 94%) correlated significantly with ITC analysis (p = 0.03). Histopathology (n = 19) revealed a larger CD34 + area in patients with grade 1/2 versus grade 0 (p = 0.03). Visual analysis of neo-vascularization by means of contrast-enhanced ultrasound imaging is accurate and reproducible, with significant correlations with ITC and histopathology.     

超声造影评价颈动脉斑块内新生血管形成与临床症状的关系

目的 分析超声造影显示颈动脉粥样硬化斑块增强强度与患者临床症状之间的关系.方法 颈动脉粥样硬化患者58例,分为有临床症状及无症状2组.常规超声评价颈动脉斑块回声类型,超声造影观察斑块内增强强度并进行分级.分析斑块回声、斑块内增强情况与患者临床症状的关系.结果 有症状组69.4％的斑块超声造影出现增强且2级以上增强者达63.3％,而在无症状组58.3％的斑块超声造影表现为不增强,2级以上增强者仅为29.2％,2组间有显著性差异.结论 实时超声造影可敏感显示斑块内的动态增强过程,反应斑块内的新生血管形成,与患者的临床症状具有相关性.     

医学影像学的技术进展

医学影像学是一门设备依赖型学科 ,医学影像学设备 ,尤其是CT、MR设备又受自然科学中发展最迅猛的尖端技术驱动 ,以名符其实的日新月异的速度在发展。在医学影像学发展的各阶段 ,都会对与之密切相关的其他临床学科产生重要的、有时是划时代的影响。当前 ,以CT、MR技术发展为代表的医学影像学的发展正是处于这样一个阶段。1　CT技术的进展1998年是CT技术发展中又一个划时代的标志。是年 ,几个主要CT设备制造厂家同时推出了四层采集的螺旋CT(多层螺旋CT) ,关于其原理已在另文中作过介绍[1 3] 。以此为起点 ,2 0 0 0年推出了 8层采集的…