New Insights into Acute Stroke using Advanced Imaging

使用高级成像对急性中风的新见解

• 批准号: 6990768
• 负责人: Alison E Baird
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6990768
• 关键词: bioimaging /biomedical imaging; biomarker; brain imaging /visualization /scanning; cardiovascular disorder risk; cerebroangiography; disease /disorder etiology; gene expression; gene expression profiling; genetically modified animals; helper T lymphocyte; human subject; inflammation; laboratory mouse; magnetic resonance imaging; proteomics; stroke

Over the past two decades developments in neuroimaging, especially in magnetic resonance imaging (MRI), have enabled enormous changes to be made in our knowledge and understanding of acute stroke. This knowledge is now being applied and extended in the clinical and translational research of the Stroke Neuroscience Unit at the National Institute of Neurological Disorders and Stroke. A recent advance in clinical MRI is rapid vascular imaging from the aortic arch to the circle of Willis using contrast-enhanced MR angiography (CE-MRA) and a neurovascular array. This has been evaluated and found to be a promising method for the rapid and early detection of extracranial vascular disease. CE-MRA may be added to acute stroke MRI protocols and could be of particular value for emergent decisions regarding acute stroke intervention (intravenous and intra-arterial thrombolysis), urgent surgical intervention and secondary stroke prevention. In new research applications, real-time, high resolution MRI is being combined with peripheral blood markers ? of gene and protein expression and inflammation - to study patterns of stroke risk, evolution and recovery. The peripheral blood is a practical source of samples as brain tissue is rarely available in the clinical setting. In a pilot study of patients with acute ischemic stroke confirmed on neuroimaging studies, a genomic fingerprint of acute stroke was defined and validated in peripheral blood mononuclear cells. The significance and potential applications of these results are under investigation: a 22 gene panel identified from the listing could form a basis for further diagnostic and prognostic fingerprinting of acute stroke. In further studies of the peripheral blood, expansion of a pro-inflammatory subset of T cell lymphocytes (CD4+CD28-) was found to be associated with stroke recurrence and death, in addition to being associated with prior stroke. Expansion of this T cell subset may occur after exposure to brain antigens, and may possibly be involved in the pathophysiological mechanisms leading to recurrent strokes and death. Ongoing and future studies include the correlation of genomic and proteomic profiles with MRI imaging patterns, and evaluation of their potential use for predicting stroke outcome and response to therapeutic interventions. A cohort from the Women?s Health Initiative is being followed to determine if a protein signature can be identified from the peripheral blood to predict future stroke risk. In bedside-to-bench studies, the pathogenic mechanisms and therapeutic potential of biomarkers such as CD4+CD28- are being determined, and promising candidate genes from gene expression profiling studies are being studied in genetic knock-out mouse models of stroke. In conjunction with accurate MR imaging patterns, these approaches may give information on new cellular and pathological mechanisms involved in the etiology and response to acute stroke, allow the development of surrogate biomarkers of stroke risk and prognosis, and ultimately lead to new drug therapies or preventive vaccines.

在过去的二十年里，神经成像的发展，特别是磁共振成像(MRI)的发展，使我们对急性中风的认识和理解发生了巨大的变化。这一知识现在正在国家神经疾病和中风研究所中风神经科学部的临床和翻译研究中得到应用和推广。临床MRI的最新进展是使用对比增强磁共振血管成像(CE-MRA)和神经血管阵列从主动脉弓到Willis环的快速血管成像。这已被评估，并被发现是一种有希望的方法，快速和早期检测颅外血管疾病。CE-MRA可被添加到急性卒中MRI方案中，对于有关急性卒中干预(静脉和动脉内溶栓)、紧急外科干预和二级卒中预防的紧急决策可能特别有价值。 在新的研究应用中，实时、高分辨率MRI正在与外周血液标记物相结合？基因和蛋白质表达与炎症--研究中风风险、进化和康复的模式。外周血液是一种实用的样本来源，因为临床环境中很少有脑组织可用。在一项对经神经成像研究证实的急性缺血性中风患者的先导性研究中，定义了急性中风的基因组指纹，并在外周血单核细胞中进行了验证。这些结果的意义和潜在应用正在调查中：从列表中确定的22基因小组可能形成进一步诊断和预测急性中风的指纹图谱的基础。在对外周血的进一步研究中，发现一个促炎T细胞亚群(CD4+CD28-)的扩张除了与既往中风有关外，还与中风复发和死亡有关。这种T细胞亚群的扩张可能发生在暴露于脑抗原后，并可能参与导致反复中风和死亡的病理生理机制。 正在进行和未来的研究包括基因组和蛋白质组谱与MRI成像模式的相关性，以及评估它们在预测中风结果和治疗干预反应方面的潜在用途。来自女性S健康倡议的一个队列正在被跟踪，以确定是否可以从外周血中识别出蛋白质特征来预测未来的中风风险。在床边到工作台的研究中，正在确定生物标记物的致病机制和治疗潜力，来自基因表达谱研究的有希望的候选基因正在中风的遗传敲除小鼠模型中进行研究。结合准确的磁共振成像模式，这些方法可能提供与急性中风的病因和反应有关的新的细胞和病理机制的信息，允许开发中风风险和预后的替代生物标记物，并最终导致新的药物治疗或预防性疫苗。