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），使我们对急性中风的认识和理解发生了巨大的变化。这些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门的临床和转化研究中得到应用和扩展。临床MRI的最新进展是使用对比增强MR血管造影（CE-MRA）和神经血管阵列从主动脉弓到威利斯圈的快速血管成像。这已被评估和发现是一种有前途的方法，快速和早期检测颅内外血管疾病。CE-MRA可以添加到急性卒中MRI方案中，对于急性卒中干预（静脉溶栓和动脉溶栓）、紧急手术干预和二级卒中预防的紧急决策尤其有价值。