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.

在过去的二十年中，神经影像学的发展，尤其是在磁共振成像（MRI）方面，已经使我们对急性中风的知识和理解进行了巨大变化。现在，在美国国家神经系统疾病和中风研究所的中风神经科学部门的临床和翻译研究中，将这些知识应用和扩展。临床MRI的最新进展是使用对比增强的MR血管造影（CE-MRA）和神经血管阵列的快速血管成像。已经对此进行了评估，并被认为是快速和早期发现颅外血管疾病的有前途的方法。 CE-MRA可能会添加到急性中风MRI方案中，并且对于有关急性中风干预（静脉内和动脉内溶栓），紧急手术干预和预防次要的急性中风干预（静脉内和动脉内溶栓）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与外周血标记相结合？基因和蛋白质表达和炎症 - 研究中风风险，进化和恢复的模式。外周血是样品的实用来源，因为在临床环境中很少有脑组织。在对神经影像学研究证实的急性缺血性中风患者的试点研究中，在外周血单核细胞中定义并验证了急性中风的基因组指纹。这些结果的显着性和潜在应用正在研究中：从列表中鉴定出的22个基因面板可能是进一步诊断和预后的急性中风指纹的基础。在对周围血液的进一步研究中，发现除与先前的中风相关外，发现T细胞淋巴细胞（CD4+CD28-）的促炎性子集（CD4+CD28-）与中风复发和死亡有关。暴露于脑抗原后，该T细胞子集的扩展可能发生，并且可能参与导致复发性中风和死亡的病理生理机制。 正在进行的和未来的研究包括基因组和蛋白质组学特征与MRI成像模式的相关性，以及评估其预测中风结果的潜在用途和对治疗干预措施的反应。遵循女性健康计划的同类，以确定是否可以从外周血中识别出蛋白质特征以预测未来的中风风险。在床头到基础的研究中，正在确定生物标志物（例如CD4+CD28-）的致病机制和治疗潜力，并且正在基因表达分析研究中的有希望的候选基因在遗传敲除小鼠的中风模型中研究。结合准确的MR成像模式，这些方法可以提供有关病因和对急性中风的反应的新细胞和病理机制的信息，允许发展中风风险和预后的替代生物标志物，并最终导致新药物疗法或预防疫苗。