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: 7143919
• 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/7143919
• 关键词: T lymphocyte; bioimaging /biomedical imaging; biomarker; blood chemistry; cardiovascular disorder risk; cardiovascular imaging /visualization; cerebrovascular imaging /visualization; gene expression profiling; genetic susceptibility; genetically modified animals; helper T lymphocyte; human subject; inflammation; laboratory mouse; magnetic resonance imaging; microarray technology; prognosis; 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 of the NIH Stroke Program 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 further studies the accuracy of CE-MRA using an 8 channel neurovascular array for the detection of vascular disease are being planned. The Principal Investigator of the Stroke Neuroscience Unit will chair a panel to formally assess MRA, as requested by the American Academy of Neurology. 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. Classes of genes included those associated with white blood cell activation and differentiation, a response to hypoxic stress, genes related to vascular repair and genes involved in the inhibition of neuronal apoptosis. There was also a partial dependence of the gene list on vascular risk conditions. The gene expression results were validated with real time polymerase chain reactions and in an independent cohort of patients and controls. 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. The accuracy of the 22 gene panel will be tested out in a cohort of patients presenting to the emergency room with various medical conditions using a custom-made gene chip. The accuracy of a vascular risk gene panel will be tested by giving a group of subjects at risk of vascular disease one of 4 doses of atorvastatin for 3 months to see if dose response changes in expression of these genes can be demonstrated. 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. Studies of inflammatory and endothelial markers are in progress. Future studies will involve 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, including the e-selectin study being carried out by Dr. Hallenbeck's section. 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 ulti

在过去的二十年里，神经影像学的发展，特别是磁共振成像（MRI），使我们对急性卒中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单位的临床和转化研究中应用和扩展。临床MRI的最新进展是使用对比增强的MR血管造影术（CE-MRA）和神经血管阵列快速进行从主动脉弓到Willis环的血管成像。这已被评估，并发现是一个有前途的方法，快速和早期检测颅外血管疾病。CE-MRA可以添加到NIH卒中项目的急性卒中MRI方案中，并且对于关于急性卒中干预（静脉内和动脉内溶栓）、紧急手术干预和二级卒中预防的紧急决策具有特别价值。在进一步的研究中，正在计划使用8通道神经血管阵列检测血管疾病的CE-MRA的准确性。根据美国神经病学学会的要求，卒中神经科学单位的主要研究者将主持一个小组，正式评估MRA。 在新的研究应用中，实时、高分辨率MRI正与外周血标志物相结合？基因和蛋白质的表达和炎症-研究中风的风险，演变和恢复的模式。外周血是一个实际的样本来源，因为脑组织在临床环境中很少可用。在神经影像学证实的急性缺血性卒中患者的初步研究中，在外周血单核细胞中定义并验证了急性卒中的基因组指纹。基因的类别包括与白色血细胞活化和分化相关的基因、对缺氧应激的反应、与血管修复相关的基因和参与抑制神经元凋亡的基因。基因列表也部分依赖于血管风险状况。基因表达结果通过真实的时间聚合酶链反应和一个独立的患者和对照队列进行验证。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个基因组可以为进一步诊断和预后急性卒中指纹图谱奠定基础。22个基因面板的准确性将在一组患有各种医疗条件的急诊室患者中使用定制的基因芯片进行测试。将通过给予一组有血管疾病风险的受试者4种剂量之一的阿托伐他汀治疗3个月来检测血管风险基因组的准确性，以观察是否可以证明这些基因表达的剂量反应变化。 在对外周血的进一步研究中，发现促炎性T细胞淋巴细胞亚群（CD 4 + CD 28-）的扩增除了与既往卒中相关外，还与卒中复发和死亡相关。这种T细胞亚群的扩增可能在暴露于脑抗原后发生，并且可能参与导致复发性中风和死亡的病理生理机制。炎症和内皮标志物的研究正在进行中。 未来的研究将涉及基因组和蛋白质组学特征与MRI成像模式的相关性，以及评估其用于预测中风结局和对治疗干预的反应的潜在用途，包括Hallenbeck博士的部门正在进行的e-选择素研究。结合准确的MR成像模式，这些方法可以提供有关急性卒中病因学和反应的新细胞和病理机制的信息，允许开发卒中风险和预后的替代生物标志物，并进一步研究急性卒中的发病机制。