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NIH中风计划的急性中风MRI方案中，对于有关急性中风干预（静脉内和手段内溶栓），紧急手术干预和预防次要中风的紧急决定可能具有特殊价值。在进一步的研究中，正在计划使用8通道神经血管阵列进行CE-MRA检测血管疾病。中风神经科学部门的主要研究员将主持一个小组，按照美国神经病学会的要求进行正式评估MRA。 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。基因类别包括与白细胞激活和分化相关的基因，对低氧应激的反应，与血管修复有关的基因以及与抑制神经元凋亡有关的基因。基因清单对血管风险状况的部分依赖性也有部分依赖性。用实时聚合酶链反应以及独立的患者和对照组对基因表达结果进行了验证。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。 22个基因面板的准确性将在使用定制基因芯片的各种医疗状况的一组患者中进行测试。血管风险基因面板的准确性将通过给予一组患有血管疾病风险的受试者在3个月内使用4剂阿托伐他汀之一，以查看这些基因表达的剂量反应变化是否可以证明这些基因的剂量反应变化。 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。炎症和内皮标记的研究正在进行中。 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，并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，包括Hallenbeck博士部分进行的E-选择性研究。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，以及Ulti