New Insights into Acute Stroke using Advanced Imaging an

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。CE-MRA的前瞻性评价已经完成，CE-MRA被证明是一种有前途的快速和早期检测颅外血管疾病的方法。CE-MRA已被加入美国国立卫生研究院卒中计划的急性卒中MRI方案，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。一项比较CE-MRA和飞行时间MRA检测颈动脉狭窄准确性的荟萃分析也已经完成。使用16通道神经血管阵列对CE-MRA检测颅外颈动脉狭窄的准确性的评估正在计划中。中风神经科学部的首席研究员正在为美国神经病学学会的技术和治疗委员会主持一个小组，该小组正在为美国神经病学学会的技术和治疗委员会评估MRA在检测颅内和外部血管疾病方面的价值。 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，定义并验证了外周血单核细胞中的缺血性中风的基因组指纹。这项工作现在已经扩展到从外周血中鉴定急性脑出血的基因表达特征。外周血液中的一组基因也可能预测一个人未来患血管疾病的风险。这个血管风险基因小组的准确性正在进行测试，方法是给一组有血管疾病风险的受试者服用4剂阿托伐他汀，为期3个月，看看这些基因表达的剂量反应变化是否能够得到证实。服用阿托伐他汀对淋巴细胞亚群(例如T细胞的CD4+CD28-和CD4+CD25+亚群)的影响也在测试中。 未来的研究将涉及基因组和蛋白质组谱与MRI成像模式的相关性(例如，与Warach博士所在部门的再灌注损伤的相关性)，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，包括Hallenbeck博士所在部门正在进行的e-选择素研究。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。

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. A prospective evaluation of CE-MRA has been completed and CE-MRA has been shown to be a promising method for the rapid and early detection of extracranial vascular disease. CE-MRA has been 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. A meta-analysis comparing the accuracy of CE-MRA and time of flight MRA for the detection of carotid artery stenoses has also been completed. An assessment of the accuracy of CE-MRA using a 16 channel neurovascular array for the detection of extracranial carotid stenoses is being planned. The Principal Investigator of the Stroke Neuroscience Unit is chairing a panel that is assessing the value of MRA for the detection of extranial and intracranial vascular disease, for the Technology and Therapeutics Committee of 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 ischemic stroke was defined and validated in peripheral blood mononuclear cells. This work has now been extended to the identification of a gene expression signature of acute intracerebral hemorrhage from the peripheral blood. A panel of genes in the peripheral blood may also be predictive of an individual's future risk of vascular disease. The accuracy of this vascular risk gene panel is being 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. The effects of atrovastatin administration on lymphocyte subsets (for example, the CD4+CD28- and the CD4+CD25+ subsets of T cells) are also being tested. Future studies will involve correlation of genomic and proteomic profiles with MRI imaging patterns (for example, with reperfusion injury in Dr. Warach's section), 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 ultimately lead to new drug therapies or preventive vaccines.