New Insights into Acute Stroke using Advanced Imaging an

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。CE-MRA的前瞻性评价已经完成，CE-MRA已被证明是一种有前途的方法，用于快速和早期发现颅外血管疾病。CE-MRA已被添加到NIH卒中项目的急性卒中MRI方案中，对于急性卒中干预（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殊价值。还完成了一项荟萃分析，比较了CE-MRA和飞行时间MRA检测颈动脉狭窄的准确性。正在计划使用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进行评估。中风神经科学部的主要研究者正在主持一个小组，该小组正在为美国神经病学学会技术和治疗委员会评估MRA检测脑血管和颅内血管疾病的价值。 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，缺血性卒中的基因组指纹在外周血单核细胞中被定义和验证。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。外周血中的一组基因也可以预测一个人未来患血管疾病的风险。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，以观察是否可以证明这些基因表达的剂量反应变化，来测试该血管风险基因组的准确性。还测试了阿托伐他汀给药对淋巴细胞亚群（例如，T细胞的CD 4 + CD 28-和CD 4 + CD 25+亚群）的影响。 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（例如，Warach博士的部分中的再灌注损伤），以及评估其用于预测卒中结局和对治疗干预的反应的潜在用途，包括Hallenbeck博士的部分正在进行的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.