New Insights into Acute Stroke using Advanced Imaging

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。这已被评估，并被发现是一种有希望的方法，快速和早期检测颅外血管疾病。CE-MRA可被添加到美国国立卫生研究院卒中计划的急性卒中MRI方案中，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。在进一步的研究中，使用8通道神经血管阵列检测血管疾病的CE-MRA的准确性正在计划中。应美国神经病学学会的要求，中风神经科学部的首席研究员将主持一个小组，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，定义了急性中风的基因组指纹，并在外周血单核细胞中进行了验证。这类基因包括与白细胞激活和分化、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细胞凋亡有关的基因。基因列表也部分依赖于血管风险状况。基因表达结果通过实时聚合酶链式反应和患者和对照组的独立队列进行了验证。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基因小组可能形成进一步诊断和预测急性中风的指纹图谱的基础。22基因小组的准确性将在一组患者中进行测试，这些患者在急诊室就诊时患有各种疾病，使用定制的基因芯片。血管风险基因小组的准确性将通过给一组有血管疾病风险的受试者服用4剂阿托伐他汀3个月来测试，看看这些基因表达的剂量反应变化是否能够被证明。 在对外周血的进一步研究中，发现一个促炎T细胞亚群(CD4+CD28-)的扩张除了与既往中风有关外，还与中风复发和死亡有关。这种T细胞亚群的扩张可能发生在暴露于脑抗原后，并可能参与导致反复中风和死亡的病理生理机制。炎症和内皮标记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谱与MRI成像模式的相关性，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，包括哈伦贝克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，这些方法可以提供与急性卒中的病因和反应有关的新的细胞和病理机制的信息，允许开发卒中风险和预后的替代生物标志物，以及溃疡

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