New Insights into Acute Stroke using Advanced Imaging and Clinical Neuroscience

利用先进成像和临床神经科学对急性中风的新见解

基本信息

批准号：
7735294
负责人：
John Hallenbeck
金额：
$ 40.48万
依托单位：
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
依托单位国家：
美国
项目类别：
财政年份：
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/7735294
关键词：
Acute Angiography Arts Biological Assay Blood Blood Vessels Carotid Stenosis Cerebral hemisphere hemorrhage Circle of Willis Clinical Clinical Research Collection Detection Development Diagnosis Dose Early Diagnosis Evaluation Evolution Fingerprint Future Gene Expression Gene Expression Profile Gene Proteins Genes Genomics Goals Human Image Individual Inflammation Institutes Intervention Intravenous Ischemic Stroke Knowledge Lymphocyte Subset Magnetic Resonance Imaging Meta-Analysis Multimodal Imaging Neurosciences Operative Surgical Procedures Outcome Patients Pattern Peripheral Blood Mononuclear Cell Pilot Projects Protocols documentation Recovery Research Resolution Risk Role Sampling Source Stroke Stroke prevention T-Lymphocyte Subsets Testing Time Tissue Sample Translational Research United States National Institutes of Health Vascular Diseases Work acute stroke aortic arch atorvastatin brain tissue improved insight nervous system disorder neuroimaging novel strategies peripheral blood programs prospective protein expression rapid technique thrombolysis

项目摘要

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. In new research applications, real-time, high resolution MRI has been 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 appears to be predictive of an individual's future risk of vascular disease. The accuracy of this vascular risk gene panel has been 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 related 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) has also been tested.

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。对CE-MRA的前瞻性评估已经完成，CE-MRA已被证明是快速和早期发现颅外血管疾病的有前途的方法。 CE-MRA已被添加到NIH中风计划的急性中风MRI方案中，对于急性中风干预（静脉内和手段内溶栓），紧急手术干预和预防继发性卒中的紧急决策可能具有特殊价值。一项比较了CE-MRA的准确性和MRA的准确性的荟萃分析也已完成。在新的研究应用中，实时，高分辨率MRI已与基因和蛋白质表达和炎症的外周血标记相结合，以研究中风风险，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，在周围血液单核细胞中定义并验证了缺血性中风的基因组指纹。现在，这项工作已扩展到鉴定外周血急性脑内出血的基因表达特征。外周血中的一组基因似乎可以预测一个人的未来血管疾病风险。该血管风险基因面板的准确性已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剂阿托伐他汀之一的受试者，以查看是否可以证明这些基因表达的剂量相关变化。也已经测试了阿特罗伐他汀对淋巴细胞亚群的影响（例如，T细胞的CD4+CD28-和CD4+CD25+亚群）也已进行了测试。