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Quantitative MR Imaging & Proton Spectroscopy in MS.

定量磁共振成像

基本信息

批准号：
8676228
负责人：
Yulin Ge
金额：
$ 16.24万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-11 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8676228
关键词：
Age Attention Concentration Axon Basal Ganglia Blood Volume Brain Brain Ischemia Cell Nucleus Cerebrovascular Circulation Cerebrum Chronic Clinical Data Development Diagnosis Diffuse Diffusion Diffusion Magnetic Resonance Imaging Disease Etiology Exhibits Fatigue Functional disorder Goals Homeostasis Impaired cognition Indium Inflammation Inflammatory Injury Iron Judgment Lead Lesion Link Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Mediating Medical Memory Metabolic Metric Microcirculation Morbidity - disease rate Multiple Sclerosis Myelin Sheath N-acetylaspartate Neurocognitive Neurocognitive Deficit Neuronal Injury Neurons Neuropsychological Tests Outcome Assessment Pathway interactions Patients Perfusion Play Predisposition Prevalence Productivity Protons Recruitment Activity Relapsing-Remitting Multiple Sclerosis Relative (related person)Research Role Spectrum Analysis Structure T-Lymphocyte Techniques Testing Thalamic structure Time United States base central nervous system injury cerebral atrophy cost experience follow-up gray matter improved indexing innovation insight magnetic field nervous system disorder neuron loss normal aging sex white matter young adult

项目摘要

Multiple sclerosis (MS) is the most common neurological disease of young adults in the United States, with a prevalence estimated to be 400,000 and with annual medical expenses and lost productivity costs of approximately $9.5 billion. We hypothesize (Central Hypothesis) that microvascular abnormalities (a consequence of the perivenous inflammation known to occur in MS) are a final common pathway leading to injury of the central nervous system. This hypothesis is based upon preliminary data we have gathered and is supported by pathological evidence of such injury. Ensuing microvascular ischemic damage to axons/neurons interferes with normal iron homeostasis, resulting in accumulation of excess iron in the deep gray matter. Neurocognitive deficits and fatigue experienced by MS patients are consequences of oxidative injury by iron accretion in the basal ganglia and thalamus. To test this hypothesis, we propose four Specific Aims: Specific Aim 1 defines baseline perfusion (cerebral blood flow; cerebral blood volume; mean transit time), magnetic resonance (MR) spectroscopy (N-acetyl aspartate), and quantitative MR metrics (diffusion tensor; diffusion kurtosis; magnetic field correlation; structural volume) at high-field (3 Tesla) in 30 early relapsing remitting MS patients and age/sex matched controls. Specific Aim 2 measures baseline cognitive impairment and fatigue and associates these results with quantitative MR metrics of the deep gray matter. Specific Aim 3 associates, over a 4 year duration, deep gray matter iron accumulation with both damage to these structures and progressive brain parenchymal loss. Specific Aim 4 associates, over a 4 year duration, the decline in neurocognitive function and fatigue with deep gray matter injury. This research will provide new insights into the pathophysiology of Multiple Sclerosis and common morbidities (cognitive decline and fatigue) experienced by MS patients. It will result in more appropriate measures to detect and quantitate the effect of the disease and will provide a rationale for innovative treatment regimes.

多发性硬化症（MS）是美国年轻人最常见的神经系统疾病，患病率估计为40万，每年的医疗费用和生产力损失约为95亿美元。我们假设（中枢假说）微血管异常（MS中已知发生的静脉周围炎症的结果）是导致中枢神经系统损伤的最终共同途径。这一假设是基于我们收集的初步数据，并得到了这种损伤的病理学证据的支持。随后对轴突/神经元的微血管缺血性损伤干扰正常的铁稳态，导致过量铁在深部灰质中积累。MS患者经历的神经认知缺陷和疲劳是由基底神经节和丘脑中的铁积累引起的氧化损伤的后果。为了验证这一假设，我们提出了四个具体目标：具体目标1定义基线灌注（脑血流量;脑血容量;平均通过时间），磁共振（MR）波谱（N-乙酰天冬氨酸）和定量MR指标（扩散张量;扩散峰度;磁场相关;结构体积）在高场（3特斯拉）在30个早期复发缓解型MS患者和年龄/性别匹配的对照。特定目标2测量基线认知障碍和疲劳，并将这些结果与深部灰质的定量MR指标相关联。特定目标3在4年的持续时间内将深部灰质铁蓄积与这些结构的损伤和进行性脑实质损失相关联。特定目标4在4年的持续时间内将神经认知功能下降和疲劳与深部灰质损伤联系起来。这项研究将为多发性硬化症的病理生理学和MS患者经历的常见疾病（认知能力下降和疲劳）提供新的见解。它将导致更适当的措施来检测和量化疾病的影响，并将为创新的治疗制度提供理论依据。