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Non-invasive Brain Sodium Quantification in Multiple Sclerosis

多发性硬化症的无创脑钠定量

基本信息

批准号：
8926893
负责人：
Matilde INGLESE
金额：
$ 59.83万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8926893
关键词：
Affect Atrophic Base of the Brain Brain Chronic Clinical Clinical Management Cognitive Corpus callosum splenium Data Demyelinating Diseases Disease Progression Experimental Models Filtration Functional disorder Goals Health Image Impaired cognition Impairment Indium Inflammation Inflammatory Injury Intervention Knowledge Lead Lesion Life Expectancy Magnetic Resonance Imaging Measures Methodology Methods Metric Monitor Multiple Sclerosis Nerve Degeneration Nervous System Trauma Neuraxis Neurodegenerative Disorders Neurologic Neuropsychological Tests Onset of illness Outcome Outcome Measure Pathologic Patients Phase Physiologic pulse Play Process Relapse Relapsing-Remitting Multiple Sclerosis Research Role Secondary Progressive Multiple Sclerosis Severities Signal Transduction Sodium Sodium Channel Specificity Technology Testing Thalamic structure Therapeutic Agents Time Tissues Walking axonal degeneration base brain tissue brain volume clinically relevant cohort disability economic impact follow-up foot improved in vivo indexing innovation neglect novel prevent quantum socioeconomics sodium ion therapeutic development tool young adult

项目摘要

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a chronic inflammatory-demyelinating and neurodegenerative disease of the central nervous system that affects 400.000 people in US. While it only slightly shortens life expectancy, MS is the leading cause of non-traumatic neurological disability in young adults. There is ever-growing evidence that neuro-axonal degeneration is the main pathological correlate of clinical disability. Despite its clinical relevance little is known about the mechanisms leading to axonal degeneration due to the lack of methods for exact identification and quantification of neurodegeneration in vivo and due to the paucity of neuropathological data. It has been suggested that the accumulation of intra-axonal sodium ions represents a key factor in the degenerative process and that partial blockade of sodium channels protects axons from degeneration in experimental models of MS. Changes in the intracellular sodium content (ISC) lead to changes in the total tissue sodium concentration (TSC) that can be measured in vivo by single quantum Sodium MR Imaging (23Na MRI). The application of triple quantum sodium filtration, allows an improvement in the specificity of TSC by measuring ISC and neglecting most of the signal contributions from the extra-cellular sodium content. Therefore, we propose that (1) excess intracellular sodium plays an important role in neuro-axonal injury in MS contributing to brain volume loss~ (2) changes in brain total sodium concentration (TSC) as well as in ISC can be measured in vivo with single and triple quantum 23Na MRI~ (3) sodium-related brain tissue damage is a critical element in the accumulation of disability. Initially, we will measure at ultra-high field MRI and compare brai TSC and ISC values in MS patients with different clinical course and healthy controls. Then, we will correlate 23Na MRI metrics with conventional MRI measure of tissue damage, neurological and cognitive impairment. Finally, we will examine whether group differences in brain volume and clinical outcomes can be explained by differences in TSC and ISC. This research is innovative because it uses a newly developed cutting-edge technology to discover the mechanisms that bridge the gap from inflammation to irreversible disability in MS. The proposed research is significant because it will advance our understanding of the pathophysiology of neurodegeneration in MS, and will help identify potential novel outcome measures of disease progression, thus improving the clinical management of patients with MS.

描述（申请人提供）：多发性硬化症（MS）是一种中枢神经系统慢性炎症性脱髓鞘和神经退行性疾病，影响美国40万人。虽然它只是稍微缩短预期寿命，但MS是年轻人非创伤性神经残疾的主要原因。越来越多的证据表明，神经轴突变性是临床残疾的主要病理相关性。尽管其临床相关性由于缺乏体内神经变性的精确鉴定和定量方法以及缺乏神经病理学数据，导致轴突变性的机制知之甚少。已经表明，轴突内钠离子的积累代表退行性过程中的关键因素，并且钠通道的部分阻断在MS的实验模型中保护轴突免于退行性变。细胞内钠含量（ISC）的变化导致总组织钠浓度（TSC）的变化，其可以通过单量子钠MR成像（23 Na MRI）在体内测量。三重量子钠过滤的应用允许通过测量ISC并忽略来自细胞外钠含量的大部分信号贡献来改善TSC的特异性。因此，我们认为：（1）细胞内过量钠在MS的神经轴突损伤中起重要作用，导致脑容量减少;（2）脑总钠浓度（TSC）和ISC的变化可以用单量子和三量子23 Na MRI在体内测量;首先，我们将在超高场MRI上测量并比较具有不同临床病程的MS患者和健康对照者的脑TSC和ISC值。然后，我们将23 Na MRI指标与组织损伤、神经和认知障碍的常规MRI测量相关联。最后，我们将研究是否可以通过TSC和ISC的差异来解释脑容量和临床结果的组间差异。这项研究是创新的，因为它使用了一种新开发的尖端技术来发现MS中从炎症到不可逆残疾的差距的机制。拟议的研究具有重要意义，因为它将促进我们对MS神经变性病理生理学的理解，并将有助于确定疾病进展的潜在新结局指标，从而改善MS患者的临床管理。