Examining the role of brain sodium content in multiplesclerosis using MRI

项目总结 多发性硬化症(MS)是一种慢性炎症性脱髓鞘和中枢神经退行性疾病 影响美国400.000人的神经系统。虽然它只会略微缩短预期寿命，但MS是 年轻人中非创伤性神经功能障碍的主要原因。越来越多的证据表明 神经轴索变性是导致临床残疾的主要病理因素。尽管它与临床相关 由于缺乏准确的方法，导致轴突变性的机制知之甚少。 由于缺乏神经病理学数据，在体内和由于缺乏神经病理学数据，神经变性的识别和量化。 已有研究表明，轴突内钠离子的积聚是导致脑出血的关键因素。 退变过程和部分阻断钠通道保护轴突免于变性 多发性硬化的实验模型细胞内钠含量(ISC)的变化导致总钠含量的变化 单量子钠磁共振成像(23Na)活体测量组织钠浓度(TSC) 核磁共振)。三重量子钠过滤的应用，通过以下方式提高了TSC的特异性 测量ISC，忽略细胞外钠含量的大部分信号贡献。 因此，我们认为：(A)过量的脑钠蓄积在神经轴突中起重要作用。 多发性硬化症的损伤导致脑损伤和临床残疾的积累；(B)脑总量的变化 用单量子和三量子~(23)Na可以在体内测量钠浓度(TSC)和在ISC中的浓度 (C)联合使用钠和弥散基础光谱成像(DBSI)可帮助更好地描述 病变和正常脑白质中TSC的变化。首先，我们将测量和比较大脑 复发-缓解期MS患者和健康对照组基线和短期的TSC和ISC值。 并进行长期随访。然后，我们将23Na MRI指标与DBSI组织损伤指标进行关联， 基线和随访时的神经和认知功能障碍。这项研究具有创新性，因为它使用了 新开发的尖端技术，以发现从炎症到 多发性硬化症中不可逆转的残疾拟议的研究具有重要意义，因为它将促进我们对 MS神经退行性变的病理生理学，并将有助于确定潜在的新的预后指标 疾病进展，从而改善了MS患者的临床管理。

PROJECT SUMMARY 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 (a) excess brain sodium accumulation plays an important role in neuro-axonal injury in MS contributing to brain damage and accumulation of clinical disability; (b) changes in brain total sodium concentration (TSC) as well as in ISC can be measured in vivo with single and triple quantum 23Na MRI; (c) combined use of sodium and diffusion basis spectrum imaging (DBSI) can help better characterize the changes in TSC in lesions and normal-appearing white matter. Initially, we will measure and compare brain TSC and ISC values in MS patients with relapsing-remitting MS and healthy controls at baseline and at short- and long-term follow-up. Then, we will correlate 23Na MRI metrics with DBSI metrics of tissue damage, neurological and cognitive impairment at baseline and follow-up. 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.