Non-invasive Brain Sodium Quantification in Multiple Sclerosis

 描述(申请人提供)：多发性硬化症(MS)是一种慢性炎症性脱髓鞘和神经变性的中枢神经系统疾病，在美国有400.000人受到影响。虽然它只会轻微缩短预期寿命，但多发性硬化症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，神经轴索变性是导致临床残疾的主要病理因素。尽管它在临床上 由于缺乏体内准确识别和量化神经变性的方法，以及神经病理学数据的缺乏，导致轴突变性的机制知之甚少。在MS的实验模型中，轴突内钠离子的积聚是退变过程中的一个关键因素，部分阻断钠通道可以保护轴突免于退变。细胞内钠含量(ISC)的变化会导致组织总钠浓度(TSC)的变化，这一变化可以通过单量子钠磁共振成像(23Na MRI)在体内进行测量。三量子钠过滤的应用，允许通过测量ISC而忽略细胞外钠含量的大部分信号贡献来提高TSC的特异度。因此，我们提出：(1)过量的细胞内钠在MS神经轴突损伤中起重要作用，导致脑体积丢失。2脑内总钠浓度(TSC)和ISC的变化可以用单量子和三量子~(23)Na MRI~(3+)活体测量。首先，我们将在超高场MRI上测量，并比较不同临床病程的MS患者和健康对照组的脑TSC和ISC值。然后，我们将23Na MRI指标与组织损伤、神经和认知障碍的常规MRI指标进行关联。最后，我们将检查是否可以用TSC和ISC的差异来解释组内脑体积和临床结果的差异。这项研究具有创新性，因为它使用了一种新开发的尖端技术来发现MS患者从炎症到不可逆转残疾之间的桥梁机制。这项拟议的研究具有重要意义，因为它将促进我们对MS神经变性的病理生理学的理解，并将有助于确定潜在的疾病进展的新结果指标，从而改善MS患者的临床管理。

 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.