Examining the role of brain sodium content in multiplesclerosis using MRI

使用 MRI 检查脑钠含量在多发性硬化症中的作用

• 批准号: 9381282
• 负责人: Matilde INGLESE
• 金额: $ 59.01万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9381282
• 关键词: Affect; Age; Autopsy; Brain; Brain Injuries; Cells; Central Nervous System Diseases; Chronic; Clinical; Clinical Management; Cognitive; Corpus Callosum; Corticospinal Tracts; Data; Demyelinating Diseases; Demyelinations; Diffusion; Disease Progression; Edema; Experimental Models; Fiber; Filtration; Functional disorder; Goals; Health; Image; Impaired cognition; Impairment; Infiltration; Inflammation; Inflammatory; Injury; International; Intervention; Knowledge; Lead; Lesion; Life Expectancy; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Methodology; Methods; Monitor; Multiple Sclerosis; Nature; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Outcome; Outcome Measure; Pathologic; Patients; Physically Handicapped; Physiologic pulse; Play; Process; Relapsing-Remitting Multiple Sclerosis; Research; Role; Severities; Signal Transduction; Sodium; Sodium Channel; Specificity; Technology; Testing; Thalamic structure; Therapeutic Agents; Time; Tissues; Treatment Efficacy; Walking; axon injury; axonal degeneration; base; brain tissue; clinically relevant; cognitive testing; cohort; disability; extracellular; follow-up; foot; improved; in vivo; indexing; innovation; multiple sclerosis patient; neglect; novel; prevent; quantum; rate of change; sex; sodium ion; spectrograph; therapeutic development; time use; tool; white matter; young adult

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.

项目摘要 多发性硬化（MS）是一种慢性中枢神经系统炎症性脱髓鞘和神经退行性疾病， 神经系统，影响美国40万人。虽然它只是稍微缩短预期寿命，MS是 导致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 神经轴索变性是临床残疾的主要病理相关性。尽管它的临床意义 由于缺乏精确的方法，导致轴突变性的机制知之甚少。 但是，由于缺乏神经病理学数据，目前还不能对体内神经变性进行鉴定和定量。 已经提出，轴突内钠离子的积累代表了在神经系统损伤中的关键因素。 变性过程，部分阻断钠通道可保护轴突免于变性， 细胞内钠含量（ISC）的变化导致总钠含量的变化。 可通过单量子钠MR成像（23 Na）在体内测量的组织钠浓度（TSC MRI）。三重量子钠过滤的应用允许通过以下方式改善TSC的特异性： 测量ISC并忽略来自细胞外钠含量的大部分信号贡献。 因此，我们提出：（a）过量的脑钠蓄积在神经轴突损伤中起重要作用。 MS中的损伤导致脑损伤和临床残疾的累积;（B）脑总损伤的变化 钠浓度（TSC）以及ISC可以用单量子和三量子23 Na在体内测量 MRI;（c）联合使用钠和扩散基础频谱成像（DBSI）可以帮助更好地表征 病变和外观正常的白色物质中TSC的变化。首先，我们将测量和比较大脑 基线和短期内MS复发缓解型MS患者和健康对照的TSC和ISC值 和长期随访。然后，我们将23 Na MRI指标与组织损伤的DBSI指标相关联， 基线和随访时的神经和认知功能障碍。这项研究是创新的，因为它使用了 新开发的尖端技术，以发现弥合从炎症到炎症的差距的机制， 提出的研究是重要的，因为它将促进我们的理解， 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结果措施， 疾病进展，从而改善MS患者的临床管理。