Optimized Sodium MR Imaging at Clinical Field Strength to Study in vivo Sodium Signal in Mild Traumatic Brain Injury

在临床场强下优化钠 MR 成像，研究轻度创伤性脑损伤中的体内钠信号

• 批准号: 10638948
• 负责人: Yvonne W Lui
• 金额: $ 67.35万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-25 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638948
• 关键词: Address; Affect; Animal Experiments; Animal Model; Animals; Axon; Biological Markers; Brain; Cell model; Cells; Characteristics; Clinical; Complex; Corpus Callosum; Craniocerebral Trauma; Data; Data Analyses; Detection; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Evaluation; Functional disorder; Goals; Guidelines; Homeostasis; Image; Imaging Techniques; In Vitro; Incidence; Individual; Injury; Ion Pumps; Link; Magnetic Resonance Imaging; Measures; Mediating; Metabolic; Metabolic Marker; Methods; Modeling; Na(+)-K(+)-Exchanging ATPase; Neurobehavioral Manifestations; Noise; Nuclear; Outcome; Pathway interactions; Patients; Physiological; Play; Population; Pre-Clinical Model; Predisposition; Protons; Public Health; Recommendation; Recovery; Relaxation; Resolution; Risk; Rodent; Role; Signal Transduction; Sodium; Sodium Channel; Structural defect; Structure; Symptoms; TBI Patients; Technology; Testing; Time; Torsion; Translating; Translations; Work; brain tissue; clinical outcome measures; cognitive performance; design; effective therapy; experimental study; human subject; image reconstruction; imaging biomarker; improved; in vivo; in vivo imaging; individual patient; innovation; magnetic resonance imaging biomarker; mild traumatic brain injury; nervous system disorder; novel; novel therapeutics; nuclear imaging; outcome prediction; pre-clinical; reconstruction; return to sport; risk prediction; voltage; white matter; white matter injury

PROJECT SUMMARY This proposal aims to use innovative advances in sodium MRI (NaMRI) and proton (1H) diffusion MRI to identify imaging biomarkers of disease in patients with Mild Traumatic Brain Injury (MTBI). NaMRI provides unique in vivo ionic information about the brain, though has historically been plagued by low signal-to-noise ratio (SNR), limiting its utility in studying clinical populations. However, recent technological advances proposed here allow translation to clinical groups such as patients with MTBI. MTBI is a major public health problem yet the underlying pathophysiology remains a mystery and ionic imbalance including sodium dysregulation has been implicated in the disease in cell and animal experiments as well as preliminary studies in human subjects. Quantifying brain sodium in MTBI and finding NaMRI biomarkers for disease is particularly exciting as this could shed light on the mechanism of injury in MTBI and open the door to the development of new treatment pathways which are badly needed. Furthermore, there are promising results from cellular and animal models of MTBI using selective sodium channel blockade that mitigate damage relating to injury, suggesting sodium plays a central but as yet unexplored role in the pathophysiology of MTBI. Our team’s combined strengths in innovative and cutting-edge NaMRI methods, diffusion microstructure imaging, and MTBI will allow us to meet the goals of this project. We propose to leverage technical advances that make NaMRI clinically feasible at 3.0T, including work from our group in multinuclear coil design, image acquisition, image reconstruction and data analysis. The work specifically seeks to quantify NaMRI signal to 1) characterize changes after injury, 2) explore the link between known white matter compromise and altered brain sodium in conjunction with advanced diffusion MRI and 3) determine if sodium mediates the relationship between microstructural changes and clinical symptoms. Identifying surrogate imaging biomarkers to better quantify injury and recovery will allow development of objective return-to-activities recommendations, address the need to develop methods to predict risk for prolonged symptoms, and point to new pathways for therapy.

项目摘要 该提案旨在利用钠MRI（NaMRI）和质子（1H）扩散MRI的创新进展来识别 轻度创伤性脑损伤（MTBI）患者疾病的成像生物标志物。NaMRI提供独特的 关于大脑的体内离子信息，尽管历史上一直受到低信噪比（SNR）的困扰， 限制了其在研究临床人群中的效用。然而，这里提出的最新技术进步允许 转化为临床组，如MTBI患者。MTBI是一个主要的公共卫生问题，但其潜在的 病理生理学仍然是一个谜，包括钠失调在内的离子失衡与 在细胞和动物实验以及人类受试者的初步研究中发现了这种疾病。量化大脑 MTBI中的钠和发现NaMRI疾病生物标志物特别令人兴奋，因为这可以揭示 研究MTBI损伤机制，并为开发新的治疗途径打开大门， needed.此外，从使用选择性免疫抑制剂的MTBI的细胞和动物模型中， 钠通道阻滞剂可以减轻与损伤相关的损害，这表明钠在其中起着重要作用，但迄今为止， 在MTBI的病理生理学中的未探索的作用。 我们的团队在创新和尖端的NaMRI方法，扩散微结构成像， MTBI将使我们能够实现这个项目的目标。我们建议利用技术进步， NaMRI在3.0T下临床可行，包括我们小组在多核线圈设计、图像采集、 图像重建和数据分析。这项工作专门寻求量化NaMRI信号，以1）表征 损伤后的变化，2）探索已知的白色物质损害和脑钠变化之间的联系， 结合先进的弥散MRI和3）确定钠是否介导 微结构变化和临床症状。识别替代成像生物标志物以更好地量化损伤 和恢复将允许制定客观的恢复活动建议，解决需要， 开发方法来预测长期症状的风险，并指出新的治疗途径。