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

项目总结 这项提议旨在利用钠磁共振成像(NaMRI)和质子(1H)扩散磁共振成像的创新进展来识别 轻度创伤性脑损伤(MTBI)患者疾病的影像生物标志物。Namri提供独特的 关于大脑的活体离子信息，尽管历史上一直受到低信噪比(SNR)的困扰， 限制了它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 翻译到临床群体，如MTBI患者。MTBI是一个主要的公共卫生问题，但潜在的 病理生理机制仍然是个谜，包括钠失衡在内的离子失衡已被牵连到 这种疾病在细胞和动物实验中以及在人体中的初步研究中都是如此。量化大脑 MTBI中的钠和寻找疾病的Namri生物标记物特别令人兴奋，因为这可能会揭示 MTBI的损伤机制和为开发新的治疗途径打开了大门 需要的。此外，使用选择性的MTBI的细胞和动物模型也有很好的结果。 钠通道阻断减轻了与损伤相关的损害，这表明钠在中枢作用，但到目前为止 在MTBI的病理生理学中的未知作用。 我们团队在创新和尖端的Namri方法、扩散微结构成像、 MTBI将使我们能够实现该项目的目标。我们建议利用技术进步使 NAMRI在3.0T临床上是可行的，包括我们团队在多核线圈设计、图像采集、 图像重建和数据分析。这项工作特别寻求量化Namri信号以1)表征 损伤后的变化，2)探索已知的脑白质损害和脑内钠离子变化之间的联系 结合高级弥散磁共振和3)确定钠是否在 显微结构改变和临床症状。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，满足以下需要 开发方法来预测延长症状的风险，并指出新的治疗途径。

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.