Quantitative Sodium MR Imaging and Proton MR Spectroscopy in Traumatic Brain Injury

项目摘要 创伤性脑损伤(TBI)是世界上导致年轻人神经功能障碍的主要原因 中年人口。计算机体层摄影术(CT)和磁共振成像(MRI)在脑血管疾病中的作用 由于与临床相关但成像隐匿性损伤的广泛存在，患者管理受到限制。 我们提出了由钠(23Na)磁共振和质子磁共振获得的脑损伤的新的量度 波谱(~1H-MRS)。中心假设是联合~(23)Na MRI/~1H MRS将提供 离子稳态丧失和神经退行性变的代谢成像标志物，将预测 患者的长期临床结果。钠核磁共振是一种基于直接检测的非侵入性检查方法 使用专门的核磁共振软件和硬件来检测Na+离子。它可以评估Na+动态平衡的丧失，这可以是 被离子失衡是细胞损伤级联背后的驱动力的过程所干扰。这个 Na+/K+交换泵可受到线粒体功能障碍引起的能量不足的影响，以及 弥漫性轴索损伤是颅脑损伤的组织病理学特征。这将导致细胞内的变化 钠浓度(C_1)，而炎症、胶质增生和细胞丢失将反映在 细胞外体积分数(α2)。我们建议将23Na指标c1和alpha2与1H相结合 MRS法测定N-乙酰天冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)和肌醇(Mi) 可用于推断神经元健康/密度(NAA)、细胞能量/密度(Cr)、膜周转率(CHO)和 星形胶质细胞激活(Mi)。具体目标是：目标1：方法论。(1)优化超短回波时间23Na 在3T有液体抑制和没有液体抑制的情况下进行磁共振成像以优化图像重建的去噪和 压缩传感，以提高信噪比、分辨率和采集速度。开发c1和 基于~(23)Na自旋动力学模拟和参考模体的α2量化。(1.b)落实 四阶匀场全脑1H MRS采集。目的2：临床应用。(2.a)比较c1 颅脑损伤患者和对照组基线时(≤后10天)的ALA2和Alpha2及其随时间的变化率(2- 根据MRI(FLAIR、SWI、DTI)和1H进行调整 MRS(2.b)将MR指标的基线值及其随时间的变化率与临床相关 两次后续行动的结果。为评估c1和alpha2对MRI和1H MRS的附加值目的3： 机械论模型。(3.a)考虑到ATP与NAA和C1之间的相互依赖关系，以确定 脑损伤相关的C1改变是神经胶质的还是神经元的。(3.b)测试是否基于机械论模型 神经变性：(I)基线~(23)Na MRI和~1H MRS表现将受到损伤严重程度的影响；(Ii) 与神经变性相一致的纵向~(23)Na MRI和~1H MRS改变将与病情恶化相关 两次随访的临床结果。(3.c)确定哪些MR测量(或其组合) 是基于机理模型和纵向数据的长期脑损伤结果的最佳预测因子。

Project Summary Traumatic brain injury (TBI) is the world's leading cause of neurological disability in the young adult and middle-aged population. The role of computed tomography (CT) and magnetic resonance imaging (MRI) in patient management is limited due to the widespread presence of clinically-relevant, but imaging-occult injury. We propose new metrics of TBI damage obtained from sodium (23Na) MRI and proton MR spectroscopy (1H MRS). The central hypothesis is that conjoint 23Na MRI/1H MRS will provide metabolic imaging markers for loss of ion homeostasis and neurodegeneration, which will predict patients’ long-term clinical outcome. Sodium MRI is a non-invasive modality based on the direct detection of Na+ ions using dedicated MRI software and hardware. It can assess loss of Na+ homeostasis, which can be disturbed by processes where ionic imbalance is the driving force behind the cascade of cell damage. The Na+/K+ exchange pump can be affected by energy deficits due to mitochondrial dysfunction, as well as by diffuse axonal injury, the histopathological signature of TBI. This would result in variations of the intracellular sodium concentration (C1), while inflammation, gliosis and cell loss would be reflected in variations of the extracellular volume fraction (alpha2). We propose to combine the 23Na metrics C1 and alpha2 with 1H MRS, from which quantification of N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) can be used to infer neuronal health/density (NAA), cellular energy/density (Cr), membrane turnover (Cho) and astrocytic activation (mI). Specific aims are: AIM 1: Methodology. (1.a) To optimize ultrashort echo-time 23Na MRI with and without fluid suppression at 3 T. To optimize image reconstruction with denoising and compressed sensing to increase signal-to-noise ratio, resolution and speed of acquisition. To develop C1 and alpha2 quantification based on 23Na spin dynamics simulation and reference phantoms. (1.b) To implement whole-brain 1H MRS acquisition with 4th order shimming. AIM 2: Clinical application. (2.a) To compare C1 and alpha2 in TBI patients and controls at baseline (≤10 days after TBI) and their rates of change over time (2- month and 1-year follow-ups for TBI, 1-year follow-up for controls), adjusted for MRI (FLAIR, SWI, DTI) and 1H MRS. (2.b) To correlate the baseline values of the MR metrics, and their rates of change over time, with clinical outcome at the two follow-ups. To assess the added value of C1 and alpha2 to MRI and 1H MRS. AIM 3: Mechanistic model. (3.a) Given the interdependence between ATP and both NAA and C1, to determine whether TBI-related changes in C1 are glial or neuronal. (3.b) To test whether, based on a mechanistic model of neurodegeneration: (i) baseline 23Na MRI and 1H MRS findings will be moderated by injury severity; (ii) longitudinal 23Na MRI and 1H MRS changes consistent with neurodegeneration will correlate with worse clinical outcome at the two follow-ups. (3.c) To determine which MR measurements (or combinations thereof) are best predictors of long-term TBI outcome, based on the mechanistic model and the longitudinal data.