Brain Metabolism and Outcome Following TBI in Children

描述（由申请人提供）：虽然创伤性脑损伤（TBI）是 是北美儿童死亡和后天残疾的主要原因， 儿童创伤性脑损伤的病理生理过程 明白我们最近发现大脑的神经代谢物标志物 细胞损伤-N-乙酰天冬氨酸（NAA）和胆碱（Cho）， 非侵入性磁共振波谱（MRS）预测TBI部位 成年人的长期认知结果。此外， 神经代谢物的变化出现在灰色与白色物质，表明不同的 影响神经元索马和轴突的过程。虽然光谱 在TBI后的儿童中观察到异常， 这些敏感的损伤标志物和认知功能之间的关系还有待进一步研究。 测定 磁共振波谱成像（SI）提供了一种独特的，时间效率高的 意味着在整个大脑中同时量化这些标记物。的目标 本研究的目的是（1）验证SI作为诊断工具的准确性， 局部TBI严重程度的体内评估，和（2）增加我们的理解 TBI后病理生理事件的演变及其与 儿童的认知结果。通过阐明年龄、TBI 严重程度和认知结果，这项研究可能有助于改善结果 预测和促进儿童TBI的治疗。由于MRS提供了 直接测量与TBI相关的潜在细胞损伤， 阐明脑发育的病理生理机制。因此，它可以 为基础研究和临床研究提供有力的结果衡量标准 审判 具体目标1至3证实并扩展了我们对成人的IH-MRS研究， TBI致受伤儿童我们建议，在儿童中， TBI后神经元损伤的神经代谢物证据（目的1），以及 选定神经代谢物浓度与总体 认知表现（目标2）。年龄效应将受到特别关注（Aim 3）。探索性目的4和5检查区域特异性神经代谢物数据 由S1捕获以非侵入性地表征脑的解剖分布 细胞损伤变化（目的4）。我们还建议调查是否 不同脑区的细胞损伤变化具有不同的认知功能 儿童后遗症（目标5）。这些分析将有助于理解 神经代谢物的区域变化的性质和意义 改变，因此，儿童TBI的临床异质性。

DESCRIPTION (provided by applicant): Although traumatic brain injury (TBI) is the leading cause of death and acquired disability in North American children, the pathophysiological processes involved in childhood TBI are poorly understood. We have recently shown that neurometabolite markers of brain cellular injury-N-acetylaspartate (NAA) and choline (Cho) measured remote from the locus of TBI by non-invasive magnetic resonance spectroscopy (MRS, predict long-term cognitive outcome in adults. Furthermore, unique patterns of neurometabolite changes emerged in gray vs. white matter, suggesting differing processes affecting neuronal soma and axons. Although spectroscopic abnormalities are seen in children after TBI, the specific relationships between these sensitive markers of injury and cognitive function are yet to be determined. Magnetic resonance spectroscopic imaging (SI) provides a unique, time-efficient means to simultaneously quantify these markers throughout the brain. The goals of this research are (1) to validate SI as a diagnostic tool for accurate in vivo assessment of regional TBI severity, and (2) to increase our understanding of the evolution of pathophysiological events after TBI and their relation to cognitive outcome in children. By elucidating the relationship between age, TBI severity, and cognitive outcome, this research may help to improve outcome prediction and facilitate treatment of childhood TBI. Since MRS provides a direct measure of the underlying cellular injury associated with TBI, it may elucidate the pathophysiological mechanism in developing brain. Hence, it may form the basis for a powerful outcome measure for basic research and clinical trials. Specific Aims 1 through 3 confirm and extend our IH-MRS studies of adults with TBI to injured children. We propose to characterize, in children, neurometabolite evidence of neuronal injury after TBI (Aim 1), as well as the relationship between selected neurometabolite concentrations and overall cognitive performance (Aim 2). Age effects will receive special attention (Aim 3). Exploratory Aims 4 and 5 examine regionally specific neurometabolite data captured by Sl to characterize noninvasively the anatomic distribution of brain cellular injury changes (Aim 4). We also propose to investigate whether cellular injury changes in diverse brain regions have different cognitive sequelae in children (Aim 5). These analyses will facilitate an understanding of the nature and significance of regional variation in neurometabolite changes, and hence, the clinical heterogeneity of TBI in children.