Neurometabolism and Outcome in Traumatic Brain Injury

创伤性脑损伤是导致年轻、健康人群死亡和发病的主要原因，造成巨大的社会和经济损失。尽管在大型研究中，常用的临床标记物在统计学上与大体功能有关，但它们在预测个别患者的认知功能方面用处较小。同样，尽管传统的神经影像研究可以指导急性临床治疗，但结果预测是不可靠的，特别是在损伤解决的早期阶段。我们实验室的初步数据显示，无创磁共振波谱测量的脑细胞损伤的神经代谢物标记物与认知功能和预后密切相关。此外，我们的数据显示，某些解剖位置的损伤比其他部位更严重(即前脑比后脑更严重)，灰质神经代谢物预测认知结果比白质更可靠，这表明对脑外伤的反应具有组织异质性。我们还表明，这些神经代谢物的恢复暂时与认知能力的改善有关。我们提出了一种新的方法来评估和研究颅脑损伤，使用定量磁共振光谱成像(SI)和MRI来量化脑细胞损伤。这些对N-乙酰天冬氨酸、含胆碱化合物和水松弛时间的测量是预测大脑功能和预后的强有力的新工具。使用这些正常(通过MRI)脑损伤的神经代谢物标记物，我们的目标是确定特定的损伤模式-解剖和/或组织类型-是否与特定形式的认知功能障碍有关。磁共振波谱成像提供了一种强大的新工具来研究脑外伤后神经元的代谢完整性，并可能为临床管理、患者异质性、结果预测和治疗方案有效性的确定提供新的见解。

Traumatic brain injury (TBI) is the leading cause of death and morbidity in young, otherwise healthy populations and results in an enormous social and economic cost. Although commonly used clinical markers are statistically linked with gross functioning in large studies, they are less useful in predicting cognitive functioning in individual patients. Similarly, although conventional neuroimaging studies can guide acute clinical management, outcome prediction is unreliable, particularly at early stages of injury resolution. Preliminary data from our laboratory show that neurometabolite markers of brain cellular injury measured by non-invasive magnetic resonance spectroscopy are strongly correlated with cognitive function and outcome. Further, our data show that certain anatomic locations are more intensely injured than others (i.e., anterior brain more than posterior), and that gray matter neurometabolites predict cognitive outcome more reliably than white matter, suggesting tissue heterogeneity of response to TBI. We also show that recovery of these neurometabolites is temporarily associated with cognitive improvement. We propose a novel approach for assessment and study of TBI using quantitative magnetic resonance spectroscopic imaging (SI) and MRI to quantify cellular brain injury. These measurements of N- acetylaspartate, choline-containing compounds, and water relaxation times are a powerful new tool for prediction of brain function and outcome. Using these neurometabolite markers of injury in normal-appearing (by MRI) brain, we aim to determine whether specific patterns-anatomic and/or tissue-type of injury are associated with specific forms of cognitive dysfunction. Magnetic resonance spectroscopic imaging offers a robust new tool to investigate the metabolic integrity of the neuron following TBI, and may provide new insight into clinical management, patient heterogeneity, prediction of outcome, and the determination of effectiveness of therapeutic options.