MRS Detects Metabolic Dysfunction after Brain Injury

这项建议的主要目的是确定是否线粒体！功能障碍，表现为 氧化代谢是创伤性脑损伤（TBI）后最终脑体积损失的预测因素。TBI是一个 脑萎缩：一种广泛的脑功能障碍状态，在正常脑组织中发生继发性细胞死亡和脑萎缩 尽管原发性解剖损伤的区域相对有限，但仍出现组织。的机理 迟发性脑萎缩尚不清楚，但可能与早期和持续的氧化代谢受损有关 这是创伤性脑损伤后的地方病氧化代谢减少（CMRO 2）是线粒体受损的结果。 功能，并已在TBI中通过正电子发射断层扫描（PET）进行测量。我们的初步研究 表明1）CMRO 2在正常出现的脑区域以及邻近挫伤的脑区域中减少，2） 正常区域中CMRO 2的减少可以通过脑微透析乳酸/丙酮酸值来监测， 3)延迟性萎缩与乳酸/丙酮酸值异常的持续时间有关，4）延迟性萎缩与 与神经/认知结果相关。因此，能源供应持续不足可能与以下因素有关： 最终导致细胞丢失和预后不良。TBI提供了一个独特的机会来研究人脑组织， 侵入性脑微透析监测和PET成像，从而能够独立测量 线粒体功能的空间（PET）和跨时间（微透析）。拟议的研究将1） 使用PET确定TBI后氧化代谢受损的程度和空间分布， 微透析，2）确定氧化代谢减少的脑区域是否注定发生脑萎缩 3）确定急性受损的氧化代谢是否对应于不良的临床结果， 4)评价磁共振波谱N-乙酰天门冬氨酸作为非侵入性替代物的有效性 氧化代谢的标志物。第四个目标是探索性的，但可能导致广泛的 磁共振波谱在缺氧中心脑外伤患者临床护理中的应用PET技术。本研究可 仅在创伤性脑损伤的情况下进行，其中侵入性监测方法是标准的 照顾。从拟议的研究中获得的知识将广泛应用于重症监护。 神经创伤患者

The main aim of this proposal is to determine if mitochondria! dysfunction as reflected by low rates of oxidative metabolism is predictive of eventual brain volume loss after traumatic brain injury (TBI). TBI is a condition of widespread brain dysfunction in which secondary cell death and brain atrophy occur in normal appearing tissue despite a relatively confined area of primary anatomical damage. The mechanism of delayed brain atrophy is not clear but may be related to early and persistent impaired oxidative metabolism that is endemic after TBI. Reduced oxidative metabolism (CMRO2) is a result of impaired mitochondrial function and has been measured in TBI by positron emission tomography (PET). Our preliminary studies indicate that 1) CMRO2 is reduced in normal appearing brain regions as well as adjacent to contusions, 2) reduction in CMRO2 in normal regions can be monitored by cerebral microdialysis lactate/pyruvate values, 3) delayed atrophy is related to the duration of abnormal lactate/pyruvate values, and 4) delayed atrophy is related to neurologic/cognitive outcome. Hence, a persistent deficit in energy supply may be related to eventual cell loss and poor outcome. TBI provides a unique opportunity to study human brain tissue with invasive cerebral microdialysis monitoring and PET imaging, thus enabling independent measurements of mitochondrial function in space (PET) and acrosstime (microdialysis). The proposed studies will 1) Determine the magnitude and spatial distribution of impaired oxidative metabolism after TBI using PET and microdialysis, 2) Determine if brain regions of reduced oxidative metabolism are destined for brain atrophy on follow-up MR),3) Determine if acute impaired oxidative metabolism corresponds to poor clinical outcome, 4) Evaluate the validity of magnetic resonance spectroscopy N-Acetyl-Aspartate as a non-invasive surrogate marker of oxidative metabolism. The fourth aim is intended to be exploratory but could lead to widespread application of MRS in clinical care for TBI patients in centers lacking oxygen PET technology. This study can only be done within the context of traumatic brain injury, in which invasive monitoring methods are standard of care. The knowledge from the proposed studies will have widespread application to critical care of neurotrauma patients.