MRS Detects Metabolic Dysfunction after Brain Injury

描述(申请人提供)：这项建议的主要目的是确定线粒体！以低氧化代谢率反映的功能障碍预示着创伤性脑损伤(TBI)后最终的脑容量损失。脑外伤是一种广泛性脑功能障碍的疾病，在这种情况下，尽管初级解剖损伤的范围相对有限，但正常组织中仍会出现继发性细胞死亡和脑萎缩。迟发性脑萎缩的机制尚不清楚，但可能与早期和持续的氧化代谢受损有关，这种损害是脑外伤后的地方性疾病。氧化代谢降低(CMRO2)是线粒体功能受损的结果，已通过正电子发射断层扫描(PET)在脑损伤中检测到。我们的初步研究表明，1)正常脑区和挫伤附近的CMRO2减少，2)正常脑区的CMRO2减少可以通过脑微透析乳酸/丙酮酸值监测，3)迟发性萎缩与乳酸/丙酮酸值异常的持续时间有关，4)迟发性萎缩与神经/认知结局有关。因此，能源供应的持续不足可能与最终的细胞损失和糟糕的结果有关。TBI为研究人脑组织提供了独特的机会，通过有创的脑微透析监测和PET成像，从而能够独立测量空间(PET)和跨时间(微透析)的线粒体功能。拟议的研究将1)使用正电子发射计算机断层扫描和微透析来确定脑外伤后氧化代谢受损的程度和空间分布，2)确定氧化代谢降低的脑区是否注定会导致脑萎缩)，3)确定急性氧化代谢受损是否对应于不良的临床结果，4)评估磁共振波谱N-乙酰-天冬氨酸作为非侵入性氧化代谢替代标记物的有效性。第四个目标是探索性的，但可能导致MRS在缺乏氧气PET技术的中心的脑损伤患者的临床护理中得到广泛应用。这项研究只能在创伤性脑损伤的情况下进行，在这种情况下，侵入性监测方法是护理的标准。来自拟议研究的知识将广泛应用于神经创伤患者的危重护理。

DESCRIPTION (provided by applicant): 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 across time (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.