MRS Detects Metabolic Dysfunction after Brain Injury

描述（由申请人提供）：本提案的主要目的是确定线粒体！低氧化代谢率所反映的功能障碍可预测创伤性脑损伤（TBI）后最终的脑容量损失。TBI是一种广泛的脑功能障碍，在正常组织中发生继发性细胞死亡和脑萎缩，尽管有相对有限的原发解剖损伤区域。迟发性脑萎缩的机制尚不清楚，但可能与TBI后特有的早期和持续性氧化代谢受损有关。氧化代谢（cro2）的减少是线粒体功能受损的结果，并已通过正电子发射断层扫描（PET）在TBI中测量。我们的初步研究表明：1)cmor2在正常出现的脑区以及邻近的挫伤区域减少，2)cmor2在正常区域的减少可以通过脑微透析乳酸/丙酮酸值来监测，3)迟发性萎缩与乳酸/丙酮酸值异常持续的时间有关，4)迟发性萎缩与神经/认知预后有关。因此，持续的能量供应不足可能与最终的细胞损失和不良预后有关。TBI提供了一个独特的机会，通过侵入性脑微透析监测和PET成像来研究人类脑组织，从而能够在空间（PET）和时间（微透析）上独立测量线粒体功能。拟开展的研究包括：1)利用PET和微透析确定TBI后氧化代谢受损的程度和空间分布；2)通过随访MR确定氧化代谢受损的脑区是否会导致脑萎缩；3)确定急性氧化代谢受损是否与不良临床结果相对应；4)评估核磁共振波谱n-乙酰-天冬氨酸作为氧化代谢无创替代标志物的有效性。第四个目标是探索性的，但可能导致MRS在缺乏氧PET技术的中心的TBI患者的临床护理中广泛应用。这项研究只能在创伤性脑损伤的背景下进行，在这种情况下，侵入性监测方法是标准的治疗方法。所提出的研究的知识将广泛应用于神经创伤患者的重症监护。

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.