MRS Detects Metabolic Dysfunction after Brain Injury

MRS 检测脑损伤后代谢功能障碍

• 批准号: 7167425
• 负责人: Paul M Vespa
• 金额: $ 31.73万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-10 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7167425
• 关键词: Acute; Anatomy; Area; Atrophic; Benign; Brain; Brain Injuries; Brain Part; Brain region; Caring; Cell Death; Cell Respiration; Cells; Cerebrum; Clinical; Cognitive; Coma; Condition; Contusions; Critical Care; Decision Making; Diagnostic; Due Process; Energy Supply; Functional disorder; Future; Human; Image; Impairment; Individual; Injury; Invasive; Knowledge; Lead; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Metabolism; Methods; Microdialysis; Mitochondria; Monitor; N-acetylaspartate; Neurologic; Outcome; Outcome Measure; Oxygen; Patients; Positron-Emission Tomography; Production; Pyruvate; Pyruvates; Rate; Research Personnel; Risk; Site; Spatial Distribution; Standards of Weights and Measures; Surrogate Markers; Synaptic Transmission; Technology; Therapeutic Intervention; Thinking; Time; Tissues; Trauma; Traumatic Brain Injury; base; brain metabolism; brain tissue; brain volume; cerebral atrophy; cognitive function; design; follow-up; frontal lobe; metabolic abnormality assessment; neurochemistry; predictive modeling; programs

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.

描述（由申请人提供）：该提案的主要目的是确定线粒体！氧化代谢率低所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。 TBI 是一种广泛的脑功能障碍，尽管原发性解剖损伤的区域相对有限，但正常组织中仍会发生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 TBI 后普遍存在的早期和持续的氧化代谢受损有关。氧化代谢减少 (CMRO2) 是线粒体功能受损的结果，在 TBI 中可以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) CMRO2 在正常出现的脑区域以及挫伤附近减少，2) 正常区域 CMRO2 的减少可以通过脑微透析乳酸/丙酮酸值进行监测，3) 延迟性萎缩与异常乳酸/丙酮酸值的持续时间有关，4) 延迟性萎缩与 神经/认知结果。因此，能量供应的持续不足可能与最终的细胞损失和不良结果有关。 TBI 提供了利用侵入性脑微透析监测和 PET 成像研究人类脑组织的独特机会，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 PET 和微透析确定 TBI 后氧化代谢受损的程度和空间分布，2) 确定氧化代谢减少的大脑区域是否注定会在后续 MR 中发生脑萎缩，3) 确定急性氧化代谢受损是否对应于不良的临床结果，4) 评估磁共振波谱的有效性 N-乙酰基-天冬氨酸作为氧化代谢的非侵入性替代标志物。第四个目标是探索性的，但可能会导致 MRS 广泛应用于缺乏氧气 PET 技术的中心对 TBI 患者的临床护理。这项研究只能在创伤性脑损伤的背景下进行，其中侵入性监测方法是标准护理方法。拟议研究的知识将广泛应用于神经创伤患者的重症监护。