MRS Detects Metabolic Dysfunction after Brain Injury

MRS 检测脑损伤后代谢功能障碍

• 批准号: 7357448
• 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/7357448
• 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; 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

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.

该提案的主要目的是确定线粒体是否！功能障碍反映出低率 氧化代谢可预测创伤性脑损伤（TBI）后最终的大脑体积损失。 TBI是一个 次要细胞死亡和脑萎缩在正常情况下发生的广泛脑功能障碍的状况 尽管相对狭窄的主要解剖损伤区域，但仍出现组织。机制 延迟的大脑萎缩尚不清楚，但可能与早期和持续性氧化代谢有关 这是TBI之后的地方性。氧化代谢降低（CMRO2）是线粒体受损的结果 功能并通过正电子发射断层扫描（PET）在TBI中进行了测量。我们的初步研究 表明1）在正常出现的大脑区域以及与挫伤相邻的正常出现的cmro2，2） 正常区域中CMRO2的降低可以通过大脑微透析乳酸/丙酮酸值监测 3）延迟萎缩与异常乳酸/丙酮酸的持续时间有关，4）延迟萎缩为 与神经/认知结果有关。因此，能源供应的持续赤字可能与 最终的细胞损失和不良结果。 TBI提供了一个独特的机会来研究人脑组织 浸润性脑透析监测和PET成像，从而实现了独立的测量 空间（PET）和Acrosstime（微透析）中的线粒体功能。拟议的研究将1） 确定使用PET和 微透析，2）确定氧化代谢降低的大脑区域是否注定针对脑萎缩 在随访中MR），3）确定急性障碍氧化代谢是否对应于临床结果不良， 4）评估磁共振光谱的有效性N-乙酰天冬氨酸作为非侵入性替代物 氧化代谢的标志。第四个目标是探索性的，但可能会导致广泛 在缺乏氧气宠物技术的中心中，在TBI患者中应用MRS在临床护理中的应用。这项研究可以 仅在创伤性脑损伤的背景下完成，其中侵入性监测方法是标准的 照顾。拟议研究的知识将广泛应用于重症监护 神经病患者。