MRS Detects Metabolic Dysfunction after Brain Injury

MRS 检测脑损伤后代谢功能障碍

基本信息

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
项目类别：
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

项目摘要

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！功能障碍表现为低比率氧化代谢可预测创伤性脑损伤 (TBI) 后最终的脑容量损失。 TBI 是一种广泛性脑功能障碍，正常情况下会发生继发性细胞死亡和脑萎缩。尽管主要解剖损伤的区域相对有限，但仍出现组织。其机制为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 TBI 后流行的情况。氧化代谢减少 (CMRO2) 是线粒体受损的结果功能，并已通过正电子发射断层扫描 (PET) 在 TBI 中进行测量。我们的初步研究表明 1) CMRO2 在正常出现的大脑区域以及邻近挫伤的区域中减少，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) 迟发性萎缩与乳酸/丙酮酸值异常的持续时间有关，4) 迟发性萎缩与与神经/认知结果相关。因此，能源供应的持续短缺可能与最终细胞损失和不良结果。 TBI 提供了研究人类大脑组织的独特机会侵入性脑微透析监测和 PET 成像，从而能够独立测量线粒体空间功能（PET）和跨时间功能（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大脑区域是否注定会发生脑萎缩后续 MR),3) 确定急性氧化代谢受损是否与不良临床结果相对应， 4) 评估磁共振波谱 N-乙酰天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，但可能会导致广泛的 MRS 在缺乏氧气 PET 技术的中心对 TBI 患者的临床护理中的应用。这项研究可以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方法的照顾。拟议研究的知识将广泛应用于重症监护神经外伤患者。