Modeling Brain Hypoxia to Predict Clinical Outcomes

模拟脑缺氧以预测临床结果

• 批准号: 7069566
• 负责人: EUGENE N BRUCE
• 金额: $ 7万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-24 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7069566
• 关键词: bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain mapping; carbon monoxide poisoning; cerebral ischemia /hypoxia; cognition disorders; computer simulation; human data; human therapy evaluation; hyperbaric oxygen therapy; magnetic resonance imaging; mathematical model; model design /development; nervous system disorder therapy; neuropathology; outcomes research; oxygen therapy; prognosis

DESCRIPTION (provided by applicant): Impaired O2 delivery to the brain is thought to be a major etiologic factor in the neurocognitive dysfunction experienced by patients after certain surgical procedures and after exposure to carbon monoxide (CO). Knowledge of the extent to which these events impair oxygen (O2) delivery to specific regions of the brain is key to understanding the extent of neurologic damage and to assessing the efficacy of treatment strategies designed to prevent neurologic sequelae in these patients. For CO-poisoned patients, for example, there is neither an accepted clinical measure that predicts neurological outcome nor agreement regarding the efficacy of normobaric (NBO) vs. hyperbaric (HBO) hyperoxia, treatments that are presumed to increase partial pressure of oxygen (PO2) in brain tissue and minimize injury. MR imaging studies of CO-poisoned patients, however, are in general agreement regarding the specific regions of the brain in which gross changes occur (e. g., frontal cortex and white matter, basal ganglia, hippocampus). We propose to develop a mathematical model of tissue PO2 distributions in specific brain regions and test the hypothesis that model-based estimates of regional brain tissue hypoxia will correlate with neurological outcome in CO-poisoned patients. Our model will represent six specific regions of the brain: frontal cortex, frontal white matter, basal ganglia, hippocampus, generic gray matter, and generic white matter. In this R03 (Small Research Grant) proposal, we will first expand our existing model of O2 delivery to one brain region so that it represents the 6 specified brain regions. Next we will use our model to estimate, by retrospective analyses of a large (existing) clinical database, the duration and degree of regional brain hypoxia in individual CO-poisoned patients during both CO exposure and therapy. Finally, we will correlate the clinical outcomes (MRI findings, neurologic sequelae) from CO-poisoned patients with model-derived indices of the degree, duration, and spatial extent of local hypoxia in specific regions of the brain. We anticipate that this modeling approach will help to explain outcome and enhance the understanding of the efficacy of HBO vs. NBO in individual cases of CO poisoning. Furthermore, with appropriate modifications, this simulation modeling approach can be applied to other clinical and experimental situations involving impaired O2 delivery to the brain such as stroke and cardiac surgery.

描述（由申请人提供）：O2向大脑的递送受损被认为是患者在某些外科手术后和暴露于一氧化碳（CO）后患者经历的神经认知功能障碍的主要病因。了解这些事件在多大程度上损害了大脑特定区域的氧气（O2）是了解神经系统损害程度的关键，并评估旨在防止这些患者的神经系统后遗症的治疗策略的功效。例如，对于共偶然的患者，既没有一种可接受的临床指标，可以预测神经系统结果，也没有关于正常（NBO）与高压（HBO）高氧的疗效的一致性的一致性，这些治疗方法被认为是增加氧气的局部压力（PO2） ）在脑组织中并最大程度地减少损伤。然而，对共偶联患者的MR成像研究一般都在大脑的特定区域一般同意，例如，大脑发生了总变化的特定区域（例如，额叶皮层和白质，基底神经节，海马）。我们建议在特定大脑区域开发组织PO2分布的数学模型，并检验以下假设：基于模型的区域脑组织缺氧的估计值将与共毒性患者的神经系统结果相关。我们的模型将代表大脑的六个特定区域：额叶皮层，额叶白质，基底神经节，海马，通用灰质和通用白质。在此R03（小型研究补助金）提案中，我们将首先将现有的O2输送模型扩展到一个大脑区域，以代表6个指定的大脑区域。接下来，我们将通过对大型（现有）临床数据库的回顾性分析，在CO暴露和治疗期间各个对偶联患者的区域性脑缺氧的持续时间和程度进行回顾性分析。最后，我们将从对大脑特定区域中特定区域的程度，持续时间和局部缺氧的程度，持续时间和空间范围的模型指数的临床结果（MRI发现，神经后遗症）相关联。我们预计，这种建模方法将有助于解释结果并增强对HBO与NBO在CO中毒各种情况下的疗效的理解。此外，通过适当的修改，这种模拟建模方法可以应用于其他临床和实验情况，涉及O2向大脑递送的受损，例如中风和心脏手术。