Modeling Brain Hypoxia to Predict Clinical Outcomes

模拟脑缺氧以预测临床结果

• 批准号: 6984490
• 负责人: EUGENE N BRUCE
• 金额: $ 7.32万
• 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 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984490
• 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 6 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 1 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）：认为向大脑输送氧气受损是某些外科手术后和暴露于一氧化碳（CO）后患者发生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）输送，是了解神经系统损伤程度和评估旨在预防这些患者神经系统后遗症的治疗策略有效性的关键。例如，对于CO中毒的患者，既没有公认的临床措施来预测神经学结果，也没有关于常压（NBO）与高压（HBO）高氧的疗效的一致意见，这些治疗被认为可以增加脑组织中的氧分压（PO2）并使损伤最小化。然而，对CO中毒患者的MR成像研究，对于发生大体变化的大脑特定区域（例如，脑白质）的看法基本一致。例如，在一个实施例中，额叶皮质和白色物质、基底神经节、海马体）。我们建议开发一个数学模型的组织PO2分布在特定的大脑区域和测试的假设，基于模型的估计区域脑组织缺氧将与CO中毒患者的神经系统的结果。我们的模型将代表大脑的6个特定区域：额叶皮质、额叶白色物质、基底神经节、海马、一般灰质和一般白色物质。在这个R03（小额研究资助）提案中，我们将首先将我们现有的O2输送模型扩展到1个大脑区域，以便它代表6个指定的大脑区域。接下来，我们将使用我们的模型来估计，通过回顾性分析一个大的（现有的）临床数据库，在CO暴露和治疗过程中，个别CO中毒患者局部脑缺氧的持续时间和程度。最后，我们将相关的临床结果（MRI结果，神经系统后遗症）从CO中毒患者的程度，持续时间和空间范围的局部缺氧在特定区域的大脑模型衍生的指数。我们预计，这种建模方法将有助于解释结果，并提高对HBO与NBO在CO中毒个案中的疗效的理解。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，涉及受损的O2输送到大脑，如中风和心脏手术。