Modeling Brain Hypoxia to Predict Clinical Outcomes

描述（由申请人提供）：脑氧输送受损被认为是某些外科手术后和暴露于一氧化碳（CO）后患者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输送，是了解神经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，对于一氧化碳中毒患者，既没有公认的临床指标来预测神经预后，也没有关于正压（NBO）与高压氧（HBO）高氧的疗效的一致意见，后者被认为可以增加脑组织中的氧分压（PO2）并将损伤降到最低。然而，一氧化碳中毒患者的MR成像研究对于发生明显变化的大脑特定区域（如额叶皮质和白质、基底神经节、海马）的看法普遍一致。我们建议建立一个特定脑区域组织PO2分布的数学模型，并验证基于模型的区域脑组织缺氧估计与co中毒患者神经系统预后相关的假设。我们的模型将代表大脑的6个特定区域：额叶皮质、额叶白质、基底神经节、海马体、一般灰质和一般白质。在这个R03（小型研究资助）提案中，我们将首先将现有的氧气输送模型扩展到1个大脑区域，使其代表6个指定的大脑区域。接下来，我们将通过对一个大型（现有）临床数据库的回顾性分析，使用我们的模型来估计一氧化碳中毒患者在一氧化碳暴露和治疗期间局部脑缺氧的持续时间和程度。最后，我们将把一氧化碳中毒患者的临床结果（MRI结果、神经系统后遗症）与大脑特定区域局部缺氧的程度、持续时间和空间范围的模型衍生指标联系起来。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在一氧化碳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涉及脑氧输送受损的临床和实验情况，如中风和心脏手术。

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.