Modeling Brain Hypoxia to Predict Clinical Outcomes

描述(由申请人提供)：氧气输送到大脑的障碍被认为是患者在某些外科手术和暴露于一氧化碳(CO)后经历神经认知功能障碍的主要病因。了解这些事件对大脑特定区域氧气输送的损害程度，对于了解神经损伤的程度和评估旨在预防这些患者神经后遗症的治疗策略的疗效至关重要。例如，对于一氧化碳中毒的患者，既没有公认的临床测量来预测神经结果，也没有关于常压(NBO)和高压氧(HBO)的疗效达成一致，这两种治疗被认为可以提高脑组织中的氧分压(PO2)，并将损伤降至最低。然而，对一氧化碳中毒患者的磁共振成像研究，对于大脑中发生大体变化的特定区域(如额叶皮质和白质、基底节、海马体)，总体上是一致的。我们建议建立一个特定脑区组织PO2分布的数学模型，并检验基于模型的局部脑组织缺氧估计将与CO中毒患者的神经预后相关的假设。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、基底节、海马体、普通灰质和普通白质。在这份R03(小型研究拨款)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，使其代表指定的6个大脑区域。接下来，我们将使用我们的模型，通过对大型(现有)临床数据库的回顾分析，估计在一氧化碳暴露和治疗期间，个别一氧化碳中毒患者的局部脑缺氧持续时间和程度。最后，我们将CO中毒患者的临床结果(MRI结果、神经后遗症)与模型衍生的大脑特定区域局部缺氧的程度、持续时间和空间范围的指数相关联。我们预计，这种模拟方法将有助于解释结果，并加强对高压氧与高压氧在个别一氧化碳中毒病例中疗效的理解。此外，经过适当的修改，这种模拟建模方法可以应用于其他临床和实验情况，包括中风和心脏手术等涉及到大脑的氧气输送受损的情况。

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.