CLINIC PATHOPHYSIOLOGY OF ACUTE BRAIN INJURY

描述（由申请人提供）：本计划项目的总体目标是研究急性脑损伤受试者在损伤和治疗期间发生的病理生理学变化。我们将探讨三种类型的急性脑损伤：脑出血，缺血性中风和头部外伤。在项目1中，Allyson Zazutia博士将研究脑出血后水肿的机制、程度和临床重要性。在项目2中，William Powers博士和Venkatesh Aiyagari博士将使用PET来确定药物降低全身动脉压对急性缺血性卒中局部脑血流量的影响。在项目3中，Michael Diringer和Robert Grubb博士将研究甘露醇和高渗盐水对缺血性卒中和头部创伤所致脑水肿的病理生理学影响。 成像核心将对项目1、2和3的PET、MR和CT数据进行采集、重建、处理和存档，并根据金标准技术验证最近开发的CBF和OEF估计的MR方法。放射化学核心将为项目1、2和3提供放射性药物，并建造一个稳态氧-15气体吸入系统，以便对未进行气管内插管或不能主动吸入的受试者进行PET研究。该项目利用了华盛顿大学独特的设施和专业知识。它结合了最先进的定量神经成像，重症神经系统患者护理的专业知识和多年研究脑血流和代谢的经验。这项研究将提供重要的病理生理学信息，指导未来的研究走向最富有成效的方法，改善急性脑损伤的破坏性影响。

DESCRIPTION (provided by applicant): The overall goal of this Program Project is to investigate the pathophysiological changes that occur during injury and treatment in human subjects with acute brain damage. We will investigate three types of acute brain injury: intracerebral hemorrhage, ischemic stroke and head trauma. In Project 1, Dr. Allyson Zazutia will investigate the mechanism, extent and clinical importance of edema following intracerebral hemorrhage. In Project 2, Drs. William Powers and Venkatesh Aiyagari will use PET to determine the effect of pharmacologic reduction of systemic arterial pressure on regional cerebral blood flow in acute ischemic stroke. In Project 3, Drs. Michael Diringer and Robert Grubb will investigate the pathophysiological effects of mannitol and hypertonic saline on brain edema due to ischemic stroke and head trauma. The Imaging Core will perform acquisition, reconstruction, processing and archiving of the PET, MR and CT data for Projects 1,2 and 3 as well as validate recently developed MR methods of CBF and OEF estimation against gold-standard techniques. The Radiochemistry Core will provide radiopharmaceuticals for Projects 1,2 and 3 as well as construct a steady state oxygen-15 gas inhalation system to permit PET studies in subjects who are not endotracheally intubated or who cannot actively inhale. This Program Project draws on a combination of facilities and expertise at Washington University that is unique. It combines state-of-the art quantitative neuroimaging, expertise in the care of critically ill neurological patients and many years experience in studying cerebral blood flow and metabolism. This research will provide fundamentally important pathophysiological information to guide future research toward the most fruitful approaches for ameliorating the devastating impact of acute brain injury.