IMAGING OXYGEN METABOLISM IN BRAIN

描述(摘自申请者的摘要)：缺血性中风是一种 常见且破坏性的疾病。这个项目的长期目标是 开发一种工具来研究中风的病理生理学，特别是 缺血半暗带。在缺血的核心血流量是正常的20% 新陈代谢几乎是不存在的。周边区域也减少了 血流量(正常的20%至50%)，但仅有轻微的代谢不足。 这个区域被称为“缺血半暗带”。事实证明，这一点 早期治疗可以挽救该区域。这些领域也涉及到 在被认为具有缺血耐受性的活性蛋白质合成中。 申请人假设在活体磁共振成像(MRI) 氧耗量可以区分半影区和梗死区 在局灶性脑缺血的背景下。为了检验这一假设， 申请人提议开发新的磁共振方法来成像脑氧 新陈代谢和血液流动。这些方法是基于对 17-0核的核磁共振，这已经被证明是一个 敏感的技术。申请者将在正常大鼠身上评估这种方法 并与现有的测量脑氧含量的方法进行对比验证 新陈代谢。然后，他将使用这种方法来研究一个可逆的模型 卒中涉及大脑中动脉闭塞。这一现象 缺血耐受性将通过将磁共振数据与 免疫组织化学方法检测蛋白表达。通过这种方式，他希望 能够将磁共振图像与蛋白质合成联系起来。这个项目将 大大提高我们对中风和中风的病理生理学的认识 可能提供一种工具，用来非侵入性地评估基因 治疗。

DESCRIPTION (Adapted from applicant's abstract): Ischemic stroke is a common and devastating disorder. The long-term goal of this project is to develop a tool to study the pathophysiology of stroke and in particular the ischemic penumbra. In the ischemic core blood flow is <20 percent of normal and metabolism is almost absent. The peripheral regions also have reduced blood flow (20 to 50 percent of normal) but are only slightly hypometabolic. This region is called the "ischemic penumbra". It has been shown that this region can be salvaged with early treatment. These areas are also involved in active protein synthesis which is thought to endow ischemic tolerance. The applicant hypothesizes that in vivo magnetic resonance imaging (MRI) of oxygen consumption can distinguish penumbral regions from infarcted regions in the setting of focal ischemia. In order to test this hypothesis the applicant proposes to develop novel MR methods to image cerebral oxygen metabolism and blood flow. The methods are based on indirect detection of the 17-0 nucleus using 1H MRI, which has already been demonstrated to be a sensitive technique. The applicant will evaluate this method in normal rats and validate it against existing methods for measuring cerebral oxygen metabolism. He will then use this method to study a reversible model of stroke involving occlusion of middle cerebral artery. The phenomenon of ischemic tolerance will be investigated by correlating MR data with immunohistochemical assays for protein expression. In this way, he hopes to be able to correlate MR images with protein synthesis. This project will greatly enhance our understanding of the pathophysiology of stroke and possibly provide a tool with which to noninvasively assess genetic therapies.