LOCALIZATION OF CEREBRAL DYSFUNCTION IN DEMENTIA (AD)

拟议研究的广泛目标是推动目前 现有的神经成像技术，以促进他们的 应用于以认知和行为障碍为特征的疾病 功能障碍 这项建议的具体目的是改善形象 用于整合解剖MR图像和功能PET的分析方法 H215O局部脑血流显像及其应用 产生认知信号的行为/生理技术， 对理解痴呆患者的局部功能障碍很有价值 患者 在图像分析的发展过程中有三个主要组成部分 方法：（1）图像配准：改进的基于曲面的方法- 拟合技术将被开发用于空间配准一组 MR图像和一系列PET发射图像，这些图像通过 在不同条件下对同一受试者注射H215O， 行为/生理条件;（2）图像插值：准确 内插方案的形状的大脑表面和 大脑图像的强度水平将使用动态 弹性力场模型生成更完整的三维脑图像数据 集;和（3）图像减影：新技术将被开发用于 检测、定位和增强认知信号， 从刺激处的图像减去基线状态处的PET图像 状态 检测到的认知信号也将被配准 与由MR图像提供的解剖图相匹配。 在开发行为/生理技术时，有三个程序将 用于产生认知诱导信号， 痴呆患者的局限性功能障碍：（1）改良斯滕贝格 程序，其中与短期记忆有关的信号将被 （2）系列反应时间程序，其中信号相关 （3）言语理解 程序，这将被用来提高全球脑流量。 这项研究的结果将有助于确定 在阿尔茨海默病痴呆中受影响的神经元系统， 相关的退行性疾病，并有助于改善 了解参与的病理生理机制， 退化过程

The broad objective of the proposed research is to advance currently available neuro-imaging techniques in order to facilitate their application to disorders characterized by cognitive and behavioral dysfunction. The specific aims of this proposal are to improve image analysis methods for integrating anatomical MR images and functional PET images of regional cerebral blood flow obtained by using H215O and apply behavioral/physiological techniques to generate cognitive signals that are valuable in understanding localized dysfunction in demented patients. There are three major components in the development of image analysis methods: (1) Image registration: Improved methods based on surface- fitting techniques will be developed for spatially registering a set of MR images with a series of PET emission images that are acquired by injecting H215O to the same subject under different behavioral/physiological conditions; (2) Image interpolation: Accurate interpolation schemes for both the shapes of the brain surface and the intensity levels of brain images will be developed using an dynamic elastic force field model to generate more complete 3-D brain image data sets; and (3) Image subtraction: New techniques will be developed for detecting, localizing, and enhancing the cognitive signals by subtracting PET images at a baseline state from images at a stimulus state. The detected cognitive signals will be also be in registration with the anatomical map provided by MR images. In developing behavioral/physiological techniques, three procedures will be used to generate cognitively induced signals for understanding localized dysfunction in demented patients: (1) Modified Sternberg procedure, in which signals related to short-term memory will be assessed; (2) Serial reaction time procedure, in which signals related to implicit memory will be evaluated; and (3) Verbal comprehension procedure, which will be employed to enhance global cerebral flow. The results of this research will be of value in determining the neuronal systems affected in the dementia of Alzheimer's disease and related degenerative disorders and contribute to an improved understanding of the pathophysiological mechanisms involved in the degenerative processes.