QUANTITATIVE IMAGING OF CEREBRAL BLOOD FLOW AND OXYGEN CONSUMPTION

该项目的主要目的是开发新的磁共振(MR)“自旋标记”方法来成像人类的脑血流(CBF)，并将这些方法应用于研究精神疾病患者的生理和药物功能障碍。新的磁共振方法使用经典示踪剂理论，但它们不使用放射性示踪剂，而是使用稳定同位素的扰动磁自旋态。本项目以前的工作：(1)找出阻碍计算人类脑血流量定量值的一些主要问题，并制定克服这些问题的理论和方法方法；(2)扩展和修订初步的PET验证实验；(3)开发新的示踪剂动力学模型，解释水在血脑屏障中的限制扩散；(4)开发三维动脉自旋标记方法，可用于研究运动激活任务中的区域激活。这些三维方法解决了使用二维方法进行激活研究所固有的许多问题，并允许更好的空间分辨率。在过去的一年里，3D方法被用来研究工作记忆认知任务中区域激活的对象内和对象间的变异性。结果表明，该方法具有良好的学科内重复性，但也表现出学科间的差异性。在接下来的几年里，这些实验将被扩展到研究特定生化和药物途径的抑制剂对认知激活过程的影响，并最终将应用于量化精神疾病患者的脑功能障碍。

The major aim of this project is to develop new magnetic resonance (MR) "spin tagging" approaches for imaging cerebral blood flow (CBF) in humans, and to apply these approaches to study physiological and pharmacological dysfunction in psychiatric patients. The new MR approaches use classical tracer theory, but instead of using radioactive tracers they use perturbed magnetic spin states of stable isotopes. Previous work in this project: (1) identified a number of major problems that had precluded the calculation of quantitative cerebral blood flow values in humans, and developed theoretical and methodological approaches for overcoming these problems; (2) extended and revised preliminary PET validation experiments; (3) developed a new tracer kinetic model that accounts for restricted diffusion of water across the blood brain barrier; (4) developed three-dimensional arterial spin tagging approaches that can be used to study regional activation during motor activation tasks. These three-dimensional approaches solve many of the problems inherent in using two-dimensional approaches for activation studies, and also allow better spatial resolution. In the last year the 3D approaches have been used to study intrasubject and intersubject variability in regional activation during working memory cognitive tasks. The results show good intrasubject reproducibilty, but also show intersubject variation. In the next few years these experiments will be extended to study the effects of inhibitors of specific biochemical and pharmacological pathways on the cognitive activation process, and will ultimately be applied to quantitate cerebral dysfunction in psychiatric patients.