PET: NORMAL CEREBRAL FUNCTION AND AFFECTIVE DISORDERS

我们建议开发和应用发射断层扫描（PET）作为分析 生物化学测定技术研究正常人脑功能， 情感障碍 目标是：1.）化学/生物化学。 将开发和/或改进快速合成技术， 用于测量的（F-18）-氟和（C-11）脱氧葡萄糖的制备 葡萄糖代谢，C-11和N-13标记的氨基酸，用于测量 用于受体测定的蛋白质合成速率和F-18配体（主要 螺哌啶，而且还开发了高比活性F-18标记 将技术应用于其他配体）。 组织生化测定和 大鼠和猴的放射自显影研究将用于结构和 定义动力学模型，并在不同的蛋白质示踪剂中进行选择 合成和受体测定。 2.）的情况。断层扫描。 NeuroECAT 将升级到提供前所未有的空间分辨率水平， 图像质量和量化必要的测量详细 这一提议所要求的大脑功能的神经解剖学组成部分。 3.）第三章示踪剂动力学建模。 脑电测量的操作方程 血流、蛋白质合成、氧代谢和受体测定将 开发和验证。 4.）名正常人 研究将 执行，以验证方法，并确定规范和变化， 局部葡萄糖和氧代谢、血流和蛋白质合成 rates. 将进行研究以确定代谢和血液流动 对特定感官刺激的反应，以激活视觉，听觉， 语言和认知功能以及这些功能的使用 刺激-反应任务作为情感障碍的激发性测试 患者 5.）患者 局部葡萄糖代谢将在 双相和单相情感障碍患者，以确定是否 存在可测量的局部生化改变，以确定 神经解剖学分布和功能变化的幅度， 客观地评估所施用药物的代谢后果 诊断上（利他林--单极、抑郁和正常志愿者， 对照）和治疗（锂-双极）。 基础成功 F-18螺哌利多的研究将使这些患者的研究， 研究躁狂抑郁症的多巴胺假说。

We propose to develop and apply emission tomography (PET) as an analytical biochemical assay technique to study normal human cerebral function and affective disorders. The objectives are: 1.) Chemistry/Biochemistry. Rapid synthetic techniques will be developed and/or improved for preparation of (F-18)-fluoro and (C-11) deoxyglucose for measurement of glucose metabolism, C-11 and N-13 labeled amino acids for measurement of protein synthesis rates and F-18 ligands for receptor assays (principally spiroperidol but also development of high specific activity F-18 labeling techniques to be applied to other ligands). Tissue biochemical assay and autoradiographic studies in rats and monkeys will be used to structure and define kinetic models and select among different tracers for protein synthesis and receptor assay measurements. 2.) Tomography. The NeuroECAT will be upgraded to provide unprecedented level of spatial resolution, image quality and quantification necessary to measure the detailed neuroanatomical components of cerebral function required by this proposal. 3.) Tracer kinetic modeling. Operational equations for measuring cerebral blood flow, protein synthesis, oxygen metabolism and receptor assays will be developed and validated. 4.) Normal Subjects. Studies will be performed to validate methods, and to determine norms and variations in local glucose and oxygen metabolism, blood flow and protein synthesis rates. Studies will be carried out to determine metabolic and blood flow responses to specific sensory stimulations to activate visual, auditory, linguistic and cognitive functions and the use of these stimulation-response tasks as provocative tests for affective disorder patients. 5.) Patients. Local glucose metabolism will be measured in patients with bipolar and unipolar affective disorders to determine if there are measurable local biochemical alterations, to establish the neuroanatomical distribution and magnitude of the functional changes and to objectively evaluate the metabolic consequences of drugs administered diagnostically (Ritalin - unipolar, depressed and also normal volunteers as controls) and therapeutically (Lithium - bipolar). Success in basic studies of F-18 spiroperidol will allow studies in these patients to examine the dopamine hypothesis of manic/depressive disorders.