CORE--BRAIN IMAGING RESEARCH CORE

脑成像研究中心（BIRC）是该中心的一个新核心，它汇集了一批在脑成像各个方面具有专业知识的高技能研究人员，如研究设计，图像分析，放射化学和动力学建模。BIRC的一般任务将包括：1）为“特定项目”研究提供专家后勤支持，2）培训年轻研究者，3）提供“中心范围”测量（MRI体积分析和电生理研究），以及4）开发与精神分裂症相关的新成像模式。“项目特定”研究通常在预定义的患者集上进行，主要由RO 1资助，而“中心范围”测量则在中心收治的所有患者上进行，并可供MHCRC的所有研究者使用。在接下来的五年里，这个核心的开发工作将针对多巴胺（DA）系统与PET，和γ-氨基丁酸（GABA）系统与MRS。这些目标的选择是指导精神分裂症中特定的皮质-皮质下神经元网络的神经化学失衡和失调的一般模型。基于初步结果和动物模型数据的总体假设提出，精神分裂症与正常大脑发育失败相关，与海马结构连接中断相关，以及前额叶皮质（PFC）中DA和/或GABA功能降低，导致皮质下DA系统失调。我们将开发和验证DA活动的措施，在PFC精神分裂症，使用D1受体放射性示踪剂，[11 C]NNC 112，和DA耗竭范例，并在内侧颞叶结构使用高亲和力D2受体放射性示踪剂，[18 F]fallypride，结合DA挑战测试。我们将开发一种D2受体激动剂，[11 C]普拉克索，以研究精神分裂症中D2受体对激动剂亲和力的潜在变化;以及D4受体的放射性示踪剂，[18 F]氟丙基-L745，870。对于GABA能系统，我们的目标是开发和验证MRS方法来测量精神分裂症PFC中的GABA浓度。结合在一起，这些发展将提供工具来测试精神分裂症中皮质-皮质下网络的不同组成部分，并将它们整合到疾病的启发式模型中。

The Brain Imaging Research Core, BIRC, a new core in this Center, has assembled a group of highly skilled investigators with expertise in various aspects of brain imaging such as study design, image analysis, radiochemistry and kinetic modeling. The general missions of the BIRC will include: 1) providing expert logistical support to "project specific" studies, 2) training young investigators, 3) providing "center wide" measurements (MRI volumetric analyses and electrophysiological studies), and 4) development new imaging modalities pertinent to schizophrenia.. "Project specific" studies are generally performed on a predefined set of patients, and are mainly funded by RO1s while "center- wide" measurements are performed on all patients admitted to the Center and are available to all investigators of the MHCRC. Over the next five years, the development effort of this core will target the dopamine (DA) system with PET, and the gamma-amino-butyric (GABA) system with MRS. The choice of these objectives is guided by a general model of neurochemical imbalances and dysregulations in specific cortico-subcortical neuronal networks in schizophrenia. The overall hypothesis, based on preliminary results and data from animal models, proposes that schizophrenia is related to a failure of normal brain development associated with disruption of hippocampal formation connectivity, and reduction of DA and/or GABA function in the prefrontal cortex (PFC), leading to a dysregulation of subcortical DA systems. We will develop and validate measures of DA activity in the PFC in schizophrenia, using a D1 receptor radiotracer, [11C]NNC 112, and a DA depletion paradigm, and in the mesial temporal structures using a high affinity D2 receptor radiotracer, [18F]fallypride, combined with DA challenge tests. We will develop a D2 receptor agonist, [11C] pramipexole, to study potential alterations in the affinity of D2 receptors for agonists in schizophrenia; and a radiotracer for the D4 receptor, [18F]fluoropropyl-L745,870. For the GABAergic system, our goal is to develop and validate an MRS method to measure GABA concentration in the PFC in schizophrenia. Combined together, these developments will provide the tools to test different components of the cortico-subcortical network in schizophrenia, and to integrate them into a heuristic model of the illness.