Simultaneous PET/fMRI mapping of local dopaminergic neurotransmission

描述（申请人提供）：在过去的15年里，使用功能磁共振成像研究认知理论已经成为可能，使用通常称为“激活研究”的方法。“然而，传统的功能磁共振成像研究没有提供关于信号转导或潜在神经化学的直接信息。 如果激活研究能够定位和识别特定的神经元群体（多巴胺能、阿片类、多巴胺能等），这将是神经影像学领域的一个重大进展。参与认知任务或行为。 在这方面，众所周知，认知激活增加神经元放电率，增加突触中的内源性神经递质水平。 原则上，由激活任务引起的神经递质水平的瞬时增加可用于改变用PET测量的放射性配体的结合动力学。 使用这种模式的研究已经在一些中心进行，有希望，但不是确定的结果。 同时扫描使用一个新的组合MR/PET扫描仪提供了一个更合理和严格的方法映射的神经传递的可能性。 本申请的目标是开发这种方法，利用PET/MR扫描仪的新功能和先进的处理方法来交叉验证PET/fMRI方法。 该方法的交叉验证将使用灵长类动物模型进行，使用涉及药物激发和充分理解的激活任务（涉及运动处理和运动规划）的逐步策略。 这将是重要的，使显着的改进方法，并开发最适合于同时MR/PET的实验设计。 “这个项目的目标是开发，演示和验证使用PET/fMRI扫描的方法，该方法能够映射神经传递对药物，行为和认知刺激的反应。 公共卫生相关性：目前的脑成像方法对血流和代谢的变化很敏感，但它们不能提供有关潜在神经化学的直接信息。 该项目的目标是利用同步MR/PET扫描绘制清醒灵长类动物大脑的空间分布图。

DESCRIPTION (provided by applicant): Over the last fifteen years, it has become possible to study theories of cognition with fMRI, using what are usually termed "activation studies." However, conventional fMRI studies give no direct information about signal transduction or the underlying neurochemistry. It would be a significant advance in the field of neuroimaging if activation studies could localize and identify specific neuronal populations (dopaminergic, opioid, serotonergic, etc.) involved in a cognitive task or behavior. In that regard, it is well known that cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level in the synapse. In principal, the transient increase in neurotransmitter level elicited by an activation task can be used to alter the binding kinetics of radioligands measured with PET. Studies using this paradigm have been performed in a few centers, with promising but not definitive results. Simultaneous scanning using a new combination MR/PET scanner offers the possibility of a more rational and rigorous approach to the mapping of neurotransmission. The goal of this application is to develop this methodology, making use of the new capability of PET/MR scanners and advanced processing methods to cross validate the PET/fMRI approach. The cross validation of the methodology will be performed with a primate model, using a stepwise strategy involving pharmaceutical challenge and well understood activation tasks that engage motor processing and motor planning. It will be important to make significant improvements in the methodology and to develop experimental designs most suitable for simultaneous MR/PET. "The goal of this project is to develop, demonstrate and validate methodology using PET/fMRI scanning which is capable of mapping neurotransmission in response to pharmaceutical, behavioral and cognitive stimuli. PUBLIC HEALTH RELEVANCE: Current brain imaging methods are sensitive to changes in blood flow and metabolism but they do not give direct information about the underlying neurochemistry. The goal of this project is to map the spatial distribution in the awake primate brain, using simultaneous MR/PET scanning.