Simultaneous PET/fMRI mapping of local dopaminergic neurotransmission

描述(由申请人提供)：在过去的15年里，使用通常被称为“激活研究”的功能磁共振成像研究认知理论已经成为可能。然而，常规的fMRI研究没有提供关于信号转导或潜在的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、阿片能、5-羟色胺能等)，这将是神经成像领域的重大进步。参与认知任务或行为的。在这一点上，众所周知，认知激活增加了神经元的放电速率，增加了突触中的内源性神经递质水平。原则上，激活任务引起的神经递质水平的瞬时增加可以用来改变用正电子发射计算机断层扫描测量的放射性配体的结合动力学。使用这种范式的研究已经在几个中心进行，结果很有希望，但并不是决定性的结果。使用一种新的组合MR/PET扫描仪的同时扫描提供了一种更合理和更严格的方法来绘制神经传递图。该应用程序的目标是开发这一方法，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在灵长类动物模型中进行，使用包括药物挑战和参与运动处理和运动规划的众所周知的激活任务的逐步策略。重要的是在方法上做出重大改进，并开发最适合同时进行磁共振/正电子发射计算机断层扫描的实验设计。这个项目的目标是开发、演示和验证使用PET/fMRI扫描的方法，这种方法能够绘制出对药物、行为和认知刺激做出反应的神经传递图。 公共卫生相关性：目前的脑成像方法对血流和新陈代谢的变化很敏感，但它们不能提供有关潜在神经化学的直接信息。这个项目的目标是利用同步的MR/PET扫描绘制清醒的灵长类动物大脑的空间分布。

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.