Simultaneous PET/fMRI mapping of local dopaminergic neurotransmission

局部多巴胺能神经传递的同步 PET/fMRI 测绘

• 批准号: 8019785
• 负责人: NATHANIEL M ALPERT
• 金额: $ 25.57万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8019785
• 关键词: Affect; Anterior; Basal Ganglia; Behavior; Behavioral; Bilateral; Binding; Binding Sites; Blood flow; Brain; Brain imaging; Cocaine; Cognition; Cognitive; Data; Detection; Dissection; Dopamine; Dopamine Agonists; Dose; Experimental Designs; Functional Magnetic Resonance Imaging; Generations; Goals; Hand; Kinetics; Ligands; Magnetic Resonance Imaging; Maps; Measurement; Measures; Metabolism; Methodology; Methods; Modeling; Motor; Neurons; Neurotransmitters; Opioid; Pharmacologic Substance; Physiological; Population; Positron-Emission Tomography; Primates; Process; Publishing; Research; Resolution; Rewards; Scanning; Signal Transduction; Spatial Distribution; Stimulus; Surrogate Markers; Synapses; System; Testing; Time; Validation; Work; awake; base; extracellular; flexibility; human subject; imaging modality; neurochemistry; neuroimaging; neurotransmission; neurotransmitter release; new technology; public health relevance; putamen; radioligand; receptor density; research study; response; serotonin transporter; theories; tool; validation studies

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.

描述（由申请人提供）：在过去的15年中，使用通常称为“激活研究”的fMRI认知理论已成为可能。但是，常规的功能磁共振成像研究没有提供有关信号转导或潜在神经化学的直接信息。 如果激活研究可以定位并鉴定参与认知任务或行为涉及的特定神经元群体（多巴胺能，阿片类药物，血清素能等），那将是神经影像学领域的重大进步。 在这方面，众所周知，认知激活会增加神经元的发射率，从而增加了突触中的内源性神经递质水平。 本质上，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测量的放射性物体的结合动力学。 使用此范式的研究已在几个中心进行，并取得了有希望的结果。 同时使用新组合MR/PET扫描仪同时进行扫描提供了更合理和严格的神经传递映射方法的可能性。 该应用程序的目的是开发这种方法，利用PET/MR扫描仪的新能力和高级处理方法跨越PET/FMRI方法。 该方法的交叉验证将使用灵长类动物模型进行，使用涉及药物挑战的逐步策略以及涉及运动处理和运动计划的激活任务的逐步策略。 重要的是要对方法进行重大改进并开发最适合同时MR/PET的实验设计。 “该项目的目的是使用PET/fMRI扫描来开发，证明和验证方法，该方法能够响应药物，行为和认知刺激来绘制神经传递。 公共卫生相关性：当前的大脑成像方法对血流和代谢的变化很敏感，但它们没有提供有关潜在神经化学的直接信息。 该项目的目的是使用同时进行MR/PET扫描来绘制清醒大脑中的空间分布。