Combined PET and fMRI imaging of dopamine and serotonin responses in depression

描述（由申请人提供）：同步PET MR是一种新的成像模式，与以前的神经递质释放标测技术相比具有明显优势。理论分析，以及在非人类灵长类动物的初步研究，支持的假设，检测和定量测量的灵敏度将是可以显着提高，使我们能够扩大范围的研究问题，可以问和回答。在此应用中，我们提出了进一步发展的方法，实验验证，并证明了抑郁症患者的主要研究。在我们目前资助的R21申请中，我们提出，由特定药理学挑战引起的MR测量血容量的变化是随时间变化的神经递质水平的函数。安非他明和多巴胺受体阻滞剂的初步研究支持并扩展了这一想法。多巴胺系统只是我们假设的更一般的方法的一个例子，在本申请中包括多巴胺能系统。我们假设，同时PET和功能磁共振成像将产生协同数据，结合我们的动力学分析方法，可以显着提高我们的能力，以检测和量化的时空模式的多巴胺能和多巴胺能神经传递在大脑中。我们的跨学科团队提出了一个应用程序，包括技术开发和精神病学调查，我们建议改进我们的动力学建模方法，开发方法，定量整合功能磁共振成像和PET数据，并评估这些方法的转化价值，以研究临床抑郁症中的多巴胺和5-羟色胺传输。

DESCRIPTION (provided by applicant): Simultaneous PET MR is a new imaging modality that offers clear advantages over previous technologies for the mapping of neurotransmitter release. Theoretical analyses, as well as preliminary studies in nonhuman primates, support the hypothesis that sensitivity for detection and quantitative measurement will be can be significantly improved allowing us to extend the range of research questions which can be asked and answered. In this application we propose further development of the methodology, experimental validation, and proof-of-principal studies in depressed patients. In our currently funded R21 application, we proposed that changes in MR measurements blood volume elicited by specific pharmacological challenges were functions of time-varying neurotransmitter levels. Preliminary work with amphetamine and dopamine receptor blockade supports and extends that idea. The dopamine system is but one example of what we postulate is a more general approach, which in this application includes the serotonergic system. We hypothesize that concurrent PET and fMRI will yield synergistic data that, combined with our kinetic analysis methods, can dramatically improve our ability to detect and quantify the spatiotemporal patterns of serotonergic and dopaminergic neurotransmission in the brain. Our interdisciplinary team puts forth an application encompassing technical development and psychiatric investigation in which we propose to refine our kinetic modeling methods, develop methods to quantitatively integrate fMRI and PET data, and assess the translational value of these methods to study dopamine and serotonin transmission in clinical depression.