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

描述（由申请人提供）：同步PET MR是一种新的成像方式，与以前的神经递质释放映射技术相比，它具有明显的优势。理论分析以及对非人类灵长类动物的初步研究支持这样的假设，即检测和定量测量的灵敏度将得到显著提高，从而使我们能够扩展可以提出和回答的研究问题的范围。在这个应用程序中，我们提出进一步发展的方法，实验验证，并证明主要研究抑郁症患者。在我们目前资助的R21申请中，我们提出了由特定药理挑战引起的MR测量血容量的变化是时变神经递质水平的功能。安非他明和多巴胺受体阻断的初步研究支持并扩展了这一观点。多巴胺系统只是我们假设的一个更普遍的方法的一个例子，在这个应用中包括血清素能系统。我们假设同时进行PET和fMRI将产生协同数据，结合我们的动力学分析方法，可以显著提高我们检测和量化大脑中血清素和多巴胺神经传递的时空模式的能力。我们的跨学科团队提出了一项涵盖技术开发和精神病学研究的应用，我们建议完善我们的动力学建模方法，开发定量整合fMRI和PET数据的方法，并评估这些方法在研究临床抑郁症中多巴胺和血清素传递的转化价值。

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.