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图谱技术相比具有明显的优势。理论分析以及对非人类灵长类动物的初步研究支持这样一种假设，即检测和定量测量的灵敏度将显著提高，从而允许我们扩大可以提出和回答的研究问题的范围。在这一应用中，我们建议进一步发展方法学、实验验证和抑郁症患者的原则证明研究。在我们目前资助的R21应用中，我们提出由特定的药物挑战引起的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。苯丙胺和多巴胺受体阻断的初步工作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方法的一个例子，在本应用中包括5-羟色胺能系统。我们假设，并行的PET和功能磁共振成像将产生协同数据，与我们的动力学分析方法相结合，可以显著提高我们检测和量化大脑中5-羟色胺和多巴胺能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，其中我们建议改进我们的动力学建模方法，开发定量集成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5-羟色胺传递方面的翻译价值。

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.