TRD1 - Multimodal Imaging for Spanning Multiple Spatial Scales in the Brain

项目总结/摘要 大脑功能是由跨多个空间组织的分层局部和长程回路介导的。 鳞片连接和跨越这些组织尺度对于理解大脑功能和 然而，没有一种现有技术可以完成这项艰巨的任务。人脑 活动和连通性可以用非侵入性磁共振（MR）方法进行研究， 整个大脑。然而，时空分辨率和保真度的神经元活动是有限的，因为 作为MR标测信号源的介入神经血管耦合。这些限制可能是 如果可以提高MR分辨率和保真度，以减少响应的异质性， 并且，此外，MR方法与同时 报告神经元和/或神经血管反应，理想情况下对一个或多个MR体素内的活动进行采样 在单个神经元、突触或血管水平上。除了询问神经元活动和大脑活动之间的联系之外， 基于MR的功能映射信号，这种技术组合的互补性质将 提供了从细胞和突触到多个空间和时间尺度的桥接手段， 水平协调活动超过数十亿神经元跨越大部分的大脑，如果不是整个大脑。 该TRD通过提议开发i）用于成像大脑的先进MR方法来解决这个问题 使用非常高的磁场，以前所未有的空间分辨率实现功能和连通性，ii）结合 这种MR测量与神经信号的多光子记录的同时测量（在 单个细胞和/或突触水平）和个体水平的相应血液动力学反应 微动脉、毛细血管和微静脉，在相同的微动脉、毛细血管和微静脉上的超高频场（UHF）磁体的环境内， 动物，在相同的实验条件下。由于光学方法的侵入性， 联合实验只能在动物模型中进行，而MR技术有待开发 也可以应用于人体成像。

Project Summary/Abstract Brain function is mediated by hierarchical local and long-range circuits organized across multiple spatial scales. Bridging and spanning these scales of organization is essential for understanding brain function and ultimately dysfunction; however, no single existing technology can accomplish this daunting task. Human brain activity and connectivity can be studied with non-invasive magnetic resonance (MR) methods that can cover the entire brain. However, the spatiotemporal resolution and fidelity to neuronal activity is limited because of the intervening neurovascular coupling that is the source of the MR mapping signals. These limitations can be overcome if MR resolutions and fidelity can be improved so as to reduce the heterogeneity of the responses within an MR voxel and, in addition, the MR method is combined with other techniques that simultaneously report on neuronal and/or neurovascular responses, ideally sampling the activity within one or more MR voxels at the single neuron, synapse or vessel level. Besides interrogating the link between neuronal activity and the MR based functional mapping signals, the complementary nature of such a combination of techniques would provide the means for bridging the multiple spatial and temporal scales, going from the cellular and synaptic level to coordinated activity over billions of neurons spanning large parts of the brain, if not the entire brain. This TRD approaches this problem by proposing to develop i) advanced MR methods for imaging brain function and connectivity at unprecedented spatial resolution using very high magnetic fields, ii) combining such MR measurements with simultaneous measurements of multi-photon recordings of neural signals (at single cell and/or synapse level) and corresponding hemodynamic responses at the level of individual arterioles, capillaries and venules, within the environment of an ultrahigh field (UHF) magnet on the same animal and under the same experimental conditions. Because of the invasive nature of the optical methods the combined experiments can only be performed in animal models while the MR techniques to be developed would be applicable to human imaging as well.