Measurement of neuronal activity with combined multifunctional micro NMR probes and micro electrodes

传统的fMRI实验是基于BOLD效应，一种局部神经元活动诱导的血氧变化，其允许通过相应的局部易感性变化来检测神经元刺激。这种局部敏感性的变化通常用T2* 敏感的EPI序列测量，时间分辨率在秒的范围内，空间分辨率为几微升。拟议的研究项目旨在克服这些限制，在空间和时间分辨率的评估基本的神经血管耦合cascades.The主要目标的更精细的细节的目标是在一个显着提高的时间分辨率和灵敏度的质子磁化的神经元活动相关的变化检测伴随着电活动的同时记录在几纳升的小体积。此外，我们将评估局部变化的神经递质，如谷氨酸，谷氨酰胺和GABA使用质子光谱与内在体积选择，以及能量代谢通过31 P光谱。为了实现这些目标，将开发一种由小型化MR线圈、用于神经元记录的微电极和安装在常见针形基板上的定制设计的ASIC组成的微系统。ASIC将执行MR和电信号的所有信号调节任务，以便在其输出端提供稳健的信号，这些信号可以使用市售ADC进行数字化。除了仅执行上述信号调节任务的ASIC之外，还将设计能够额外提供激励自旋系综所需的RF电流的TX/RX ASIC。总的来说，所设想的系统将能够捕获单层内的局部活动，并且优选地捕获不同细胞成分（树突、体等）的区域内的局部活动。与电记录相结合，可以在高时间和空间分辨率下进行神经血管耦合的直接研究，以估计血流动力学响应函数的局部依赖性。此外，设想的小型化多模态记录系统将允许在非常精细的时间尺度上评估神经血管耦合，从而能够解决电信号与质子磁化变化之间的相关性，其远低于通常假设的几秒的时间滞后（快速耦合）。

Conventional fMRI experiments are based on the BOLD effect, a local neuronal activity induced change in blood oxygenation, which allows for the detection of neuronal stimulation through the corresponding local susceptibility changes. This change in local susceptibility is usually measured with T2* sensitive EPI sequences with a temporal resolution in the range of seconds and spatial resolutions of several microliters. The proposed research projects aims to overcome these limitations in spatial and temporal resolution with the goal of assessing finer details of the basic neurovascular coupling cascade.The main goal of this project is the detection of neuronal activity-related changes of proton magnetization at a significantly improved temporal resolution and sensitivity within small volumes of a few nanoliters accompanied by simultaneous recording of electrical activity. In addition, we will assess local changes of neurotransmitters such as Glutamate, Glutamine and GABA using proton spectroscopy with intrinsic volume selection, as well as energy metabolism via 31P spectroscopy. To achieve these goals, a microsystem consisting of a miniaturized MR coil, microelectrodes for neuronal recording and a custom designed ASIC mounted on a common needle-shaped substrate will be developed. The ASIC will perform all signal conditioning tasks for both the MR and the electrical signals in order to provide robust signals at its output which can be digitized using commercially available ADCs. In addition to the ASICs which will only perform the aforementioned signal conditioning tasks, TX/RX ASICs which can additionally provide the RF current necessary to excite the spin ensemble will also be designed. This local excitation will mitigate all problems associated with RF current induced tissue heating.Overall, the envisioned system will be able to capture localized activity within single layers and preferably within regions of different cellular components (dendrites, bodies, etc.). In combination with electrical recording, direct study of neurovascular coupling can be performed at high temporal and spatial resolution to estimate the local dependence of hemodynamic response functions. In addition, the envisioned miniaturized multimodal recording system will allow assessing neurovascular coupling on an exceptionally fine time scale enabling to resolve correlations between electrical signals and proton magnetization changes far below the commonly assumed time lag of several seconds (fast coupling).