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，即局部神经元活动引起的血氧变化，通过相应的局部敏感性变化来检测神经元的刺激。这种局部敏感性的变化通常用T2*敏感的EPI序列来测量，其时间分辨率在秒范围内，空间分辨率为几微升。拟议的研究项目旨在克服这些空间和时间分辨率的限制，以评估基本神经血管耦合级联的更精细细节。该项目的主要目标是在几纳升的小体积内以显着提高的时间分辨率和灵敏度检测质子磁化的神经元活动相关变化，并同时记录电活动。此外，我们将使用质子光谱和本质体积选择来评估谷氨酸、谷氨酰胺和GABA等神经递质的局部变化，并通过31P光谱来评估能量代谢。为了实现这些目标，将开发一种微系统，该系统由小型化的MR线圈、用于神经元记录的微电极和安装在普通针状基板上的定制设计的ASIC组成。ASIC将执行MR和电信号的所有信号调理任务，以便在其输出端提供可使用市售adc数字化的鲁棒信号。除了仅执行上述信号调理任务的asic外，还将设计能够额外提供激发自旋集合所需的RF电流的TX/RX asic。这种局部激励将减轻与射频电流引起的组织加热相关的所有问题。总的来说，设想的系统将能够捕获单层内的局部活动，最好是在不同细胞成分（树突、体等）的区域内。结合电记录，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，以估计血流动力学反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，从而解决电信号和质子磁化变化之间的相关性，远远低于通常假设的几秒钟的时间滞后（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).