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

传统的fMRI实验基于BOLD效应，这是一种局部神经元活动引起的血液氧合变化，它允许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，其时间分辨率在秒的范围内，空间分辨率在几微升的范围内。拟议的研究项目旨在克服这些空间和时间分辨率的限制，目标是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个纳米升的小体积内检测与神经元活动相关的质子磁化变化，同时显著提高时间分辨率和灵敏度，并同时记录电活动。此外，我们将使用固有体积选择的质子光谱来评估谷氨酸、谷氨酰胺和GABA等神经递质的局部变化，以及通过31P光谱来评估能量代谢。为了实现这些目标，将开发一个由微型磁共振线圈、用于神经元记录的微电极和安装在普通针状衬底上的定制设计的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，这些信号可以使用商用ADC进行数字化。除了仅执行上述信号调节任务的ASIC外，还将设计TX/RX ASIC，它可以额外提供激励自旋系综所需的射频电流。这种局部激发将缓解与射频电流诱导的组织加热相关的所有问题。总体而言，设想的系统将能够捕获单层内的局部活动，并且最好是在不同细胞成分(树突、小体等)的区域内。与电记录相结合，可以在高时间和空间分辨率下直接研究神经血管耦合，以估计血流动力学反应函数的局部依赖性。此外，设想的小型化多模式记录系统将能够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，远远低于通常假设的几秒的时间延迟(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).