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NIMH Instrumentation Core Facility

NIMH 仪器核心设施

基本信息

批准号：
10922461
负责人：
George Dold
金额：
$ 226.74万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10922461
关键词：
3D Print Address Affect Anatomy Area Attention Award BRAIN initiative Behavioral Biochemical Brain Brain imaging Brain region Calibration Cell surface Cinnamon - dietary Clinical Collaborations Computer software Consult Core Facility Custom Dedications Development Devices Drosophila genus Electrodes Electroencephalography Electronic Mail Electronics Electrophysiology (science)Elements Engineering Environment Equipment Event Face Fiber Optics Fluorescence Microscopy Functional Magnetic Resonance Imaging Functional disorder Goals Grant Head Hour Human Image Individual Individual Differences Industrialization Insecta Investigational Therapies Kinetics Knowledge Learning Light Location Magnetic Resonance Imaging Magnetism Magnetoencephalography Measurement Measures Mechanics Memory Metals Microscope Mission Modification Monitor Mus National Center for Complementary and Integrative Health National Institute of Child Health and Human Development National Institute of Mental Health National Institute of Neurological Disorders and Stroke Noise Occupations Optics Outcome Patients Perfusion Positioning Attribute Prefrontal Cortex Primates Procedures Pump Radiochemistry Rattus Recommendation Research Research Personnel Research Project Grants Research Support Resolution Rewards Rodent Safety Scientist Seizures Services Shapes Side Signal Transduction Source Surface System Techniques Telephone Testing Time Titanium Titrations Variant Visualization Walking behavior test data acquisition density design design and construction electric field experience fabrication improved instrument instrumentation locust magnetic dipole manufacture multi-electrode arrays new technology nonhuman primate novel optical fiber programs prototype response restraint sensor software development trafficking two photon microscopy voltage

项目摘要

This past year, our Section had the unique opportunity to support the research of various Labs & Sections within NIMH, NINDS, NICHD, and NCCIH. During the past twelve months, investigators from these labs and branches requested 332 formal projects from our staff. Each of these requests was documented and the time recorded to complete the job. In addition to the formal requests, we are available daily for numerous walk-in, phone call or e-mail requests for assistance. In general, our technical support this past year can be divided into the following research areas: Electrophysiology: The Section on Instrumentation staff continuously strives to improve the utility of various components that comprise electrophysiology. We have continued to improve the engineering and fabrication of multiple-hole grid arrays that allow precise, repeatable placement of a single or multiple electrodes over a wide area. fMRI/MRI: The Section on Instrumentation provides a wide range of support for fMRI-related research. Fabrication of devices for use in MRI environments is a specialized area of expertise, with great attention given to design without ferrous metals and minimization of all metal components. In addition, commercial industrial fiber optic components and systems are evaluated and integrated into many designs and devices we fabricate. SI continues to provide considerable effort in the design and fabrication of primate chair systems to incorporate new features as requested by researchers. Non-Human Primate (NHP): Our group is responsible for providing a wide range of engineering and fabrication services to support non-human primate research. Many of the mechanical assemblies that are necessary for this type of research are engineered and fabricated in-house. Our group provides a diverse array of custom systems and components to many different investigators, such as custom primate chairs, high-strength restraints, MRI positioning systems, custom head coils, reward systems, data acquisition, analysis and optical response systems, plus a wide range of small mechanical components. Human and Clinical: Optically pumped magnetometer sensor array system. During the last four years, the SI assisted the NIMH Magnetoencephalography (MEG) Core facility with a project central to their research program. In 2019, Dr. Allison Nugent was awarded a Brain Initiative grant to develop an array of optically pumped magnetometer sensors designed to image the brain with unprecedented spatial resolution. The project required the design and fabrication of a fixture to hold the sensors, as well as a calibration jig and electronics. This involved close collaboration between the SI and the MEG Core Facility. The design of the sensor array fixture required several considerations. First, it had to be extremely accurate so that the location of the sensors was known precisely. Second, the goal was to place the rectangular sensors as close together as possible. Third, the sensors needed to be on a curve so that the sensors would be as close as possible to the head, while allowing for different head shapes. Finally, the sensors produced heat, so that thermal dissipation was a consideration. The final array we developed in collaboration with the MEG Core Facility addressed all of these needs. The other major element of this project was the design of a calibration jig and associated electronics. Because the sensors were assembled into the array, deviations of the sensors from their exact locations in the array were possible. In addition, there could be manufacturing inconsistencies that resulted in small differences in the orientation or gains of each sensor. In order to calibrate the precise locations and orientations of each sensor, as well as their gains, known magnetic sensor sources were required. In collaboration with the MEG core facility, we designed two iterations of this project. The final iteration consisted of a five-sided prism, with each face having four magnetic dipole coils. The calibration electronics were designed to take a signal from a function generator to produce a current in each coil individually. In addition, to obtain the most precise measurements, the current in each coil needed to be measured and returned, so that the fields produced by each coil are known precisely. SI continues the development of a novel ECT system (MIST). In collaboration with the Experimental Therapeutics & Pathophysiology Branch, the Section on Instrumentation is developing a multi-channel ECT system (iLAST). While modifications of ECT have improved its safety and tolerability, none of the currently used procedures individualize the current amplitude for each patient despite knowledge that anatomical variation significantly impacts the strength of the current delivered to the brain. iLAST introduces three areas of improvement over conventional ECT. 1) Conventional ECT uses two large disc electrodes that are spaced widely apart, which leads to a non-focal electric field distribution in the brain. In iLAST, we use a multi-electrode array to selectively target regions of the brain similar to one employed in high-definition tDCS studies. 2) Conventional ECT uses a high and fixed current amplitude (800 mA). The fixed current amplitude is much higher than necessary to elicit an adequate seizure, and also results in individual differences in the amount of current entering the brain, possibly leading to variability in clinical outcome. In iLAST, we titrate the amplitude of the current for each patient. 3) Conventional ECT monitors seizure induction with two-channel EEG recording in the prefrontal cortex, which does not characterize seizure topography. In iLAST, we will use high-density EEG electrodes that are weaved into the multi-stimulation electrode array so that topographical ictal EEG is recorded. The ECT system is a multi-year collaboration, incorporating the development of a considerable amount of custom electronics and custom software development. SI has completed the design of the individual channel boards and the main motherboard. Considerable effort remains on software development and testing the system with high voltages and currents. This past FY, SI used some of the software concepts and hardware from the Cinnamon ECT system to quickly design and fabricate a single channel version with an enhanced user interface for testing ECT on NHPs. This system is currently being used successfully for ECS titration studies. Behavioral: Several different types of mazes are used to study spatial learning and memory in rats. These studies have been used to help understand general principles about learning that can be applied to humans, and to determine how different treatments affect learning and memory in mice. We continue to produce a variety of custom T and Y mazes for behavioral testing. Imaging: The Section on Instrumentation continues to produce a variety of equipment that supports two-photon microscopy, such as novel titanium headposts and stereotaxic frames, faraday cages for electronic and light shielding and custom mirror mounts. In addition, behavioral testing equipment such as low-inertia mouse wheels are fabricated for use with two-photon microscopy. SI is redesigning and fabricated several behavioral testing systems that will be used to provide a platform for studies using a technique known as total internal reflection fluorescence microscopy. Key events in cellular trafficking occur at the cell surface, and it is desirable to visualize these events without interference from other regions deeper within. The technique has many other applications as well, most notably for studying biochemical kinetics and single biomolecule dynamics at surfaces.

去年，我们的部门获得了独特的机会来支持 NIMH、NINDS、NICHD 和 NCCIH 内各个实验室和部门的研究。在过去 12 个月中，这些实验室和分支机构的研究人员向我们的员工索取了 332 个正式项目。每个请求都被记录下来，并记录完成工作的时间。除了正式请求外，我们每天还可以接受大量上门、电话或电子邮件请求以寻求帮助。总的来说，我们这一年的技术支持可以分为以下几个研究领域：电生理学：仪器部门的工作人员不断努力提高构成电生理学的各种组件的实用性。我们不断改进多孔网格阵列的工程和制造，允许在大面积上精确、可重复地放置单个或多个电极。功能磁共振成像/磁共振成像：仪器部分为功能磁共振成像相关研究提供广泛的支持。 MRI 环境中使用的设备的制造是一个专门的专业领域，非常注重不含黑色金属的设计和最小化所有金属组件。此外，商业工业光纤组件和系统经过评估并集成到我们制造的许多设计和设备中。 SI 继续在灵长类动物座椅系统的设计和制造方面投入大量精力，以纳入研究人员要求的新功能。非人类灵长类动物 (NHP)：我们的团队负责提供广泛的工程和制造服务以支持非人类灵长类动物研究。此类研究所需的许多机械组件都是内部设计和制造的。我们的团队为许多不同的研究人员提供各种定制系统和组件，例如定制灵长类动物椅子、高强度约束装置、MRI 定位系统、定制头部线圈、奖励系统、数据采集、分析和光学响应系统，以及各种小型机械组件。人类和临床：光泵磁力计传感器阵列系统。在过去四年中，SI 协助 NIMH 脑磁图 (MEG) 核心设施开展了一个对其研究计划至关重要的项目。 2019 年，Allison Nugent 博士获得了大脑计划资助，用于开发一系列光泵磁力计传感器，旨在以前所未有的空间分辨率对大脑进行成像。该项目需要设计和制造固定传感器的夹具以及校准夹具和电子设备。这涉及 SI 和 MEG 核心设施之间的密切合作。传感器阵列夹具的设计需要考虑几个因素。首先，它必须非常精确，以便准确地知道传感器的位置。其次，目标是将矩形传感器尽可能靠近放置。第三，传感器需要位于曲线上，以便传感器尽可能靠近头部，同时允许不同的头部形状。最后，传感器会产生热量，因此散热是一个考虑因素。我们与 MEG 核心设施合作开发的最终阵列满足了所有这些需求。该项目的另一个主要元素是校准夹具和相关电子设备的设计。由于传感器被组装到阵列中，因此传感器可能偏离其在阵列中的确切位置。此外，可能存在制造不一致，导致每个传感器的方向或增益存在微小差异。为了校准每个传感器的精确位置和方向及其增益，需要已知的磁传感器源。我们与 MEG 核心设施合作，设计了该项目的两个迭代。最终的迭代由一个五面棱镜组成，每个面都有四个磁偶极子线圈。校准电子设备被设计为从函数发生器获取信号，以在每个线圈中单独产生电流。此外，为了获得最精确的测量，需要测量并返回每个线圈中的电流，以便准确地了解每个线圈产生的磁场。 SI 继续开发新型 ECT 系统 (MIST)。仪器科与实验治疗与病理生理学分部合作，正在开发多通道 ECT 系统 (iLAST)。虽然 ECT 的修改提高了其安全性和耐受性，但目前使用的程序都没有为每个患者提供个性化的电流幅度，尽管我们知道解剖结构的变化会显着影响传递到大脑的电流强度。 iLAST 与传统 ECT 相比在三个方面进行了改进。 1) 传统ECT使用两个间隔较远的大圆盘电极，这导致大脑中出现非焦点电场分布。在 iLAST 中，我们使用多电极阵列选择性地瞄准大脑区域，类似于高清 tDCS 研究中使用的区域。 2) 传统ECT使用高且固定的电流幅度（800 mA）。固定电流幅度远高于引发充分癫痫发作所需的幅度，并且还会导致进入大脑的电流量存在个体差异，可能导致临床结果的差异。在 iLAST 中，我们滴定每位患者的电流幅度。 3) 传统的 ECT 通过前额叶皮层的双通道脑电图记录来监测癫痫发作诱发，这并不表征癫痫发作的地形。在 iLAST 中，我们将使用编织成多刺激电极阵列的高密度脑电图电极，以便记录地形发作期脑电图。 ECT 系统是一项多年合作成果，融合了大量定制电子产品的开发和定制软件的开发。 SI已经完成了各个通道板和主主板的设计。软件开发和高电压高电流系统测试仍需付出大量努力。上个财年，SI 使用 Cinnamon ECT 系统中的一些软件概念和硬件来快速设计和制造具有增强用户界面的单通道版本，用于在 NHP 上测试 ECT。该系统目前已成功用于 ECS 滴定研究。行为：几种不同类型的迷宫用于研究大鼠的空间学习和记忆。这些研究被用来帮助理解可应用于人类的学习的一般原理，并确定不同的治疗如何影响小鼠的学习和记忆。我们继续生产各种用于行为测试的定制 T 和 Y 迷宫。成像：仪器部门继续生产各种支持双光子显微镜的设备，例如新型钛头柱和立体定位框架、用于电子和光屏蔽的法拉第笼以及定制镜子安装座。此外，还制造了低惯性鼠标轮等行为测试设备，用于双光子显微镜。 SI 正在重新设计和制造多个行为测试系统，这些系统将用于为使用全内反射荧光显微镜技术的研究提供一个平台。细胞运输中的关键事件发生在细胞表面，并且希望在不受内部其他区域干扰的情况下可视化这些事件。该技术还有许多其他应用，最显着的是用于研究表面的生化动力学和单个生物分子动力学。