Distributed electrode system for high-fidelity cardio-neural mapping

用于高保真心神经标测的分布式电极系统

• 批准号: 9507273
• 负责人: JEFFREY L ARDELL
• 金额: $ 10.77万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9507273
• 关键词: Acute; Address; Amplifiers; Animal Model; Area; Arrhythmia; Autonomic ganglion; Biological Neural Networks; Brain Stem; Cardiac; Cervical; Chest; Chronic; Collection; Custom; Data; Development; Disease Progression; Electrodes; Electrophysiology (science); Encapsulated; Event; Evolution; Exercise; Feedback; Film; Ganglia; Head; Heart; Heart Abnormalities; Heart Atrium; Heart Diseases; Heart failure; Implant; Knowledge; Mechanics; Methods; Microelectrodes; Myocardial Ischemia; Nervous system structure; Neurons; Nodose Ganglion; Parasympathetic Nervous System; Pathologic; Pathology; Peripheral; Peripheral Nervous System; Play; Resolution; Risk; Role; Sampling; Sensory; Sensory Ganglia; Site; Spinal Cord; Spinal Ganglia; Stream; Structure of superior cervical ganglion; Surface; Sympathetic Nervous System; System; Techniques; Technology; Thinness; Time; Tissues; Up-Regulation; Ventricular; Ventricular Arrhythmia; Ventricular Tachycardia; Work; base; density; design; flexibility; heart electrical activity; indexing; information processing; innovation; method development; miniaturize; neuroadaptation; neuronal cell body; physiologic stressor; public health relevance; relating to nervous system; sample fixation; sudden cardiac death

 DESCRIPTION (provided by applicant): The cardiac neuronal hierarchy is made up of interdependent feedback loops comprising somata located in i) intrinsic cardiac ganglia, ii) intrathoracic extracardiac (stellate, middle cervical) as well as iii) the spinal cord, iv) brainstm and v) higher centers (up to the insular cortex). Each of these processing center contains afferent, efferent and interactive (local circuit ones in peripheral ganglia) neurons which interac locally and in an interdependent fashion with other levels to coordinate regional cardiac indices on a beat-to-beat basis. It is now recognized that autonomic dysregulation is central to the evolution of heart failure and arrhythmias. With respect to heart disease and the cardiac nervous system, there is an upregulation of the sympathetic nervous system and a corresponding decrease in parasympathetic activity. Many of these changes are driven by alterations in afferent transduction and processing of that information at multiple levels of the cardiac nervous system. There is little understanding of how such neural systems adapt during disease progression. There are two critical unmet needs in the field of cardio-neural mapping: 1) Development and optimization of 2D and 3D electrode arrays for chronic, high-fidelity neural recording from peripheral ganglia and 2) Integration of neural recordings with chronic high-fidelity recording of cardiac electrophysiological function. To address this need three aims are proposed. Specific aim 1: To develop 2D and 3D microelectrode arrays and systems for chronic, high-fidelity neural recording from intrinsic cardiac ganglia. Proposed methods include development of thin-film based flexible microelectrode arrays with up to 256 electrode contacts. Once proof of concept is established in the acute setting, chronic packages and fixation techniques will be developed to enable chronic recordings from large animal models. Specific aim 2: To develop 3D electrode arrays and systems for chronic, high-fidelity neural recording in peripheral encapsulated sympathetic (stellate) and sensory (nodose) ganglia. Proposed methods include development of thin-film based 3D penetrating microelectrode arrays (up to 256 electrode contacts). Once proof of concept is established in the acute setting, chronic packages and fixation techniques will be developed to enable chronic recordings from encapsulated peripheral ganglia from large animal models. Specific aim 3: To develop conformal high-definition grid electrodes for chronic, high-resolution electrophysiological mapping from atrial and ventricular epicardial surfaces. These `HD grid electrodes' will have up to 512 sites. Similar to and in conjunction with Aims 1 and 2, chronic packages and fixation techniques will be developed to enable chronic high-fidelity cardiac-neural mapping for up to 28 days. New Knowledge and Innovation: Creation of a distributed electrode system for chronic and continuous high fidelity cardio-neural mapping in normal and pathological states.

 描述（由申请人提供）：心脏神经元层次结构由相互依赖的反馈环路组成，包括位于 i) 内在心脏神经节、ii) 胸腔内心外神经节（星状、中颈）以及 iii) 脊髓、iv) 脑干和 v) 高级中心（直至岛叶皮质）的体细胞。 每个处理中心都包含传入神经元、传出神经元和交互神经元（外周神经节中的局部回路神经元），这些神经元以相互依赖的方式与其他级别局部交互，以在逐次心跳的基础上协调区域心脏指数。 现在人们认识到自主神经失调是心力衰竭和心律失常演变的核心。 对于心脏病和心脏神经系统，交感神经系统上调，副交感神经活动相应减少。 其中许多变化是由心脏神经系统多个层面的传入转导和信息处理的改变驱动的。 人们对这种神经系统在疾病进展过程中如何适应知之甚少。 心脏神经标测领域有两个关键的未满足需求：1）开发和优化用于外周神经节慢性高保真神经记录的 2D 和 3D 电极阵列；2）将神经记录与心脏电生理功能的慢性高保真记录相集成。 为了满足这一需求，提出了三个目标。 具体目标 1：开发 2D 和 3D 微电极阵列和系统，用于从内在心脏神经节进行慢性、高保真神经记录。 提出的方法包括开发具有多达 256 个电极触点的基于薄膜的柔性微电极阵列。 一旦在急性环境中建立概念验证，将开发慢性包和固定技术，以实现大型动物模型的慢性记录。 具体目标 2：开发 3D 电极阵列和系统，用于外周封装交感神经（星状）和感觉（结状）神经节的慢性、高保真神经记录。 提议的方法包括开发基于薄膜的 3D 穿透微电极阵列（最多 256 个电极触点）。 一旦在急性环境中建立了概念验证，将开发慢性包和固定技术，以便能够对大型动物模型的封装外周神经节进行慢性记录。 具体目标 3：开发适形高清网格电极，用于心房和心室心外膜表面的长期、高分辨率电生理测绘。 这些“HD 网格电极”将拥有多达 512 个站点。 与目标 1 和 2 类似并结合，将开发慢性包和固定技术，以实现长达 28 天的长期高保真心脏神经标测。 新知识和创新：创建分布式电极系统，用于正常和病理状态下长期和连续的高保真度心脏神经映射。