Distributed electrode system for high-fidelity cardio-neural mapping

 描述（由申请人提供）：心脏神经元层级由相互依赖的反馈回路组成，包括位于i）心内神经节，ii）胸内心外（星状，中颈）以及iii）脊髓，iv）脑干和v）更高中心（直到岛叶皮质）的胞体。 这些处理中心中的每一个都包含传入、传出和交互（外周神经节中的局部回路）神经元，这些神经元在局部以相互依赖的方式与其他水平相互作用，以在心跳到心跳的基础上协调区域心脏指数。 现在认识到，自主神经失调是心力衰竭和心律失常演变的核心。 关于心脏病和心脏神经系统，存在交感神经系统的上调和副交感神经活性的相应降低。 这些变化中的许多是由心脏神经系统多个水平的传入转导和信息处理的改变驱动的。 人们对这些神经系统在疾病进展过程中如何适应的了解甚少。 在心脏神经标测领域中存在两个关键的未满足的需求：1）用于来自外周神经节的慢性高保真神经记录的2D和3D电极阵列的开发和优化，以及2）神经记录与心脏电生理功能的慢性高保真记录的整合。 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，用于心内神经节的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了概念证明，将开发慢性包装和固定技术，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，用于外周包裹的交感神经（星状）和感觉（结节状）神经节中的慢性、高保真神经记录。 所提出的方法包括开发基于薄膜的3D穿透微电极阵列（多达256个电极触点）。 一旦在急性环境中建立了概念证明，将开发慢性包装和固定技术，以实现对大型动物模型的包囊外周神经节的慢性记录。 具体目标3：开发用于心房和心室心外膜表面慢性、高分辨率电生理标测的适形高清网格电极。 这些“HD网格电极”将有多达512个位点。 与目标1和2类似并结合目标1和2，将开发慢性包装和固定技术，以实现长达28天的慢性高保真心脏-神经标测。 新知识与创新：创建分布式电极系统，用于正常和病理状态下的慢性和连续高保真心脏神经标测。

 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.