Soft wireless multimodal cardiac implantable devices for long-term investigating heart failure pathogenesis

用于长期研究心力衰竭发病机制的软无线多模式心脏植入装置

基本信息

批准号：
10735395
负责人：
Luyao Lu
金额：
$ 58.12万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10735395
关键词：
Acute Address American Anesthesia procedures Animal Experiments Animal Model Animals Biophysics Cardiac Cardiology Cardiovascular Physiology Cell Culture Techniques Cells Chronic Clinical Color Communities Complex Conscious Coronavirus Development Devices Diabetes Mellitus Diagnostic Disadvantaged Disease Electrophysiology (science)Energy Metabolism Energy harvesting Flavin-Adenine Dinucleotide Functional disorder Future Genetic Goals Heart Heart Abnormalities Heart Diseases Heart Research Heart failure Human Imaging technology Implant In Vitro Individual Infection Investigation Label Life Link Magnetic Resonance Spectroscopy Malignant Neoplasms Maps Measurement Measures Mechanics Metabolic Metabolic Diseases Metabolic dysfunction Microelectrodes Microfabrication Modality Modeling Modification Morphologic artifacts Motion Myocardial Nicotinamide adenine dinucleotide Optics Outcomes Research Pathogenesis Physiological Process Property Qualifying Quality of life Radioactive Tracers Rattus Research Resolution Role Scheme Signal Pathway Statistical Data Interpretation Surface System Techniques Technology Testing Therapeutic Thoracic cavity structure Time Tissues Work bioelectronics biophysical properties cardiac device cardiac implant cardiac pacing cardiac resynchronization therapy computerized data processing data acquisition data communication density design electrical property experimental study fabrication graphical user interface heart function heart rhythm implantable device in vivo innovation light emission microsystems miniaturize multimodality novel strategies operation optical imaging power harvesting skills therapeutic development therapy outcome tool wireless wireless implant

项目摘要

Project Summary The goal of this R01 proposal is to develop an ultra-soft, fully implantable, wireless label-free cardiac mapping and modulation system and apply it to identify chronic electrophysiological and metabolic changes and their links during heart failure (HF) development, progression, and pacing treatment in unrestrained conscious animals at cellular and whole heart levels. To achieve this, a miniaturized, mechanically compliant platform that integrates high-density, high-resolution sensing and modulation channels with wireless energy harvesting, storage, control, and data communication module is proposed. The resulting systems will greatly reduce motion artifacts and allow bidirectional high-content electrical and metabolic mapping and pacing in live animals. Those devices are innovative because they directly address the current limitations in chronically quantifying the individual roles and interplay between vital cardiac biophysical parameters during heart disease pathogenesis and will be used to fundamentally investigate the complex disease mechanisms involved in pathophysiological conditions leading to lethal HF and its therapeutic treatment. Once realized, this technology will be highly valuable to the cardiac research community. In the long term this work will enable closed-loop multiparametric cardiac mapping and pacing systems and offer new approaches to study the precise mechanisms and optimize the diagnostic and therapeutic strategies of other life-threatening heart diseases beyond HF. The three specific aims are: Aim 1 will establish ultra-soft multimodal cardiac systems for label-free cellular-resolution mapping of the excitation-contraction-metabolic waves and cardiac pacing. The mechanically compliant highly stretchable systems consist of high-density arrays (~300 channels in total) of (1) transparent microelectrodes for electrical mapping and stimulation; (2) multicolor micro-light-emitting diodes, and micro-photodetectors to excite and measure the autofluorescence of major endogenous fluorescent markers of cellular energy metabolism. Aim 2 will develop fully implantable wireless schemes for power harvesting, storage, control, and data communication to chronically operate the platforms in Aim 1 within a closed thoracic cavity in freely behaving small animals, which is beyond any possibility supported by current techniques. Graphical user interfaces will be developed for device configuration, real-time bidirectional control, data acquisition and processing. The integrated systems will be characterized, validated, and optimized by iterative benchtop measurements. Aim 3 will systematically investigate the precise mechanisms of HF pathogenesis and therapy using a battery of tests in rat models of HF. The functions of the proposed systems will be assessed in both ex vivo and in vivo studies. The implantable cardiac devices will identify the individual roles and links between local metabolic and electrical properties during different time points and stages of HF development and progression, and thoroughly evaluate the effects of cardiac-resynchronization therapy.

项目概要 R01 提案的目标是开发一种超软、完全植入、无线无标签心脏测绘和调制系统并应用它来识别慢性电生理和代谢变化及其联系在心力衰竭 (HF) 发展、进展和起搏治疗过程中，对不受约束的清醒动物进行细胞和整个心脏水平。为了实现这一目标，需要一个小型化、机械兼容的平台，该平台集成了高密度、高分辨率传感和调制通道，具有无线能量收集、存储、控制、并提出了数据通信模块。由此产生的系统将大大减少运动伪影和允许在活体动物中进行双向高内涵电和代谢测绘和起搏。这些设备是创新是因为它们直接解决了当前长期量化个人角色的局限性，心脏病发病机制中重要的心脏生物物理参数之间的相互作用，将用于从根本上研究导致病理生理状况的复杂疾病机制致命性心力衰竭及其治疗方法。一旦实现，这项技术将对心脏非常有价值研究社区。从长远来看，这项工作将使闭环多参数心脏测绘成为可能起搏系统并提供新方法来研究精确机制并优化诊断和心力衰竭以外的其他危及生命的心脏病的治疗策略。这三个具体目标是：目标 1 将建立超软多模态心脏系统，用于无标记细胞分辨率绘图兴奋-收缩-代谢波和心脏起搏。机械顺应性高拉伸性系统由高密度阵列（总共约 300 个通道）组成，该阵列由 (1) 个透明微电极组成，用于电学绘图和刺激； (2)多色微型发光二极管和微型光电探测器来激发和测量细胞能量代谢的主要内源荧光标记的自发荧光。目标 2 将开发用于能量收集、存储、控制和数据的完全植入式无线方案沟通以在封闭胸腔内长期自由操作目标 1 中的平台小动物，这是目前技术无法支持的。图形用户界面将为设备配置、实时双向控制、数据采集和处理而开发。这集成系统将通过迭代台式测量进行表征、验证和优化。目标 3 将系统地研究 HF 发病机制和使用电池的治疗的精确机制 HF 大鼠模型的测试。所提出的系统的功能将在体外和体内进行评估研究。植入式心脏装置将识别个体的作用以及局部代谢和心脏之间的联系。 HF发展和进展的不同时间点和阶段的电特性，并彻底评估心脏再同步治疗的效果。