Picosecond pulse technology for non-invasive electrostimulation

用于无创电刺激的皮秒脉冲技术

• 批准号: 8636788
• 负责人: Andrei G Pakhomov
• 金额: $ 21.08万
• 依托单位: OLD DOMINION UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8636788
• 关键词: 3-Dimensional; Action Potentials; Address; Adverse effects; Apoptotic; Area; Biological; Brain; Cell membrane; Cells; Computer Simulation; Deep Brain Stimulation; Dependency; Development; Disease; Dose; Dyes; Dystonia; Electric Stimulation; Electrodes; Electromagnetic Energy; Endoplasmic Reticulum; Engineering; Feasibility Studies; Fura-2; Head; Heart; Human; Human body; Image; Implant; In Vitro; Individual; Intractable Pain; Life; Measurement; Measures; Medical; Membrane; Mental disorders; Methods; Microscope; Microscopy; Modeling; Monitor; Necrosis; Neuromuscular Diseases; Neurons; Pain; Parkinson Disease; Pathway interactions; Penetration; Physiologic pulse; Process; Resolution; Safety; Signal Transduction; Spottings; Stimulus; Structure; System; Technology; Testing; Time; Tissues; Training; Transcranial magnetic stimulation; base; cell injury; cellular imaging; electric field; improved; in vivo; lens; millisecond; models and simulation; nanosecond; novel strategies; patch clamp; prototype; public health relevance; ratiometric; relating to nervous system; response; simulation; time interval; voltage

DESCRIPTION (provided by applicant): Electric stimulation of cells and tissues is the basis of diverse medical treatments. However, stimulation of deep structures is usually invasive and relies on electrodes that are inserted or permanently implanted into the body. Transcranial magnetic stimulation (TMS) is an example of a non-invasive technology, but its penetration depth and precision are limited. Thus far, deep-penetrating but non-invasive electrostimulation has not been possible. However, recent developments in picosecond pulse technology offer an opportunity to overcome physical limitations and to deliver electric stimuli deep into the human body without using electrodes. We propose to employ intense picosecond-duration electric pulses (psEP) as a substitute for conventional electric stimulation with longer (micro- and millisecond) pulses. Instead of electrodes, psEP can be delivered by ultrawideband antennas in the form of electromagnetic waves, and focused at a depth in the human body without insertion of electrodes. Computer simulations predict significantly deeper penetration and better focusing of 200-ps pulses in comparison with TMS. Also, we have assembled and tested a prototype of an in vitro psEP exposure system and, for the first time, were able to demonstrate that 200-ps EP can indeed evoke action potentials in cultured neurons. This interdisciplinary project combines an engineering effort to develop and characterize psEP exposure systems with biological analyses of the efficiency and safety of electrostimulation by psEP. Specifically, this project consists of five Aims intended to 1) develop a microscopy- and patch clamp- compatible system for psEP studies in vitro, 2) perform high-resolution computer simulations of psEP delivery in a realistic human head model, 3) quantify electrostimulation parameters in vitro for single pulses and trains of 200-ps pulses, 4) analyze Ca2+ dynamics in psEP-treated excitable and non-excitable cells, and 5) determine the safety margin between stimulatory effects and cell damage. This study will provide guidance for engineering of a high voltage picosecond pulser and antenna for deep-brain stimulation. It will also lay the ground for first in vivo trials of no-invasive psEP electrostimulation.

描述（由申请人提供）：细胞和组织的电刺激是多种医学治疗的基础。 然而，深层结构的刺激通常是侵入性的，并且依赖于插入或永久植入体内的电极。 经颅磁刺激（TMS）是非侵入性技术的一个例子，但其穿透深度和精度有限。 到目前为止，深穿透但非侵入性的电刺激还不可能实现。 然而，皮秒脉冲技术的最新发展提供了克服物理限制并在不使用电极的情况下将电刺激深入人体的机会。 我们建议采用强烈的皮秒持续时间的电脉冲（psEP）作为更长（微秒和毫秒）脉冲的传统电刺激的替代品。 psEP 可以代替电极，通过超宽带天线以电磁波的形式传输，并聚焦在人体深处，无需插入电极。 计算机模拟预测，与 TMS 相比，200 ps 脉冲的穿透力明显更深，聚焦效果更好。 此外，我们还组装并测试了体外 psEP 暴露系统的原型，并首次证明 200-ps EP 确实可以在培养的神经元中激发动作电位。 这个跨学科项目将开发和表征 psEP 暴露系统的工程工作与 psEP 电刺激的效率和安全性的生物学分析结合起来。 具体来说，这 该项目由五个目标组成，旨在 1) 开发用于体外 psEP 研究的显微镜和膜片钳兼容系统，2) 在真实的人体头部模型中对 psEP 传递进行高分辨率计算机模拟，3) 量化单脉冲和 200 ps 脉冲串的体外电刺激参数，4) 分析 psEP 处理的可兴奋和不可兴奋细胞中的 Ca2+ 动力学，以及 5) 确定刺激作用和细胞损伤之间的安全裕度。 这项研究将为深部脑刺激的高压皮秒脉冲发生器和天线的工程提供指导。 它还将为首次无创 psEP 电刺激体内试验奠定基础。