Picosecond pulse technology for non-invasive electrostimulation

用于无创电刺激的皮秒脉冲技术

• 批准号: 8811947
• 负责人: Andrei G Pakhomov
• 金额: $ 18.26万
• 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 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811947
• 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; Health; 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; ratiometric; relating to nervous system; response; simulation; time interval; voltage; 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; Health; 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; 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不同医疗治疗的基础。 但是，对深结构的刺激通常是侵入性的，并且依赖于被插入或永久植入体内的电极。 经颅磁刺激（TMS）是非侵入技术的一个例子，但其穿透深度和精度受到限制。 到目前为止，不可能进行深度渗透但无创静脉刺激。 但是，皮秒脉冲技术的最新发展为克服物理局限性并在不使用电极的情况下将电刺激深入到人体深处。 我们建议采用强烈的皮秒次尿电脉冲（PSEP）作为较长（微和毫秒）脉冲的常规电刺激的替代品。 PSSEP代替电极，可以通过电磁波的形式通过超级带天线传递，并在不插入电极的情况下聚焦在人体的深度上。 与TMS相比，计算机模拟预测了更深的渗透和更好地关注200-PS脉冲。 同样，我们已经组装并测试了体外PSEP暴露系统的原型，并且首次能够证明200-ps EP确实可以唤起培养的神经元中的动作电位。 这个跨学科的项目结合了工程学的努力，以开发和表征PSEP暴露系统以及PSEP效率和安全性的生物学分析。 具体来说，这是 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）确定刺激效应和细胞损伤之间的安全余量。 这项研究将为高压皮秒脉冲器和天线进行工程提供指导，以进行深度脑刺激。 它还将为无创PSEP电刺激的首次体内试验奠定基础。