Picosecond pulse technology for non-invasive electrostimulation

描述（由申请人提供）：细胞和组织的电刺激是各种医学治疗的基础。 然而，深部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，深度穿透但非侵入性的电刺激还不可能。 然而，皮秒脉冲技术的最新发展提供了一个机会，以克服物理限制，并提供电刺激深入人体，而不使用电极。 我们建议采用强烈的皮秒持续时间的电脉冲（psEP）作为替代传统的电刺激较长（微和毫秒）脉冲。 代替电极，psEP可以通过超宽带天线以电磁波的形式传递，并在不插入电极的情况下聚焦在人体的某一深度。 计算机模拟预测显着更深的渗透和更好的聚焦200 ps的脉冲相比，TMS。 此外，我们已经组装并测试了一个原型的体外psEP曝光系统，并首次能够证明，200 ps的EP确实可以在培养的神经元中引起动作电位。 这个跨学科的项目结合了工程的努力，开发和表征psEP暴露系统与生物学分析的效率和安全性的电刺激的psEP。 具体来说， 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）在真实的人类头部模型中执行psEP递送的高分辨率计算机模拟，3）在体外量化单脉冲和200 ps脉冲序列的电刺激参数，4）分析psEP处理的可兴奋和不可兴奋细胞中的Ca2+动力学，和5）确定刺激作用和细胞损伤之间的安全界限。 本研究将为脑深部电刺激的高压皮秒脉冲发生器和天线的设计提供指导。 它还将为无创psEP电刺激的首次体内试验奠定基础。

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.