Targeted Neuromodulation by Nanosecond Pulsed Electric Fields

纳秒脉冲电场的靶向神经调节

基本信息

  • 批准号:
    10669767
  • 负责人:
  • 金额:
    $ 24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Nanosecond pulsed electric field (nsPEF) is a new modality for neuromodulation, with unique capabilities qualitatively different from the conventional electrostimulation. The potential benefits of nsPEF include but are not limited to prolonged stimulation with little or no electrochemical side effects; excitation at lower thresholds; selectivity based on cell charging time constant; the capability of choosing between stimulation, inhibition, and ablation; and achieving these effects non-invasively, either for outpatient deep brain stimulation or for tumor ablation. The primary effect of nsPEF is a rapid build-up of cell membrane potential (MP). Real-time measurements of MP kinetics are a key to predicting the outcomes of nsPEF stimulation. They are also a key to understanding bipolar cancellation, a unique feature that enables interference targeting of nsPEF for non-invasive neuromodulation. However, membrane charging by nsPEF occurs on a nanosecond time scale, much faster than could be resolved by the existing electrophysiological and imaging methods. We have addressed this challenge by implementing strobe pulsed laser microscopy for MP imaging with better than 50 ns accuracy. In this one-of-a-kind set-up, cells loaded with a fast voltage-sensitive fluorescence dye are exposed to high-power momentary laser flashes (5 kW, 6 ns). The flashes are dynamically synchronized with nsPEF stimulation of target cells. Photos of fluorescence taken at different times during and after nsPEF show the real-time dynamics of MP changes and how these changes culminate in downstream effects, such as opening of voltage gated ion channels, initiation of action potentials, and nanoelectroporation. We will employ this all-new set-up for understanding fine mechanisms and principles how neurons respond to the nanosecond electric stress. We will characterize nsPEF parameters needed to evoke the desired neuromodulation effect and tune the interference targeting protocols to achieve this effect at a distance from stimulating electrodes. We will perform finite element modeling of the electric field thresholds and use our in vitro results to define the feasibility and nsPEF requirements for non-invasive deep brain stimulation. This project will generate new basic knowledge of neuronal function, including nanosecond-scale biophysics of the cell membrane and ion channels. We will systematically characterize nsPEF neuromodulation effects and link them to dielectric and physiological properties of neurons and to nsPEF stimulation parameters. This in vitro project will utilize R21 “high risk, high reward” concept to collect mechanistic and quantitative data necessary for animal and human studies of nsPEF neuromodulation.

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Real-time imaging of individual electropores proves their longevity in cells.
单个电孔的实时成像证明了它们在细胞中的寿命。
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Andrei G Pakhomov的其他基金

Next Generation Temporal Interference Stimulation for Non-Invasive Neuromodulation
用于非侵入性神经调节的下一代时间干扰刺激
  • 批准号:
    10615485
    10615485
  • 财政年份:
    2023
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Targeted Neuromodulation by Nanosecond Pulsed Electric Fields
纳秒脉冲电场的靶向神经调节
  • 批准号:
    10515459
    10515459
  • 财政年份:
    2022
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Low Energy Defibrillation with Nanosecond Pulsed Electric Field
纳秒脉冲电场低能量除颤
  • 批准号:
    8941895
    8941895
  • 财政年份:
    2015
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Low Energy Defibrillation with Nanosecond Pulsed Electric Field
纳秒脉冲电场低能量除颤
  • 批准号:
    9278268
    9278268
  • 财政年份:
    2015
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
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
    8636788
  • 财政年份:
    2014
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
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
    8811947
  • 财政年份:
    2014
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Mechanisms and Implications of Nanoelectroporation in Living Cells
活细胞纳米电穿孔的机制和意义
  • 批准号:
    8099680
    8099680
  • 财政年份:
    2010
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Mechanisms and Implications of Nanoelectroporation in Living Cells
活细胞纳米电穿孔的机制和意义
  • 批准号:
    7984696
    7984696
  • 财政年份:
    2010
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Mechanisms and Implications of Nanoelectroporation in Living Cells
活细胞纳米电穿孔的机制和意义
  • 批准号:
    8500364
    8500364
  • 财政年份:
    2010
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:
Mechanisms and Implications of Nanoelectroporation in Living Cells
活细胞纳米电穿孔的机制和意义
  • 批准号:
    8298579
    8298579
  • 财政年份:
    2010
  • 资助金额:
    $ 24万
    $ 24万
  • 项目类别:

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Targeted Neuromodulation by Nanosecond Pulsed Electric Fields
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