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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：
10515459
负责人：
Andrei G Pakhomov
金额：
$ 24万
依托单位：
OLD DOMINION UNIVERSITY
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

来源：
https://reporter.nih.gov/project-details/10515459
关键词：
Ablation Action Potentials Address Affect Animals Apoptotic Biophysics Bypass Cations Cell Size Cell membrane Cell physiology Cells Charge Chronic Complex Cytoskeleton Data Deep Brain Stimulation Disease Distant Dyes Electric Stimulation Electric Stimulation Therapy Electrodes Electrophysiology (science)Elements Ensure Event Exposure to Fluorescence Future Goals Health Human Image In Vitro Interdisciplinary Study Ion Channel Ion Channel Gating Ions Kinetics Knowledge Laser Microscopy Lasers Link Maps Medical Membrane Membrane Potentials Membrane Proteins Methods Modality Modeling Monitor Necrosis Neural Inhibition Neurons Neurophysiology - biologic function Neurosciences Outpatients Phosphatidylinositol 4,5-Diphosphate Photography Physiologic pulse Physiological Property Protocols documentation Research Resolution Rest Scientist Second Messenger Systems Signal Transduction Stimulus Stress Swelling Testing Time Tissues Work base bioelectricity design dielectric property electric field fluorescence imaging high reward high risk imaging modality in vivo innovation nano nanopore nanosecond neural network neuroregulation novel outcome prediction receptor response side effect temporal measurement tool tumor ablation voltage

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.

纳秒脉冲电场（nsPEF）是一种新的神经调节方式，具有独特的功能