Open-source computational modeling of Spinal Cord Stimulation (SCS) to enhance dissemination of 1R01NS112996

脊髓刺激 (SCS) 的开源计算模型可增强 1R01NS112996 的传播

• 批准号: 10413556
• 负责人: MAROM BIKSON
• 金额: $ 31.4万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413556
• 关键词: 3-Dimensional; 3D Print; Absence of pain sensation; Action Potentials; Acute; Address; Anatomy; Animal Disease Models; Architecture; Award; BRAIN initiative; Biophysical Process; Blood flow; Brain; Cell model; Clinical; Clinical Trials; Computer Models; Convection; Coupled; Couples; Coupling; Custom; Data; Dependence; Development; Device Designs; Devices; Disease model; Dorsal; Dose; Electric Stimulation; Electrophysiology (science); FDA approved; Family suidae; Foundations; Frequencies; Goals; Heating; Human; Hydrogels; Implant; Interneurons; Lead; Masks; Measurement; Membrane; Metabolism; Meteor; Methods; Mission; Modality; Modeling; Molds; Neurobiology; Neurons; Neurostimulation procedures of spinal cord tissue; Pain management; Parents; Paresthesia; Patients; Perfusion; Pharmaceutical Preparations; Physics; Physiologic pulse; Procedures; Property; Public Health; Research; Resolution; Resources; Spatial Distribution; Spinal; Spinal Canal; Spinal Cord; System; Techniques; Technology; Temperature; Testing; Time; Tissues; Validation; Vertebral column; Width; Work; base; biophysical model; chronic pain; clinical efficacy; clinically relevant; computational network modeling; computerized tools; design; dorsal horn; electric field; improved; in vivo; in vivo Model; innovation; network models; neural stimulation; neuromechanism; neuroregulation; next generation; novel; open source; opioid epidemic; pain processing; pain relief; pain signal; porcine model; predictive modeling; predictive tools; pressure; product development; response; safety testing; sensor; side effect; spatiotemporal; theories; tool

Project Summary / Abstract (unchanged from original proposal, except supplement in red) There is a need to understand the mechanisms of neural stimulation technologies (RFA-NS-18-018). The impact of such research increases with both the clinical relevance of a neuromodulation technology and the extent mechanisms are unknown. Spinal Cord Stimulation at kHz frequencies (kHz SCS) has undergone a meteoric clinical and market rise, in the absence of an accepted mechanistic hypothesis. The most peculiar feature of kHz SCS mechanistically is that rapid biphasic stimulation undermines traditional mechanisms of electrical stimulation. But, we note this same feature of rapid pulsing results in high stimulation power leading to our hypothesis that kHz SCS increases tissue temperature. Our proposal that a clinically-established implanted electrical stimulation device would unexpectantly function by joule heating is disruptive and innovative and so requires, as the first step, to establish the degree of temperature increase during kHz SCS. To this end, our research plan develops state-of-the-art tools for multi-physics bioheat modeling (Aim 1), multi-compartment 3D- lattice phantom verification (Aim 2), and validation in a swine model (Aim 3) to methodically test the hypothesis that kHz SCS produces a 0.5-2 oC temperature rise. The multi-physics model (Aim 1) will be state-of-the-at in anatomical resolution, internal lead architecture, and the first to couple joule heat, heat conduction and convection (CSF flow), metabolism, and blood flow perfusion. The heat phantom (Aim 2) will be the first for spinal cord stimulation based on novel 3D-lattice printed compartments. The swine model (Aim 3) is selected for anatomical similarities to the human spinal cord and vertebral canal, and will include a custom fabricated combination lead/sensor array for in vivo temperature mapping. The most peculiar clinical feature of kHz SCS is lack of paresthesia, associated with conventional SCS. We will develop a dorsal horn network model of heating- based analgesia (Aim 4) by integrating experimentally validated temperature increases, pain processing network dynamics, and membrane sensitivity to temperature (Q10). We hypothesize a 0.5-2 0C temperature rise generates pain relief through the same final MoA as conventional SCS (gate-control) but without pacing associated paresthesia. While device design, disease models, and clinical trials are explicitly outside RFA scope, establishing a novel MoA and state-of-the-art tools developed in each Aim implicitly drive and underpin such developments. Directly RFA responsive, we “improve understanding of the neurobiological underpinnings of existing methods and lay the foundation for the next generation technologies by developing models (Aim 1, 4), systems (Aim 2), and procedures (Aim 3) to guide the design of better neuromodulation tools”. Indeed, because the heating MoA is fundamentally innovative, new tools are needed. Responsive to NOT-NS-21-014, this supplement enhances within-scope resource dissemination of the awarded 1R01NS112996 parent award by developing an open-source SCS modeling tool that predicts current flow and heating.

项目摘要/摘要（除红色补充部分外，与原提案内容一致）