Focused Ultrasound Neuromodulation of Dorsal Root Ganglion for Noninvasive Mitigation of Low Back Pain

背根神经节聚焦超声神经调节无创缓解腰痛

• 批准号: 10705012
• 负责人: VIOLA RIEKE
• 金额: $ 94.07万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-25 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705012
• 关键词: Acoustics; Acute; Address; Adult; Affect; American; Analgesics; Animal Model; Attenuated; Back Pain; Behavior assessment; Behavioral; Biomechanics; Brain; Categories; Chronic; Chronic low back pain; Clinical; Clinical Trials; Data; Development; Devices; Diagnosis; Diagnostic; Electroencephalography; Electrophysiology (science); Failure; Family suidae; Fiber; Focused Ultrasound; Funding; Goals; Health Expenditures; Hematoma; Human; Human Volunteers; Image; Implant; Infection; Inflammatory; Interruption; Intervention; Life; Low Back Pain; Magnetic Resonance; Magnetic Resonance Imaging; Measurable; Measures; Methodology; Methods; Mission; Modality; Modeling; Monitor; Muscle; Nerve; Neural Conduction; Neuritis; Neurons; Neuropathy; Neurostimulation procedures of spinal cord tissue; Nociception; Operative Surgical Procedures; Opioid; Outcome; Pain; Pain management; Patients; Peripheral Nerve Stimulation; Peripheral nerve injury; Persistent pain; Phase; Physiologic pulse; Positioning Attribute; Prevalence; Procedures; Process; Public Health; Radiation exposure; Radiofrequency Interstitial Ablation; Research; Risk; Safety; Sensory; Signal Transduction; Site; Somatosensory Evoked Potentials; Sonication; Source; Specificity; Spinal; Spinal Ganglia; Spine pain; Stimulus; Supratentorial; System; Techniques; Technology; Testing; Time; Tissues; Toxic effect; Transducers; Translating; Translations; Ultrasonic Transducer; United States; United States National Institutes of Health; Vertebral column; Wages; abuse liability; behavior test; chronic pain management; clinical practice; clinical translation; cost; design and construction; disability; effective therapy; first-in-human; high resolution imaging; image guided; in vivo; innovative technologies; neuroinflammation; neurophysiology; neuroregulation; non-invasive system; novel; pain patient; pain perception; pain sensation; porcine model; pre-clinical; programs; prototype; radiation risk; radio frequency; response; sensory cortex; simulation; somatosensory; technology research and development; translation to humans

Project Summary The goal of this project is to develop a completely non-invasive, precise and durable treatment option for low back pain, which is estimated to cost $30 billion in direct health care expenditures annually. Chronic LBP is often a diagnostic and management challenge due to multiple potential pain sources with both biomechanical and inflammatory mechanisms. The failure of systemic analgesic drugs, such as opioids, is often due to their off-target toxicity, development of tolerance, and abuse potential. Interventional pain procedures provide target specificity but lack long-term efficacy and are associated with procedural risks. Understanding the supratentorial effects of such treatments may be an important part of developing effective treatment modalities. Focused ultrasound (FUS) is a lower risk, completely non-invasive modality that enables the delivery of spatially-confined acoustic energy to a small tissue region (dorsal root ganglion [DRG]) under magnetic resonance (MR) imaging guidance to treat axial low back pain by neuromodulation. The central goal of this study is to demonstrate neuromodulation of the DRG with FUS to decrease nerve conduction, which can be used to attenuate pain sensation. In the first Aim, we will establish electrophysiologic normative data for detecting changes in pain in neuritis models and normals measured by EEG and somatosensory evoked potentials. In the second Aim, we will demonstrate FUS neuromodulation of the DRG in pigs by (a) exploring FUS sonication parameters that results in DRG neuromodulation as assessed by SEPs during nerve stimulation and (b) evaluating the safety and efficacy of non-invasive FUS neuromodulation in neuritis pig model and controls by performing longitudinal unique behavioral assessments, which specifically test behaviors indicative of supraspinal pain sensation. In the third Aim, we will design and construct an LBP-specific MRgFUS device for rapid translation to patients with back pain by fully characterizing FUS sonications for DRG neuromodulation using regulatory standards, constructing an MRI radiofrequency coil and transducer mount to allow targeting of the DRG in humans, and evaluating the prototype for image and sonication quality. This exploratory study will demonstrate 1) using FUS on the DRG to interrupt and modulate nerve conduction, 2) using somatosensory evoked potentials to monitor brain changes and unique behavioral assessments in a pig model after modulating the effect of pain stimuli, 3) the safety of FUS DRG neuromodulation, and 4) a prototype for human use. Importantly, the low risk associated with FUS neuromodulation, compared to invasive procedures, will result in rapid clinical translation. We propose that FUS is a noninvasive modality to treat chronic low back pain with neuromodulation and has the potential to replace current invasive or systemically detrimental treatment modalities. By demonstrating that neuromodulation with FUS can alter pain perception with cortical monitoring and with behavioral assessments, with the ultimate goal of developing a completely non-invasive system to treat low back pain and adjust the treatment in real-time depending on the cortical response. The lower risk associated with neuromodulation, compared to more invasive procedures, will result in fast translation to humans.

项目摘要 该项目的目的是为Low开发一种完全无创，精确和耐用的治疗选择 背痛，据估计每年的直接医疗保健支出耗资300亿美元。慢性LBP是 通常由于多种潜在的疼痛来源而引起的诊断和管理挑战 和炎症机制。全身性镇痛药的失败，例如阿片类药物，通常是由于它们 非目标毒性，宽容的发展和滥用潜力。介入疼痛程序提供目标 特异性但缺乏长期疗效，并且与程序风险有关。了解 此类疗法的尖头影响可能是发展有效治疗方式的重要组成部分。 聚焦超声（FUS）是一种较低的风险，完全非侵入性方式，可以交付 在磁性下到磁性的小组织区域（背根神经节[DRG]）的空间限制的声能 共振（MR）成像指导通过神经调节治疗轴向腰痛。 这项研究的核心目的是证明DRG的神经调节与FUS降低神经 传导，可用于减轻疼痛感。在第一个目标中，我们将建立 用于检测神经炎模型疼痛变化的电生理规范数据 通过脑电图和体感测量的诱发电位。在第二个目标中，我们将展示FUS 通过（a）探索FUS超声处理参数的猪中DRG的神经调节，从而导致DRG 神经调节在神经刺激期间由SEP评估的神经调节以及（b）评估的安全性和功效 神经炎模型中的非侵入性FUS神经调节和对照，通过执行纵向独特 行为评估，该评估专门测试表明上脊髓疼痛的行为。在第三 目的，我们将设计和构建一个LBP特异性的MRGFU设备，以快速转化为患者 通过充分表征使用调节标准的DRG神经调节的FUS Sonications的背痛， 构建MRI射频线圈和换能器支架，以允许人类靶向DRG，并且 评估图像和超声处理质量的原型。 这项探索性研究将证明1）在DRG上使用FUS中断和调节神经传导， 2）使用体感诱发的潜力来监视大脑变化和独特的行为评估 猪模型调节疼痛刺激的作用后，3）FUS DRG神经调节的安全性，4）A 用于人类使用的原型。重要的是，与侵入性相比，与FUS神经调节相关的低风险 程序将导致快速的临床翻译。 我们建议FUS是一种无创的方式，用于治疗神经调节的慢性腰痛，并且具有 替代当前侵入性或系统上有害治疗方式的潜力。通过证明这一点 用FUS进行神经调节可以通过皮质监测和行为评估来改变疼痛感知， 最终的目标是开发完全无创的系统来治疗下背痛并调整 实时治疗取决于皮质反应。与神经调节相关的较低风险， 与更具侵入性的程序相比，将导致对人类的快速翻译。