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: 10375977
• 负责人: VIOLA RIEKE
• 金额: $ 82.04万
• 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/10375977
• 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; Infection; Inflammation; Inflammatory; Interruption; Intervention; Investigation; 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; 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; neurophysiology; neuroregulation; non-invasive system; novel; pain patient; pain perception; pain sensation; porcine model; pre-clinical; programs; prototype; radiation risk; radio frequency; relating to nervous system; 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 该项目的目标是开发一种完全非侵入性，精确和持久的治疗选择， 据估计，背痛每年造成300亿美元的直接卫生保健支出。慢性LBP 通常是诊断和管理的挑战，因为有多种潜在的疼痛来源， 和炎症机制。全身性镇痛药物（如阿片类药物）的失败通常是由于其 脱靶毒性、产生耐受性和滥用潜力。介入性疼痛手术提供了目标 特异性，但缺乏长期疗效，并与手术风险相关。了解 这种治疗的幕上效应可能是开发有效治疗方式的重要部分。 聚焦超声（FUS）是一种风险较低、完全无创的方式， 在磁场作用下，将空间受限的声能传递到小组织区域（背根神经节[DRG]） 共振（MR）成像引导通过神经调节治疗轴性腰痛。 本研究的中心目标是证明FUS对DRG的神经调节，以减少神经刺激。 传导，其可用于减弱疼痛感。在第一个目标中，我们将建立 检测神经炎模型和正常人疼痛变化的电生理标准数据 通过脑电图和体感诱发电位测量。在第二个目标中，我们将演示FUS 通过（a）探索导致DRG神经调节的FUS超声处理参数， 在神经刺激期间通过SEP评估的神经调节，以及（B）评估 在神经炎猪模型和对照中通过进行纵向独特的FUS神经调节 行为评估，专门测试指示脊髓上疼痛感觉的行为。第三 目的是，我们将设计和构建一种LBP特异性MRgFUS装置，用于快速翻译至患有 通过使用监管标准充分表征用于DRG神经调节的FUS声处理， 构建MRI射频线圈和换能器支架，以允许靶向人体DRG，以及 评估原型的图像和声处理质量。 本探索性研究将证明1）在DRG上使用FUS中断和调节神经传导， 2)使用体感诱发电位监测大脑变化和独特的行为评估， 在调节疼痛刺激的作用后的猪模型，3）FUS DRG神经调节的安全性，和4） 人类使用的原型。重要的是，与侵入性相比，FUS神经调节的风险较低， 这将导致快速的临床翻译。 我们认为FUS是一种通过神经调节治疗慢性腰痛的非侵入性方法， 取代目前侵入性或对全身有害的治疗方式的潜力。通过证明 用FUS进行神经调节可以用皮层监测和行为评估改变疼痛感知， 其最终目标是开发一种完全非侵入性的系统来治疗腰痛并调整 根据皮质反应进行实时治疗。与神经调节相关的风险较低， 与更具侵入性的程序相比，将导致快速转化为人类。