Non-Thermal Pulsed FUS for Treatment of Intervertebral Disc Degeneration

非热脉冲 FUS 治疗椎间盘退变

• 批准号: 9316930
• 负责人: Chris John Diederich
• 金额: $ 19.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316930
• 关键词: Acoustics; Acute; Alginates; Animal Model; Animals; Anti-inflammatory; Back Injuries; Back Pain; Biological; Biomechanics; Bone necrosis; Cartilage; Cell Culture System; Cell Culture Techniques; Cell Survival; Cell Volumes; Cells; Characteristics; Chest; Chronic low back pain; Clinical; Collagen; Complex; Coupling; Cultured Cells; Custom; Data Set; Degenerative polyarthritis; Development; Diagnostic; Dimensions; Disease; Dose; Evaluation; Extracellular Matrix; Focused Ultrasound; Fracture Healing; Frequencies; Future; Gene Expression; Genes; Geometry; Goals; Grant; Growth Factor; Heating; Histology; Housing; Human; In Vitro; Inflammation; Inflammatory Response; Injury; Intervention; Intervertebral disc structure; Investigation; Lead; Lighting; Low Back Pain; Macrophage Activation; Measures; Mechanics; Metabolism; Methods; Modeling; Musculoskeletal; Operative Surgical Procedures; Pain; Patient Representative; Patients; Pattern; Performance; Phase; Physiologic pulse; Positioning Attribute; Probability; Procedures; Proteoglycan; Prothrombin; Protocols documentation; Public Health; Rattus; Regimen; Regulation; Reproducibility; Research; Sampling; Specimen; Spine surgery; Surgical incisions; System; Tail; Techniques; Technology; Therapeutic; Therapeutic Intervention; Tissues; Transducers; Ultrasonic Therapy; Ultrasonography; Up-Regulation; Vertebral column; Water; Wound Healing; base; bone; cell behavior; clinical application; clinical practice; cost; culture plates; design; disc regeneration; experience; healing; image guided; improved; in vitro Model; in vivo; in vivo Model; innovation; intervertebral disk degeneration; models and simulation; novel; novel strategies; prevent; reduce symptoms; regenerative; repaired; response; simulation; spinal disk injury; three dimensional cell culture; tissue regeneration; tool

PROJECT ABSTRACT: The overall goal of this grant is to develop improved methods of treating axial back pain via extracorporeal application of non-thermal or mechanical pulsed focused ultrasound (p-FUS) Recent in vitro studies have shown that low intensity pulsed ultrasound (LIPUS) stimulation can induce disease-modifying activities in intervertebral disc cells. These observations suggest that LIPUS or p-FUS may be a valuable non-invasive therapeutic strategy for the estimated 3 million low back pain sufferers who have failed conservative therapy and whose only other option is risky, spinal surgery. However, practicable p-FUS dose settings that optimize desirable disc cell behaviors and tissue regeneration have not been established; further, methods to deliver ultrasound energy to the disc appear feasible based upon ultrasound imaging protocols applied to the spine, but practical methods to deliver the energy for LIPUS to the disc remain to be evaluated. The goals of this R21 application are to: 1) use an established 3D human degenerative disc cell culture system to characterize and optimize cell behaviors in response to varying LIPUS or p-FUS regimens, using a custom calibrated ultrasound exposimetry system specifically designed to deliver a targeted ultrasound intensity while preventing heating, reflections, and standing waves within cell culture plates; 2) establish the LIPUS disease-modifying activity in vivo using an established rat-tail injury model, using a p-FUS system designed specifically for isolated calibrated exposure of the targeted disc; and 3) apply existing diagnostic data sets and employ complex 3D acoustic and thermal modeling to define feasibility and limitations of clinical p- FUS delivery. Points of innovation include a novel approach for in vitro studies to deliver quantifiable LIPUS without sample heating or standing waves, a broad optimization of frequency and energy effects of LIPUS on damaged disc cells as required for consideration of deep targets in the spine, and to also investigate and characterize components of the healing and remodeling response in vivo. This research team has significant experience with developing, characterizing, and the in vivo evaluation of ultrasound systems as well as in vitro and in vivo models of intervertebral disc degeneration and regeneration. Consequently, these proposed studies with important clinical implications and significance have high probability of being completed successfully. Completion of this proposed study has potential to lead to a novel and improved non-invasive method for treating back injury and related pain.

项目摘要： 该补助金的总体目标是开发通过体外治疗轴性背痛的改进方法 非热或机械脉冲聚焦超声（p-FUS）的应用最近的体外研究 低强度脉冲超声（LIPUS）刺激可以诱导疾病改善活动， 椎间盘细胞这些观察结果表明，LIPUS或p-FUS可能是一种有价值的非侵入性检查方法。 为估计300万保守治疗失败的腰痛患者提供治疗策略 而他唯一的选择就是冒险的脊椎手术然而，可优化的实用p-FUS剂量设置 还没有建立理想的椎间盘细胞行为和组织再生;此外， 基于应用于脊柱的超声成像协议将超声能量施加到椎间盘似乎是可行的， 但将LIPUS能量输送到椎间盘的实用方法仍有待评估。 该R21应用的目标是：1）使用已建立的3D人类退行性椎间盘细胞培养物 一种系统，用于响应于不同的LIPUS或p-FUS方案来表征和优化细胞行为， 定制校准的超声暴露测量系统，专门设计用于提供靶向超声 强度，同时防止细胞培养板内的加热、反射和驻波; 2）建立 使用p-FUS系统，使用已建立的大鼠尾部损伤模型的体内LIPUS疾病改善活性 专门设计用于目标椎间盘的隔离校准曝光;以及3）应用现有的诊断数据 设置并采用复杂的3D声学和热建模，以确定临床p的可行性和局限性， FUS交付。创新点包括体外研究的新方法，以提供可量化的LIPUS 在没有样品加热或驻波的情况下，对LIPUS的频率和能量效应进行了广泛的优化， 考虑脊柱深部目标所需的受损椎间盘细胞，并进行调查， 表征体内愈合和重塑反应的组分。 该研究团队在开发，表征和体内评价方面具有丰富的经验， 超声系统以及椎间盘退变和再生的体外和体内模型。 因此，这些具有重要临床意义和意义的拟议研究具有很高的价值。 成功完成的可能性。这项拟议研究的完成有可能导致一种新的 以及用于治疗背部损伤和相关疼痛的改进的非侵入性方法。