Focused ultrasound-induced cavitation in elastic, anisotropic tissues: a treatment for tendinopathies

弹性各向异性组织中聚焦超声诱导空化：肌腱病的治疗方法

• 批准号: 10708190
• 负责人: Julianna Simon
• 金额: $ 57.69万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708190
• 关键词: Acoustics; Affect; Animals; Anisotropy; Annual Reports; Biomechanics; Chronic; Collagen; Collagen Fiber; Development; Devices; Dose; Dryness; Elasticity; Family suidae; Feedback; Focused Ultrasound; Focused Ultrasound Therapy; Fractionation; Gel; Human; Hydrogels; Image; Injections; Injury; Insulin-Like Growth Factor I; Location; Mechanics; Modeling; Monitor; Needles; Pain; Patient-Focused Outcomes; Patients; Perfusion; Photography; Physical therapy; Predisposition; Property; Protocols documentation; Publications; Rattus; Reporting; Severities; Shock; Speed; TGFB1 gene; Techniques; Tendinopathy; Tendon Injuries; Tendon structure; Testing; Therapeutic; Time; Tissues; Transducers; Transforming Growth Factor beta; Transforming Growth Factors; Translations; United States; Work; biomechanical model; collagenase; common treatment; cost; cost estimate; experimental study; healing; improved; in vivo; injured; innovation; loss of function; mechanical properties; novel; patient variability; personalized medicine; porcine model; preservation; quantitative imaging; quantitative ultrasound; real time monitoring; real-time images; response; success; therapy development; traditional therapy; treatment effect; treatment planning; ultrasound; Acoustics; Affect; Animals; Anisotropy; Annual Reports; Biomechanics; Chronic; Collagen; Collagen Fiber; Development; Devices; Dose; Dryness; Elasticity; Family suidae; Feedback; Focused Ultrasound; Focused Ultrasound Therapy; Fractionation; Gel; Human; Hydrogels; Image; Injections; Injury; Insulin-Like Growth Factor I; Location; Mechanics; Modeling; Monitor; Needles; Pain; Patient-Focused Outcomes; Patients; Perfusion; Photography; Physical therapy; Predisposition; Property; Protocols documentation; Publications; Rattus; Reporting; Severities; Shock; Speed; TGFB1 gene; Techniques; Tendinopathy; Tendon Injuries; Tendon structure; Testing; Therapeutic; Time; Tissues; Transducers; Transforming Growth Factor beta; Transforming Growth Factors; Translations; United States; Work; biomechanical model; collagenase; common treatment; cost; cost estimate; experimental study; healing; improved; in vivo; injured; innovation; loss of function; mechanical properties; novel; patient variability; personalized medicine; porcine model; preservation; quantitative imaging; quantitative ultrasound; real time monitoring; real-time images; response; success; therapy development; traditional therapy; treatment effect; treatment planning; ultrasound

PROJECT SUMMARY/ABSTRACT Almost 30 million tendon injuries are reported annually in the United States, with estimated costs of $114 billion. Even with treatment, some of these tendon injuries become chronic, with pain and loss of function persisting for more than 3 months. Conservative therapeutic techniques that induce microdamage to promote healing, such as dry needling (DN) and extracorporeal shock wave therapy (ESWT), produce mixed results with 0-85% of patients showing improvement. Inconsistencies in parameter reporting, alignment, dosing protocols, and real-time monitoring contribute to the wide range in patient outcomes. We seek to overcome many of the limitations of existing tendinopathy treatments by developing a novel focused ultrasound (fUS) therapy for tendinopathies with integrated passive cavitation and tissue Doppler imaging for alignment and quantitative monitoring of the fUS therapy. Recently, we showed that a narrow range of fUS parameters caused localized collagen fiber separation and fraying in ex vivo rat tendons through the creation, oscillation, and collapse of cavitation bubbles. When tested in an in vivo rat tendinopathy model, fUS preserved tendon mechanical properties as well as or better than the traditional DN therapy; the release of IGF1 and TGFβ healing factors was similar between DN and fUS. However, chronic tendinopathy will influence the mechanical properties of tendon, which will influence the fUS parameters that result in collagen fiber disruption. This prompts the need for testing in tendinopathic tendons of similar size to humans and the development of quantitative passive cavitation and tissue Doppler imaging for real-time monitoring of the tendon treatment progression. Here, we propose to use experiments and modeling to: 1) assess novel fUS to induce ranges of mechanical fractionation in healthy and tendinopathic ex vivo large animal tendons; 2) integrate PCI and tissue Doppler imaging for quantitative, real-time assessment of the fUS therapy; and 3) evaluate fUS to treat chronic tendinopathy. Innovations include a determination of how fUS parameters are affected by the change in mechanical properties of healthy versus injured tendons and the development of integrated passive cavitation and tissue Doppler imaging for quantitative analysis of fUS treatment progression. Additional novelty arises from testing the fUS therapy in a large-animal chronic tendinopathy model and comparing to conventional DN and ESWT therapies. These experimental results will feed into a large animal biomechanical model for treatment planning and the development of a framework for personalized treatment planning based on healing, and cellular and mechanical properties after fUS therapy. Long-term, we will seek translation into humans based on the in vivo experimental results and the models developed for treatment planning.

项目摘要/摘要 每年在美国报告近3000万肌腱受伤，估计费用为114美元 十亿。即使治疗，其中一些肌腱损伤也会变得慢性，疼痛和功能丧失 持续3个月以上。保守的治疗技术，诱导微型塑料促进 康复，例如干针刺（DN）和体外冲击波疗法（ESWT），产生了混合的结果 0-85％的患者表现出改善。参数报告，对齐，给药的不一致 协议和实时监控有助于患者预后的广泛范围。 我们试图通过开发一种小说来克服现有肌腱病治疗的许多局限性 针对肌腱病的聚焦超声（FUS）疗法，具有综合的被动气蚀和组织多普勒 成像进行对齐和定量监测FUS疗法。最近，我们证明了一个狭窄的 FUS参数的范围导致局部胶原纤维分离和在离体大鼠肌腱中的磨损 空化气泡的创造，振荡和崩溃。在体内大鼠肌腱病模型中测试时， FUS保留的肌腱机械性能以及比传统DN疗法更好或更好；发行 DN和FUS之间的IGF1和TGFβ愈合因子相似。但是，慢性肌腱病将影响 肌腱的机械性能，这将影响导致胶原蛋白纤维的FUS参数 破坏。这促使需要在与人类和人类相似的肌腱疗法肌腱中进行测试 开发定量的被动气态和组织多普勒成像，以实时监测 肌腱治疗进展。 在这里，我们建议将实验和建模用于：1）评估新型FUS诱导机械范围 在健康和肌腱疗法的大型动物肌腱中分离； 2）集成的PCI和组织多普勒 对FUS疗法进行定量的实时评估成像； 3）评估FUS治疗慢性 肌腱病。创新包括确定FUS参数如何受到更改的影响 健康与受伤肌腱的机械性能以及综合被动气蚀的发展 和组织多普勒成像，用于定量分析FUS治疗进展。出现了其他新颖性 通过在大动画肌腱病模型中测试FUS疗法，并与常规DN进行比较 和ESWT疗法。这些实验结果将以大型动物生物力学模型为食 治疗计划和开发基于康复的个性化治疗计划框架， FUS治疗后的细胞和机械性能。长期，我们将寻求翻译成人类 基于体内实验结果和用于治疗计划的模型。