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

基本信息

批准号：
10586628
负责人：
Julianna Simon
金额：
$ 50.72万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
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/10586628
关键词：
Acoustics Affect Animals Anisotropy Annual Reports Biomechanics Chronic Collagen Collagen Fiber Development Devices Dose Family suidae Feedback Focused Ultrasound Focused Ultrasound Therapy Fractionation Gel Human Human Development Hydrogels Image Injections Injury Insulin-Like Growth Factor I Location Mechanics Modeling Monitor Needles Pain Patient-Focused Outcomes Patients Perfusion Photography Physical therapy Property Protocols documentation Publications Rattus Reporting Severities Shock Speed Techniques Tendinopathy Tendon Injuries Tendon structure Testing Therapeutic Time Tissues Transducers Transforming Growth Factor beta Transforming Growth Factors Translations United States Work base biomechanical model collagenase common treatment cost cost estimate experimental study healing improved in vivo injured innovation loss of function mechanical properties novel personalized medicine porcine model preservation quantitative imaging quantitative ultrasound real time monitoring real-time images response success tendon development therapy development traditional therapy treatment effect treatment planning ultrasound

项目摘要

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.

项目概要/摘要美国每年报告近 3000 万例肌腱损伤，估计费用为 114 美元即使经过治疗，其中一些肌腱损伤也会变成慢性，伴有疼痛和功能丧失。持续3个月以上诱导微损伤的保守治疗技术。干针疗法 (DN) 和体外冲击波疗法 (ESWT) 等治疗方法会产生不同的结果 0-85% 的患者在参数报告、调整、剂量方面表现出不一致。协议和实时监测有助于改善患者的治疗结果。我们寻求通过开发一种新的方法来克服现有肌腱病治疗的许多局限性结合被动空化和组织多普勒的聚焦超声 (fUS) 疗法治疗肌腱病最近，我们证明了 fUS 治疗的对齐和定量监测的成像。 fUS 参数范围导致离体大鼠肌腱局部胶原纤维分离和磨损在体内大鼠肌腱病模型中进行测试时，空化气泡的产生、振荡和破裂。 fUS 保留的肌腱力学性能与传统 DN 疗法一样好，甚至更好； DN 和 fUS 之间的 IGF1 和 TGFβ 愈合因子相似，但慢性肌腱病会产生影响。肌腱的机械性能，这将影响产生胶原纤维的 fUS 参数这提示需要对与人类和人类大小相似的肌腱病肌腱进行测试。开发定量被动空化和组织多普勒成像，用于实时监测肌腱治疗进展。在这里，我们建议使用实验和建模来：1）评估新颖的 fUS 以诱导机械范围健康和腱病离体大型动物肌腱的分割 2) PCI 和组织多普勒；成像以定量、实时评估 fUS 治疗；3) 评估 fUS 治疗慢性病的效果；创新包括确定 fUS 参数如何受到肌腱病变化的影响。健康与受伤肌腱的机械特性以及集成被动空化的发展用于定量分析 fUS 治疗进展的组织多普勒成像出现了额外的新颖性。在大型动物慢性肌腱病模型中测试 fUS 疗法并与传统 DN 进行比较这些实验结果将输入大型动物生物力学模型中。治疗计划和基于康复的个性化治疗计划框架的开发，以及 fUS 治疗后的细胞和机械特性长期来看，我们将寻求将其转化为人类。基于体内实验结果和为治疗计划开发的模型。