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

项目摘要/摘要 据报道，美国每年有近3000万人肌腱受伤，估计费用为114美元 十亿美元。即使接受治疗，这些肌腱损伤中的一些也会变成慢性损伤，伴有疼痛和功能丧失。 坚持3个月以上。导致微损伤的保守治疗技术促进 治疗，如干针疗法(DN)和体外冲击波疗法(ESWT)，产生的结果好坏参半 有0-85%的患者有改善。参数报告、对齐、配药不一致 协议和实时监测有助于患者结果的广泛范围。 我们试图通过开发一种新的方法来克服现有肌腱病治疗方法的许多局限性。 被动空化与组织多普勒联合应用聚焦超声治疗肌腱病 用于FUS治疗的对准和定量监测的成像。最近，我们展示了一个狭窄的 FUS参数范围通过以下途径引起大鼠肌腱局部胶原纤维分离和磨损 空化气泡的产生、振荡和破裂。当在活体大鼠肌腱病模型中进行测试时， FUS保留了肌腱的力学性能，达到或优于传统的糖尿病肾病治疗； 胰岛素样生长因子1和转化生长因子β在糖尿病肾病和糖尿病肾病患者中的愈合因子相似。然而，慢性肌腱病会影响 肌腱的力学性能，这将影响导致胶原纤维的FUS参数 颠覆。这促使了对与人类大小相似的肌腱病变肌腱进行测试的必要性 定量被动空化和组织多普勒成像实时监测的研究进展 肌腱治疗进展。 在这里，我们建议使用实验和建模来：1)评估新的FU以诱导机械范围 健康和肌腱病态大动物肌腱的分割2)组织多普勒与经皮冠状动脉介入治疗的结合 成像用于定量、实时评估FUS治疗；以及3)评估FUS治疗慢性 肌腱病。创新包括确定FUS参数如何受 健康肌腱与损伤肌腱的力学性能及综合被动空化的发展 组织多普勒成像定量分析FUS治疗进展。出现了额外的新颖性 在大型动物慢性肌腱病模型上测试FUS疗法并与传统糖尿病肾病进行比较 和体外冲击波治疗。这些实验结果将被提供给一个大型动物生物力学模型 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性能。从长远来看，我们将寻求转化为人类 基于体内实验结果和为治疗计划开发的模型。

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.