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.

PROJECT NARRATIVE Almost 30 million tendon injuries are reported each year, but therapeutic techniques produce mixed successes, with 0-85% of patients showing improvement. We have shown that focused ultrasound (fUS) can be used to create mild collagen fiber fraying and separation in rat tendons, and that the fUS treatment preserves mechanical properties of tendons as well as or better than the conventional dry needling. Our objective is to develop fUS therapy for the treatment of chronic tendinopathies and integrate passive cavitation and tissue Doppler imaging for quantitative feedback of the fUS therapy.