Importance of muscle-subtendon units in Achilles tendinopathy - Project Summary Achilles tendinopathy is a prevalent and painful condition that hinders physical activity, with a significant incidence in the general population. Current treatments primarily involve calf-strengthening exercises, but success rates vary, leading to persistent symptoms in many patients. The Achilles tendon is composed of three subtendons twisted into a bundle and each linked to one of three individual muscles in the triceps surae, with each subtendon-muscle unit serving a distinct function. This intricate anatomy – which has yet to be considered in the development of treatment options for tendinopathy – may explain the varied responses to treatment. This study aims to explore the complex structure of the Achilles tendon to understand why some patients respond to generalized exercise treatments while others do not. This proposal integrates advanced in vivo techniques, including novel biomechanical sensors and cutting-edge medical imaging, with state-of-the-art modeling approaches to assess the structure and function of Achilles subtendons in patients with Achilles tendinopathy. The long-term goal of this work is to develop diagnostic and therapeutic strategies tailored to the individual structures of muscle-subtendon units. As a critical first step, this proposal will advance our understanding of the relationship between muscle-subtendon unit anatomy and Achilles tendinopathy and employs a three-stage approach. In Specific Aim 1, we will complete a longitudinal assessment of specific muscle responses to standard-of-care exercise treatments. To do this, we will track changes in muscle-subtendon units in 50 patients with tendinopathy over 12 weeks of exercise treatment. Using MRI, ultrasound, elastography, and biomechanical assessments, the study will analyze how different muscle-subtendon units respond to standard treatment. In Specific Aim 2, we will perform a high-field MRI study to assess the subtendon-specific damage incurred in Achilles tendinopathy. Using a research-grade MRI scanner and our newly-developed techniques, we will image tendons in patients with Achilles tendinopathy in high-resolution, allowing us to create previously inaccessible 3D subtendon reconstructions and region-specific effects of tendinopathy, providing detailed anatomical maps of tendon damage. Finally, in Specific Aim 3, we will develop and interrogate subject-specific computational models to simulate therapeutic loading via targeted muscle activation intervention. These models will compare the mechanical effects of generalized versus subtendon-specific treatment, predicting mechanical effects and potential failure modes based on individualized anatomy. Our interdisciplinary team aims to create a new paradigm for understanding the muscle-subtendon unit specific responses to Achilles tendinopathy treatment, exploiting the unique structure of each patient's Achilles tendon. This research will enhance understanding of anatomic variability in Achilles tendinopathy and lead to more effective, personalized clinical interventions.
