Tendinopathy is a common pathology of tendons characterized by pain and a decrease in function resulting from changes in the tissue's structure and/or composition due to injury. Diagnosis of tendinopathy is determined by the qualitative analysis of a trained physician usually with assistance from an imaging modality. Although physicians can often identify tendinopathy, there are no quantitative metrics to evaluate tendon fatigue, damage, or healing. Physical therapy (PT) is a common treatment for patients with tendinopathy, and recent studies have investigated Focused Ultrasound (FUS) for its treatment of tendons. Developments in the use of FUS as a therapeutic have led to studies of the underlying mechanisms by which it operates. Digital Image Correlation (DIC) is a non-contact method of quantifying tissue displacements and strains of a deforming material using high resolution imaging DIC programs can evaluate and interpolate strain data by applying statistical image processing algorithms and solid continuum mechanics principles using a set of sequential image frames capturing the mechanical deformation of the specimen during testing. The studies presented in this thesis investigate methodologies for using DIC with ultrasound imaging of mouse Achilles tendons to characterize strains resulting from FUS therapies. The first method is based upon an orthogonal configuration of therapy and imaging transducers while the second investigates a coaxial experimental configuration. This work explores DIC as a viable means of quantifying the mechanical stimulation caused by FUS therapies on tendon tissue through ultrasound imaging to better understand the underlying mechanisms of FUS therapy. / Master of Science / Tendinopathy is a common injury that many people will experience in their lifetime. Pain and swelling are common symptoms and can make daily actions uncomfortable to perform. Physical therapy (PT) is one of the most common ways to help relieve the symptoms of this condition. A therapy being investigated to help treat tendinopathy utilizes Focused Ultrasound (FUS) technology to help the healing process. PT can be difficult and painful for those experiencing tendinopathy, but if a therapeutic like FUS could mimic the effects of PT, then some patients would not need to perform these physically demanding tasks. To understand if this treatment is viable, we need to better understand the underlying mechanisms by which it operates. Therefore, we are investigating the mechanical stimulation that FUS imparts on tendons because it is believed that the mechanical stimulations from exercise are a primary contributor to healing. Specifically, we want to evaluate the kind of strains applied by FUS therapies to inform decisions about dosage. One method uses Digital Image Correlation (DIC). DIC is a method of evaluating displacements and strains using non-contact high resolution imaging. DIC works using statistically motivated algorithms to calculate the deformation between subsequent video frames in a given material undergoing a state of stress. Using this technology along with ultrasound imaging, this work gives a preliminary exploration of using DIC as a means of quantifying strain to better understand the underlying mechanisms of the mechanical stimulations caused by FUS therapy.

Chan, Lai Shan. / Thesis submitted in: Dec. 2008. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 148-152). / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.I / PUBLICATIONS --- p.II / ABBREVIATION --- p.III-IV / INDEX OF FIGURES --- p.V-IX / INDEX OF TABLES --- p.X / ABSTRACT (English) --- p.XI-XIII / ABSTRACT (Chinese) --- p.XIV / Chapter CHAPTER 1 --- INTRODUCTION --- p.1-22 / Chapter CHAPTER 2 --- METHODOLOGY --- p.23-49 / Chapter CHAPTER 3 --- RESULTS --- p.50-97 / Chapter CHAPTER 4 --- DISCUSSION --- p.98-117 / BIBLIOGRAPHY / APPENDIX

Rotator cuff tendinopathy accounts for the majority of cases of shoulder pain, however, the aetiology and pathophysiology of the condition is poorly understood and treatment interventions for the condition have been introduced on an empirical basis, guided only by unproven theories of biological and structural changes in and around the affected tissue. This thesis explores changes in the provision of surgical interventions for rotator cuff tendinopathy, showing a rapid, sustained increase over the last decade. Investigation into the use of ultrasound as a clinical and research tool led to the development of an independent learning method for surgeons using the modality for shoulder imaging and highlighted the technological limitations of contrast enhanced ultrasound in assessing the microvascularity of the supraspinatus tendon. Development of a novel biopsy method for sampling the supraspinatus tendon permitted collection of tissue samples from several cohorts of individuals with rotator cuff tendinopathy. These studies, for the first time, described tissue changes across the whole spectrum of pathology suggesting the possibility of an early inflammatory phase of the condition followed by tissue senescence and reduced viability as pathology progressed. Paired samples taken before and after treatment identified reduced tissue activity in response to glucocorticoid therapy and a potential healing response from the supraspinatus tendon following surgical repair. Significant deterioration in tissue activity and viability was shown as age increased in a large cohort of individuals, highlighting the major impact of ageing as a factor in the onset and progression of rotator cuff tendinopathy. The techniques introduced provide standardised, reproducible methods for further evaluation of rotator cuff tendinopathy and the development of novel therapeutic interventions.

Midportion Achilles tendinopathy (tendinosis) is a troublesome painful condition, often characterised by pain, local swelling, tenderness and functional disability. Despite extensive research, the pathogenesis is poorly understood and treatment remains challenging. Features related to the peritendinous connective tissue can be of importance. Recently it has been suggested that the plantaris tendon might be involved in this condition. Furthermore, it has been hypothesised that tendon pain and the tendinosis-related tissue changes in tendinopathy might be mediated by signalling substances such as glutamate and acetylcholine. A clinical observation, not scientifically evaluated, has been that unilateral treatment for bilateral Achilles tendinosis can lead to an effect on the contralateral side.      The aim of this work was to examine the morphology and innervation patterns in the plantaris tendon and the peritendinous connective tissue in between the Achillles and plantaris tendons in midportion Achilles tendinopathy, and to evaluate if plantaris tendon removal has an effect on Achilles tendon structure. Another aim was to determine if unilateral treatment for Achilles tendinopathy targeting the peritendinous connective tissue can result in bilateral recovery. Furthermore the presence of non-neuronal cholinergic and glutamate systems was examined.      Sections of plantaris tendons with adjacent peritendinous connective tissue from patients with midportion Achilles tendinopathy were stained for morphology (H&E), and innervation patterns were evaluated using antibodies against general nerve marker (PGP9.5), sensory (CGRP) and sympathetic (TH) nerve fibres and Schwann cells (S-100β). Furthermore immunostainings against non-neuronal aceylcholine (ChAT) and glutamate signalling components (glutamate, VGluT2, NMDAR1) were performed. Plantaris tendon cells were cultured and also stained for glutamate signalling components, and were stimulated with glutamate and glutamate receptor agonist NMDA. Furthermore, Ultrasound Tissue Characterisation (UTC) was used to monitor the integrity of the Achilles tendon collagen structure after plantaris tendon removal.      Plantaris tendons exhibited tendinosis-like tissue patterns such as hypercellularity, collagen disorganisation and large numbers of blood vessels. The peritendinous connective tissue between the plantaris and Achilles tendons contained large numbers of fibroblasts and blood vessels and to some extent macrophages and mast cells. A marked innervation was found in the peritendinous connective tissue and there were also nerve fibres in the loose connective tissue spaces within the tendon tissue proper. Most nerve fibres were identified as sensory fibres. Some nerve fascicles in the peritendinous connective tissue showed absence of axons but homogenous reactions for Schwann cell marker. Tenocytes and cells in the peritendinous connective tissue expressed ChAT, glutamate, VGluT2 and NMDAR1. Tendon cells in vitro expressed VGluT2, NMDAR1 and glutamate. UTC showed significant improvement of Achilles tendon integrity 6 months after surgical plantaris tendon removal and scraping procedure. Eleven out of thirteen patients reported of a bilateral recovery after unilateral surgical treatment.      The results of this work show that plantaris tendons exhibit tendinosis-like tissue changes, internal innervation and features that suggest occurrence of glutamate and acetylcholine production and signalling. Plantaris removal improves Achilles tendon structure suggesting possible compressive/shearing interference between the Achilles and plantaris tendons in tendinopathy. The peritendinous connective tissue shows marked innervation, which thus might transmit pain when being compressed. The partial absence of axons indicates a possible nerve degeneration. On the whole, the study gives new evidence favouring that the plantaris tendon and the peritendinous connective tissue might be of importance for pain and the tendinopathy process in midportion Achilles tendinopathy.

Microcurrent therapy (MCT) involves the application of sub-sensory electric current and can promote tissue repair, possibly by mimicking endogenous electrical cues for healing. It has been used successfully to treat recalcitrant bone fractures and skin ulcers, but its effects on other forms of tissue have received little attention. This study aimed to investigate the potential of MCT to promote healing and alleviate symptoms in a selected soft connective tissue disorder. A systematic review of human studies involving MCT for soft connective tissue damage was conducted. A survey of 93 musculoskeletal physiotherapists was used to help select a common, recalcitrant disorder to treat with microcurrent in a clinical trial. Novel sonographic scales to quantify tendon structural abnormality and tissue healing were developed, and their measurement properties evaluated along with several clinical and patient-rated outcome measures. Two preliminary clinical trials, involving 62 people with the selected disorder – chronic tennis elbow - were conducted, comparing four different types of microcurrent applied daily for 3 weeks. The review found fair quality evidence that certain forms of MCT can relieve symptoms, and low quality evidence that they can promote healing, in several soft connective tissue disorders, including those affecting tendons. Optimal treatment parameters are unknown. In the survey, clinicians identified frozen shoulder, plantar fasciitis and tennis elbow as particularly problematic, and tennis elbow was selected for treatment in the trials. The sonographic scales of hyperaemia had fair-to-good inter-rater and test-retest reliability. Minimum Detectable Change values are calculated for the sonographic scales and for pain-free grip strength measurements. The trials suggest that monophasic microcurrent of peak amplitude 50 µA applied for 35 hours was most effective in symptom alleviation, with a 93% treatment success rate three months after treatment. By final assessment, pain-free grip strength increased by 31% (95%CI:5,57%), pain measured on a multiple-item questionnaire reduced by 27% (95%CI:16,38%) and patient-rated functional disability by 26% (95%CI:14,28%). MCT with a current amplitude of 500 µA was significantly less effective, and varying the waveform appeared less important in determining outcomes. Differences between groups were non-significant on several measurs, though there was a risk of type II error in the tests used. No significant differences between any groups were seen in sonographic assessments, although consistent patterns in bloodflow chage suggested that MCT may modulate hyperaemia levels. Higher baseline hyperaemia was associated with sustained falls in hyperaemia levels after treatment, and with improved clinical outcome. MCT’s analgesic effect does not rely on sensory stimulation, and further investigation of its influence on tendinous blood flow and vascularity, or on the local biochemical milieu, may help elucidate its mechanism of action. On the basis of this investigation, a fully-powered controlled clinical trial is justified. A protocol, combining MCT with an exercise programme, is proposed.

Epidemiologic data suggest 25% to 75% of all runners experience an overuse injury each year. Commonly cited biomechanical factors related to overuse injuries such as Achilles tendinopathy or medial tibial stress syndrome include excessive amounts or velocities of foot pronation. However, there is conflicting evidence in the literature supporting this theory. An alternative hypothesis suggests it is not necessarily the amount or velocity of pronation which is important for injury development; rather it is the duration the foot remains in a pronated position throughout stance that is the important variable. This project examined this hypothesis by first identifying biomechanical markers of prolonged pronation. Second, it assessed whether individuals currently symptomatic with injuries typically attributed to excessive pronation instead demonstrate the biomechanical markers of prolonged pronation. Finally, musculoskeletal modeling techniques were used to examine musculotendinous kinematics in injured and healthy runners, as well as healthy runners with prolonged pronation. The results suggest the two most robust measures for identifying individuals with prolonged pronation are the period of pronation and the eversion of the rear foot at heel off. Individuals with prolonged pronation can also be identified with a set of clinically feasible measures including higher standing tibia varus angles, reduced static hip internal rotation range of motion, and increased hip internal rotation during stance phase. Finally, individuals with prolonged pronation display a more medially located center of pressure trajectory during stance. Compared to healthy controls, individuals currently symptomatic with Achilles tendinopathy or medial tibial stress syndrome did not differ in the amount or velocity of pronation. However, they did demonstrate the biomechanical markers of prolonged pronation. Injured individuals also demonstrated greater average musculotendinous percent elongation than healthy controls, especially through mid and late stance. Currently healthy individuals demonstrating prolonged pronation exhibited musculotendinous percent elongations intermediate to the healthy and injured groups. As a whole, the results from this study suggest prolonged pronation may play a role in the development of common overuse running injuries. It is suggested future studies on injury mechanisms consider pronation duration as an important variable to examine. This dissertation includes unpublished co-authored material.

Recorded on July 27, 2007 by Eugene Barsky, Physiotherapy Outreach Librarian, UBC / N/A

Recorded by Eugene Barsky, Physiotherapy Outreach Librarian, UBC / This is a Systematic Review Presentation titled - "Pain-enduring Eccentric Exercise for the Treatment of Chronic Achilles Tendinopathy", created by Master of Physical Therapy Graduating Students, University of British Columbia - 2006, Presented on September 14-15, 2006 , Vancouver, BC, Canada

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