A novel noncontact ultrasound indentation system for measurement of tissue material properties using water jet compression

Author name used in this publication: M. H. LuAuthor name used in this publication: Y. P. ZhengAuthor name used in this publication: Q. H. Huang2004-2005 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Measurement of Load-Induced Electrical Potentials at the Surface of the Knee

RÉSUMÉ L'arthrose (OA), la maladie chronique la plus répandue chez les personnes âgées, est l'une des principales causes d'invalidité dans notre société avec une incidence qui s’accroit dans le monde entier. L'arthrose résulte de la détérioration ou de la perte du cartilage articulaire qui agit comme un coussin de protection entre les os. Comme l'incidence de l'arthrose est en progression constante, il y a un besoin urgent de techniques d'évaluation non invasives pouvant être efficaces avant le début de la dégradation irréversible du cartilage. Les techniques actuelles d’évaluation comprennent l'évaluation clinique, l'arthroscopie et les modalités d'imagerie telles que les rayons X, l’imagerie par résonance magnétique (IRM) et la tomographie par ordinateur (CT). Bien que ces techniques soient couramment utilisées pour le diagnostic de l'arthrose en évaluant la formation d'ostéophytes, le pincement articulaire et les lésions osseuses, aucune d'elles ne peut détecter les changements précoces dus à l'arthrose du genou. La nécessité d'une évaluation précoce et précise de l'intégrité du cartilage a incité de nombreux chercheurs à explorer une variété de techniques. Par exemple, la transduction électromécanique du cartilage, connu sous le nom de « potentiels d'écoulement », est un indice sensible de l'intégrité du cartilage articulaire qui a été validé par de nombreuses expériences in vitro. Le mécanisme sous-jacent est associé à la séparation des charges négatives fixes et des contre-ions mobiles dans la phase liquide du cartilage durant sa compression. Un instrument arthroscopique (Arthro-BST) a ainsi été conçu pour mesurer les potentiels d’écoulement directement sur la surface du cartilage articulaire comprimé pour en évaluer la qualité lors d’une intervention chirurgicale. Une approche similaire, mais non invasive, a ensuite été développée pour mesurer les potentiels apparaissant à la surface du genou pendant son chargement et reflétant les potentiels d'écoulement sous-jacents. Cette technique est appelée électroarthrographie (EAG). La mise en charge du cartilage consiste simplement, pour un sujet debout, à déplacer son poids sur la jambe instrumentée. Même si les premières mesures de l’EAG étaient reproductibles, une certaine variabilité des signaux EAG enregistrés chez le même sujet a été observée, ce qui peut entraver son application comme outil de diagnostic de l'arthrose. Le but de notre étude était donc d'étudier la nature de la variabilité des signaux EAG afin de contribuer à l'élaboration de meilleures techniques de mesure.----------ABSTRACT Osteoarthritis (OA), the most prevalent chronic progressive disease of the elderly, is one of the leading causes of disability in our society with increasing incidence throughout the world. OA results from the deterioration or loss of articular cartilage acting as protective cushion between the bones. As the incidence of OA is on a continuous increase, there is an urgent need for noninvasive assessment techniques that can be effective before the onset of irreversible degradation. Current technologies to assess the joint function include clinical evaluation, arthroscopy and imaging techniques such as X-ray, magnetic resonance imaging (MRI) and computed tomography (CT). Although these techniques are widely used to assist the diagnosis of OA by evaluating osteophyte formation, joint space narrowing and bone damage, none of them can show osteoarthritic changes of the knee until the later OA stages. The need for an early and accurate evaluation of the integrity of cartilage has prompted many investigators to explore a variety of techniques. For example, the electromechanical transduction of cartilage, known as streaming potentials, is a sensitive index of the integrity of articular cartilage that has been validated by many in-vitro experiments. The underlying mechanism is associated with the separation of fixed negative charges and mobile counterions in the liquid phase of the cartilage under compression. A hand-held arthroscopic instrument (Arthro-BST) has thus been designed to measure the electrical potentials directly over compressed articular cartilage to assess its quality. A non-invasive approach, electroarthrography (EAG) was later developed to measure the electrical potentials appearing on the surface of knee during loading and reflecting the underlying streaming potentials. Mechanical loading simply consisted of shifting the body weight of the erect subject to the instrumented leg. Even though the first EAG measurements were repeatable, variability in the EAG signals recorded in the same subject was observed, which can hamper its application as a diagnostic tool for OA. The aim of our study was thus to investigate the nature of the variability of the EAG signals and to contribute to the development of better measurement techniques. The first objective of this study was to investigate how the contraction of certain leg muscles in supine subjects affects the contact force of the knee joint and, in turn, the EAG values. Voluntary isometric muscle contractions were repeatedly conducted to selectively activate four leg muscle groups while six subjects were lying on their back. Two EAG signals were recorded on bot

Possibilities of Articular Cartilage Quantification Based on High-Frequency Ultrasound Scans and Ultrasound Palpation

In der Diagnostik und Reparatur von hyalinem Gelenkknorpel sind neue Methoden zur Quantifizierung von Struktur und mechanischer Belastbarkeit gefragt, um die Behandlung von Knorpelschäden an Millionen von Patienten weltweit zu verbessern. Mittels hochfrequentem, fokussierten Ultraschall werden Oberflächenparameter für Reflektivität und Rauheit an Gelenkknorpel bestimmt. Es wird gezeigt wie die Oberflächenneigung kontrolliert werden kann. Die Ergebnisse vermitteln ein besseres Verständnis über die Zusammensetzung der Ultraschallsignale aus reflektierten und gestreuten Komponenten. 3D Ultraschallscans von Knorpelregeneraten erlauben die Defektstellen volumetrisch zu Quantifizieren. Die Proben wurden zusätzlich nach etablierten Bewertungssystemen benotet, welche auf makroskopischer Beurteilungen, MRT-Scans und Histologie basieren. Die ultraschallbasierten Volumendaten zeigten dabei gute Korrelationen mit den Punktwertungen. Die im Labor verwendeten Messaufbauten zur biomechanischen Charakterisierung von Gelenkknorpel können am Patienten nicht angewandt werden. Daher können Ärzte die Festigkeit von Knorpel bisher nur mittels manueller Palpation abschätzen. Diese Arbeit entwickelt eine Methode der Ultraschall-Palpation (USP), die es erlaubt, die während der manuellen Palpation erzeugte Kraft und Deformation, basierend auf Ultraschallechos, aufzunehmen. Es wurde einen Prototyp entwickelt womit gezeigt werden konnte, dass USP eine ausreichende Genauigkeit und Reproduzierbarkeit aufweist. Wiederholte Messungen können zusätzlich zeitabhängige biomechanische Parameter von Knorpel ableiten. Zusammenfassend zeigt diese Arbeit verbesserte und neue Möglichkeiten zur strukturellen und biomechanischen Charakterisierung von hyalinem Gelenkknorpel bzw. den Ergebnissen von Knorpelreparatur basierend auf Ultraschalldaten. Diese Methoden haben das Potenzial die Diagnostik von Gelenkknorpel und die Quantifizierung von Knorpelreparatur zu verbessern.In the diagnostics and repair of hyaline articular cartilage, new methods to quantify structure and mechanical capacity are required to improve the treatment of cartilage defects for millions of patients worldwide. This thesis uses high frequency focused ultrasound to derive surface parameters for reflectivity and roughness from articular cartilage. It is shown how to control the inclination dependency to gain more reliable results. Furthermore, the results provided a better understanding of the composition of ultrasonic signals from reflected and scattered components. 3D ultrasound scans of cartilage repair tissue were performed to quantify defect sites after cartilage repair volumetrically. The samples were also graded according to established scoring systems based on macroscopic evaluation, MRI scans and histology. The ultrasound-based volumetric parameters showed good correlation with these scores. Complex biomechanical measurement setups used in laboratories cannot be applied to the patient. Therefore, currently physicians have to estimate the stiffness of cartilage by means of manual palpation. In the last part of this thesis, a method denoted as ultrasound palpation is developed, which allows for measuring the applied force and strain during manual palpation in real time, solely based on the evaluation of the time of flight of ultrasound pulses. A prototype was developed and its measurement accuracy and reproducibility were characterized. It could be shown that ultrasound palpation has sufficient accuracy and reproducibility. Additionally, by repeated measurements it was possible to derive time-dependent biomechanical parameters of cartilage. In summary, this work shows improved and new possibilities for structural and biomechanical characterization of hyaline articular cartilage and the outcomes of cartilage repair based on ultrasound data. The methods have the potential to improve the diagnostics of articular cartilage and quantification of its repair

EFFECTS OF LOCAL MUSCLE VIBRATION ON CARTILAGE DEFORMATION IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTED INDIVIDUALS ACUTELY AFTER WALKING

Objectives: To examine the effects of local muscle vibration (LMV) on cartilage deformation acutely after walking in individuals with anterior cruciate ligament reconstruction (ACLR). Design: Cross-over study. Participants: 12 ACLR individuals ages 18-35. Interventions: Participants performed isometric squats while being exposed to LMV or no vibration (control). Interventions were delivered in a counterbalanced design. Main outcome measures: Cartilage cross-sectional area (CSA) (mm2), quadriceps and hamstring co-activation. Results: Downward trends were noted in co-activation indices, at preparatory (P = 0.188), heelstrike (P = 0.148), and weight acceptance (P = 0.363) time points. No differences noted in cartilage strain, either between conditions, or within. No significant correlations noted between co-activation and cartilage deformation. Conclusions: These findings imply potential benefits to using LMV as an adjunct to traditional rehabilitation programs post ACLR. Future work is necessary to identify mechanisms by which co-activation is altered, as well as direct mechanisms of cartilage strain.Master of Art

Investigations of Articular Cartilage Delamination Wear and a Novel Laser Treatment Strategy to Increase Wear Resistance

There are limited treatment options available today to slow down progression of osteoarthritis in its early stages and most interventions, such as highly invasive partial and total joint replacement surgeries, are performed only at the late stages of the disease. Understanding the mechanism of early articular cartilage stress-mediated wear and failure can aid in the design of new treatment options that are introduced at earlier stages of the disease, presenting the potential to slow down osteoarthritis progression and thus significantly improve patient outcomes. This dissertation aims to provide a basic science understanding of wear propagation and repair of articular cartilage in the absence of traumatic events under the normal reciprocal sliding motion of the articular layers at physiologic load magnitudes. In this dissertation there are three main thrusts: (1) characterize cartilage delamination wear under normal sliding (2) define a chemical environment that promotes cartilage explant homeostasis to enable long-term wear-and-repair studies (3) investigate a practical treatment modality capable of stopping or slowing down structural degeneration of articular cartilage in OA. We hypothesize that the mode of cartilage damage is delamination wear that progresses by fatigue failure of the extracellular matrix (ECM) under physiologic sliding, even when cartilage layers are subject to physiologic load magnitudes and contact stresses and even when the friction coefficient μ remains low (H1a). Based on prior literature findings regarding the role of synovial fluid (SF) boundary lubricants on the reduction of friction and wear, we also test the hypothesis (H1b) that SF delays the onset of cartilage delamination when compared to physiological buffered saline (PBS). We then test a third hypothesis (H1c) that loading cartilage against cartilage delays the onset of delamination wear compared to testing glass on cartilage, since contacting porous cartilage layers exhibit a much smaller solid-on-solid contact area fraction than impermeable glass contacting porous cartilage. Next, we hypothesize that the homeostatic dysregulation previously observed in cultured immature cartilage explants results from the presence of non-physiologic levels of important metabolic mediators in the culture medium. To this end, we hypothesize that: (H2a) immature bovine cartilage explants cultured in native synovial fluid will maintain homeostasis as characterized by maintenance of their mechanical properties and ECM contents at initial (post- explantation) levels, and (H2b) explants cultured in a physiologic-based medium, consisting of physiologic levels of key metabolic mediators, will maintain a similar homeostasis over long- term culture. Finally, a laser treatment strategy is explored that has the capability to reform collagen crosslinks, replacing those lost during OA progression. This novel therapy acts without injuring the cells and without any chemical additive or thermal ablation. The laser treatment protocol used in this application can specifically target the subsurface region, located 200 μm of the articular surface. By strengthening this region with enhanced crosslinking, we hypothesize (H3a) that cartilage will demonstrate greater resistance to fatigue failure than untreated controls. We then hypothesized (H3b) that this treatment protocol would also be effective on devitalized fibrillated human articular cartilage from OA joints with overall Outerbridge score OS1-3. We find that for both cartilage-on-cartilage and glass-on-cartilage sliding configurations at physiologic applied loads, long-term sliding with a low friction coefficient causes wear in the form of delamination. We show that the use of synovial fluid as a lubricant delays the onset of wear; and, similarly, that sliding with a cartilage counterface also reduces the incidence of wear. In subsequent studies we fully characterize a homeostatic culture medium to emulate cartilage in vitro behavior in synovial fluid. We show that explants cultured in this medium can maintain their properties for at least one month and have no loss in cell viability. Laser treatment is then tested on both living and devitalized bovine and devitalized human cartilage and the treatment is shown to improve the wear resistance of the tissue without harming embedded cells. Overall this work has led to novel insights that have clinical applicability. One strength of the in vitro investigations described in this body of work is the ability to separate out mechanically-mediated events from biochemically-mediated events, which would be impossible in vivo. Parsing out such specific mechanisms of cartilage wear can help guide better understanding of disease progression and drive therapeutic intervention. Intervening during the early stages of OA offers the promise of preventive care that currently does not exist and could provide significant benefits to a patient’s quality of life. This dissertation asserts that focusing on delaying or preventing wear by improving the resiliency of the extant intact cartilage in early OA is a viable strategy to improve patient outcomes and offers an innovative approach over existing regenerative techniques

Novel indentation techniques for measurement of soft tissue elasticity : a brief introduction

2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Development of post-traumatic osteoarthritis models to evaluate the effects of impact injury on joint health for clinical disease treatment and prevention

Osteoarthritis is one of the most common, debilitating, musculoskeletal diseases in the world. Currently, there is no cure. It is well-known that a traumatic, joint injury increases the risk of developing post-traumatic osteoarthritis (PTOA). Therefore, in order to improve clinical treatment and prevention strategies for post-traumatic osteoarthritis (PTOA), a series of translational studies were conducted to develop research models to evaluate the effects of impact injury. The first section of this dissertation (Ch. 1-2) provides a comprehensive introduction and literature review related to both clinical PTOA as well as previous research investigations of PTOA. The second section of this dissertation (Ch. 3-6) describes the methodology of optimizing a servo-hydraulic test machine to deliver a controlled impact injury (Ch. 3) as well as subsequent studies using this device to injure articular cartilage (Ch. 4) and cartilage-bone explants (Ch. 5-6). Further, the effects of dynamic, compressive loading to mimic walking after impact injury of cartilage-bone explants was investigated (Ch. 6). The third section of this dissertation (Ch. 7-8) details the development of an impactor device that may be used for pre-clinical, animal models. Many significant findings were discovered through this dissertation work. Specifically, by using the proportional-integral-derivative (40, 0, 0) values, a large (25kN) servo-hydraulic test machine may be used to deliver a controlled impact injury to explants (Ch. 3). Biomarkers glycosaminoglycan (GAG) and prostaglandin E2 (PGE2) were elevated after cartilage impact injury with PGE2 having the highest mechanosensitivity than any other biomarker (Ch. 4). Energy absorbed during cartilage-bone injury is dependent upon trauma severity; PGE2 and monocyte attractant protein (MCP-1) were elevated following cartilage-bone injury (Ch. 5). Dynamic, compressive loading retained cell viability in non-impacted cartilage-bone explants and mitigated GAG release in impacted explants; GAG and PGE2 were elevated due to cartilage-bone injury whereas matrix metalloproteinase-2 (MMP-2) and interleukin-8 (IL-8) were elevated due to injury plus dynamic, compressive loading (Ch. 6). The development of a 8mm diameter impactor does create articular cartilage damage (Ch. 7), albeit a smaller, 2mm diameter impactor creates higher impact stresses and may be used arthroscopically for pre-clinical animal models (Ch. 8).Includes bibliographical references

Distal limb osteoarthritis in the horse

The aim of this thesis was to study two objective methods of osteoarthritis (OA) diagnosis in horses and use them on the assessment of new intra-articular treatments. The studied methods were a new inertial-sensor based system of lameness detection and cartilage biomarkers in serum. It was found that distal limb flexion is significantly correlated to the presence of metacarpo-phalangeal OA in hind limbs and that inertial-sensors are sensitive in detecting asymmetry in these cases. A positive and significant correlation was observed between Coll2-1 concentration in serum and the presence of joint disease in males and young horses. Fib3-2 measurement has good potential to be used since it is not influenced by sex or age. Using an experimental model of OA, adipose stem cells pre-activated with interferon-gamma decreased joint inflammation and radiographic lesions. In clinical cases, a single injection of high-concentrated and high-molecular weight hyaluronic-acid decreased joint inflammation and biomarkers’ concentration; OSTEOARTRITE DO MEMBRO DISTAL NO CAVALO Resumo: A finalidade desta tese foi estudar dois métodos de diagnóstico objetivo de osteoartrite (OA) em equinos e aplicá-los na avaliação de novas terapias intra-articulares. Utilizou-se um sistema de sensores de movimento e foi avaliada a concentração de biomarcadores de cartilagem no soro. Concluiu-se que a flexão distal positiva está correlacionada com OA na articulação metacarpofalângica nos membros posteriores e que os sensores são sensíveis na detecção de assimetria nestes casos. Existe uma correlação positiva e significativa entre as concentrações de Coll2-1 e a presença de doença articular, sobretudo em machos e jovens. A dosagem de Fib3-2 tem utilidade por não ser influenciada pelo sexo nem idade. Num modelo experimental da doença, a terapia à base de células estaminais reduziu a inflamação articular e as lesões radiográficas. Em casos clínicos, o tratamento com ácido-hialurónico de alta concentração e peso molecular provoca uma diminuição da inflamação articular e dos biomarcadores no soro

Preclinical trial to examine the efficacy and safety of the treatment with the autologous chondrocyte transplantation ovine test sample co.don chondrosphere® (ACT3D-S)

Purpose of this study was to show the efficacy and safety of the investigational product co.don chondrosphere® (ACT3D-S). ACT3D-S is a product for autologous chondrocyte transplantation that we used in an animal model, the merino land sheep. We compared the treatment of ACT3D-S (Group A: Investigational product) with an untreated control (Group B: Control Intervention) in a bilateral model, what means that by randomization one hind limb was chosen to be treated with ACT3D-S while the remaining hind limb was left without treatment