Shear Wave propagation speeds and estimation of mechanical properties in soft, fibrous, nonlinear anisotropic materials

The mechanical properties of brain tissue may reflect or influence growth, remodeling, development, aging, and disease. However, brain tissue, especially white matter, is structurally anisotropic and has nonlinear strain-stress relationships, so common methods are not very useful to describe the mechanical properties of brain tissue. Magnetic resonance elastography (MRE), based on the MRI imaging technique, can be used for measuring tissue mechanical properties non-invasively. Therefore, the mathematical model that describes the relation between wave speed and tissue mechanical properties will essentially influence the accuracy of the prediction. The objective of this dissertation is to investigate the relationship between shear wave speeds and mechanical properties of soft fibrous anisotropic material. This was achieved through pursuit of the following aims: (1) to predict shear wave speeds from given material parameters and, conversely, to estimate parameters from the shear wave speed values in the nearly-incompressible transversely isotropic (NITI) HGO model; (2) to extend the HGO one-fiber family model to a locally orthotropic model and a HGO two-fiber family model; (3) to develop an artificial neural network-based approach for estimating material properties of transversely isotropic materials

Subtle Changes in Hyperelastic Properties of Myocardium With Cardiotoxicity Remodeling From Cardiac Magnetic Resonance

La doxorubicine (DOX) est un puissant agent antinéoplasique fréquemment administré dans le traitement de nombreux cancers pédiatriques, notamment la leucémie lymphoblastique aiguë (LLA). La doxorubicine possède une efficacité démontrée dans le traitement du cancer, mais elle engendre également un large spectre d'effets cardiaques indésirables. Les changements structurels du myocarde s'accompagnent de modifications progressives de la géométrie de la paroi du myocarde du ventricule gauche (VG). La détérioration de la fonction myocardique peut progresser silencieusement pendant des années et se manifester sans avertissement ou même ne devenir apparente que longtemps après la fin du traitement. Des doses cumulatives plus élevées de DOX augmentent le risque d'effets nocifs associés au traitement. La faisabilité de la résonnance magnétique cardiaque (RMC) a été établie et plusieurs logiciels de modélisation géométrique 3D du coeur ont été développés pour évaluer la fraction d'éjection, l'épaisseur de la parois, et le volume télésystolique et le volume télédiastolique du VG. La modélisation par éléments finis (EF) de la mécanique du ventricule gauche et les stratégies inverses d'identification des paramètres des matériaux ont ensuite été introduites pour tenir compte du comportement mécanique passif du tissu myocardique. Compte tenu de cela, nous avons entrepris une étude visant à analyser en détail les subtils changements asymptomatiques dans la géométrie et dans la fonction du ventricule gauche chez 84 survivants de la LLA infantile traités par chimiothérapie utilisant la doxorubicine (dose faible à modérée). Étant donné le grand potentiel de la modélisation numérique du coeur, cette évaluation a été réalisée à l'aide d'une approche basée sur un modèle EF qui intègre la forme et le mouvement spécifiques de la chambre ventriculaire directement à partir des données RMC. 84 survivants de la LLA, âgés de 23 ± 7 ans, ont été recrutés prospectivement et répartis en deux groupes distincts, nommés respectivement risque standard (SR, n = 19) et risque élevé en fonction du risque de récidive. En outre, les sujets du groupe associé à un risque élevé de récidive ont été subdivisés en deux sous-groupes selon qu’ils avaient reçu (HRdex, n = 36) ou non (HR, n = 45) la thérapie cardioprotectrice (dexrazoxane) dans le but de réduire le risque de lésions cardiaques à long terme. Par ailleurs, à des fins de comparaison, 10 volontaires en santé, d’âge similaire aux survivants (22 ± 4 ans) et n’ayant jamais été atteints de leucémie aiguë ou de cardiomyopathie, ont formé un groupe témoin. Dans le cadre de l'étude de la cardiotoxicité tardive, tous les sujets ont subi une imagerie RMC, une échocardiographie transthoracique et des tests d'effort. À partir des données RMC acquises, un opérateur formé a extrait la forme et le mouvement spécifiques du ventricule gauche à l'aide d'un cadre de points de repère (CIM v8.1, University of Auckland, Nouvelle-Zélande). Les bordures intérieures et extérieures des parois du ventricule gauche ont été dessinées semi-automatiquement à partir de six points de guidage placés par l'opérateur, puis corrigés manuellement en cas d'erreurs d'alignement. À partir de ce tracé, on a calculé la fraction d'éjection, le volume de course, la masse myocardique, l'épaisseur de la paroi, le volume diastolique final et le volume systolique final pour chacun des participants de l'étude. Par la suite, la reproductibilité inter- et intra-observateurs des résultats de la segmentation a été quantifiée par des coefficients de corrélation intra-classe (ICC) sur quatre reconstructions de 15 survivants du cancer, chacune étant réalisée par quatre opérateurs formés, et sur trois reconstructions du même sujet, chacune étant effectuée par un seul opérateur. Pour un sous-ensemble de la population des survivants de la leucémie (n = 48), un modèle 3D conçu par éléments finis a été utilisé pour calculer la propriété hyperélastique (C1) à partir d’une stratégie d'identification des paramètres inverses des matériaux basés sur la géométrie du VG lors de la diastase. Au départ, nous avons supposé des valeurs physiologiquement raisonnables de 0.75, 1.0 et 1.25 kPa comme contraintes de charge de pression pour tous les participants. Une fois les pressions ventriculaires spécifiques au sujet (au repos et à l'exercice maximal) connues, nous avons incorporé ces données dans le modèle et répété l'analyse aux éléments finis. Les valeurs résultantes de C1 ont été notées et comparées entre les groupes pour chacun des cinq scénarios de charge. Les comparaisons statistiques ont été effectuées par analyse de variance à sens unique (ANOVA) sur les paramètres géométriques globaux et régionaux et par analyse de variance à mesures répétées bidirectionnelles sur les paramètres géométriques dépendants du temps. Enfin, une analyse de sensibilité a été effectuée pour évaluer la dépendance de la propriété hyperélastique de la diastase et de la pression. Dans le cas de notre étude, la reproductibilité intra-observateur était bonne pour les paramètres géométriques régionaux (ICC, 0.60-0.74) et excellente pour les paramètres géométriques globaux (ICC, 0.75-1.00), alors que la reproductibilité inter-observateur était excellente pour les deux types de paramètres (ICC, 0.75-1.00). Aucune différence significative entre les quatre groupes n’a été observée relativement à la fraction d’éjection, au débit systolique, à la masse, au volume systolique final et au volume diastolique final. Quelques différences de volume épicardique ont été observées, mais seulement entre la phase finale de la systole et la diastase (p<0.01) à l’intérieur des groupes HRdex et HV ou SR, et parmi les groupes HV et HR. Il est intéressant de noter que la propriété hyperélastique pour les pressions standard était légèrement plus faible dans le groupe HR comparativement au groupe HRdex ou SR et aussi relativement au groupe contrôle (p<0.05). En revanche, aucune différence appréciable n’a pu être détectée dans la propriété hyperélastique à des pressions intraventriculaires au repos (p>0.5) et à l’exercice maximal (p>0.6). Il ressort clairement de cette analyse que les paramètres géométriques globaux et régionaux ne sont pas suffisamment sensibles pour détecter les changements subtils induits par la cardiotoxicité tardive de la doxorubicine dans la structure et la fonction du ventricule gauche. Toutefois, les paramètres globaux dépendants du temps constituent des preuves préliminaires que l’exposition à la doxorubicin a un effet plus néfaste sur la diastole précoce que sur la systole ou la diastole tardive. La propriété hyperélastique, plus faible dans le groupe HR, suggère un tissu myocardique plus enclin à la dilatation si une pression intra-ventriculaire plus élevée est appliquée, comparativement aux autres groupes d'étude. Cette constatation concorde avec ce qui a été observé chez les survivants à long terme ayant eu la leucémie adulte et traités par chimiothérapie à forte dose à base de doxorubicine. Il convient toutefois de noter que ces estimations ne peuvent tenir compte que des effets géométriques du remodelage du myocarde sur la mécanique ventriculaire passive, puisque la pression intra-ventriculaire gauche spécifique au sujet n'était pas incluse dans ces simulations. Des résultats similaires ont été obtenus lors de l'application de pressions intra-ventriculaires mesurées au repos et pendant l'exercice maximal. En conclusion, cette étude démontre que la cardiotoxicité subclinique de la doxorubicine peut être évaluée par l’analyse du comportement mécanique du ventricule gauche sur des images RMC. Nos résultats doivent toutefois être confirmés par des analyses additionnelles avant d’en tirer une conclusion solide sur la signification pronostique, à long terme, des altérations de la raideur myocardique et de leur relation avec le statut de risque dans la cohorte de survivants étudiée ou dans une cohorte similaire. Il serait très pertinent, dans le cadre d’études ultérieures, d’inclure la simulation de la mécanique ventriculaire, avec la méthode des éléments finis, pendant la diastole précoce et la systole afin de mieux analyser les changements de rigidité dans les groupes. Dans le même but, il pourrait être utile d'augmenter la résolution temporelle des données d'imagerie chez les survivants de la leucémie et les sujets témoins. Mots-clés : survivants de la leucémie lymphoblastique aiguë, cardiotoxicité induite par la doxorubicine, imagerie par résonance magnétique cardiaque, rigidité passive du myocarde, modélisation par éléments finis personnalisée, mécanique ventriculaire gauche.----------ABSTRACT Doxorubicin (DOX) is a potent chemotherapeutic agent routinely administered in the treatment of several pediatric malignancies, including acute lymphoblastic leukemia (ALL). Despite its efficacy to improve the outlook of cancer patients, doxorubicin is known to cause a wide spectrum of cardiac adverse effects. The structural changes in the myocardium are accompanied by progressive changes in LV myocardial wall geometry. The deterioration of myocardial function can progress silently for many years before the manifestation of clinical symptoms and become apparent even long time after completion of treatment. Higher cumulative doses of this agent increase the risk for late cardiac complications. The feasibility of CMR imaging has been established and a variety of software for 3D geometric modeling of the heart have been developed to assess wall thicknesses, ejection fraction, end-systolic and end-diastolic volumes. Finite element (FE) modelling and inverse material parameter identification strategies were then introduced to take into account the passive mechanical behavior of the myocardial tissue. In light of the above, we undertook a study to assess the asymptomatic changes in LV structure and function in a group of long-term survivors of childhood ALL treated with low to moderate doses of doxorubicin therapy. Given the high potential of numerical cardiac modeling, this evaluation was conducted using a FE model-based approach that integrates the subject-specific shape and motion of the ventricular chamber directly from imaging data. Eighty-four ALL survivors (23±7 years old) were prospectively enrolled and stratified into two different groups, designated as standard-risk (SR, n=19) and high-risk groups, according to their risk of tumor recurrence. Subjects treated for high-risk ALL were further divided into two groups depending upon whether they did (HRdex, n=36) or did not (HR, n=45) receive the protective therapy (dexrazoxane) in an attempt to reduce the likelihood of late cardiotoxicity. Furthermore, for purposes of comparison, 10 healthy volunteers (HV, 22±4 years), with no prior history of cancer or cardiac pathologies and similar in age to the survivors, were used as controls. As a part of the investigation of late-onset cardiotoxicity, all subjects underwent CMR imaging, transthoracic echocardiography, and exercise stress testing. From the acquired CMR data, a trained operator extracted the subject-specific shape and motion of the LV using a guide-point framework (CIM v8.1, University of Auckland, New Zealand). The inner and outer borders of the LV walls were semi-automatically drawn from six guidepoints placed by the operator at end-systole and then manually corrected for mis-registration errors. From this tracing, ejection fraction, stroke volume, myocardial mass, wall thickness, end-diastolic and end-systolic volumes were computed for each of the study participants. After that, inter- and intraobserver repeatability of the segmentation results were quantified by intra-class coefficients (ICC) on four reconstructions of 15 leukemia survivors, each by four trained operators, and on three reconstructions of the same subject, each by a single operator. For a subset of the leukemia survivor population (n=48), a 3D finite element model was used to quantify the hyperelastic property (C1) from inverse material parameters identification strategies based on the LV geometry at diastasis. This biomechanical parameter was initially calculated by assuming physiologically realistic values of 0.75, 1.0, and 1.25 kPa as pressure loading constraints for all participants. Once the subject-specific LV pressures (at rest and peak exercise) became available, we incorporated such data in the model and repeated the FE analysis. The resulting values of C1 were reported and compared between groups for each of the five loading scenarios. Statistical comparisons were performed by one-way analysis of variance (ANOVA) on global and regional geometrical parameters, and two-way repeated-measures ANOVA on time-dependent geometrical parameters. Ultimately, a sensitivity analysis was conducted to evaluate the dependence of the hyperelastic property on the diastasis frame and the pressure load. In our experience, inter-observer repeatability was good for regional geometrical parameters (ICC, 0.60-0.74) and excellent for global geometrical parameters (ICC, 0.75-1.00), while intra-observer repeatability was excellent for both regional and global parameters (ICC, 0.75-1.00). Groups had similar LV function values. No significant differences were observed among the four study groups in ejection fraction, stroke volume, mass, end-diastolic or end-systolic volumes. Some differences were detected in epicardial volume only between end-systole and diastasis phases (p<0.01) among the HRdex and HV or SR groups, and among the HV and HR groups. Interestingly, the hyperelastic property for standard pressures was slightly lower in the HR group when compared against the HRdex or SR group, and also when compared against the control group (p<0.05). In contrast, no appreciable difference could be noted in the hyperelastic property for intra-ventricular pressures at rest (p>0.5) and peak exercise (p>0.6). From this analysis, it is clear that the global and regional geometrical parameters are not sufficiently sensitive to capture the subtle changes induced by late doxorubicin cardiotoxicity in LV structure and function. Nevertheless, the time-dependent global parameters provided preliminary evidence that early diastole was more affected by doxorubicin exposure than systole or late diastole. The smaller hyperelastic property in the high-risk group suggested a myocardial tissue more prone to dilatation if increased intra-ventricular pressure is applied than in the other study groups. This finding is consistent with what has been observed in long-term survivors of adult leukemia treated with high-dose doxorubicin-based chemotherapy. It should be noted, however, that these estimates could account only for the geometrical effects of myocardial remodeling on the passive ventricular mechanics since the subject-specific LV cavity pressure was not included in these simulations. Similar results were obtained when applying intra-ventricular pressures at rest and peak exercise. In conclusion, this study demonstrated that the subclinical cardiotoxicity of doxorubicin can be non-invasively assessed through the mechanical behavior analysis of the LV on CMR images. Additional investigations will be necessary to confirm our results and draw a firm conclusion about the long-term prognostic significance of alterations in myocardial stiffness and their relationship with ALL risk status in this or similar cohort of survivors. In future works, we hope to include the FE simulation of the left ventricular mechanics during systole and early diastole in order to better capture the changes in stiffness across groups. To the same purpose, it might be convenient to increase the temporal resolution of the image data in both leukemia survivors and control subjects. Keywords: acute lymphoblastic leukemia survivors, doxorubicin-mediated cardiotoxicity, cardiac magnetic resonance imaging, passive myocardial stiffness, personalized FE modeling, in vivo left ventricular mechanics

Multiphysical modelling of mechanical behaviour of soft tissue : application to prostate

The aim of this thesis is to propose computational methodologies to analyse how the morphological and microstructural changes in the soft tissues, caused by various pathological conditions, influence the mechanical properties of tissue. More importantly, how such understanding could provide more insights into the mechanical properties of tissue for the purpose of quantitative diagnosis. To achieve this objective, statistical analysis of tissue microstructure based on image processing of tissue histology has been carried out. The influence of such microstructural changes due to different pathological conditions has also been compared to the mechanical properties of the tissue by means of the homogenization approach. To understand better the influence of fluid movement in viscoelastic behaviour of tissue, an optimization based method using numerical homogenization that is integrated with fluid-structure interaction (FSI) modelling is presented. The microstructures of soft tissue are treated as bi-phasic materials, solid material representing the cells and extracellular materials and fluid phase for the interstitial fluid. Such proposed method would be beneficial for quantitative assessment of mechanical properties of soft tissue, as well as understanding the role of multiscale microstructural features of soft tissues in its functionality. It is envisaged that this work will pave the road towards more precise characterization of mechanical properties of soft tissue which can be implemented to non-invasive diagnostic techniques, in order to improve the effectiveness of a range of diagnostic methods such as palpation for primary prostate diagnosis and, more importantly, the life quality of patients

Book of Abstracts 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization

In this edition, the two events will run together as a single conference, highlighting the strong connection with the Taylor & Francis journals: Computer Methods in Biomechanics and Biomedical Engineering (John Middleton and Christopher Jacobs, Eds.) and Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization (JoãoManuel R.S. Tavares, Ed.). The conference has become a major international meeting on computational biomechanics, imaging andvisualization. In this edition, the main program includes 212 presentations. In addition, sixteen renowned researchers will give plenary keynotes, addressing current challenges in computational biomechanics and biomedical imaging. In Lisbon, for the first time, a session dedicated to award the winner of the Best Paper in CMBBE Journal will take place. We believe that CMBBE2018 will have a strong impact on the development of computational biomechanics and biomedical imaging and visualization, identifying emerging areas of research and promoting the collaboration and networking between participants. This impact is evidenced through the well-known research groups, commercial companies and scientific organizations, who continue to support and sponsor the CMBBE meeting series. In fact, the conference is enriched with five workshops on specific scientific topics and commercial software.info:eu-repo/semantics/draf

Biomechanics and Remodelling for Design and Optimisation in Oral Prosthesis and Therapeutical Procedure

The purpose of dental prostheses is to restore the oral function for edentulous patients. Introducing any dental prosthesis into mouth will alter biomechanical status of the oral environment, consequently inducing bone remodelling. Despite the advantageous benefits brought by dental prostheses, the attendant clinical complications and challenges, such as pain, discomfort, tooth root resorption, and residual ridge reduction, remain to be addressed. This thesis aims to explore several different dental prostheses by understanding the biomechanics associated with the potential tissue responses and adaptation, and thereby applying the new knowledge gained from these studies to dental prosthetic design and optimisation. Within its biomechanics focus, this thesis is presented in three major clinical areas, namely prosthodontics, orthodontics and dental implantology. In prosthodontics, the oral mucosa plays a critical role in distributing occlusal forces a denture to the underlying bony structure, and its response is found in a complex, dynamic and nonlinear manner. It is discovered that interstitial fluid pressure in mocosa is the most important indicator to the potential resorption induced by prosthetic denture insertion, and based on this finding, patient-specific analysis is performed to investigate the effects caused by various types of dentures and prediction of the bone remodelling activities. In orthodontic treatments, a dynamic algorithm is developed to analyse and predict potential bone remodelling around the target tooth during orthodontic treatment, thereby providing a numerical approach for treatment planning. In dental implantology, a graded surface morphology of an implant is designed to improve osseointegration over that of a smooth uniform surface in both the short and long term. The graded surface can be optimised to achieve the best possible balance between the bone-implant contact and the peak Tresca stress for the specific clinical application need

A computational neuromuscular model of the human upper airway with application to the study of obstructive sleep apnoea

Includes bibliographical references.Numerous challenges are faced in investigations aimed at developing a better understanding of the pathophysiology of obstructive sleep apnoea. The anatomy of the tongue and other upper airway tissues, and the ability to model their behaviour, is central to such investigations. In this thesis, details of the construction and development of a three-dimensional finite element model of soft tissues of the human upper airway, as well as a simplified fluid model of the airway, are provided. The anatomical data was obtained from the Visible Human Project, and its underlying micro-histological data describing tongue musculature were also extracted from the same source and incorporated into the model. An overview of the mathematical models used to describe tissue behaviour, both at a macro- and microscopic level, is given. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group to a priori unknown external forces was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. The response of the various muscles of the tongue to the complex loading developed during breathing is determined, with a particular focus being placed to that of the genioglossus. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus. A comparison is then made to the response determined under quasi-static conditions using the pressure distribution extracted from computational fluid-dynamics results. An analytical model describing the time-dependent response of the components of the tongue musculature most active during oral breathing is developed and validated. It is then modified to simulate the activity of the tongue during sleep and under conditions relating to various possible neural and physiological pathologies. The retroglossal movement of the tongue resulting from the pathologies is quantified and their role in the potential to induce airway collapse is discussed