Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 6 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 5 uppsatser.

Thesis (D.Phil.(Biokinetics, Sport and Leisure Sciences))--University of Pretoria, 2008. / Summary in English and Afrikaans. Includes bibliographical references.

Thesis (Ph. D. in Biomedical Engineering)--Vanderbilt University, Dec. 2004. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 84-94).

The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties. In some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity, but not yet been explored to understand tendon regeneration. The general objective of this thesis is to develop computational approaches to enhance the knowledge of the role that mechanical factors play in fibre re-organisation in healing tendons, by proposing an appropriate constitutive formulation, followed by analysing the mechano-adaptation of the models created when regulated by different biophysical stimuli. Curve fitting of an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits (0.9903 < R² < 0.9986). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model had almost equal influence on the fitting. The mechano-adaptation of the healing tendons when regulated by axial and principal strain predicted fibre re-organisation comparable to experimental findings, in contrast to models regulated by deviatoric strain. Also, mechano-adaptive models regulated by deviatoric strain were more spatially and temporally sensitive to different boundary conditions - length and loading magnitudes - than those regulated by axial and principal strain. This thesis describes that a hyperelastic fibre-reinforced mechano-adaptive model regulated by axial or principal strain is generally capable of describing the mechanobiological behaviours of healing tendons, and that further experiments should focus on establishing the localised structural and material parameters of collagen fibres and their mechano-adaptive behaviours in the healing tissue.

Biomechanical imaging (BMI) is the process of non-invasively measuring the spatial distribution of mechanical properties of biological tissues. The most common approach uses ultrasound to non-invasively measure soft tissue deformations. The measured deformations are then used in an inverse problem to infer local tissue mechanical properties. Thus quantifying local tissue mechanical properties can enable better medical diagnosis, treatment, and understanding of various diseases. A major difficulty with ultrasound biomechanical imaging is getting accurate measurements of all components of the tissue displacement vector field. One component of the displacement field, that parallel to the direction of sound propagation, is typically measured accurately and precisely; the others are available at such low precision that they may be disregarded in the first instance. If all components were available at high precision, the inverse problem for mechanical properties could be solved directly, and very efficiently. When only one component is available, the inverse problem solution is necessarily iterative, and relatively speaking, computationally inefficient. The goal of this thesis, therefore, is to develop a processing method that can be used to recover the missing displacement data with sufficient precision to allow the direct reconstruction of the linear elastic modulus distribution in tissue. This goal was achieved by using a novel spatial regularization to adaptively enforce and locally relax a special form of momentum conservation on the measured deformation field. The new processing method was implemented with the Finite Element Method (FEM). The processing method was tested with simulated data, measured data from a tissue mimicking phantom, and in-vivo clinical data of breast masses, and in all cases it was able to recover precise estimates the full 2D displacement and strain fields. The recovered strains were then used to calculate the material property distribution directly.

abstract: The objective of this research is to develop a biocompatible scaffold based on dextran and poly acrylic acid (PAA) with the potential to be used for soft tissue repair. In this thesis, physical and chemical properties of the scaffold were investigated. The scaffolds were made using electrospinning and cross-linked under high temperature. After heat treatment, Scanning Electron Microscope (SEM) was used to observe the structures of these scaffolds. Fourier transform infrared spectroscopy (FTIR) was used to measure the cross-linking level of scaffold samples given different times of heat treatment by detecting and comparing the newly formed ester bonds. Single-walled carbon nanotubes (SWCNT) were added to enhance the mechanical properties of dextran-PAA scaffolds. Attachment of NIH-3T3 fibroblast cells to the scaffold and the response upon implantation into rabbit vaginal tissue were also evaluated to investigate the performance of SWCNT dextran-PAA scaffold. SEM was then used to characterize morphology of fibroblast cells and rabbit tissues. The results suggest that SWCNT could enhance cell attachment, distribution and spreading performance of dextran-PAA scaffold. / Dissertation/Thesis / Masters Thesis Bioengineering 2014

Os sarcomas de partes moles constituem um grupo diverso de neoplasias que podem surgir nos tecidos conjuntivos praticamente de qualquer região do corpo. A ressonância magnética (RM) é atualmente o exame de escolha para detecção, estadiamento regional e acompanhamento desses tumores. A segmentação das lesões a partir das imagens de RM da rotina permite extrair dados quantitativos, que tem potencial para adicionar informações a análise. O propósito do estudo é avaliar a reprodutibilidade da segmentação manual de sarcomas de partes moles em imagens de RM de pacientes com diagnóstico definitivo confirmado por meio da histopatologia. Como objetivo secundário foi realizada a comparação da segmentação manual e semiautomática a fim de validar a segmentação semiautomática como método alternativo para segmentação desses tumores. Foi estudada uma coorte retrospectiva de 15 pacientes consecutivos com diagnóstico confirmado de sarcoma de partes moles acompanhados em nosso serviço, no período de janeiro de 2006 até janeiro de 2016, com imagens de RM adquiridas previamente ao tratamento e disponíveis para análise no formato DICOM. Foi utilizado o software 3D Slicer para realizar as segmentações pelos métodos manual e semiautomático. Três radiologistas fizeram as segmentações de forma independente e às cegas para permitir avaliação interobservador. Os resultados obtidos demonstram haver alta reprodutibilidade intraobservador com coeficiente de similaridade de Dice entre as segmentações variando de 0,849 a 0,979 e as distâncias Hausdorff variando de 3,53 mm a 20,96 mm e uma boa reprodutibilidade interobservador com coeficientes de similaridade de Dice variando de 0,741 a 0,972 e distâncias Hausdorff variando de 5,83 a 60,84 mm. Foi encontrada uma concordância substancial entre as segmentações realizadas pelo método semiautomático quando comparadas com as segmentações realizadas pelo método manual com coeficientes de similaridade de Dice variando de 0,871 a 0,973 e distâncias Hausdorff variando de 5,43 mm a 31,75 mm. Em relação ao tempo de segmentação não houve diferença estatisticamente significativa do método semiautomático quando comparado ao método manual (p>0,05). Também foram calculados os volumes obtidos nas diferentes segmentações e houve concordância quase perfeita entre as duas segmentações manuais realizadas pelo radiologista 1, entre as segmentações realizadas pelo radiologista 1 e pelo radiologista 2, entre as segmentações realizadas pelo radiologista 1 e pelo radiologista 3, e entre a segmentação manual e semiautomática realizadas pelo radiologista 1, sendo obtidos coeficientes de correlação intraclasse (ICC) entre 0,9927 e 0,9990. Os resultados obtidos demonstram boa reprodutibilidade intra e interobservador da segmentação manual utilizando o software 3D Slicer validando dessa forma esse método como ferramenta confiável para servir de padrão de referência em futuros estudos quantitativos desses tumores. Foi encontrada concordância quase perfeita entre as segmentações realizadas pelo método semiautomático quando comparadas com as segmentações realizadas pelo método manual, mas nossos resultados não demonstraram diferença significativa de tempo de segmentação do método semiautomático em relação ao método manual. / Soft tissue sarcomas constitute a diverse group of neoplasms that can arise in the connective tissues from virtually any region of the body. Magnetic resonance imaging (MRI) is currently the examination of choice for detection, regional staging and followup of these tumors. The segmentation of the lesions from the routine MR images allows the extraction of quantitative data, which has the potential to add information to the analysis. The purpose of the study is to evaluate the reproducibility of manual segmentation of soft tissue sarcomas in MRI images of patients with definitive diagnosis confirmed by histopathology. As a secondary objective, a comparison of manual and semiautomatic segmentation was performed to validate semiautomatic segmentation as an alternative method for segmentation of these tumors. We studied a retrospective cohort of 15 consecutive patients with confirmed diagnosis of soft tissue sarcoma accompanied at our service from January 2006 to January 2016 with MR images acquired prior to treatment and available for analysis in the DICOM format. The software was used 3D Slicer to perform segmentation by manual and semiautomatic methods. Three radiologists did the segmentations independently and blindly to allow inter-observer evaluation. The results obtained show high intraobserver reproducibility with Dice similarity coefficient between the segmentations ranging from 0.849 to 0.979 and Hausdorff distances ranging from 3.53 mm to 20.96 mm and good interobserver reproducibility with Dice similarity coefficients ranging from 0.741 to 0.972 and Hausdorff distances varying from 5.83 to 60.84 mm. A substantial agreement was found between the segmentations performed by the semiautomatic method when compared to the segmentations performed by the manual method with Dice similarity coefficients ranging from 0.871 to 0.973 and Hausdorff distances ranging from 5.43 mm to 31.75 mm. Regarding the segmentation time, there was no statistically significant difference of the semiautomatic method when compared to the manual method (p> 0.05). The volumes obtained in the different segmentations were also calculated and there was almost perfect agreement between the two manual segmentations performed by the radiologist 1, between the segmentations performed by radiologist 1 and radiologist 2, between the segmentations performed by radiologist 1 and radiologist 3, and between The manual and semi-automatic segmentation performed by the radiologist 1, and intraclass correlation coefficients (ICC) between 0.9927 and 0.9990 were obtained. The results obtained demonstrate good intra and interobserver reproducibility of the manual segmentation using 3D Slicer software, thus validating this method as a reliable tool to serve as a reference standard in future quantitative studies of these tumors. Almost perfect agreement was found between the segmentations performed by the semiautomatic method when compared to the segmentations performed by the manual method, but our results did not show a significant difference in segmentation time of the semiautomatic method in relation to the manual method.

Modeling and simulations are useful tools to help understand knee function and injuries. As there are more muscles in the human knee joint than equations of motion, optimization protocols are required to solve a problem. The purpose of this thesis was to improve the biofidelity of these simulations by adding in vivo constraints derived from experimental intra-cortical pin data and stability-inspired objective functions within an OpenSim-Matlab forward-inverse dynamics simulation framework on lower limb muscle activation predictions. Results of this project suggest that constraining the model knee joint’s ranges of motion with pin data had a significant impact on lower limb kinematics, especially in rotational degrees of freedom. This affected muscle activation predictions and knee joint loading when compared to unconstrained kinematics. Furthermore, changing the objective will change muscle activation predictions although minimization of muscle activation as an objective remains more accurate than the stability inspired functions, at least for gait. /// La modélisation et les simulations in-silico sont des outils importants pour approfondir notre compréhension de la fonction du genou et ses blessures. Puisqu’il y a plus de muscles autour du genou humain que d’équations de mouvement, des procédures d’optimisation sont requises pour résoudre le système. Le but de cette thèse était d’explorer l’effet de changer l’objectif de cette optimisation à des fonctions inspirées par la stabilité du genou par l’entremise d’un cadre de simulation de dynamique directe et inverse utilisant MatLab et OpenSim ainsi qu'un model musculo-squelétaire contraint cinématiquement par des données expérimentales dérivées de vis intra-corticales, sur les prédictions d’activation musculaire de la jambe. Les résultats de ce projet suggèrent que les contraintes de mouvement imposées sur le genou modélisé ont démontré des effets importants sur la cinématique de la jambe et conséquemment sur les prédictions d'activation musculaire et le chargement du genou. La fonction objective de l'optimisation change aussi les prédictions d’activations musculaires, bien que la fonction minimisant la consommation énergétique soit la plus juste, du moins pour la marche.