Phenomenological model of diffuse global and regional atrophy using finite-element methods

The main goal of this work is the generation of ground-truth data for the validation of atrophy measurement techniques, commonly used in the study of neurodegenerative diseases such as dementia. Several techniques have been used to measure atrophy in cross-sectional and longitudinal studies, but it is extremely difficult to compare their performance since they have been applied to different patient populations. Furthermore, assessment of performance based on phantom measurements or simple scaled images overestimates these techniques' ability to capture the complexity of neurodegeneration of the human brain. We propose a method for atrophy simulation in structural magnetic resonance (MR) images based on finite-element methods. The method produces cohorts of brain images with known change that is physically and clinically plausible, providing data for objective evaluation of atrophy measurement techniques. Atrophy is simulated in different tissue compartments or in different neuroanatomical structures with a phenomenological model. This model of diffuse global and regional atrophy is based on volumetric measurements such as the brain or the hippocampus, from patients with known disease and guided by clinical knowledge of the relative pathological involvement of regions and tissues. The consequent biomechanical readjustment of structures is modelled using conventional physics-based techniques based on biomechanical tissue properties and simulating plausible tissue deformations with finite-element methods. A thermoelastic model of tissue deformation is employed, controlling the rate of progression of atrophy by means of a set of thermal coefficients, each one corresponding to a different type of tissue. Tissue characterization is performed by means of the meshing of a labelled brain atlas, creating a reference volumetric mesh that will be introduced to a finite-element solver to create the simulated deformations. Preliminary work on the simulation of acquisition artefa- - cts is also presented. Cross-sectional and

Experimental and numerical characterization of the viscoelastic behaviour of cartilages and soft tissues of the human nose

Dissertação de mestrado integrado em Engenharia BiomédicaThe facial plastic surgery, and particularly the area of rhinoplasty, is undoubtedly a growing up market. Surgical techniques have been evolving to respond to very specific patient desires not only for functional reasons, but also to resolve aesthetic issues. Actually, it is moving plenty of money around the world, being a great scientific and commercial opportunity among researchers. The human nose is composed of three major portions separated by two well-defined regions of transition (K-area and S-area) that are very complicated to deal with in postoperative periods. The viscoelastic behaviour of soft biological tissues, especially that of nasal cartilages and adjacent subcutaneous/fatty tissues, is barely known. There are no studies on the viscoelastic characterization of the mechanical properties of nasal septum (NS), upper lateral cartilages (ULC), and lower lateral cartilages (LLC) in creep and relaxation (basic viscoelasticity features) neither on the determination of frequency- and temperature-dependent properties of these tissues through dynamic mechanical analysis (DMA) in tension and compression. General information on thermal degradations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) is also missing. Therefore, part of this work intends to fill this lack of the literature giving some insights into the cartilage internal composition and architecture, as well as the specificity of the activated mechanisms under constant stress or strain. Furthermore, numerical simulations were performed based on a hyper-viscoelastic mathematical formulation using a home-made open-source finite element (FE) solver (V-Biomech) in order to find a set of basic constitutive parameters that allow to replicate the experimental creep and relaxation behaviours of nasoseptal cartilage specimens from distinct regions of the quadrilateral cartilage (QLC). Thus, a complete standard biphasic poro-hyper-viscoelastic constitutive law was developed and validated. Finite Element Models (FEM) are gaining relevance to analyse soft biological components. As example, numerical simulations of the viscoelastic behaviours of the specimens harvested from anterior part of the QLC were performed to understand which of the constitutive parameters were more sensitive to achieve the best numerical-experimental agreement. The tools to reproduce these simulations in a more complex geometry (the whole nasal structure, with bony and cartilaginous components) were also developed and presented. The work still goes on it.A cirurgia plástica facial, e em particular a área da rinoplastia, é indubitavelmente um mercado em crescimento. As técnicas cirúrgicas têm evoluído no sentido de dar resposta aos desejos mais específicos de cada paciente não só por razões funcionais, mas também para resolução de problemas estéticos. Atualmente, é uma área que movimenta muito dinheiro em todo o mundo, tornando-se numa evidente oportunidade científica e comercial. O nariz humano está dividido em três regiões principais separadas por duas zonas de transição (áreas K e S) que são muito difíceis de manipular em períodos de recuperação pós-cirurgia. O comportamento viscoelástico de tecidos moles, especialmente o das cartilagens nasais e dos tecidos subcutâneo/adiposo adjacentes, é pouco conhecido. Atualmente, não existem estudos sobre a caracterização de propriedades mecânicas da cartilagem septal nem das cartilagens laterais superiores ou inferiores em fluência e relaxação (características de comportamentos viscoelásticos). A determinação de propriedades mecânicas em função da frequência de oscilação e da temperatura para estes mesmos materiais através de uma análise de DMA em tensão e compressão, assim como informações gerais sobre fenómenos de degradação térmica por DSC e TGA, também não são reportados. Assim sendo, parte desta dissertação pretende preencher esta lacuna da literatura, contribuindo para a compreensão da composição e arquitetura internas da cartilagem e da especificidade dos mecanismos ativados sob influência de uma tensão ou deformação constantes. Além disso, foram levadas a cabo simulações numéricas baseadas numa formulação matemática de híper-viscoelasticidade num software de elementos finitos desenvolvido na Instituição (V-Biomech) e foram encontrados os valores dos parâmetros que permitem replicar o comportamento experimental de fluência e relaxação de cartilagens de diferentes regiões do septo nasal. Assim, uma lei constitutiva que agrega conceitos de híper-elasticidade, viscoelasticidade e permeabilidade, acoplando o distinto comportamento de materiais sólidos e fluidos, foi desenvolvida e validada. Além das simulações do comportamento viscoelástico das amostras colhidas a partir da região anterior do septo, um conjunto de outras ferramentas para aplicação dos mesmos conceitos numa geometria mais complexa foi também desenvolvido e apresentado. Um trabalho que ainda continua

Mechanical characterisation and FEM modelling of biological deformation for surgical simulation

This thesis sought to explore the use of minimally invasive surgery via biomechanical simulation of soft tissue deformation and needle path planning insertion. When surgeons are placed under mechanical stress, human brain cells exhibit the viscoelastic behaviour of solid structures. However, the behavioural mechanisms of tissues/cells are not yet fully understood, and more information is needed to reliably calculate tissue/cell deformation. The research objectives and methodologies were: First, to objectively investigate and characterise the mechanical properties of biological tissues/cells by using experimental atomic force microscopy (AFM) data (see CHAPTER 3). This method was used to analyse the cell's mechanical behaviours with a developed numerical algorithm. The difference between two human brain cells (normal HNC-2 and U87 cancer cells) was studied to determine their mechanical properties so that these could then be applied to our proposed 3D model (see CHAPTER 5). Second, using the measured experimental AFM data, a system identification of AFM characterisation was implemented in another chapter (CHAPTER 4), which for comparison, was based on a MATLAB algorithm. The results showed that the model that was identified for AFM matched the measured experimental AFM data. Third, to establish a finite element method (FEM) for real-time modelling of nonlinear soft tissue deformation behaviours using a three-dimensional (3D) dynamic nonlinear FEM; this method was developed to establish the large-range deformation of tissue/cells with second- order Piola-Kirchhoff stress (CHAPTER 5). A Newmark numerical process was implemented to solve the partial differential equations (PDEs) that resulted from the FEM. Experimental analysis of biological human brain cells was conducted to verify and validate the nonlinear FEM for simulating deformation. Fourth, to establish a method for real-time motion plan modelling of nonlinear needle deflection during needle insertion using the third objective to implement the nonlinear FEM for needle path planning. Last, to use an application of bio-heat transfer of potential needle tip path planning by applying a bioheat transfer-based method (CHAPTER 6); this method was established for optimal path planning for needle insertion in the presence of soft tissue deformation. A bio- heat transfer was used to develop a temperature distribution for path planning to reach the target and avoid obstacles in cubic, liver and brain cell models. The algorithm defines the optimal path for needle tip placement; the needle tip placement is determined by the temperature distribution, which in turn, is based on soft tissue deformation that occurs in the process of needle insertion. When force was applied during the needle penetration process, the deflection accrued was based on the geometry of nonlinear material. Based on our simulation of 3D FEM discretisation of the Pennes' Bio-heat Transfer Equation, the distribution of the temperature from single point temperature sources was performed to determine the degree of transient thermal. Furthermore, the distribution was used to model thermal stresses and strains within the cell/tissue, which result from the heat source. The main contribution to this field is building a new conceptual design methodology for characterisation of the mechanical properties of biological cells by extracts of the mechanical properties of two biological human brain cells (normal HNC-2 and cancer U87 MG cells), and the experimental use of AFM for the first time. Also, linear FEM for soft tissue/needle insertion with large deformation is developed and adapted to our three-dimensional dynamic FEM soft tissue/cell modelling using numerical integration methods. Verification of the experimental work and the proposed method is examined mathematically and systematically using a system identification schema. Moreover, bio-heat transfer for needle insertion is implemented based on the proposed FEM soft tissue deformation modelling to represent path planning. The investigation of needle insertion into soft tissue/cell deformation using bioheat transfer FEM has not been done before

Polarized cortical tension drives zebrafish epiboly movements

The principles underlying the biomechanics of morphogenesis are largely unknown. Epiboly is an essential embryonic event in which three tissues coordinate to direct the expansion of the blastoderm. How and where forces are generated during epiboly, and how these are globally coupled remains elusive. Here we developed a method, hydrodynamic regression (HR), to infer 3D pressure fields, mechanical power, and cortical surface tension profiles. HR is based on velocity measurements retrieved from 2D+T microscopy and their hydrodynamic modeling. We applied HR to identify biomechanically active structures and changes in cortex local tension during epiboly in zebrafish. Based on our results, we propose a novel physical description for epiboly, where tissue movements are directed by a polarized gradient of cortical tension. We found that this gradient relies on local contractile forces at the cortex, differences in elastic properties between cortex components and the passive transmission of forces within the yolk cell. All in all, our work identifies a novel way to physically regulate concerted cellular movements that might be instrumental for the mechanical control of many morphogenetic processes.Peer ReviewedPostprint (author's final draft

Anisotropic microsphere-based approach to damage in soft fibered tissue

The final publication is available at Springer via http://dx.doi.org/10.1007/s10237-011-0336-9An anisotropic damage model for soft fibered tissue is presented in this paper, using a multi-scale scheme and focusing on the directionally dependent behavior of these materials. For this purpose, a micro-structural or, more precisely, a microsphere-based approach is used to model the contribution of the fibers. The link between micro-structural contribution and macroscopic response is achieved by means of computational homogenization, involving numerical integration over the surface of the unit sphere. In order to deal with the distribution of the fibrils within the fiber, a von Mises probability function is incorporated, and the mechanical (phenomenological) behavior of the fibrils is defined by an exponential-type model. We will restrict ourselves to affine deformations of the network, neglecting any cross-link between fibrils and sliding between fibers and the surrounding ground matrix. Damage in the fiber bundles is introduced through a thermodynamic formulation, which is directly included in the hyperelastic model. When the fibers are stretched far from their natural state, they become damaged. The damage increases gradually due to the progressive failure of the fibrils that make up such a structure. This model has been implemented in a finite element code, and different boundary value problems are solved and discussed herein in order to test the model features. Finally, a clinical application with the material behavior obtained from actual experimental data is also presented.Peer ReviewedPostprint (author's final draft