Abstract Hip fracture is the most severe complication of osteoporosis. The occurrence of hip fracture is increasing worldwide as a result of the ageing of the population. The clinical assessment of osteoporosis and to some extent hip fracture risk is based on the measurement of bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, it has been demonstrated that most hip fractures occurring after a fall involve non-osteoporotic populations and that the geometry plays a critical role in the fracture risk assessment. A potential alternative for the assessment of hip fracture risk is finite element modelling, which is a computational method allowing simulation of mechanical loading. The aim of this study was to investigate different finite-element (FE) methods for predicting hip fracture type and eventually hip failure load in the simulation of a fall on the greater trochanter. An experimental fall on the greater trochanter was performed on over 100 cadaver femurs in order to evaluate the failure load and fracture type. In all studies, assessment of BMD, measurement of geometrical parameters and generation of finite element models were performed using DXA, digitized plain radiographs and computed tomography scans. The present study showed that geometrical parameters differ between specific hip fracture types. FE studies showed feasible accuracy in the prediction of hip fracture type, even by using homogeneous material properties. Finally, a new method to generate patient-specific volumetric finite element models automatically from a standard radiographic picture was developed. Preliminary results in the prediction of failure load and fracture type were promising when compared to experimental fractures. / Tiivistelmä Lonkkamurtuma on osteoporoosin vakavin seuraus. Lonkkamurtumatapaukset kasvavat maailmanlaajuisesti väestön ikääntymisen myötä. Osteoporoosin ja osin myös lonkkamurtumariskin kliininen arviointi perustuu luun mineraalitiheyden mittaamiseen kaksienergisellä röntgenabsorptiometrialla (Dual-energy X-ray absorptiometry, DXA). On kuitenkin osoitettu, että suurin osa kaatumisen seurauksena tapahtuvista lonkkamurtumatapauksista tapahtuu henkilöillä joilla ei ole todettua osteoporoosia, ja että myös luun muoto on tärkeä tekijä arvioitaessa lonkkamurtumariskiä. Laskennallinen mallintaminen elementtimenetelmällä mahdollistaa mekaanisen kuormituksen simuloinnin ja on potentiaalinen vaihtoehto lonkkamurtumariskin arviointiin. Tämän työn tarkoituksena on tutkia elementtimenetelmiä lonkkamurtumatyypin ja lopulta lonkan murtolujuuden ennustamiseksi simuloimalla kaatumista sivulle. Yli sataa reisiluuta kuormitettiin kokeellisesti murtolujuuden ja murtumatyypin määrittämiseksi. Luun mineraalitiheyden arviointi, muotoparametrien mittaus ja elementtimallit tehtiin käyttäen DXA:a, digitalisoituja röntgenkuvia ja tietokonetomografiakuvia. Tämä tutkimus osoittaa, että luun muotoparametrit vaihtelevat eri lonkkamurtumatyyppien välillä. Lonkkamurtumatyyppi voitiin ennustaa hyvällä tarkkuudella elementtimenetelmän avulla silloinkin, kun käytettiin homogeenisia materiaaliominaisuuksia. Lopuksi kehitettiin uusi menetelmä yksilöllisten kolmiulotteisten elementtimallien automaattiseen luontiin tavallisista röntgenkuvista. Alustavat tulokset lonkan murtolujuuden ja murtumatyypin ennustamisessa ovat lupaavia.

L’Ostéotomie Tibiale de Valgisation (OTV) par ouverture médiale est un traitement conservatif efficace dans le traitement de la gonarthrose médiale chez le patient jeune et actif présentant un défaut d’alignement du membre inférieur. Ce défaut entraine un déséquilibre dans la répartition des charges transitant dans le genou et est un facteur de risque la gonarthrose. L’objectif est de corriger l’alignement en corrigeant une déformation osseuse du tibia proximal. Une coupe osseuse médiolatérale incomplète partant du bord médial de la métaphyse tibiale et orientée vers l’articulation tibio-fibulaire permet de créer une ouverture sur le bord médial par rotation autour de la charnière latérale, épaisseur d’os non-coupée sur le bord latéral. L’importance de l’ouverture dépend de la déformation osseuse et du stade d’arthrose. La réussite de l’OTV par ouverture médiale est conditionnée par une correction précise, un montage d’ostéosynthèse stable et une charnière latérale préservée pendant l’ouverture. L’objectif de cette thèse était de proposer une méthodologie de planification préopératoire à associer à une instrumentation patient-spécifique réalisée en impression 3D. Cette instrumentation devait permettre d’appliquer la correction souhaitée dans les plans frontal et sagittal mais aussi de préserver la charnière latérale pendant la chirurgie. Nos résultats ont montré, grâce aux études in-vitro et in-vivo réalisées au cours de la thèse, que le guide de coupe patient-spécifique développé permet de reproduire avec précision la planification préopératoire en apportant de la sécurité au geste opératoire tant au niveau de la précision que de la préservation de la charnière latérale. / Medial Opening Wedge High Tibial Osteotomy (MOWHTO) is an efficient conservative surgical treatment for young and active patients with moderate medial gonarthrosis and varus lower limb malalignment. Varus malalignment unbalances load distribution in the knee, which is a gonarthrosis risk factor. MOWHTO aims to correct the lower limb alignment by correcting the proximal tibia bony deformity. Incomplete mediolateral cut is performed in the proximal tibia from the medial side of the tibial metaphysis towards the tibiofibular joint, and then opened by rotation around the lateral hinge which is the remaining uncut bone thickness on the lateral side. Amount of the opening depends on the importance of the proximal tibial deformity and on the medial gonarthrosis stage. MOWHTO success remains on precise correction, stable osteosynthesis system and lateral hinge preservation during the opening. Objective of this thesis was to propose a preoperative planning methodology to be associated with 3D printed patientspecific instrumentation. This instrumentation was intended to apply the correction chosen by the surgeon in the frontal and sagittal planes, but also to preserve the lateral hinge during the surgery. Our in-vitro and in-vivo results have shown that the developed patient-specific cutting guide make it possible to accurately reproduce the preoperative planning with security to the surgical gesture by bringing accuracy and lateral hinge preservation.

La sensibilité des cellules de mélanomes aux molécules de thérapies ciblées dépend du microenvironnement tumoral (interactions cellule-cellule et cellule-matrice extracellulaire). Les systèmes tridimensionnels (3D) de culture in vitro reflètent mieux l’architecture structurelle native des tissus et sont attrayants pour l’étude des interactions cellulaires. Nous avons développé et comparé plusieurs modèles de mélanome métastatique : les cellules de mélanomes (SK-MEL-28 et SK-MEL-3, mutées BRAF V600E et SK-MEL-2, BRAF sauvages) cultivées en monocouche (2D) et co-cultivées en 3D sur des équivalents de derme avec des fibroblastes, afin de mieux comprendre les facteurs modulant la sensibilité cellulaire à un inhibiteur de BRAF (BRAFi, Vémurafenib) et au Vémurafenib associé à un inhibiteur de MEK (MEKi, Cobimetinib). La sensibilité cellulaire aux traitements a été évaluée sous différents aspects : prolifération cellulaire (numération cellulaire, incorporation d'EdU, test MTS), analyse des voies de signalisation MAPK et PKB / Akt (Western-blot), apoptose (TUNEL), libération de cytokines et de facteurs de croissance (ELISA) et histologie (modèles 3D). Un effet cytostatique de BRAFi a été observé sur les cellules SK-MEL-28 et SK-MEL-3 cultivées dans les modèles 2D et 3D. La lignée cellulaire SK-MEL-2 était résistante au BRAFi lorsqu'elle a été cultivée en monocouche, mais sensible lorsqu'elle a été co-cultivée avec des fibroblastes incorporés dans une matrice de collagène de type I. Les milieux conditionnés par les fibroblastes 3D (équivalents de derme) ont sensibilisé les cellules SK-MEL-2 (2D) au BRAFi. L'analyse des surnageants de culture cellulaire a révélé que les équivalents de derme libéraient certains facteurs solubles (IL-6, IL-8, HGF, TGF-β) : ces sécrétions ont été modifiées au cours du traitement par Vémurafenib. La combinaison du traitement avec MEKi a renforcé l'action du Vémurafenib sur les cellules de mélanomes métastatiques tout en diminuant la capacité de prolifération des fibroblastes. Des populations de cellules contenant des cellules de mélanomes ou des fibroblastes associés au cancer (CAFs) ont été isolées à partir d'une biopsie de métastase cutanée provenant d'une patiente atteinte d'un mélanome métastatique. Ces cellules ont permis de réaliser des modèles de mélanome métastatique patient-spécifique afin d’étudier in vitro la sensibilité des cellules de la patiente aux traitements dans un microenvironnement tumoral (sécrétion paracrine de cellules stromales et matrice de collagène). Ces modèles prédictifs 3D patient-spécifique pourront être utilisés pour déterminer des stratégies de thérapies personnalisées, ainsi que pour comprendre les phénomènes de résistance des cellules de mélanomes aux traitements. / Melanoma cell sensitivity to targeted therapy molecules is dependent on the tumor microenvironment (cell-cell and cell-extracellular matrix interactions). Three dimensional (3D) in vitro cell culture systems better reflect the native structural architecture of tissues and are attractive to investigate cellular interactions. We have developed and compared several metastatic melanoma models: melanoma cells (SK-MEL-28 and SK-MEL-3, BRAF V600E mutant and SK-MEL-2 BRAF wt) cultured as a monolayer (2D) and co-cultured on 3D dermal equivalents with fibroblasts to better unravel factors modulating cell sensitivity to a BRAF inhibitor (BRAFi, Vemurafenib) and a BRAFi combined with a MEK inhibitor (MEKi, Cobimetinib). Cell sensitivity to treatments was evaluated under various aspects: cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK and PKB/Akt signaling pathway analysis (Western-blotting), apoptosis (TUNEL), cytokine and growth factor release (ELISA) and histology (3D models). A cytostatic effect of BRAFi was observed on SK-MEL-28 and SK-MEL-3 cells in both models. SK-MEL-2 cell line was clearly resistant to BRAFi when cultured as a monolayer but not when co-cultured with 3D fibroblasts embedded in a type I collagen matrix. Conditioned media provided by 3D fibroblasts (dermal equivalents) underlined 2D SK-MEL-2 sensitivity to BRAFi. Cell culture supernatant analysis revealed that dermal equivalents released some soluble factors (IL-6, IL-8, HGF, TGF-β): these secretions were modified during vemurafenib treatment. The combination of treatment with MEKi enhances the action of Vemurafenib on metastatic melanoma cells while decreasing the proliferation capacity of fibroblasts. Cell populations containing melanoma cells or fibroblasts associated with cancer (CAFs) were isolated from a cutaneous metastasis biopsy of a patient with metastatic melanoma. These cells allowed the realization of patient-specific models of metastatic melanoma in order to study in vitro the sensitivity of the patient’s melanoma cells to treatments in a tumor microenvironment (paracrine secretion of stromal cells and collagen matrix). These 3D predictive patient-specific models could be used to determine personalized therapy strategies, as well as to understand the resistance phenomena of melanoma cells to treatments

No description available.

No description available.

Se cree que la medicina in silico supondrá uno de los cambios más disruptivos en el futuro próximo. A lo largo de la última década se ha invertido un gran esfuerzo en el desarrollo de modelos computacionales predictivos para mejorar el poder de diagnóstico de los médicos y la efectividad de las terapias. Un punto clave de esta revolución, será la personalización, que conlleva en la mayoría de los casos, la creación de modelos computacionales específicos de paciente, también llamados gemelos digitales. Esta práctica está actualmente extendida en la investigación y existen en el mercado varias herramientas de software que permiten obtener modelos a partir de imágenes. A pesar de eso, para poderse usar en la práctica clínica, estos métodos se necesita reducir drásticamente el tiempo y el trabajo humano necesarios para la creación de los modelos numéricos. Esta tésis se centra en la propuesta de la versión basada en imágenes del Cartesian grid Finite Element Method (cgFEM), una técnica para obtener de forma automática modelos a partir de imágenes y llevar a cabo análisis estructurales lineales de huesos, implantes o materiales heterogéneos. En la técnica propuesta, tras relacionar la escala de los datos de la imágen con valores de propiedades mecánicas, se usa toda la información contenida en los píxeles para evaluar las matrices de rigidez de los elementos que homogenizan el comportamiento elástico de los grupos de píxeles contenidos en cada elemento. Se h-adapta una malla cartesiana inicialmente uniforme a las características de la imágen usando un procedimiento eficiente que tiene en cuenta las propiedades elásticas locales asociadas a los valores de los píxeles. Con eso, se evita un suavizado excesivo de las propiedades elásticas debido a la integración de los elementos en áreas altamente heterogéneas, pero, no obstante, se obtienen modelos finales con un número razonable de grados de libertad. El resultado de este proceso es una malla no conforme en la que se impone la continudad C0 de la solución mediante restricciones multi-punto en los hanging nodes. Contrariamente a los procedimientos estandar para la creación de modelos de Elementos Finitos a partir de imágenes, que normalmente requieren la definición completa y watertight de la geometrá y tratan el resultado como un CAD estandar, con cgFEM no es necesario definir ninguna entidad geométrica dado que el procedimiento propuesto conduce a una definición implícita de los contornos. Sin embargo, es inmediato incluirlas en el modelo en el caso de que sea necesario, como por ejemplo superficies suaves para imponer condiciones de contorno de forma más precisa o volúmenes CAD de dispositivos para la simulación de implantes. Como consecuencia de eso, la cantidad de trabajo humano para la creación de modelos se reduce drásticamente. En esta tesis, se analiza en detalles el comportamiento del nuevo método en problemas 2D y 3D a partir de CT-scan y radiográfias sintéticas y reales, centrandose en tres clases de problemas. Estos incluyen la simulación de huesos, la caracterización de materiales a partir de TACs, para lo cual se ha desarrollado la cgFEM virtual characterisation technique, y el análisis estructural de futuros implantes, aprovechando la capacidad del cgFEM de combinar fácilmente imágenes y modelos de CAD. / Es creu que la medicina in silico suposarà un dels canvis més disruptius en el futur pròxim. Al llarg de l'última dècada, s'ha invertit un gran esforç en el desenvolupament de models computacionals predictius per millorar el poder de diagnòstic dels metges i l'efectivitat de les teràpies. Un punt clau d'aquesta revolució, serà la personalització, que comporta en la majoria dels casos la creació de models computacionals específics de pacient. Aquesta pràctica està actualment estesa en la investigació i hi ha al mercat diversos software que permeten obtenir models a partir d'imatges. Tot i això, per a poder-se utilitzar en la pràctica clínica aquests métodes es necessita reduir dràsticament el temps i el treball humà necessaris per a la seva creació. Aquesta tesi es centra en la proposta d'una versió basada en imatges del Cartesian grid Finite Element Method (cgFEM), una técnica per obtenir de forma automàticament models a partir d'imatges i dur a terme anàlisis estructurals lineals d'ossos, implants o materials heterogenis. Després de relacionar l'escala del imatge a propietats macàniques corresponents, s'usa tota la informació continguda en els píxels per a integrar les matrius de rigidesa dels elements que homogeneïtzen el comportament elàstic dels grups de píxels continguts en cada element. Es emphh-adapta una malla inicialment uniforme a les característiques de la imatge usant un procediment eficient que té en compte les propietats elàstiques locals associades als valors dels píxels. Amb això, s'evita un suavitzat excessiu de les propietats elàstiques a causa de la integració dels elements en àrees altament heterogénies, però, tot i això, s'obtenen models finals amb un nombre raonable de graus de llibertat. El resultat d'aquest procés és una malla no conforme en la qual s'imposa la continuïtat C0 de la solució mitjançant restriccions multi-punt en els hanging nodes. Contràriament als procediments estàndard per a la creació de models d'Elements finits a partir d'imatges, que normalment requereixen la definició completa i watertight de la geometria i tracten el resultat com un CAD estàndard, amb cgFEM no cal definir cap entitat geométrica. No obstant això, és immediat incloure-les en el model en el cas que sigui necessari, com ara superfícies suaus per imposar condicions de contorn de forma més precisa o volums CAD de dispositius per a la simulació d'implants. Com a conseqüéncia d'això, la quantitat de treball humà per a la creació de models es redueix dràsticament. En aquesta tesi, s'analitza en detalls el comportament del nou métode en problemes 2D i 3D a partir de CT-scan i radiografies sintétiques i reals, centrant-se en tres classes de problemes. Aquestes inclouen la simulació d'ossos, la caracterització de materials a partir de TACs, per a la qual s'ha desenvolupat la cgFEM virtual characterisation technique, i l'anàlisi estructural de futurs implants, aprofitant la capacitat del cgFEM de combinar fàcilment imatges i models de CAD. / In silico medicine is believed to be one of the most disruptive changes in the near future. A great effort has been carried out during the last decade to develop predicting computational models to increase the diagnostic capabilities of medical doctors and the effectiveness of therapies. One of the key points of this revolution, will be personalisation, which means in most of the cases creating patient specific computational models, also called digital twins. This practice is currently wide-spread in research and there are quite a few software products in the market to obtain models from images. Nevertheless, in order to be usable in the clinical practice, these methods have to drastically reduce the time and human intervention required for the creation of the numerical models. This thesis focuses on the proposal of image-based Cartesian grid Finite Element Method (cgFEM), a technique to automatically obtain numerical models from images and carry out linear structural analyses of bone, implants or heterogeneous materials. In the method proposed in this thesis, after relating the image scale to corresponding elastic properties, all the pixel information will be used for the integration of the element stiffness matrices, which homogenise the elastic behaviour of the groups of pixels contained in each element. An initial uniform Cartesian mesh is h-adapted to the image characteristics by using an efficient refinement procedure which takes into account the local elastic properties associated to the pixel values. Doing so we avoid an excessive elastic property smoothing due to element integration in highly heterogeneous areas, but, nonetheless obtain final models with a reasonable number of degrees of freedom. The result of the process is non-conforming mesh in which C0 continuity is enforced via multipoint constraints at the hanging nodes. In contrast to the standard procedures for the creation of Finite Element models from images, which usually require a complete and watertight definition of the geometry and treat the result as a standard CAD, with cgFEM it is not necessary to define any geometrical entity, as the procedure proposed leads to an implicit definition of the boundaries. Nonetheless, they are straightforward to include in the model if necessary, such as smooth surfaces to impose the boundary conditions more precisely or CAD device volumes for the simulation of implants. As a consequence, the amount of human work required for the creation of the numerical models is drastically reduced. In this thesis, we analyse in detail the new method behaviour in 2D and 3D problems from CT-scans and X-ray images and synthetic images, focusing on three classes of problems. These include the simulation of bones, the material characterisation of solid foams from CT scans, for which we developed the cgFEM virtual characterisation technique, and the structural analysis of future implants, taking advantage of the capability of cgFEM to easily mix images and CAD models. / Giovannelli, L. (2018). Direct creation of patient-specific Finite Element models from medical images and preoperative prosthetic implant simulation using h-adaptive Cartesian grids [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/113644

This thesis deals with the analysis of brain function in Magnetic Resonance Imaging (MRI) using two sequences: BOLD functional MRI (fMRI) and Arterial Spin Labelling (ASL). In this context, group statistical analyses are of great importance in order to understand the general mechanisms underlying a pathology, but there is also an increasing interest towards patient-specific analyses that draw conclusions at the patient level. Both group and patient-specific analyses are studied in this thesis. We first introduce a group analysis in BOLD fMRI for the study of specific language impairment, a pathology that was very little investigated in neuroimaging. We outline atypical patterns of functional activity and lateralisation in language regions. Then, we move forward to patient-specific analysis. We propose the use of robust estimators to compute cerebral blood flow maps in ASL. Then, we analyse the validity of the assumptions underlying standard statistical analyses in the context of ASL. Finally, we propose a new locally multivariate statistical method based on an a contrario approach and apply it to the detection of atypical patterns of perfusion in ASL and to activation detection in BOLD functional MRI.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / FAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas Gerais / O tratamento endodôntico associado à restauração direta com resina composta tem sido utilizado para restaurar molares severamente destruídos em pacientes jovens. O objetivo deste estudo foi avaliar o efeito de diferentes níveis de perda de estrutura dentária antes e após a realização de tratamento endodôntico e restauração com resina composta bulk fill na distribuição de tensões e magnitude da força de mordida. Foram selecionados três pacientes jovens (9, 10 and 12 anos de idade) com primeiros molares com cárie extensa e envolvimento pulpar com diferentes níveis de perdas de estrutura dentária: PI, manutenção das duas cristas marginais e de todas as cúspides; PII, manutenção de pelo menos uma crista marginal e perda mínima de uma cúspide; e PIII, perda de ambas as cristas marginais, mantendo apenas as cúspides vestibulares. Os molares foram tratados endodonticamente utilizando técnica de instrumentação rotatória e obturados com guta-percha e cimento AHPlus (Dentsply) e em seguida foram restaurados com Filtek Bulk Fill Posterior (3M ESPE). A força de mordida em Newtons (N) foi mensurada antes e após a intervenção endodôntica e restauradora na posição habitual de oclusal usando aparelho de força de mordida por meio de uma célula de carga (Kratos). Tomografias computadorizadas cone beam foram realizadas antes e após o procedimento endodôntico/restaurador, e arquivos DICOM (.dcm) foram exportados para o software Mimics, 3-Matic (Materialize) e Patran (MSC Software) para criação dos modelos específicos dos pacientes nos dois momentos experimentais. A aplicação de carga foi simulada por contato oclusal dos dentes antagonistas nas cargas mensuradas clinicamente em cada momento. Nos modelos que representam as condições iniciais foram aplicados tanto os valores de força de mordida (N) mensurados no momento inicial quanto após o procedimento reabilitador: PI. 30,1/136,6; PII. 34,3/133,4 e PIII. 47,9/124,1 e para os modelos que representam a condição final foram utilizados os valores obtidos após a intervenção endodôntica e restauradora: PI. 136,6; PII. 133,4 e PIII. 124,1. As restaurações foram avaliadas após 2 anos. Após intervenção endodôntica e restauradora a força de mordida aumentou em 260% (de 36,7±11,6 para 12 131,9±17,8). Antes da intervenção endodôntica e restauradora, as tensões se concentraram na estrutura coronal e, após a reabilitação foram transferidas de forma homogênea para a dentina radicular, independente do nível de perda de estrutura dentária. Quando a carga final foi aplicada nos modelos de condições iniciais, evidenciou-se elevada concentração de tensão em áreas enfraquecidas e na região de furca. As restaurações apresentaram desempenho adequado após 2 anos. A presença de cárie extensa com envolvimento pulpar afetou negativamente a carga de mordida e aumentou a concentração de tensão na estrutura frágil o que pode favorecer à ocorrência de fratura dental. O tratamento endodôntico associado à restauração direta em resina composta bulk fill demonstrou ser um método eficiente para restabelecer o desempenho mastigatório e a eficiência biomecânica dos molares jovens com comprometimento severo da estrutura coronária. / Endodontic treatment (ETT) followed by direct composite resin restoration has been used for rehabilitating the severely damage molar teeth in young patients. The aim of this study was to evaluate the effect of the molar teeth with different levels of the dental structure loss before and after the ETT and direct restoration with bulk fill resin composite on the stress distribution and the bite force magnitude. Three young patients (with 9, 10 and 12 years old), with the first mandibular molar teeth with deep occlusal caries with pulp involvement were selected attending with different levels of the dental structure loss: PI, both marginal ridge and all cusps; PII, maintenance of one marginal ridge and loss of one cusp; and PIII, loss of both marginal ridge, maintaining only buccal cusps. ETT was restored using Filtek Bulk Fill Posterior (3M ESPE). The bite forces in Newtons were measured initially and postoperatively for all teeth in habitual bite force using a miniload cell. Cone-beam tomography imaging was performed, and the Digital Imaging and Communication in Medice (.dcm) files were exported to Mimics, 3-Matic (Materialise) and Patran (MSC Software) software to create a patient-specific FEA models. Bite load was carry out using contact load applied by antagonist teeth in two moments: without ETT and restoration: PI. 30.1/136.6; PII. 34.3/133.4 and PIII. 47.9/124.1; and after restorative procedure: PI. 136.6; PII. 133.4 and PIII. 124.1 N. Performing ETT and bulk fill resin composite restoration the bite load increased 260% (36.7±11.6) to 131.9±17.8). The restorations were evaluated after 2 years. Before rehabilitation the stresses concentrated on weakened coronal dental structure and after rehabilitation they were homogeneously transferred to root dentin, irrespective of the level of the tooth structure loss. When the postoperatively bite load was applied on nontreated tooth models, high stress concentration on weakened areas was verified. The restorations performed perfectly after 2 years. The extensive caries with pulp involvement affected negatively the bite load and increased the stress concentration on weakened areas and at furcation favoring the tooth fracture. The ETT and bulk fill resin composite restoration showed to be an efficient method for rehabilitate the biomechanical performance of molar teeth of young patients severely compromised structurally. / Dissertação (Mestrado)

L'ablation par radiofréquence (ARF) de tumeurs abdominales est rendue difficile par l’influence des vaisseaux sanguins et les variations de la conductivité thermique, compliquant la planification spécifique à un patient donné. En fournissant des outils prédictifs, les modèles biophysiques pourraient aider les cliniciens à planifier et guider efficacement la procédure. Nous introduisons un modèle mathématique détaillé des mécanismes impliqués dans l’ARF des tumeurs du foie comme la diffusion de la chaleur et la nécrose cellulaire. Il simule l’étendue de l’ablation à partir d’images médicales, d’après lesquelles des modèles personnalisés du foie, des vaisseaux visibles et des tumeurs sont segmentés. Dans cette thèse, une nouvelle approche pour résoudre ces équations basée sur la méthode de Lattice Boltzmann est introduite. Le modèle est d’abord évalué sur des données de patients qui ont subi une ARF de tumeurs du foie. Ensuite, un protocole expérimental combinant des images multi-modales, anatomiques et fonctionnelles pré- et post-opératoires, ainsi que le suivi de la température et de la puissance délivrée pendant l'intervention est présenté. Il permet une validation totale du modèle qui considère des données les plus complètes possibles. Enfin, nous estimons automatiquement des paramètres personnalisés pour mieux prédire l'étendu de l’ablation. Cette stratégie a été validée sur 7 ablations dans 3 cas cliniques. A partir de l'étude préclinique, la personnalisation est améliorée en comparant les simulations avec les mesures faites durant la procédure. Ces contributions ont abouti à des résultats prometteurs, et ouvrent de nouvelles perspectives pour planifier et guider l’ARF. / The outcome of radiofrequency ablation (RFA) of abdominal tumors is challenged by the presence of blood vessels and time-varying thermal conductivity, which make patient-specific planning extremely difficult. By providing predictive tools, biophysical models may help clinicians to plan and guide the procedure for an effective treatment. We introduce a detailed computational model of the biophysical mechanisms involved in RFA of hepatic tumors such as heat diffusion and cellular necrosis. It simulates the extent of ablated tissue based on medical images, from which patient-specific models of the liver, visible vessels and tumors are segmented. In this thesis, a new approach for solving these partial differential equations based on the Lattice Boltzmann Method is introduced. The model is first evaluated against clinical data of patients who underwent RFA of liver tumors. Then, a comprehensive pre-clinical experiment that combines multi-modal, pre- and post-operative anatomical and functional images, as well as the interventional monitoring of the temperature and delivered power is presented. This enables an end-to-end validation framework that considers the most comprehensive data set for model validation. Then, we automatically estimate patient-specific parameters to better predict the ablated tissue. This personalization strategy has been validated on 7 ablations from 3 clinical cases. From the pre-clinical study, we can go further in the personalization by comparing the simulated temperature and delivered power with the actual measurements during the procedure. These contributions have led to promising results, and open new perspectives in RFA guidance and planning.

[ES] El acceso a una atención sanitaria de alta calidad es un marcador importante del desarrollo de las sociedades humanas. Los aportes tecnológicos a la medicina han mostrado un potencial relevante para descubrir procedimientos efectivos a nivel preventivo, diagnóstico y terapéutico. En particular, los métodos computacionales permiten el procesamiento eficaz de datos médicos y, por tanto, pueden modelar sistemas biológicos complejos. Esto ha influido en el desarrollo de la Medicina Personalizada (MP) durante las últimas décadas, donde la obtención de conocimiento específico de cada caso permite realizar intervenciones a medida, todo ello a un coste de recursos accesible. La simulación de remodelación ósea es un campo prometedor en el contexto de la MP. Predecir un proceso de adaptación ósea en un caso concreto puede dar lugar a numerosas aplicaciones en el campo de las enfermedades óseas, tanto a nivel clínico como experimental. Mediante la combinación del Método de Elementos Finitos (FEM) y los algoritmos de remodelación ósea, es posible obtener modelos numéricos de un hueso específico a partir de datos médicos (por ejemplo, una tomografía computarizada). Todo ello puede dar lugar a una revolución en la medicina personalizada. / [CA] L'accés a una atenció sanitària d'alta qualitat és un marcador important del desenvolupament de les societats humanes. Les aportacions tecnològiques a la medicina han mostrat un potencial rellevant per a descobrir procediments efectius a nivell preventiu, diagnòstic i terapèutic. En particular, els mètodes computacionals permeten el processament eficaç de dades mèdiques i, per tant, poden modelar sistemes biològics complexos. Això ha influït en el desenvolupament de la Medicina Personalitzada (MP) durant les últimes dècades, on l'obtenció de coneixement específic de cada cas permet realitzar intervencions a mesura, tot això a un cost de recursos accessible. La simulació de remodelació òssia és un camp prometedor en el context de la MP. Predir un procés d'adaptació òssia en un cas concret pot donar lloc a nombroses aplicacions en el camp de les malalties òssies, tant a nivell clínic com experimental. Mitjançant la combinació del Mètode d'Elements Finits (*FEM) i els algorismes de remodelació òssia, és possible obtindre models numèrics d'un os específic a partir de dades mèdiques (per exemple, una tomografia computada). Tot això pot donar lloc a una revolució en la medicina personalitzada. / [EN] Access to high-quality healthcare is an important marker of the development of human societies. Technological contributions to medicine have shown relevant potential to discover effective procedures at a preventive, diagnostic and therapeutic level. In particular, computational methods enable efficient processing of medical data and can therefore model complex biological systems. This has influenced the development of Personalized Medicine (PM) over recent decades, where obtaining specific knowledge of each case allows for tailored interventions, all at an affordable resource cost. Simulation of bone remodeling is a promising field in the context of PM. Predicting a bone adaptation process in a specific case can lead to numerous applications in the field of bone diseases, both clinically and experimentally. By combining the Finite Element Method (FEM) and bone remodeling algorithms, it is possible to obtain numerical models of a specific bone from medical data (for example, a CT scan). All of this can lead to a revolution in personalized medicine. / Thanks to the Valencian funding programme FDGENT/2018, for providing economic resources to develop this long-term work. / Gutiérrez Gil, J. (2023). Personalization of Bone Remodelling Simulation Models for Clinical Applications [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/202059