<p>The prediction and characterisation of chemical and biochemical processes are fundamental tasks in computational chemistry. Small chemical systems can be characterised by the stationary points on potential energy surface and reaction paths linking them. For large biological systems, statistical sampling is required to characterising their average properties.</p> <p>This thesis presents my Ph.D. work on developing new methods to predict and characterise chemical and biological processes. Two path-finding methods for finding the minimum energy reaction path and alternative reaction paths for small gas-phase reactions have been elucidated with examples, and molecular dynamic simulations have been used to characterise the binding affinity of protein-ligand complex and the free energy of protonation processes in a protein.</p> <p>Specifically, the fast marching method (FMM) has been used to find the minimum energy path (MEP) on the potential energy surface (PES) for small gas-phase reactions. In this thesis, FMM is shown to be one of the most general and reliable surface-walking algorithms for finding the MEP. However, it is an expensive method. Some improvements have been illustrated in chapter 2 and chapter 3.</p> <p>I also proposed a new method (called QSM-NT) for finding all stationary points, accordingly all alternative reaction paths on the PES. Unlike other path-finding methods, QSM-NT overcomes the need of an initial guess of the path, and it can find all stationary points on the PES. QSM-NT has been proven to be efficient and reliable through applications on analytical PES and real chemical reaction. The difficulties and pitfalls associated with QSM-NT have been elucidated with examples.</p> <p>Molecular dynamic (MD) simulation and associated postprocessing procedures have been used to study the binding properties of caffeine-A_2A complex. The binding affinities of different binding modes have been calculated using MM/PBSA method. The binding pocket has been characterised with MM/GBSA energy decomposition. Our computational work provides significant insight to the targeted drug design of the adenosine A_2A receptor.</p> <p>The pH-dependent properties of a protein play important roles in the fundamental biological processes. The protonation states, namely, the pK_a values of ionisable residues, especially active-site residues are the prerequisites to understanding of the mechanisms of many biological processes. In this thesis, acetoacetate decarboxylase (AADase) is used as a test case for studying different types of pK_a prediction methods. Our computational results have shown that the site-site interactions from other ionisable residues are crucial to the pK_a prediction of the target residue.</p> <p>This thesis covers the range from small gas phase reaction prediction to large complex biological systems characterisation using quantum mechanical and molecular mechanical methods.</p> / Doctor of Philosophy (PhD)

Diffusion Tensor Magnetic Resonance Imaging (DT-MRI), also known as Diffusion Tensor Imaging (DTI), is a unique medical imaging modality that provides non-invasive estimates of White Matter (WM) connectivity based on local principal directions of anisotropic water diffusion. DTI tractography estimates are a macroscopically sampled description of underlying microscopic structure, and are therefore of limited validity. The under-sampling of underlying white matter structure in DTI data gives rise to Intra-Voxel Orientational Heterogeneity (IVOH), a condition in which white matter structures of multiple different orientations are averaged into a single DTI voxel sample, causing a loss of validity in the diffusion tensor model. Fast Marching Tractography (FMT) algorithms based on fast marching level set methods have been proposed to better handle the presence of IVOH in DTI data when compared to older Streamline Tractography (SLT) methods. However, the actual performance advantage of any tractography algorithm over another cannot be conclusively stated until a ground truth standard of comparison is developed. This work develops an optimized version of the FMT algorithm that is dubbed the Front Propagation Tractography (FPT) algorithm. The FPT algorithm includes unique approaches to the speed function, connectivity estimation, and likelihood estimation components of the FMT framework. The performance of the FPT algorithm is compared against the SLT algorithm using ground truth software phantom data and human brain data. Software phantom ground truth experiments compare the performance of each algorithm in single tract and crossing tract structures for varying levels of diffusion tensor field perturbation. Human brain estimates in the corpus callosum yield qualitative comparisons from inspection of 3D visualizations. A final area of exploration is the construction and analysis of a ground truth physical DTI phantom manifesting IVOH. / Master of Science

L'imagerie intravasculaire ultrasonore (IVUS) est une technologie médicale par cathéter qui produit des images de coupe des vaisseaux sanguins. Elle permet de quantifier et d'étudier la morphologie de plaques d'athérosclérose en plus de visualiser la structure des vaisseaux sanguins (lumière, intima, plaque, média et adventice) en trois dimensions. Depuis quelques années, cette méthode d'imagerie est devenue un outil de choix en recherche aussi bien qu'en clinique pour l'étude de la maladie athérosclérotique. L'imagerie IVUS est par contre affectée par des artéfacts associés aux caractéristiques des capteurs ultrasonores, par la présence de cônes d'ombre causés par les calcifications ou des artères collatérales, par des plaques dont le rendu est hétérogène ou par le chatoiement ultrasonore (speckle) sanguin. L'analyse automatisée de séquences IVUS de grande taille représente donc un défi important. Une méthode de segmentation en trois dimensions (3D) basée sur l'algorithme du fast-marching à interfaces multiples est présentée. La segmentation utilise des attributs des régions et contours des images IVUS. En effet, une nouvelle fonction de vitesse de propagation des interfaces combinant les fonctions de densité de probabilité des tons de gris des composants de la paroi vasculaire et le gradient des intensités est proposée. La segmentation est grandement automatisée puisque la lumière du vaisseau est détectée de façon entièrement automatique. Dans une procédure d'initialisation originale, un minimum d'interactions est nécessaire lorsque les contours initiaux de la paroi externe du vaisseau calculés automatiquement sont proposés à l'utilisateur pour acceptation ou correction sur un nombre limité d'images de coupe longitudinale. La segmentation a été validée à l'aide de séquences IVUS in vivo provenant d'artères fémorales provenant de différents sous-groupes d'acquisitions, c'est-à-dire pré-angioplastie par ballon, post-intervention et à un examen de contrôle 1 an suivant l'intervention. Les résultats ont été comparés avec des contours étalons tracés manuellement par différents experts en analyse d'images IVUS. Les contours de la lumière et de la paroi externe du vaisseau détectés selon la méthode du fast-marching sont en accord avec les tracés manuels des experts puisque les mesures d'aire sont similaires et les différences point-à-point entre les contours sont faibles. De plus, la segmentation par fast-marching 3D s'est effectuée en un temps grandement réduit comparativement à l'analyse manuelle. Il s'agit de la première étude rapportée dans la littérature qui évalue la performance de la segmentation sur différents types d'acquisition IVUS. En conclusion, la segmentation par fast-marching combinant les informations des distributions de tons de gris et du gradient des intensités des images est précise et efficace pour l'analyse de séquences IVUS de grandes tailles. Un outil de segmentation robuste pourrait devenir largement répandu pour la tâche ardue et fastidieuse qu'est l'analyse de ce type d'images. / Intravascular ultrasound (IVUS) is a catheter based medical imaging technique that produces cross-sectional images of blood vessels. These images provide quantitative assessment of the vascular wall, information about the nature of atherosclerotic lesions as well as the plaque shape and size. Over the past few years, this medical imaging modality has become a useful tool in research and clinical applications, particularly in atherosclerotic disease studies. However, IVUS imaging is subject to catheter ring-down artifacts, missing vessel parts due to calcification shadowing or side-branches, heterogeneously looking plaques and ultrasonic speckle from blood. The automated analysis of large IVUS data sets thus represents an important challenge. A three-dimensional segmentation algorithm based on the multiple interface fast-marching method is presented. The segmentation is based on region and contour features of the IVUS images: a new speed fonction for the interface propagation that combines the probability density functions (PDFs) of the vessel wall components and the intensity gradients is proposed. The segmentation is highly automated with the detection of the lumen boundary that is fully automatic. Minimal interactions are necessary with a novel initialization procedure since initial contours of the external vessel wall border are also computed automatically on a limited number of longitudinal images and then proposed to the user for acceptance or correction. The segmentation method was validated with in-vivo IVUS data sets acquired from femoral arteries. This database contained 3 subgroups: pullbacks acquired before balloon angioplasty, after the intervention and at a 1 year follow-up examination. Results were compared with validation contours that were manually traced by different experts in IVUS image analysis. The lumen and external wall boundaries detected with the fast-marching method are in agreement with the experts' manually traced contours with similarly found area measurements and small point-to-point contour differences. In addition, the 3D fast-marching segmentation method dramatically reduced the analysis time compared to manual tracing. Such a valdiation study, with comparison between pre- and post-intervention data, has never been reported in the IVUS segmentation literature. In conclusion, the fast-marching method combining the information on the gray level distributions and intensity gradients of the images is precise and efficient to analyze large IVUS sequences. It is hoped that the fast-marching method will become a widely used tool for the fastidious and difficult task of IVUS image processing.

La simulation numérique est indissociable du calcul haute performance. Ces vingt dernières années,l'informatique a connu l'émergence d'architectures parallèles multi-niveaux. Exploiter efficacement lapuissance de calcul de ces machines peut s'avérer être une tâche délicate et requérir une expertise à la foistechnologique sur des notions avancées de parallélisme ainsi que scientifique de part la nature même desproblèmes traités.Le travail de cette thèse est pluri-disciplinaire s'appuyant sur la conception d'une librairie de calculparallèle réutilisable pour la résolution des équations Hamilton-Jacobi-Bellman. Ces équations peuventse retrouver dans des domaines diverses et variés tels qu'en biomédical, géophysique, ou encore robotiqueen l'occurence sur les applications de planification de mouvement et de reconstruction de formestri-dimensionnelles à partir d'images bi-dimensionnelles. Nous montrons que les principaux algorithmesnumériques amenant a résoudre ces équations telles que les méthodes de type fast marching, ne sont pasappropriés pour être efficaces dans un contexte parallèle. Nous proposons la méthode buffered fast iterativequi permet d'obtenir une scalabilité parallèle non obtenue jusqu'alors. Un des points sensibles relevésdans cette thèse est de parvenir à trouver une recette de compromis entre abstraction, performance etmaintenabilité afin de garantir non seulement une réutilisabilitédans le sens classique du domaine de génielogiciel mais également en terme de réutilisabilité séquentielle/parallèle / Numerical simulation is strongly bound with high performance computing. Programming scientificsoftwares requires at the same time good knowledge on the mathematical numerical models and alsoon the techniques to make them efficient on today's computers. Indeed, these last twenty years, wehave experienced the rising of multi-level parallel architectures. The work in this thesis dissertation ismultidisciplinary by designing a reusable parallel numerical library for solving Hamilton-Jacobi-Bellmanequations. Such equations are involved in various fields such as in biomedical, geophysics or robotics. Inparticular, we will show interests in path planning and shape from shading applications. We show thatthe methods to solve these equations such as the widely used fast marching method, are not designedto be used effciently in a parallel context. We propose a buffered fast iterative method which givesan interesting parallel scalability. This dissertation takes interest in the challenge to find compromisesbetween abstraction, performance and maintainability in order to combine both software reusability andalso sequential/parallel reusability. We propose code abstraction allowing algorithmic and data genericitywhile trying to keep a maintainable and performant code potentially parallelizable

L'imagerie intravasculaire ultrasonore (IVUS) est une technologie médicale par cathéter qui produit des images de coupe des vaisseaux sanguins. Elle permet de quantifier et d'étudier la morphologie de plaques d'athérosclérose en plus de visualiser la structure des vaisseaux sanguins (lumière, intima, plaque, média et adventice) en trois dimensions. Depuis quelques années, cette méthode d'imagerie est devenue un outil de choix en recherche aussi bien qu'en clinique pour l'étude de la maladie athérosclérotique. L'imagerie IVUS est par contre affectée par des artéfacts associés aux caractéristiques des capteurs ultrasonores, par la présence de cônes d'ombre causés par les calcifications ou des artères collatérales, par des plaques dont le rendu est hétérogène ou par le chatoiement ultrasonore (speckle) sanguin. L'analyse automatisée de séquences IVUS de grande taille représente donc un défi important. Une méthode de segmentation en trois dimensions (3D) basée sur l'algorithme du fast-marching à interfaces multiples est présentée. La segmentation utilise des attributs des régions et contours des images IVUS. En effet, une nouvelle fonction de vitesse de propagation des interfaces combinant les fonctions de densité de probabilité des tons de gris des composants de la paroi vasculaire et le gradient des intensités est proposée. La segmentation est grandement automatisée puisque la lumière du vaisseau est détectée de façon entièrement automatique. Dans une procédure d'initialisation originale, un minimum d'interactions est nécessaire lorsque les contours initiaux de la paroi externe du vaisseau calculés automatiquement sont proposés à l'utilisateur pour acceptation ou correction sur un nombre limité d'images de coupe longitudinale. La segmentation a été validée à l'aide de séquences IVUS in vivo provenant d'artères fémorales provenant de différents sous-groupes d'acquisitions, c'est-à-dire pré-angioplastie par ballon, post-intervention et à un examen de contrôle 1 an suivant l'intervention. Les résultats ont été comparés avec des contours étalons tracés manuellement par différents experts en analyse d'images IVUS. Les contours de la lumière et de la paroi externe du vaisseau détectés selon la méthode du fast-marching sont en accord avec les tracés manuels des experts puisque les mesures d'aire sont similaires et les différences point-à-point entre les contours sont faibles. De plus, la segmentation par fast-marching 3D s'est effectuée en un temps grandement réduit comparativement à l'analyse manuelle. Il s'agit de la première étude rapportée dans la littérature qui évalue la performance de la segmentation sur différents types d'acquisition IVUS. En conclusion, la segmentation par fast-marching combinant les informations des distributions de tons de gris et du gradient des intensités des images est précise et efficace pour l'analyse de séquences IVUS de grandes tailles. Un outil de segmentation robuste pourrait devenir largement répandu pour la tâche ardue et fastidieuse qu'est l'analyse de ce type d'images. / Intravascular ultrasound (IVUS) is a catheter based medical imaging technique that produces cross-sectional images of blood vessels. These images provide quantitative assessment of the vascular wall, information about the nature of atherosclerotic lesions as well as the plaque shape and size. Over the past few years, this medical imaging modality has become a useful tool in research and clinical applications, particularly in atherosclerotic disease studies. However, IVUS imaging is subject to catheter ring-down artifacts, missing vessel parts due to calcification shadowing or side-branches, heterogeneously looking plaques and ultrasonic speckle from blood. The automated analysis of large IVUS data sets thus represents an important challenge. A three-dimensional segmentation algorithm based on the multiple interface fast-marching method is presented. The segmentation is based on region and contour features of the IVUS images: a new speed fonction for the interface propagation that combines the probability density functions (PDFs) of the vessel wall components and the intensity gradients is proposed. The segmentation is highly automated with the detection of the lumen boundary that is fully automatic. Minimal interactions are necessary with a novel initialization procedure since initial contours of the external vessel wall border are also computed automatically on a limited number of longitudinal images and then proposed to the user for acceptance or correction. The segmentation method was validated with in-vivo IVUS data sets acquired from femoral arteries. This database contained 3 subgroups: pullbacks acquired before balloon angioplasty, after the intervention and at a 1 year follow-up examination. Results were compared with validation contours that were manually traced by different experts in IVUS image analysis. The lumen and external wall boundaries detected with the fast-marching method are in agreement with the experts' manually traced contours with similarly found area measurements and small point-to-point contour differences. In addition, the 3D fast-marching segmentation method dramatically reduced the analysis time compared to manual tracing. Such a valdiation study, with comparison between pre- and post-intervention data, has never been reported in the IVUS segmentation literature. In conclusion, the fast-marching method combining the information on the gray level distributions and intensity gradients of the images is precise and efficient to analyze large IVUS sequences. It is hoped that the fast-marching method will become a widely used tool for the fastidious and difficult task of IVUS image processing.

Dans cette these nous nous interessons a l'utilisation des méthodes de chemins minimaux et des méthodes de contours actifs par Ensembles de Niveaux, pour l'extraction de courbes et de surfaces dans des images medicales 3D. Dans un premier temps, nous nous sommes attaches a proposer un éventail varié de techniques d'extraction de chemins minimaux dans des images 2D et 3D, basees sur la résolution de l'équation Eikonal par l'algorithme du Fast Marching. Nous avons montre des resultats de ces techniques appliquees a des problèmes d'imagerie médicale concrets, notamment en construction de trajectoires 3D pour l'endoscopie virtuelle, et en segmentation interactive, avec possibilité d'apprentissage. Dans un deuxieme temps, nous nous sommes interessés a l'extraction de surfaces. Nous avons developpé un algorithme rapide de pré-segmentation, sur la base du formalisme des chemins minimaux. Nous avons étudié en détail la mise en place d'une collaboration entre cette méthode et celle des Ensembles de Niveaux, dont un des avantages communs est de ne pas avoir d'a priori sur la topologie de l'objet a segmenter. Cette méthode collaborative a ensuite ete testée sur des problèmes de segmentation et de visualisation de pathologies telles que les anevrismes cerebraux et les polypes du colon. Dans un troisième temps nous avons fusionné les résultats des deux premières parties pour obtenir l'extraction de surfaces, et des squelettes d'objets anatomiques tubulaires. Les squelettes des surfaces fournissent des trajectoires que nous utilisons pour déplacer des cameras virtuelles, et nous servent a definir les sections des objets lorsque nous voulons mesurer l'étendue d'une pathologie. La dernière partie regroupe des applications de ces méthodes a l'extraction de structures arborescentes. Nous étudions le cas des arbres vasculaires dans des images médicales 3D de produit de contraste, ainsi que le problème plus difficile de l'extraction de l'arbre bronchique sur des images scanners des poumons.

Wildfire hazard and its destructive consequences have become a growing issue around the world especially in the context of global warming. An effective and efficient fire simulation model will make it possible to predict the fire spread and assist firefighters in the process of controlling the damage and containing the fire area. Simulating wildfire spread remains challenging due to the complexity of fire behaviors. The raster-based method and the vector-based method are two major approaches that allow one to perform computerized fire spread simulation. In this thesis, we present a scheme we have developed that utilizes a level set method to build a fire spread simulation model. The scheme applies the strengths and overcomes some of the shortcomings of the two major types of simulation method. We store fire data and local rules at cells. Instead of calculating which are the next ignition points cell by cell, we apply Huygens' principle and elliptical spread assumption to calculate the direction and distance of the expanding fire by the level set method. The advantage to storing data at cells is that it makes our simulation model more suitable for heterogeneous fuel and complex topographic environment. Using a level set method for our simulation model makes it possible to overcome the crossover problem. Another strength of the level set method is its continuous data processing. Applying the level set method in the simulation models, we need fewer vector points than raster cells to produce a more realistic fire shape. We demonstrate this fire simulation model through two implementations using narrow band level set method and fast marching method. The simulated results are compared to the real fire image data generated from Troy and Colina fires. The simulation data are then studied and compared. The ultimate goal is to apply this simulation model to the broader picture to better predict different types of fires such as crown fire, spotting fires, etc.

The performance prediction of solid propellant rocket motor depends on the calculation of internal aerodynamics of the motor through its operational life. In order to obtain the control volume, in which the solutions will be carried out, a process called &ldquo / grain burnback calculation&rdquo / is required. During the operation of the motor, as the interface between the solid and gas phases moves towards the solid propellant in a direction normal to the surface, the combustion products are generated and added into the control volume. This phenomenon requires handling of moving boundaries as the solution proceeds. In this thesis, Fast Marching Method is implemented to the problem of grain burnback. This method uses the upwinding nature of the propellant interface motion and solves the Eikonal type equations on a fixed three-dimensional tetrahedron mesh. The control volume is coupled to a one-dimensional and a three-dimensional Euler aerodynamic solver in order to obtain the performance of the engine. The speed by which the interface moves depends on the static pressure on the surface of the propellant and comes from the solver. Therefore an iterative method has been proposed between the interface capturing algorithms and the flow solver. Both of the calculation results, which are obtained from one-dimensional and three-dimensional solvers are compared with actual rocket firing data and validated.

Image segmentation is a process to identify regions of interest from digital images. Image segmentation plays an important role in medical image processing which enables a variety of clinical applications. It is also a tool to facilitate the detection of abnormalities such as cancerous lesions in the brain. Although numerous efforts in recent years have advanced this technique, no single approach solves the problem of segmentation for the large variety of image modalities existing today. Consequently, brain MRI segmentation remains a challenging task. The purpose of this thesis is to demonstrate brain MRI segmentation for delineation of tumors, ventricles and other anatomical structures using Insight Segmentation and Registration Toolkit (ITK) routines as the foundation. ITK is an open-source software system to support the Visible Human Project. Visible Human Project is the creation of complete, anatomically detailed, three-dimensional representations of the normal male and female human bodies. Currently under active development, ITK employs leading-edge segmentation and registration algorithms in two, three, and more dimensions. A goal of this thesis is to implement those algorithms to facilitate brain segmentation for a brain cancer research scientist.

Modern reservoir management typically involves simulations of geological models to predict future recovery estimates, providing the economic assessment of different field development strategies. Integrating reservoir data is a vital step in developing reliable reservoir performance models. Currently, most effective strategies for traditional manual history matching commonly follow a structured approach with a sequence of adjustments from global to regional parameters, followed by local changes in model properties. In contrast, many of the recent automatic history matching methods utilize parameter sensitivities or gradients to directly update the fine-scale reservoir properties, often ignoring geological inconsistency. Therefore, there is need for combining elements of all of these scales in a seamless manner. We present a hierarchical streamline-assisted history matching, with a framework of global-local updates. A probabilistic approach, consisting of design of experiments, response surface methodology and the genetic algorithm, is used to understand the uncertainty in the large-scale static and dynamic parameters. This global update step is followed by a streamline-based model calibration for high resolution reservoir heterogeneity. This local update step assimilates dynamic production data. We apply the genetic global calibration to unconventional shale gas reservoir specifically we include stimulated reservoir volume as a constraint term in the data integration to improve history matching and reduce prediction uncertainty. We introduce a novel approach for efficiently computing well drainage volumes for shale gas wells with multistage fractures and fracture clusters, and we will filter stochastic shale gas reservoir models by comparing the computed drainage volume with the measured SRV within specified confidence limits. Finally, we demonstrate the value of integrating downhole temperature measurements as coarse-scale constraint during streamline-based history matching of dynamic production data. We first derive coarse-scale permeability trends in the reservoir from temperature data. The coarse information are then downscaled into fine scale permeability by sequential Gaussian simulation with block kriging, and updated by local-scale streamline-based history matching. he power and utility of our approaches have been demonstrated using both synthetic and field examples.