Enormous advances in computing power in recent decades have made it possible to perform accurate numerical simulations of a wide range of systems in condensed matter physics. At the forefront of this progress has been density functional theory (DFT), a very popular approach to tackling the complexity of quantum-mechanical systems that very often strikes a good balance between accuracy and tractability in light of the finite computational resources available to researchers. This thesis describes work utilising DFT methods to tackle two distinct problems. Firstly, the theoretical prediction of stable and metastable periodic structures under specified conditions using the ab initio random structure searching (AIRSS) method, which involves a large scale exploration of the Born-Oppenheimer energy surface, and secondly the use of a vibrational self-consistent field (VSCF) approach to investigate the effects of nuclear motion and anharmonicity in crystal systems, which involves a local exploration of the Born-Oppenheimer energy surface. The AIRSS crystal structure prediction method is here applied to a study of defect structures in graphene. It is also applied to a study of the xenon-oxygen binary system under a range of geological pressures (83–200 GPa). Novel xenon oxide structures are predicted and characterised theoretically. This work was carried out in collaboration with an experimental study of the system at the lower end of the pressure range. The VSCF approach to investigating anharmonicity is here applied to the study of tin selenide (SnSe), a material that has recently been shown to demonstrate consider- able promise as a thermoelectric material. In this thesis, the effects of the anharmonic nuclear motion on the vibrational and electronic properties of SnSe are investigated quantitatively.

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<p>The diagnosis and treatment of pulmonary diseases still rely on pulmonary function tests that offer archaic or insensitive biomarkers of lung structure and function. As a consequence, chronic obstructive pulmonary disease is the third leading cause of death in the US, and the hospitalization costs for asthma are on the order of $29 Billion. Pulmonary diseases have created a large and unsustainable economic burden, and hence there is still a dire need for biomarkers that can predict early changes in lung function. The work presented in this thesis looks to address this very issue, by taking advantage of the unique properties of hyperpolarized (HP) <super>129</super>Xe in conjunction with magnetic resonance imaging (MRI), to probe the fundamental function of the lung - gas-exchange. </p><p>While a bulk of the inhaled HP <super>129</super>Xe stays in the alveolar spaces, its moderate solubility in the pulmonary tissues causes a small fraction of this xenon in the alveolar spaces to diffuse into the pulmonary barrier tissue and plasma, and further into the red blood cells (RBC). Additionally, when in either of these compartments, xenon experiences a unique shift in its resonance frequency from the gas-phase (barrier - 198 ppm, RBC - 217 ppm). These unique resonances are collectively called the dissolved-phase of xenon. As the pathway taken by xenon to reach the RBCs is identical to that of oxygen, this dissolved-phase offers a non-invasive probe to study the oxygen transfer pathway, and imaging its distribution, to first order, would give us an image of gas-exchange in the lung.</p><p>Gas-exchange is controlled by ventilation, perfusion, and lastly diffusion of gases across the capillary membrane. This process of diffusion is dictated by Fick's first law of diffusion, and hence the volume of gas taken up by the capillary blood stream depends on the alveolar surface area, and the interstitial thickness. Interestingly, changes in these factors can be measured using the resonances of xenon. Changes in the alveolar surface area brought on by diseases like emphysema will increase the diffusion of xenon within the alveolus. Thus, by using diffusion-weighted imaging of the gas-phase of <super>129</super>Xe, which is the focus of chapter 3, one can extract the `apparent diffusion coefficient' (ADC) of xenon, that is sensitive to the changes in the alveolar surface area. The dissolved-phase on the other hand, while sensitive to the surface area, is also sensitive to subtle changes in the interstitial thickness. In fact, after the application of an RF pulse on the dissolved-phase, the recovery time for the xenon signal in the RBCs is significantly delayed by micron scale thickening of the interstitium. This delayed signal recovery can be used as a sensitive marker for diffusion impairment in the lung. </p><p>While direct imaging of the dissolved-phase was shown to be feasible, truly quantifying gas-exchange in the lung will require two additional technical advances - 1) As the gas-phase is the source magnetization for the dissolved-phase signal, it is imperative to acquire both the gas and dissolved-phase images in a single breath. The technical details of this achievement are discussed in chapters 4 and 5. 2) As the dissolved-phase consists of both the barrier and the RBC components, obtaining a fundamental image of gas-exchange in the lung will require creating independent images of <super>129</super>Xe in the barrier and <super>129</super>Xe in the RBCs. This goal first required creating a global metric of gas-transfer in the lung (chapter 6), which aided the implementation of the 1-point Dixon acquisition strategy to separate the components of the dissolved-phase. In conjunction with aim 1, it was finally possible to image all three resonances of <super>129</super>Xe in a single breath (chapter 7). These <super>129</super>Xe-RBC images were acquired in healthy volunteers and their efficacy was tested in subjects with idiopathic pulmonary fibrosis (IPF). These IPF subjects are known for their characteristic diffusion limitation, and in regions of fibrosis shown on their CT scans, the <super>129</super>Xe-RBC images showed gas-transfer defects. </p><p>Hyperpolarized <super>129</super>Xe MRI thus provides a non-invasive, ionizing radiation free method to probe ventilation, microstructural changes and most importantly, gas-exchange. These preliminary results indicate that xenon MRI has potential as a sensitive tool in therapeutic clinical trials to evaluate longitudinal changes in lung function.</p> / Dissertation

Neste trabalho foi desenvolvida uma nova metodologia de produção de iodo-125, que resultou na primeira produção deste radionuclídeo no Brasil. Cápsulas de alumínio foram projetadas, fabricadas e avaliadas para que suportassem condições de pressão, temperatura e fluxo de nêutrons no reator nuclear IEA-R1 do IPEN sem a ocorrência de liberação de material radioativo. Foram projetados, desenvolvidos e fabricados sistemas de carregamento, descarregamento e recuperação dos gases para a manipulação do gás xenônio e do iodo. Foi desenvolvido um novo método de lavagem da cápsula, para dissolução do iodo-125 adsorvido nas paredes, por meio de imersão em banho ultrassônico. Foram irradiadas três cápsulas no reator nuclear IEA-R1, por um período de aproximadamente 60 h contínuas, a um fluxo de nêutrons de 5,5 x 1013 n cm-2 s-1. Foi produzido um total de 13,53 GBq (365,73 mCi) de iodo-125, e o único contaminante encontrado foi o radionuclídeo iodo-126. Na análise radioquímica, pelo método de cromatografia em papel ascendente, o iodo-125 em solução de NaOH apresentou percentual de iodeto acima de 98%, superior à exigência da farmacopeia americana para soluções de iodo radioativo que é de 95%. Para a análise radionuclídica foi desenvolvida uma fonte planar, a base de resina epoxídica, para a contagem do iodo-125 em detector de germânio de alta pureza. A correlação entre o iodo-125 e o iodo-126 produzido apresentou valores entre 0,5 e 0,7% após um período de decaimento de 10 d, grau de pureza suficiente para a utilização em técnicas de radioimunoensaio. / A new methodology of iodine-125 production was developed in this work, performing the first production of iodine-125 in Brazil. Aluminium capsules were designed, manufactured and evaluated to support condition as pressure, temperature and neutron flux in IEA-R1 Nuclear Reactor without releasing radioactive material into reactor pool. It was designed, developed and manufactured systems to load, unload and recover gases to manipulate the xenon gas and the iodine. A new method of capsule rinsing was developed, to dissolve the iodine-125 adsorbed in the walls, using immersion in ultrasonic bath. Three capsules were irradiated in IEA-R1 Nuclear Reactor for approximately 60 h continuous, at a neutron flux of 5.5 x 1013 n cm-2 s-1. It was produced a total of 13.53 GBq (365.73 mCi) of iodine-125 and the radionuclide iodine-126 was the only contaminant found. In radiochemical analysis, by ascending paper chromatography method, the iodine-125 in NaOH solution presented a percentage over 98%, higher than American pharmacopeia requirements for iodine radioactive solutions which is 95%. A planar source was developed, based on epoxy resin, to iodine-125 radionuclidic analysis in high purity germanium detector. The correlation between iodine-125 and iodine-126 produced showed values between 0.5 and 0.7% after a 10 d decay period, a purity grade enough to apply in radioimmunoassay techniques.

L'Imagerie par Résonance Magnétique (IRM) est une technique d’imagerie très utilisée de nos jours, notamment pour le diagnostic médical. L’utilisation d’agents de contraste lors d’un examen IRM permet d’obtenir des images de bonne qualité. Cependant, le manque de sensibilité de cette technique d’imagerie a conduit à l’utilisation d’espèces hyperpolarisées (3He, 13C, 129Xe) en IRM. Le xénon (Xe) apparait aujourd’hui comme un composé très prometteur pour de telles applications mais son manque de sélectivité rend l’imagerie moléculaire impossible. Le développement et l’utilisation de molécules cages capable d’encapsuler le xénon et de l’amener vers la cible à imager est donc indispensable. Dans ce contexte, nous nous sommes intéressés au cours de cette thèse à l’élaboration de telles molécules, et plus précisément, à l’obtention de nouveaux cryptophanes qui présentent la plus forte affinité pour le xénon afin de pouvoir utiliser ces molécules en tant qu’outils pour l’IRM Xe. Une nouvelle voie de synthèse du cryptophane ayant la plus grande affinité pour le xénon a été mise au point ; ce composé a été fonctionnalisé pour la première fois au laboratoire et ceci dans le but d’obtenir les premières biosondes dérivées de composé. Le greffage d’antenne de reconnaissance sur ces biosondes permettrait alors de faire de l’imagerie ciblée. Une sonde pour la détection du peroxyde d’hydrogène (H2O2) a été synthétisée. Le peroxyde d’hydrogène est impliqué dans le développement de stress oxydant cellulaire et présent en ces de maladies neurodégénératives (Parkinson, Alzheimer). La sonde obtenue a permis d’imager H2O2 par IRM Xe pour la première fois. Un hybride composé de nanotube de carbone et de cryptophanes a aussi été synthétisé en vue de disposer d’outil présentant une forte concentration de cryptophanes et d’améliorer la sensibilité de la technique d’imagerie utilisant du xénon. / Magnetic Resonance Imaging (MRI) is widely used today for early medical diagnosis. During the MRI examination, the use of contrast agent allows the obtention of well resolved images. However the lack of sensibility of this technic lead to the utilization of hyperpolarized species (3He, 13C, 129Xe) in MRI. The xenon (Xe) is the more promising but due to its weak selectivity, it cannot be used in molecular imaging. So, the development and utilization of host molecules able to encapsulate the xenon and bring it to a targeted biological tissue or organ is necessary. In these conditions, during this thesis, we worked on the elaboration of such molecules, and particularly, in cryptophanes since these compounds have strong affinity for xenon and could be used as tools for MRI by hyperpolarized xenon (Hp Xe). A new route synthesis of cryptophane-111, that has the highest affinity for xenon, was developed; first functionalized derivatives of this compound have been also obtained in order to obtain the first biosensors based on cryptophane-111. The coating of specific ligand on these functionalized compounds could allow targeted MRI. A probe for hydrogen peroxide (H2O2) detection was synthesized. Hydrogen peroxide is implicated in cellular oxidative stress and present in case of neurodegeneratives diseases (Parkinson, Alzheimer). The probe obtained allowed the imaging of H2O2 by MRI Xe for the first time. Nanotubes functionalized with strong concentration of cryptophane have been synthesized in order to increase the sensitivity of the imaging technic that uses xenon.

L’Imagerie par Résonance Magnétique (IRM) est une technique prometteuse largement répandue dans les milieux hospitaliers. Elle est non invasive, présente une bonne résolution spatiale et permet de visualiser en profondeur dans un organisme vivant. Elle possède cependant quelques défauts, dont sa faible sensibilité. Pour palier ce problème, il est possible d'utiliser des espèces hyperpolarisables telles que le xénon. Cependant, n’étant spécifique d’aucun récepteur biologique, le xénon nécessite d’être vectorisé. Pour ce faire, des auteurs ont proposé son encapsulation dans une cage moléculaire capable de reconnaître la cible biologique à imager. Les meilleurs candidats à ce jour sont les cryptophanes.Nous nous sommes fixés comme objectif dans cette thèse de concevoir et de synthétiser de nouvelles cages plus adaptées pour les applications en IRM 129Xe ainsi que des biosondes pertinentes pour se rapprocher d’applications in vivo. Dans une première partie de ma thèse, nous nous sommes intéressés au développement de nouvelles cages afin d’étudier et d’affiner les propriétés d’encapsulation du xénon au sein des cryptophanes. Dans les parties suivantes, nous nous sommes concentrés sur la conception de biosondes par fonctionnalisation de cryptophanes déjà décrits pour diverses applications d’intérêt biologique. D’une part, nous avons évalué la possibilité de détecter des métaux de manière plus spécifique et plus sensible grâce à l’IRM xénon hyperpolarisé. D’autre part, nous avons travaillé sur la conception de biosondes bimodales, afin de coupler des techniques complémentaires d’imagerie médicale. / Today, Magnetic Resonance Imaging (MRI) is a powerful clinically used imaging method which provides three-dimensional images with excellent resolution. However, conventional molecular MRI techniques that rely on the observation of water protons still suffer from reduced sensitivity and often lack selectivity. The use of hyperpolarized xenon can improve both the selectivity and sensitivity of the MRI method. As xenon has no specificity for any biological receptor, it needs to be vectorized. For this purpose, authors have proposed to encapsulate xenon inside molecular cages functionalized to recognize specific biological targets. The best candidates so far as biosensors are cryptophanes.The aim of this work is to design and synthesize new cryptophanes that are better suited for 129Xe MRI applications and relevant biosensors for future in vivo applications. In a first part, new cages were developed in order to study the encapsulation properties of xenon inside different cryptophanes. Then, biosensors were synthesized by functionnalization of known water-soluble cryptophanes for different applications of biological interest. We have therefore assessed the possibility of detecting metal ions specifically in a very sensitive way thanks to 129Xe MRI. New bimodal sensors were also designed and tested.

An abundance of cosmological evidence suggests that cold dark matter exists and makes up 83% of the matter in the universe. At the same time, this dark matter has eluded direct detection and its identity remains a mystery. Many large international collaborations are actively searching for dark matter through its potential annihilation in high-density regions of the universe, its creation in particle accelerators, and its interaction with Standard Model particles in low-background detectors. One of the most promising dark matter candidates is the weakly interacting massive particle (WIMP) which falls naturally out of extensions of the Standard Model. A variety of detectors have been employed in the search for WIMPs, which are expected to scatter with atomic nuclei, yet none have been more successful than dual-phase liquid xenon time projection chambers (TPCs). The first ton-scale liquid xenon TPC, XENON1T, began operating in 2016 and with only 34.2 days of data has set the most strict limits on the WIMP-nucleon interaction cross sections for WIMP masses above 10 GeV/c^2, with a minimum of 7.7 × 10−47 cm^2 for 35 GeV/c^2 WIMPs. One of the major keys to success for liquid xenon TPCs is our understanding of interactions in the medium through myriad measurements. Given that the expected WIMP scattering rate increases with decreasing interaction energy, there has been more focus in recent years in pushing our understanding of interactions in liquid xenon to lower energies. Additionally, as liquid xenon TPCs operate with a large electric field in the medium, an effort has been made to understand how the signal response of xenon changes as a function of the applied electric field. In this thesis, I describe the details of XENON1T, its calibration and characterization, with a special emphasis on the electronic and nuclear recoil calibrations, and the inaugural WIMP search of XENON1T. I then discuss a dedicated measurement, made in the calibration-optimized liquid xenon TPC neriX, of the signal response of low energy nuclear recoils in liquid xenon at electric fields relevant to the dark matter search. The measurements of signal response in XENON1T and neriX were performed using an analysis framework that I developed to allow a more sophisticated examination of recoil responses using GPU-accelerated simulations.

<b>Purpose</b> Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. The standard method for assessing lung function in COPD is spirometry, which provides global lung function information but is a poor predictor of disability and quality of life. The overall aim of this thesis is to develop utility of hyperpolarised xenon gas magnetic resonance imaging (HP ¹²⁹Xe-MRI) as a technique to evaluate regional lung function. <b>Methods</b> Studies were approved by the National Research Ethics Service (NRES). Eleven volunteers and 25 patients with COPD underwent HP ¹²⁹Xe-MRI, pulmonary function tests (PFTs) and quantitative computerised tomography (QCT). Gravitational-dependent gradients of HP ¹²⁹Xe-MRI were compared between prone and supine postures in healthy volunteers. Lobar quantification of HP ¹²⁹Xe-MRI was completed in COPD patients, who also underwent time-resolved HP ¹²⁹Xe-MRI and HP ¹²⁹Xe-MRI pre- and post-salbutamol to determine feasibility of detecting regional delayed ventilation and post-intervention change. The relationship between study measures was assessed using Pearson's correlation coefficient. <b>Results</b> HP ¹²⁹Xe-MR ventilation gradients were more marked in the supine than prone posture in healthy volunteers, whereas diffusion-weighted gradients were more uniform. HP ¹²⁹Xe-MRI was successfully quantified according to pulmonary lobes and correlated with lobar lung anatomy (QCT) and global functional transfer capability (TLCO) (r=-0.61, p&LT;0.005). Delayed ventilation was observed with time-resolved breath-hold HP ¹²⁹Xe-MRI. Differential regional ventilation change was detected with HP ¹²⁹Xe-MRI post-salbutamol. <b>Conclusion</b> These data demonstrate technical optimisation of HP ¹²⁹Xe-MRI in healthy volunteers and COPD patients. Successful generation of lobar HP ¹²⁹Xe-MRI parameters offers an automated analysis method that can be adopted into the clinical workflow. Finally proof-of-principle data have identified roles for HP ¹²⁹Xe-MRI in evaluating regional treatments and assessing therapeutic response. Future work will evaluate the role of HP ¹²⁹Xe-MRI in patient selection for lung volume reduction therapy and as a surrogate end-point in drug development studies.

Les réactions 136Xe + p et 136Xe + 12C à 1 GeV par nucléon d’énergie cinétique du projectile dans le centre de masse ont été étudiées en cinématique inverse à l’aide du dispositif expérimental SPALADIN, installé auprès de l’accélérateur d’ions lourds de GSI. Ma thèse décrit l’analyse de ces collisions réalisées au printemps 2009. La détection en coïncidence des fragments de l’état final (résidu du projectile, neutrons et fragments légers chargés) avec une grande efficacité géométrique est obtenue par la combinaison de la cinématique inverse, d’un aimant dipolaire de grande ouverture physique et de l’utilisation de grands détecteurs. Ces coïncidences, mesurées événement par événement, nous ont permis de sélectionner, indépendamment du modèle de désexcitation, le pré-fragment, noyau excité issu de la cascade intranucléaire en fonction de son énergie d’excitation. Ainsi, nous avons pu étudier l’évolution du mécanisme de désexcitation (par exemple, l’évaporation de particules légères, la cassure binaire asymétrique ou la fragmentation multiple simultanée) en fonction de l’énergie d’excitation du pré-fragment. Les données de la réaction 136Xe + p sont comparées principalement à trois modèles de désexcitation (SMM, GEMINI++ et ABLA07) couplés au code de cascade intranucléaire INCL4. Si ces modèles semblent décrire globalement les observables de notre expérience, des désaccords significatifs sont apparus notamment en ce qui concerne la production des fragments de masse intermédiaire (IMF). La comparaison des données 136Xe + 12C avec celles de la réaction 136Xe + p fait apparaître une grande similitude dans la désexcitation des pré-fragments qui laisse entrevoir que la cascade intranucléaire mène, dans les deux cibles, aux mêmes types de pré-fragments sur la plage d’énergie d’excitation commune aux deux réactions (0 à 4 MeV par nucléon). Le régime d’excitation au-dessus de 4 MeV par nucléon, accessible uniquement pour la réaction 136Xe + 12C, montre une différence qualitative dans la désexcitation du pré-fragment, avec notamment une production beaucoup plus importante d’IMF, avec des multiplicités élevées par événement, qui croît avec l’énergie d’excitation. / The collision of 136Xe with the proton and with 12C at 1 GeV per nucleon of projectile kinetic energy in the centre of mass has been studied in inverse kinematics using the SPALADIN experimental setup at the GSI facility. This manuscript describes the analysis of these collisions realized in spring 2009. The detection in coincidence of the final state fragments (projectile residues, neutrons and light charged fragments) with a large geometrical efficiency is provided by the inverse kinematics combined with a large aperture dipole magnet and large detectors. Such a coincidence, measured on an event basis, allows selecting, in a model-independent way, the prefragment, the excited nuclear system formed after the intranuclear cascade as a function of its excitation energy. Hence, we were able to study the evolution of the prefragment deexcitation mechanism (evaporation of light particles, asymmetric binary decay, multiple fragmentation…) as a function of its excitation energy. The data of the 136Xe + p reaction have been compared mainly to three deexcitation models (SMM, GEMINI++ and ABLA07) coupled to the intranuclear cascade code INCL4. Despite the relatively good and global agreement between these models and our data, significant discrepancies appeared concerning in particular the production of intermediate mass fragments (IMF). Comparison between the 136Xe + 12C and the 136Xe + p data exhibits an important similarity in the deexcitation of the pre-fragments. This suggests that the nuclear cascade leads, for both targets, to similar prefragment types in the range of excitation energy (0 to 4 MeV per nucleon) common to both reactions. Higher excitation energies, reached only in the 136Xe + 12C reaction, show a qualitative difference in the deexcitation of the pre-fragment, with much higher multiplicities of IMF per event, increasing with the excitation energy.