Le paysage des thérapies inhalées connaît de profondes évolutions depuis les deux dernières décennies, avec pour objet la considération nouvelle du poumon comme un site de transfert des agents thérapeutiques vers le compartiment sanguin. Cette approche originale est apparue par la combinaison de développements théoriques et pratiques multiples impliqués dans la mise au point de nombreux médicaments, depuis le traitement de la douleur et du diabète jusqu'à la vaccination et le traitement de certains cancers. La quantité effective de médicament délivrée par aérosols est pondérée par de nombreux facteurs dont le mode et les conditions d’inhalation, les propriétés physiques des gaz en jeu, la morphologie des voies respiratoires ou encore les propriétés physico-chimiques des particules véhiculées. Les développements en cours ces quatre dernières années ont été conditionnés par des résultats encore mal compris, soulignant les limites des connaissances sur le transport et le dépôt d'aérosols dans le poumon. Ces manques mettent en avant le besoin d'outils performants pour l'évaluation du dépôt de particules dans les voies respiratoires.Les techniques d’imagerie permettent à la fois l’évaluation spatiale et quantitative du dépôt, avec pour seules références aujourd’hui, les techniques de médecine nucléaire. Outre l’aspect ionisant de ces techniques, elles bénéficient d’une sensibilité de détection encore inégalée. Elles demeurent néanmoins limitées par des résolutions spatiale et temporelle faibles, rendant le plus souvent difficile tant l’interprétation du dépôt que le rôle joué par les principaux mécanismes de clairance dans les voies aériennes. Depuis la fin des années 1990, les techniques de résonance magnétique imagent des noyaux hyperpolarisés (hélium-3 et xenon-129) et établissent de nouveaux standards dans l’exploration de la fonction pulmonaire.Cette thèse établit, sur la base de l’IRM de l’hélium-3 hyperpolarisé, une nouvelle modalité d’imagerie pour détecter et quantifier le dépôt d’aérosols dans les voies aériennes.Dans un premier temps, et dans un contexte où l’imagerie par résonance magnétique ne s’était pas encore penchée sur la problématique des aérosols thérapeutiques, un vaste travail d’investigation a été mené pour évaluer la sensibilité de l’IRM de l’hélium-3 hyperpolarisé au dépôt d’aérosols marqués à base d’oxyde de fer superparamagnétique. Le second volet de ce travail s’est porté sur la validation de notre méthode d’évaluation, et sur le développement de la quantification du dépôt d’aérosols. Nous avons enfin pu tester la reproductibilité de notre méthode d’évaluation du dépôt in vivo chez le rat, grâce à la réalisation d’une plateforme de ventilation et d’administration de gaz et d’aérosols dédiée, SAGAS. / Inhalation therapy has broadened its field of application over the last two decades by considering the lung not only as an organ to cure, but also as a portal toward systemic circulation. This new approach is being made possible by the emergence of biotherapeutics and a greater understanding of the absorption properties of the lung. Systemic delivery across the oronasal route was then investigated for a number of indications including migraine, diabetes, pain, and cancer. However, progress into the market of systemic aerosolized drug delivery has been slowed down to-date by a number of confounding factors including rapid clearance, instability, long-term toxicity, and dosing issues. Final drug distribution in such complex geometries strongly depends on a variety of parameters like the aerosol administration protocol, particle size, density, and physicochemical properties, as well as the airway geometry. Independently of drug formulation and pharmacokinetic considerations, these parameters determine the deposition distribution throughout the lung. Quantification and spatial localization are primordially needed to better control and optimize drug concentration at specific or less- and nonspecific sites. Nuclear medicine techniques are currently the only available modalities that combine both aerosol quantification and regional localization. They are considered as reference techniques even though they remain limited by their spatial and temporal resolutions as well as by patient exposure to radiations. With regard to lung imaging, hyperpolarized helium-3 MRI has been developed as a powerful tool to quantitatively characterize the parenchyma and the organ function and morphology. The technique is innocuous and provides millimeter and sub-second resolutions with rather high signal to noise ratios. In this thesis, a new imaging modality was developed on the grounds of hyperpolarized helium-3 MRI to probe and quantify aerosol deposition in the airways. In the first part of the thesis, I describe the potential of helium-3 MRI to probe aerosol deposition by using superparamagnetic contrast agents. The second part mainly focuses on the validation of this new modality by comparing it to a reference technique, single photon emission computed tomography (SPECT), and computational fluid dynamics. The last part of the manuscript is dedicated to aerosol administration and in vivo measurements in rat lungs. This experiment was possible by designing and building an MR compatible gas administrator and ventilator dedicated to small animals, SAGAS (Small Animal Gas Administration System). Its complete hardware and software description is presented in the same chapter.

<p>Measurements of the three-body photodisintegration of <super>3</super>He were performed at the High Intensity &gamma-ray Source (HI&gammaS). Neutrons emitted in this reaction inside a <super>3</super>He gas target were detected with seven 12.7 cm diameter liquid scintillator detectors. Time-of-flight (TOF) and pulse-shape discrimination (PSD) techniques were used to identify neutron events. The absolute differential cross sections for the <super>3</super>He(&gamma, n)pp reaction as a function of outgoing neutron scattering angle and energy were determined from the measurements at the incident &gamma-ray energies of 11.4, 12.8, 13.5, and 14.7 MeV to within a precision better than +/- 6 %.</p><p>The absolute cross sections at each incident energy are compared to the results of Gorbunov [Gor74], phase space calculations, and state-of-the-art three-body calculations. The inclusion of the Coulomb interaction in the three-body problem has been a long-standing challenge in theoretical nuclear physics. The present experimental data were found to be in good agreement with the state-of-the-art theory, which includes a full treatment of the Coulomb interaction between</p><p>the protons in the final state [Del05].</p> / Dissertation

<p>An experiment measuring the analyzing power A_y(&theta;) for neutron&ndash;helium-3 (<italic>n</italic>-<super>3</super>He) elastic scattering over broad angular distributions for a range of incident neutron energies from 1.60 to 5.54 MeV has been conducted at the Triangle Universities Nuclear Laboratory. These measurements represent an effort to resolve the long-standing discrepancy between experiment and theory in low-energy three-nucleon analyzing powers, through the evaluation of analyzing powers in the four-nucleon systems, which are expected to exhibit sensitivities not accessible with fewer nucleons. The present work is described in terms of the experimental setup and data reduction techniques; a comparison of the results with rigorous calculations using both nucleon-nucleon and, as recently has become available, three-nucleon potential models is presented. While a discrepancy between calculation and measurement was observed, at low energies substantially better agreement was achieved than in related measurements of the proton&ndash;helium-3 (<italic>p</italic>-<super>3</super>He) analyzing power, suggesting a sizeable dependence on isospin in the four-nucleon systems.</p> / Dissertation

The heat capacity of 3He adsorbed on Grafoil (exfoilated graphite) preplated with four layers of 4He was measured between 1 and 50mK. The heat capacity was found to be linear up to 4OmK. At 3He surface densities below 4nm-2 two dimensional Fermi liquid behaviour was found and values of the hydrodynamic effective mass and Landau parameter Ff inferred. Subsequent steps in the heat capacity as a function of coverage were taken as evidence of independent 2D Fermi fluids. A low field DC SQUID pulsed NMR spectrometer was developed for future studies of magnetic order in 2D solid 3He films at ultralow temperatures

No description available.

L’exploration des interactions fondamentales entre les particules subatomiquesa abouti à la construction du Modèle Standard de la physique des particules qui n’a été misen défaut par aucune expérience en laboratoire. Cependant, de sérieuses indications théoriqueset cosmologiques révèlent des insuffisances au Modèle Standard et des déviationssont attendues. Cette nouvelle physique est recherchée auprès des grands collisionneursmettant en jeu des énergies de l’ordre de l’échelle électrofaible et au-delà. A contre-courant,la nouvelle physique pourrait aussi se manifester à très basse énergie, nécessitant des techniquesexpérimentales atypiques. Cette thèse traite des nouvelles forces de courte portéedépendantes du spin, sujet au coeur de la physique de précision à basse énergie. Un gazd’hélium 3 hyperpolarisé a été utilisé comme sonde de cette nouvelle interaction de portéesubmillimétrique. Ce manuscrit présente la meilleure exclusion sur l’intensité du couplagescalaire-pseudoscalaire gsgp pour des portées entre 1 μm et 100 μm correspondant à desmasses inférieures à 1 eV. / The exploration of fundamental interactions between subatomic particles ledto the particle physics Standard Model which remains unchallenged by any lab experiment.However, some serious theoretical and cosmological clues reveal shortcomings inthe Standard Model and deviations are expected. This new physics is searched for at largecolliders with energies of the order of the electroweak scale and beyond. With a differentphilosophy, one can expect the new physics to show up at very low energy using atypicalexperimental techniques. This thesis deals with short-range spin-dependent new forceswhich are at the heart of the low energy precision physics. A hyperpolarized helium 3 gaswas used as a probe of this new sub-mm interaction. This manuscript present the bestexclusion limit on the strength of a scalar-pseudoscalar coupling gsgp for ranges between1 μm and 100 μm, which correspond to sub-eV masses.

What constitutes the spin of the nucleon? The answer to this question is still not completely understood. Although we know the longitudinal quark spin content very well, the data on the transverse quark spin content of the nucleon is still very sparse. Semi-inclusive Deep Inelastic Scattering (SIDIS) using transversely polarized targets provide crucial information on this aspect. The data that is currently available was taken with proton and deuteron targets. The E06-010 experiment was performed at Jefferson Lab in Hall-A to measure the single spin asymmetries in the SIDIS reaction n↑(e,éπ±/K±)X using transversely polarized 3He target. The experiment used the continuous electron beam provided by the CEBAF accelerator with a beam energy of 5.9 GeV. Hadrons were detected in a high-resolution spectrometer in coincidence with the scattered electrons detected by the BigBite spectrometer. The kinematic coverage focuses on the valence quark region, x = 0.19 to 0.34, at Q2 = 1.77 to 2.73 (GeV/c)2. This is the first measurement on a neutron target. The data from this experiment, when combined with the world data on the proton and the deuteron, will provide constraints on the transversity and Sivers distribution functions on both the u and d-quarks in the valence region. In this work we report on the single spin asymmetries in the SIDIS n↑(e,éπ+)X reaction.

Polarized helium-3 is used as a contrast agent for lungs magnetic resonance imaging that has recently reached the pre-clinical applications. One method to hyperpolarize 3He is the metastability exchange optical pumping (MEOP). Optical pumping is performed in standard conditions at low pressure (~ 1 mbar) and low magnetic field (~ 1 Gauss). In this work, the complete update of a low field polarizer dedicated to small animal lungs imaging is presented. The implementation of a new 10 W laser, new peristaltic compressor and others components resulted in a production of 3-4 scc/min for a polarization between 30 to 40%. Images of rat lungs made with better resolution and a new dynamic radial sequence are presented as a validation of the system. Since few years, MEOP has also been studied at higher pressures and higher magnetic fields in small sealed cells. It showed that, thanks to hyperfine decoupling effect induced by high magnetic field, it was also possible to efficiently polarize at higher pressure (67 mbar). Experiments done at 4.7 and 1.5 T are reported in this work. The first ones show a benefic (higher polarization values) and a negative effect (lower production rates) of the magnetic field. The seconds highlight the advantage of using an annular beam shape of the laser that matches the distribution of 23S state atoms at higher pressure. Nuclear polarization values of 66.4% at 32 mbar and 31% at 267 mbar were obtained in 20 mL sealed cells and a 10 times increase in the production rate compare to best standard conditions. These promising results were the first motivation for building a high-field polarizer working inside MRI scanner in hospital. The design and the construction of such a polarizer are described in detail in the last part of the dissertation. The polarizer produces hyperpolarize 3He at 30-40% with a 4 times higher flow than the low field polarizer (10-15 scc/min). The first good quality human lungs images made in Poland with healthy volunteers are the main result of this work.

L’étude de la structure du nucléon est un sujet actif de la recherche et un des objectifs majeurs du Thomas Jefferson National Accelerator Facility (Jefferson Lab). Dans cette optique et afin d’obtenir des résultats statistiquement significatifs, il est essentiel d’avoir une cible polarisée ayant à la fois une haute polarisation et une densité de matériel polarisé élevée. Cette thèse présente les principes et utilisations d’une cible de deutérure d’hydrogène (ou cible de HD) qui remplit les deux conditions précédemment énoncées. Bien qu’il ait été prouvé que la cible de HD pouvait être utilisée avec succès sous un faisceau de photons de haute intensité, il restait à montrer si elle pouvait résister un faisceau d’électrons de courant relativement élevé (nA). Dans ce but, la cible de HD a été testée pour la première fois dans son mode de “spin gelé” sous un faisceau d’électrons pendant l’expérience g14 dans le Hall B de Jefferson Lab en 2012. Deux méthodes de polarimétrie sont également décrites dans cette thèse : une par Resonance Magnétique Nucléaire appliquée à la cible de HD pendant les tests sous un faisceau d’électrons, et une autre utilisant la réaction de diffusion élastique d’un faisceau d’électrons sur une cible en utilisant des données élastiques sur l’hélium-3 prises en 2003 pendant l’expérience E97-110 dans le Hall A de Jefferson Lab. / The study of the nucleon structure has been a major research focus in fundamental physics in the past decades and still is the main research line of the Thomas Jefferson National Accelerator Facility (Jefferson Lab). For this purpose and to obtain statistically meaningful results, a highly efficient polarized target is essential. This means high polarization and high relative density of polarized material. This dissertation presents the principles and usage procedures of a Hydrogen Deuteride (HD) target that presents both such characteristics. Although the HD target has been shown to work successfully under a high intensity photon beam, it remained to be seen if the target could stand an electron beam of reasonably high current (nA). In this perspective, the HD target was tested for the first time in its “frozen spin” mode under an electron beam during the g14 experiment in the Jefferson Lab’s Hall B in 2012. Two methods of polarimetry are also discussed in this dissertation : one with Nuclear Magnetic Resonance of this HD target during the electron beam tests, and another with the elastic scattering of electrons off a polarized target by using data taken on helium-3 during the E97-110 experiment that occurred in Jefferson Lab’s Hall A in 2003.

Doctor of Philosophy / Department of Mechanical and Nuclear Engineering / Douglas S. McGregor / The microstructured semiconductor neutron detector (MSND) was investigated and previous designs were improved and optimized. In the present work, fabrication techniques have been refined and improved to produce three-dimensional microstructured semiconductor neutron detectors with reduced leakage current, reduced capacitance, highly anisotropic deep etched trenches, and increased signal-to-noise ratios. As a result of these improvements, new MSND detection systems function with better gamma-ray discrimination and are easier to fabricate than previous designs. In addition to the microstructured diode fabrication improvement, a superior batch processing backfill-method for 6LiF neutron reactive material, resulting in a nearly-solid backfill, was developed. This method incorporates a LiF nano-sizing process and a centrifugal batch process for backfilling the nanoparticle LiF material. To better transition the MSND detector to commercialization, the fabrication process was studied and enhanced to better facilitate low cost and batch process MSND production. The research and development of the MSND technology described in this work includes fabrication of variant microstructured diode designs, which have been simulated through MSND physics models to predict performance and neutron detection efficiency, and testing the operational performance of these designs in regards to neutron detection efficiency, gamma-ray rejection, and silicon fabrication methodology. The highest thermal-neutron detection efficiency reported to date for a solid-state semiconductor detector is presented in this work. MSNDs show excellent neutron to gamma-ray (n/γ) rejection ratios, which are on the order of 106, without significant loss in thermal-neutron detection efficiency. Individually, the MSND is intrinsically highly sensitive to thermal neutrons, but not extrinsically sensitive because of their small size. To improve upon this, individual MSNDs were tiled together into a 6x6-element array on a single silicon chip. Individual elements of the array were tested for thermal-neutron detection efficiency and for the n/γ reject ratio. Overall, because of the inadequacies and costs of other neutron detection systems, the MSND is the premier technology for many neutron detection applications.