No description available.

Damage to dura mater may occur during intracranial or spinal surgeries, which can result in cerebrospinal fluid leakage as well as other potentially fatal physiological changes. As a result, biological scaffolds derived from xenogeneic materials are typically used to repair and regenerate dura mater post intracranial or spinal surgeries. In this study we explore the mechanics, structure, and immunological capacity of xenogeneic dura mater to be considered as a replacement for human dura. A comparative analysis is done between native porcine dura and a commercially available bovine collagen-based dura graft. Native porcine dura mater was decellularized and subjected to mechanical and histological analysis. Our decellularized porcine dura was able to maintain the overall morphological/structural integrity and held an increased extensibility without sacrificing strength, which provides a solid foundation as a functional grafting material. The histological observations showed that the orientation of fibers was maintained after decellularization. We investigated the biocompatibility of native and decellularized porcine dura reseeded with fibroblast cells for in vitro study. Cell proliferation, cell viability, and mechanical properties of dural grafts were evaluated post reseeding on days 3, 7, and 14. Live-dead staining and resazurin salts quantified cell viability and cell proliferation, respectively. This in vitro study showed that the acellular porcine dural graft provided a favorable environment for rat fibroblast cell infiltration. The results of micro indentation testing show that the cell-seeded porcine dural graft provides a favorable environment for rat fibroblast cell infiltration. The mechanics and biocompatibility results provide promising insight for the potential use of porcine dura in future cranial dura mater graft applications. Lastly, a subcutaneous in vivo study of dura graft compared with the market available Lyoplant®. Grafts were evaluated for inflammation by evaluating macrophage and leukocyte invasion on 3, 7, and 14 days post implantation. Histological analysis of both implants revealed macrophage (and leukocyte infiltration, supporting reabsorption, and thus encouraging the regeneration at 14 days. Cell markers also revealed that inflammation and leukocytes decreased as the number of days increased. Future work will involve a long-term subcutaneous implantation up to 30 days and 60 days to determine the long-term immune response.

Résumé : La tomographie d’émission par positrons (TEP) permet une imagerie fonctionnelle et moléculaire qui peut bénéficier de l’utilisation conjointe de la tomodensitométrie (TDM), d’abord pour fournir un support anatomique aux images TEP, mais aussi pour permettre une correction plus précise des images TEP. Les appareils existants sont composés de deux scanners juxtaposés nécessitant un déplacement du sujet entre les deux acquisitions, ce qui peut causer des artéfacts de mouvement dans l’image fusionnée TEP/TDM. De plus, le mode de fonctionnement des scanners TDM, basé sur l’intégration du flux de rayons X, délivre une dose de radiations relativement élevée qui peut interférer avec la réalisation d’études/protocoles d’imagerie longitudinales. La réalisation d’un appareil TEP/TDM partageant le même système de détection basé sur le détecteur LabPET II pourrait remédier à ces problèmes. Dans un premier temps, le module de détection LabPET II a été caractérisé pour la TEP et la TDM. Les premières études d’imagerie TDM avec ce détecteur ont aussi été conduites avec un simulateur. Ce travail a permis de déceler un phénomène de diaphonie optique au sein du module de détection. La recherche d’une solution à ce problème a motivé l’évaluation de nouveaux types de réflecteurs métallisés, donc plus opaques, pour en limiter les effets. Le signal relativement faible détecté en TDM a par la suite mené à explorer des scintillateurs alternatifs présentant un rendement lumineux supérieur. L’un de ces scintillateurs permettra d’améliorer sensiblement les performances du scanner LabPET I et pourrait être retenu pour la génération future de scanners LabPET II. || Abstract : Positron emission tomography (PET) provides functional and molecular imaging capabilities that can benefit from joint use with computed tomography (CT), first to provide anatomical support to PET images, but also to allow a more precise correction of PET images. Existing devices are composed of two back-to-back scanners which require displacing the subject between the two acquisitions, possibly causing motion artifacts in the fused PET/CT images. Moreover, the operation mode of CT scanners based on the X-ray signal integration delivers a relatively high radiation dose that can interfere with longitudinal imaging studies/protocols. The realization of a PET/CT scanner sharing the same detection system for both 511 keV and X-ray photons and based on the LabPET II could remedy these problems. As a first step, a characterization of the detection module LabPET II was performed in PET and CT mode. The first CT imaging studies with this detector were also conducted with a simulator. This work allowed identifying an optical crosstalk phenomenon in the detection module. The search for a solution to this problem has motivated the evaluation of new types of metallized, more opaque, reflectors to limit crosstalk effects. The relatively low signal detected in CT led us to explore alternative scintillators having a higher light output. One of these scintillators will significantly improve the performance of the LabPET I scanner and could be used for the next generation of LabPET II scanners.

Pour répondre à des questions biologiques émergentes, l’IRM 3D in vivo est une approche de choix, mais elle souffre principalement d’une faible résolution temporelle en raison d’une faible sensibilité. Par ailleurs, l’IRM gagnerait à une meilleure sensibilité aux agents de contrastes exogènes. Il est proposé ici des développements en IRM du petit animal permettant de réduire considérablement la durée d’acquisition des images à trois dimensions chez la souris, ou la détection de très faibles quantités d’agents de contraste. Ces développements reposent sur la manipulation de l’espace-k (espace des données acquises). La première partie de ce travail a reposé sur la mise en place d’une méthode d’acquisition rapide de l’imagerie 3D permettant de conserver la qualité de l’image. Le «keyhole» 3D a été la technique choisie pour accéder à une résolution temporelle très élevée. Ainsi, le temps d’acquisition en imagerie ciné 3D cardiaque, chez la souris, a été réduit par un facteur 4 tout en conservant la qualité de l’image (SSB) et les informations extraites. Le «keyhole» 3D est aussi une méthode favorable à la mesure de prise de contraste. La biodistribution d’agent de contraste, peut être suivie en imagerie 3D à contrastes T1 et T2* dans le corps entier de la souris en quasi temps réel. La manipulation de l’espace-k permet aussi d’améliorer la qualité de l’image en réalisant une imagerie très sensible au contraste T2*. Pour cela, la correction de mouvements intrinsèques, comme ceux issus de la respiration au niveau de l’abdomen, générant un effet de perte de résolution spatiale, est indispensable. L’utilisation d’un écho navigateur permettant de détecter et de supprimer tous les signaux indésirables apporte une amélioration nette de la qualité d’image. Le seuil de détection de l’agent de contraste testé est d’ailleurs inférieur à 100 picomole de fer par kilogramme dans l’abdomen de souris. L’utilisation des propriétés de l’espace-k montre à quel point la qualité de l’image peut être améliorée et adaptée à l’information souhaitée. C’est un moyen peu couteux et efficace pour rendre l’imagerie par résonance magnétique encore plus performante en terme de résolution spatiale et de résolution temporelle. / In vivo 3D MRI is a powerful method which can be used to answer emerging biological issues. However, low temporal resolution due to intrinsic low sensitivity is one of its main drawbacks. Similarly, breakthroughs are needed to detect by MRI low-concentrated contrast agents used for molecular imaging. In this work, several methodology developments in small animals are proposed to greatly reduce acquisition times of 3D MRI and to increase contrast sensitivity to T2* agents. Both achievements were performed through the manipulation of the k-space, i.e the acquired data space in a retrospective approach. To achieve very high temporal resolution a 3D keyhole technique was chosen. This allowed the acquisition time in cardiac 3D-cine imaging in mice to be reduced by a factor 4. Image quality (signal-to-noise ratio) and the extracted functional data were preserved. Interestingly, 3D keyhole imaging also allowed the evaluation of T1 and T2* contrast enhancement and biodistribution in real time in the whole mouse body. In the last part of the work, the goal was to generate highly T2*-sensitive 3D images in mouse abdomen to detect diluted iron-oxide-based contrast agents. The use of a navigator echo enabled efficient motion correction and detection threshold of less than 100 picomol iron per kilogram. The results are discussed in a general frame of future applications and development of fast and highly-resolved 3D imaging.

L’imagerie préclinique dans le domaine de la cancérologie est en plein essor. Elle permet grâce à des modèles animaux représentatifs de cancers humains de comprendre les mécanismes de développement des pathologies et d’évaluer l’efficacité thérapeutique d’un nouveau traitement. Le principal objectif de ce travail a été de développer deux modèles orthotopiques de cancer (pancréas et colon) et d’évaluer des traitements de références ainsi qu’une nouvelle stratégie thérapeutique par plasma froid fibré appelée Plasma Gun. Les 2 modèles de cancers développés ont montré une bonne représentativité vis-à-vis des cancers humains, avec l’apparition de métastases à distance et la présence de zones hypoxiques. Le 5-fluorouracile pour le modèle orthotopique de carcinome colorectal HCT116-luc et la gemcitabine pour le modèle d’adénocarcinome pancréatique MIA PaCa2-luc ont induit à faible dose des effets discrets pouvant être mis en évidence grâce aux modalités d’imageries mises en oeuvre. Après validation de nos démarches expérimentales une nouvelle stratégie thérapeutique, le Plasma Gun, a été évaluée et a montré des effets significatifs sur l’inhibition de la croissance tumorale. Le second objectif de ma thèse a été de mettre en oeuvre des outils pour l’induction et la caractérisation des métastases osseuses ainsi que pour l’imagerie haute résolution de la vascularisation. D’une part, les métastases osseuses obtenues par injection de cellules PC3M-luc en intracardiaque ont été évaluées et quantifiées grâce à différentes modalités d’imagerie (bioluminescence, scintigraphie et scanner X). D’autre part, la réalisation d’une imagerie haute résolution de la vascularisation a été possible grâce à la technique de casting qui permet de recréer la structure 3D de l’architecture vasculaire suite à l’injection d’une résine dans la circulation. Les développements réalisés lors de cette thèse ont ainsi permis d’apporter des outils pour l’évaluation préclinique de nouvelles thérapies anticancéreuses. / Preclinical imaging in oncology is booming. It allows, using representative animal models of human cancers, to understand the mechanisms of development of pathologies and to assess the therapeutic efficiency of a new treatment. The main objective of this work was to develop two orthotopic models of cancer (pancreas and colon) and to assess on them the reference treatments as well as a new therapeutic strategy by non thermal plasma so called Plasma Gun. The two cancer models developed showed good representation in relation to human cancers, with the appearance of distant metastases and hypoxia. 5-fluorouracil for the HCT116-luc orthotopic model of colorectal carcinoma and gemcitabine for the MIA PaCa2-luc pancreatic adenocarcinoma model, have induced discrete effects at low dose wich can be detected thanks imaging modalities. After validation of our experimental steps, a new therapeutic strategy, Plasma Gun was evaluated and showed significant effects on tumor growth inhibition. The second objective was to carry out tools for the induction and the characterization of bone metastases and for high resolution imaging of the vasculature. On the one hand, bone metastases obtained by injection of PC3M-luc cells intracardially, was evaluated and quantified with different imaging modalities (bioluminescence, scintigraphy and Computed Tomography). And the other hand, the achievement of a high resolution imaging of vascularization, was possible by the casting method that restores the 3D structure of the vascular architecture following injection of a resin in the circulation.

Motivated by the need to standardize preclinical imaging for image-guided radiation therapy (IGRT), we examine the parameters that influence microcomputed tomography (microCT) scans in the realm of image quality and absorbed dose to tissue, including therapy beam measurements of small fields. Preclinical radiation research aims to understand radiation-induced effects in living tissues to improve quality of life. Small targets and low kilovoltage x-rays create challenges that do not arise in clinical radiation therapy. Evidence based on our multi-institutional study reveals a considerable aberration in microCT image quality from one institution to the next. We propose the adoption of recommended tolerance levels to provide a baseline for producing satisfactory and reproducible microCT image quality scans for accurate dose delivery in preclinical IGRT. Absorbed dose imparted by these microCT images may produce deterministic effects that can negatively influence a radiobiological study. Through Monte Carlo (MC) methods we establish absorbed microCT imaging dose to a variety of tissues and murine sizes for a comprehensive combination of imaging parameters. Radiation beam quality in the small confines of a preclinical irradiator is also established to quantify the effects of beam scatter on half-value layer measurements. MicroCT scans of varying imaging protocols are also compared for murine subjects. Absorbed imaging dose to tissues are established and presented alongside their respective microCT images, providing a visual bridge to systematically link image quality and imaging dose. We then characterize a novel small plastic scintillating dosimeter to experimentally measure microCT imaging and therapy beams in real-time. The presented scintillating dosimeter is specifically characterized for the low energies and small fields found in preclinical research. Beam output is measured for small fields previously only achievable using film. Finally, quality assurance tests are recommended for a preclinical IGRT unit. Within this dissertation, a narrative is presented for guiding preclinical radiotherapy towards producing high quality microCT images with an understanding of the absorbed imaging dose deposited to tissues, including providing a tool to measure small radiation fields. / Graduate

<p>Developmental biology is a field in which explorations are made to answer how an organism transforms from a single cell to a complex system made up of trillions of highly organized and highly specified cells. This field, however, is not just for discovery, it is crucial for unlocking factors that lead to diseases, defects, or malformations. The one key ingredient that contributes to the success of studies in developmental biology is the technology that is available for use. Optical coherence tomography (OCT) is one such technology. OCT fills a niche between the high resolution of confocal microscopy and deep imaging penetration of ultrasound. Developmental studies of the chicken embryo heart are of great interest. Studies in mature hearts, zebrafish animal models, and to a more limited degree chicken embryos, indicate a relationship between blood flow and development. It is believed that at the earliest stages, when the heart is still a tube, the purpose of blood flow is not for convective transport of oxygen, nutrients and waster, bur rather to induce shear-related gene expressions to induce further development. Yet, to this date, the simple question of "what makes blood flow?" has not been answered. This is mainly due limited availability to adequate imaging and blood flow measurement tools. Earlier work has demonstrated the potential of OCT for use in studying chicken embryo heart development, however quantitative measurement techniques still needed to be developed. In this dissertation I present technological developments I have made towards building an OCT system to study chick embryo heart development. I will describe: 1) a swept-source OCT with extended imaging depth; 2) a spectral domain OCT system for non-invasive small animal imaging; 3) Doppler flow imaging and techniques for quantitative blood flow measurement in living chicken embryos; and 4) application of the OCT system that was developed in the Specific Aims 2-5 to test hypotheses generated by a finite element model which treats the embryonic chick heart tube as a modified peristaltic pump.</p> / Dissertation

This project examines small mammal faunas from cave sites in south-west England and south Wales. The aims are threefold: To examine the rapid environmental changes taking place in the Late Pleistocene and early Holocene: To understand the processes by which small mammal remains were deposited in the caves examined: To demonstrate the value of small mammal studies as an archaeological tool. All identifiable small mammal remains from twelve selected sites are listed. Ten of the sites are new material. As the species examined here are seldom exploited by humans, the small mammals provide a record of the past environment unaffected by human selection of particular species, as might be the case in larger mammal assemblages. An examination of possible agents of accumulation is provided for each site to identify any bias introduced by prey selection. Reconstructions of the environment local to each cave at the time of deposition are offered. The evidence provided by the small mammals is related to the archaeological findings from each cave, to demonstrate the effect of human habitation of cave sites on the depositional and post-depositional processes shown by the microfauna. The environmental evidence provided by the study reflects a wider landscape rather than merely the immediate surroundings of the cave, and so gives a basis for human exploitation patterns in the area accessible from the cave. Reconstructions of the ecological mosaics formed by the rapidly changing climate of the period and the topographic variation around the cave sites are provided, demonstrating the potential complexity of the environment in which the humans and other fauna of the period existed. It is hoped that this will encourage archaeologists to look beyond the general division of environmental boundaries in this period, and to examine the local variation in habitat availability and use.

No description available.

L'objectif de cette thèse est d’étudier temporellement des phénomènes évolutifs à l'aide de la tomographie d'émission monophotonique (TEMP). La première partie de cette thèse traite le problème du mouvement respiratoire dans les images TEMP de souris. Nous présentons ici une méthode permettant de détecter ce mouvement respiratoire dans les images TEMP 4D, d'extraire un signal respiratoire intrinsèque, et de déterminer la phase du cycle respiratoire sans mouvement la plus large possible. Les données enregistrées durant ces phases sans mouvement sont alors utilisées pour reconstruire une seule image TEMP 3D sans artefact de mouvement par acquisition. Les images ainsi reconstruites présentent un bon compromis en terme de statistiques et de précision des mesures par rapport aux images TEMP 3D de base et TEMP 4D. Dans la deuxième partie, nous étudions la cinétique d'incorporation de l'iode dans l'estomac de souris à partir d'images TEMP 4D. Afin de comprendre le rôle biologique de cette accumulation dans l'estomac, nous avons modélisé le phénomène par une approche d'analyse compartimentale avec un modèle simplifiée à deux compartiments (paroi et cavité stomacale) et une entrée (sang). Les courbes temps-activité (TAC) de chaque compartiment sont déduites des observations et une première estimation des paramètres a été obtenue. / The aim of this thesis is to investigate temporally evolving phenomena with the use of single photon emission computed tomography (SPECT).The first part of this thesis addresses the problem of respiratory motion in SPECT images of mice. The presented method permits us to detect the respiratory motion in 4D SPECT images, to extract an intrinsic respiratory signal and to determine the widest possible phase of the respiratory cycle without movement. The data recorded during these motionless phases are then used to reconstruct a single 3D SPECT image without motion artefacts per acquisition. Reconstructed motionless SPECT images present a good compromise in terms of statistics and accuracy of the measurements with respect to basic 3D SPECT and 4D SPECT images. In the second part, we study the iodide uptake kinetics in the stomach 99mTc-pertechnetate biodistribution with the of mice through the study of use of 4D SPECT images. To understand the biological role of the iodide accumulation in the stomach, we modelled the phenomenon with a compartmental analysis approach using a simplified two-compartment (stomach wall and cavity) model with one input (blood). Time activity curves (TAC) of each compartment are deduced from observations and a first estimation of the parameters was obtained.