No description available.

Le traitement des gliomes de haut grade constitue aujourd'hui encore un réel enjeu médical. Les techniques actuellement disponibles sont principalement palliatives et permettent d'augmenter la survie des patients de quelques mois seulement. Une technique innovante de radiothérapie consiste à renforcer la dose déposée dans la tumeur grâce à l'injection d'atomes lourds de manière spécifique dans celle-ci au préalable d'une irradiation de photons de basse énergie (50-100 keV). Cette technique a fait l'objet d'essais précliniques et maintenant d'essais cliniques de phases I et II sur la ligne médicale du synchrotron Européen dont le rayonnement monochromatique et intense est particulièrement adapté pour l'application. L'utilisation d'un agent de contraste (AC) iodé (Z=53) injecté par voie veineuse permet d'améliorer le bénéfice de la radiothérapie mais n'est cependant pas suffisante pour l'élimination complète de la tumeur. En effet, l'accumulation passive d'atomes lourds dans la tumeur n'est pas assez importante et le caractère extracellulaire d'un AC ne maximise pas l'efficacité biologique de l'irradiation. Les nanoparticules (NPs) métalliques apparaissent comme un moyen efficace pour repousser ces limites. Dans le cadre de cette thèse, des études ont été conduites sur la lignée cellulaire de gliome F98 afin de caractériser la toxicité et l'internalisation de trois types de nanoparticules différents : nanoparticules de gadolinium (GdNPs 3 nm), d'or (AuNPs 13 nm) et de platine (PtNPs 6 nm). La survie cellulaire a également été évaluée après différentes conditions d'irradiation de photons monochromatiques en présence de ces nano-objets. La dépendance de la réponse cellulaire à l'énergie du rayonnement incident ainsi qu'à la distribution subcellulaire des NPs a permis de mettre en évidence plusieurs mécanismes mis en jeu dans ce traitement. A concentration identique, les NPs diminuent la survie cellulaire de manière plus importante qu'un AC, validant ainsi l'intérêt microdosimétrique des NPs. L'effet est préférentiel à basse énergie (keV) indiquant que la photoactivation des atomes lourds est en partie responsable la réponse cellulaire. Par ailleurs, les GdNPs et les PtNPs se sont aussi montrées efficaces pour diminuer la survie cellulaire en combinaison à une irradiation à haute énergie (1.25 MeV) indiquant qu'un mécanisme de radiosensibilisation différent de la photoactivation intervient également. Les études précliniques, ont montré que le recouvrement complet de la tumeur par les NPs constitue un point clé pour garantir le bénéfice thérapeutique du traitement. Dans cette optique, une méthode de tomographie à deux énergies développée au synchrotron, a été caractérisée dans le cadre de ce travail. L'étude a permis d'imager de manière quantitative et simultanée la tumeur (mise en évidence par un AC iodé) et son recouvrement par des GdNPs (injectées par voie directe) chez le rongeur porteur d'un gliome. La correspondance entre la distribution de l'AC et la tumeur a également été étudiée à l'aide de techniques d'imagerie à haute résolution (IRM, tomographie X par contraste de phase et histologie). / Gliomas treatment is still a serious challenge in medicine. Available treatments are mainly palliative and patients' survival is increased by a few months only. An original radiotherapy technique consists in increasing the dose delivered to the tumor by loading it with high Z atoms before an irradiation with low energy X-rays (50-100 keV). Preclinical studies have been conducted using iodine contrast agent (CA) (Z=53) and 50 keV X-rays. The increase of the animals' survival leads today to the beginning of clinical trials (phases I and II) at the medical beamline of the European synchrotron, where the available monochromatic and intense photons beam is well suited for this treatment. The use of intravenously injected CA is however insufficient for curing rat's bearing glioma. Indeed, the contrast agent's accumulation is limited by the presence of the BBB and it remains extracellular. Metallic nanoparticles (NPs) appear interesting for improving the treatment efficacy. During this work, three different types of NPs have been studied: GdNPs (3 nm), AuNPs (13 nm) and PtNPs (6 nm). Their toxicity and internalization have been evaluated in vitro on F98 rodent glioma cells. Cells' survival has also been measured after different irradiation conditions in presence of these NPs and with monochromatic photons beams. Several mechanisms implicated in the treatment have been highlighted by the study of the cells' response dependence to the incident particles energy and to the sub cellular NPs distribution during irradiation. For identical concentrations, NPs were more efficient in cells killing than CA, illustrating their microdosimetric potential. The effect was also preferential for low energy X-rays, indicating that photoactivation of heavy atoms plays a role in the cells' death. GdNPs and PtNPs have also lead to an effect in combination to high energy photons (1.25 MeV), indicating that another mechanism may also increase the cell sensitivity to radiations with such NPs. Preclinical trials, performed on rats bearing F98 glioma, have shown that the complete tumor's overlap with NPs is a key point for the success of this treatment. Dual energy computed tomography (CT) has been developed at the synchrotron medical beamline and evaluated during this PhD thesis. The study has allowed quantitatively and simultaneously imaging the tumor (highlighted by iodinated CA) and the GdNPs distribution injected intracerebrally in rodents bearing glioma. The comparison between the CA distribution and the tumor's volume has also been performed using high spatial resolutions imaging methods (MRI, X-rays phase contrast tomography and histology).

It is of clinical interest to decompose a three material mixture into its constituted substances using dual-energy CT. In radiation therapy, for example material decomposition can be used to determine tissue properties for the calculation of dose in treatment planning. Due to use of polychromatic spectrum in CT, beam hardening artifacts prevent to achieve fully satisfactory results. Here an iterative reconstruction algorithm proposed by A. Malusek, M. Magnusson, M.Sandborg, and G. Alm Carlsson in 2008 is implemented to achieve this goal. The iterative algorithm can be implemented with both single- and dual-energy CT. The material decomposition process is based on mass conservation and volume conservation assumptions. The implementation and evaluation of iterative reconstruction algorithm is done by using simulation studies of analyzing mixtures of water, protein and adipose tissue. The results demonstrated that beam hardening artifacts are effectively removed and accurate estimation of mass fractions of each base material can be achieved with the proposed method. We also compared our novel iterative reconstruction algorithm to the commonly used water pre-correction method. Experimental results show that our novel iterative algorithm is more accurate.

The treatment plan for radiation therapy with protons is based on images from a computed tomography (CT) scanner. This is problematic since the photons in the x-ray beam from the CT scanner and the protons are affected differently by the tissue in the patient, which introduce an uncertainty in the track length of the protons. The hypothesis of this study is that a new generation of CT scanners (DECT), with the capacity to simultaneously scan the patient with two photon spectra of different mean energy, will improve the tissue characterisation and which in turn reduce the uncertainty in the track length of the protons. In this study, the accuracy and precision of a DECT-based method from the literature is compared to the conventional calibration method used today at the University clinics in Sweden to relate the attenuation of the photon beam to the slowing down of the protons. The methods are tested on CT images of a phantom, a plastic body containing tissue equivalent plastic inserts of known elemental composition. The results turned out to be inconclusive as there were large uncertainties in the measurements. The method has potential, as has been shown in the literature, but there are many questions that need to be answered before the method is ready to be implemented at the clinic. / En proton som färdas genom människokroppen deponerar endast en liten del av sin energi längs vägen innan den plötsligt deponerar allt i slutet på dess bana. Hur lång dess bana är beror på protonens ursprungliga energi och den atomära sammansättningen hos vävnaden den passerar igenom. Om sammansättningen är känd går det genom att justera den initiala energin bestämma banlängden. Denna egenskap gör protonen väldigt attraktiv för strålterpi, då det innbär möjligheten att behandla med hög precision samt bespara frisk vävnad onödig dos. Strålterapi med protoner planeras idag med bilder från en skiktröntgen (CT) som underlag. Ett problem med det är att röntgenstrålarna från CT-skannern påverkas annorlunda än protonerna av vävnaden, vilket introducerar en osäkerhet i protonernas banlängd. Hypotesen i denna studie är att en ny generation av CT-scanner (DECT), med möjlighet att simultant skanna patienten med två fotonspektran av olika medelenergi, på ett bättre sätt ska kunna bestämma den atomära sammansättningen för vävnaden och därmed reducera osäkerheten i protonernas banlängd. Noggrannhet och precision för en DECT-baserad metod från litteraturen jämförs med den SECT-baserade kalibreringsmetoden, som idag används på Universitetssjukhusen i Sverige för att relatera fotonstrålens dämpning i vävnaden till protonernas inbromsning. Metoderna testas på CT bilder av ett fantom, en plastkropp innehållandes olika cylindrar av vävnadsekvivalent plast med känd atomär sammansättning. Resultatet av den här studien är inte starkt nog för att bevisa hypotesen för studien. Det insamlade bildmaterialet innehåller höga brusnivåer jämfört med de som rapporteras i literaturen. Brusnivåer är så höga att det mesta av resultatet inte kan anses som statistiskt signifikant. Det är dessutom svårt att göra en direkt jämförelse av prestanda med befintlig teori för vävnadskaraktärisering, då bildmaterialet från de CT skanners som jämfördes är av olika typer. De resultat som publicerats i litteraturen visar att den DECT-baserade metoden har potential, men den här studien gör tydligt att det fortfarande finns frågor som måste besvaras innan metoden är redo att implementeras kliniskt.

The purpose of this project was to explore the performance of methods for estimating stopping power ratio (SPR) from Hounsfield units (HU) using dual energy CT scans, rather than the standard single energy CT scans, with the aim of finding a method which could outperform the current single energy stoichiometric method. Such a method could reduce the margin currently added to the target volume during treatment which is defined as 3.5 % of the range to the target volume + 1 mm . Three such methods, by Taasti, Zhu, and, Lalonde and Bouchard, were chosen and implemented in MATLAB. A phantom containing 10 tissue-like inserts was scanned and used as a basis for the SPR estimation. To investigate the variation of the SPR from day-to-day the phantom was scanned once a day for 12 days. The resulting SPR of all methods, including the stoichiometric method, were compared with theoretical SPR values which were calculated using known elemental weight fractions of the inserts and mean excitation energies from the National Institute of Standards and Technology (NIST). It was found that the best performing method was the Taasti method which had, at best, an average percentage difference from the theoretical values of only 2.5 %. The Zhu method had, at best, 4.8 % and Lalonde-Bouchard 15.6% including bone tissue or 6.3 % excluding bone. The best average percentage difference of the stoichiometric method was 3.1 %. As the Taasti method was the best performing method and shows much promise, future work should focus on further improving its performance by testing more scanning protocols and kernels to find the ones yielding the best performance. This should then be supplemented with testing different pairs of energies for the dual energy scans. The fact that the Zhu and Lalonde-Bouchard method performed poorly could indicate problems with the implementation of those methods in this project. Investigating and solving those problems is also an important goal for future projects. Lastly the Lalonde-Bouchard method should be tested with more than two energy spectra.

Dans le cadre de ses actions de R&D sur la caractérisation non destructive, le CEA dispose d’un système d'imagerie photonique de haute énergie. Ce dispositif, unique en France, permet de réaliser des radiographies et des tomographies sur des objets de grands volumes, tels que des colis de déchets radioactifs. Le Laboratoire de Mesures Nucléaires, qui mène les projets de recherche sur cette installation, a engagé une évolution majeure du système en lançant l'approvisionnement d'une nouvelle source X d'énergie augmentée et d'un banc mécanique de positionnement d'une capacité de 5 tonnes afin de pouvoir caractériser des objets de grande épaisseur : jusqu'à 140 cm de béton. Les travaux qui ont fait l'objet de cette thèse s'inscrivent dans ce contexte de caractérisation et de mise en service du nouveau tomographe, qui permet la mise en place de nouvelles modalités d'examen telles que la tomographie bi-énergie.La première partie de la thèse consiste en une étude approfondie des performances du nouveau tomographe en termes de capacité de pénétration et de résolution spatiale. Elle concerne à la fois la source X et le système de détection. La source X est un accélérateur linéaire Saturne reconditionné pour atteindre des énergies comprises entre 15 et 20 MeV pour des débits de dose supérieurs à 100 Gy/min. Les caractéristiques attendues de cette source sont évaluées par simulation : spectres, taches focales et débits de dose. En parallèle, la recherche d'un système de détection adapté conduit à mettre en compétition trois détecteurs : une série de semi-conducteurs CdTe non jointifs, une caméra linéaire à scintillateur CdWO4 segmenté et des écrans horizontaux de CsI filmés par des caméras bas bruit. Tous trois font l'objet d'une analyse par comptage de quanta (Quantum Accounting Diagram) permettant de mettre en lumière les qualités et limites de chacun à travers l'évaluation et la comparaison d'indicateurs complémentaires de leurs performances : efficacité quantique de détection, rapport signal sur bruit, résolution spatiale et gamme dynamique. Cette étude théorique est complétée, corrigée et validée par des campagnes de mesures expérimentales et permet finalement de prévoir les performances attendues avec l'accélérateur Saturne, et ainsi définir le meilleur détecteur pour l'imagerie des objets ciblés.La seconde partie de la thèse concerne le développement d'une nouvelle méthode de caractérisation des matériaux par tomographie bi-énergie afin d’identifier au mieux le numéro atomique effectif du matériau et sa densité. L'état de l'art sur les techniques actuelles fait ressortir une méthode potentiellement intéressante pour les besoins de la caractérisation de colis de déchets nucléaires : la décomposition en double effet. Initialement développée pour l'imagerie de plus basse énergie, elle a été adaptée à la gamme d’énergie du tomographe en modifiant les interactions photon-matière prises en compte dans le procédé. La méthode a été testée et validée sur des simulations d'examens tomographiques obtenues avec le code de simulation MODHERATO.Il ressort de ces travaux de thèse que le nouveau système d'imagerie du CEA Cadarache devrait être en mesure à la fois d'accueillir et caractériser des objets massifs avec une qualité d'image satisfaisante et une résolution spatiale submillimétrique, mais également de mettre en œuvre des examens de tomographie bi-énergie permettant d'évaluer le numéro atomique et la densité des matériaux composant les objets examinés. / As part of its research and development activities on non-destructive characterisation, CEA utilizes a high-energy photonic imaging system. This instrument, unique in France, allows radiographic and tomographic analyses on large objects (e.g., nuclear waste drums). The "Laboratoire de Mesures Nucléaires", responsible for running research projects in the facility, has launched a major upgrade of the system by providing a new higher energy X-ray source and a new mechanical bench possessing a 5 t load, which allows the characterisation of thick objects (up to 140 cm concrete thickness). This PhD thesis concerns the characterisation and commissioning of the new computed tomography (CT) system and introduces new examination modalities, such as dual-energy CT.The first part of the thesis is a comprehensive study of the performance of the upgraded CT system, specifically regarding penetration capacity and spatial resolution and concerning both the X-ray source and the detection system. The X-ray source is a linear accelerator called Saturne, which has been repackaged to reach energies between 15 and 20 MeV with dose rates greater than 100 Gy/min. Simulation is used to assess the expected features of this source: spectra, focal spots and dose rates. Parallel comparison among three detectors -a series of non-abutting CdTe semiconductor sensors, a linear camera with segmented CdWO4 scintillators and horizontal screens of CsI filmed by low noise cameras - assessed the most suitable detection system. All three detection systems are studied using a quantum accounting analysis that highlights potentials and limitations of each system and enables measurement of complementary indicators of their performance: detector quantum efficiency, signal to noise ratio, spatial resolution and dynamic range. This theoretical study is completed, corrected and validated by experimental measurement campaigns. This extensive study predicts the expected performance when combined with the Saturne accelerator, allowing selection of the most appropriate detector for the imaging of large objects.The second part of the thesis concerns the development of a new method for the characterisation of materials by dual-energy CT, allowing a better assessment of the effective atomic number and the density of the material. The state of the art of current techniques highlights the potential interesting method for the characterising nuclear waste: the double effect decomposition. Initially developed for lower energy X-ray imaging, it has been adapted to match the energy range of the CT system by adapting the photon/matter interactions taken into account in the process. The method has been tested and validated on tomographic simulations obtained with the simulation code MODHERATO.This PhD work has shown that the new CT system of the CEA Cadarache has the potential to characterise massive objects with a satisfactory image quality and milli-scale spatial resolution. It also opens opportunities for the execution of dual-energy CT evaluations allowing the assessment of the atomic number and density of materials composing the examined objects.

Polymethylmethacrylate (PMMA) removal during septic total joint arthroplasty revision is associated with a high fracture and perforation risk. Ultrasonic cement removal is considered a bone-preserving technique. Currently, there is still a lack of sound data on efficacy as it is difficult to detect smaller residues with reasonable technical effort. However, incomplete removal is associated with the risk of biofilm coverage of the residue. Therefore, the study aimed to investigate the efficiency of ultrasonic-based PMMA removal in a human cadaver model. The femoral components of a total hip and a total knee prosthesis were implanted in two cadaver femoral canals by 3rd generation cement fixation technique. Implants were then removed. Cement mantle extraction was performed with the OSCAR-3-System ultrasonic system (Orthofix®). Quantitative analysis of cement residues was carried out with dual-energy and microcomputer tomography. With a 20 µm resolution, in vitro microcomputer tomography visualized tiniest PMMA residues. For clinical use, dual-energy computer tomography tissue decomposition with 0.75 mm resolution is suitable. With ultrasound, more than 99% of PMMA was removed. Seven hundred thirty-four residues with a mean volume of 0.40 ± 4.95 mm3 were identified with only 4 exceeding 1 cm in length in at least one axis. Ultrasonic cement removal of PMMA was almost complete and can therefore be considered a highly effective technique. For the first time, PMMA residues in the sub-millimetre range were detected by computer tomography. Clinical implications of the small remaining PMMA fraction on the eradication rate of periprosthetic joint infection warrants further investigations.

This diploma thesis deals with reduction of metal artifacts in CT data with submicron resolution. The first part of this thesis briefly describes x-ray computed tomography followed by the description of artifacts of tomographic images and existing approaches of the reduction of metal artifacts. In the second part proposed methods of reduction of metal artifacts and their implementation in Matlab programming environment are described. Finally functionality of algorithms is tested on a newly created database and the results are compared, evaluated and discussed.