Introdução: No momento, pouco se conhece sobre o desempenho diagnóstico da angiotomografia de coronárias com 64 colunas de detectores (Angio-TC 64) frente aos achados do ultrassom intracoronário com técnica de histologia virtual (USIC-HV). Este estudo compara a capacidade diagnóstica de ambos os métodos para a avaliação das dimensões vasculares e para avaliação da composição da placa aterosclerótica através da análise de toda extensão dos três vasos epicárdicos principais. Métodos e Resultados: Um total de 21 pacientes com diagnóstico de doença arterial coronária obstrutiva foi incluído neste estudo. Angio-TC 64 foi realizada em todos os pacientes antes da realização do USIC-HV, com intervalo<72horas entre os dois exames. No total, 70 vasos foram avaliados (3,3 vasos por paciente) e divididos em 641 subsegmentos de 4 mm de extensão cada. Um total de 5.972 cortes seccionais de USIC-HV e 5.233 cortes seccionais da Angio-TC 64 foram analisados. As medidas de área luminar, área do vaso, área da parede arterial e carga de placa à Angio-TC 64 e ao USIC-HV foram significativamente correlacionadas (r-Spearman: 0,81; 0,78; 0,55 e 0,49; respectivamente - p<0,001 para todas as correlações). A Angio-TC 64 subestimou a área luminar ao USIC-HV (em mediana: 0,4mm2 ,variando entre -5,6 mm2 e 10,2 mm2). A Angio-TC 64 superestimou a área do vaso, a área da parede arterial (placa+média) e a carga de placa (em mediana: 3,0 mm2; 3,2 mm2 e 13,9%, respectivamente). O aumento da densidade média da placa à Angio-TC 64 foi significativamente associado com o aumento da contribuição percentual dos componentes cálcio denso e núcleo necrótico ao USIC-HV. O aumento da densidade média da placa à Angio-TC 64 foi significativamente associado com a diminuição da contribuição percentual do componente fibro-lipídico ao USIC-HV. Parâmetros de qualidade da imagem (atenuação luminar, ruído da atenuação luminar e relação sinal ruído) influenciaram significativamente os resultados da Angio-TC 64. Conclusão: Nosso estudo demonstra que as imagens da Angio-TC 64 se correlacionam significativamente com as imagens do USIC-HV. Estes achados indicam que a Angio-TC 64 pode ser uma ferramenta útil para a avaliação quantitativa da luz arterial e da placa aterosclerótica; bem como para a avaliação da composição da placa aterosclerótica in vivo / Background: Currently, little is known about the comparative diagnostic performance for coronary assessment of 64-slice multidetector computed tomography (64-MDCT) versus virtual histology intravascular ultrasound technique (VH-IVUS). The present study compares the diagnostic ability of both methods for the evaluation of coronary lumen and vessel wall dimensions as well as plaque composition in a three-vessel whole-artery analysis protocol. Methods and Results: A total of 21 patients with diagnosed obstructive coronary artery disease was included. 64-MDCT was performed within 72 hours before the VH-IVUS examination. Overall, 70 vessels were imaged (3.3 vessels per patient), and divided into 641 subsegments of 4 mm each. A total of 5,972 VH-IVUS cross-sections and 5,233 64-MDCT cross-sections were analyzed. 64-MDCT and VH-IVUS measurements for luminar area, vessel area, arterial wall area (plaque plus media area) and plaque burden were significantly correlated (r-Spearman: 0.81; 0.78; 0.55 e 0.49; respectively - p<0,001 for all correlations). 64-MDCT underestimated VH-IVUS measurements for luminar area (median: 0.4mm2, range: -5.6 mm2 to 10,2 mm2). 64-MDCT overestimated VH-IVUS measurements for vessel area, arterial wall area, and plaque burden (median: 3.0 mm2; 3.2 mm2 e 13.9%, respectively). Increasing plaque density at 64-MDCT was significantly associated with increasing dense calcium and necrotic core percent composition at VH-IVUS. Increasing plaque density at 64-MDCT was significantly associated with decreasing fibrofatty percent composition, and decreasing necrosis-to-calcium ratio at VH-IVUS. Image quality parameters (i.e. lumen attenuation, image noise, signal-to-noise ratio) significantly influenced the results of 64-MDCT. Conclusion: Our study shows that 64-MDCT imaging significantly correlates with VH-IVUS. These findings indicate that 64-MDCT may be a useful non-invasive tool for quantitative evaluation of lumen and plaque parameters, as well as for the in vivo assessment of atherosclerotic plaque composition

The diploma thesis deals with the design of three length standards, which will serve to ensure metrological traceability between Rigaku nano3DX, SIOS NMM-1, Zeiss UPMC Carat 850 and other devices located at ÚVSSR BUT and CEITEC Brno. The first part of the thesis focuses on the theoretical acquaintance with concepts closely related to the issue of ensuring metrological traceability. In addition, this section deals with computed tomography and the description of individual devices. The second part of the thesis is devoted to design, production process and testing of individual standards. The last part describes the ensuring the calibration of the smallest standard, the so-called Nano standard and the calculation of the uncertainty of measuring its calibrated length. At the end of the thesis, the outputs of these activities are evaluated.

La tomodensitométrie par rayons-X (CT) est une modalité d’imagerie produisant une carte tridimensionnelle du coefficient d’atténuation des rayons-X d’un objet. En radiothérapie, le CT fournit de l’information anatomique et quantitative sur le patient afin de permettre la planification du traitement et le calcul de la dose de radiation à livrer. Le CT a plusieurs problèmes, notamment (1) une limitation au niveau de l’exactitude des paramètres physiques quantitatifs extraits du patient, et (2) une sensibilité aux biais causés par des artéfacts de durcissement du faisceau. Enfin, (3) dans le cas où le CT est fait en présence d’un agent de contraste pour améliorer la planification du traitement, il est nécessaire d’effectuer un deuxième CT sans agent de contraste à des fins de calcul de dose, ce qui augmente la dose au patient. Ces trois problèmes limitent l’efficacité du CT pour certaines modalités de traitement qui sont plus sensibles aux incertitudes comme la protonthérapie. Le CT spectral regroupe un ensemble de méthodes pour produire plusieurs cartes d’atténuation des rayons-X moyennées sur différentes plages énergétiques. L’information supplémentaire, pondérée en énergie qui est obtenue permet une meilleure caractérisation des matériaux analysés. Le potentiel de l’une de ces modalités spectrales, le CT bi-énergie (DECT), est déjà bien démontré en radiothérapie, alors qu’une approche en plein essor, le CT spectral à comptage de photons (SPCCT), promet davantage d’information spectrale à l’aide de détecteurs discriminateurs en énergie. Par contre, le SPCCT souffre d’un bruit plus important et d’un conditionnement réduit. Cette thèse investigue la question suivante : y a-t-il un bénéfice à utiliser plus d’information résolue en énergie, mais de qualité réduite pour la radiothérapie ? La question est étudiée dans le contexte des trois problèmes ci-haut. Tout d’abord, un estimateur maximum a posteriori (MAP) est introduit au niveau de la caractérisation des tissus post-reconstruction afin de débruiter les données du CT spectral. L’approche est validée expérimentalement sur un DECT. Le niveau de bruit du pouvoir d’arrêt des protons diminue en moyenne d’un facteur 3.2 à l’aide de l’estimateur MAP. Celui-ci permet également de conserver généralement le caractère quantitatif des paramètres physiques estimés, le pouvoir d’arrêt variant en moyenne de 0.9% par rapport à l’approche conventionnelle. Ensuite, l’estimateur MAP est adapté au contexte de l’imagerie avec agent de contraste. Les résultats numériques démontrent un bénéfice clair à utiliser le SPCCT pour l’imagerie virtuellement sans contraste par rapport au DECT, avec une réduction de l’erreur RMS sur le pouvoir d’arrêt des protons de 2.7 à 1.4%. Troisièmement, les outils développés ci-haut sont validés expérimentalement sur un micro-SPCCT de la compagnie MARS Bioimaging, dont le détecteur à comptage de photons est le Medipix 3, qui est utilisé pour le suivi de particules au CERN. De légers bénéfices au niveau de l’estimation des propriétés physiques à l’aide du SPCCT par rapport au DECT sont obtenus pour des matériaux substituts à des tissus humains. Finalement, une nouvelle paramétrisation du coefficient d’atténuation pour l’imagerie pré-reconstruction est proposée, dans le but ultime de corriger les artéfacts de durcissement du faisceau. La paramétrisation proposée élimine les biais au niveau de l’exactitude de la caractérisation des tissus humains par rapport aux paramétrisations existantes. Cependant, aucun avantage n’a été obtenu à l’aide du SPCCT par rapport au DECT, ce qui suggère qu’il est nécessaire d’incorporer l’estimation MAP dans l’imagerie pré-reconstruction via une approche de reconstruction itérative. / X-ray computed tomography (CT) is an imaging modality that produces a tridimensional map of the attenuation of X-rays by the scanned object. In radiation therapy, CT provides anatomical and quantitative information on the patient that is required for treatment planning. However, CT has some issues, notably (1) a limited accuracy in the estimation of quantitative physical parameters of the patient, and (2) a sensitivity to biases caused by beam hardening artifacts. Finally, (3) in the case where contrast-enhanced CT is performed to help treatment planning, a second scan with no contrast agent is required for dose calculation purposes, which increases the overall dose to the patient. Those 3 problems limit the efficiency of CT for some treatment modalities more sensitive to uncertainties, such as proton therapy. Spectral CT regroups a set of methods that allows the production of multiple X-ray attenuation maps evaluated over various energy windows. The additional energy-weighted information that is obtained allows better material characterization. The potential of one spectral CT modality, dual-energy CT (DECT), is already well demonstrated for radiation therapy, while an upcoming method, spectral photon counting CT (SPCCT), promises more spectral information with the help of energy discriminating detectors. Unfortunately, SPCCT suffers from increased noise and poor conditioning. This thesis thus investigates the following question: is there a benefit to using more, but lower quality energy-resolved information for radiotherapy? The question is studied in the context of the three problems discussed earlier. First, a maximum a posteriori (MAP) estimator is introduced for post-reconstruction tissue characterization for denoising purposes in spectral CT. The estimator is validated experimentally using a commercial DECT. The noise level on the proton stopping power is reduced, on average, by a factor of 3.2 with the MAP estimator. The estimator also generally con- serves the quantitative accuracy of estimated physical parameters. For instance, the stopping power varies on average by 0.9% with respect to the conventional approach. Then, the MAP estimation framework is adapted to the context of contrast-enhanced imaging. Numerical results show clear benefits when using SPCCT for virtual non-contrast imaging compared to DECT, with a reduction of the RMS error on the proton stopping power from 2.7 to 1.4%. Third, the developed tools are validated experimentally on a micro-SPCCT from MARS Bioimaging, which uses the Medipix 3 chip as a photon counting detector. Small benefits in the accuracy of physical parameters of tissue substitutes materials are obtained. Finally, a new parametrization of the attenuation coefficient for pre-reconstruction imaging is pro- posed, whose ultimate aim is to correct beam hardening artifacts. In a simulation study, the proposed parametrization eliminates all biases in the estimated physical parameters of human tissues, which is an improvement upon existing parametrizations. However, no ad- vantage has been obtained with SPCCT compared to DECT, which suggests the need to incorporate MAP estimation in the pre-reconstruction framework using an iterative reconstruction approach.

<div>The mechanical behaviors of different kinds of biological tissues, including muscle tissues, cortical bones, cancellous bones and skulls, were studied under various loading conditions to investigate their strain-rate sensitivities and loading-direction dependencies. Specifically, the compressive mechanical behaviors of porcine muscle were studied at quasi-static (<1/s) and intermediate (1/s─10^2/s) strain rates. Both the compressive and tensile mechanical behaviors of human muscle were investigated at quasi-static and intermediate strain rates. The effect of strain-rate and loading-direction on the compressive mechanical behaviors of human frontal skulls, with its entire sandwich structure intact, were also studied at quasi-static, intermediate and high (10^2/s─10^3/s) strain rates. The fracture behaviors of porcine cortical bone and cancellous bone were investigated at both quasi-static (0.01mm/s) and dynamic (~6.1 m/s) loading rates, with the entire failure process visualized, in real-time, using the phase contrast imaging technique. Research effort was also focused on studying the dynamic fracture behaviors, in terms of fracture initiation toughness and crack-growth resistance curve (R-curve), of porcine cortical bone in three loading directions: in-plane transverse, out-of-plane transverse and in-plane longitudinal. A hydraulic material testing system (MTS) was used to load all the biological tissues at quasi-static and intermediate loading rates. Experiments at high loading rates were performed on regular or modified Kolsky bars. Tomography of bone specimens was also performed to help understand their microstructures and obtain the basic material properties before mechanical characterizations. Experimental results found that both porcine muscle and human muscle exhibited non-linear and strain-rate dependent mechanical behaviors in the range from quasi-static (10^(-2)/s─1/s) to intermediate (1/s─10^2/s) loading rates. The porcine muscle showed no significant difference in the stress-strain curve between the along-fiber and transverse-to-fiber orientation, while it was found the human muscle was stiffer and stronger along fiber direction in tension than transverse-to fiber direction in compression. The human frontal skulls exhibited a highly loading-direction dependent mechanical behavior: higher ultimate strength, with an increasing ratio of 2, and higher elastic modulus, with an increasing ratio of 3, were found in tangential loading direction when compared with those in the radial direction. A transition from quasi-ductile to brittle compressive mechanical behaviors of human frontal skulls was also observed as loading rate increased from quasi-static to dynamic, as the elastic modulus was increased by factors of 4 and 2.5 in the radial and tangential loading directions, respectively. Experimental results also suggested that the strength in the radial direction was mainly depended on the diploë porosity while the diploë layer ratio played the predominant role in the tangential direction. For the fracture behaviors of bones, straight-through crack paths were observed in both the in-plane longitudinal cortical bone specimens and cancellous bone specimens, while the cracks were highly tortuous in the in-plane transverse cortical bone specimens. Although the extent of toughening mechanisms at dynamic loading rate was comparatively diminished, crack deflections and twists at osteon cement lines were still observed in the transversely oriented cortical bone specimens at not only quasi-static loading rate but also dynamic loading rate. The locations of fracture initiations were found statistical independent on the bone type, while the propagation direction of incipient crack was significantly dependent on the loading direction in cortical bone and largely varied among different types of bones (cortical bone and cancellous bone). In addition, the crack propagation velocities were dependent on crack extension over the entire crack path for all the three loading directions while the initial velocity for in-plane direction was lower than the other two directions. Both the cortical bone and cancellous bone exhibited higher fracture initiation toughness and steeper R-curves at the quasi-static loading rate than the dynamic loading rate. For cortical bone at a dynamic loading rate (5.4 m/s), the R-curves were steepest, and the crack surfaces were most tortuous in the in-plane transverse direction while highly smooth crack paths and slowly growing R-curves were found in the in-plane longitudinal direction, suggesting an overall transition from brittle to ductile-like fracture behaviors as the osteon orientation varies from in-plane longitudinal to out-of-plane transverse, and to in-plane transverse eventually.</div>

Im Rahmen der vorliegenden Dissertationsschrift „Semi-quantitative röntgentomographische Untersuchungen zur Biodistribution von magnetischen Nanopartikeln in biologischem Gewebe“ wurden tomographische Untersuchungen an biologischen Objekten durchgeführt. Bei diesen Objekten handelt es sich um Gewebeproben nach minimal-invasiven Krebstherapien wie zum Beispiel magnetischem Drug Targeting und magnetischer Wärmebehandlung. Der Erfolg dieser Therapien ist sowohl abhängig von der korrekten Verteilung der magnetischen Nanopartikel als auch von der Tatsache, dass diese in der Zielregion in einer ausreichenden Menge vorhanden sind. Das Vorliegen dieser beiden Voraussetzungen ist in der vorliegenden Arbeit untersucht worden. Dabei lag der Schwerpunkt der Arbeit auf der Quantifizierung von magnetischem Material in unterschiedlichen biologischen Gewebeproben mittels Röntgenmikrocomputertomographie (XµCT). Für diesen Zweck wurde ein Kalibrationssystem mit speziellen Phantomen entwickelt, mit dessen Hilfe eine Nanopartikelkonzentration einem Grauwert voxelweise zugewiesen werden kann. Mit Hilfe der Kalibration kann der Nanopartikelgehalt sowohl in monochromatischen als auch in polychromatischen tomographischen Daten im Vergleich zu magnetorelaxometrischen Ergebnissen mit wenigen Prozent Abweichung ermittelt werden. Trotz Polychromasie und damit einhergehenden Artefakten können 3-dimensionale röntgentomographische Datensätze mit einer geringfügigen Konzentrationsabweichung im Vergleich zur quantitativen Messmethode Magnetorelaxometrie semi-quantitativ ausgewertet werden. / The success of the minimal invasive cancer therapies, called magnetic drug targeting and magnetic heating treatment, depends strongly on the correct distribution of the magnetic nanoparticles on one side. On the other side it depends on the fact that a sufficient amount of magnetic nanoparticles carrying drugs is accumulated in the target region. To study whether these two requirements are fulfilled motivates this PhD thesis „Semi-quantitative X-ray-tomography examinations of biodistribution of magnetic nanoparticles in biological tissues“. The analysis of the distribution of the magnetic nanoparticles in tumours and other tissue examples is realized by means of X-ray-micro computer tomography (XμCT). The work focuses on the quantification of the magnetic nanoparticles in different biological tissue samples by means of XµCT. A calibration of the tomographic devices with adequate phantoms, developed in the frame of this work, opens now the possibility to analyze tomographic data in a semi-quantitative manner. Thus, the nanoparticle concentration can be allocated voxel-wise to the grey values of the three-dimensional tomographic data. With the help of calibration of the tomography equipments used, polychromatic as well as monochromatic three-dimensional representations of objects can be analyzed with regard to the biodistribution of magnetic nanoparticles as well as with regard to their quantity. The semi-quantitative results have been compared with results obtained with a quantitative measurement method magnetorelaxometry (MRX). Thereby a good agreement of the semi-quantitative and quantitative data has been figured out.

The majority of UK’s intermediate level radioactive waste is currently stored in 316L and 304L austenitic stainless steel containers in interim storage facilities for permanent disposal until a geological disposal facility has become available. The structural integrity of stainless steel canisters is required to persevere against environmental degradation for up to 500 years to assure a safe storage and disposal scheme. Hitherto existing severe localised corrosion observances on real waste storage containers after 10 years of exposure to an ambient atmosphere in an in-land warehouse in Culham at Oxfordshire, however, questioned the likelihood occurrence of stress corrosion cracking that may harm the canister’s functionality during long-term storage. The more corrosion resistant duplex stainless steel grade 2205, therefore, has been started to be manufactured as a replacement for the austenitic grades. Over decades, the threshold stress corrosion cracking temperature of austenitic stainless steels has been believed to be 50-60°C, but lab- and field-based research has shown that 304L and 316L may suffer from atmospheric stress corrosion cracking at ambient temperatures. Such an issue has not been reported to occur for the 2205 duplex steel, and its atmospheric stress corrosion cracking behaviour at low temperatures (40-50°C) has been sparsely studied which requires detailed investigations in this respect. Low temperature atmospheric stress corrosion cracking investigations on 2205 duplex stainless steel formed the framework of this PhD thesis with respect to the waste storage context. Long-term surface magnesium chloride deposition exposures at 50°C and 30% relative humidity for up to 15 months exhibited the occurrence of stress corrosion cracks, showing stress corrosion susceptibility of 2205 duplex stainless steel at 50°C.The amount of cold work increased the cracking susceptibility, with bending deformation being the most critical type of deformation mode among tensile and rolling type of cold work. The orientation of the microstructure deformation direction, i.e. whether the deformation occurred in transverse or rolling direction, played vital role in corrosion and cracking behaviour, as such that bending in transverse direction showed almost 3-times larger corrosion and stress corrosion cracking propensity. Welding simulation treatments by ageing processes at 750°C and 475°C exhibited substantial influences on the corrosion properties. It was shown that sensitisation ageing at 750°C can render the material enhanced susceptible to stress corrosion cracking at even low chloride deposition densities of ≤145 µm/cm². However, it could be shown that short-term heat treatments at 475°C can decrease corrosion and stress corrosion cracking susceptibility which may be used to improve the materials performance. Mechanistic understanding of stress corrosion cracking phenomena in light of a comprehensive microstructure characterisation was the main focus of this thesis.

Im Rahmen der vorliegenden Dissertationsschrift „Semi-quantitative röntgentomographische Untersuchungen zur Biodistribution von magnetischen Nanopartikeln in biologischem Gewebe“ wurden tomographische Untersuchungen an biologischen Objekten durchgeführt. Bei diesen Objekten handelt es sich um Gewebeproben nach minimal-invasiven Krebstherapien wie zum Beispiel magnetischem Drug Targeting und magnetischer Wärmebehandlung. Der Erfolg dieser Therapien ist sowohl abhängig von der korrekten Verteilung der magnetischen Nanopartikel als auch von der Tatsache, dass diese in der Zielregion in einer ausreichenden Menge vorhanden sind. Das Vorliegen dieser beiden Voraussetzungen ist in der vorliegenden Arbeit untersucht worden. Dabei lag der Schwerpunkt der Arbeit auf der Quantifizierung von magnetischem Material in unterschiedlichen biologischen Gewebeproben mittels Röntgenmikrocomputertomographie (XµCT). Für diesen Zweck wurde ein Kalibrationssystem mit speziellen Phantomen entwickelt, mit dessen Hilfe eine Nanopartikelkonzentration einem Grauwert voxelweise zugewiesen werden kann. Mit Hilfe der Kalibration kann der Nanopartikelgehalt sowohl in monochromatischen als auch in polychromatischen tomographischen Daten im Vergleich zu magnetorelaxometrischen Ergebnissen mit wenigen Prozent Abweichung ermittelt werden. Trotz Polychromasie und damit einhergehenden Artefakten können 3-dimensionale röntgentomographische Datensätze mit einer geringfügigen Konzentrationsabweichung im Vergleich zur quantitativen Messmethode Magnetorelaxometrie semi-quantitativ ausgewertet werden. / The success of the minimal invasive cancer therapies, called magnetic drug targeting and magnetic heating treatment, depends strongly on the correct distribution of the magnetic nanoparticles on one side. On the other side it depends on the fact that a sufficient amount of magnetic nanoparticles carrying drugs is accumulated in the target region. To study whether these two requirements are fulfilled motivates this PhD thesis „Semi-quantitative X-ray-tomography examinations of biodistribution of magnetic nanoparticles in biological tissues“. The analysis of the distribution of the magnetic nanoparticles in tumours and other tissue examples is realized by means of X-ray-micro computer tomography (XμCT). The work focuses on the quantification of the magnetic nanoparticles in different biological tissue samples by means of XµCT. A calibration of the tomographic devices with adequate phantoms, developed in the frame of this work, opens now the possibility to analyze tomographic data in a semi-quantitative manner. Thus, the nanoparticle concentration can be allocated voxel-wise to the grey values of the three-dimensional tomographic data. With the help of calibration of the tomography equipments used, polychromatic as well as monochromatic three-dimensional representations of objects can be analyzed with regard to the biodistribution of magnetic nanoparticles as well as with regard to their quantity. The semi-quantitative results have been compared with results obtained with a quantitative measurement method magnetorelaxometry (MRX). Thereby a good agreement of the semi-quantitative and quantitative data has been figured out.