Ce travail s’inscrit dans le cadre du développement d’une médecine davantage personnalisée et préventive, pour laquelle la fusion d’informations multi modale et de différentes représentations d'une même modalité sont nécessaires afin d'aboutir à une quantification fiable des images médicales en oncologie. Dans cette étude nous présentons deux applications de traitement et d'analyse des images médicales: le débruitage des images TEP et la détermination des volumes anatomo-fonctionnels des tumeurs en imagerie multi modale TEP/TDM. Pour le débruitage des images TEP, nous avons mis en place une approche intitulée "WCD" permettant de bénéficier des caractéristiques complémentaires de la transformée en ondelettes et la transformée en Curvelets afin de mieux représenter les structures isotropiques et anisotropiques dans ces images, ce qui permet de réduire le bruit tout en minimisant les pertes d'informations utiles dans les images TEP. En ce qui concerne la deuxième application, nous avons proposé une méthode de segmentationTEP/TDM intitulée "WCHMT" permettant d'exploiter la spécificité des arbres de Markov caché de prendre en compte les dépendances statistiques entre l’ensemble des données. Ce modèle permet de gérer simultanément les propriétés complémentaires de l’imagerie fonctionnelle et l’imagerie morphologique dans un cadre unifié où les données sont représentées dans le domaine des Contourlets. Le débruitage en TEP a abouti à une hausse significative du rapport signal sur-bruit (SNR) en garantissant la moindre variation de l'intensité et du contraste local. Quant à la segmentation multimodale TEP/TDM, elle a démontré une bonne précision lors de la détermination du volume tumoral en terme du coefficient de Dice (DSC) avec le meilleur compromis entre la sensibilité (SE) et la valeur prédictive positive (PPV) par rapport à la vérité terrain. / This thesis is a part of the development of more personalized and preventive medicine, for which a fusion of multi modal information and diverse representations of the same modality is needed in order to get accurate and reliable quantification of medical images in oncology. In this study we present two applications for image processing analysis: PET denoising and multimodal PET/CT tumor segmentation. The PET filtering approach called "WCD" take benefit from the complementary features of the wavelet and Curvelets transforms in order to better represent isotropic and anisotropic structures in PET images. This algorithm allows the reduction of the noise while minimizing the loss of useful information in PET images. The PET/CT tumor segmentation application is performed through a Markov model as a probabilistic quadtree graph namely a Hidden Markov Tree (HMT).Our motivation for using such a model is to provide fast computation, improved robustness and an effective interpretational framework for image analysis on oncology. Thanks to two efficient aspects (multi observation and multi resolution), when dealing with Hidden Markov Tree (HMT), we exploit joint statistical dependencies between hidden states to handle the whole data stack. This model called "WCHMT" take advantage of the high resolution of the anatomic imaging (CT) and the high contrast of the functional imaging (PET). The denoising approach led to the best trade-off between denoising quality and structure preservation with the least quantitative bias in absolute intensity recovery. PET/CT segmentation's results performed with WCHMT method has proven a reliable segmentation when providing high Dice Similarity Coeffcient (DSC) with the best trade-off between sensitivity (SE) and positive predictive value (PPV).

Automated spine or vertebra detection and segmentation from CT images is a difficult task for several reasons. One of the reasons is unclear vertebra boundaries and indistinct boundaries between vertebra. Next reason is artifacts in images and high degree of anatomical complexity. This paper describes the design and implementation of vertebra detection and classification in CT images of cancer patients, which adds to the complexity because some of vertebrae are deformed. For the vertebra segmentation, the Otsu’s method is used. Vertebra detection is based on search of borders between individual vertebra in sagittal planes. Decision trees or the generalized Hough transform is applied for the identification whereas the vertebra searching is based on similarity between each vertebra model shape and planes of CT scans.

Dans le contexte du traitement du cancer de la prostate, l’utilisation de la tomodensitométrie à faisceau conique (CBCT) pour la radiothérapie guidée par l’image, éventuellement adaptative, présente certaines difficultés en raison du faible contraste et du bruit important dans les images pelviennes. L’objectif principal de cette thèse est d’apporter des contributions méthodologiques pour le recalage automatique entre l’image scanner CT de référence et l’image CBCT acquise le jour du traitement. La première partie de nos contributions concerne le développement d’une stratégie de correction du positionnement du patient à l’aide du recalage rigide (RR) CT/CBCT. Nous avons comparé plusieurs algorithmes entre eux : (a) RR osseux, (b) RR osseux suivi d’un RR local dans une région qui correspond au clinical target volume (CTV) de la prostate dans l’image CT élargie d’une marge allant de 1 à 20 mm. Une analyse statistique complète des résultats quantitatifs et qualitatifs utilisant toute la base de données, composée de 115 images cone beam computed tomography (CBCT) et de 10 images computed tomography (CT) de 10 patients atteints du cancer de la prostate, a été réalisée. Nous avons également défini une nouvelle méthode pratique et automatique pour estimer la distension rectale produite dans le voisinage de la prostate entre l’image CT et l’image CBCT. A l’aide de notre mesure de distension rectale, nous avons évalué l’impact de la distension rectale sur la qualité du RR local et nous avons fourni un moyen de prédire les échecs de recalage. Sur cette base, nous avons élaboré des recommandations concernant l’utilisation du RR automatique pour la localisation de la prostate sur les images CBCT en pratique clinique. La seconde partie de la thèse concerne le développement méthodologique d’une nouvelle méthode combinant le recalage déformable et la segmentation. Pour contourner le problème du faible rapport qualité/bruit dans les images CBCT qui peut induire le processus de recalage en erreur, nous avons imaginé une nouvelle énergie composée de deux termes : un terme de similarité globale (la corrélation croisée normalisée (NCC) a été utilisée, mais tout autre mesure de similarité pourrait être utilisée à la place) et un terme de segmentation qui repose sur une adaptation locale du modèle de l’image homogène par morceaux de Chan-Vese utilisant un contour actif dans l’image CBCT. Notre but principal était d’améliorer la précision du recalage comparé à une énergie constituée de la NCC seule. Notre algorithme de recalage est complètement automatique et accepte comme entrées (1) l’image CT de planification, (2) l’image CBCT du jour et (3) l’image binaire associée à l’image CT et correspondant à l’organe d’intérêt que l’on cherche à segmenter dans l’image CBCT au cours du recalage. / The use of CBCT imaging for image-guided radiation therapy (IGRT), and beyond that, image-guided adaptive radiation therapy (IGART), in the context of prostate cancer is challenging due to the poor contrast and high noise in pelvic CBCT images. The principal aim of the thesis is to provide methodological contributions for automatic intra-patient image registration between the planning CT scan and the treatment CBCT scan. The first part of our contributions concerns the development of a CBCT-based prostate setup correction strategy using CT-to-CBCT rigid registration (RR). We established a comparison between different RR algorithms: (a) global RR, (b) bony RR, and (c) bony RR refined by a local RR using the prostate CTV in the CT scan expanded with 1- to-20-mm varying margins. A comprehensive statistical analysis of the quantitative and qualitative results was carried out using the whole dataset composed of 115 daily CBCT scans and 10 planning CT scans from 10 prostate cancer patients. We also defined a novel practical method to automatically estimate rectal distension occurred in the vicinity of the prostate between the CT and the CBCT scans. Using our measure of rectal distension, we evaluated the impact of rectal distension on the quality of local RR and we provided a way to predict registration failure. On this basis, we derived recommendations for clinical practice for the use of automatic RR for prostate localization on CBCT scans. The second part of the thesis provides a methodological development of a new joint segmentation and deformable registration framework. To deal with the poor contrast-to-noise ratio in CBCT images likely to misguide registration, we conceived a new metric (or enery) which included two terms: a global similarity term (the normalized cross correlation (NCC) was used, but any other one could be used instead) and a segmentation term based on a localized adaptation of the piecewise-constant region-based model of Chan-Vese using an evolving contour in the CBCT image. Our principal aim was to improve the accuracy of the registration compared with an ordinary NCC metric. Our registration algorithm is fully automatic and takes as inputs (1) the planning CT image, (2) the daily CBCT image and (3) the binary image associated with the CT image and corresponding to the organ of interest we want to segment in the CBCT image in the course of the registration process.

Asphalt joints are potentially weakest parts of every pavement. Despite of their importance, reliable tools for measuring their mechanical properties for design and performance assessments are still scarce. This is particularly true for cold joints when attaching a new hot pavement to a cold existing one as in case of large patches for pavement repair. In this study, three static fracture testing methods, i.e. indirect tensile test (IDT), direct tension test (DTT) and 4 point bending (4PB), were adapted and used for evaluating different laboratory made joints. The results suggested that joints with inclined interfaces and also the ones with combined interface treatments (preheated and sealed) seemed to show more promising behaviors than the vertical and untreated joints. It was also confirmed that compacting from the hot side towards the joint improved the joint properties due to imposing a different flow pattern as compared to the frequent compaction methods. The latter finding highlighted the importance of asphalt particle rearrangements and flow during the compaction phase as a very little known subject in asphalt industry. Studies on compaction are of special practical importance since they may also contribute to reducing the possibility of over-compaction and aggregate crushing. Therefore, in this study, a new test method, i.e. Flow Test (FT), was developed to simulate the material flow during compaction. Initially, asphalt materials were substituted by geometrically simple model materials to lower the level of complexity for checking the feasibility of the test method as well as modeling purposes. X-ray radiography images were also used for capturing the flow patterns during the test. Results of the FT on model materials showed the capability of the test method to clearly distinguish between specimens with different characteristics. In addition, a simple discrete element model was applied for a better understanding of the test results as a basis for further improvements when studying real mixtures. Then, real mixtures were prepared and tested under the same FT configuration and the results were found to support the findings from the feasibility tests. The test method also showed its potential for capturing flow pattern differences among different mixtures even without using the X-ray. Therefore, the FT was improved as an attempt towards developing a systematic workability test method focusing on the flow of particles at early stages of compaction and was called the Compaction Flow Test (CFT). The CFT was used for testing mixtures with different characteristics to identify the parameters with highest impact on the asphalt particle movements under compaction forces. X-ray investigations during the CFT underlined the reliability of the CFT results. In addition, simple discrete element models were successfully generated to justify some of the CFT results. / <p>QC 20151104</p>

A presença da Medicina Nuclear como modalidade de obtenção de imagens médicas é um dos principais procedimentos utilizados hoje nos centros de saúde, tendo como grande vantagem a capacidade de analisar o comportamento metabólico do paciente, traduzindo-se em diagnósticos precoces. Entretanto, sabe-se que a quantificação em Medicina Nuclear é dificultada por diversos fatores, entre os quais estão a correção de atenuação, espalhamento, algoritmos de reconstrução e modelos assumidos. Neste contexto, o principal objetivo deste projeto foi melhorar a acurácia e a precisão na análise de imagens de PET/CT via processos realísticos e bem controlados. Para esse fim, foi proposta a elaboração de uma estrutura modular, a qual está composta por um conjunto de passos consecutivamente interligados começando com a simulação de phantoms antropomórficos 3D para posteriormente gerar as projeções realísticas PET/CT usando a plataforma GATE (com simulação de Monte Carlo), em seguida é aplicada uma etapa de reconstrução de imagens 3D, na sequência as imagens são filtradas (por meio do filtro de Anscombe/Wiener para a redução de ruído Poisson caraterístico deste tipo de imagens) e, segmentadas (baseados na teoria Fuzzy Connectedness). Uma vez definida a região de interesse (ROI) foram produzidas as Curvas de Atividade de Entrada e Resultante requeridas no processo de análise da dinâmica de compartimentos com o qual foi obtida a quantificação do metabolismo do órgão ou estrutura de estudo. Finalmente, de uma maneira semelhante imagens PET/CT reais fornecidas pelo Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) foram analisadas. Portanto, concluiu-se que a etapa de filtragem tridimensional usando o filtro Anscombe/Wiener foi relevante e de alto impacto no processo de quantificação metabólica e em outras etapas importantes do projeto em geral. / The presence of Nuclear Medicine as a medical imaging modality is one of the main procedures utilized nowadays in medical centers, and the great advantage of that procedure is its capacity to analyze the metabolic behavior of the patient, resulting in early diagnoses. However, the quantification in Nuclear Medicine is known to be complicated by many factors, such as degradations due to attenuation, scattering, reconstruction algorithms and assumed models. In this context, the goal of this project is to improve the accuracy and the precision of quantification in PET/CT images by means of realistic and well-controlled processes. For this purpose, we proposed to develop a framework, which consists in a set of consecutively interlinked steps that is initiated with the simulation of 3D anthropomorphic phantoms. These phantoms were used to generate realistic PET/CT projections by applying the GATE platform (with Monte Carlo simulation). Then a 3D image reconstruction was executed, followed by a filtering process (using the Anscombe/Wiener filter to reduce Poisson noise characteristic of this type of images) and, a segmentation process (based on the Fuzzy Connectedness theory). After defining the region of interest (ROI), input activity and output response curves are required for the compartment analysis in order to obtain the Metabolic Quantification of the selected organ or structure. Finally, in the same manner real images provided from the Heart Institute (InCor) of Hospital das Clínicas, Faculty of Medicine, University of São Paulo (HC-FMUSP) were analysed. Therefore, it is concluded that the three-dimensional filtering step using the Ascombe/Wiener filter was preponderant and had a high impact on the metabolic quantification process and on other important stages of the whole project.

A presença da Medicina Nuclear como modalidade de obtenção de imagens médicas é um dos principais procedimentos utilizados hoje nos centros de saúde, tendo como grande vantagem a capacidade de analisar o comportamento metabólico do paciente, traduzindo-se em diagnósticos precoces. Entretanto, sabe-se que a quantificação em Medicina Nuclear é dificultada por diversos fatores, entre os quais estão a correção de atenuação, espalhamento, algoritmos de reconstrução e modelos assumidos. Neste contexto, o principal objetivo deste projeto foi melhorar a acurácia e a precisão na análise de imagens de PET/CT via processos realísticos e bem controlados. Para esse fim, foi proposta a elaboração de uma estrutura modular, a qual está composta por um conjunto de passos consecutivamente interligados começando com a simulação de phantoms antropomórficos 3D para posteriormente gerar as projeções realísticas PET/CT usando a plataforma GATE (com simulação de Monte Carlo), em seguida é aplicada uma etapa de reconstrução de imagens 3D, na sequência as imagens são filtradas (por meio do filtro de Anscombe/Wiener para a redução de ruído Poisson caraterístico deste tipo de imagens) e, segmentadas (baseados na teoria Fuzzy Connectedness). Uma vez definida a região de interesse (ROI) foram produzidas as Curvas de Atividade de Entrada e Resultante requeridas no processo de análise da dinâmica de compartimentos com o qual foi obtida a quantificação do metabolismo do órgão ou estrutura de estudo. Finalmente, de uma maneira semelhante imagens PET/CT reais fornecidas pelo Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) foram analisadas. Portanto, concluiu-se que a etapa de filtragem tridimensional usando o filtro Anscombe/Wiener foi relevante e de alto impacto no processo de quantificação metabólica e em outras etapas importantes do projeto em geral. / The presence of Nuclear Medicine as a medical imaging modality is one of the main procedures utilized nowadays in medical centers, and the great advantage of that procedure is its capacity to analyze the metabolic behavior of the patient, resulting in early diagnoses. However, the quantification in Nuclear Medicine is known to be complicated by many factors, such as degradations due to attenuation, scattering, reconstruction algorithms and assumed models. In this context, the goal of this project is to improve the accuracy and the precision of quantification in PET/CT images by means of realistic and well-controlled processes. For this purpose, we proposed to develop a framework, which consists in a set of consecutively interlinked steps that is initiated with the simulation of 3D anthropomorphic phantoms. These phantoms were used to generate realistic PET/CT projections by applying the GATE platform (with Monte Carlo simulation). Then a 3D image reconstruction was executed, followed by a filtering process (using the Anscombe/Wiener filter to reduce Poisson noise characteristic of this type of images) and, a segmentation process (based on the Fuzzy Connectedness theory). After defining the region of interest (ROI), input activity and output response curves are required for the compartment analysis in order to obtain the Metabolic Quantification of the selected organ or structure. Finally, in the same manner real images provided from the Heart Institute (InCor) of Hospital das Clínicas, Faculty of Medicine, University of São Paulo (HC-FMUSP) were analysed. Therefore, it is concluded that the three-dimensional filtering step using the Ascombe/Wiener filter was preponderant and had a high impact on the metabolic quantification process and on other important stages of the whole project.

Electrical Impedance Tomography (EIT) is a non linear inverse problem in which the electrical conductivity or resistivity distribution across a closed domain of interest is reconstructed from the surface potentials measured at the domain boundary by injecting a constant sinusoidal current through an array of surface electrodes. Being a non-invasive, non-radiating, non-ionizing, portable and inexpensive methodology, EIT has been extensively studied in medical diagnosis, biomedical engineering, biotechnology, chemical engineering, industrial and process engineering, civil and material engineering, soil and rock science, electronic industry, defense field, nano-technology and many other fields of applied physics. The reconstructed image quality in EIT depends mainly on the boundary data quality and the performance of the reconstruction algorithm used. The boundary data accuracy depends on the design of the practical phantoms, current injection method and boundary data measurement process and precision. On the other hand, the reconstruction algorithm performance is highly influenced by the mathematical modeling of the system, performance of the forward solver and Jacobian computation, inverse solver and the regularization techniques. Hence, for improving the EIT system performance, it is essential to improve the design of practical phantom, instrumentation and image reconstruction algorithm. As the electrical impedance of biological materials is a function of tissue composition and the frequency of applied ac signal, the better assessment of impedance distribution of biological tissues needs multifrequency EIT imaging. In medical EIT, to obtain a better image quality for a complex organ or a body part, accurate domain modelling with a large 3D finite element mesh is preferred and hence, the computation speed becomes very expensive and time consuming. But, the high speed reconstruction with improved image quality at low cost is always preferred in medical EIT. In this direction, a complete multifrequency multifunction EIT (MfMf-EIT) system is developed and multifrequency impedance reconstruction is studied to improve the bioimpedance imaging. The MfMf-EIT system consists of an MfMf-EIT instrumentation (MfMf-EITI), high speed impedance image reconstruction algorithms (IIRA), a Personal Computer (PC) and a number of practical phantoms with EIT sensors or electrodes. MfMf-EIT system and high speed IIRA are studied tested and evaluated with the practical phantoms and the multifrequency impedance imaging is improved with better image quality as well as fast image reconstruction. The MfMf-EIT system is also applied to the human subjects and the impedance imaging is studied for human body imaging and the system is evaluated. MfMf-EIT instrumentation (MfMf-EITI) consists of a multifrequency multifunction constant current injector (MfMf-CCI), multifrequency multifunction data acquisition system (MfMf DAS), a programmable electrode switching module (P-ESM) and a modified signal conditioner blocks (M-SCB) or data processing unit (DPU). MfMf-CCI, MfMf-DAS, P-ESM and M-SCBs are interfaced with a LabVIEW based data acquisition program (LV-DAP) controlled by a LabVIEW based graphical user interface (LV-GUI). LV-GUI controls the current injection and data acquisition with a user friendly, fast, reliable, efficient measurement process. The data acquisition system performance is improved by the high resolution NIDAQ card providing high precision measurement and high signal to noise ratio (SNR). MfMf-EIT system is developed as a versatile data acquisition system with a lot of flexibilities in EIT parameter selection that allows studying the image reconstruction more effectively. MfMf-EIT instrumentation controls the multifrequency and multifunctioned EIT experimentation with a number of system variables such as signal frequency, current amplitude, current signal wave forms and current injection patterns. It also works with either grounded load CCI or floating load CCI and collects the boundary data either in grounded potential form or differential form. The MfMf-EITI is futher modified to a battery based MfMf-EIT (BbMfMf-EIT) system to obtain a better patient safety and also to improve the SNR of the boundary data. MfMf-EIT system is having a facility of injecting voltage signal to the objects under test for conducting the applied potential tomography (APT). All the electronic circuit blocks in MfMf-EIT instrumentation are tested, evaluated and calibrated. The frequency response, load response, Fast Fourier Transform (FFT) studies and DSO analysis are conducted for studying the electronic performance and the signal quality of all the circuit blocks. They are all evaluated with both the transformer based power supply (TBPS) and battery based power supply (BBPS). MfMf-DAS, P-ESM and LV-DAP are tested and evaluated with digital data testing module (DDTM) and practical phantoms. A MatLAB-based Virtual Phantom for 2D EIT (MatVP2DEIT) is developed to generate accurate 2D boundary data for assessing the 2D EIT inverse solvers and its image reconstruction accuracy. It is a MATLAB-based computer program which defines a phantom domain and its inhomogeneities to generate the boundary potential data by changing its geometric parameters. In MatVP2DEIT, the phantom diameter, domain discretization, inhomogeneity number, inhomogeneity geometry (shape, size and position), electrode geometry, applied current magnitude, current injection pattern, background medium conductivity, inhomogeneity conductivity all are set as the phantom variables and are chosen indipendently for simulating different phantom configurations. A constant current injection is simulated at the phantom boundary with different current injection protocols and boundary potential data are calculated. A number of boundary data sets are generated with different phantom configurations and the resistivity images are reconstructed using EIDORS (Electrical Impedance Tomography and Diffuse Optical Tomography Reconstruction Software). Resistivity images are evaluated with the resistivity parameters and contrast parameters estimated from the elemental resistivity profiles of the reconstructed impedance images. MfMf-EIT system is studied, tested, evaluated with a number of practical phantoms eveloped with non-biological and biological materials and the multifrequency impedance imaging is improved. A number of saline phantoms with single and multiple inhomogeneities are developed and the boundary data profiles are studied and the phantom geometry is modified. NaCl-insulator phantoms and the NaCl-vegetable phantoms with different inhomogeneity configurations are developed and the multifrequency EIT reconstruction is studied with different current patterns, different current amplitudes and different frequencies using EIDORS as well as the developed IIRAs developed in MATLAB to evaluate the phantoms and MfMf-EIT system. Real tissue phantoms are developed with different chicken tissue backgrounds and high resistive inhomogeneities and the resistivity image reconstruction is studied using MfMf-EIT system. Chicken tissue phantoms are developed with chicken muscle tissue (CMTP) paste or chicken tissue blocks (CMTB) as the background mediums and chicken fat tissue, chicken bone, air hole and nylon cylinders are used as the inhomogeneity to obtained different phantom configurations. Resistivity imaging of all the real tissue phantoms is reconstructed in EIDORS and developed IIRAs with different current patterns, different frequencies and the images are evaluated by the image parameters to assess the phantoms as well as the MfMf-EIT system. Gold electrode phantoms are developed with thin film based flexible gold electrode arrays for improved bioimpedance and biomedical imaging. The thin film based gold electrode arrays of high geometric precision are developed on flexible FR4 sheet using electro-deposition process and used as the EIT sensors. The NaCl phantoms and real tissue phantoms are developed with gold electrode arrays and studied with MfMf-EIT system and and the resiulsts are compared with identical stainless steel electrode phantoms. NaCl phantoms are developed with 0.9% NaCl solution with single and multiple insulator or vegetable tissues as inhomogeneity. Gold electrode real tissue phantoms are also developed with chicken muscle tissues and fat tissues or other high resistive objects. The EIT images are reconstructed for the gold electrode NaCl phantoms and the gold electrode real tissue phantoms with different phantom geometries, different inhomogeneity configurations and different current patterns and the results are compared with identical SS electrode phantoms. High speed IIRAs called High Speed Model Based Iterative Image Reconstruction (HSMoBIIR) algorithms are developed in MATLAB for impedance image reconstruction in Electrical Impedance Tomography (EIT) by implementing high speed Jacobian calculation techniques using “Broyden’s Method (BM)” and “Adjoint Broyden’s Method (ABM)”. Gauss Newton method based EIT inverse solvers repeatitively evaluate the Jacobian (J) which consumes a lot of computation time for reconstruction, whereas, the HSMoBIIR with Broyden’s Methods (BM)-based accelerated Jacobian Matrix Calculators (JMCs) provides the high speed schemes for Jacobian (J) computation which is integrated with conjugate gradient scheme (CGS) for fast impedance reconstruction. The Broyden’s method based HSMoBIIR (BM-HSMoBIIR) and Adjoint Broyden’s method based HSMoBIIR (ABM-HSMoBIIR) algorithm are developed for high speed improved impedance imaging using BM based JMC (BM-JMC) and ABM-based JMC (ABM-JMC) respectively. Broyden’s Method based HSMoBIIR algorithms make explicit use of secant and adjoint information that can be obtained from the forward solution of the EIT governing equation and hence both the BM-HSMoBIIR and ABM-HSMoBIIR algorithms reduce the computational time remarkably by approximating the system Jacobian (J) successively through low-rank updates. The impedance image reconstruction is studied with BM-HSMoBIIR and ABM-HSMoBIIR algorithms using the simulated and practical phantom data and results are compared with a Gauss-Newton method based MoBIIR (GNMoBIIR) algorithm. The GNMoBIIR algorithm is developed with a Finite Element Method (FEM) based flexible forward solver (FFS) and Gauss-Newton method based inverse solver (GNIS) working with a modified Newton-Raphson iterative technique (NRIT). FFS solves the forward problem (FP) to obtain the computer estimated boundary potential data (Vc) data and NRIT based GNIS solve the inverse problem (IP) and the conductivity update vector [Δσ] is calculated by conjugate gradient search by comparing Vc measured boundary potential data (Vm) and using the Jacobian (J) matrix computed by the adjoint method. The conductivity reconstruction is studied with GNMoBIIR, BM-HSMoBIIR and ABM-HSMoBIIR algorithms using simulated data a practical phantom data and the results are compared. The reconstruction time, projection error norm (EV) and the solution error norm (Eσ) produced in HSMoBIIR algorithms are calculated and compared with GNMoBIIR algorithm. Results show that both the BM-HSMoBIIR and ABM-HSMoBIIR algorithms successfully reconstructs the conductivity distribution of the domain under test with its proper inhomogeneity and background conductivities for simulation as well as experimental studies. Simulated and practical phantom studies demonstrate that both the BM-HSMoBIIR and ABM-HSMoBIIR algorithms accelerate the impedance reconstruction by more than five times. It is also observed that EV and Eσ are reduced in both the HSMoBIIR algorithms and hence the image quality is improved. Noise analysis and convergence studies show that both the BM-HSMoBIIR and ABM-HSMoBIIR algorithms works faster and better in noisy conditions compared to GNMoBIIR. In low noise conditions, BM-HSMoBIIR is faster than to ABM-HSMoBIIR algorithm. But, in higher noisy environment, the ABM-HSMoBIIR is found faster and better than BM-HSMoBIIR. Two novel regularization methods called Projection Error Propagation-based Regularization (PEPR) and Block Matrix based Multiple Regularization (BMMR) are proposed to improve the image quality in Electrical Impedance Tomography (EIT). PEPR method defines the regularization parameter as a function of the projection error contributed by the mismatch (difference) between the data obtained from the experimental measurements (Vm) and calculated data (Vc). The regularization parameter in the reconstruction algorithm gets modified automatically according to the noise level in measured data and ill-posedness of the Hessian matrix. The L-2 norm of the projection error is calculated using the voltage difference and it is used to find the regularization parameter in each iteration in the reconstruction algorithm. In BMMR method, the response matrix (JTJ) obtained from the Jacobian matrix (J) has been partitioned into several sub-block matrices and the highest eigenvalue of each sub-block matrices has been chosen as regularization parameter for the nodes contained by that sub-block. The BMMR method preserved the local physiological information through the multiple regularization process which is then integrated to the ill-posed inverse problem to make the regularization more effective and optimum for all over the domain. Impedance imaging with simulated data and the practical phantom data is studied with PEPR and BMMR techniques in GNMoBIIR and EIDORS and the reconstructed images are compared with the single step regularization (STR) and Modified Levenberg Regularization (LMR). The projection error and the solution error norms are estimated in the reconstructions processes with PEPR and the BMMR methods and the results are compared with the errors estimated in STR and modified LMR techniques. Reconstructed images obtained with PEPR and BMMR are also studied with image parameters and contrast parameters and the reconstruction performance with PEPR and BMMR are evaluated by comparing the results with STR and modified LMR. PEPR and BMMR techniques are successfully implemented in the GNMoBIIR and EIDORS algorithms to improve the impedance image reconstruction by regularizing the solution domain in EIT reconstruction process. As the multifrequency EIT is always preferred in biological object imaging for better assessments of the frequency dependent bioimpedance response, multifrequency impedance imaging is studied with MfMf-EIT system developed for biomedical applications. MfMf-EIT system is studied, tested and evaluated with practical phantoms suitably developed for multifrequency impedance imaging within a wide range of frequency. Different biological materials are studied with electrical impedance spectroscopy (EIS) and a number of practical biological phantoms suitable for multifrequency EIT imaging are developed. The MfMf-EIT system is studied, tested and evaluated at different frequency levels with different current patterns using a number of NaCl phantoms with single, multiple and hybrid vegetable tissue phantoms as well as with chicken tissue phantoms. BbMfMf-EIT system is also studied and evaluated with the multifrequency EIT imaging using the developed biological phantoms. The developed MfMf-EIT system is applied on human body for impedance imaging of human anatomy. Impedance imaging of human leg and thigh is studied to visualize the muscle and bone tissues using different current patterns and different relative electrode positions. Ag/AgCl electrodes are attached to the leg and thigh using ECG gel and the boundary data are collected with MfMf-EIT EIT system by injecting a 1 mA and 50 kHz sinusoidal constant current with neighbouring and opposite current injection patterns. Impedance images of the femur bone of the human thigh and the tibia and fibula bones of the human leg along with the muscle tissue backgrounds are reconstructed in EIDORS and GNMoBIIR algorithms. Reconstructed resistivity profiles of bone and muscles are compared with the resistivity data profiles reported in the published literature. Impedance imaging of leg and thigh is studied with MfMf-EIT system for different current patterns, relative electrode positions and the images are evaluated to assess the system reliability. Battery based MfMf-EIT system (BbMfMf-EIT) is also studied for human leg and thigh imaging and it is observed that MfMf-EIT system and BbMfMf-EIT system are suitable for impedance imaging of human body imaging though the BbMfMf-EIT system increases the patiet safety. Therefore, the developed MfMf-EIT and BbMfMf-EIT systems are found quite suitable to improve the bio-impedance imaging in medical, biomedical and clinical applications as well as to study the anatomical and physiological status of the human body to diagnose, detect and monitor the tumors, lesions and a number of diseases or anatomical abnormalities in human subjects.

<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.

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.