Caractérisation géométrique par la logique floue et simulation de la résorption cellulairement assistée de substituts poreux pour tissus osseux par microtomographie à rayons X

The objective of this thesis is to provide an improved characterization of porous scaffolds. A more focused objective is to provide a computational model simulating the cell mediated resorption process of resorbable bone substitutes. The thesis is structured in three scientific manuscripts. The first manuscript used fuzzy-based image treatment methods to analyse images generated by micro-computed tomography. From the literature, it is known that the fuzzy-based method helps to improve the accuracy of the characterization, in particular for scaffolds featuring a relatively small pore size. In addition, a new algorithm was introduced to determine both pore and interconnection sizes. The surface area of bone substitutes was quantified by using marching cube algorithm. Besides, the so-called Lattice Boltzmann method was used to characterize the permeability of the investigated scaffolds. Scaffolds made of [béta]-tricalcium phosphate ([béta]-Ca[subscript 3](PO[subscript 4])[subscript 2]) and presenting a constant porosity and four variable pore sizes were examined. The average pore size (diameter) of the four bone substitute groups (denominated with a letter from group A to D) was measured to be 170.3«1.7, 217.3«5.2, 415.8«18.8 and 972.3«10.9 [micro]m. Despite this significant change in pore size, the pore interconnection size only increased slightly, in the range of 61.7 to 85.2 [micro]m. The average porosity of the four groups was 52.3«1.5 %. The surface density of scaffolds decreased from 11.5 to 3.3 mm[superscript -1], when the pore size increased. The results revealed that the permeability of scaffolds is in the same order of magnitude and increased from 1.1?10[superscript -10] to 4.1?10[superscript -10] m[superscript 2] with increasing the pore size. The second manuscript was devoted to the use of subvoxelization algorithm and high-resolution scanner, in an attempt to further improve the accuracy of the results, in particular, of the small pore scaffolds. As expected, an increase of the image resolution from 15 to 7.5 [micro]m significantly eased the segmentation process and hence improved scaffold characterization. Subvoxelization also improved the results specifically in terms of interconnection sizes. Specifically, much smaller interconnection sizes were yielded after applying the subvoxelization process. For example, the mean interconnection size of small pore size groups, group A and B, dropped from 63 to 20 and 30 [micro]m, respectively. Furthermore, due to more details obtained from subvoxelization and high-resolution scanning, additional effects so called"boundary effects" were observed. The boundary effects can yield misleading results in terms of interconnection sizes. The means to reduce these effects were proposed. The third manuscript focused on the simulation and understanding of cell mediated resorption of bone graft substitutes. A computer model was developed to simulate the resorption process of four bone substitute groups. [mu]CT data and new"image processing" tools such as labelling and skeletonization were combined in an algorithm to perform the steps of resorption simulation algorithm. The proposed algorithm was verified by comparing simulation results with the analytical results of a simple geometry and biological in vivo data of bone substitutes. A correlation coefficient between the simulation results and both analytical and experimental data, was found to be larger than 0.9. Local resorption process revealed faster resorption in external region specifically at earlier resorption time. This finding is in agreement with the in vivo results. Two definitions were introduced to estimate the resorption rate; volume resorption rate and linear resorption rate. The volume resorption rate was proportional to accessible surface and decreased when the pore size increased, while the linear resorption rate was proportional to thickness of material and increased with increasing the pore size. In addition, the simulation results revealed no effect of resorption direction on resorption behaviour of substitutes. However, the resorption rate of small pore size samples was decreased with increasing the minimum interconnection size required for cell ingrowth, to 100 [micro]m. This thesis combined novel"image processing" tools and subvoxelization method to improve the characterization of porous bone substitutes used in the bone repair process. The improved characterization allowed a more accurate simulation process. The simulation data were consistent with previously obtained biological data of the same group and allows understanding the local resorption process. The available tools and results are expected to help with the design of optimal substitute for bone repair."--Résumé abrégé par UMI

In vivo morphometric and mechanical characterization of trabecular bone from high resolution magnetic resonance imaging

La osteoporosis es una enfermedad ósea que se manifiesta con una menor densidad ósea y el deterioro de la arquitectura del hueso esponjoso. Ambos factores aumentan la fragilidad ósea y el riesgo de sufrir fracturas óseas, especialmente en mujeres, donde existe una alta prevalencia. El diagnóstico actual de la osteoporosis se basa en la cuantificación de la densidad mineral ósea (DMO) mediante la técnica de absorciometría dual de rayos X (DXA). Sin embargo, la DMO no puede considerarse de manera aislada para la evaluación del riesgo de fractura o los efectos terapéuticos. Existen otros factores, tales como la disposición microestructural de las trabéculas y sus características que es necesario tener en cuenta para determinar la calidad del hueso y evaluar de manera más directa el riesgo de fractura. Los avances técnicos de las modalidades de imagen médica, como la tomografía computarizada multidetector (MDCT), la tomografía computarizada periférica cuantitativa (HR-pQCT) y la resonancia magnética (RM) han permitido la adquisición in vivo con resoluciones espaciales elevadas. La estructura del hueso trabecular puede observarse con un buen detalle empleando estas técnicas. En particular, el uso de los equipos de RM de 3 Teslas (T) ha permitido la adquisición con resoluciones espaciales muy altas. Además, el buen contraste entre hueso y médula que proporcionan las imágenes de RM, así como la utilización de radiaciones no ionizantes sitúan a la RM como una técnica muy adecuada para la caracterización in vivo de hueso trabecular en la enfermedad de la osteoporosis. En la presente tesis se proponen nuevos desarrollos metodológicos para la caracterización morfométrica y mecánica del hueso trabecular en tres dimensiones (3D) y se aplican a adquisiciones de RM de 3T con alta resolución espacial. El análisis morfométrico está compuesto por diferentes algoritmos diseñados para cuantificar la morfología, la complejidad, la topología y los parámetros de anisotropía del tejido trabecular. En cuanto a la caracterización mecánica, se desarrollaron nuevos métodos que permiten la simulación automatizada de la estructura del hueso trabecular en condiciones de compresión y el cálculo del módulo de elasticidad. La metodología desarrollada se ha aplicado a una población de sujetos sanos con el fin de obtener los valores de normalidad del hueso esponjoso. Los algoritmos se han aplicado también a una población de pacientes con osteoporosis con el fin de cuantificar las variaciones de los parámetros en la enfermedad y evaluar las diferencias con los resultados obtenidos en un grupo de sujetos sanos con edad similar.Los desarrollos metodológicos propuestos y las aplicaciones clínicas proporcionan resultados satisfactorios, presentando los parámetros una alta sensibilidad a variaciones de la estructura trabecular principalmente influenciadas por el sexo y el estado de enfermedad. Por otra parte, los métodos presentan elevada reproducibilidad y precisión en la cuantificación de los valores morfométricos y mecánicos. Estos resultados refuerzan el uso de los parámetros presentados como posibles biomarcadores de imagen en la enfermedad de la osteoporosis.Alberich Bayarri, Á. (2010). In vivo morphometric and mechanical characterization of trabecular bone from high resolution magnetic resonance imaging [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8981Palanci

Caractérisation d’échaffaudages explantés en b-TCP après résorption in-vivo en utilisant des techniques d’analyse d’images raffinées corrélées avec de la micro tomodensitométrie à rayons-X

L’utilisation de substituts osseux synthétiques est de plus en plus courante dans les procédés de réparation osseuse. Les biomatériaux de phosphate de calcium (CaP) sont les substituts dont la composition chimique se rapproche le plus de celle des os. Outre leur composition chimique, les propriétés géométriques des substituts osseux et, partant, leur macro et microporosité, ont une incidence sur leur efficacité et leur performance in vivo. Un grand nombre d’études se sont penchées sur le rôle des macro et microstructures des substituts dans le processus de guérison des os. Cependant, le rôle que la structure des substituts joue dans le processus de guérison reste à démontrer et est encore nébuleux en raison, entre autres, de la quasi inexistence de méthodes de caractérisation précises des phases des biopsies d’explants. La présente thèse comportait par conséquent deux objectifs généraux. Le premier consistait à élaborer, à appliquer et à valider des méthodes novatrices de traitement de l’image utilisant des ensembles de données de microtomographie par rayons X après implantation afin de réaliser avec précision la caractérisation des phases des biopsies d’explants de substituts osseux de modèles in vivo. Une importante difficulté de l’analyse des ensembles de données de microtomographie par rayons X après implantation provient du fait que les résidus osseux et céramiques des images microtomographiques présentent une densité similaire ; il devient par conséquent ardu de différencier les résidus céramiques du tissu osseux dans le matériel prélevé par biopsie. Le second objectif, tel que détaillé ci-dessous, concerne une méthode pour analyser avec précision le dépôt osseux microscopique dans les parois des substituts céramiques. Ainsi, le premier objectif impliquait la combinaison d’algorithmes de traitement d’images pour procéder à une étude précise des phases relevées dans les biopsies d’explants, et ainsi mieux comprendre le lien qui existe entre le processus de guérison et la structure du substitut. Plus précisément, l’alignement géométrique en 3D du substitut avant implantation sur les résidus du substitut a fourni des données sur la densité des particules osseuses par rapport à celle des résidus céramiques ; cela a donc permis de différencier avec encore plus de précision les phases relevées de la biopsie. Les résultats algorithmiques ont été entièrement validés au moyen de la théorie des matrices similaires et de la comparaison des résultats algorithmiques de cinq images choisies au hasard comprenant au total 556 800 pixels avec ceux obtenus manuellement par un scientifique expert en traitement de l’image. La validation a fait ressortir une concordance à 94 pour cent. Les clichés histologiques ont en outre confirmé les résultats de validation. Le nouvel algorithme en 3D permet donc d’analyser globalement et localement des effets macroscopiques comme la néoformation osseuse et la résorption céramique du processus de guérison. Globalement, ces effets sont analysés pour tout le substitut ; localement, ces effets peuvent être analysés pour chacune des distributions de pores du substitut. Cette approche novatrice aide ainsi à intégrer la conception structurelle du substitut osseux au processus de guérison. Les méthodes et les résultats relatifs à cet objectif sont expliqués plus en détail au chapitre 3. Le second objectif de la présente thèse impliquait l’élaboration d’une nouvelle catégorie d’algorithmes servant à analyser avec précision des effets microscopiques comme la néoformation osseuse dans les pores microscopiques du substitut céramique, permettant ainsi l’étude des effets microscopiques du processus de guérison. Plus particulièrement, les structures matérielles observées dans les images à haute définition en 2 D de l’histologie et des techniques MEB étaient alignées géométriquement sur la structure en 3D de l’ensemble des données de microtomographie par rayons X du même substitut avant et après implantation. Par conséquent, les ensembles de données de microtomographie par rayons X en 3D avant implantation ont été utilisés pour définir la référence géométrique de la céramique qui se résorbe, ce qui par conséquent a permis d’effectuer une analyse précise des phases matérielles des clichés à haute résolution en 2D des coupes d’évaluation histologiques. Plus précisément, une fois que les images produites au moyen des techniques d’imagerie multimodale ont été combinées et alignées, l’information couleur provenant de l’histologie et la valeur de gris obtenue au moyen des images MEB ont été utilisées pour analyser les images histologiques ; celles-ci possédaient une résolution moyenne de 1,2 microns, ce qui a rendu possible l’étude des effets microscopiques à l’aide de clichés histologiques en 2D. Les méthodes et les résultats relatifs au second objectif sont au chapitre 4. Toujours au regard du second objectif, les nouveaux algorithmes ont servi à l’analyse des effets microscopiques et macroscopiques pour deux groupes de substituts b-TCP dont la taille des pores s’accroissait progressivement (diamètre de pore moyen = 510 et 1220 microns), implantés dans un modèle ovin pendant 6 semaines. Trois échantillons prélevés dans chaque groupe ont servi à étudier la néoformation osseuse et la résorption céramique. Des taux très élevés de néoformation osseuse et de résorption céramique ont été mesurés chez le groupe de substituts dont la taille des pores était la plus petite. Outre le taux plus élevé de néoformation osseuse, le groupe dont la taille des pores était plus petite présentait spécifiquement un important effet de surface ; en effet, le ratio de conversion de la surface de céramique résorbée en tissu osseux était beaucoup plus élevé que chez les deux autres groupes. Des études plus approfondies devront être menées afin d’analyser les effets de surface et les interactions entre le substitut osseux et le processus de guérison osseuse. Les méthodes et les algorithmes connexes de la présente thèse ont fourni un moyen novateur et original d’évaluer les effets microscopiques et macroscopiques du processus de guérison. Tout comme d’autres méthodes, les nouvelles méthodes mises au point sont limitées. Cellesci, exigeantes en termes de calculs, ont nécessité la présence d’un nombre suffisant d’éléments géométriques dans le substitut explanté afin d’aligner ces éléments sur ceux de la structure avant implantation.Abstract: Synthetic bone substitutes are being increasingly used in bone repair procedures. Calciumphosphate (CaP) substitute biomaterials have the closest chemical composition to bone. Besides the chemical composition, the geometrical properties and hence the macro and micro-porosity of the bone substitutes affect their in vivo effectiveness and performance. A large number of studies have investigated the role of the substitute’s macro- and micro-structure in the bone healing process. The role that the substitute’s structure plays in the healing process, however, remains debatable and unclear because of, among other reasons, the lack of accurate characterization methods of the phases in the explanted biopsies. This thesis accordingly had two overall objectives. The first was to develop, implement and validate novel image-processing methods for using the post-implantation mCT datasets to help accurately characterize the phases in bone substitute biopsies explanted from in vivo models. One important difficulty in analyzing the post-implantation mCT datasets is that bone and ceramic remnants in the mCT images appear to have similar density; differentiating between ceramic remnants and bone tissue in the biopsies therefore becomes difficult. The second objective, as detailed below, related to a method to accurately analyze the microscopic bone deposition into the bone substitute’s ceramic wall. Accordingly, undertaking the first objective involved developing image-based algorithms to accurately study the phases found in the explanted biopsies and thus better understand the relationship of the healing process and the substitute’s structure. Specifically, the 3D geometric alignment of the pre-implantation substitute with the substitute’s remnants provided access to data on the density characteristics of the bone versus the ceramic remnants; this accordingly allowed a more accurate differentiation of the phases found in the biopsy. The algorithmic results were thoroughly validated, using the similarity matrix theory and by comparing the algorithmic results of five randomly selected images — comprising a total of 556,800 pixels — with those obtained by a skilled image-processing scientist. The validation showed a 94-percent agreement. Histology photographs further confirmed the validation results. Accordingly, the new 3D algorithm helps to globally and locally analyze macroscopic effects such as bone deposition and ceramic resorption of the healing process. Globally, these effects are analyzed for the entire substitute, and locally, these effects can be studied for each pore of the substitute. The novel approach thus helps relate the bone substitute’s structural design to the healing process. The methods and the results related to this objective are detailed in Chapter 3. The second objective of the present thesis entailed developing a new class of algorithms to accurately analyze the microscopic effects such as the bone deposition in the microscopic porosity of the ceramic substitute, thereby allowing the study of microscopic effects of the healing process. Specifically, the material structures seen in the high-resolution 2D images of the histology and SEM techniques were geometrically aligned with the 3D structure in the mCT dataset of the same substitute before and after implantation. Accordingly, the 3D pre-implantation mCT datasets were used to define the geometric reference of the resorbing ceramic, and therefore allowed an accurate analysis to be made of the material phases in the high-resolution 2D photographs of the histology evaluation cuts. Specifically, once the images from the multimodal imaging techniques were combined and aligned, the color information from histology and the grey value information from SEM images were used to analyze the histology images; the latter had an average resolution of 1.2 microns and this made studying the microscopic effects using the 2D histology photographs possible. The methods and the results related to the second objective are in Chapter 4. Still in line with the second objective, the new algorithms were used to analyze the microscopic and macroscopic effects of two b-TCP substitute groups of incrementally increasing pore size (mean pore diameter = 510 and 1220 microns), implanted in an ovine model for 6 weeks. Three samples were selected per group to investigate the microscopic and macroscopic bone deposition and ceramic resorption. Significantly higher bone deposition and ceramic resorption were measured in the substitute group with the smaller pore size. In addition to the higher micro-bone deposition, the smaller pore-size group specifically featured an important surface effect; namely, the conversion ratio of resorbed surface ceramic into bone tissue was significantly higher compared to the two other groups. Further studies are still required to investigate the surface effects and the related interactions between the bone-substitute design and the bone-healing process. The present thesis’ methods and related algorithms provided novel and original means to evaluate microscopic and macroscopic effects of the healing process. Like other methods, the newly developed ones have limitations. The methods are computationally demanding, and required that a sufficient number of geometric features be present in the explanted substitute so as to align these features with those of the pre-implantation structure

Contour tree connectivity and analysis of microstructures

The connectivity of microstructures is directly related to the physical properties of materials. Currently, the Euler number is the most popular measure of connectivity. It is an elegant topological invariant, however, it does not provide information about cavities or the proximities and sizes of objects. In this thesis, an alternative measure called contour tree connectivity (CTC) is developed and its applications for the analysis of microstructures are studied. CTC is derived from contour trees that are used in the first publication to represent complex binary images with simple graphs. By analyzing contour trees, CTC produces new connectivity information that is not provided by other approaches described in the literature. Contour tree representation of binary images and CTC can be computed for any dimensions of data and topology as explained in the second publication. Moreover, CTC is designed to be a scalar between 0 and 1, which makes it easy to use and understand. In this thesis, the use of CTC for analyzing microstructures is presented in two studies. In the first study, the microstructure of trabecular bone is analyzed in relation to its mechanical strength. In the second study, the relationship between microstructures and the fluid flow within materials are examined. The results from these studies show that CTC contributes to the understanding of how the structural properties of materials are linked to their physical properties. To conclude, with its unique properties, CTC complements the structural information provided by currently used measures. This makes it an important image analysis tool for the study of the microstructures of materials such as soil, paper, filters and food products as well as biomaterials and biological tissues

Machine learning-based automated segmentation with a feedback loop for 3D synchrotron micro-CT

Die Entwicklung von Synchrotronlichtquellen der dritten Generation hat die Grundlage für die Untersuchung der 3D-Struktur opaker Proben mit einer Auflösung im Mikrometerbereich und höher geschaffen. Dies führte zur Entwicklung der Röntgen-Synchrotron-Mikro-Computertomographie, welche die Schaffung von Bildgebungseinrichtungen zur Untersuchung von Proben verschiedenster Art förderte, z.B. von Modellorganismen, um die Physiologie komplexer lebender Systeme besser zu verstehen. Die Entwicklung moderner Steuerungssysteme und Robotik ermöglichte die vollständige Automatisierung der Röntgenbildgebungsexperimente und die Kalibrierung der Parameter des Versuchsaufbaus während des Betriebs. Die Weiterentwicklung der digitalen Detektorsysteme führte zu Verbesserungen der Auflösung, des Dynamikbereichs, der Empfindlichkeit und anderer wesentlicher Eigenschaften. Diese Verbesserungen führten zu einer beträchtlichen Steigerung des Durchsatzes des Bildgebungsprozesses, aber auf der anderen Seite begannen die Experimente eine wesentlich größere Datenmenge von bis zu Dutzenden von Terabyte zu generieren, welche anschließend manuell verarbeitet wurden. Somit ebneten diese technischen Fortschritte den Weg für die Durchführung effizienterer Hochdurchsatzexperimente zur Untersuchung einer großen Anzahl von Proben, welche Datensätze von besserer Qualität produzierten. In der wissenschaftlichen Gemeinschaft besteht daher ein hoher Bedarf an einem effizienten, automatisierten Workflow für die Röntgendatenanalyse, welcher eine solche Datenlast bewältigen und wertvolle Erkenntnisse für die Fachexperten liefern kann. Die bestehenden Lösungen für einen solchen Workflow sind nicht direkt auf Hochdurchsatzexperimente anwendbar, da sie für Ad-hoc-Szenarien im Bereich der medizinischen Bildgebung entwickelt wurden. Daher sind sie nicht für Hochdurchsatzdatenströme optimiert und auch nicht in der Lage, die hierarchische Beschaffenheit von Proben zu nutzen. Die wichtigsten Beiträge der vorliegenden Arbeit sind ein neuer automatisierter Analyse-Workflow, der für die effiziente Verarbeitung heterogener Röntgendatensätze hierarchischer Natur geeignet ist. Der entwickelte Workflow basiert auf verbesserten Methoden zur Datenvorverarbeitung, Registrierung, Lokalisierung und Segmentierung. Jede Phase eines Arbeitsablaufs, die eine Trainingsphase beinhaltet, kann automatisch feinabgestimmt werden, um die besten Hyperparameter für den spezifischen Datensatz zu finden. Für die Analyse von Faserstrukturen in Proben wurde eine neue, hochgradig parallelisierbare 3D-Orientierungsanalysemethode entwickelt, die auf einem neuartigen Konzept der emittierenden Strahlen basiert und eine präzisere morphologische Analyse ermöglicht. Alle entwickelten Methoden wurden gründlich an synthetischen Datensätzen validiert, um ihre Anwendbarkeit unter verschiedenen Abbildungsbedingungen quantitativ zu bewerten. Es wurde gezeigt, dass der Workflow in der Lage ist, eine Reihe von Datensätzen ähnlicher Art zu verarbeiten. Darüber hinaus werden die effizienten CPU/GPU-Implementierungen des entwickelten Workflows und der Methoden vorgestellt und der Gemeinschaft als Module für die Sprache Python zur Verfügung gestellt. Der entwickelte automatisierte Analyse-Workflow wurde erfolgreich für Mikro-CT-Datensätze angewandt, die in Hochdurchsatzröntgenexperimenten im Bereich der Entwicklungsbiologie und Materialwissenschaft gewonnen wurden. Insbesondere wurde dieser Arbeitsablauf für die Analyse der Medaka-Fisch-Datensätze angewandt, was eine automatisierte Segmentierung und anschließende morphologische Analyse von Gehirn, Leber, Kopfnephronen und Herz ermöglichte. Darüber hinaus wurde die entwickelte Methode der 3D-Orientierungsanalyse bei der morphologischen Analyse von Polymergerüst-Datensätzen eingesetzt, um einen Herstellungsprozess in Richtung wünschenswerter Eigenschaften zu lenken

Content-aware approach for improving biomedical image analysis: an interdisciplinary study series

Biomedicine is a highly interdisciplinary research area at the interface of sciences, anatomy, physiology, and medicine. In the last decade, biomedical studies have been greatly enhanced by the introduction of new technologies and techniques for automated quantitative imaging, thus considerably advancing the possibility to investigate biological phenomena through image analysis. However, the effectiveness of this interdisciplinary approach is bounded by the limited knowledge that a biologist and a computer scientist, by professional training, have of each other’s fields. The possible solution to make up for both these lacks lies in training biologists to make them interdisciplinary researchers able to develop dedicated image processing and analysis tools by exploiting a content-aware approach. The aim of this Thesis is to show the effectiveness of a content-aware approach to automated quantitative imaging, by its application to different biomedical studies, with the secondary desirable purpose of motivating researchers to invest in interdisciplinarity. Such content-aware approach has been applied firstly to the phenomization of tumour cell response to stress by confocal fluorescent imaging, and secondly, to the texture analysis of trabecular bone microarchitecture in micro-CT scans. Third, this approach served the characterization of new 3-D multicellular spheroids of human stem cells, and the investigation of the role of the Nogo-A protein in tooth innervation. Finally, the content-aware approach also prompted to the development of two novel methods for local image analysis and colocalization quantification. In conclusion, the content-aware approach has proved its benefit through building new approaches that have improved the quality of image analysis, strengthening the statistical significance to allow unveiling biological phenomena. Hopefully, this Thesis will contribute to inspire researchers to striving hard for pursuing interdisciplinarity

Advanced Image Acquisition, Processing Techniques and Applications

"Advanced Image Acquisition, Processing Techniques and Applications" is the first book of a series that provides image processing principles and practical software implementation on a broad range of applications. The book integrates material from leading researchers on Applied Digital Image Acquisition and Processing. An important feature of the book is its emphasis on software tools and scientific computing in order to enhance results and arrive at problem solution

An Investigation of Diabetes Mellitus in Postmortem Human Remains

Diabetes mellitus is one of the most prevalent and significant metabolic diseases impacting modern human populations. The goal of this research is to explore several analytical methods to better appreciate how diabetes impacts the skeleton, and to determine if this effect can be recognized in postmortem remains. Anthropologists are tasked with elucidating the relationship between nutrition, metabolism, growth, development, and skeletal health. Diabetes represents a crucial point of interface between these factors. Furthermore, as the percentage of diabetics increases in the general population, so will their representation in forensic cases. This study will provide tools for identifying characteristics of diabetes in the postmortem material available to anthropologists. Diabetes is a disease process that can alter the function of many tissues and systems. For these reasons, three analytical approaches were conducted including: blood serum protein analysis using ELISA, bone mineral density (BMD) scans with a dual-energy x-ray absorptiometry (DXA) scanner, and macroscopic osteological analysis. This study was completed employing a sample of 80 known skeletal donations and 20 blood samples from the William M. Bass Donated Skeletal Collection at the University of Tennessee, Knoxville. Results indicated that pro-inflammatory biomarkers may be quantified in postmortem blood samples, and that diabetics showed slightly higher average concentrations of cytokines associated with diabetes and lower concentrations of those related to insulin sensitivity. Bone density analysis revealed that diabetics and non-diabetics significantly differ in BMD, but this relationship varies between the sexes. Female diabetics had consistently denser bones in all measured variables of the lower limb, and one-third of forearm variables. Results based on male data did not display a similar outcome, with little difference observed between male diabetics and non-diabetics. Analysis of skeletal pathologies identified a set of three osteological variables, concentrated in the feet, as having the highest discriminatory potential. An accuracy rate of 83% was achieved in classifying individuals into diabetic versus non-diabetic categories

CT Scanning

Since its introduction in 1972, X-ray computed tomography (CT) has evolved into an essential diagnostic imaging tool for a continually increasing variety of clinical applications. The goal of this book was not simply to summarize currently available CT imaging techniques but also to provide clinical perspectives, advances in hybrid technologies, new applications other than medicine and an outlook on future developments. Major experts in this growing field contributed to this book, which is geared to radiologists, orthopedic surgeons, engineers, and clinical and basic researchers. We believe that CT scanning is an effective and essential tools in treatment planning, basic understanding of physiology, and and tackling the ever-increasing challenge of diagnosis in our society