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No description available.

No description available.

A major health concern for subjects with diabetes is weaker bones and increased fracture risk. Current clinical assessment of the bone strength is performed by measuring Bone Mineral Density (BMD), where low BMD-values are associated with an increased risk of fracture. However, subjects with Type 2 Diabetes (T2D) have been shown to have normal or higher BMD-levels compared to healthy controls, which does not reflect the recognized bone fragility among diabetics. Thus, there is need for more research about diabetes-related bone fragility to find other factors of impaired bone health. One potential biomarker that has recently been studied is Bone Marrow Fat (BMF). The data in this project consisted of whole-body water-fat Magnetic Resonance Imaging (MRI) volumes from the UK Biobank Imaging study (UKBB). Each subject in this data has a water volume and a fat volume, allowing for a quantitative assessment of water and fat content in the body. To analyze and perform quantitative measurements of the bones specifically, a Deep Learning (DL) model was trained, validated, and tested for performing fully automated and objective skeleton segmentation, where six different bones were segmented: spine, femur, pelvis, scapula, clavicle and humerus. The model was trained and validated on 120 subjects with 6-fold cross-validation and tested on eight subjects. All ground-truth segmentations of the training and test data were generated using two semi-automatic pipelines. The model was evaluated for each bone separately as well as the overall skeleton segmentation and achieved varying accuracy, performing better on larger bones than on smaller ones. The final trained model was applied on a larger dataset of 9562 subjects (16% type 2 diabetics) and the BMF, as well as bone marrow volume (BMV) and cortical bone volume (CBV), were measured in the segmented bones of each subject. The results of the quantified biomarkers were compared between T2D and healthy subjects. The comparison revealed possible differences between healthy and diabetic subjects, suggesting a potential for new findings related to diabetes and associated bone fragility.

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第21218号 / 情博第671号 / 新制||情||116(附属図書館) / 京都大学大学院情報学研究科通信情報システム専攻 / (主査)教授 佐藤 亨, 教授 山本 衛, 教授 松田 哲也 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

No / Human migration is a hallmark of the species and there is significant interest in methods that can determine the past migrations of humans and associated fauna. We present a new method that utilizes collagen oxygen, carbon and nitrogen isotopes from histologically informed samples of cortical bone. The utility of this multi-isotopic, life history approach is demonstrated in migrating Dutch whalers, and both the possibilities and limitations of the method are described.

As osteotomias mandibulares são procedimentos consagrados para o tratamento de prognatismo e para outros reposicionamentos cirúrgicos mandibulares. As técnicas mais utilizadas são: a osteotomia sagital de mandíbula (OSM) e a osteotomia vertical de ramo mandibular (OVRM), cada técnica tem suas indicações e limitações. A OVRM é considerada efetiva devido ao sucesso clínico e análise imaginológica, entretanto não existem estudos que descrevam seu processo de reparação óssea, pois nesta técnica o osso mandibular fica sobreposto num contato cortical sobre cortical. O objetivo deste trabalho foi avaliar a reparação óssea cortical-cortical da técnica de osteomia vertical de ramo mandibular em mandíbulas de coelho. Após aprovação do Comitê de Ética e Pesquisa em Animais da Faculdade de Odontologia da Universidade de São Paulo (Protocolo: 014/2014) foram utilizados 12 animais, divididos em quatro grupos de três. Os animais foram submetidos a osteotomia em -L? invertido no ângulo mandibular bilateralmente, este fragmento ósseo obtido foi deslizado anteriormente e fixado com parafuso sobre a basal mandibular anterior, num dos lados de um animal de cada grupo foi realizada somente a osteotomia, sendo este utilizado como controle cirúrgico; um dos grupos foi submetido a processo de infiltração de marcadores fluorcromáticos. Os animais foram divididos em G1 (eutanasiados em 15 dias), G2 (eutanasiados em 30 dias), G3 (eutanasiados em 45 dias) e G4 (protocolo de marcadores fluorocromáticos e eutanasiados com 56 dias). Após a realização dos procedimentos cirúrgicos, os animais foram mantidos em biotério padrão, nos tempos determinados foram eutanasiados, as mandíbulas foram dissecadas, tomografadas em tomógrafo de feixe cônico e analisadas sob microscopia de fluorescência. Na análise tomográfica observou-se que existe correlação entre os valores de densidades nas áreas operadas e na região do controle, e que há correlação significativa entre as áreas de sobreposição óssea e onde foi realizado somente a osteotomia (controle cirúrgico). Com relação a análise de microscopia de fluorescência, observa-se que as proporções do marcador alizarina são superiores a calceína no osso neoformado, tanto na área operada, quanto na região onde foi feita somente a osteotomia (controle cirúrgico). Concluímos que houve consolidação óssea quando da sobreposição cortical-cortical, e que os valores de densidades tomográficas quando da sobreposição óssea ou não, são similares, e que há maior formação óssea no primeiro mês no processo de reparação. / Mandibular osteotomy is a well-established intervention for the treatment of prognathism and other conditions requiring mandibular repositioning. The most commonly used osteotomy techniques are intraoral vertical ramus osteotomy (IVRO) and sagittal split ramus osteotomy (SSRO), each of which has particular indications and limitations. Although IVRO is considered effective owing to observations of clinical success and imaging analyses, there are no studies describing the bone repair processes that follow IVRO because, in this technique, the mandibular bone is overlaid at a cortical-cortical contact site. The purpose of this study was to evaluate cortical-cortical bone repair in rabbit mandibles following IVRO. After approval of the Ethics and Research Committee on Animals of the Faculty of Dentistry of the University of São Paulo (Protocol: 014/2014), 12 rabbits, divided into four groups of three, were used. The four groups, G1, G2, G3, and G4, were euthanized 15 days, 30 days, 45 days, and 56 days post-IVRO; the animals in G4 were also infused with fluorochemical markers. All 12 animals were submitted to a bilateral inverted \"L\" osteotomy at the mandibular angle. On one side, the released bone fragment was advanced anteriorly and fixed with a screw onto the anterior mandibular basal bone; on the other side, only the osteotomy was performed to serve as a within-animal control site. After the operations, the animals were kept in a standard room until they were euthanized at the group-designated time points. Upon euthanasia, the mandibles were dissected, imaged digitally by conical beam tomography, and analyzed under fluorescence microscopy. The tomographic analysis results revealed a correlation between density values in the operated IVRO sites of bone overlap and the contralateral osteotomy-only surgical control sites. Fluorescence microscopy analysis revealed the presence of elevated alizarin marker (above calcein levels) in the neoformed bone, both in the operated side and in the osteotomy-only control side. Bone growth was greater at the 15-day and 30-day time points than at the later time points. In conclusion, bone consolidation occurred at cortical-cortical overlap sites, tomographic densities were similar between bone overlapping and nonoverlapping (control) sides, bone formation was maximal during the first month of repair.

O objetivo principal foi investigar se o osso cortical apresenta comportamento bimodular, ou seja, se os valores de módulo de elasticidade (E) dependem do tipo de carregamento que o método utiliza. Para alcançá-lo foi preciso: (1) \"calibrar\" os diferentes métodos em um material conhecidamente unimodular, para afastar a possibilidade de erros ligados à execução de um método. (2) Depurar os métodos já calibrados para torná-los exequíveis em osso cortical. O que foi feito em espécimes de resina composta, que é um material unimodular e com E parecido com o do osso cortical. Foi investigado se o método de medida interfere no valor do E obtido neste material (pois, pelas informações da literatura, existia uma dúvida consistente). Finalmente, (3) foi avaliado se o método de medida, a região anatômica e o indivíduo interferem nos valores de E em espécimes de osso cortical. Adicionalmente, (4) verificou-se a possibilidade de se encontrar e validar uma correlação entre E e dureza Knoop (KH), para medir o E de resinas compostas indiretamente. Espécimes de latão (n = 5) tiveram o seu E calculado por quatro métodos estáticos diferentes (flexão em três pontos; tração; compressão e método de Marshall), que foram calibrados até que todos medissem o valor esperado; os valores de cada método foram comparados por análise de variância de medidas repetidas (o método foi o fator vinculado e o nível de significância foi de 5%). Espécimes (n = 4) de cinco marcas diferentes de resina composta, também foram submetidos aos quatro métodos, fazendo as adaptações pertinentes (depuração), e tiveram o seu E calculado. Estes valores foram submetidos à análise de variância de medidas repetidas (o método foi o fator vinculado e o nível de significância foi de 5 %). Espécimes (n = 48) obtidos em diferentes regiões (periósteo, endósteo e \"transversal\") de fêmures de quatro bois diferentes tiveram seu E calculado através dos métodos devidamente depurados (flexão em três pontos, tração indireta e compressão). Os valores de E foram submetidos a análises de variâncias (nível de significância de 5 %) para avaliar a influência do método, da região e do indivíduo (bois diferentes) sobre os valores de E. O método experimental de tração não foi utilizado para analisar o comportamento bimodular, porque durantes os ensaios com osso cortical, ele apresentou valores com viés. Por isso, os valores de tração foram calculados de forma indireta (Eti) através de uma equação e dos valores experimentais de flexão em três pontos (Eb) e compressão (Ec). Para validar o uso de valores de Eti, eles foram comparados com os respectivos valores de tração experimental (Et) calculados previamente nos espécimes de resinas compostas por análise de variância de medidas repetidas, e não foram achadas diferenças significantes (p > 0,05). Para encontrar e validar a correlação entre E e KH, os valores médios de E em cada espécime de resina (média do E obtido nos 4 métodos em cada espécime) foram submetidos ao teste de correlação de Pearson (nível de significância de 5%) com os respectivos valores experimentais de dureza Knoop (KH) e foi obtida uma equação de regressão linear. Para validar a equação foi confeccionado um segundo grupo de espécimes de resina (de marcas diferentes das utilizadas anteriormente) que teve seu E calculado pelo ensaio de flexão (Eb) e pela equação de regressão proposta previamente (Er); verificou-se então se a correlação entre estes valores (Eb x Er) era significante (nível de significância de 5 %), e se a nova reta de regressão apresentava coeficiente angular não diferente de 1, e coeficiente constante não diferente de zero (critérios de validação). A análise de variância não apontou diferença significante (p > 0,05) entre os valores de E calculados para o metal pelos 4 métodos, e os valores obtidos não diferiram do E conhecido do latão (ao redor de 100 GPa). As depurações necessárias foram realizadas e com elas os diferentes métodos calcularam o E dos espécimes de resina composta de modo consistente: a análise de variância encontrou diferenças significantes (p < 0,05) entre marcas (cujos E médios cobriram a faixa entre 3 e 20 GPa) e não significantes entre os 4 métodos (p > 0,05). Nos espécimes de osso cortical o valor de E foi significantemente dependente (p < 0,05) do método de obtenção (Eti > Eb > Ec). O E dos espécimes obtidos na região \"transversal\" foi menor que o E dos espécimes obtidos na região do endósteo (p < 0,05); no entanto, não houve diferença significante (p > 0,05) entre o E dos espécimes obtidos nas regiões do endósteo e periósteo e entre o E dos espécimes obtidos nas regiões do periósteo e \"transversal\". Ao considerar somente os valores obtidos no ensaio de compressão (Ec), um dos indivíduos apresentou valores de E maiores que os demais (p < 0,05). As médias de E (dos quatro métodos) em cada espécime de resina apresentaram correlação significante com os respectivos valores de KH (p < 0,05) e a equação de regressão linear: E = 0,1602 KH. Também foi significante (p < 0,05) a correlação dos valores de Eb com os respectivos valores de Er (calculados pela regressão E = 0,1602 KH); além disso, a reta de regressão linear desta nova correlação (Eb = 1,0088Er + 0,0475) apresentou coeficiente angular não diferente de 1 e coeficiente constante não diferente de zero. Pode-se concluir que: (1) Quatro métodos de medir o E apresentaram resultados semelhantes em um material metálico. (2) Estes mesmos métodos foram depurados com sucesso para sua utilização em espécimes de osso cortical ao constatar que também não interferiram no valor do E obtido em espécimes semelhantes aos de osso, confeccionados com resinas compostas. (3) Os valores de E de osso cortical dependem do método de medida, o que demonstra seu comportamento bimodular. A região anatômica e o indivíduo também afetam os valores de E dos espécimes de osso cortical (o indivíduo só foi um fator significante ao considerar somente os valores obtidos no ensaio de compressão). (4) Foi encontrada e validada uma correlação entre E e KH em resinas compostas, que permite calcular o E deste material através da regressão E = 0,1602 KH. / The main objective was to investigate whether the cortical bone has a bimodular behavior, that is, if the values of elastic modulus (E) depend on the load type used by the method. To achieve this, it was necessary: (1) \"calibrate\" the different methods in a material with well-known unimodular behavior, for excluding the possibility of systematic errors in the execution of the methods. (2) Depurate the calibrated methods to make them executable in cortical bone. This was made on specimens of composite resin, which is a unimodular material and has an E similar to that of cortical bone. It was also investigated if the method of measuring the E influences the obtained value in this material (because there was a consistent doubt in the literature). Finally (3), we assessed whether the E values in cortical bone are influenced by the measurement method, by the anatomical region and by the individual. Additionally, (4) it was verified if it would be possible suggesting and validating a correlation between E and Knoop hardness (KH), to indirectly measure the E of composite resins. Brass specimens (n = 5) had their E calculated by four different static methods (three point bending, tensile, compression and Marshall\'s method), which were calibrated until all the methods were capable of measuring the expected value; the E values of each method were compared by analysis of variance of repeated measures (the method was the linked factor and the significance level was 5%). Specimens (n = 4) of five different composite resins were also subjected to the four methods, making the relevant adjustments (depuration), and had their E calculated. These values were subjected to analysis of variance of repeated measures (the method was the linked factor and the significance level was 5%); Specimens (n = 48) obtained in different regions (periosteum, endosteum and \"transverse\") of bovine femurs from four different individual had their E calculated using the depurated methods (three point bending, indirect tensile and compression). The E values were subjected to analyzes of variance (significance level of 5%) to evaluate the influence of the method, of the region and of the individual (different cattle) in the E values. The experimental tensile method was not used to analyze the bimodular behavior because during tests on cortical bone, this method showed values with bias. Therefore, the tensile values were indirectly calculated (Eti) by a formula and by the experimental values of E calculated by three point bending (Eb) and compression (Ec). To validate the use of Eti values, they were compared with the corresponding tensile experimental values (Et) previously measured in the composite resins specimens by analysis of variance (repeated measures), and no significant difference was found (p > 0.05). For suggesting and validating the correlation between E and KH, the average values of E of each composite specimen (mean of E obtained considering the values of the four methods in each specimen) were submitted to the Pearson\'s correlation test (significance level of 5 %) with the corresponding experimental KH values and it was obtained the linear regression equation. To validate this equation, it was made a second group of composite resins specimens (with different brands of the previously used) in which the E was calculated by three point bending test (Eb) and by regression equation previously proposed (Er); then it was checked whether the correlation between these values (Eb x Er) was significant (significance level of 5 %), and if the new regression line showed angular coefficient no different from one, and constant coefficient no different from zero (validation criteria). The analysis of variance showed no significant difference (p > 0.05) among the E values calculated for the metal specimens by the four methods; the obtained values did not differ from the known E of the brass (about 100 GPa). The necessary adjustments (depuration) were made and then the different methods calculated the E of the composite resin specimens consistently: the analysis of variance found significant difference (p < 0.05) between composite brands (whose E mean covered the range between 3 and 20 GPa) and no significant difference among the four methods (p> 0.05). In the specimens of cortical bone, the E values were significantly dependent (p < 0.05) of the obtainment method (Eti > Eb> Ec). The E values of the \"transversal\" specimens were lower than the endosteum specimens (p < 0.05); but there was no significant difference (p > 0.05) between the E of endosteum specimens and periosteum specimens and between the E of periosteum specimens and \"transversal\" specimens. When considering just E values of the compression method, one cattle showed higher E values than the others (p < 0.05). The mean of the four methods for each specimen composite resin exhibited a significant correlation with the respective KH values (p < 0.05) and the linear regression equation: E = 0.1602 KH. It was also significant (p < 0.05) the correlation between Eb and the respective Er values (calculated by the regression E = 0.1602 KH); furthermore, the linear regression of this new correlation (Eb = 1.0088Er + 0.0475) presented angular coefficient no different from 1, and constant coefficient no different from zero. It can be concluded that: (1) Four methods of E measuring showed similar results in a metallic material. (2) The same methods were successfully depurated for their execution in cortical bone specimens, since the measurement method did not affect the obtained E value in resin composites (that is a material with E value similar to cortical bone); (3) The E values of cortical bone depend on the measurement method, which demonstrates its bimodular behavior. The anatomical region and the individual also affect the E values of the cortical bone specimens (the individual was a significant factor only when considering just the E values obtained in the compression test). A correlation between E and KH that allows the E estimation by the regression E = 0.1602 KH was suggested and validated in composite resins.

L’os présente la propriété remarquable de s’adapter à son environnement et s’est forgé au cours de l’évolution des caractéristiques exceptionnelles qui fascinent les scientifiques mais aussi les ingénieurs : léger mais d’une rigidité à toute épreuve, une capacité de résistance à la fracture hors norme tout en gardant une certaine flexibilité. Ces propriétés mécaniques de l’os sont l’œuvre d’une optimisation de sa composition et d’une structure fortement hiérarchisée et organisée en multiples niveaux allant de l'échelle nanométrique à l'échelle macroscopique. L’amélioration de la prise en charge des maladies osseuses, l’optimisation des implants orthopédiques et la conception de nouveaux matériaux bio-inspirés passent par une connaissance approfondie des multiples facteurs qui déterminent les propriétés mécaniques de l’os. Dans ce travail, nous mettons l’accent sur les propriétés élastiques de l'os cortical humain à la fois aux échelles millimétrique et micrométrique. Nous avons caractérisé l’élasticité (à l’échelle mésoscopique), la composition et la microstructure de l’os cortical, à partir d’échantillons de fémur, tibia et radius prélevés sur des donneurs âgés, à l’aide d’une batterie de tests expérimentaux comportant des mesures en résonance ultrasonore spectroscopique, micro-tomographie par rayonnement synchrotron, microscopie infrarouge à transformée de Fourier et analyse biochimique. Ces mesures mettent à jour le rôle prépondérant joué par la porosité et le degré de minéralisation dans la détermination de l’élasticité et suffisent à eux seuls à en expliquer les variations. En particulier, les caractéristiques de la microstructure, comme la forme des pores, leur nombre, taille ou connectivité ne semblent pas avoir d’effets mesurables sur l’élasticité à l’échelle mésoscopique. Dans un second temps, une nouvelle approche d’homogénéisation inverse introduite dans cette thèse a permis l’estimation du tenseur des coefficients élastiques de la matrice osseuse à l’échelle microscopique. Connaissant l’élasticité de la matrice, nous avons évalué la gamme des microdéformations qui se produisent localement en réponse à des contraintes physiologiques. Les microdéformations étant à l’origine des signaux qui déclenchent la réponse des cellules mécanosensibles, ce dernier résultat devrait contribuer à une meilleure compréhension du comportement mécanique osseux au niveau microscopique. En conclusion, ce travail de thèse a permis l’obtention d’une base de données unique sur les caractéristiques élastiques de l’os cortical humain et la caractérisation des relations qui existent entre l’élasticité, la microstructure et la composition. / Bone as an important organ in human body is an extraordinary material which exhibits highly optimized properties, strong yet light weight, stiff yet flexible. Its distinct mechanical properties which fascinates not only scientists but also engineers are the results of the highly hierarchized and organized structure and the compositional properties spanning over several lengths from the nanoscale to the macroscale. Hence, a deep understanding of the parameters affecting bone mechanical behavior is necessary to better predict and treat bone diseases, improve orthopedic implants design, and engineer bio-inspired materials. In this work, a special focus is placed on human cortical bone elastic properties both at the millimeter and micrometer scales. Based on a multimodal approach (resonant ultrasound spectroscopy, synchrotron radiation micro-computed tomography, Fourier transform infrared microspectroscopy and biochemistry experiments) involving an exhaustive amount of microstructural and compositional properties, our results provide strong evidence that intra-cortical porosity and degree of mineralization are the most important determinants of bone stiffness at millimeter scale in an elderly population. Further, the other microstructure characteristics independent of porosity have non measurable effects on bone stiffness at this level. At the micrometer scale, a novel inverse homogenization approach is introduced in this work which can evaluate bone matrix anisotropic elastic properties with a good accuracy for all the stiffness constants. Based on the determined bone matrix elasticity data, we investigated the possible range of the magnitude of microstrain experienced by bone matrix. This work opens a way to better evaluate and understand bone mechanical behaviour at the micrometer level, such as the microstrain that can be sensed by osteocytes and builds the bridge to comprehensively investigate the connections between bone anisotropic properties at the millimeter and micrometer scale, and between the anisotropic microelastic properties and the characteristics at the nanometer scale.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 4 uppsatser. Även tryckt utgåva.