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

Mapping Trabecular Bone Fabric Tensor by in Vivo Magnetic Resonance Imaging

The mechanical competence of bone depends upon its quantity, structural arrangement, and chemical composition. Assessment of these factors is important for the evaluation of bone integrity, particularly as the skeleton remodels according to external (e.g. mechanical loading) and internal (e.g. hormonal changes) stimuli. Micro magnetic resonance imaging (µMRI) has emerged as a non-invasive and non-ionizing method well-suited for the repeated measurements necessary for monitoring changes in bone integrity. However, in vivo image-based directional dependence of trabecular bone (TB) has not been linked to mechanical competence or fracture risk despite the existence of convincing ex vivo evidence. The objective of this dissertation research was to develop a means of capturing the directional dependence of TB by assessing a fabric tensor on the basis of in vivo µMRI. To accomplish this objective, a novel approach for calculating the TB fabric tensor based on the spatial autocorrelation function was developed and evaluated in the presence of common limitations to in vivo µMRI. Comparisons were made to the standard technique of mean-intercept-length (MIL). Relative to MIL, ACF was identified as computationally faster by over an order of magnitude and more robust within the range of the resolutions and SNRs achievable in vivo. The potential for improved sensitivity afforded by isotropic resolution was also investigated in an improved µMR imaging protocol at 3T. Measures of reproducibility and reliability indicate the potential of images with isotropic resolution to provide enhanced sensitivity to orientation-dependent measures of TB, however overall reproducibility suffered from the sacrifice in SNR. Finally, the image-derived TB fabric tensor was validated through its relationship with TB mechanical competence in specimen and in vivo µMR images. The inclusion of trabecular bone fabric measures significantly improved the bone volume fraction-based prediction of elastic constants calculated by micro-finite element analysis. This research established a method for detecting TB fabric tensor in vivo and identified the directional dependence of TB as an important determinant of TB mechanical competence

Quantification of bone using a 3.0 tesla clinical magnetic resonance scanner

The work in this thesis examines the potential of using magnetic resonance imaging and spectroscopy (MRI & MRS) as a quantitative tool for diagnosing bone abnormalities at multiple skeletal sites, which could be used in conjunction with routine clinical imaging.MRI and MRS are routinely used in the clinical setting for the diagnosis of various types of diseases and abnormalities due to its advantages of providing excellent soft tissue contrast and also providing physiological and metabolic information. The use of MRI and MRS as a direct diagnostic tool for bone abnormalities is very limited at the moment due to issues of costs and standardisation. The aim in this thesis was to use the clinical 3.0 T MR scanner to acquire data from bone and bone marrow for identification of structural and chemical properties and to use those features to identify differences in bone strength and condition. The volunteers in this thesis were part of the high bone mass (HBM) study and they had additional acquisitions from dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT).MR acquisition protocols have been successfully optimised for each type of bone region and in-house software has also been created to process the acquired data and quantify various types of structural and chemical properties.The MR data from distal radius and tibia demonstrated good correlation with pQCT data (e.g. Figure 8-2 & Figure 8-3) and were also able to differentiate between HBM-affected and control populations (e.g. Figure 8-26). The MR data from lumbar vertebrae also demonstrated good correlation with DEXA data and some of the measurements were also able to differentiate between the HBM-affected and control populations.The combined results from this thesis demonstrate that both MRI and MRS are sensitive techniques for measurement of bone quantity and quality, and they are ready to be applied for clinical investigation as part of routine clinical imaging to identify bone strength in relation to abnormalities and treatments

Reporting guidelines, review of methodological standards, and challenges toward harmonization in bone marrow adiposity research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society

The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical or clinical BMA researchers, searched the literature for articles investigating BMA and discussed the results during personal and telephone conferences. According to the consensus opinion, both based on the review of the literature and on expert opinion, we describe existing methodologies and discuss the challenges and future directions for (1) histomorphometry of bone marrow adipocytes, (2

Bone marrow Fat - A Novel Quantification Method and Potential Clinical Applications

Ageing bone is characterised by increased marrow fat infiltration altering its composition and microstructure, thus predisposing the person to osteoporosis. Yet to date, non-invasive quantifications of marrow fat are limited to special MRI techniques, and clinical studies examining marrow fat in the ageing skeleton are scarce. Thus, the key aims of this thesis are to: · Validate a new non-invasive technique of marrow fat quantification using CT technology · Determine the effects of dietary fatty acids on marrow fat · Measure marrow fat content in different skeletal regions in healthy older men · Determine the effect of exercise and calcium on marrow fat. The imaging techniques employed in our animal and human studies were micro CT (µCT) and quantitative CT (QCT) respectively. All images were analysed with the imaging software Slice O Matic version 4.1 (Tomovision). Regions of interest [ROIs] were Volumes of interests (VOIs) of bone, fat and blood measured in µm3 or mm3. Individual tissue volumes, expressed as percentages of the total marrow volume, and ratios of tissue volumes were also used in the analysis. Global and local thresholds for individual tissue volumes were determined separately for µCT and QCT. Thresholds for µCT were those derived from the initial validation study, whereas those for QCT were based on previous published data. To account for partial volume averaging effects, further manual refinement of threshold ranges were undertaken by inspection of individual pixels and their neighbours. This manual process was carried out for both µCT and QCT to derive local thresholds for use in manual segmentation and computation of volumes. Our validation study showed that quantification of marrow fat using µCT was reliable and accurate compared to the gold standard technique- histology- when reliably defined thresholds were used. Good agreement between tissue volumes measured by histology and those computed by the imaging software was demonstrated. We applied this technique to quantify marrow fat in an animal model of senile osteoporosis, and showed that fatty acids (ω- 3 and ω-6) had dual effects on bone. With QCT studies, we confirmed the age related increase in marrow adiposity, and more significantly, different ratios between fat and bone in common fracture regions. Similarly, exercise affects marrow fat differently in different regions, and there was a trend to statistically significant changes to marrow fat with exercise. In conclusion, this body of work showed that quantification of marrow fat using CT is promising, and has future clinical implications. However, significantly more clinical studies are needed to confirm these findings and refine shortfalls in quantification capabilities

A qualitative and quantitative investigation of structural morphology in the neonatal ilium

Cortical and trabecular bone characteristics can be used to make predictions regarding previous loading regimes and developmental milestones which a bone has encountered. This has led to the suggestion that in the adult pelvis, bone patterning is related to the remodeling forces generated during bipedal locomotion. However, during the neonatal period the pelvic complex is non-load bearing, therefore, structural organisation of the ilium cannot reflect direct stance related forces. This study considers the cortical and trabecular bone structure in the ilium of the fetal and newborn infant, a structural configuration which until now has remained largely neglected in the literature. Only recently, with the advent of imaging modalities, has a greater insight and understanding of previously unexplored human bone structural composition and developing bone structure been made possible. In this study, multiple imaging techniques were applied to establish the optimal modality for application to the assessment of bone microstructure. Plain plate macroradiography and micro-computed tomography were identified as the gold standard imaging modalities for bone structural analysis for respective qualitative and quantitative assessment. These techniques were applied to gain a perspective of bone form from a sample of fetal and neonatal ilia selected from the Scheuer collection of juvenile remains. Initially, qualitative analysis highlighted consistent and well-defined patterns of cortical and trabecular bone organisation within the fetal and neonatal ilium, which corresponded with previously recognised regions in the adult that have been attributed directly to forces associated with bipedal locomotion. This was highly unexpected as the early developmental ilium is non-load bearing. Subsequently, quantification of the neonatal cortical and trabecular structure reinforced radiographic observations by identifying regions of significant architectural arrangement. Further investigation of this precocious patterning led to a revised proposal for the mode of growth in the human ilium during the neonatal developmental period. Analysis revealed statistically significant differences in regional trabecular characteristics and cortical thicknesses which have formed the basis of a proposed growth model for the ilium. The presence of ‘progressive growth regions’ and ‘restricted growth regions’ which appear to relate to metaphyseal and non-metaphyseal borders of the ilium have been demonstrated. Analysis of the early iliac bone pattern is important for understanding the relationship between trabecular bone patterning and cortical bone structure during the earliest stages of development in response to the specific functional forces acting during this period. It is suggested that the seemingly organised rudimentary scaffold observed in the early developmental ilium may be attributable to early ossification patterning, non-weight bearing anatomical interactions or even to a predetermined genetic blueprint. It must also be postulated that whilst the observed patterning may be indicative of a predetermined inherent template, early non-load bearing locomotive influences may subsequently be superimposed upon this scaffolding and perhaps reinforced and likely remodelled at a later age. Ultimately, the analysis of this fundamental primary pattern has core implications for understanding the earliest changes in iliac trabecular architecture and provides a baseline insight into future ontogenetic development and bipedal capabilities. Finally, the structural data and statistical analysis presented challenge the current concept of implied centrifugal ossification within the human ilium and present evidence of an alternative pattern of ossification that is largely dictated and controlled by basic anatomical principles.EThOS - Electronic Theses Online ServiceLeng TrustWenner-Gren FoundationBiotechnology and Biological Sciences Research CouncilGBUnited Kingdo

A qualitative and quantitative investigation of structural morphology in the neonatal ilium

Cortical and trabecular bone characteristics can be used to make predictions regarding previous loading regimes and developmental milestones which a bone has encountered. This has led to the suggestion that in the adult pelvis, bone patterning is related to the remodeling forces generated during bipedal locomotion. However, during the neonatal period the pelvic complex is non-load bearing, therefore, structural organisation of the ilium cannot reflect direct stance related forces. This study considers the cortical and trabecular bone structure in the ilium of the fetal and newborn infant, a structural configuration which until now has remained largely neglected in the literature. Only recently, with the advent of imaging modalities, has a greater insight and understanding of previously unexplored human bone structural composition and developing bone structure been made possible. In this study, multiple imaging techniques were applied to establish the optimal modality for application to the assessment of bone microstructure. Plain plate macroradiography and micro-computed tomography were identified as the gold standard imaging modalities for bone structural analysis for respective qualitative and quantitative assessment. These techniques were applied to gain a perspective of bone form from a sample of fetal and neonatal ilia selected from the Scheuer collection of juvenile remains. Initially, qualitative analysis highlighted consistent and well-defined patterns of cortical and trabecular bone organisation within the fetal and neonatal ilium, which corresponded with previously recognised regions in the adult that have been attributed directly to forces associated with bipedal locomotion. This was highly unexpected as the early developmental ilium is non-load bearing. Subsequently, quantification of the neonatal cortical and trabecular structure reinforced radiographic observations by identifying regions of significant architectural arrangement. Further investigation of this precocious patterning led to a revised proposal for the mode of growth in the human ilium during the neonatal developmental period. Analysis revealed statistically significant differences in regional trabecular characteristics and cortical thicknesses which have formed the basis of a proposed growth model for the ilium. The presence of ‘progressive growth regions’ and ‘restricted growth regions’ which appear to relate to metaphyseal and non-metaphyseal borders of the ilium have been demonstrated. Analysis of the early iliac bone pattern is important for understanding the relationship between trabecular bone patterning and cortical bone structure during the earliest stages of development in response to the specific functional forces acting during this period. It is suggested that the seemingly organised rudimentary scaffold observed in the early developmental ilium may be attributable to early ossification patterning, non-weight bearing anatomical interactions or even to a predetermined genetic blueprint. It must also be postulated that whilst the observed patterning may be indicative of a predetermined inherent template, early non-load bearing locomotive influences may subsequently be superimposed upon this scaffolding and perhaps reinforced and likely remodelled at a later age. Ultimately, the analysis of this fundamental primary pattern has core implications for understanding the earliest changes in iliac trabecular architecture and provides a baseline insight into future ontogenetic development and bipedal capabilities. Finally, the structural data and statistical analysis presented challenge the current concept of implied centrifugal ossification within the human ilium and present evidence of an alternative pattern of ossification that is largely dictated and controlled by basic anatomical principles.EThOS - Electronic Theses Online ServiceLeng TrustWenner-Gren FoundationBiotechnology and Biological Sciences Research CouncilGBUnited Kingdo