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

Bone Marrow Lesions and Subchondral Cysts in Association with Severity of Structural Degeneration in Hip Osteoarthritis

This item is only available electronically.Thesis (BHlthMSc(Hons)) -- University of Adelaide, Adelaide Medical School, YEA

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

In vivo imaging of cortical porosity by synchrotron phase contrast micro computed tomography

Cortical bone is a dynamic tissue which undergoes adaptive and pathological changes throughout life. An improved understanding of the spatio-temporal process of remodeling holds great promise for improving our understanding of bone development, maintenance and senescence. The use of micro-computed tomography (µCT) on living animals is relatively new and allows the three dimensional quantification of change in trabecular bone microarchitecture over time. The use of in vivo µCT is limited by the radiation dose created by the x-ray beam, with commercially available in vivo systems generally operating in the 10-20 um resolution range and delivering an absorbed dose between 0.5-1 Gy. Because dose scales to the power of four with resolution, in vivo imaging of the cortical canal network, which requires a higher resolution, has not been achieved. I hypothesized that using synchrotron propagation phase contrast µCT, cortical porosity could be imaged in vivo in rats at a dose on the same level as those used currently for trabecular bone analysis. Using the BMIT-BM beamline, I determined the optimal propagation distance and used ion chamber and lithium fluoride crystal thermoluminescent dosimetry to measure the absorbed dose of my in vivo protocol as well as several ex vivo protocols using synchrotron phase contrast µCT at 5 µm, 10 µm, and 11.8 µm and conventional desktop in vivo protocols using commercial µCT systems. Using synchrotron propagation phase contrast µCT, I scanned the forelimb of two adult Sprague-Dawley rats and measured an absorbed dose of 2.53 Gy. Using two commercial µCT system, I measured doses between 1.2-3.6 Gy for protocols at 18µm that are in common use. This thesis represents the first in vivo imaging of rat cortical porosity and demonstrates that an 11.8 µm resolution is enough to visualize cortical porosity in rats, with a dose within the scope of those used for imaging trabecular bone in vivo

Imaging technologies for preclinical models of bone and joint disorders

Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers. The combined use of imaging modalities also holds significant potential for the assessment of disease pathogenesis in animal models of musculoskeletal disorders, minimising the use of conventional invasive methods and animal redundancy

Survey of mri usefulness for the clinical assessment of bone microstructure

open8siFunding: E.S. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant agreement No713750. Additionally, it has been carried out with the financial support of the Regional Council of Provence Alpes-Côte d’Azur and with the financial support of the A*MIDEX (n◦ ANR- 11-IDEX-0001-02), funded by the “Investissements d’Avenir” project funded by the French Government, managed by the French National Research Agency (ANR). No authors is affiliated to an Intergovernmental Organization.Bone microarchitecture has been shown to provide useful information regarding the evaluation of skeleton quality with an added value to areal bone mineral density, which can be used for the diagnosis of several bone diseases. Bone mineral density estimated from dual‐energy x‐ray absorptiometry (DXA) has shown to be a limited tool to identify patients’ risk stratification and therapy delivery. Magnetic resonance imaging (MRI) has been proposed as another technique to assess bone quality and fracture risk by evaluating the bone structure and microarchitecture. To date, MRI is the only completely non‐invasive and non‐ionizing imaging modality that can assess both cortical and trabecular bone in vivo. In this review article, we reported a survey regarding the clinically relevant information MRI could provide for the assessment of the inner trabecular morphology of different bone segments. The last section will be devoted to the upcoming MRI applications (MR spectroscopy and chemical shift encoding MRI, solid state MRI and quantitative susceptibility mapping), which could provide additional biomarkers for the assessment of bone microarchitecture.openSoldati E.; Rossi F.; Vicente J.; Guenoun D.; Pithioux M.; Iotti S.; Malucelli E.; Bendahan D.Soldati E.; Rossi F.; Vicente J.; Guenoun D.; Pithioux M.; Iotti S.; Malucelli E.; Bendahan D

Multi-scale imaging and modelling of bone

The multi-level organization of bone facilitates the exploitation of in-vivo micro-scale information which is currently lacking for clinical applications. The three sub-projects presented in this thesis investigate the human skeletal system at multiple scales using magnetic resonance imaging (MRI) with the aim of providing new techniques for extracting finer scale information in-vivo. At the whole organ level, human knee joint kinematics was studied using a combined MRI strategy. This new strategy enables the in-vivo investigation of tibiofemoral locomotion under body weight-bearing conditions by modelling the knee flexion angle as a function of the femur and tibia cartilage surfaces in contact. The resultant "contact" trajectory may potentially be used to understand the mechanical cause of cartilage degeneration and as a biomarker to detect abnormalities in the lower limb. At the molecular level, in-vivo MR diffusion tensor imaging (DTI) has been performed for the first time in the human tibia epiphysis. By tracking the water molecules inside the red marrow, the organization of trabecular bone network may be understood as the streamlines formed by anisotropic diffusion trajectories. This sub-project aims to understand the organization of trabecular bone networks non-invasively, which is usually performed ex-vivo through biopsies. The feasibility and reproducibility of DTI is studied. Finally, a new MR imaging protocol named multi-directional sub-pixel enhancement (mSPENT) is proposed and developed to quantify the trabecular bone structural arrangement at the meso-scale. By modulating a dephasing gradient to manipulate the underlying spin system inside each voxel, the resulting mSPENT image contrast varies with gradient at different directions based on the magnetization at the corresponding voxel. A tensor-based method is further developed to model this contrast change, leading to a localized quantification of tissue structural orientation beyond the conventional MR imaging resolution