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

Development of procedures to perform nanoindentation tests on different bone structures

Negli ultimi anni, la nanoindentazione è emersa come potente tecnica per indagare le proprietà micromeccaniche dell'osso. L'indentazione consiste nel premere una punta rigida con una forza nota in un semispazio semi-infinito e nel misurare direttamente o indirettamente l'area di contatto. L'obiettivo principale di questo lavoro è stato quello di sviluppare una procedura per eseguire test di nanoindentazione al fine di studiare le proprietà elastiche e inelastiche di diverse strutture ossee. Dalle misure di nanoindentazione sono stati ricavati i valori di reduced modulus, hardness, indentation modulus ed elastic modulus. L'idea era di eseguire test di nanoindentazione sia per applicazioni precliniche che cliniche e per questo motivo, i tests sono stati effettuati sia su ossa di topo che su ossa umane affette da una particolare condizione patologica, chiamata Osteogenesi Imperfetta. È la prima volta che questi tests vengono eseguiti su tibie di topo, nello specifico su fette di quattro tibie di due ceppi (C57B1/6 e Balb/C), sia su osso corticale che trabecolare. Abbiamo trovato che il modulo elastico varia tra 16.50 ± 7.10 GPa (C57B1/6, osso trabecolare) e 25.08 ± 5.21 GPa (Balb/C, osso corticale). L’hardness varia tra 0.62 ± 0.27 GPa (C57B1/6, osso trabecolare) e 0.96 ± 0.20 GPa (Balb/C, osso corticale). Le nanoindentazioni sul campione di OI (proveniente dall’arto superiore) sono state condotte su diverse fette, per analizzare le potenziali differenze tra le due regioni e le quattro sezioni. Abbiamo trovato un modulo elastico di 12.14 ± 5.79 GPa e l’hardness di 0.49 ± 0.21 GPa. In conclusione, abbiamo sviluppato questo nuovo protocollo che può essere applicato a diversi lavori futuri. Ad esempio, per le applicazioni precliniche aumentando il numero di topi diversi o per applicazioni cliniche aumentando il numero dei campioni di OI, raccogliendo campioni con diversi tipi di OI, indagando l'effetto dei trattamenti o confrontando le ossa di OI con osso sano

Integrating Nanomechanical Property Testing into a Correlative Imaging Workflow

This work is aimed at creating a cohesive workflow between correlative imaging techniques and nanomechanical property testing for materials analysis. There exist multiple features of a material, on varying length scales, that can determine its performance in its desired function. As technology advances new materials are developed to address new problems with more and more taking their inspiration from nature. The use of different techniques individually has been able to shed light on either the structure, property, or function of the materials, either manufactured or biological. Understanding has developed that the three aspects; structure, property, and function are related and should be considered together when analysing a material. Combining multiple techniques in a workflow will allow for revealing the ‘whole picture’ of the material. The methods of materials analysis used in this research are X-ray micro-CT, scanning electron microscopy (SEM), light microscopy, X-ray fluorescence (XRF), and nanoindentation. Each of the methods used here requires specific preparation methods prior to testing and one testing method may make the sample unsuitable for another testing method. Therefore, planning the sequence of testing before commencing is of high importance. Putting into place a workflow will not only reduce the likelihood of inhibiting further testing procedures but also reduce the time taken for completing a comprehensive analysis. The workflow proposed here takes into consideration what information can be gained as well as preparation techniques. Initially, this thesis will discuss correlative imaging detailing, sample preparation, and the capabilities of these techniques in uncovering the internal nano – to the macro-structure of antler bone and barnacle plate organisation, as well as the chemical uniformity of the inorganic phase of antler bone across the cross-section and the elongated crystallographic structures unique to the barnacle ala. Secondly, XRF will be explored for its role in the chemical analysis of biological materials and where this technique can be placed into the workflow to impact the overall understanding of the chemical composition in this instance in the application of antlers. Finally covered will be nanomechanical property testing for both stand-alone equipment and in-situ indentation. The suggested position for this technique in the workflow will be explained as it is used as the final connecting piece in determining the structure-function-property relationship of the material due to how the previous methods have directed the research process. Correlating the accelerated property mapping technique to the crystallographic structures in barnacle plates showed a reduced hardness in the elongated crystal region. Nanoindentation of the antler bone showed differences in modulus between the transverse and cross-sections as well as a reduction in average hardness between the male antler and the female reindeer that had calves and those that did not. Each of the individual pieces of information in this workflow when brought together unveils the hidden structure-property-function relationship in materials to provide an in-depth understanding

A review of the state of art in applying Biot theory to acoustic propagation through the bone

Understanding the propagation of acoustic waves through a liquid-perfused porous solid framework such as cancellous bone is an important pre-requisite to improving the diagnosis of osteoporosis by ultrasound. In order to elucidate the propagation dependence upon the material and structural properties of cancellous bone, several theoretical models have been considered to date, with Biot-based models demonstrating greatest potential. This paper describes the fundamental basis of these models and reviews their performance

Contributions of anisotropic and heterogeneous tissue modulus to apparent trabecular bone mechanical properties

The highly optimized hierarchical structure of trabecular bone is a major contributor to its remarkable mechanical properties. At the micro-scale level, individual plate-like and rod-like trabeculae are interconnected, forming a complex trabecular architecture. It is widely believed that bone strength, an important mechanical characteristic that describes the capability of bone to resist fracture, is largely determined by the tissue-level material properties of these microscopic trabecular elements. However, due to the complicated microstructure and irregular morphology of trabecular bone, a link between the tissue-level and the apparent level mechanics in trabecular bone has never been established. Thus, the goal of this thesis is to examine the tissue-level material properties of trabecular bone and their contribution to apparent-level bone mechanics, and ultimately to improve our fundamental understanding and assessment of bone strength in diseased and healthy patients. At the micro-scale level, plate-like and rod-like trabeculae are distinctly aligned along different orientations on the anatomical axis of the skeleton. Also, the highly organized underlying ultrastructure of bone tissue suggests trabecular bone might possess an anisotropic tissue modulus, i.e. different modulus in the axial and lateral cross-section of a trabecula. In this thesis, we studied this tissue-level anisotropy by examining mechanical properties of individual trabecular plates and rods aligned longitudinally, obliquely, and transversely on the anatomical axis using micro-indentation. We discovered that, despite the different orientations of trabeculae, tissue moduli are higher in the axial direction than in the lateral direction for both plates and rods. We also discovered that plates have a higher tissue modulus than rods, suggesting different degrees of mineralization. Furthermore, the tissue mineral density correlated strongly but distinctly with tissue modulus in the axial and lateral directions, providing descriptions on how spatially heterogeneous mineralization at the tissue level affects the tissue modulus. After characterization of the anisotropic and heterogeneous modulus of trabecular bone at the tissue level, we then sought to investigate its contribution to apparent-level mechanical properties, including apparent Young’s modulus and yield strength. Non-linear FE voxel models incorporating experimentally determined anisotropy and heterogeneity were created from micro-computed tomography (µCT) images of healthy trabecular bone samples. Apparent Young's modulus and yield strength predicted by the models were compared to and correlated with gold standard mechanical testing measurements, as well as to the same FE models without incorporation of anisotropy and/or heterogeneity. We discovered that the anisotropic model prediction was highly correlated and indistinguishable from mechanical testing measurements. However, the prediction power of the model was not enhanced by incorporating anisotropy and heterogeneity (compared to a homogeneous and isotropic model), suggesting that variances in tissue-level material properties contribute minimally to the apparent level bone behaviors in healthy bone. However, the possibility remained that a more substantial contribution could arise in diseased bone, particularly diseases in which tissue-level properties are compromised. Therefore, we studied trabecular bone in two diseased conditions – subchondral bone in human knees affected by osteoarthritis and pelvic bone affected by adolescent idiopathic sclerosis – to see how disease can alter the tissue-level and, consequently, apparent-level bone mechanics. In OA bone, we found a significant decrease in tissue modulus in the subchondral bone under severely damaged cartilage compared to control, which provides an explanation for a minimal increase in apparent stiffness with an almost doubled bone volume fraction. In AIS bone, no differences were found in tissue-level or apparent level Young’s modulus compared to control. However, the mineral density was found to play a distinct role in the modulus of growing bone tissue compared to mature bone

Characterization of structural bone properties through portable single-sided nmr devices: State of the art and future perspectives

Nuclear Magnetic Resonance (NMR) is a well-suited methodology to study bone composition and structural properties. This is because the NMR parameters, such as the T2 relaxation time, are sensitive to the chemical and physical environment of the1H nuclei. Although magnetic resonance imaging (MRI) allows bone structure assessment in vivo, its cost limits the suitability of conventional MRI for routine bone screening. With difficulty accessing clinically suitable exams, the diagnosis of bone diseases, such as osteoporosis, and the associated fracture risk estimation is based on the assessment of bone mineral density (BMD), obtained by the dual-energy X-ray absorptiometry (DXA). However, integrating the information about the structure of the bone with the bone mineral density has been shown to improve fracture risk estimation related to osteoporosis. Portable NMR, based on low-field single-sided NMR devices, is a promising and appealing approach to assess NMR properties of biological tissues with the aim of medical applications. Since these scanners detect the signal from a sensitive volume external to the magnet, they can be used to perform NMR measurement without the need to fit a sample inside a bore of a magnet, allowing, in principle, in vivo application. Techniques based on NMR single-sided devices have the potential to provide a high impact on the clinical routine because of low purchasing and running costs and low maintenance of such scanners. In this review, the development of new methodologies to investigate structural properties of trabecular bone exploiting single-sided NMR devices is reviewed, and current limitations and future perspectives are discussed

Structure-Function Relationships of Bighorn Sheep Horncore Bone and Horn-Horncore Interface Materials for Energy Absorption Applications

Bighorn sheep rams do not show overt signs of traumatic brain injury from head impacts experienced during intraspecific combat. Rams’ cranial appendages bear the brunt of ramming impacts and are composed of a keratin-rich horn anchored to a bony horncore via a soft connective tissue interface. The horncore is filled with velar bone which has a unique porous architecture with a comparable bone volume fraction, but larger strut thickness and separation than typical mammalian trabecular bone. Velar bone absorbs more energy than the horn and substantially reduces post-impact brain cavity accelerations in computational models of bighorn sheep ramming. These findings have implications for brain injury mitigation, but are limited by assumed material properties of the horncore bone and horn-horncore interfacial tissue as these were previously unknown. Since bone adapts to mechanical stimuli, and the horncore is exposed to a high impact environment, horncore bone material and the velar bone architecture are expected to have superior energy absorption than other mammalian bone tissues. Furthermore, the horn-horncore interface is expected to have an interdigitated microstructure like other dermo-epidermal junctions (e.g., the equine hoof-bone interface) to facilitate load transfer between the impacted horn and energy absorbing horncore. This dissertation explored these possibilities by quantifying the composition, microstructure, and mechanical properties of horncore bone and the horn-horncore interface tissue. In addition, computational modeling was used to provide a preliminary comparison between velar and trabecular bone architectures under compressive loading. Horncore bone materials and the velar bone architecture were not shown to increase energy absorption compared to other mammalian bone tissues or trabecular bone architectures. Interestingly, velae had osteons which are rare in trabeculae. Velar osteons may provide crack arrest and deflection to increase microdamage accumulation (i.e., microcrack toughening) and increase the energy absorption of the entire horncore compared to a similar volume of trabecular bone. Furthermore, the horn-horncore interface displayed a 4-fold increase in microscopic contact area, but did so with a morphology unlike other dermo-epidermal junctions. Despite morphological differences, lap-shear properties were comparable to the equine hoof-bone interface and were positively correlated with the microscopic contact area

7 Tesla?????? ????????? ????????? ???????????? ????????? ?????? ?????? ???????????? ????????? ??????

Department of Biomedical EngineeringMagnetic susceptibility contrast MRI using local magnetic field gradients or inhomogeneities is expected to provide low-resolution quantification of tissue microarchitecture, as magnetic resonance (MR) transverse relaxation times (T2 and T2*) are influenced by field inhomogeneity arising from susceptibility mismatch of tissues. By aid of ultra-high field MRI scanner, MR transverse relaxation times is promising to further increase their sensitivity to detecting subtle structural changes in tissue microstructures. However, one of the main technical difficulty of ultra-high field MRI is unwanted variations of signal and contrast, or even worse, nullify the MR signal due to increased macroscopic static magnetic field inhomogeneities which are prone to misinterpretation and loss of structural information. This study focuses on improving the sensitivity and the robustness of ultra-high field MRI (particularly for 7 T) from unwanted signal variations due to magnetic field inhomogeneities and shortened MR transverse relaxation times. MR transverse relaxation times were investigated for the low-resolution assessment of tissue microstructures, such as trabecular bone microstructure and cerebral microvasculature. As a result, T2 relaxation time without having an effect of macroscopic field inhomogeneities may be suitable for the assessment of trabecular structural indices and robust with degrading spatial resolution with reduced scan time at 7 T. For the assessment of cerebral microvasculature, the diffusion-time-dependent stimulated-echo-based MR relaxation-rates was demonstrated as robust measures for assessing small (diameter < 5 ??m) cerebral microvasculature, where macroscopic field inhomogeneities from bone (air)-tissue interfaces and influences of large vessels in cortical region are significant. Finally, the quantification of MR longitudinal relaxation time (T1) was optimized by variable repetition-delay turbo-spin echo method with sparse encoding technique.clos

Imaging techniques for the assessment of the bone osteoporosis-induced variations with particular focus on micro-ct potential

For long time, osteoporosis (OP) was exclusively associated with an overall bone mass reduction, leading to lower bone strength and to a higher fracture risk. For this reason, the measurement of bone mineral density through dual X-ray absorptiometry was considered the gold standard method for its diagnosis. However, recent findings suggest that OP causes a more complex set of bone alterations, involving both its microstructure and composition. This review aims to provide an overview of the most evident osteoporosis-induced alterations of bone quality and a résumé of the most common imaging techniques used for their assessment, at both the clinical and the laboratory scale. A particular focus is dedicated to the micro-computed tomography (micro-CT) due to its superior image resolution, allowing the execution of more accurate morphometric analyses, better highlighting the architectural alterations of the osteoporotic bone. In addition, micro-CT has the potential to perform densitometric measurements and finite element method analyses at the microscale, representing potential tools for OP diagnosis and for fracture risk prediction. Unfortunately, technological improvements are still necessary to reduce the radiation dose and the scanning duration, parameters that currently limit the application of micro-CT in clinics for OP diagnosis, despite its revolutionary potential