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

Determining If Lowering the Level of Dietary Calcium and Vitamin D in AIN-93G Diet Supports Normal Bone Development and Intestinal Integrity in Female CD-1 Mice

Current levels of vitamin D (vit D) and calcium (Ca) in the reference AIN-93G rodent diet may be higher than required for healthy bone structure and bone mineral density (BMD). Other studies suggest that intestinal integrity may be altered by lowering levels of vit D or Ca. The study objective was to determine if lower diet levels of Ca and vit D support development of healthy bone structure and BMD in female CD-1 mice at 2 and 4 months of age without altering intestinal integrity. Lowering the levels of vit D (100 IU/kg) and Ca (3.5 g/kg) did not alter bone structure or BMD. Effects on intestinal integrity are less clear and requires further study using more comprehensive measures. Findings from this study suggest that dietary Ca and/or vit D at current levels in the AIN-93G reference diet may mask potential benefits of nutritional interventions aimed at promoting bone health

In vivo assessment of changes in bone due to osteoporosis and its possible treatments

Osteoporosis is a skeletal disease characterized by a decrease in bone mass and deterioration of bone microarchitecture, resulting from an unbalance in the amount of bone formed and resorbed during bone remodeling. It often takes place after menopause in women due to estrogen deficiency and results in decreased bone strength and, subsequently, a greater risk of fracture. Pharmaceutical treatments for osteoporosis can roughly be divided into bone resorption inhibitors and bone formation enhancers. To evaluate possible treatments, postmenopausal osteoporosis can be simulated in animals by performing an ovariectomy, which leads to estrogen deficiency and subsequent bone loss. This loss of bone mass and the subsequent microarchitectural deterioration is often analyzed by micro-CT, which until recently was only possible to do ex vivo, after sacrifice. Recently, however, in vivo micro-CT scanners have become available with which bone in living rats can be scanned. In vivo micro-CT, combined with image registration software, offers a potentially more powerful method to identify effects of osteoporosis and treatments over time. Additionally, local changes in bone within the same animal can be monitored over time, which taken together can provide novel and unique information In this dissertation, we focused on the development of osteoporosis and several treatments in rats. We first concentrated on bone resorption inhibitors and then on bone formation enhancers. Changes over time in bone microstructure were determined as well as mechanical properties after sacrifice using mechanical tests or finite element models. We first ruled out that radiation damage due to scanning affected our studies. Then two different animal models that simulate bone loss due estrogen-deficiency (i.e. after menopause) and immobilization (e.g. after long bed resting) were compared, as their effects on bone structure and strength may differ. In the metaphysis, the loss of bone volume fraction was found to be similar for both models, while structure and strength were more affected after immobilization. In the epiphysis, changes in bone volume fraction and structure were different. The difference in response between the meta- and epiphysis may be related to different mechanisms underlying the bone loss after estrogen-deficiency and immobilization. These findings offer insight into the aetiology and possible treatment of different types of osteoporosis. Zoledronic acid (ZOL) is a novel, potent bone resorption inhibitor. In the rat tibia, we found that preventive treatment with ZOL prevented all bone microstructural changes seen after ovariectomy. Recovering treatment significantly improved bone microstructure, though not back to original levels. These results indicate that the timepoint of initiation of treatment is important for the final bone microstructure and strength. Both preventive and recovering treatments also led to inhibition of loss of bone mass and static compressive strength in the lumbar vertebra, a clinically relevant site. However, no significant influence of time-point of treatment was found here. Vertebral fractures mostly result from cyclic loading. ZOL may influence mineralization and lead to accumulation of microdamage, possibly affecting fatigue behavior. A method was developed to assess compressive fatigue properties in rat vertebrae. ZOL treated rats were found to have similar fatigue properties as normal rats, indicating that any altered mineralization and accumulated microdamage due to ZOL treatment did not affect fatigue properties. After exploring the effects of bone resorption inhibitors, we continued with studying the effects of bone formation enhancers. It was found that PTH leads to a linear, constant increase in trabecular and cortical bone mass over time and that mechanical properties improved. Micro-analysis showed that bone was formed on trabeculae, there where most beneficial for structure and strength. This indicates that bone formation resulting from PTH may be mechanically driven. In another study, the effects of a daily period on a vibration platform, which has been described in the literature to increase bone formation, were studied in osteoporotic rats over time. Within six weeks, no significant effects were found to take place. The potential of vibration as treatment for osteoporosis thus could not be established. Summarizing, for the first time, the comparison between two types of osteoporosis and the effects of several treatments for osteoporosis on bone microstructure were analyzed over time in vivo, offering insight into the temporal and spatial effects of bone resorption inhibitors and bone formation enhancers in osteoporotic rats

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

Simulation of fracture strength improvements of a human proximal femur using finite element analysis.

The most common hip fracture in the elderly occurs as a result of a fall to the side with impact over the greater trochanter resulting in a fracture of the proximal femur. The fracture usually involves the femoral neck or the intertrochanteric region. It has recently been determined that the fracture crack of a hip fracture typically initiates on the superior-lateral cortex of the femoral neck and then propagates across the femoral neck, resulting in a complete fracture. The strength of the superior-lateral cortex of the femoral neck is likely determined by the combined properties of the generally thin cortex (outer layer) and the underlying trabecular bone in this region. The objective of this study was to determine the relative effects of increasing or decreasing the thickness of these bone tissues on the overall failure strength of the proximal femur. The clinical significance of this work relates to hip fracture risk with various potential treatment options to improve either cortical or trabecular bone quality. A human femur obtained from a 68 year old female donor was scanned using computed tomography at 60-micron voxel resolution and a series of high-resolution finite element models were generated. The models were constructed with a base-element dimension of 120 microns and models included a basic model with cortical and trabecular thicknesses representative of the cadaver specimen from the original scan. Other models used a standardized algorithm to either dilate or erode the trabecular and cortical bone compartments of the femoral neck so that a total of nine models were created including the basic model. Each model was used to simulate a fall-to-the-side loading condition with appropriate boundary and loading conditions as used in previous models and experiments. An experimental test of the cadaver femur was also performed with three strain gauges placed on the proximal femur: on the superior-lateral cortex, on the inferior-medial cortex, and on the medial cortex positioned distal to the lesser trochanter. This femur was loaded at a rate of 100 mm/s until fracture of the femoral neck using a standard fall-to-the-side setup and the applied load and gauge strains were recorded. The femur neck fractured at a load of 2140 N. To validate the basic finite element model, the strain gauge strains at the load levels of 1000 N and 2000 N were compared to the calculated strains from the basic model at the same loads and same location as the gauge on the cadaver femur. After the basic model was validated, a failure criterion was determined as the volume percentage of the elements in the model that had exceeded 7000 µε at the failure load corresponding to the load at which the cadaver femur failed. Subsequently, this failure criterion was applied to the other eight models as a parametric analysis to estimate the increase or decrease in failure strength caused by the changes in cortical and trabecular thickness. The validation test results showed that the basic finite element model calculated strain on the superolateral cortex was within 2.1% of the experimentally measured strain at 1000 N loading. The validated basic model was then used to determine that the percentage of finite elements (by volume of the model) in excess of 7000 µε at the failure load was 4.2%. This failure criterion was then used to estimate the failure load for the other eight models with different combinations of either thicker (+120 µm) or thinner (-120 µm) cortex and trabeculae in the femoral neck. The calculated failure loads ranged from 324 N for the model with thinned cortex and thinned trabeculae to 3336 N for the model with thickened cortex and thickened trabeculae. The model with normal cortex and thickened trabeculae had a failure load of 3242 N, which is only 2.8% less than the strongest case. The largest single parameter effect on proximal femoral strength is realized by an increase in trabecular thickness. This is somewhat surprising considering that cortical bone is typically stronger than cancellous bone. However, the spatial arrangement of trabecular bone and the buttress support it provides to the thin cortex apparently plays an important role in the ability of a global increase in thickness to have a significant beneficial effect

Quantitative imaging of sex and age differences in human cortical bone osteocyte lacunae

Osteocytes, the most abundant cell within bone, have been linked to the processes of mechanosensation and transduction. Based upon relatively limited empirical evidence, variations in their abundance and morphology have been linked to sex, age, biomechanics and disease. In order to better elucidate lacunar variation within a healthy cohort, samples from 30 women aged 20-86 and 36 men aged 18-92 were studied utilizing synchrotron radiation micro-CT. Initial studies of normal variation within the femoral proximal shaft cross-section found high variation in lacunar density (up to ~54%) and associated morphological differences linked to biomechanical regions. In women, a non-significant trend in lacunar density reduction was apparent with age; however, a significant reduction in lacunar volume with age (~30%) was observed. Also noted were differences in lacunar morphology, with the lacunae of younger women characterized as flatter and less equant than their older counterparts. The males, who demonstrated lacunar density decline with age and a tendency towards more equant and less elongate lacunae, did not share these characteristics. Intriguingly, the previously noted reductions in lacunar volume were not observed in males. The results of this research indicate that normal variation in osteocyte lacunar parameters is high. To our knowledge the observation that lacunar volume differs in women with age is novel, potentially resulting from preferential surface infilling within the extracellular space. The functional impact of this infilling is unclear but such a change in scale likely impacts the mechanosensing function of the osteocyte network. This hypothesis warrants further investigation as, if confirmed, it would represent a profound negative impact on the osteocyte network and may provide new insights into age-related bone loss

Mechanical and morphometric characterization of cancellous bone

[EN] Bone fracture is a social health problem of increasing magnitude because of its prevalence in aged population due to osteoporosis. Bone quality is often characterized by bone mineral density (BMD) measured at cancellous bone regions using dual-energy X-ray absorptiometry (DXA). However, BMD alone cannot predict several cases because not only density is important, but also microstructure plays an important role in cancellous bone strength. The mechanical properties can be used as indicators of bone integrity as a function of age, disease or treatment. Therefore, cancellous bone fracture characterization and its relationship to microstructure has not been completely solved in the literature and is relevant to improve fracture prediction. In this thesis, we aim at characterizing cancellous bone morphometry and mechanical behavior. Morphometry is estimated through the analysis of micro-computed tomography (micro-CT) images of vertebral cancellous bone specimens. With regards to the mechanical behavior, we calculate elastic, yield and failure properties at the apparent and tissue levels. To determine them, we followed different approaches: compression tests, finite element models and micro-CT phantoms. We have developed finite element models that reproduce the elastic and failure response of cancellous bone under compression conditions. We modeled failure as a combination of continuum damage mechanics and the element deletion technique. The numerical models permitted to estimate elastic and failure properties. Failure properties were consistent with results reported in the literature. Specifically, our results revealed that yield strain is relatively constant (0.7 %) over a range of apparent densities, while failure strain presents a wider range of variation. A single strain parameter (equivalent strain) was found as an accurate descriptor of cancellous bone compression failure. Image-based numerical models usually need for the action of a technician to segment the images. Therefore, we studied the sensitivity to variations of the segmentation threshold on the morphometry and the elastic properties of vertebral cancellous bone specimens of different bone volume fractions. The apparent modulus is highly sensitive to the segmentation threshold. We report variations between 45 and 120 % for a ± 15 % threshold variation. Other parameters, such as BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D and fractal dimension were influenced significantly. Digital image correlation (DIC) was applied to images taken during compression testing to analyze displacement fields at failure and characterize them. Some variables were explored to describe failure and a study is done about how DIC parameters influence the strain field obtained. Facet and step sizes have a relevant effect on the failure strain estimation, and an increment of both parameters reduces the strain estimation up to 40 %. Besides, several parameters combination led to correct failure pattern detection, so values reported in the literature should be referred to the parameters used. Furthermore, we explored if cancellous bone microstructure acts (non-speckle/texture approach) as a proper pattern to calculate displacements using DIC technique. As regards relationships between microstructure and mechanics, single and multiple parameter analysis were performed to assess the morphometric variables that control the explanation of mechanical properties variation. Bone volume fraction (BV/TV), bone surface to volume ratio (BS/BV), mean trabecular thickness (Tb.Th) and fractal dimension (D) presented the best linear correlations to the elastic properties, while both the yield and failure strains did not show correlation to any morphometric parameter. The regressions obtained permit to estimate those mechanical properties that describe the state of a specimen.[ES] Las fracturas óseas constituyen un problema social de salud con magnitud creciente por su prevalencia en la población de edad avanzada debido a la osteoporosis. La calidad del hueso suele caracterizarse mediante la estimación de la densidad mineral ósea (DMO) en regiones de hueso trabecular, utilizando absorciometría de rayos X de energía dual (DXA). No obstante, la DMO por si sola no es capaz de predecir numerosos casos de fractura porque no solo importa la pérdida de densidad, sino que la microestructura también tiene un papel principal en la resistencia del hueso. Las propiedades mecánicas del hueso pueden usarse como indicadores de su integridad en función de la edad, enfermedad o tratamiento. Por lo tanto, la caracterización de la fractura de hueso trabecular y su relación con la microestructura no se ha resuelto de forma completa en la literatura y es relevante para mejorar las predicciones de fractura. En esta tesis, nuestro principal objetivo es caracterizar la morfometría y el comportamiento mecánico del hueso trabecular. Estimamos la morfometría a través del análisis de imágenes obtenidas por micro tomografía computerizada (micro-CT) de muestras de hueso trabecular vertebral de cerdo. Respecto al comportamiento mecánico, calculamos propiedades elásticas, de plasticidad y fractura a escala aparente y de tejido. Para determinar esas propiedades, hemos seguido diferentes procedimientos: ensayos a compresión, modelos de elementos finitos y fantomas de calibración micro-CT. Los modelos de elementos finitos desarrollados reproducen la respuesta elástica y de fallo bajo condiciones de compresión en hueso trabecular, modelando el fallo como combinación de mecánica del daño contínuo y la técnica de eliminación de elementos. Los modelos numéricos desarrollados han permitido estimar propiedades elásticas y de fallo. En concreto, las deformaciones de inicio de fallo estimadas son relativamente constantes para las muestras analizadas (0.7 %), mientras que las deformaciones últimas de fallo presentan un rango de variación mayor. Por otro lado, encontramos que la deformación equivalente es el descriptor más preciso del fallo a compresión del hueso trabecular. Normalmente, los modelos numéricos basados en imágenes suelen necesitar la acción de un técnico para segmentar las imágenes. En este sentido, estudiamos la sensibilidad de la morfometría y la estimación de propiedades elásticas ante variaciones en el umbral de segmentación en muestras con distinta fracción en volumen. Hemos obtenido que la rigidez aparente es muy sensible a cambios en el umbral de segmentación, con variaciones entre 45 y 120 % para una variación de ± 15 % del umbral de segmentación. Otros parámetros, como BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D y la dimensión fractal se ven afectados significativamente. Por otro lado, hemos aplicado la técnica correlación digital por imagen (DIC) para caracterizar campos de desplazamientos en el fallo a compresión del hueso trabecular, a partir del análisis de imágenes tomadas durante el ensayo de las muestras. Además, estudiamos la influencia de algunos parámetros de la técnica DIC en el campo de deformaciones obtenido. También, hemos explorado la aplicación DIC sin el uso de moteado, utilizando como patrón de reconocimiento la propia microestructura trabecular. En relación al estudio de la influencia de la microestructura en la respuesta mecánica, hemos calculado correlaciones de uno y varios parámetros para analizar qué variables morfométricas explican la variación de las propiedades mecánicas. La fracción en volumen de hueso (BV/TV), la relación entre el área y el volumen de hueso (BS/BV), el espesor trabecular medio (Tb.Th) y la dimensión fractal (D) presentan las mejores correlaciones lineales respecto a las propiedades elásticas, mientras que las deformaciones de inicio de plasticidad y fractura no mostraron correlación con ningún parámetro morfométrico.[CA] Les fractures òssies constitueixen un problema social de salut amb magnitud creixent per la seua prevalença en la població d'edat avançada a causa de l'osteoporosi. La qualitat de l'os sol caracteritzar-se mitjançant l'estimació de la densitat mineral òssia (DMO) en regions d'os trabecular, utilitzant absorciometria de raigs X d'energia dual (DXA). No obstant això, la DMO per si sola no és capaç de predir nombrosos casos de fractura perquè no sols importa la pèrdua de densitat, sinó que la microestructura també té un paper principal en la resistència de l'os. Les propietats mecàniques de l'os poden usar-se com a indicadors de la seua integritat en funció de l'edat, malaltia o tractament. Per tant, la caracterització de la fractura d'os trabecular i la seua relació amb la microestructura no s'ha resolt de manera completa en la literatura i és rellevant per a millorar les prediccions de fractura. En aquesta tesi, el nostre principal objectiu és caracteritzar la morfometria i el comportament mecànic de l'os trabecular. Estimem la morfometria a través de l'anàlisi d'imatges obtingudes per micro tomografia automatitzada (micro-CT) de mostres d'os trabecular vertebral de porc. Respecte al comportament mecànic, calculem propietats elàstiques, de plasticitat i fractura a escala aparent i de teixit. Per a determinar aqueixes propietats, hem seguit diferents procediments: assajos a compressió, models d'elements finits i fantomas de calibratge micro-CT. Hem desenvolupat models d'elements finits que reprodueixen la resposta elàstica i de fallada sota condicions de compressió en os trabecular, modelant la fallada com a combinació de mecànica del dany continu i la tècnica d'eliminació d'elements. Els models numèrics desenvolupats han permés estimar propietats elàstiques i de fallada. Les nostres estimacions respecte a propietats de fallada són consistents amb valors reportats en la literatura. En concret, les deformacions d'inici de fallada estimades són relativament constants per a les mostres analitzades (0.7 %), mentre que les deformacions últimes de fallada presenten un rang de variació major. D'altra banda, trobem que la deformació equivalent és el descriptor més precís de la fallada a compressió de l'os trabecular. Els models numèrics basats en imatges solen necessitar l'acció d'un tècnic per a segmentar les imatges. En aquest sentit, estudiem la sensibilitat de la morfometria i l'estimació de propietats elàstiques davant variacions en el llindar de segmentació en mostres amb diferent fracció en volum. Hem obtingut que la rigidesa aparent és molt sensible a canvis en el llindar de segmentació, amb variacions entre 45 i 120 % per a una variació de ± 15 % del llindar de segmentació. Altres paràmetres, com BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D i la dimensió fractal es veuen afectats significativament. D'altra banda, hem aplicat la tècnica correlació digital per imatge (DIC) per a caracteritzar camps de desplaçaments en la fallada a compressió de l'os trabecular, a partir de l'anàlisi d'imatges preses durant l'assaig de les mostres. A més, estudiem la influència d'alguns paràmetres de la tècnica DIC en el camp de deformacions obtingut. També, hem explorat l'aplicació DIC sense l'ús de clapejat, utilitzant com a patró de reconeixement la pròpia microestructura trabecular. En relació a l'estudi de la influència de la microestructura en la resposta mecànica, hem calculat correlacions d'un i diversos paràmetres per a analitzar quines variables morfomètriques expliquen la variació de les propietats mecàniques. La fracció en volum d'os (BV/TV), la relació entre l'àrea i el volum d'os (BS/BV), la espessor trabecular mitjà (Tb.th) i la dimensió fractal (D) presenten les millors correlacions lineals respecte a les propietats elàstiques, mentre que les deformacions d'inici de plasticitat i fractura no van mostrar correlació amb cap paràmetre morfomètric.Belda González, R. (2020). Mechanical and morphometric characterization of cancellous bone [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/149376TESI