Browsing by Author "Boyd, Steven"

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    Assessment of the Efficacy of MRI for Detectionof Changes in Bone Morphology in a MouseModel of Bone Injury
    (Wiley, 2013-07-11) Taha, May A; Manske, Sarah; Kristensen, Erika; Taiani, Jaymi; Krawetz, Roman; Wu, Ying; Ponjevic, Dragana; Matyas, John; Boyd, Steven; Rancourt, Derrick; Dunn, Jeffrey F.
    Purpose To determine whether magnetic resonance imaging (MRI) could be used to track changes in skeletal morphology during bone healing using high-resolution micro-computed tomography (μCT) as a standard. We used a mouse model of bone injury to compare μCT with MRI. Materials and Methods Surgery was performed to induce a burr hole fracture in the mouse tibia. A selection of biomaterials was immediately implanted into the fractures. First we optimized the imaging sequences by testing different MRI pulse sequences. Then changes in bone morphology over the course of fracture repair were assessed using in vivo MRI and μCT. Histology was performed to validate the imaging outcomes. Results The rapid acquisition with relaxation enhancement (RARE) sequence provided sufficient contrast between bone and the surrounding tissues to clearly reveal the fracture. It allowed detection of the fracture clearly 1 and 14 days postsurgery and revealed soft tissue changes that were not clear on μCT. In MRI and μCT the fracture was seen at day 1 and partial healing was detected at day 14. Conclusion The RARE sequence was the most suitable for MRI bone imaging. It enabled the detection of hard and even soft tissue changes. These findings suggest that MRI could be an effective imaging modality for assessing changes in bone morphology and pathobiology.
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    Bone and 3D Joint Space Width Analysis in Knee Osteoarthritis using Weight Bearing CT
    (2024-01-26) Waungana, Tadiwa Hanson; Manske, Sarah; Edwards, William Brent; Boyd, Steven
    Osteoarthritis (OA) is the most common type of joint disorder in the world and a major cause of disability in the adult population. Globally, it is one of the fastest-growing health conditions and OA prevalence is expected to continue rising due to an aging global population. The knee is the most affected joint in OA, accounting for approximately 80% of the global OA burden, making it an important joint to consider in the context of OA. Knee OA is characterized by bone and joint structural changes, such as changes in the apparent bone mineral density, thickening of the subchondral bone plate and joint space narrowing. Detection of these changes has traditionally been considered the reserve of X-ray radiography, which is challenged by inherent anatomical overlap of a 2D imaging modality. Weight bearing computed tomography (WBCT) has recently been utilized to image and investigate OA-related structural changes in the knee, as it provides a 3D visualization of the joint whilst in a functionally relevant loaded stance. In this thesis, the utility of WBCT in measuring bone mineral density (BMD) was investigated. Next, methods to measure joint space width (JSW) subchondral bone plate thickness (SBP.Th) were implemented and tested on end-stage knee OA cohort with age- and sex- matched healthy controls. The first study showed that BMD measurement accuracy is influenced by the apparent BMD at the measurement site, with greater accuracy in trabecular bone regions. The second study demonstrated that the JSW and SBP.Th measurement methods implemented in this thesis were comparable to existing methods and able to distinguish between healthy and OA knees. A narrower JSW and thicker lateral SBP.Th in the load-bearing region of the femur was found in OA knees compared to control knees. These results show that WBCT and the implemented analysis methods may be used to measure OA-related bone and joint changes in vivo at the knee.
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    Bone micro-architecture, estimated bone strength, and muscle strength in elite athletes: an hr-pqct study
    (2012) Schipilow, John David Shearer; Boyd, Steven
    Athletes participating in sports characterized by specific loading modalities have exhibited different levels of augmentation of bone properties; however, it remains unclear to what extent these loading environments affect bone micro-architecture and estimated bone strength. Furthermore, the relative role of impact forces versus muscle forces in determining bone properties remains unclear. The objective of this study was to examine the influence of impact loading on bone micro-architecture and estimated bone strength in elite athletes, and to investigate the relationship between these bone parameters and muscle strength in elite athletes. The results of this study suggest that impact loading is highly, positively associated with bone micro-architecture and estimated bone strength. Additionally, muscle strength and bone properties were positively associated, but these associations were often weak. This study has provided a unique analysis of the relation between impact loading, muscle strength, and bone micro-architecture and estimated bone strength.
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    Bone Quality of Elite Winter Endurance Athletes
    (2022-04) Wyatt, Paige; Boyd, Steven; Burt, Lauren; Billington, Emma; Stellingwerff, Trent; Hart, David
    Athletes are often assumed to have strong bones due to their high level of physical activity. However, because of their high energy expenditure, endurance athletes may be at greater risk of Relative Energy Deficiency in Sport (RED-S). One of the established quantitative measures that can be used to evaluate RED-S risk in athletes is low bone mineral density (BMD). The objective of this study was to investigate differences in bone quality between groups at low-risk and at-risk of RED-S in an elite winter endurance athlete cohort. Athletes were screened as being either at-risk or at low-risk of RED-S based on reported symptoms and dual X-ray absorptiometry (DXA) Z-score at the lumbar spine, femoral neck, and hip. Additionally, athletes were scanned using high resolution peripheral quantitative computed tomography (HR-pQCT). Parametric and non-parametric tests were used to examine differences in bone quality between athletes screened as at-risk and those at low-risk of RED-S. Correlations between total RED-S risk and bone measures were also conducted. The results of this study suggest that differences in bone can be observed between athletes at low-risk and those at-risk of RED-S using HR-pQCT. Twenty-eight athletes, 14 males and 14 females, were screened as low-risk of RED-S and 14 athletes, three males and 11 females, were screened as at-risk. When sexes were grouped, cortical area (CtAr) at the radius and failure load at the tibia were significantly different between groups (p < 0.05). When split for sex, males screened as at-risk of RED-S had poorer bone quality than those at low-risk. Significant differences in CtAr and failure load were noted at the tibia assessed with HR-pQCT and at the lumbar spine, femoral neck and hip using DXA. However, few differences were observed between female athlete groups as only cortical porosity (CtPo) was found to significantly differ, being higher in the at-risk group compared with the low-risk group. No differences were observed between female groups with DXA. The novel aspect of this study is its use of HR-pQCT to investigate RED-S risk. In the future, longitudinal studies utilizing bone change over time may provide greater insight into RED-S risk.
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    Clinical assessment of bone quality
    (2007) MacNeil, Joshua Allen Michael; Boyd, Steven
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    Cortical Porosity in Bone
    (2014-05-14) Jorgenson, Britta; Boyd, Steven
    Osteoporosis (porous bones) is a disease that is characterized by decreased bone strength and increased risk of fracture due to loss of bone strength from decreased bone mass and deterioration of bone micro-architecture. In particular, cortical porosity (CtPo) significantly impacts bone strength and has been associated with the progression of the disease and the occurrence of fracture. Very recently, it has become possible to assess CtPo in the appendicular skeleton in vivo through the use of high-resolution peripheral quantitative computed tomography (HR-pQCT). There are two approaches to assessing CtPo from HR-pQCT imaging data based on a threshold-based or a density-based approach. The performance of both methods was compared against gold-standard synchrotron radiation micro computed tomography (SRu CT) measurements. The threshold-based approach was found to be more highly correlated with true values of CtPo than a density-based approach. Improved CtPo measures may lead to better imaging diagnostics to detect and monitor osteoporosis.
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    Differences in Bone and Cartilage Between Women with Anterior Cruciate Ligament Tears and Healthy Controls
    (2017) Bhatla, Jennifer; Boyd, Steven; Dunn, Jeffrey; Shrive, Nigel
    Anterior cruciate ligament (ACL) tears increase the risk of osteoarthritis (OA) leading to degradation of cartilage and bone. While the contribution of bone in OA development is unclear, evidence suggests that bone changes accompany cartilage degradation. This study aims to explore the relationship between subchondral compact bone thickness and cartilage thickness by comparing women with ACL reconstructions (ACLR) 5 years post-injury to uninjured controls using magnetic resonance imaging (MRI) and high resolution peripheral quantitative computed tomography (HR-pQCT). We found that ACLR knees had thicker subchondral compact bone in the lateral femur than contralateral knees (12.9% thicker, p=0.013) and injured participants had more subchondral compact bone thickness side-to-side variation than controls (>6.4 times increase, p<0.004). We did not detect cartilage thickness differences (p>0.06). This study demonstrates that subchondral compact bone thickness differences are prominent following injury, as measured by HR-pQCT, which may provide novel insight into OA pathogenesis.
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    Effects of Minimalist Footwear and Stride Length Reduction on Metatarsal Strains and the Probability of Stress Fracture in Running
    (2016) Firminger, Colin Robert; Edwards, William Brent; Boyd, Steven; Rolian, Campbell
    Stress fractures are common running injuries associated with the mechanical fatigue of bone. The metatarsal bones in the foot frequently develop stress fractures due to the repetitive loading they experience while running. Similar to basic engineering materials, the number of loading cycles to bone failure (i.e., stress fracture) increases exponentially with the applied magnitude of loading. Therefore, the objective of this thesis was to examine the relative effects of two potential stress-reducing mechanisms – shoe type and stride length adjustment – on metatarsal strains and the probability of failure in running. Running in a minimalist shoe increased metatarsal strains and the probability of failure, while running with a 10% stride length reduction was not effective at reducing metatarsal strains or the probability of failure. These findings offer an explanation for why metatarsal stress fractures are frequently observed in minimalist shoe users, and suggest that running in traditional footwear lowers metatarsal strains.
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    Establishing in vivo micro-ct for use in mouse models of osteoprosis
    (2007) Klinck, Robert Joshua; Boyd, Steven
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    In vivo monitoring of longitudinal changes in bone micro-architecture using high-resolution peripheral computed tomography
    (2012) Pauchard, Yves; Vigmond, Edward J.; Boyd, Steven
    Osteoporosis is a disease characterized by low bone quality and increased risk of fracture. In order to improve osteoporosis treatment, it is essential to monitor bone quality and its changes over time in healthy, diseased and treated bones. V/ith the recent development of in vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) it became possible to capture bone micro-architecture, an important determinant of bone quality, in humans. The aim of this dissertation was to propose new ways to analyze the resulting time series of three-dimensional (3D) image data to gain novel insight into bone behaviour. In a first step. a novel method for tracking and predicting micro-architectural changes using deformable image registration was validated. Applied to an osteoporotic and healthy pre-clinical model, this study demonstrated successful prediction of 3D archi­tecture based on a time series of images without knowledge of disease state. Prior to extending the monitoring of changes to human bone, the problem of subject motion artifacts in HR-pQCT imaging was addressed. An automatic, fast and objective method was developed to quantify three separate components of subject motion using projection data. \i\Tith this tool, guidelines for image quality management in the pres­ence of subject motion were established. Understanding and managing these artifacts is pivotal for guaranteeing consistent image quality in large multi-centre studies. In ad­dition to motion quantification, a novel method for compensating movement artifacts was developed. The proposed method for motion compensation paves the way for future research into improving image quality, potentially increasing viable data benefiting drug trials and studies of rare diseases with small sample sizes. Lastly, in order to monitor bone micro-architecture changes in humans, an automated registration methodology was devised to align 3D HR-pQCT images and techniques to visualize local architectural changes were developed. It was possible to visualize local changes due to normal bone remodelling, and in response to osteoporosis treatment, aiding interpretation of changes in traditional bone quality parameters. The developed methods form the foundation for tracking bone adaptation over time, ultimately further­ing our understanding of bone mechanisms in humans.
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    An Inverse Interface Evolution Problem to Identify Participant-Specific Bone Microarchitecture Adaptation
    (2021-05-13) Kemp, Tannis Danielle; Boyd, Steven; Zinchekno, Yuriy; Bertram, John; Edwards, W Brent
    Bone’s microarchitecture, strength and density change throughout our lifetime through the natural process of bone adaptation. With age, the mechanisms that normally maintain bone’s mechanical competence are disrupted and rapid bone loss ensues. In an attempt to understand these mechanisms, many theories and computational models were developed. But to date, few of these models have been rigorously tested in vivo. The first objective of this thesis was to develop a computational technique to validate bone adaptation models in vivo. Specifically, an inverse problem was defined that identifies participant-specific bone adaptation parameters from high-resolution computed tomography (CT) image data of changing bone microarchitecture. The inverse problem was based on a model of advection and mean curvature flow (curvature-driven bone adaptation). The inverse technique was accurate for synthetic data that exactly obeyed the curvature-driven model; it was insensitive and robust to small amounts of salt-and-pepper. Based on a solver that was accurate for data that obeyed the curvature-driven model, it was possible to test the model itself on longitudinal in vivo data. Sixteen astronauts who spent between four and seven months on the International Space Station received high-resolution peripheral quantitative computed tomography (HR-pQCT) scans before and after flight. The inverse problem was solved for each participant, and bone samples were simulated to match the HR-pQCT images at each measurement. Predicted and observed static morphometry (trabecular thickness, separation, number and bone volume fraction) agreed well, but dynamic morphometry (bone formation and resorption rates) indicated a poor fit. While the mean curvature model did not predict local bone adaptation in astronauts, a framework was developed that will allow researchers to test any model in vivo on a participant-specific basis. The inverse problem is versatile and general and could easily be adjusted for other models (i.e., strain-driven or other geometric flows). By rigorously testing hypotheses regarding bone adaptation in vivo, researchers will better understand the mechanisms of bone loss in space and on Earth.
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    An Investigation of Local Microarchitecture Topology Changes in Long-Duration Spaceflight
    (2022-11-16) Mielczarek, Conrad; Boyd, Steven; Manske, Sarah; Federico, Salvatore
    Microgravity-related bone loss presents a challenge to astronauts undergoing long-duration spaceflight. Astronauts undergo a period of substantial bone apposition upon return to Earth, which provides a unique opportunity to examine the mechanisms of bone remodeling. The objective of this study was to detect new trabecular bone connections in the form of topological bridging and quantify anisotropy changes in astronaut bone returning from the International Space Station (ISS). Seventeen United States Orbital Segment (USOS) astronauts participating in ISS missions of varying lengths (3.5-7 months) had their distal tibia and radius imaged using high-resolution peripheral quantitative computed tomography (HR-pQCT) before spaceflight, at landing (R+0M), and at 12 months post-flight (R+12M). Bone images were three-dimensionally rigid registered (3DR) longitudinally. A skeletonization decomposed the R+12M images to their underlying structure, allowing superimposition to the R+0M image where the difference highlighted areas of bone apposition during recovery. Anisotropy changes were tracked using mean intercept length (MIL). To compare the sensitivity of topology and anisotropy changes in astronauts, a reference was established using same-day repeat HR-pQCT distal tibia (n=90) and radius (n=89) images from control participants. The topology and anisotropy difference significance was assessed using a Wilcoxon rank-sum test between astronauts and control, while the anisotropic precision was determined from control scan root-mean-square coefficient of variation (RMSCV%). Astronauts’ group median apposition site average size was 1.2 times larger in the tibia and the same in the radius when compared to controls (p<0.01, p=0.64 respectively). Qualitatively examining the astronaut apposition sites revealed instances of bone bridging the space between two adjacent structures, indicating trabecular topological reconnection. Estimated precision for anisotropy measures from the control scans ranged from 0.9 to 1.3%, while the astronauts’ change in anisotropy ranged from -2.9 to 6.4% (group median -0.02%) during in-flight loss and -5.0 to 6.8% (group median 0.1%) during post-flight recovery. Bone resorption and apposition varied considerably between astronauts, with evidence of new topological connections across all participants. Several astronauts demonstrated a substantial change in anisotropy, suggesting directional alterations are concurrent with topology adaptation that occurs upon recovery on Earth.
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    Layer-wise Relevance Propagation and its Applications in Running Biomechanics
    (2022-07) Hoitz, Fabian Christoph; Nigg, Benno; Kuo, Arthur; Edwards, William Brent; Eskofier, Bjoern; Boyd, Steven; Jacob, Christian; Schollhorn, Wolfgang
    Biomechanics has entered an era of ’big data’, where human locomotion data is generated rapidly and in large quantities. This poses new challenges because conventional analysis methods are ineffective in the presence of the myriad of interacting variables that describe human locomotion in contemporary datasets. Consequently, there is a need for novel, more appropriate analysis methods that can help direct attention towards the ’right’ variables. The purpose of this thesis was to apply layer-wise relevance propagation, a novel analysis method, within the context of human locomotion to isolate variables from large datasets that describe highly relevant movement characteristics that may inspire and direct future biomechanics research. Specifically, the challenges of separating unique / generic movement characteristics of runners, and forming functional groups based on runner-specific movement adaptations (induced by footwear interventions) were addressed. It was shown that (1) unique locomotion characteristics of novice runners were best described by variables belonging to the movement trajectories of the coronal and transverse plane during early stance within a dataset of lower extremity kinematics and ground reaction forces. Further, (2) kinematic variables that describe unique locomotion characteristics of highly trained runners were associated with movements of the spine and lower extremities during mid-stance and mid-swing, while generic locomotion characteristics were associated with sagittal plane movements of the spine during early and late stance within a dataset of full body kinematics. Finally, (3) groups of runners who adopt similar kinematic movement responses to a given footwear intervention were identified by clustering relevance patterns of subject-specific artificial neural network models. Based on the presented findings it was concluded that layer-wise relevance propagation is a promising analysis method that can help direct a researcher’s focus towards those variables that are most relevant for black-box machine learning models such as artificial neural networks. It, therefore, addresses many of the emerging challenges that biomechanics research faces during the contemporary era of ’big data’.
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    Mapping Anisotropy of the Proximal Femur for Improved Image-Based Finite Element Analysis
    (2013-08-09) Enns-Bray, William; Boyd, Steven
    Finite element (FE) models of bone derived from clinical quantitative computed tomography (QCT) rely on realistic material properties to accurately predict patient-specific bone strength in vivo. QCT cannot resolve microarchitecture, therefore QCT-based FE models lack the directionality apparent within trabecular bone. Maps of anisotropy were constructed from high-resolution peripheral QCT (HR-pQCT) images of seven femur specimens using a „direct mechanics‟ method to measure local anisotropy. The resulting directionality reflected all the major structural patterns visible within the microarchitecture of the proximal femur. Principal stiffness directions were interpolated into QCT-based femur models, and whole bone stiffness was calculated for orthotropic and isotropic models in a sideways fall configuration. Comparing model stiffness to experimental data revealed no difference in correlation (R2ORTH = 0.780, R2ISO = 0.788). These results suggest that the variability in stiffness explained by anisotropy at the microarchitecture level does not scale to whole bone models for this specific loading configuration.
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    Medical Image Registration using OpenCL
    (2012) Dwarkan, Sachitsing; Mitchell, J. Ross; Boyd, Steven
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    Muscle disuse and vibration effects on bone morphology
    (2010) Manske, Sarah Lynn; Boyd, Steven; Zernicke, Ronald F.
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    p21−/− mice exhibit enhanced bone regeneration after injury
    (2017-11-09) Premnath, Priyatha; Jorgenson, Britta; Hess, Ricarda; Tailor, Pankaj; Louie, Dante; Taiani, Jaymi; Boyd, Steven; Krawetz, Roman
    Abstract Background p21(WAF1/CIP1/SDI1), a cyclin dependent kinase inhibitor has been shown to influence cell proliferation, differentiation and apoptosis; but more recently, p21 has been implicated in tissue repair. Studies on p21(−/−) knockout mice have demonstrated results that vary from complete regeneration and healing of tissue to attenuated healing. There have however been no studies that have evaluated the role of p21 inhibition in bone healing and remodeling. Methods The current study employs a burr-hole fracture model to investigate bone regeneration subsequent to an injury in a p21−/− mouse model. p21−/− and C57BL/6 mice were subjected to a burr-hole fracture on their proximal tibia, and their bony parameters were measured over 4 weeks via in vivo μCT scanning. Results p21−/− mice present with enhanced healing from week 1 through week 4. Differences in bone formation and resorption potential between the two mouse models are assessed via quantitative and functional assays. While the μCT analysis indicates that p21−/− mice have enhanced bone healing capabilities, it appears that the differences observed may not be due to the function of osteoblasts or osteoclasts. Furthermore, no differences were observed in the differentiation of progenitor cells (mesenchymal or monocytic) into osteoblasts or osteoclasts respectively. Conclusions Therefore, it remains unknown how p21 is regulating enhanced fracture repair and further studies are required to determine which cell type(s) are responsible for this regenerative phenotype.
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    pyCellAnalyst: Extensive Software for Three-dimensional Analysis of Deforming Cells
    (2016) Sibole, Scott C.; Herzog, Walter; Federico, Salvatore; Epstein, Marcelo; Edwards, Brent; Boyd, Steven; Alim, Usman
    Laser scanning microscopy has proven to be a transformative tool in the biomedical sciences. The technology provides a means to image three-dimensional, time-varying, micro-scale features within living tissue, which in turn has borne exciting avenues for the experimental investigation of the relationship between the hierarchical spatial scales within organisms. By coupling laser scanning microscopes to mechanical testing systems, one can study the relationships between mechanics at the organ, tissue, and cellular scales. In practice, while a controlled mechanical state is applied to intact tissue, images of the cells within can be obtained via microscopy; however, extracting the geometric information from these images and characterizing deformation has been a challenge to the field. pyCellAnalyst is an extensive software framework for such analysis of these image data. It provides an accessible interface to reconstruct cellular geometries from images, characterize deformation, and perform finite element analyses informed by the experimental observations.