PRISM :: Browsing by Author "Boyd, Steven Kyle"

Browsing by Author "Boyd, Steven Kyle"

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Open Access
A 3D in-situ model for patellofemoral joint contact analysis in the normal and anterior cruciate ligament deficient knee
(1997) Boyd, Steven Kyle; Ronsky, Janet L.
Open Access
The assessment of fragility fracture risk using HR-pQCT as a novel tool for diagnosis of osteoporosis
(2021-08) Whittier, Danielle Elizabeth Wein; Boyd, Steven Kyle; Schneider, Prism Steorra; Manske, Sarah Lynn; Edwards, William Brent; Forkert, Nils Daniel; Hallgrimsson, Benedikt; Jepsen, Karl
Osteoporosis is a systemic skeletal disease, characterized by reduced bone density and deterioration of bone microarchitecture, leading to increased fracture risk. However, current diagnosis using dual-energy X-ray absorptiometry (DXA) only accounts for density and consequently fails to capture most individuals who fracture. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a medical imaging modality capable of characterizing three-dimensional bone microarchitecture at peripheral skeletal sites, and has demonstrated that bone microarchitecture can improve prediction of fracture risk. However, to date the improvement is modest, as interpretation of the interaction between fracture and the numerous parameters provided by HR-pQCT is complex. The objective of this dissertation was to elucidate the key microarchitectural characteristics that underpin bone fragility, and use these insights to improve assessment of fracture risk with HR-pQCT. First, reference data in the form of centile curves was established for HR-pQCT parameters using a population-based cohort (n=1,236, age 18–90 years), and a new intuitive parameter called void space was developed to capture localized regions of bone loss in HR-pQCT images. In a separate prospective multi-center cohort (n=5,873, age 40–90 years), unsupervised machine learning was implemented to identify common groupings (i.e., phenotypes) of bone microarchitecture in older adults. Three phenotypes were identified and characterized as low density, structurally impaired, and healthy bone, where the low density phenotype had the strongest association with incident osteoporotic fractures (hazard ratio = 3.28). Using the same cohort, a fracture risk assessment tool, called µFRAC, was developed using supervised machine learning methods to provide a 5-year risk of major osteoporotic fracture based on HR-pQCT parameters, and was demonstrated to significantly outperform DXA in predicting fracture risk. Finally, a new retrospective cohort of patients with fragility fractures at the hip (n=108, age 56–96 years) was used to characterize bone fragility. Hip fracture patients were significantly associated with the low density phenotype and had bone void spaces that were 2–3 times larger than controls. Together, these findings provide insight into the characteristics of bone that lead to osteoporotic fractures and introduces tools that enable insightful interpretation of HR-pQCT data for clinical use.
Open Access
Bone as an Orientable, Smooth Surface: Distance Transforms, Morphometry, and Adaptation
(2021-08) Besler, Bryce Albert Alphonsus; Boyd, Steven Kyle; Fear, Elise Carolyn; Forkert, Nils Daniel; Manske, Sarah Lynn; Cooper, David Michael Lane; Nielsen, Jorgen S
Age-related changes in bone fundamentally occur at the surface. Understanding and modeling these changes is the primary means of understanding and preventing age-related fractures. However, this is a challenging task, as the bone microarchitecture changes topology during adaption when rods disconnect and plates form holes. The primary objective is to handle topological changes mathematically and develop computational methods for the simulation of bone adaptation. This thesis develops a model of age-related bone loss based on the axioms that the bone surface is orientable and smooth. First, a novel artifact is discovered and described for the distance transform of sampled signals that limits their applicability in simulation and morphometry. Second, a new transform is defined termed the ``high-order signed distance transform'' that is better than the so-called exact signed distance transform in the sense that it has an order of accuracy greater than one. However, this transform does not permit a unique solution on sampled binary images, and another method is needed. Third, an algorithm is presented for computing the unique, high-order signed distance transform of biphasic materials from computed tomography data. Fourth, a method of performing morphometry on closed surfaces is described that relates existing global bone morphometric techniques to local curvature values. This method works on binary images without the need for signed distance transforms when small changes in the bone volume are permitted. Finally, the morphometry and high-order signed distance transform are integrated into a model of age-related bone loss. Principally, this work establishes bone adaptation as a geometric flow, simulated using level set methods that are efficient and naturally handle topological changes. The contribution of this thesis is the establishment of a strong mathematical foundation for modeling bone adaptation. High accuracy computational methods are defined to integrate the theory into practice. The theory and methods form a rigorous basis for biological theories of bone adaptation and provide techniques for measuring and falsifying theories.
Open Access
Characterization of OA Severity in Knee Articular Cartilage in-Vivo Using MR Imaging and Loading Techniques
(2017) Dai, Xu; Ronsky, Janet Lenore; Frayne, Richard; Schmidt, Tannin; Boyd, Steven Kyle; Nowicki, Edwin Peter; Holdsworth, David W.
Early osteoarthritis (OA) is primarily associated with proteoglycan (PG) loss and changes in collagen structure. MR T2 imaging of knee under in-vivo loading may help to further reveal the differences between healthy and OA cartilage. This study investigated the in-vivo loading effect on MR T2 values of human knee patellar cartilage. The results demonstrated T2 value distributions in patellar cartilage were inhomogeneous. In-vivo loading had a site-specific influence on participants’ T2 values. The in-vivo loading produced a significant difference on T2 values in the middle region of interest (ROI) of patellar cartilage (p=0.004＜0.025), but not at the superior or inferior ROIs. The T2 value variation for the OA group during loading was lower than that of the healthy group (p=0.016＜0.025). The T2 recovery ratio was presented in this study as a new variable. The findings indicated the T2 recovery ratio of the OA group was significantly lower than the healthy group (p=0.042＜0.05) in the patellar cartilage middle ROI. It suggests that the OA cartilage had weaker ability to restore its original status after off-loading than healthy cartilage. This study examined the glycosaminoglycan (GAG) mass% concentration (relating PG) in human cadaveric patellar cartilages using biochemical assay. Results showed that the GAG mass% concentrations in OA lesion positions were lower than that in comparative healthy positions (p＜0.001). MR T2 imaging of healthy and OA cadaver knee joints were performed. Correlations between T2 values and the GAG mass(%) of cadaver patellar cartilage specimens were established. As PG concentration of in-vivo human articular cartilage cannot be directly measured non-invasively, the correlation of cadaveric patellar cartilage may serve as an important bridge between the T2 value and GAG mass% for living human assessment. The findings provide an indirect approach to estimate PG concentration of in-vivo patellar cartilage based on an individual’s cartilage T2 values to evaluate the extent of degradation within cartilage. This subject specific method is especially suitable for longitudinal evaluation of OA. By position-matched comparison of previous and current T2 images, the GAG mass% variation may be estimated to assess OA progression non-invasively.
Open Access
Concurrent Assessment of Knee Cartilage Morphology and Bone Microarchitecture using Contrast-Enhanced HR-pQCT Imaging
(2018-05-22) Michalak, Geoffrey Jan; Boyd, Steven Kyle; Edwards, William Brent; Walker, Richard E. A.
Osteoarthritis (OA) is a prevalent articular disease characterized by degradation of articular cartilage and bone. Presently, no single imaging modality concurrently captures these changes. This study sought to develop and validate a novel joint imaging technique, contrast enhanced high resolution peripheral quantitative computed tomography (CEHR-pQCT), to concurrently assess bone microarchitecture and cartilage morphology. Cadaveric knees were harvested (n=10) and scanned using magnetic resonance imaging (MRI), HR-pQCT without contrast, and HR- pQCT following intra-articular injection of non-ionic contrast media. Joints were disarticulated, and the articular cartilage thickness measured by needle probe. Measures of cartilage morphology were found to be significantly different between MRI, needle probing and CEHR- pQCT. Bone microarchitecture was found to be significantly different in CEHR-pQCT, where cortical bone mineral density (BMD) was depressed, and trabecular BMD increased. This study contributes toward the advancement of whole joint imaging techniques, laying the foundation to perform in vivo scanning of knee cartilage and bone.
Open Access
Effect of Increased 25(OH)D on Bone Health, a High Resolution Peripheral Computed Tomography Study
(2016) Hildebrandt, Erin Marie; Boyd, Steven Kyle; Hanley, David Arthur; Bertram, John Edward Arthur; Nettel-Aguirre, Alberto; Kothandaraman, Maitreyi; Edwards, William Brent
Vitamin D is important for normal bone health, however, there is still debate over the intake for optimal bone health. The objective of this study is to assess the relationship between large changes in 25(OH)D to bone health, and the safety of taking up to 10,000 IU/day of vitamin D over one-year using a pilot cohort of a three-year ongoing randomized control trial. The results suggest that with increased 25(OH)D there was an improvement in trabecular and cortical BMD, as well as a decrease in cortical area and thickness, while maintaining bone strength. Based on biomarker data, taking doses of vitamin D up to 10,000 IU/day for one year was found to be safe within the population studied. This study has provided new insight into the understanding of large changes in 25(OH)D on bone health and demonstrates the importance of 25(OH)D for maintaining bone health in a healthy adult population.
Open Access
Enhanced Longitudinal Analysis of Bone Strength Estimated by 3D Bone Imaging and the Finite Element Method
(2020-10-06) Plett, Ryan Michael; Boyd, Steven Kyle; Duncan, Neil A.; Manske, Sarah Lynn; Kim, Keekyoung; Edwards, William Brent
Three-dimensional (3D) imaging with high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element (FE) analysis provides important insight into bone health. Longitudinal analyses of bone morphology maximize precision by using 2D slice-matching registration (SM) or 3D rigid-body registration (3DR) to account for repositioning error between scans, however, the compatibility of these techniques with FE for longitudinal bone strength estimates is limited. This work developed and validated a FE approach for longitudinal HR-pQCT studies using 3DR to maximize reproducibility by fully accounting for misalignment between images. Using a standard imaging protocol, ex vivo (N=10) and in vivo (N=40) distal radius HR-pQCT images were acquired to estimate the efficacy of 3DR to reduce longitudinal variability due to repositioning error and assess the sensitivity of this method to detect true changes in bone strength. In our proposed approach, the full common bone volume defined by 3DR for serial scans was used for FE. Standard FE parameters were estimated by no registration (NR), SM, and 3DR. Ex vivo reproducibility was estimated by the least significant change (LSC) in each parameter with a ground truth of zero change in longitudinal estimates. In vivo reproducibility was estimated by the standard deviation of the rate of change (σ) with an ideal value that was minimized to define true changes in longitudinal estimates. Group-wise comparisons of ex vivo and in vivo reproducibility found that FE reproducibility was improved by both SM (CVRMS<0.80%) and 3DR (CVRMS<0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Although 3D registration did not negate motion artifacts, it played an important role in detecting and reducing variability in FE estimates for longitudinal study designs. Therefore, 3D registration is ideally suited for estimating in vivo effects of interventions in longitudinal studies of bone strength.
Open Access
Experimental Validation of Finite Element Predicted Bone Strain in the Human Metatarsal
(2017) Fung, Anita; Edwards, William Brent; Boyd, Steven Kyle; Schmidt, Tannin; Li, Leping; Wiley, James Preston
The objective of this study was to verify and validate a finite element modeling routine for the human metatarsal, which is a common location for stress fractures. Experimental strain measurements on 33 human cadaveric metatarsals subject to cantilever bending were compared with strain predictions from finite element (FE) models generated from computed tomography images. For the material property assignment of the FE models, a published density-elasticity relationship was compared with density-elasticity equations developed using optimization techniques. The correlations between the measured and predicted and predicted strains were very high (r2≥0.94) for all of the density-elasticity equations. However, the utilization of an optimized density-elasticity equation improved the accuracy of the finite element models, reducing the maximum error between measured and predicted strains by 10% to 20%. The finite element modeling routine could be used for investigating potential interventions to minimize metatarsal strains and the occurrence of metatarsal stress fractures.
Open Access
In Vivo Assessment of Bone Microarchitecture and Estimated Bone Strength
(2012-10-30) Nishiyama, Kyle Kenji Stephen; Boyd, Steven Kyle
Osteoporosis is a disease characterized by loss of bone mass and structural deterioration leading to increased risk of fracture. Currently, osteoporosis is assessed by areal bone mineral density; however, this does not provide structural information, which is a key determinant of bone strength. Recent advances allow for the assessment of bone structure in vivo using quantitative computed tomography (QCT) and high-resolution peripheral QCT (HR-pQCT). The overall objective of this thesis was to improve the assessment of bone structure and strength using three-dimensional imaging technologies. First, measurements of cortical porosity from HR-pQCT were validated against micro-CT (R2 = 0.80) and applied to a population-based sample (N = 280, Ages: 18-99 yrs.) of healthy, osteopenic, and osteoporotic, pre- and postmenopausal women. Cortical porosity was higher in postmenopausal women and those with disease. Measurements of cortical porosity were also applied to another group with high fracture incidence: children and adolescents (N = 398, Ages: 9-22 yrs.). Boys were found to have higher porosity than girls, and those at earlier pubertal stages had higher porosity than those post-pubertal. Bone quality measurements were also combined with finite element estimates of bone strength to determine if the measurements could distinguish women with fracture from fracture-free controls. High accuracy was achieved using both HR-pQCT scans of peripheral sites (83.3%) and QCT scans of the proximal femur (84.3%) when classifying the groups using support vector machines. Together, these results provide insight into the differences in bone microstructure and strength with age and disease. In addition, this work demonstrates the ability of novel 3D technologies and methods to better discriminate individuals with and without fracture.
Open Access
The Influence of Intracortical Microarchitecture on the Mechanical Fatigue of Bone
(2020-07-07) Loundagin, Lindsay Lessel; Edwards, William Brent; Boyd, Steven Kyle; Schmidt, Roel Kuijer Tannin; Duncan, Neil A.; Cooper, David Michael Lane; Taylor, David; Manske, Sarah Lynn
Mechanical fatigue is the predominant etiology of stress fracture, a known contributor to atypical femoral fracture, and may also play a critical role in fragility fracture. While these fatigue-related fractures are well-documented in humans, they are poorly understood. Extensive research has attempted to characterize the fatigue behavior of cortical bone; however, owing to the inherent variability in bone tissue, samples that appear identical in macrostructure can exhibit a large degree of scatter in fatigue life. The overarching hypothesis of this thesis is that the variance in fatigue-life data can be attributed to intracortical microarchitecture, including the size, spacing, and density of vascular canals and osteocyte lacunae. A series of studies were conducted that utilized ex vivo mechanical testing, high-resolution imaging, and finite element modeling to establish the relationship between intracortical microarchitecture and the fatigue life of bone in compression. Both porosity and canal diameter demonstrated a strong negative relationship with fatigue life, whereas lacunar density was positively correlated. The reduced fatigue life associated with higher porosity was a result of larger, rather than more abundant canals, indicating that canals act as stress concentrators that may impair the fatigue resistance of bone beyond increasing overall porosity. The stress concentrations caused by vascular canals were quantified as stressed volume (i.e., the volume of material above yield) which was positively correlated to porosity and canal diameter. Furthermore, stressed volume proved to be a strong predictor of fatigue-life variance across multiple loading magnitudes. The findings from this thesis suggest that a majority of the fatigue-life variance of cortical bone in compression is driven by intracortical microarchitecture, and fatigue failure may be predicted by quantifying the stress concentrations associated with vascular canals.
Open Access
Investigating Bone Remodelling in Knee Osteoarthritis using HR-pQCT Imaging
(2023-05-12) Kaketsis, Daphne Angelique; Manske, Sarah Lynn; Bertram, John Edward Arthur; Boyd, Steven Kyle; Edwards, William Brent; Zimmermann, Elizabeth Ann
Osteoarthritis (OA) is the most common type of arthritis and a significant cause of disability worldwide. With an aging population in Canada, the prevalence and burden of OA is expected to increase. Knee OA is the most common form of OA, comprising upwards of 30% of cases. Early-stage OA can be difficult to diagnose, as often times pain and radiographical evidence do not align; however, abnormal subchondral bone remodelling has been considered to have an important role in OA pathogenesis, and some propose that it could offer a target for OA treatment. Clinically, measures of bone remodelling have been performed on iliac crest bone biopsies that are invasive and do not capture local changes. Recently, high resolution peripheral quantitative computed tomography (HR-pQCT) has been utilized in several different ways to analyse bone dynamics, or how the bone changes over time. These measurements are sensitive to several factors such as noise and motion but have yet to be validated in humans. The purpose of this study was to determine whether HR-pQCT can be used to measure longitudinal bone remodelling at the knee in humans with knee OA. Longitudinal bone remodelling results were compared to same-day rescan images to conduct a repeatability analysis. There were no significant differences between longitudinal and rescan results for bone formation (p = 0.47), bone resorption (p = 0.12), or net bone remodelling (p = 0.748). Additionally, the least detectable changes measured were 10.88% for bone formation, 10.53% for bone resorption, and 4.05% for net bone remodelling. These results indicate that with the current imaging procedures, there is too much error in the scans and processing pipeline to measure bone remodelling longitudinally in-vivo in the knee.
Open Access
Large Scale Elasto-plastic Modelling for in vivo Assessment of Bone Strength from High Resolution Peripheral Quantitative Computed Tomography
(2013-08-09) Owoc, Jan Stanislaw; Boyd, Steven Kyle
Osteoporosis is a "silent epidemic" of weakening bones, often leading to fracture. To predict fracture, the finite element method based on micro-computed tomography can be used, modelling bone behaviour under load. Elasto-plastic finite element modelling is able to directly calculate bone strength, but until recently it has been computationally expensive. Advancements in GPU technology have exponentially increased the computational power available in consumer-grade hardware and enabled the implementation of a custom elasto-plastic finite element solver for large-scale models. Both analytical and mechanical validation of the elasto-plastic solver was performed. Elasto-plastic finite element models based on tomography data were able to predict failure load with a correlation coefficient of 0.81. These new developments in elasto-plastic finite element modelling have enabled the direct estimation of patient-specific yield properties on consumer-grade hardware.
Open Access
Longitudinal assessment of mechanical strength of trabecular bone underlying bone marrow lesions following acute anterior cruciate ligament injuries.
(2019-06-17) Shtil, Mariya; Boyd, Steven Kyle; Edwards, William Brent; Manske, Sarah Lynn
Anterior cruciate ligament tears are common injuries that are often accompanied by traumatic bone marrow lesions (BML) that occur in the knee. These lesions may be linked to osteoarthritis and by understanding the indication of a bone marrow lesion, we can move towards better understanding the causes of osteoarthritis. This study explores the strength of bone within BMLs using micro-finite element modeling based on MRI and HR-pQCT images throughout an 8- month period following an ACL tear. In the BML region in the injured knee, the bone strength decreased by 20.1% (P<0.001) at ~175 days post injury relative to the corresponding region on the contralateral knee followed by a semi-recovery period. Bone strength in the reference region surrounding the BML decreased by 15.3% (P=0.002) at ~142 days post injury relative to the contralateral reference region, and 15.3% (P=0.003) at ~146 days post injury in the full injured femoral condyle relative to the contralateral condyle, followed by a gradual recovery. However, the bone in the BML region experienced accelerated loss in bone strength relative to the surrounding bone and the contralateral knee and did not fully recover. This may be indicative of long-term or potentially permanent changes in bone strength that when weakened, provides less support for articular cartilage and can lead to damage or degeneration, and further progression to osteoarthritis.
Open Access
Microstructural bone adaptation in an experimental model of osteoarthritis
(2001) Boyd, Steven Kyle; Zernicke, Ronald F.
Open Access
Microstructural bone adaptation in an experimental model of osteoarthrits
(2001) Boyd, Steven Kyle; Zernicke, Ronald F.
Open Access
Photogrammetric Modelling for 3D Reconstruction from a Dual Fluoroscopic Imaging System
(2019-01-03) Al Durgham, Kaleel Mansour; Lichti, Derek D.; Kuntze, Gregor; Wang, Ruisheng; Shortis, Mark R.; Boyd, Steven Kyle; Ronsky, Janet L.
Biplanar videoradiography (BPVR), or clinically referred to as dual fluoroscopy (DF), imaging systems are increasingly being used to study the in-vivo skeletal biomechanics of human and animal locomotion. DF imaging provides a novel solution to quantify the six-degree-of-freedom (6DOF) skeletal kinematics of humans and animals with high accuracy and temporal resolution. Using low-dose X-ray radiation, DF systems provide accurate bone rotation and translation measurements. In this research domain, a DF system comprises two X-ray sources, two image intensifiers and two high-speed video cameras. The combination of these elements allows for the stereoscopic imaging of the bones of a joint at high temporal resolution (e.g., 120-250 Hz), from which bone kinematics can be estimated. The utilization of X-ray-based imaging results in challenges that are uncommon in optical photogrammetry. Unlike optical images, the inherent lack of colour information in DF images complicates fundamental tasks such as the derivation of image observations for the system calibration. Furthermore, the incorporation of an image-intensifier to produce DF images results in high distortion artifacts that are uncommon in optical photogrammetry. The use of image intensifiers also results in non-uniform intensity response in the DF images. Unlike optical images with well-established camera models, the systematic distortion behaviour in DF images is empirically modelled. The novelty in this research work is in providing a complete, scientific, straightforward and accurate photogrammetric framework for deriving 3D measurements from a DF imaging system. This research work provides means for automating the DF calibration procedure and introduces solutions for improving the methodology of 3D reconstruction from DF imaging. A thorough photogrammetric analysis over the system aspects points out the weaknesses in the iii traditional 3D reconstruction procedures and suggests accurate alternatives. The dissertation presents five scientific contributions: (1) a semi-automated methodology to derive the image observations from time series DF calibration images, (2) validation of an empirical DF sensor model (bundle adjustment-based) for the calibration of the DF system and introducing it as a superior replacement for the traditional direct linear transformation-based (DLT) calibration approaches, (3) a rigorous accuracy assessment methodology for the evaluation of the DF system reconstruction capabilities, (4) a novel methodology for the temporal stability analysis of an imaging system calibration parameters, and (5) a virtual-3D-model means to facilitate establishing the alignment between stereoscopic DF image pair and an MRI/CT model (2D-to3D registration).
Open Access
The progression of bone microarchitecture changes following an acute knee injury in young adults
(2019-03-18) Kroker, Andres Mauricio; Boyd, Steven Kyle; Walker, Richard E. A.; Matyas, John Robert; Manske, Sarah Lynn; Van-Rietbergen, Bert; Doyle-Baker, Patricia K.
Anterior cruciate ligament (ACL) tears are activity-related knee injuries associated with an elevated risk of developing post-traumatic osteoarthritis 10-20 years post-injury. Immediately after the injury bone mass is lost. This is followed by a recovery period, though full recovery is not achieved even years later. Due to a lack of appropriate imaging modalities, no information is available on how the underlying bone microarchitecture is affected. In addition, the effects of concurrent soft-tissue injuries, such as meniscus tears or traumatic bone marrow lesions, on the underlying bone microarchitecture in human knees are not known. In this thesis, a new method for in vivo assessment of bone microarchitecture of the human knee is introduced. Next, in two cross-sectional studies this technique is applied to populations that experienced unilateral ACL tears six to nine years earlier. Both studies revealed that bone is primarily affected in the femur of the injured knee. Trabecular bone mass is lower in the medial femur (-4.8% to -10.4%) while the subchondral bone plate is thicker in the lateral femur (9% to 29.6%) as compared to the contralateral knee. Further, the thicker subchondral bone plate is associated with surgical meniscus treatment (meniscectomy or repair) at the time of ligament reconstruction. In a year-long longitudinal study, the new imaging technique is applied to a cohort with acute unilateral ACL tears to investigate how early injury-induced bone changes affect microstructure. Immediately following the injury, trabecular bone is lost throughout the injured knee (-4.9% to -15.8%), driven by a loss of trabecular elements and increased trabecular separation. Concurrently, the subchondral bone plate of the lateral femur thins (-9%). The trabecular bone changes are further accelerated in traumatic bone marrow lesions (-18.2% to -20.6%). These findings show that while initial bone mass loss following the injury may recover six to nine years later (primarily in the tibia), the femur is affected long-term. The underlying structural changes are believed to be permanent, and while it is not known which individuals will develop osteoarthritis, limiting early injury-induced bone changes may reduce long-term risk of joint degradation.
Open Access
Quantifying and Visualizing Regional Bone Changes in the Knee following an ACL Tear
(2023-07) Morrison, Alida Claire; Boyd, Steven Kyle; Edwards, William Brent; Barnabe, Cheryl Carmelle Marie
ACL tears are a common type of injury that often happens during sports activities. While some people may regain knee function after healing, the development of post-traumatic osteoarthritis (PTOA) is a possible long-term outcome of a knee injury. The integrity of many tissues is affected by the injury including bone, which typically experiences density loss. Sub-regional analysis of bone density using medical imaging provides more detailed insight into bone status after an acute knee injury, however these spatial positions may overlook areas with significant local change. This work examined patterns of bone change through the distal femur and proximal tibia following an ACL tear using computed tomography (CT) images of 10 participants. Clinical CT and high resolution peripheral quantitative CT (HR-pQCT) scans of injured knees were measured at baseline and 1-year follow-up time points. The longitudinal data were registered, and the voxel-wise differences were visualized to identify regions of significant bone changes and compare the two modalities. Patterns of bone density changes were assessed in the context of individual patient locations of bone contusions, fractures, and osteochondral injuries, as described in baseline magnetic resonance imaging (MRI) reports. In the femur, bone loss was observed at both condyles and, for 90% of participants, bone loss was also observed at the site of insertion of the ACL. Posterior horn meniscus injury typically corresponded to bone loss on the associated femoral condyle, and on the posterior tibial plateau. Widespread changes to bone density in the injured knee are influenced not only by ACL tear, but by concurrent injuries such as meniscal damage. These significant changes within the first year post injury may play an important role in the long term health of the knee.
Open Access
A quantitative computed tomography approach towards opportunistic osteoporosis screening
(2020-03-20) Michalski, Andrew Steven; Boyd, Steven Kyle; Edwards, William Brent; Powell, James N.; Johnston, James B.; Salo, Paul T.; Manske, Sarah Lynn
Opportunistic computed tomography (oCT) complements dual X-ray absorptiometry (DXA) by screening for osteoporosis and determining subject-specific fracture risk. Quantitative CT-based bone mineral density (BMD) and finite element (FE) estimated bone strength outcomes are known to improve fracture prediction, as compared to DXA areal BMD. However, there are shortcomings of oCT, which limit its ability to be clinically integrated as a skeletal health assessment tool for the purpose of identifying individuals at high risk of fracture that have not yet had any additional osteoporosis screening, such as a DXA scan. In this dissertation, the oCT limitation of understanding how CT scan acquisition parameters influence the skeletal health assessment is first investigated by identifying differences between CT reconstruction kernels. By using a bone-type kernel, the estimated FE failure load was increased by 18.2%, as compared to a standard-type kernel, suggesting that a standardized reconstruction kernel should be used when performing any oCT analyses. An internal density calibration method was then developed and validated to overcome the limitation of requiring a density calibration phantom within the scan field-of-view to perform oCT skeletal assessment. The developed internal calibration approach uses five reference regions and relates the known Hounsfield Units to equivalent mass attenuation values and then to equivalent bone density values. This approach was validated both in cadavers and an in vivo cohort, and it was shown to have a precision of 7.2% for skeletal health assessment outcomes. Finally, an oCT screening cohort was established using clinically acquired abdominal CT scans and was used to predict low energy fracture at known major osteoporotic fracture sites. Using this cohort, oCT screening resulted in a maximum predictive value of 0.710 for the area under the receiver operator characteristic curve to predict women with low energy fractures. These findings overcome some of the shortcomings currently preventing oCT screening from being clinically integrated. By using the millions of CT scans performed each year, oCT screening can repurpose these scans to assess skeletal health and reduce the costs and burden of fracture to both the healthcare system and society.
Embargo
Spectrum of Microarchitectural Bone Disease in Inborn Errors of Metabolism
(2020-08-27) Sidhu, Karamjot Kaur; Boyd, Steven Kyle; Khan, Aneal; Kline, Gregory Alan; Manske, Sarah Lynn; Aspinall, Alexander I.
Inborn errors of metabolism (IBEMs) are a heterogeneous group of inherited disorders caused by a defect in the synthesis, metabolism, transport, and/or storage of metabolites. Diagnosed patients can often present with compromised bone health and an increased risk for fragility fractures. The current standard for measuring bone health in the general population is bone density assessed by dual-energy X-ray absorptiometry (DXA). However, its utilization in understanding bone status in IBEMs is limited. The primary limiting factor is DXA’s inability to assess cortical and trabecular bone independently, which is important in understanding bone loss that is a result of complex disease processes. In this thesis, macro- and microarchitectural properties of bone were monitored in a wide range of IBEM disorders using new three-dimensional technology, high-resolution peripheral quantitative computed tomography (HR- pQCT). Moreover, bone strength was estimated by employing finite element techniques on HR- pQCT image data. A further examination of these measurements in relationship to genetic mutations, clinical history, and treatment status was investigated in Gaucher disease and hypophosphatasia as a case report and cohort study, respectively. In IBEM patients, both bone density and microarchitecture were impaired when compared to a reference database. The degree of impairment varied between IBEM subtypes, and was significantly greater in IBEMs associated with decreased bone mass mineralization, including hypophosphatasia. Cortical bone density and microarchitecture were also significantly lower in IBEM patients with previous fractures when compared to IBEM patients with no fracture history. Estimated bone strength was also significantly lower in certain IBEM disorders when compared to a reference database, including IBEM disorders of metabolism requiring diet restrictions and disorder of the nervous or muscular system resulting in impaired mobility. Investigations in Gaucher disease and hypophosphatasia suggested disease-targeting therapy may aid in preventing or delaying accelerated bone mass loss that is thought to occur from the IBEM diagnosis. In conclusion, bone density and microarchitecture are largely affected in IBEMs. Future work in understanding how therapeutic interventions, such as bone-altering therapies, impact bone density and microarchitecture in IBEMs may be highly valuable.