Browsing by Author "Boyd, Steven K."
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Item Open Access Computer Aided Detection of Early Ischemic Changes in Non-Contrast CT Images of Acute Ischemic Stroke(2014-09-24) Thomson, Quinn Parker; Boyd, Steven K.; Mitchell, J. RossAn ischemic stroke occurs from a brain artery blockage. Rapid treatment improves outcomes. However, there are two treatment prerequisites. First, early ischemic changes (EIC) in brain tissue must be established, often by interpreting a computed tomography (CT) scan. However, EIC identification from CT is difficult. Second, treatments are only effective within the first few hours. Consequently, the maximum delay between stroke onset and brain imaging must be estimated. This is difficult if the stroke onset was not observed. The goal of my PhD research was to create computer-aided detection (CADe) tools to: a) improve assessment of EIC in CT images; and, b) estimate the delay between stroke onset and brain imaging using CT scan features. My algorithm evaluated CT image features associated with EIC. Three stages of assessment determined software performance. First, I determined physician reliability when outlining EIC on CT images. Next, I determined how closely my algorithm matched physician driven outlines. Finally, I determined physician reliability when assisted by my algorithm. My CADe methods were used to calculate a new stroke severity index (SSI). The relationship between SSI and the delay between stroke onset and imaging time was then examined. Results showed that my CADe method identified EIC and helped physicians. Unassisted, the inter-rater reliability of identifying EIC was moderate. My software identified areas of EIC, but not as well as the unassisted physicians. With my software, physicians achieved a higher measure of agreement (Dice coefficient) than stroke fellows. However, fellows still achieved a Dice coefficient close to that of the physicians without software assistance. Inter- and intra-rater reliabilities were similar between the physicians and the fellows. The SSI did not correlate time from stroke onset, but did fit with known understanding of ischemic stroke pathology. This thesis showed that stroke CADe may have clinical utility. It quickly identified EIC in early CT images and increased the reliability of EIC identification by physicians. My ischemic stroke CADe tool brought quantitative methods to a subtle, subjective field.Item Open Access Computer-aided Diagnosis of Plus Disease via Quantitative Analysis of the Vascular Architecture in Retinal Fundus Images of Preterm Infants(2015-12-22) Oloumi, Faraz; Rangayyan, Rangaraj M.; Ells, Anna L.; Smith, Michael R.; Boyd, Steven K.; Parhi, Keshab K.Retinopathy of prematurity (ROP) is a disorder of the eye that may develop in preterm-born infants. If left untreated, ROP may lead to retinal detachment and ultimately blindness. A warrant for treatment of ROP is the detection of plus disease, which is clinically diagnosed by the presence of certain levels of increase in the tortuosity and thickness of retinal vessels. The openness of the major temporal arcade (MTA), the thickest branch of the venules, has also been observed to decrease in the presence of plus disease. It has been shown that there is interexpert disagreement on diagnosis of plus disease, even among expert ophthalmologists and retinal specialists, which calls for development of image processing techniques to detect and diagnose plus disease more accurately by analysis of retinal fundus images of preterm infants. This work presents image processing methods for the extraction of diagnostic features from retinal fundus images of preterm infants, for the purpose of computer-aided diagnosis (CAD) of plus disease. The features include measures of the thickness and openness of the MTA as well as tortuosity of retinal vessels. The methods include directionally sensitive Gabor filters for the detection and extraction of vessels, as well as morphological techniques for segmentation, binarization, and skeletonization of the vasculature. Methods are proposed for tracking and segmentation of only the MTA. Using geometrical modeling and analysis, the openness and thickness of the MTA are quantified. Tortuosity of vessels is quantified by analyzing the variation in the dominant orientation of vessels obtained by the application of Gabor filters. Receiver operating characteristic (ROC) analysis of the diagnostic performance of the measures of thickness, openness, and tortuosity resulted in area under the ROC curves of 0.75, 0.70, and 0.98, respectively. The methods may be used in a clinical or teleophthalmological setting for CAD of plus disease.Item Open Access Development and characterization of a synthetic bone analogue for surgical training(2016-01-18) Blair-Pattison, Aubrey; Anglin, Carolyn; Anglin, Carolyn; Ramirez-Serrano, Alejandro; Di Martino, Elena; Boyd, Steven K.; Hu, Richard WSpinal surgeries often require screws to be placed through small cylindrical pedicles in the vertebra, beside the spinal cord, to anchor rods for spinal fusion and correction. More experienced surgeons have fewer malplaced pedicle screws. In the current training paradigm, residents primarily learn the procedure on live patients. The objective of this research was to create a synthetic bone analogue with realistic tactile feedback to improve resident training. Forces encountered during pedicle cannulation and breaching were measured ex vivo. These were used to create a cost-effective bone model that replicated the forces as well as specific heterogeneous features of bone, distinct from current bone models. Of six residents who used the new bone analogues, five had fewer breaches in the simulated environment after practice than before.Item Open Access Dynamic In-Vivo Knee Cartilage Contact With Aging(2020-07-27) Kupper, Jessica C.; Ronsky, Janet L.; Boyd, Steven K.; Lichti, Derek; Edwards, W. Brent; Rainbow, MichaelJoint contact mechanics are important to the study of cartilage health and disease. Risk factors such as aging are speculated to result in altered cartilage contact locations, magnitudes, and sliding velocities, leading to altered loading of typical cartilage contact and non-contact areas. Altered contact patterns are speculated to be an influential mechanism associated with osteoarthritis-related cartilage changes such as softening, stiffening, or swelling. It is unknown whether knee joint contact patterns differ in an asymptomatic aging population compared to their younger counterparts.This feasibility study aimed to enhance understanding of relations amongst contact mechanics, cartilage health, and functional status and aging. This work applied high-speed biplanar videoradiography and magnetic resonance imaging to non-invasively measure a weighted centroid (WC) of tibiofemoral cartilage contact during gait in participants between the ages of 20-30 years (n = 5), and 50-60 years (n = 5). Cartilage contact regions during walking were linked to cartilage-health imaging outcomes (i.e., T2 relaxometry).Assessment of techniques for calculating the WC revealed that interval-based weighting factors provided the optimal approach, showing low sensitivity to errors but high sensitivity to clinically relevant changes. In aging vs. younger participants, no significant differences were found in WC location (median difference between heel strike and first force peak of gait cycle: younger 5.21-9.69%, older 2.12-7.44%), sliding distance (at onset of terminal swing: younger 0.50-1.15 mm, older 0.74-1.84 mm), or phase plot slope (change in sliding velocity over the surface of the joint; for swing phase: younger 4.14-14.99 mm/s%, older 6.15-14.47 mm/s%). For the first time, a functional relationship was found between T2 relaxometry and the gait cycle with lower T2 values during stance compared to prior to terminal swing. No differences were detected (younger vs. older) in T2 relaxometry values (medial tibial compartment at first force peak of gait: younger 29.8-43.1 ms, older 31.0-37.6 ms). These findings could not support differences in contact mechanics in older asymptomatic tibiofemoral joints compared to younger joints. Nevertheless, some potentially atypical patterns in older participants provide motivation to better understand linkages amongst aging, contact mechanics and cartilage health status across the cartilage degeneration spectrum.Item Open Access Impact of Growth Hormone on Adult Bone Quality in Turner Syndrome - A High Resolution Peripheral Quantitative Computed Tomography Study(2014-02-03) Nour, Munier Anwar; Boyd, Steven K.Caused by total or partial X-monosomy, Turner Syndrome (TS) is the most common chromosomal disorder in females. Commonly associated features include short stature, ovarian failure and osteoporosis in adult years. Childhood short-stature in TS is commonly treated with growth hormone (GH). This historic cohort-study using dual x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to determine the effect of childhood GH treatment on adult bone quality in TS women. Karyotype confirmed TS women aged 16-45 years were recruited (N=28). GH-treated subjects were 7.4 cm taller than non-GH-treated (p<0.05). Groups were similar in regard to known bone health risk factors. GH-treated subjects had significantly larger bone areas (9-25%, p<0.05) by DXA and HR-pQCT. Bone densities, micro-architecture and estimated fracture thresholds were not different among treatment groups. While no micro-architectural benefits were observed with GH-treatment, the persistent macro-structural differences may provide advantages in future fracture risk.Item Open Access Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency(Hindawi Publishing Corporation, 2012-01-02) Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.Item Open Access Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency(2012-03-13) Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27–52% net deficit compared to normal mice (). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD.Item Open Access Shoe Bending Stiffness and Muscle-Tendon Unit Function in Running(2021-01-08) Čigoja, Saša; Nigg, Benno Maurus; Edwards, William Brent; Stefanyshyn, Darren John; von Tscharner, Vinzenz; Boyd, Steven K.; Hoogkamer, WouterThe latest records set during long-distance running competitions have been attributed to recent footwear midsole innovations. One of these midsole innovations that has been claimed to have large effects on biomechanical, physiological, and performance variables is the use of a carbon fibre plate to increase the longitudinal bending stiffness of a shoe. Several mechanisms were proposed to be associated with performance improvements when running in footwear with carbon fibre plates. One of these mechanisms, the principle of optimising muscle function is currently not well understood. Therefore, this thesis aimed to investigate the effects of midsole bending stiffness of athletic footwear on muscle and muscle-tendon unit function in running. The first part of this thesis showed that running in stiff footwear resulted in a redistribution of positive work from proximal to distal lower limb joints. Specifically, it was found that a fatigue-induced redistribution of joint work from distal to proximal joints can be delayed when running in stiff footwear. The second part of this thesis dealt with the shortening velocities of muscle-tendon units. Estimated shank muscle-tendon unit shortening velocities were reduced when running in stiffer shoes. Experimental results using ultrasound imaging of the gastrocnemius medialis muscle revealed that the muscle shortened to a lesser extent and with lower average velocities in stiff running footwear. These findings could have implications for long-distance running performance. Positive work generation at more distal joints (i.e., ankle) may result in lower active muscle volume, which has been shown to be the main determinant of changes in the energetic cost of running. Slower shortening velocities of the gastrocnemius medialis could allow the muscle to operate on a more favourable position on its force-velocity relationship. This could allow for more economical force generation for a longer period during long-distance running. Altered muscle function could be a source of improved performance when running in stiff shoes.Item Open Access The Effect of Genetic Variation on Mouse Bone Strength(2016) Britz, Hayley M.; Hallgrimsson, Benedikt; Boyd, Steven K.; Jirik, Frank; Rolian, CampbellOsteoporosis is a heritable bone disease which is characterized by decreased bone mass and a deterioration in bone microarchitecture. This leads to a decrease in bone strength and therefore the risk of fracturing is greater in people who have been diagnosed as being osteoporotic. The mechanism by which osteoporosis is inherited is still unknown, as are the underlying microarchitectural causes of changes in bone strength. Without knowing more about these two mechanisms we cannot begin to develop more effective treatment plans or even a cure for this disease. The aim of this dissertation was to determine whether bone strength can be influenced by vascular canal microarchitecture and whether bone strength is a heritable trait, which is determined by specific quantitative trait loci. Using the CC founder strains and their F1 crosses in a diallel analysis we found that non-additive variance accounted for the same amount or more of the heritability than additive variance. Using the same CC mice we also found that BMD, canal connectivity, canal diameter, canal orientation, cortical area, cortical thickness, and percent porosity were all heritable determinants of bone strength. The bone strength measures used in this thesis were found to be highly correlated (0.702) and there was no statistical difference between methods (p=1.000). Employing the DO population we found a significant QTL for Imax on Chromosome 1 that is 1.43 cM wide and contained 19 candidate genes, of which Cacna1e looks the most promising. The QTL analysis for MaxF and BMD also found suggestive and near suggestive QTLs on Chromosome 1, which would indicate that Chromosome 1 is important in the genetic determination of bone strength.Item Open Access The Role of Mechanical Interactions between Cells and the Extracellular Matrix on Mineralization in a Stem Cell-Seeded Scaffold: a Multi-Scale Approach(2017) Nasr, Saghar; Duncan, Neil A.; Matyas, John R; Boyd, Steven K.Fracture healing is a complex phenomenon, which is not always successful, especially in elderly osteoporotic bones with a diminished capacity to bear load. Tissue engineering with stem cells may offer an approach to augment the healing rate in difficult-to-heal cases. Cell-collagen gel constructs have been recently used in several studies to promote mineralization. However, the role of mechanical factors to accelerate fracture repair has not been optimized nor is fully understood. The goal of this study was to investigate the role of mechanical environment, at tissue (macro) and cellular (micro) level, on tissue differentiation within a stem cell-seeded collagen construct. At the macro-scale, it was demonstrated that bone healing is influenced by fixation stability, aging, and bone quality. The studies performed at the tissue level provided insight into the potential of combination of stem cell-seeded constructs and mechanical pre-stimulation to accelerate fracture healing in elderly/osteoporotic bones. Our computational predictions were compared against experimental studies, and the “overall” tissue patterns matched relatively well with experimental observations. Experiments and imaging techniques were conducted to characterize the structure of collagen fibril network, cellular attachment patterns, and structure of initial mineralized structures in collagen-I gels seeded with murine embryonic stem cells. This data was used to develop a model representing the heterogeneous nature of the cell-collagen gel construct and verify our micro-scale computational simulations. An image-based micro-scale model containing the collagen fibril network, cells, and non-fibrous tissue was developed. A multi-scale approach was adopted to study the load transfer from tissue to cellular level, and formation of initial nodules of mineralization was predicted in a cell-collagen gel construct. Each macro-scale model was linked to a micro-scale model using a fully automated algorithm developed in MATLAB combined with python scripts and user-defined FORTRAN subroutines (UMAT, ORIENT, and USDFLD) for ABAQUS simulations. Not only the strain magnitudes were different at the macro-scale compared to those from the micro-scale, but also the strain field was found to be highly non-homogeneous at the cellular level. Local micro-environment affected cellular responses and differentiation patterns. Similar to our experimental observations, mineralization started from cell boundary, enlarged in size, and propagated along the collagen fibrils. Overall, a multi-scale approach can be a better representative of the heterogeneous nature of stem cell-seeded collagen gels and may lead to predictions that are more realistic. The proposed model seems to be a promising tool to predict cellular responses and control the cell fate in a cell-collagen gel construct under different loading regimes. This knowledge can be used to identify the optimal conditions to accelerate bone formation and facilitate development of an efficient cell-based therapy.