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The University of Calgary master and doctoral theses archive. Full text is made available when possible.
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Browsing Graduate Studies by Department "Biomedical Engineering"
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Item Open Access A Computational Model of Aneurysmal Flow at the Abdominal Aorta(2013-12-19) Nobakht, Samaneh; Di Martino, ElenaAbdominal Aortic Aneurysm is a dilatation of the aortic artery that occurs in response to degradation of the wall structure. The present research focused on developing a realistic hemodynamic model of the aneurysm using a new method to assign boundary conditions. A three element Windkessel model was coupled to the 3D geometry model of the disease in order to couple inlet flow with outlet pressure. This model resulted in more precise hemodynamic conditions for pulsatile flow: 1- in terms of realistic wall pressure values and pressure curves, 2- realistic geometry effect. Contours of wall shear stress, mean wall shear stress, static pressure, and velocity streamlines were calculated and results were compared for two patients and an ideal geometry of the aneurysm. Finally maps of mean wall shear stress were produced to investigate relationship between values of the mean wall shear stress and histological profiling of aneurysm specimens obtained during surgery.Item Open Access A coupled eulerian-langrangian mechanical model of the breast(2010) Kuhlmann, Martin; Ramirez-Serrano, Alejandro; Fear, Elise; Federico, SalvatoreItem Open Access A New Method for Assessing Tissue Alignment using Clinical MRI in Multiple Sclerosis(2017) Sharma, Shrushrita; Zhang, Kunyan; Pike, Bruce; Dunn, Jeffery FrankChanges in the alignment of white matter tracts are common in many neurological disorders such as multiple sclerosis (MS). Currently advanced MRI methods including diffusion-weighted imaging is the mainstay in assessing tissue coherency and anisotropy. In this thesis, I have implemented and verified a novel image-processing method for this purpose using conventional MRI. This is done based on Fourier transform power spectrum. Outcomes were evaluated in 3 steps: 1) testing feasibility using brain areas with highly aligned nerve fiber tracks in T2- weighted MRI; 2) confirming pathological relevance using postmortem brain sample; and 3) assessing utility by comparing with diffusion tensor imaging. To improve the accuracy of comparison with pathology, I have also conducted quantitative histology besides traditional analysis of the staining density of myelin and axons. The results suggest that advanced analysis of clinical MRI may provide valuable information as powerful as advanced MRI to enhance the measurement of tissue property.Item Open Access A photogrammetric system for 3d reconstruction of a scoliotic torso(2008) Chang, Yu-Chuan; Habib, AymanItem Open Access A Proposed Mechanism for Enhanced Titin-Based Force during Ca2+-activation(2017) Powers, Krysta; Herzog, Walter; Pollack, Gerald; Schmidt, Tannin; Syme, Douglas; Nishikawa, Kiisa; Shemanko, Carrie; Federico, SalvatoreWhen an active skeletal muscle sarcomere is stretched, it generates more force after the stretch is completed when compared to a contraction at the same corresponding length. This mechanical property of skeletal muscle defies explanation by any conventional mechanism of contraction. Surmounting evidence indicates that the explanation for enhanced force following active stretch may be provided by the titin protein in the sarcomere, which becomes stiffer during Ca2+-activation. This thesis explores the mechanisms by which titin force is enhanced in actively stretched sarcomeres. Known to stiffen in the presence of Ca2+, the first study quantifies the contribution of Ca2+ to enhanced titin force, showing that an alternative mechanism accounts for the majority of titin force enhancement. The mechanism is further investigated using chemical inhibition of cross-bridges which shows that titin force enhancement is initiated with the development of contractile force. The next set of studies increase support for an interdependence of titin force enhancement and contractile force, showing that titin force enhancement is essentially eliminated and contractile force is decreased in sarcomeres with muscular dystrophy with myositis (mdm), a genetic mutation affecting the titin protein. The final study seeks to determine whether mechanical deficiencies in titin force enhancement are observed in a less reduced, single fiber preparation. Mutant fibers generated comparable contractile force and total force following active stretch beyond filament overlap as control fibers. Titin force enhancement was abolished in some mutant fibers and measured in other mutant fibers suggesting that the mdm mutation differentially affects fibers (and titin) in skeletal muscle. Passive force was increased in mutant fibers, showing that alternative structural components in a fiber can re-establish enhanced active stiffness in the absence of titin force enhancement. Collectively, the findings from this thesis show that titin-based force enhancement is an inherent property of skeletal muscle. The mechanism of titin force enhancement is crucial to sarcomere mechanics; as in its absence, sarcomeres generate less force and alternative structures to titin establish a comparable increase in active stiffness.Item Open Access Accelerated Quantitative Magnetization Transfer (qMT) Imaging(2018-10-24) Mclean, Melany Ann; Pike, G. Bruce; Forkert, Nils Daniel; Lebel, Robert MarcQuantitative magnetization transfer (qMT) is an advanced magnetic resonance imaging (MRI) technique with enhanced specificity to myelin. The acquisition of many images with unique magnetization transfer (MT) saturation results in a signal response curve known as the z-spectrum. The two-pool tissue model, which describes properties of nuclei with free and restricted motion, can be fit to the z-spectrum to provide details of macromolecular tissue content (including myelin) beyond what can be seen from conventional single saturation approaches (e.g. MT ratio). Widespread use of qMT has been hindered by long acquisition times inherent to z-spectrum-based imaging techniques including qMT and chemical exchange saturation transfer (CEST). This thesis uses sparseSENSE, a combined parallel imaging and compressed sensing technique, to accelerate MT-weighted images. In this thesis, sparsifying reconstruction algorithms are shown to enable high-quality image reconstruction from 4D qMT datasets, retrospectively under-sampled by factors of up to 32. MT-weighted images demonstrate exceptional image quality at high acceleration factors, which is shown to translate well to accelerated z-spectra. However, qMT parametric maps produced from accelerated z-spectra are shown to be sensitive to acceleration artifacts and can only be accelerated by a factor of 4 with minimal loss of image quality. Nonetheless, this acceleration can yield a significant acquisition time savings when applied to prospectively under-sampled data. In addition, time savings created by acceleration can be used to increase spatial resolution or collect more MT-weighted images, enabling even higher acceleration factors. Long acquisition times have often been cited as a limitation of the qMT method. This work has addressed that limitation, making qMT protocols more feasible for in vivo research studies, particularly in youth and patient populations.Item Open Access ACL transection and electrical stimulation training of the quadriceps in the rabbit: effects on strength and osteoarthritis(2008) Szabo, Eva; Herzog, WalterItem Open Access An assessment of the potential for recovery of bone quality after osteoporotic bone loss(2011) Campbell, Graeme Michael; Boyd, StevenItem Open Access An Experimental Approach to Explore Abdominal Aortic Aneurysms in Rabbit Model(2017) Altamimi, Manal Nasser; Di Martino, Elena; Mitha, Alim; Shrive, Nigel; Appoo, JehangirThe diagnosis of an Abdominal Aortic Aneurysm (AAA) is currently made based on maximum diameter, which fails to accurately predict risks of rupture. The purpose of this study was to advance our understanding of AAA evolution using a rabbit model. AAAs were developed in rabbits using a periaortic incubation of CaCl2 and elastase. Rabbits were imaged using 3D angiography at 0 (healthy), 2, 4, and 6 weeks. Material properties and histological analyses were obtained for each stage. Results showed an increase in maximum diameter and wall thickness with aneurysmal tissue. The healthy aorta was stronger than all aneurysmal tissue. Tissue at 6 weeks had the stiffest and strongest properties compared to aneurysmal tissue. Elastin degradation and separation between wall layers was observed in all aneurysmal tissue with the highest collagen remodeling at 6 weeks. Because human aneurysms are diagnosed at an unknown time after initial formation, control animal experiments are necessary to understand the evolution of the mechanical and histological properties of the aortic tissue.Item Open Access An integrated finite element modeling/cryomicroscopy investigation of osmotic environment and ice structure during freezing of tissues(2003) Liu, Zhihong; Wan, Richard G.; Muldrew, KenItem Open Access Automatic Classification of Idiopathic Parkinsonian Disease and Progressive Supranuclear Palsy using Multi-Spectral MRI Datasets: A Machine Learning Approach(2018-09-19) Talai, Aron Sahand; Forkert, Nils Daniel; Monchi, Oury; Chan, SonnyParkinson's disease, which is characterized by a range of motor and non-motor symptoms is categorized into classical Parkinsonian disease (PD) and atypical Parkinsonian syndromes (APS), such as progressive supranuclear palsy Richardson’s syndrome (PSP-RS). The differential diagnosis between PD and PSP-RS is often challenged by similarity of early symptoms, effectively resulting in considerable misclassification rates. The aim of this thesis is to assess the benefits of using biomarkers from multi-modal MRI datasets in the accurate classification of PD vs. PSP-RS. Multi-spectral information form T1-, T2-, and diffusion-weighted (DWI) MRI from 38 healthy controls (HC), 45 PD, and 20 PSP-RS subjects were available for this study. In detail, morphological (category 1), brain iron marker (category 2), and diffusion features (category 3) were employed. In the last category, all feature types were combined (combinational) for the development of a machine learning model. Nested leave-one-out-cross validation was used to evaluate the classification performance in each category followed by a 1000 permutation test to assess classification significance. The results suggest that, the DWI based classifier tied with the combinational approach in terms of overall accuracy. However, in the former, the specificity was lower by 10%. In detail, 4 PSP-RS and 1 PD subjects are incorrectly classified as PD and PSP-RS in the combinational approach resulting in a sensitivity and specificity of 91.67% and 94.12%, respectively. The obtained results indicate that features extracted from T1- and T2-weighted MRI perform worst based on overall accuracy. All classification categories were statistically significant (p<0.001). In conclusion, combination of features from different MRI modalities such as T1-, T2-, and diffusion-weighted datasets improves the multi-level classification performance of HC vs. PD vs.PSP-RS compared to single modality features, particularly in terms of PD vs. other differentiation. The results and concepts discussed in this research thesis have wide ranging implication for future developments of computer-aided diagnosis of PD sub-syndromes.Item Open Access Better diagnoses of stroke and epilepsy with quantitative mr assessment(2011) Kosior, Robert Karl; Frayne, RichardItem Open Access Biomaterials for intervertebral disc repair(2012-07-24) Lee, Haeyeon; Sen, ArindomEach intervertebral disc (IVD) in the spine has an inner gel-like nucleus pulposus (NP) surrounded by an outer annulus fibrosus (AF). IVD degeneration has been linked to low back pain, a medical condition that affects millions of people and has significant socioeconomic consequences. The goal of this study was to assess the properties of different biomaterials to determine their utility in IVD repair strategies. Different compositions of gellan gum were investigated for NP repair. Through optimization of gellan gum properties, it was found that 2% (w/v) low acyl gellan gum had the best mechanical properties while having a suitable gelling temperature for cell encapsulation. When gellan gum, fibrin, and chitosan/gelatin/glycerol phosphate hydrogels were compared for sealing defects in the AF, it was found none could withstand pressures as high as intact IVDs. Therefore, a triphasic prototype construct composed of Kryptonite bone cement, gellan gum, and reinforcing fibre was evaluated to determine if it could contribute to AF repair. Whereas, it was found that constructs with sutures had better tensile properties than those with electrospun fibres, overall the current generation of constructs was not sufficient for AF repair. This thesis represents an important step in understanding the use of biomaterials for IVD repair.Item Open Access Biomechanical assessment of CAD/CAM and hand-cast prostheses for transtibial amputees(2009) Thannhauser, Steven Victor; Ronsky, Janet L.Item Open Access Biomechanical Measures of the Muscle-Bone Unit in Postmenopausal Females: A Pilot Study(2016) Pangka, Aleen; Edwards, W. BrentBone is a dynamic tissue that adapts its stiffness and strength to the habitual loading environment. Muscles attach to bone and the largest loads experienced by bone come from voluntary muscle contractions. The objective of this study was to quantify the relationship between functional measures of muscle loading (i.e., joint moments, isometric muscle strength, and physical activity questionnaire scores) and bone stiffness, strength, and volumetric bone mineral density (vBMD). Moderate correlations were observed between peak joint moments and bone stiffness (r=0.480, p=0.032) and strength (r=0.490, p=0.028). No relationship was observed between joint moments and vBMD, or between any bone measurements and muscle strength or physical activity. These findings suggest that muscle loading may influence bone stiffness and strength through alterations in bone quality rather than quantity, and that the functional relationship between muscle and bone may be best reflected by habitual measures of skeletal loading.Item Open Access Biophysical Evidence for a Molecular Interaction between Proteoglycan 4 and Hyaluronan in Solution: Effect of Exposure to a Zwitterionic Detergent on Cartilage Boundary Lubricating Function(2016) Morin, Alyssa; Schmidt, TanninProteoglycan 4 (PRG4) and hyaluronan (HA) are key synovial fluid constituents that contribute synergistically to cartilage boundary lubrication through an undefined mechanism. PRG4 monomers and multimers have previously been separated using size exclusion chromatography with a buffer containing the zwitterionic detergent CHAPS. However, CHAPS may alter the ability of PRG4 to interact with HA and synergistically reduce friction. The objectives of this thesis were to (1) assess the size distribution of PRG4, HA, and PRG4+HA in solution, and (2) determine the effect of exposing PRG4 to CHAPS on the size distribution, cartilage boundary lubricating ability, and cartilage adsorption of PRG4+HA. The size distribution of PRG4+HA was less than PRG4 and HA. Exposure to CHAPS irreversibly altered the size distribution, cartilage boundary lubricating ability, and cartilage adsorption of PRG4+HA. These results suggest a hydrophobic molecular interaction exists between PRG4 and HA, both in solution and at the articular cartilage surface.Item Open Access Bioprocess Development for Large-Scale Production of Skin Derived Precursor Schwann Cells(2018-08-16) Walsh, Tylor Douglas; Kallos, Michael S.; Schmidt, Tannin A.; Biernaskie, Jeff A.Peripheral nerve and spinal cord injuries are debilitating, leading to lifelong complications and reduced quality of life. Cellular therapies have demonstrated beneficial outcomes when treating these injuries especially when using Schwann cells. However, there is currently no robust and reproducible method for producing Schwann cells at clinical scale. Bioprocesses that use bioreactors have significant advantages when scaling-up cellular therapies. Therefore, the research in this thesis was done to address this gap and develop methods, tools, and protocols to create a bioprocess for the large-scale expansion of Schwann cells. The hydrodynamics of the bioreactor were investigated by using CFD modeling, comparing velocity, shear rate, and energy dissipation rate at different agitation rates and their effect on cell expansion. The model that was generated can be used to scale up processes to larger, clinical and manufacturing scale, bioreactors. Upstream and downstream unit operations were then developed. Commercially available microcarriers were evaluated and tested in bioreactors to find the microcarrier that supported both inoculation and expansion of SKP-SCs. Different bioreactor platforms were evaluated, showing that controlling the process parameters increased cell densities. An in-depth DOE was conducted to find the best inoculation conditions, investigating which parameters had significant effects on cell attachment, distribution, and expansion. Detachment of SKP-SCs from microcarriers was investigated with different enzymes and agitation rates to develop an in-vessel passaging protocol that can easily be scale-up. After harvest, cryopreservation medium and cell density were investigated to ensure a quality product can be frozen and delivered to the patient. After the process was developed, 3 rat lines and 1 human line were tested. The process was reproducible and robust and easily adapted to human cells. Additional development is needed to use this process for nerve derived Schwann cells. This process was then integrated together and 150 x106 cells were produced from 3x106 in 7 days. Lastly, the expansion design space was investigated to determine the effects of pH, DO, and agitation on the expansion of SKP-SCs. All the tools and methods developed in this thesis can easily be adapted to nearly any bioprocess that utilize bioreactors for cellular therapies.Item Open Access Bioprocessing for Expansion and Standardization of Embryonic Stem Cell Cultures(2013-03-06) Hunt, Megan; Kallos, Michael; Gates, IanSince their derivation in 1998, human embryonic stem cells (ESCs) have been of great interest within the realm of regenerative medicine. Their ability to differentiate into any cell type of the adult body makes them an incredibly powerful and exciting tool with respect to potential treatments for long-term degenerative diseases. Stirred suspension bioreactors have been the focus of many publications anticipating the need for high numbers of clinically-relevant cells for therapeutic applications. As evidenced by the wide range of published protocols and resulting culture output, the field is currently lacking in well designed, systematic investigations into the true effect of varying culture parameters not only in suspension conditions but also within standard static cultures. This research was carried out to address gaps that currently exist within current ESC culture protocols first by establishing a base line for culture kinetics, during which the issue of morphological evaluation was identified. With the goal of eliminating the subjective nature of morphological evaluation, fractal geometry was utilized to assign a quantitative value (fractal dimension) to ESC cultures. Results indicate a significant difference between fractal dimensions determined for pluripotent cells versus differentiating cells suggesting that fractal geometry may be used to monitor culture health. A more standardized methodology for static culture monitoring will allow for more homogeneous population of ESCs as inoculum for large scale expansion efforts. Finally, a 3^2 factorial experimental design was developed and executed for stirred suspension culture of ESCs illustrating the potential for interaction effects and suggesting for the first time that the use of the conventional stepwise optimisation approach to stirred suspension culture is not appropriate.Item Open Access Bioprocessing of human bone marrow mesecnchymal stem cells for the treatment of intervertebral disc degeneration(2012) Yuan, Yifan; Kallos, Michael S.; Sen, ArindomLower back pain is a major medical problem in North America. From the biological point of view, the degeneration of intervertebral disc may be the main cause for lower back pain. The current study focused on using stem cell to differentiation into large number of healthy intervertebral disc cells. Human bone marrow mesenchymal stem cells (hBMMSCs) were used. This project has been divided into two parts: I. hBM-MSCs expansion, 2. hBM-MSCs differentiation. Experiments were carried out manipulating culture medium components ( oxygen tension, calcium, serum, pH) and agitation to improve the expansion of hBM-MSCs in bioreactors. After 33 days of culture under the developed protocol, approximately I 03 fold increase over the inoculation density had been obtained in suspension bioreactor culture. The differentiation of MSCs to nucleus pulposus-like cells was performed by using multiple growth factor cocktails and notochordal conditioned medium. There was higher expression of genes and proteins specific for nucleus pulposus cells, after exposure of MSCs to conditioned medium over 21 days than in basal medium.Item Open Access Bone micro-architecture, estimated bone strength, and muscle strength in elite athletes: an hr-pqct study(2012) Schipilow, John David Shearer; Boyd, StevenAthletes 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.