Open Theses and Dissertations
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Browsing Open Theses and Dissertations by Department "Biomedical Engineering"
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- ItemOpen AccessA 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.
- ItemOpen AccessA 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.
- ItemOpen AccessA 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.
- ItemOpen AccessAccelerated 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.
- ItemOpen AccessAn 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.
- ItemOpen AccessAutomatic 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.
- ItemOpen AccessBiomaterials 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.
- ItemOpen AccessBiomechanical 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.
- ItemOpen AccessBiophysical 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.
- ItemOpen AccessBioprocess 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.
- ItemOpen AccessBioprocessing 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.
- ItemOpen AccessBoundary Lubricating Ability of Proteoglycan 4 at an Articular Cartilage-Meniscus Biointerface(2015-10-08) Dorosz, Samuel; Schmidt, TanninProteoglycan 4 (PRG4) is a glycoprotein in synovial fluid (SF) and on the articular cartilage surface, where it acts as a boundary lubricant. Hyaluronan (HA) is another SF constituent that acts as a boundary lubricant at the cartilage-cartilage biointerface and interacts with PRG4 to synergistically lower friction. The meniscus is a fibrocartilaginous pad in the knee, on which PRG4 exists, that is critical for joint health. This thesis aimed to develop an in vitro lubrication test to determine the boundary lubricating ability of PRG4 and HA, alone and in combination, at the cartilage-meniscus biointerface, and assess the surface adsorption of recombinant human PRG4 (rhPRG4). A novel cartilage-meniscus test demonstrated that (rh)PRG4 and HA, alone and in combination, act as effective boundary lubricants at this biointerface. rhPRG4 adsorbed to the meniscal surface. This work contributes to the understanding of meniscus lubrication and potential development of osteoarthritis biotherapeutic treatments.
- ItemOpen AccessBracing of Pectus Carinatum: A Quantitative Analysis(2017) Bugajski, Tomasz; Ronsky, Janet; Murari, Kartikeya; Lopushinsky, StevenPectus Carinatum (PC) presents as an overgrowth of costal cartilages resulting in a sternal protrusion. Treatment of PC is performed with a pectus carinatum orthosis (PCO) that compresses the protrusion. Injuries may arise when this PCO is over-tightened. For the first time, a force measurement system (FMS) was constructed that measured PCO forces. The purpose of this study was to determine if participants could accurately attain their clinically prescribed force (CF) over time, and if the protrusion stiffness (PS) influences the participant-applied forces (PF) and correction rate (CR). Results demonstrated that most PFs (75%) exceeded their associated CF (0.46-5.01 lbs). Further investigation is required to determine clinical significance. PS had a positive relationship with PF, but no relationship with CR. Future studies focusing on improved displacement measurements would enhance the ability to quantify PS. Developing a FMS to provide real-time feedback should also be considered to improve PCO efficacy.
- ItemOpen AccessBrain Development During Childhood and Adolescence(2016-01-15) Mah, Alyssa; Lebel, Catherine; Frayne, Richard; Wei, Xing-Chang; Forkert, Nils; Dyck, RichardBrain development is a combination of complex physiological changes, and various magnetic resonance imaging (MRI) techniques can help explain observed changes during development in vivo. Building upon observations from post-mortem studies, advancements in imaging and modelling techniques provide new means to further interpret the understanding of healthy brain development during childhood and adolescence. It is, however, a challenge to capture specific physiological changes, such as myelination, using MRI. This thesis uses MRI techniques – neurite orientation dispersion and density imaging (NODDI), inhomogenous magnetization transfer (ihMT), and multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) – that further characterize development in white and subcortical grey matter regions in the brain by improving specificity of the MRI signal compared to conventional techniques. Measures from NODDI, ihMT, and mcDESPOT suggest an increase in myelination and/or axonal packing during development from 0-13 years.
- ItemOpen AccessCartilage boundary lubrication and rheology of proteoglycan 4 + hyaluronan solutions and synovial fluid(2014-06-12) Ludwig, Taryn Elaine; Schmidt, Tannin ASynovial fluid (SF) is the viscous fluid present within articular joints that contributes to load bearing and lubrication functions. Proteoglycan 4 (PRG4) and hyaluronan (HA) in SF contribute synergistically to cartilage boundary lubrication. However, changes in SF PRG4 and HA content with osteoarthritis (OA) and associated effects on cartilage boundary lubricating function are not fully understood. Furthermore, the effects of PRG4+HA interaction on solution viscosity have not been thoroughly characterized. The objectives of this thesis were to 1) investigate the relationship between PRG4 and HA composition and boundary lubricating function of normal and OA SF, and 2) to investigate how the concentration and structure of PRG4 contributes to interactions with itself and HA, and subsequently the boundary lubricating and rheological properties of SF. Novel and previously characterized biochemical and biomechanical methods were used to evaluate boundary lubricant composition and lubricating ability of SF. While not all OA SF samples had low PRG4, samples that had low PRG4 concentration and decreased HA molecular weight (MW) demonstrated decreased cartilage boundary lubricating ability in vitro, which could be restored by addition of PRG4. SF aspirated after a flare reaction to intra-articular injection that had low PRG4 and an approximately normal HA MW distribution demonstrated normal cartilage boundary lubricating ability. In purified solutions of PRG4 and HA, decreased PRG4 or decreased high MW HA limited cartilage boundary lubricating ability. PRG4 and recombinant human PRG4 increased the viscosity of HA solutions at low concentrations, but decreased the viscosity of high concentration HA solutions. The intra- and inter-molecular disulfide bonded structure of PRG4 was observed to be important for its contributions to both PRG4+HA cartilage boundary lubricating ability and PRG4+HA solution viscosity. These results demonstrate that alterations in both PRG4 and HA content in SF may have negative effects on SF cartilage boundary lubricating and rheological function, and are consistent with a non-covalent, crowding mechanism of interaction. They suggest that maintaining PRG4 and HA content in SF during injury and disease, through the development of new PRG4±HA biotherapeutic treatments, may be able to both protect cartilage from degeneration and restore SF viscosity in vivo.
- ItemOpen AccessCellular Therapy for Saccular Intracranial Aneurysms: A Proof-of-Concept Study(2015-09-23) Adibi, Mohammad Amin; Sen, Arindom; Mitha, AlimIntracranial aneurysms are pathological dilations of arteries in the brain. Rupture of an aneurysm would be catastrophic, resulting in death in half of the cases and permanent neu- rological deficits in half of the survivors. The current standard-of-care for treating aneurysms is endovascular coiling, a procedure that involves packing the aneurysm with soft platinum- made coils that cause the blood within the aneurysm to clot, consequently slowing the flow of blood into the aneurysm. This is followed by a healing response that remodels the clot into fibrous tissue and regenerates a neointima layer that covers the neck of the aneurysm and isolates it from the parent vessel. Lack of proper healing in about one-fifth of the patients results in recurrence of the aneurysm. Building on a growing body of literature, this project evaluated the potential therapeutic effects of mesenchymal stem/stromal cells (MSCs) on the healing of coiled aneurysms in a rabbit model.
- ItemOpen AccessCentroid of Volume: A Surface Topography Measure used to Detect Changes in Adolescent Idiopathic Scoliosis(2016-02-03) Melia, Alexandra; Ronsky, Janet; Joughin, Elaine; Habib, AymanAdolescent Idiopathic Scoliosis (AIS) is a complex three-dimensional (3D) deformity that affects 2-3% of the population. Current methods of diagnosing and monitoring AIS are repeated two-dimensional X-rays every 6-12 months. Repeated radiographs have been shown to increase cancer risk and do not account for 3D changes in the spine. To overcome these drawbacks, the University of Calgary Scoliosis group has developed a non-radiographic imaging technique to analyze 3D deformities using Surface Topography (ST). The overarching objective is to validate a set of ST indices to reliably detect scoliosis. A new ST index, Centroid of Volume (COV), that is a 3D measure of torso balance, is investigated in this thesis. This work found that COV detected differences between healthy and AIS groups and was moderately correlated to the Cobb angle. This index shows promise to detect AIS, which could help advance ST as a clinical tool for monitoring or detecting scoliosis.
- ItemOpen AccessCharacterization 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.
- ItemOpen AccessCharacterization of Proteoglycan 4 Supramolecular Structure and its Effect on Lubricating Function(2018-09-14) Martens, Kayla; Schmidt, Tannin; MacCallum, Justin; Derksen, Darren; Sen, ArindomProteoglycan 4 (PRG4) is a mucin-like glycoprotein that is a key synovial fluid constituent, functioning as a cartilage boundary lubricant. PRG4 has been suggested to exist as a supramolecular structure. The objectives of this thesis were to (1) characterize the supramolecular structure of recombinant human PRG4 (rhPRG4) and its dependency on concentration, (2) elucidate the molecular forces underlying the formation of the supramolecular structure, and (3) assess the lubricating ability of the supramolecular structure. rhPRG4’s ability to form a supramolecular structure and reduce friction was concentration dependent. Arginine (0.2M) disrupted the formation of the supramolecular structure of rhPRG4 and diminished its lubricating ability. Conversely, 20 mM calcium enhanced the formation of rhPRG4 supramolecular structure and enhanced its lubricating ability. These results suggest non-covalent interactions mediate rhPRG4’s supramolecular structure, shown here to exist for the first time, which in turn is a functionally (lubrication) determinant property.
- ItemOpen AccessCharacterizing Turbulence Modification via Red-Blood-Cell Analogs in Free Shear Layers using Particle Tracking Velocimetry(2015-02-02) Kaucky, Lucie; Wood, David; Rival, DavidThe turbulence modification of red blood cells is evaluated using a basic experimental approximation to blood, which specifically accounts for its particle-laden and dense concentration in vivo. The contribution of super absorbent polymer beads to a developing free shear layer is quantified using particle tracking velocimetry. Results showed that the presence of a particle-phase reduced mean velocities, kinetic energy, and the gradient of kinetic energy, implying that the free shear layer was diffused. Furthermore, similar fluid behaviour resulted between the suspension cases when Reynolds number was increased from 1,143 to 10,490. This suggests that red blood cells act to diffuse flow features that can subsequently lead to instabilities from which transitional and eventually turbulent behaviour can develop. These findings indicate that a two-phase model, specifically accounting for the dense particle-phase of blood, may be necessary for arterial blood flow where transition and turbulence can occur.