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<p>Research in the field of human injury biomechanics with respect to athletes has indicated that head acceleration events (HAEs) suffered during participation in a contact sport can cause long-term neurological changes that present asymptomatically. This concept has been referred to as “mild” traumatic brain injury (mTBI). This mirrors results found in soldiers, where it is also now thought that traumatic brain injury, coupled with psychological trauma can lead to posttraumatic stress disorder (PTSD). Current consensus amongst the neurotrauma research community is that all HAEs matter, whether caused by blast, blunt force, or directed energy weapons.</p> <p><br></p> <p>Previous research has focused on the long-term changes that have been demonstrated and quantified, however very little research has been done to quantify the effects of a single insult to the brain. Several studies have had participants perform head motions while in a magnetic resonance imaging (MRI) scanner. Digital twins may be used to simulate the effects of an insult, be it blast, blunt force, or directed energy to an object. Finite element models of the human head and brain have a long history of development from the earliest models in the 1970s to today. Currently, numerous software packages allow for the regularization and comparison of MRI datasets. Some software packages offer additionally the ability to create subject specific finite element meshes interactively from a single MRI image. Previous research in the HIRRT Lab reduced the time to generate simulation geometry to approximately 48 hours to generate a patient specific finite element mesh. This represented a substantial reduction in the processing time for a single scan, which to the knowledge of the authors required on the time scale of weeks to process a single geometry including the skull robustly or required costly software licenses, and still required user interactive processes. The architecture and deployment of the HIRRT Lab Cluster, a high-performance computing system that is a cost-optimized research tool to enable rapid processing of scans to simulation geometry using batch processes on a Slurm cluster. There are software optimizations, operating system optimizations, and Linux kernel-level optimization (and selections) utilized that enable the hardware selected to perform optimally. </p> <p><br></p> <p>To the knowledge of the author, no single pipeline enables the automated generation of robust, patient specific finite element meshes from raw datasets fresh from an MRI. This package addresses those limitations with a design heavily tilted towards Linux cluster implementations. The author has created a pipeline of code designed to run on a Linux-based compute cluster that is capable of processing 1700 scans from raw T1-weighted MRI scans to a finite element mesh with regions of interest (ROIs) identified as element sets, and white matter fiber orientation determined from diffusion tensor imaging (DTI) scans in under 7 days using the current hardware available in the HIRRT Lab Cluster with appropriate software licensing. This represents a speed up of over 1200x compared to the original program overall at just mesh processing, and a speed up of 22x for a single scan being processed, with additional features and detail not captured by the original code. </p> <p><br></p> <p>Accurate representative models for subpopulations via their immutable traits (e.g. size, biological sex, ethnicity/ancestry, or age) can further reduce the number of simulations that are required to accurately assist in the improvement of finite element models that may be used to improve the design of personal protective equipment, create new techniques, or aid in the design of new vehicles capable of reducing the exposure of individuals to potentially traumatic damage. The use of subpopulation groupings rather than the simulation of each unique individual, even models consisting of bounding cases, such as the largest or smallest representative members of a subpopulation can reduce the amount of data that needs to be processed to generate useful design feedback for engineers. </p> <p><br></p> <p>Subject-specific models allow for greater variation in strain due to geometric differences between individuals brains and should be used where possible to describe a given individual’s strain history more accurately, which can be used to assess the formation of damage as indicated by biomarkers. To understand the long-term effects of blast overpressures on brain structure, function, and chemistry, and subsequently develop appropriate mitigation strategies, computational models of individual soldiers must be developed. These models must integrate blast physics and neuroimaging of actual tissue damage to the brain. There is a need to develop constitutive equations capable of being used in multi-scale models to relate various insults directly to damage in the brain. These equations should be linked to damage as indicated through various MRI scan types and used to robustly assess individuals over the course of their unique impact histories. Through the development of a digital twin in this manner, unique predictive medicine may be used to proactively identify those athletes and warfighters who may be at higher risk for long term detrimental effects from further exposure to HAEs.</p>

Heart rate variability (HRV) and music have been demonstrated to have a relationship in previous literature. The primary objective of this study is to further investigate that relationship by observing HRV during periods of listening to relaxing and exciting music and comparing the results to a baseline as well as the other condition. The secondary objective of this study is to investigate the efficacy and potential usage of the Polar H10 chest strap monitor in measuring HRV parameters. The results of the Polar H10 will be compared to the iWorx TA-220 and iWorx-ECG12, the existing gold standard in HRV and ECG recording. The data will be exported to Matlab and Excel and analyzed to see if particular types of music display any trends for these HRV parameters, as well as heart rate (HR). Polar data will be gathered and analyzed using the EliteHRV app. Analysis included Fast Fourier Transform (FFT), Low Frequency/High Frequency Ratio (LF/HF), standard deviation of NN intervals (SDNN). Data was gathered in 10 minute intervals of No Music, Relaxing Music, Exciting Music. Results showed notable changes in LF/HF ratio in both directions. SDNN and Mean RR interval had moderate decreases in both relaxing and exciting music, with Total Power having a significant decrease in both. Comparison of Polar H10 and iWorx-ECG data showed strong agreement in heart rate and RR interval data, but significant differences in other data. This suggests differences in calculation by the software used.

found that most of these factors are directly or indirectly linked to subjects’ BMI (body mass index). Thus, from a statistical perspective, BMI could be an overall indicator of the probability of femur fracture from a sideways fall. Using a biomechanics approach coupled with statistical data we investigate this relationship with a large cohort of postmenopausal women aged 50-79 from WHI-OS (Women’s Health Initiative Observational Cohort). The cohort is divided into six sub-cohorts by BMI where each fall-related factor is examined and compared with each other. Significant differences are discovered among cohorts in terms of femur size, aBMD (areal bone mineral density), peak fall force based on kinematics, and maximum von Mises stresses induced in the proximal femur. Through a probabilistic margin of safety approach which has been recently applied to orthopedic application, we found the margin of safety predicted probability to be decreasing faster with increasing BMI and better v fitted with medical record of the identical cohort compared to that found using a deterministic risk factor approach. To promote the application in other situations, tumor damaged femur bones are examined and tested for possible stress concentration effect in terms of probability of failure. The influence of tumor lesion turned out to be size and location sensitive. The superior side of the femoral neck has the highest stress concentration effect from tumor lesion where a 4mm diameter lesion could result in a 1.7 times greater maximum von Mises stress and 2.95 times greater probability of failure.

<div>As aging proceeds, the occurrence of cardiovascular diseases increases independent of other risk factors. At atherosclerotic sites, the rise in the senescent cell population was also observed. Patients with Hutchinson Gilford Progeria Syndrome (HGPS) also showed accelerated aging syndromes and extensive atherosclerosis progression, which was due to missense mutations on the LMNA gene that led to the production of progerin, an aberrant lamin A isoform instead of regular lamin A protein. Lamins act as structural and functional components in nuclear lamina, and recent findings suggested that the ectopic expression of mutant lamin A or lamin A precursor (prelamin A) not only caused defects in cell mechanics but also disturbed mechanotransduction pathways involving lamin A, both of which may contribute to vascular dysregulation. Moreover, the observation of the accumulation of prelamin A in normal aged vascular cells further suggests shared dysregulations involving lamin A in the vascular system between aged people and HGPS patients.</div><div>In the vascular system, endothelial cells were well regulated by hemodynamic forces in vivo to maintain vascular homeostasis. Endothelial dysfunction, including impaired vasodilation and increased permeability, was regarded as the initial marker of atherosclerosis. Despite recent advancements and discussions about the potential mechanisms of progerin-induced vascular disorders, how progerin triggers endothelial dysfunction in a mechanical environment as an early event during atherosclerotic lesion formation has not been studied intensively.</div><div>To help answer the gap question, we first set our goal to understand the effect of laminar flow at arterial levels on endothelial lamins as part of the aging process. Spatial and temporal changes in lamin A/C expression were observed as cell passage went up without flow present. As shear stress was applied, lamin A/C expressions were modulated on both transcriptional and translational levels, which were also dependent on PDL. To further examine how progerin was involved in EC functions with a particular focus on the flow effects, we next generated a stable endothelial cell line that expressed progerin as our EC aging model. Endothelial wound repair under laminar flow at different rates was characterized, and differential cell proliferation activities, as well as migration deficiencies in progerin-expressing ECs during the process, were also recognized. Furthermore, we also showed the overactivated mTORC2 pathway and unusual actin polymerization activities in these cells after flow application. Our results reported changes in cell migration by progerin with flow application for the first time and provided potential candidate pathways that were disturbed by progerin under arterial flow, which may help explain the high occurrence of atherosclerotic lesions in HGPS vasculature, even at straight portion. The reported progerin-induced wound recovery defects in endothelial cells in the presence of physiological flow may also suggest a mechanism of how progerin disturbs endothelial integrity and functions under mechanical stimuli in the development of vascular pathologies.</div><div>Further extended studies may help to understand the roles of progerin in initiating atherosclerosis, which will aid in the development of potential therapies for those suffering from prelamin A-associated accelerated aging syndromes.</div>

<p>A high-fat diet can adversely affect bone mechanical properties, but it is unknown how these changes affect bone adaptation. Bone adaptation occurs in response to strain-related mechanisms, and strain in the bone is affected by the size and mechanical properties of the bone.The purpose of this study was to compare the strain during loading in femurs from rats fed a high-fat (HF) or normal control (NC) diet. At 3 weeks of age, male and female Wistar rats were randomly assigned to receive a NC (NC–17% fat; N=8 per gender) or HF diet (HF–41% fat; N=8 per gender) until termination (39 weeks of age). Right femurs were loaded <em>ex vivo</em> in 3-point bending to physiologic levels and mechanical strain was measured. The mechanical properties of the left femurs were determined by 3-point bend tests to failure. The dietary effects were limited in both genders. Femoral cross-sectional area properties (bone area, moment of inertia), determined from µCT scans, were significantly greater in HF femurs vs. NC for males and females. Elastic modulus was calculated from strain and deformation data and no dietary effects were seen in either gender. At the applied loads, despite significantly larger cross-sectional area properties in the HF femurs, there was no significant difference in strain between HF and NC femurs for either gender. It appears that adaptive modeling occurs during growth in the HF bones to target a predetermined level of strain to preserve bone structural integrity.</p> / Master of Applied Science (MASc)

<p>Microfluidic devices using electroosmotic flows (EOFs) in microchannels have been developed and widely applied in chemistry, biology and medicine. Advantages of using these devices include the reduction of reagent consumption and duration for analysis. Moreover the velocity profile of EOFs, in contrast to the parabolic profile found in pressure-driven flows, has a plug-like profile which contributes significantly less to solute dispersion. It also requires no valve to control the flow, which is done with the appropriate application of electrical potentials, thus becomes one of the favourite techniques for sample separation. However, high potentials of several hundred volts are usually required to generate sufficient EOF. These high potentials are not practical for general usage and could cause electrical hazard in some applications. One of the possible solutions is the introduction of zeta potential modulation. The EOF in a microchannel can be controlled by the zeta potential at the liquid/solid interface upon the application of external gate potentials across the channel walls. Combined with AC EOF, it can rectify the oscillating flows and generate pressure that can be used for microfluidic pumping applications. Since the flow induced by the alternating electric field is unsteady and periodic, it is critical to visualize the flow with high spatial and temporal resolutions in order to understand fluid dynamics. A novel method to obtain high temporal resolution for high frequency periodic electrokinetic flows using phase sampling technique in micro particle image velocimetry (PIV) measurements are first developed in order to characterize the AC electroosmotic flow. After that, the principle of zeta potential modulation is demonstrated to transport particles, cells, and other micro organisms using rectified AC EOF in open microchannels. The rectified flow is obtained by synchronous zeta-potential modulation with the driving potential in the microchannel. Subsequently, we found that PDMS might not be the best material for some pumping and biomedical applications as its hydrophobic surface property makes the priming process more difficult in small microchannels and also causes significant protein adsorption from biological samples. A more hydrophilic and biocompatible material, polyurethane (PU), was chosen to replace PDMS. A polyurethane-based soft-lithography microfabrication including its bonding, interconnect integration and in-situ surface modification was developed providing better biocompatibility and pumping performance. Finally, an electroosmotic pumping device driven by zeta potential modulation and fabricated by PU soft lithography was presented. The problem of channel priming is solved by the capillary force induced by the hydrophilic surface. Its flow rate and pressure output were found to be controllable through several parameters such as driving potential, gate potential, applied frequency, and phase lag between the driving and gate potentials.</p> / Doctor of Philosophy (PhD)

Soft material-enabled electronics can demonstrate extreme mechanical flexibility and stretchability. Such compliant, comfortable electronics allow continuous, long-term measurement of biopotentials on the skin. Manufacturing of the stretchable electronic devices is enabled by the recent development combining materials transfer printing and microfabrication. However, the existing method using inorganic materials and multi-layered polymers requires long material preparation time and expensive processing cost due to the requirement of microfabrication tools and complicated transfer printing steps. Here, this study develops a new fabrication method of soft electronics via a micro-replica-molding technique, which allows fast production, multiple use, and low cost by avoiding microfabrication and multiple transfer printing. The core materials, carbon nanomaterials integrated with soft elastomers, further reduces the entire production cost, compared to costly metals such as gold and silver, while offering mechanical compliance. Collectively, skin-wearable electrodes, designed by optimized materials and fabrication method enable a high-fidelity measurement of non-invasive electromyograms on the skin for advanced human-machine interface, targeting prosthesis.

Silk fibroin from silkworm cocoons is found in numerous applications ranging from textiles to medical implants. Its recent adoption as a biomaterial is due to the material's strength, biocompatibility, self-assembling behavior, programmable degradability, optical clarity, and its ability to be functionalized with antibodies and proteins. In the field of bioengineering it has been utilized as a tissue scaffolding, drug delivery system, biosensor, and implantable electrode. This work suggests a new application for porous silk in a microscale chromatography column. We demonstrate in situ cryotropic polymerization of highly porous structures in microscale geometries by freezing aqueous silk with a solvent. The resulting cryogels are experimentally characterized using flow parameters common in chromatography design; tortuosity, global pressure drop, pore diameter, and porosity. These empirical parameters are put into porous flow models to calculate an order-of-magnitude increase in functional surface area over the blank capillaries and packed-sphere columns used in traditional designs. Additionally, the pressure requirements to produce relevant flow rates in these structures are found not to threaten the integrity of microfluidic seals or connectors.

La Radio/Hadron-thérapie consiste à déposer une dose létale de rayonnement dans la tumeur tout en réduisant l'impact de cette dose sur les tissus sains. Les mouvements internes, en particulier ceux engendrés par la respiration modifient la forme, la position et la densité des organes, source d'erreur et d'incertitude sur la position du dépôt de dose. Lorsque la tumeur se trouve sur un organe en mouvement, la dificulté majeure est de cibler la tumeur pendant le traitement. Cette incertitude sur la position rend indispensable la mise en place d'une stratégie permettant la prédiction du mouvement tumoral. Ceci permet en eet de guider le faisceau de rayons ionisants de sorte qu'il suive les mouvements tumoraux. De plus, le traitement par hadronthérapie nécessite également l'accès à une description précise de la densité de l'ensemble des organes traversés par le faisceau, car la position du dépôt maximal de l'énergie véhiculée par les ions (le pic de Bragg) en dépend. Malheureusement, le mouvement respiratoire est complexe et sa prédiction n'est pas une tâche simple – en particulier, la respiration est commandée par l'action indépendante des muscles de la cage thoracique et du diaphragme. Les techniques actuelles basées sur l'imagerie, telles que le Cone-Beam ou le recalage dé- formable d'images, tentent de prédire la position des tumeurs pulmonaires. Ces méthodes font l'hypothèse d'un mouvement reproductible de l'appareil respiratoire dans le temps. D'autres techniques basées sur l'emploi de deux caméras à rayons X (cyberknife, tracking mis au point par l'équipe du Centre carbone d'Heildelberg [HIT]) peuvent permettre la pré- diction de la position des tumeurs, quand leur segmentation et leur contourage automatique en temps réel est possible. Cependant, ces méthodes sont, si ce n'est risquées, invasives, et elles ne permettent pas de calculer l'évolution des organes environnants, une information indispensable pour déterminer la position du pic de Bragg. Ainsi déduire le mouvement de la tumeur à partir de seules séries d'images médicales apparaît comme insuffisant. Une solution peut alors résider dans le développement d'un modèle biomécanique patient-spécifique du système respiratoire intégrant la variabilité du mouvement respiratoire. Pour que ce modèle soit précis, il doit comprendre la modélisation de la cage thoracique, du diaphragme et des poumons. Il est tout aussi important que ce modèle puisse être piloté par des paramètres mesurés en externe (capteurs 3D, spiromètre, etc.) an de préserver un caractère non-invasif et de corréler le mouvement externe du thorax et de l'abdomen, ainsi que le ux d'air échangé avec les mouvements internes. Les changements de propriétés mécaniques des milieux traversés par le faisceau doivent également être modélisés an de satisfaire les besoins de l'hadronthérapie. / The 4D computational patient specic of the respiratory system could be potentially used in various medical contexts; for diagnosis, treatment planning, laparoscopic, dose computation or the registration between online imaging systems such as positron emission tomography (PET), computed-tomography (CT) as well as high delity and precise computer-based training simulators. The main novelty of this PhD project lies in the context of radiation therapy; we have developed a patient-specic biomechanical model of the respiratory system enabling the correlation of the internal organs motion with respiratory surrogate signal(s) during the treatment. This permits to take into account the respiratory motion variabilities. The deformation of the dierent structures is controlled and driven by simulated rib cage (mimic the external intercostal muscles) and diaphragm actions. For the diaphragm, we have applied the radial direction of muscle forces, and simple homogeneous dirichlet boundary condition is applied to the lower part of the diaphragm, which is attached to the rib cage. For each rib a rigid transformation is calculated automatically by nite helical axis method (rigid translation and rotation) and used to dene displacement boundary conditions. The resulting widening of the thoracic cavity forces the lungs to expand due to an applied negative pressure in the pleural cavity. Other novelty of the PhD project, that the amplitude of the lung pressure and diaphragm force are patient-specic, and determined at dierent respiratory states by an optimization framework based on inverse FE analysis methodology, by minimizing the volume lungs errors, between the respiratory volume (calculated from CT scan images at each state) and the simulated volume (calculated by biomechanical simulation). All other structures are linked to each other, but feature dierent deformation behavior due to the assigned material properties. Our results are quite realistic compared to the 4D CT scan images and the proposed physically-based FE model is able to predict correctly the respiratory motion