http://hdl.handle.net/2268.2/2004 Mon, 07 Sep 2026 15:22:33 GMT 2026-09-07T15:22:33Z http://hdl.handle.net/2268.2/26202 Title: Master thesis : Micromechanical Investigation of Trabecular and Cortical Bone During Aging (including introduction to research methodology) Abstract: Population ageing has become a major societal and healthcare challenge worldwide. As life expectancy increases, age-related deterioration of the musculoskeletal system becomes increasingly prevalent, leading to a progressive loss of bone strength and a higher risk of fragility fractures. Among the skeletal sites affected by age-related bone loss, the distal radius is particularly vulnerable, with wrist fractures frequently occurring early in the progression of skeletal fragility. Although age-related changes in trabecular and cortical bone microarchitecture have been extensively documented, their mechanical consequences and spatial distribution within the distal radius remain incompletely understood. This thesis investigates how ageing affects the microstructure and local mechanical behaviour of the distal radius in postmenopausal women, with particular emphasis on the relationships between age-related morphological deterioration and deformation patterns within trabecular and cortical bone. To achieve this objective, a multiscale and region-specific approach combining high-resolution micro-computed tomography (micro-CT) and voxel-based micro-finite element (micro-FE) modelling was developed. Twelve distal radii from postmenopausal female donors were analysed and divided into middle-aged and old groups. Following micro-CT acquisition and image processing, trabecular and cortical morphometric parameters were quantified using image analysis techniques. In parallel, voxel-based micro-finite element models were generated directly from the segmented images and solved using the ParOSol solver under physiological loading conditions. The resulting strain and stress distributions were then compared with morphological parameters extracted from image analysis at several spatial scales. In particular, local trabecular analyses were performed using 5 mm cubic volumes of interest combined with numerical homogenization, while local cortical analyses were conducted by dividing the cortex into sixteen angular sectors to investigate the spatial relationships between cortical thickness and deformation. The results obtained revealed a clear age-related deterioration of both trabecular and cortical bone microarchitecture. At the scale of the whole distal radius, older specimens exhibited lower trabecular bone volume fraction, reduced trabecular thickness, thinner cortices, smaller cortical areas and increased intracortical porosity. However, when the analysis was restricted to the clinically relevant region, age-related trabecular differences became negligible, suggesting that most trabecular deterioration is concentrated in the distal epiphyseal region. In contrast, cortical alterations remained pronounced and closely reflected those observed at the scale of the whole distal radius. In addition, mechanical analyses demonstrated higher deformation levels in older individuals in both compartments, with a proportionally greater age-related increase observed in cortical bone. At a more local scale, trabecular analyses further showed that effective strain could not be explained by the homogenized Young’s modulus alone. Although regions with higher bone volume fractions generally exhibited higher apparent stiffness, cubes displaying similar homogenized elastic properties often experienced markedly different deformation levels depending on their anatomical location within the trabecular compartment. Finally, the cortical sector-based analysis revealed strong spatial heterogeneity, with the anterior cortex consistently exhibiting the highest deformation levels despite remaining the thickest cortical region. Overall, this work demonstrates that the mechanical consequences of ageing arise from complex interactions between trabecular deterioration, cortical degradation and whole-bone load redistribution mechanisms. Age-related fragility cannot be explained by a single morphological parameter or by the deterioration of a single anatomical region. Instead, the local mechanical response of the distal radius depends on the combined influence of bone microstructure, anatomical location and structural interactions occurring across multiple spatial scales. Taken together, these findings contribute to a better understanding of the mechanisms underlying distal radius fragility during ageing. Sun, 28 Jun 2026 22:00:00 GMT http://hdl.handle.net/2268.2/26202 2026-06-28T22:00:00Z http://hdl.handle.net/2268.2/26190 Title: Master thesis : Investigation of Homeostatic Compensatory Mechanisms to Maintain Slow and Regular Pacemaking in Midbrain Dopamine Neurons Abstract: Midbrain dopaminergic neurons are cells capable of spontaneously generating a slow and regular rhythmic electrical activity, known as pacemaking activity. This property is essential for maintaining a basal concentration of dopamine in the striatum and plays a central role in motor control and reward-related behaviors. In the context of Parkinson's disease, the progressive degeneration of these neurons is directly linked to mitochondrial oxidative stress triggered by the continuous influx of calcium through L-type calcium channels (Cav1.3), which are active during pacemaking. The pharmacological blockade of these channels using isradipine had been proposed as a neuroprotective strategy, supported by promising results in mice. However, the clinical trial conducted in 2020 demonstrated no significant benefit in humans, suggesting an incomplete understanding of the underlying biophysical mechanisms such as the homeostatic compensatory mechanisms. Furthermore, the precise identity of the current responsible for pacemaking remains debated, and a recent hypothesis proposes the existence of a current called I,XG or I,Pace as the primary engine of the autonomous rhythm. This work aims to investigate, through numerical simulation, the homeostatic compensatory mechanisms that allow dopaminergic neurons to maintain their pacemaking activity when faced with targeted pharmacological perturbations. To this end, a homeostatic controller based on intracellular calcium dynamics is integrated into two distinct conductance-based models: the Yu model, a classical reference model, and the Fyon model, which incorporates the gPace conductance representing the hypothesized I,XG current. Simulations are first conducted on a single average neuron and then extended to heterogeneous populations of 200 neurons, in order to account for the biological variability observed in vivo. The results reveal a fundamental difference in robustness between the two models. The Fyon model faithfully reproduces known physiological characteristics: the blockade of HCN channels or A-type potassium channels does not significantly disrupt pacemaking activity at the population scale, in agreement with experimental data. In contrast, the Yu model fails to maintain this activity when faced with the same perturbations, illustrating its intrinsic fragility linked to non-physiological activation parameters. Upon the blockade of Cav1.3 channels, the homeostatic controller drives the calcium concentration back toward its target value in both models, but only the Fyon model preserves rhythmic electrical activity in a large majority of neurons (79%), thanks to the presence of gPace which provides the residual depolarizing current required to cross the excitability threshold. This long-term calcium recovery, observed across the entire population, directly neutralizes the reduction in calcium influx initially induced by the blockade, thereby undermining the neuroprotective effect that was sought. This observation furthermore highlights a fundamental distinction between calcium homeostasis and electrical rhythm homeostasis: the recovery of the calcium signal does not, on its own, guarantee the restoration of pacemaking. At the population scale, blocking L-type channels in the Fyon model reveals a trend toward frequency deceleration and the emergence of bursting activities, suggesting that chronic homeostatic compensations could further counteract the desired neuroprotective effect. Finally, the complete blockade of gPace leads to a loss of activity in 96.5% of the neurons in the population, validating the indispensable role of this conductance as the engine of the autonomous rhythm. Ultimately, this work provides two complementary computational perspectives on the reasons behind the failure of the isradipine clinical trial: first, the long-term homeostatic recovery of calcium influx directly neutralizes the intended neuroprotective effect; second, the compensatory mechanisms drive a subset of neurons toward bursting discharge regimes that are potentially less neuroprotective. These findings underscore the importance of a detailed understanding of the biophysical mechanisms of pacemaking for designing therapeutic strategies capable of anticipating long-term homeostatic compensations. Sun, 28 Jun 2026 22:00:00 GMT http://hdl.handle.net/2268.2/26190 2026-06-28T22:00:00Z http://hdl.handle.net/2268.2/26183 Title: Master thesis : Optimization of a tomosynthesis trajectory on an existing CT system (including introduction to research methodology) Abstract: This master thesis investigates the optimization of tomosynthesis acquisition trajectories for the Dx-Box C5 multi-axis X-ray inspection system developed by X-RIS. The Dx-Box C5 combines a C-arm with a five-axis motion stage, enabling flexible acquisition geometries for industrial non-destructive testing. The objective of this work is to identify the acquisition trajectories that achieve the best image quality. Four simple trajectories and several combined configurations were evaluated through numerical simulations performed using the gVXR framework. Image quality was assessed using a composite score combining contrast and depth resolution metrics. The results show that rotational trajectories provide better depth localization, while translation trajectories yield higher contrast. Among all configurations evaluated, the R1-R2 combination (combining C-arm rotation and turntable rotation) achieved the highest overall score and is identified as the most suitable trajectory for implementation on the Dx-Box C5 system. Sun, 28 Jun 2026 22:00:00 GMT http://hdl.handle.net/2268.2/26183 2026-06-28T22:00:00Z http://hdl.handle.net/2268.2/26149 Title: Master thesis : Multi-echo 23Na MRI Sequence Evaluation for Quantitative Mapping (including introduction to research methodology) Abstract: Sodium magnetic resonance imaging (23Na MRI) is a promising imaging modality that provides information on tissue viability and cellular homeostasis beyond what can be obtained with conventional hydrogen MRI. However, its clinical and research applications remain challenging because of the low sodium concentration in vivo, its lower gyromagnetic ratio, and the rapid decay of the MR signal, which result in a low signal-to-noise ratio (SNR). The first objective of this thesis was to optimize sodium MRI acquisition parameters in order to maximize SNR while maintaining clinically acceptable acquisition times and respecting specific absorption rate (SAR) constraints. A theoretical optimization framework based on the signal equation of spoiled gradient-echo imaging was developed and experimentally validated using homogeneous sodium phantoms. This approach enabled the determination of an optimal combination of repetition time, flip angle, and number of radial projections. The second objective was the development and evaluation of quantitative sodium relaxation mapping methods. Longitudinal relaxation times (T1) were estimated using the variable flip angle method, while effective transverse relaxation times (T2*) were obtained from multi-echo acquisitions combined with voxel-wise fitting procedures. The performance of conventional Ultra-Short Echo Time (UTE) imaging was compared with Density-Adapted Radial Acquisition (DARAD), a sampling strategy designed to improve acquisition efficiency and image quality in sodium MRI. Phantom experiments demonstrated that DARAD acquisitions produced more homogeneous parameter maps and narrower relaxation time distributions than conventional UTE acquisitions. The proposed methodology was subsequently applied to human brain imaging, where quantitative T1 and T2* maps were generated. The results suggest that density-adapted radial sampling improves the robustness and precision of sodium relaxation parameter estimation. Overall, this work demonstrates the feasibility of quantitative sodium relaxation mapping at 7T and highlights the advantages of DARAD acquisitions for sodium MRI. Sun, 28 Jun 2026 22:00:00 GMT http://hdl.handle.net/2268.2/26149 2026-06-28T22:00:00Z