Introduction: A prosthesis can be used to regain function after an amputation of the lower limbs. Conventionally, the prosthesis is connected to the stump using a tight fitting socket. The socket often leads to sweating, skin problems or discomfort while sitting. A new way of prosthetic attachment is by osseointegration. During osseointegration surgery a titanium implant is fixed to the remainder of the femur. The prosthesis can be attached to the extra- corporeal part of the implant called the abutment. In this way, socket related problems can be avoided. Qualitative analyses have reported improved walking ability, prosthetic use and a higher prosthesis related quality of life in patients using an osseointegrated prosthesis, but not much is known yet on quantitative improvements in gait measured in a clinical setting. Therefore this study mainly aims to compose and execute a measurement protocol for clin- ical quantitative gait analysis of unilateral transfemoral amputees using an osseointegrated prostheses. Furthermore, a biomechanical model will be created using OpenSim and will be validated using the data recorded using the clinical measurements.
Method: A measurement protocol for quantative gait analysis in a clinical setting was cre- ated and carried out by measuring one participant using an osseointegrated prosthesis. The participant walked at self selected walking speed across a runway with force plates built in and walked on the floor next to the runway with equal conditions around. The protocol also included measurements for stability and direction of attention during gait trials. A biome- chanical model of a unilateral transfemoral amputee with an osseointegrated prosthesis was developed using OpenSim. Bones and muscles of one leg were replaced by prosthetic ge- ometry and settings were altered. The model was used to analyse kinematics and kinetics. Results: Spatiotemporal differences were found between the floor and runway condition. Kinematic comparison showed significantly different knee flexion for the intact leg for a small phase in the gait cycle. Despite the spatiotemporal differences were significant, these were mostly small. Together with the lack of kinematic differences, the difference between the two was not considered clinically relevant and only the runway condition was included in the results section. Kinematic and kinetic results were plotted against control values mea- sured with healthy controls. Compared to these controls the prosthetic side showed a larger hip extension peak, no ankle plantairflexion peak, a larger hip flexion moment, absence of a characteristic knee flexion moment and a lower ankle plantairflexion moment. For the intact side the most noticeable differences were a knee flexion and ankle plantairflexion peak later in the gait cycle, lower hip extension moment and a higher knee flexion moment. Further- more, prosthetic side Margin of Stability was higher, around 60% of the bodyweight was carried by the intact leg during standing up from and sitting down on a chair and the direc- tion of attention was more focused downwards during the floor condition measurement. Conclusion: The aim of that the development of a measurement protocol including a biome- chanical model to measure and analyse the gait of a transfemoral amputee using an os- seointegrated prosthesis is achieved. The results from several analyses were compareable to results found in literature, which served as a validation for the model developed in this study.

The ability to simulate the impact on performance of military body-borne loads enables effective analysis and optimisation of load and equipment configurations for military personnel performance. Additionally, these simulations can reduce research & development costs of new equipment by analysing its impact in an early stage of development. While research has been done into the effects of body borne loads on kinematics, ground reaction forces (GRF) and metabolic cost of transport, the accuracy and reliability of simulations are not clear yet.
This study set out to predict loaded gait kinematics and GRFs and estimate metabolic cost of transport for gait at 1.5 m/s, carrying different types of military relevant body-borne loads, to evaluate the applied methods for implementation in a future load configuration optimisation tool.
The kinematic/GRF prediction was performed by forward dynamics simulations in SCONE/hyfydy, using a planar musculoskeletal model and a 2 gait-state controller, simulating 15 solutions for each load condition. While only 60% of experimentally measured differences between load conditions were correctly predicted, the expected differences from literature were all correctly predicted. It was assessed that improving the number of gait states and the number of optimisations per load condition is expected to improve these results.
The metabolic cost of transport (mCoT) estimation was performed by the Computed Muscle Control algorithm of OpenSim, using experimental kinematics and ground reaction forces. However, small compounding errors in experimental data and data processing prevented accurate mCoT estimations. Although the applied kinematic/GRF and mCoT simulation methods could not be validated yet, based on these results, the study as a whole does show promise for the continued development of these models and their future implementation for loaded gait performance optimisation.

Background: Abnormal patellofemoral joint loading patterns may cause patellofemoral pain and may be caused by patellar maltracking. Treatment is aimed at restoring normative patellofemoral kinematics. For this, an accurate estimation of the patellofemoral kinematics is necessary. While 4-dimensional computed tomography (4D-CT) can provide this by capturing bone geometries, this equipment is not commonly available in clinical settings and requires radiation. Optical Motion Capture (OMC) with a grid of markers overlying the bone has shown promising results for measuring scapular and patellofemoral kinematics.
Objective: The aim of this study is to develop and validate a new method to estimate patellofemoral kinematics from OMC by applying a shape fitting algorithm to a knee marker grid.
Methods: Five participants were equipped with a knee marker grid and performed a prone extension-flexion movement during which kinematics were measured using OMC and 4D-CT. Patellofemoral kinematics were estimated using three methods: Geometry-based 4D-CT, Grid-based 4D-CT, and Grid-based OMC. In Geometry-based 4D-CT, PF kinematics were obtained from bone geometries. In both Grid-based methods, a shape fitting algorithm using an Iterative Closest Point algorithm estimated the patellofemoral kinematics from the locations of the grid markers. For validation, both 4D-CT methods were compared, as well as both Grid-based methods. To quantify the validity of the new method, root mean square errors (RMSEs) of the differences between the methods and Spearman correlation coefficients were computed.
Results: For Geometry-based 4D-CT vs. Grid-based 4D-CT, the RMSEs of the differences were 7° for flexion and 3 to 10 mm for all translations, combined with very high correlations. The RMSEs for tilt and spin were over 18°, combined with low and moderate negative correlations. For Grid-based 4D-CT vs. Grid-based OMC, RMSEs were smallest for ML translation (4 mm) and spin and tilt (< 6°), but these were paired with moderate correlations. On the other hand, the higher RMSEs for flexion (9°) and AP and SI translation (> 10 mm) were paired with moderate to very high correlations.
Conclusion: Comparing the 4D-CT methods indicated that spin and tilt could not be measured accurately using the marker grid, which are both clinical relevant. Comparing the Grid-based methods showed large differences between OMC and 4D-CT, probably introduced by the accuracy of the measurement system. Overall, the shape fitting algorithm thus seems to be able to estimate PF flexion and all three PF translations from a marker grid, but applying it to OMC data is not valid yet.

The knee is the most common joint affected by osteoarthritis (OA). Evaluating knee cartilage in MRI is usually done under non-loading conditions. However, load-bearing is a key capacity of cartilage, so using compression may be a tool for clinicians to identify early OA. A loading device could simulate weight-bearing conditions in a supine position. This report presents the development of an MRI-compatible knee loading device, following the double diamond method and the V-model.

The most important requirement are that the device must apply an axial, accurate, and adjustable load through the foot to the patient’s knee in a supine position. The device should be able to apply different small knee flexion angles. Existing loading devices, MRI procedures, knee biomechanics, and potential risks were analyzed to establish a comprehensive set of requirements. A knee loading device has been developed where a balance needed to be found between feasibility, functionality and complexity, with feasibility as the main priority to ensure a working foundation for further enhancements.

A biomechanical analysis was conducted to understand the impact of applying compression to the knee in a supine position on the internal joint moments, which reflects the effort that needs to be provided by the patient. Adjustments in knee flexion angle and the height of the applied load at the foot were made to evaluate their effect. The results showed that a 10° knee flexion with a load application through the ankle requires the least effort from the patient, making it the most feasible loading condition to maintain stable for several minutes. For the design, this meant that the height of the footplate was set twice the distance between the bottom of the calcaneus and the position where the load goes through the ankle. Although 10° knee flexion might the most feasible loading condition, it does not necessarily mean it is
the best indicator for early OA. Therefore, the device still needs to enable different knee flexion angles.

The load is applied at the foot through a footplate, which slides along axes. To generate the load, elongating elastic material was chosen because of its practicality and safety. Suspended weights were excluded, as they require an inconvenient set-up and are not safe in case of emergency. Since a setup with suspended weights requires more space and covers both the patient bed and MRI table, it is not possible to disconnect the MRI table from the MRI scanner rapidly. The final design of the MRI knee loader ensures the patient can be positioned, and the load could be applied without having to change the position. To make the load generation feasible for radiology laboratory personnel, a driving wheel and pulley systems were incorporated to reduce the force required at the wheel. Additionally, a knee support is implemented to apply a knee flexion angle to the patient.

A prototype has been manufactured to evaluate the functional application of the applied load and knee flexion angle, as well as patient compatibility. It included the essential functional components: the footplate, knee support and the plates they are connected to. The prototype demonstrated the capability of applying a load to the foot in an experimental set-up. A linear relation was found between the input force and the measured force at the footplate, mimicking the load that is applied at the foot. Unfortunately, the measured force was not sufficiently accurate and the variation between the repeated measurements was found substantial. It was argued that this was due to the friction in the current design.

Further design improvements are required to overcome the limitations of this design. Compromises were done to improve feasibility, but it could be analysed how the functionality and accuracy could be improved. A starting point could be to find a better fit between the bearings in the footplate and the axes, to reduce friction and ensure a more accurate application of the load. The footplate should be redesigned so it does not clamp. Moreover, the complete final design of the MRI knee loader (including the footplate, knee support and their connection plate, as manufactured in the prototype, as well as the driving wheel and the table with the double bottom embedding the cable and elastic) must be produced to verify and validate the device’s overall functionality, patient compatibility, suitability within the MRI
environment and workflows, and operational ability by the MRI laboratory personnel.

Osteoarthritis (OA) is a progressive joint degeneration disease resulting in joint pain, stiffness, and loss of mobility. Among patients with anterior cruciate ligament reconstruction (ACLR), OA incidence is increased. Articular cartilage (AC) degeneration is irreversible, therefore prevention and early detection are essential. Specifically, the possibility to predict the risk of AC degeneration would provide options for patient-specific early interventions.

This thesis presents a Finite Element (FE) workflow for a patient-specific FE knee model of a patient with ACLR. A degeneration algorithm is implemented to predict AC degeneration. Uncertainties in the parameters of a FE workflow can affect the model's outcome. The sensitivity of the workflow to the AC and meniscal Young's moduli should be determined, as these influence the stress distribution in the joint but in-vivo measurement is not possible for patient-specific values. Therefore, the developed FE knee model is used to answer the main research question: how sensitive is the predicted AC degeneration of a patient-specific Finite Element ACL reconstructed knee model to changes in the AC and meniscal Young's moduli?

The FE knee model was created based on patient-specific MRI and gait analysis data. For the sensitivity analysis, 24 models were simulated with AC and meniscal Young's moduli varying between 5 MPa and 35 MPa, and 59 MPa and 80 MPa, respectively. A degeneration algorithm was implemented for the calculation of AC degeneration, based on max principal stresses.

Minimal AC degeneration was calculated for both the tibial AC and the femoral AC, ranging from no degeneration to a degeneration level of 0.9812, and 0.9694, respectively. The 5-year follow-up MRI showed no AC degeneration either. Statistical analysis was performed with the volume of degenerated AC. A multiple regression analysis showed an exponential relationship between the degenerated volume and the AC Young's modulus for the tibial AC (R² = 0.995, p<0.05), and the femoral AC (R² = 0.989, p<0.05). The meniscal Young's modulus did not affect the degenerated volume. The sensitivity analysis demonstrated that increasing AC Young's modulus resulted in an exponentially larger volume of degeneration.

In conclusion, the established FE workflow showed promise for the calculation of AC degeneration following ACLR. A foundation was laid for future development of the model. The sensitivity of the workflow to the AC Young's modulus was determined, highlighting the need for patient-specific estimation of the AC Young's modulus for reliable patient-specific AC degeneration results.

Anterior cruciate ligament tears are a common injury, with over two million people affected annually. Typically, magnetic resonance imaging is used to diagnose the injury, but this technique is less sensitive in evaluating incomplete or concomitant injuries. Four-dimensional computed tomography is a relatively new technique that can become commonly available in the clinical setting. It allows for dynamic imaging, which may be suited for evaluating a change in knee kinematics after ACL in movements like flexion/extension. This may be used to gain insight into the function of the anterior cruciate ligament or surrounding ligaments which informs surgical decision-making and might prevent or alter intended surgeries.
This thesis aims to answer the following research question; How can four-dimensional computed tomography scans of the tibiofemoral joint made during unloaded flexion/extension movements be meaningfully visualized and can it be used to detect kinematic differences between a knee with a complete anterior cruciate ligament tear and an uninjured one? To do so, both knees of eight patients with a unilateral complete anterior cruciate ligament tear were scanned during a simultaneous flexion/ex- tension movement in the four-dimensional computed tomography scanner. A workflow was created that consists of four steps; the segmentation, the registration, the definition of anatomical coordinate systems, and the visualization of the kinematic measures in three different ways. Almost all steps of this workflow were automated and open-source programs were used where possible throughout the workflow to facilitate easy usage. However, some manual steps are still required. The kinematic measures were expressed in three different ways. First, the rotations between the anatomical coordinate systems of the femur and tibia were calculated using Euler decomposition alongside the translations. In addition, a plot of the intercondylar axes was made, which shows the movement of the mediolateral axis of the femur relative to the tibia during flexion/extension. Finally, to obtain the kinematics at the articulation surface, an OpenSim Joint and Articular Mechanics simulation was set up to simulate the movement using the patient-specific information obtained from the four-dimensional computed tomography scans. Based on this simulation, the centres of proximity were plotted for both the tibia and the femur. The distances between the subsequent centres of proximity were then evaluated for a set of flexion angles to gain insight into the type of movement occurring (e.g., roll or slip).
Minor differences for the mean translations and rotations were seen between the anterior cruciate ligament deficient and the uninjured knees. Only in the anterior-posterior translation a statistically significant (p=0.023) increase could be seen at extension and the lower flexion angles (±-5∘ to ±15∘) for the anterior cruciate ligament deficient knees. No noteworthy differences were present for all other degrees of freedom. Differences were more apparent in the plots of the intercondylar axes. Here, the increased anterior-posterior translation was more prominent for anterior cruciate ligament deficient knees than for uninjured ones. Lastly, the centres of proximity showed substantial differences among patients, obscuring the determination of a pattern to distinguish between anterior cruciate ligament deficient and uninjured knees. However, these plots did show a substantial difference compared to the plots of the intercondylar axes. This may be due to slip occurring at the articulation surface and would mean that plotting the intercondylar axes does not adequately represent the kinematics of the articular surface throughout the whole range of motion of the knee.
Overall, some minor kinematic differences during flexion/extension can be seen in the graphs of the translations and rotations and the plots of the intercondylar axes. The plots of the intercondylar axes showed the most apparent differences, but they may not represent the situation at the articulation surface. Therefore the centres of proximity are better suited to gain information about the articulation surface. Still, due to the differences among patients, a pattern to distinguish between anterior cruciate ligament deficient and uninjured knees could not be determined. Altogether, this technique may not be suited as a tool to evaluate knee injuries in all patients, but only in patients that are expected to cope very well with the injury or where a concomitant injury is expected. However, future research should still evaluate the performance of the workflow for these situations.

Children with cerebral palsy (CP) commonly have bony deformities of the foot, which lead to pain and gait problems. One of the causes of such a deformity is an imbalance in muscle forces around the foot. In turn, the bony deformity can also alter muscle function, due to, for example, altered muscle moment arm lengths. In this study, the altered muscle function due to hindfoot varus deformities in children with CP was investigated using musculoskeletal models. The first aim of this study was to create personalized musculoskeletal models of the foot based on weight-bearing computed tomography (WBCT) data. Secondly, we applied the model to get insight in how joint axis orientations and muscle moment arms are altered in varus feet, and how this leads to differences in muscle function during gait.
Models were created in OpenSim for seven children with a hindfoot varus deformity due to CP, and four adults with neutral feet. Each model was based on WBCT scans and included five degrees of freedom in the foot (talocrural, subtalar, Chopart, Lisfranc and metatarsophalangeal joints). The orientations of the foot joint axes and moment arms of the extrinsic foot muscles were calculated. Subsequently, the models were combined with motion capture and ground reaction force data to calculate muscle activations during gait.
The joint axis orientations showed greater variability in the group of children with CP compared to the control group; in most subjects, changes in axis orientation were observed that may lead to a more rigid foot. Furthermore, the dorsiflexion moment arm of the tibialis anterior decreased, while the inversion moment arm increased; thus, the tibialis anterior became an even more effective invertor when a varus deformity of the foot was present. On the other hand, the eversion moment arms of the peroneal muscles tended to become smaller, meaning they would be less effective in resisting the varus deformity. Static Optimization results showed decreased activity in the tibialis muscles, and increased activity in the peroneal muscles. This increased activity might be necessary due to the smaller moment arms, and/or to stabilize the ankle.
This is the first study in which a musculoskeletal foot model was developed based on personalized bone data of feet with bony deformities in weight-bearing conditions. Distinct changes were shown in muscle function when a varus deformity is present, which might lead to progression of the deformity. This contributes to a better understanding of the altered muscle function due to foot deformities, which may eventually contribute to improvement of treatment to prevent the progression of foot deformities.