Muscle-tendon paths vary between individuals, and musculoskeletal models show sensitivity to these variations when estimating muscle and joint forces. Accurate estimations of these internal forces allow for a more comprehensive approach to researching debilitating musculoskeletal pathologies such as osteoarthritis. However, defining subject-specific muscle-tendon paths is labour-intensive and requires expert knowledge, which is not as repeatable. Therefore, in this study, the accuracy of determining subject-specific muscle points and volumes based on lower limb Magnetic Resonance (MR) scans with the nnU-net is evaluated. Two models are trained using the open-source pipeline, referred to as the point and volume model. The volume model aims to segment muscle-tendon volumes and is trained on the open-source augmented dataset of Henson et al. (2023). The point model localises attachment and via points describing muscle action lines for a subset of relevant muscles of the volume model. Since U-net is not designed for predicting points, a workaround is introduced by creating cubes around the points as labels. The 3D volume model scored a median Dice Similarity Coecient of 92.7 % and shows some generalisation capability. The 3D point model scored a median Euclidean error of 5.1 mm. Compared to intra-operator variability for attachment points, this approach yields lower and more repeatable accuracy without required manual intervention. The nnU-net pipeline is capable of producing accurate models that can define subject-specific muscle-tendon paths based on MR scans.

Knee osteoarthritis (KOA) is one of the most prevalent joint disease worldwide. Musculoskeletal modeling (MSM) provides a useful tool to investigate knee joint biomechanics and potential development and progression of KOA. However, for clinical usage, it is crucial to understand how patient-specific properties affect MSM outcomes. This study investigated how uncertainty in the tendon slack length (TSL) of lower limb muscles affect knee joint reaction forces (JRFs) in gait analysis. Two sensitivity analyses were performed, one approach used reported TSL variation in literature and the other approach used a percentage TSL variation. Anatomical variation was investigated through a literature review. The JRF estimations of both approaches together resulted in a maximum variation of 0.27 x BW in AP direction, 2 x BW in SI direction and 0.13 x BW in ML direction. Maximum JRF estimations resulting from reported TSL variation were larger in the loading response in all direction. Maximum JRF estimations in ML direction were resulting from percentage variation. TSL of muscles that were found to be most influential in JRF estimations were medial gastrocnemius, rectus femoris, vastus lateralis and psoas. This research confirmed that within patient-specific MSM for clinical purposes, uncertainty in TSL should be limited. Future research should aim to investigate how this influences AC degeneration for KOA.

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.

Knee osteoarthritis is a common joint disease, affecting the knee joint. To help slow down the degeneration of cartilage, changing people's gait is a known solution. The most common modification is teaching people to walk toeing-in or toeing-out, changing their foot progression angle (FPA). However, it is still unclear what the effect is of changing the FPA on other gait parameters and lower joint kinetics. Changing the FPA, also changes gait parameters such as gait speed, step width, stride length, trunk lean, and medial thrust. It is hypothesized that lower joint kinetics are negatively affected when altering the FPA. This thesis focuses on the effect on the lower joint kinetics and on the gait parameters when changing the FPA.

Tests are done on healthy subjects with four FPA alterations besides normal gait, a small and large angle toeing-in and toeing-out. A haptic feedback device is used that contains vibrating motors located at the medial and lateral side of the calf to teach participants to walk in the desired angle. First participants are asked about the ease of use and comfort of the haptic feedback system. Second, the knee adduction moment (KAM) and knee flexion moment (KFM) are measured for each participant to evaluate the effect of the different FPA's. Third, the moments in the lower joints, hip and ankle, are measured to research the effect of different FPA's on the loading within these joints. This load is measured at peak value and as area under the graph. Lastly, there is researched what gait parameters participants alter when changing the FPA. The thesis mainly focuses on the effect on the lower joint kinetics since literature still shows a gap here.

The haptic feedback resulted comfortable for most participants, the ease to achieve a high amount of correct steps within the asked FPA appeared more difficult. Changing the FPA to reduce the KAM, showed for the participants different angles that maximally reduces the KAM. Highlighting the importance of a personalized approach. The hip adduction moment and ankle moment both increase overall for the participants. While the hip rotation and flexion moment show a mean reduction. Making it important to focus most on the hip adduction moment and ankle moment, and how to lower these increases in moment. Otherwise this could result in hip osteoarthritis. Different FPA's also change the impact of the gait parameters for the participants. Indicating participants to change their entire posture when adapting different angles. Resulting more aspects to focus on when learning participants to walk differently.

To conclude, changes in the FPA have effect on the KAM, gait parameters, and on the lower joint kinetics. The reduction on KAM differs per participant, indicating a personalized approach. Gait parameters change when applying FPA's, mainly gait speed, stride length and step width change for most participants. Measurements on the lower joint kinetics show interesting insights on the effect of changing the FPA. Highlighting the hip adduction moment and ankle moment to focus on to prevent possible excessive load and damage.

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.

Image registration combines data from multiple imaging modalities or time points by aligning images. Existing 2D-3D registration methods often require manual intervention, introducing variability and increasing processing time, and rely on Computed Tomography (CT) imaging, which exposes patients to radiation. This study aims to develop an automated registration pipeline that ensures accurate registration between 3D Magnetic Resonance Imaging (MRI) and 2D fluoroscopic images by preprocessing techniques.

This study involved two registration experiments to evaluate the pipeline. The DiffDRR package was used with normalized cross-correlation (NCC) as similarity metric and gradient-based Adam optimizer for optimization. The first experiment validated the accuracy of registration between 3D MRI models (solid bone, empty shell, and filled shell) and 2D CT-derived digitally reconstructed radiographs (DRRs) with known rotations and translations as reference standard. The second experiment aimed to determine the most effective fluoroscopy preprocessing technique for aligning 3D MRI models with 2D fluoroscopic images. Preprocessing techniques for the fluoroscopic images included contrast enhancement via thresholding and normalization, and region of interest selection or segmentation.

Validation results showed smaller rotational and translational errors for both shell models compared to the solid bone model. In-plane errors for the shell models were 0.1-3.3mm and out-of-plane 15.8-55.0mm, while solid bone reported in-plane errors of 1.0-4.7mm and out-of-plane of 68.3-282.7mm. Registration between empty shell models and differently preprocessed fluoroscopic images showed that segmentation of the bones in fluoroscopic images yielded the highest NCC values. However, visual assessment revealed inconsistencies in plausible bone positioning.

This automated 2D-3D registration method shows potential for registration between 3D MRI and 2D fluoroscopic images of the knee joint. The current method requires further refinement, particularly in integrating soft tissue data, possibly via synthetic CTs, and adopting more anatomically sensitive metrics, such as mutual information or gradient correlation.

Critically ill, mechanically ventilated patients require a substantial amount of energy to meet their basic metabolic demands, as well as for their recovery, spontaneous breathing, gaining of strength, and weaning from the ventilator. It is important for patients to use their energy as efficient as possible at all stages of the disease and recovery. Physicians need to estimate and match the energy cost of the treatment regimen with the patient’s ability for energy expenditure. If the demands of the treatment regimen, such as weaning from the ventilator, are too high, it will lead to exertion and fatigue. On the other hand, if the patient is not challenged enough, it could lead to a slower recovery and prolonged admission to the Intensive Care Unit (ICU). For example, it is known that a too slow reduction in ventilator support can lead to atrophy of the diaphragm, resulting in prolonged ventilation time.
Predicting successful extubation is crucial for mechanically ventilated ICU patients. Prolonged intubation leads to prolonged mechanical ventilation, which is known to have adverse effects. Up to 20 % of all ICU patients fail to wean from mechanical ventilation. Therefore, it is crucial to investigate different parameters of effort. This will be elaborated on in Chapter 1 of the thesis. The oxygen consumption seems to be a good new parameter to add in standard of care.

To measure oxygen consumption (VO2) breath-by-breath, it is necessary to synchronize flow and oxygen concentration data. To create this algorithm, it was necessary to design an in vitro test setup that correctly mimics the mechanically ventilated ICU patient. This setup and the plan of requirements is described in Chapter 2. In the test setup a cylinder was used with N2 and CO2 to simulate oxygen consumption and CO2 production.

The algorithm developed using the data generated with the test setup using the Hamilton Mechanical Ventilator C6 flow data and the Masimo ISA OR+ oxygen concentration data, is used to synchronize the data from the two devices and to determine the VO2. As the rise time of the oxygen sensor in the Masimo was slow, this signal needed some adaptions. Furthermore, the time stamps were not the same, as with the sample frequency. After the synchronization, the VO2 was derived by taking the integral of the two synchronized signals per breath. These values were compared to predicted values, derived from breath-by-breath parameter data of the two devices. All the preprocessing, synchronization and eventual oxygen consumption measurements are described in Chapter 3.

As there were too many assumptions in the design of the in vitro test setup, it was necessary to create a new setup with minimized number of assumptions. This new test setup had two extra flow sensors in order to monitor all leaks and flows. Next to the more reliable data from the setup, some simulation data was created using Python. Both data were used to validate the algorithm. These steps were explained in Chapter 4.

In Chapter 5 some perspectives for the future were explained. This includes the integration of the VO2 in clinical practice and the steps that still need to be taken to come that far. These include testing on patient data and performing more clinical trials.

Background: Knee Osteoarthritis (KOA) is the predominant form of osteoarthritis, and its incidence is anticipated to rise due to an ageing and increasingly overweight population. Altering the Foot Progression Angle (FPA) has demonstrated potential in mitigating the progression of KOA. Wearable feedback methods, especially those utilising single IMU sensors, have gained prominence for their cost-effectiveness, time efficiency, and potential for real-world application in FPA alteration training. This study collaboratively advances the "Knee Wear project" with the objective of designing and validating an FPA estimating algorithm during straight-line walking using the Xsens DOT sensor.

Methods: This study proposed a calibration method for sensor-to-foot orientation by developing a sensor-to-shoe fixture for consistent sensor alignment with foot direction. While static calibration remained necessary, it eliminated the need for complete sensor fixation to the shoe or dynamic calibration before each use. The fixture's concept was verified by measuring sensor-to-shoe orientation post-fixture attachment to the shoe together with the sensor's fixating capability on the shoe. Additionally, the difference in FPA estimation utilising the dynamic and the fixture calibration method was examined. The FPA algorithm that estimated the FPA during the mid-stance phase, utilised the orientation estimation of the Xsens DOT sensor, in combination with a heading reset to compensate for magnetic disturbances. Two FPA estimation approaches were tested: one utilising the trajectory estimation of the stride and another the peak deceleration point during the late swing phase. Experiments on 13 participants (5 males, 8 females) aimed to validate the algorithm against an optical motion capture system under three walking conditions (natural, toe-in and toe-out walking) and the efficacy of the Xsens DOT in mitigating the effects of magnetic disturbances over prolonged use.

Results: The sensor's alignment to the foot after attachment of the fixture to the shoe provided consistency but had pronounced outliers ranging from -10° to 6,5°, yielding inaccurate FPA estimates utilising this calibration method. No change in the orientation of the fixture was noted during natural walking. However, fixture rotations of 1.1° externally and 0.6° internally were observed in toe-in and toe-out walking respectively. The dynamic calibration method and Peak Deceleration point algorithm yielded the most accurate FPA estimates, with mean absolute error (MAE) of less than 3.5° for all walking conditions. Notably, the FPA algorithm seemed to produce an overshooting FPA estimation, and its consistency decreased for higher FPA values. The FPA estimation over a period of 10 minutes suggested a potential minimal decline in accuracy over time, with an increase in 2,28° RMSE after 10 minutes.

Conclusion: This thesis contributes to the ongoing development of wearable technologies aimed at managing KOA. By the development of an FPA estimation algorithm, evaluating multiple calibration methods, and validating its accuracy and feasibility, this study is a step towards the “Knee Wear project’s” smart-wearable feedback device, simplifying gait retraining interventions for people with KOA. While the proposed fixture calibration method needs refining for foot direction alignment, the proposed FPA algorithm, especially when combined with the dynamic calibration method, provided accurate FPA estimations. While the accuracy of the method is not absolute, the MAE magnitude of less than 3.5° is accurate enough to provide feedback on the FPA. Additional research should be done on the use of the proposed FPA estimating method by the demographic intended for the FPA feedback device.

Pompe disease is a progressive muscular disorder that will affect the respiratory muscles, in particular the diaphragm, thereby seriously limiting the respiratory function. Respiratory function is typically assessed using spirometry. However early stages of diaphragm impairment may not be detected by conventional spirometry measurements due to compensatory efforts of other inspiratory muscles. In this study we aimed to use 3D MRI as a sensitive method to assess diaphragm function and identify diaphragm impairment.

Static breath-hold 3D MRI scans at maximal inspiration and maximal expiration were obtained from a previously used dataset in 18 healthy controls and 35 Pompe patients with varying degrees of diaphragm weakness. Images were segmented using an automatic script. The segmentations were used to create an anatomically accurate 3D mesh model of the lungs. The surface of the mesh was divided into topographical segments based on the anatomical surfaces of the lungs. Vital capacity (VC) measurements were retrieved from the mesh model (VCmesh) and compared against spirometry VC measurements made during the MRI acquisition (VCspiro) in order to validate the mesh model. Segmental volumes, derived from the topographical segments identified on the surface of the mesh model, were reallocated based on changes in lung dimensions to provide a more accurate functional topographical representation of the underlying diaphragm and intercostal muscle functions. The relative contributions of the diaphragm and intercostal muscles to the total increase in lung volume during inspiration were assesses for differences between healthy controls and Pompe patients and compared against common spirometry and 2D analysis outcomes.

A large and significant correlation was established between VCmesh and VCspiro, rs = 0.971, p < 0.001. Median VCspiro was significantly larger than median VCmesh across all population groups (p < 0.001), by an average amount of 0.31 L. This represented a mean difference between the two measurement methods of 9.3% of the mean VC measurements. It has also been demonstrated that median changes in diaphragm volume (p < 0.001) and the median relative contribution of the diaphragm to the total increase in lung volume during inspiration (p = 0.009) were lower in Pompe patients with decreased spirometry results when compared against healthy controls. Changes in diaphragm volumes correlated well with conventional VC and FVC measurements (rs = 0.997, p < 0.001) as well as with changes in superoinferior lung sizes (rs = 0.936, p < 0.001). In some Pompe patients with decreased spirometry results no indication for diaphragm impairment was found when assessing the relative contribution of the diaphragm to the total increase in lung volume during inspiration.

A mesh model based on 3D MRI segmentations provides an accurate method of assessing diaphragm function. Changes in diaphragm volume and the contribution of the diaphragm to the increase in lung volume during inspiration allow for the assessment of diaphragm impairment in Pompe patients. These biomarkers of diaphragm function may prove to be highly useful in determining a personalized treatment plan for Pompe patients as well as a sensitive outcome in trials to test future treatment modalities.

Neuromuscular diseases often result in elevated passive joint impedance (PJI), impacting the daily lives of affected individuals. To be able to apply assistive devices that compensate for PJI, it is essential to identify the PJI correctly. This study aims to identify and model the PJI of the elbow joint, to improve the control of force-based controlled active-assistance exoskeleton devices by distinguishing the voluntary from the passive forces. We used an elbow device to measure the PJI in twelve healthy males with the shoulder abducted at a 90˚ angle. The study investigates both static and dynamic conditions, encompassing various contraction velocities (≤ 0.20 rad/s) and shoulder flexion positions (0˚ and ±45˚). The analysis estimates the hysteresis, equilibrium position, and elastic property. Subsequently, based on the average elbow PJI, we developed a regression model, with the statistical analysis revealing no significant differences between the conditions, except for the observed hysteresis under varying velocities. Based on the tested conditions, the findings indicate that a single low-velocity dynamic measurement can serve as the basis for deriving a general elbow PJI regression model.

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.

DMD (Duchenne muscular dystrophy) is a genetic disorder characterized by progressive muscle weakness, leading to the eventual loss of muscle function. After losing lower extremity function, DMD patients lose the ability to use their arms. To assist individuals with DMD, an upper extremity exoskeleton is being developed to provide support.

The device is required to provide proper weight compensation for the weight of both the user and the support system. Previous literature review has highlighted three strategies for achieving compensation: Model, Calibration dynamic and Calibration static. However, the review lacks a conclusive understanding of the differences between these strategies. Thus, this study aims to validate a weight compensation model by comparing the joint torque with two different measurements: Calibration static and Calibration dynamic on non-disabled participants with a one DOF (Degree of freedom) elbow support system.

The weight compensation model was designed to accurately account for the weight of the user's arms and the exoskeleton device itself. It incorporates multiple inputs, including shoulder flexion, shoulder abduction, elbow joint angle, arm mass, and arm center of mass to calculate the required compensation torque for the motor located at the elbow joint.

The model was validated by a dead weight experiment. The weight compensation model was validated by comparing the joint torque measurements from Calibration dynamic and Calibration static results. Afterwards, experiments were performed on 12 male non-disabled participants. The weight compensation model results does not align well with the measurements from non-disabled participants. Analysis suggests that joint impedance caused these discrepancies. However, even after accounting for joint impedance, the weight compensation model still exhibits a tendency to overestimate the required compensation torque. A fitted model was used to decrease the product value of mass and center of mass to decrease overestimation. Furthermore, the comparative analysis indicates that dynamic and static measurements yielded similar mean values for joint torque.

While the weight compensation model demonstrates accuracy in a dead weight experiment under the assumption of an accurate estimation of its mass and center of mass, its performance is sub-optimal during the human experiment. This is attributed to the absence of joint impedance consideration and the overestimation of the forearm plus hand mass and center of mass for the user. Comparison between dynamic and static measurements the mean difference between dynamic and static measurements obtained from non-disabled participants indicates no substantial disparity in terms of joint torque.

Future plans for this research involve expanding the current one DOF configuration to a four DOF configuration and incorporating an inertial measurement unit (IMU) for more accurate angle measurements. Additionally, different compensation strategies will be compared in terms of task performance using metrics such as external interaction force or sEMG (surface electromyography). Lastly, the overestimation of forearm plus hand mass and center of mass will be further investigated.

Liver cancer ranks seventh in global cancer prevalence and stands as the third leading cause of cancer-related deaths. Surgical resection is considered the gold standard for treatment of liver malignancies and has witnessed a shift toward minimally invasive techniques in recent decades. Surgeons rely on laparoscopic observations, preoperative imaging, and laparoscopic ultrasound for image guidance. However, these methods pose challenges in accurately representing the complex three-dimensional (3D) structure of the liver in a two-dimensional (2D) view. Surgical navigation devices aim to enhance this process by providing additional information for improved lesion localization and vascular structure visualization with respect to tracked surgical instruments. This study's objective was to establish an electromagnetically guided laparoscopic liver resection workflow at Netherlands Cancer Institute – Antoni van Leeuwenhoek (NKI-AvL) to be implemented into clinical practice.

A method was developed for tracking instruments in laparoscopic surgery, with a focus on the laparoscopic sealer/ divider. An adapter was developed with an embedded electromagnetic sensor to allow tracking. Calibration employed a dedicated device, followed by a comprehensive validation process encompassing usability, sterilizability, attachment reproducibility, and calibration accuracy. The adapter was produced from a non-ferromagnetic material, ensuring sterilizability and straightforward surgeon attachment, exhibiting positive results in reproducibility and virtual visualization. Nevertheless, the calibration accuracy, at 2.5 mm, could be enhanced, primarily through calibration method adjustments. Additionally, a fast calibration method for the laparoscopic ultrasound (LUS) probe adapter was developed, involving a dedicated calibration tool. Validation assessments to ascertain its reproducibility showed positive results. However, accuracy measurements can be further improved as ultrasound calibration method evaluation showed a root mean squared error (RMSE) of 3.6 mm. This is important as the navigation performance relies on the calibration accuracy of the tracked LUS probe. The workflow for navigated laparoscopic liver resection was tested using a liver phantom. It demonstrated the navigation system's capacity to register preoperative and intraoperative images with a mean target registration error (TRE) of 3.7 mm and showed promising augmented reality views. Additionally, this test led to workflow enhancements related to liver sensor placement and visualization techniques.

The developed navigation workflow for laparoscopic liver resection integrated Aurora EM tracking, tracked laparoscopic instruments, and software for intraoperative liver 3D model visualization. While feasible in an operating setting during phantom tests, further enhancements in visualization and accuracy are needed. A clinical study will be conducted to determine intraoperative feasibility, providing valuable experience to technical physicians and surgeons. In the near future, the presented navigation method may enhance laparoscopic resection accuracy and reduce disease recurrence. A clinical study at NKI-AvL will soon validate this navigation system for clinical use.

Purpose: Proton therapy has been proposed as an alternative to conventional photon therapy for the treatment of locally advanced cervical cancer (LACC) since these patients experience toxicities. Proton therapy may allow for significant sparing of the organs at risk, reducing the incidence of treatment-related morbidities. The aim of this study is to develop a treatment strategy that is robust to motion and uncertainties in intensity-modulated proton therapy (IMPT) for the treatment of LACC.
Materials and methods: Data from 14 LACC patients was included in this study. For each patient, a full and empty bladder planning CT (pCT) scan before treatment and four weekly repeat CT (reCT) scans after daily fraction were available. The full and empty pCT scans were used to create the patient-specific motion model of the cervix-uterus. An anisotropic CTV-to-ITV margin to expand this motion model was explored to account for uterine interfraction target motion. Subsequently, the motion model was divided into subranges to create a library of 1 to 4 plans, depending on the uterine motion due to bladder filling. Range and geometric uncertainties in the treatment of LACC are accounted for by robust optimization and evaluation. For each plan in the plan library, a treatment plan is created using the Erasmus-iCycle treatment planning system, taking into account EMBRACE-II constraints. To investigate whether the combination of margins, plan library, and robustness recipe is safe considering geometric and range uncertainties, ten treatments for each of the fourteen patients were simulated. These simulations were performed by recalculating the optimized treatment plans on the reCT scans with added uncertainties. We assumed that the target coverage was sufficient if the D95 of the target volumes was greater than or equal to 95% in at least 90% of the patients.
Results: Of the 3430 margin recipes that were tested, the margin recipe with 95% cervix-uterus overlap and the smallest target volume was 1, 5, 7, 3, and 3 mm in the left/right, posterior, anterior, cranial, and caudal directions, respectively. The subranges of the motion model were expanded with the anisotropic margin recipe, after which robust optimization (setup robustness 5 mm, range robustness 3%) and evaluation (32 scenarios) of the treatment plans were performed. The treatment simulations showed that the D95 was greater than 42.75 for 99% and 92% of the patients for the cervix-uterus target volume and nodal target volume, respectively.
Conclusion: The anisotropic margin and robustness recipe was robust to motion, geometric uncertainties, and range uncertainties when treating LACC patients with IMPT. Both values comfortably met the delivered dose criterion, indicating the strategy can be further improved.

While bracing has been proven to be an effective treatment strategy for adolescent idiopathic scoliosis, its effectiveness is often found to be inconsistent in practice. One of the main reasons for this is that the forces applied by the brace may be subject to constant change, while its required effect is expected to change over time as well. Brace treatment becomes even more complicated when considering that both the patient and the practitioner are provided with limited to no information on how this relation may be changing over time. While measurements of the pressure distribution may be used for evaluation of the brace, most commercially available devices are too expensive or unsuitable to be integrated in a brace. This study therefore sought to investigate the possibility of designing a cost effective monitoring system based on force sensitive resistors (FSR) that can be implemented in the brace to evaluate brace performance.

Several metrics were defined to evaluate different functional aspects of the brace. This simultaneously served as a basis for the system requirements, which focused on finding a cost effective solution for evaluating brace performance, while no restrictions on dimensions and mass of the prototype were set at this time. The hardware of the system was based on an Arduino Mega microcontroller connected to custom designed PCBs for voltage regulation and signal conditioning, which were integrated in a purposely designed belt. The belt was connected to a sensor pad with a total of 15 integrated FSRs (FSR402 by Interlink Electronics) and was designed to fit the pad located in the lumbar area of the brace. The FSRs in the sensor pad were calibrated in the 0 - 26kPa range using a model developed for creep and hysteresis compensation. When tested with a consistent actuation system, a random error of 4% was found. The model also showed to yield a decent approximation of the hysteresis behavior of the FSRs using a parametric third order polynomial function, but further research is required for this to be validated.

In order to evaluate the three dimensional effect of the brace forces on the spinal column, the spatial geometry of the spine and the sensor pad had to be reconstructed. A generative design algorithm was developed for doing this using only a surface model of the torso, an AP radiograph of the spine, standard vertebra dimensions and the geometry of the sensor pad including the relative two dimensional locations of the integrated FSRs. The method yields a low resolution reconstruction of the required geometry and serves as a proof of concept for acquiring data that normally would require sophisticated equipment which may not always be available.

Validation showed that the system could effectively be used to measure pressure distribution inside a scoliosis brace. Differences were measured related to posture and respiratory movement, which was found to have an effect on the mean pressure and the pressure distribution in the lumbar area. Combining the measurements with the spatial geometry allowed for computation of equivalent bending moments, which seemed to be in line with the expected function of the brace.

Although this research showed promising results for an FSR based pressure measurement system for scoliosis braces, further research is required to optimize the different aspects of its design.

BACKGROUND: Research on the role of patellar biomechanics in patellofemoral (PF) joint pathologies requires accurate and reliable measurement of the patella relative to the femur (patellar tracking) but current methods have limitations. In vivo measurement of PF kinematics is done using medical imaging techniques but these are expensive, involve radiation exposure or only allow slow, supine motions. A widely used alternative is optical motion capture combined with musculoskeletal modeling. However, due to the large motion of the skin relative to the patella, the typical approach using anatomical calibrated skin-markers is unsuitable. As the shape of the patella is grossly visible underneath the skin, placement of a grid of skin-mounted markers on the skin covering the patella might offer an alternative for patellar tracking.
OBJECTIVE: The objective of this study was to develop a patellar tracking framework designed to measure in vivo PF translations using a grid of skin-mounted markers and to compare it to in vivo measures derived from dynamic CT images and musculoskeletal model estimates.
MATERIALS AND METHODS: Two participants performed a supine knee flexion-extension motion with a grid of 42 retroreflective markers placed on the right knee during four-dimensional computed tomography (4D-CT) measurement and optical motion capture. A patellar identification algorithm (PIA) was developed to estimate the PF translations in the medial – lateral (ML), superior- inferior (SI) and anterior – posterior (AP) directions. PF translations were determined by four different methods: CT bone geometry-based (CT_BONES), CT marker grid-based (CT_GRID), optical motion capture marker grid-based (OMC_GRID) and by musculoskeletal modeling (OMC_MODEL). To evaluate the feasibility of our method we first compared CT_BONES to CT_GRID. Next, results obtained by different measurement types (CT_GRID and OMC_GRID) and results obtained by two different marker-based methods (OMC_GRID and OMC_MODEL) were compared. To compare ranges of motions, patellar excursions relative to the femur were evaluated and compared for all knee angles (KA_ALL) and for knee angles > 20° (KA_ENGAGED).
RESULTS: Differences in patellar excursions given by CT_BONES and CT_GRID during KA_ENGAGED were less than 4 mm and RMSEs less than 3 mm. These differences were less than 5 mm between CT_GRID and OMC_GRID (RMSE: 5 mm) and less than 16 mm between OMC_GRID and OMC_MODEL (RMSE: 10 mm) for knee angles lower than 20°. Larger differences in patellar excursions and RMSEs were seen during KA_ALL.
CONCLUSION: PF translations could be measured using a marker grid with an accuracy within 3 mm for knee angles larger than 20° (i.e. during patellar engagement). However, our method performed worse for knee angles smaller than 20° flexion (an accuracy within 12 mm). The findings of this study provide valuable baseline knowledge for non-invasive, marker-based patellar tracking. Future studies should include larger sample sizes to allow for proper validation.

Duchenne Muscular Dystrophy (DMD) is a neuromuscular disorder characterized by progressive muscle weakness as well as progressive muscle fat replacement. Absence of functional dystrophin in muscles is believed to cause membrane instability, making the sarcolemma susceptible to damage when subjected to mechanical stress. However, the process leading from dystrophin-absence to muscle degeneration, and ultimately fat replacement, is still not well understood. Therefore, several hypotheses currently co-exist. Interestingly, muscles of DMD patients are not equally affected, and a more or less consistent successive pattern of muscle fat replacement exists in the lower extremities. The aim of this study was to investigate a possible mechanical role in explaining differential muscle fat replacement in the legs of DMD patients. Based on a published preliminary study, it was hypothesized that eccentric contraction, during which a muscle generates force while lengthening, is associated to muscle fat replacement during gait.

3D gait analysis data of a small cross-sectional sample of typically developing children was used to predict muscle contributions during gait in OpenSim. In one analysis, negative work, the time-integral of force multiplied by lengthening velocity, was normalized to account for differences in physiological cross-sectional area (PCSA) and fiber length, and was subsequently tested for a relation with muscle fat replacement. Furthermore, since muscle architecture parameters PCSA and fiber length are associated to muscle fat replacement, separate effects of total negative work and muscle volume (PCSA*fiber length) on muscle fat replacement were also analyzed.

Normalized negative work was significantly associated with muscle fat replacement, where upper leg muscles generally showed higher fat fractions than lower leg muscles. Furthermore, both the effect of total negative work as well as muscle volume on muscle fat replacement were significant. The effect of total negative work on muscle fat replacement was stronger if muscle volume was smaller. In contrast, normalized and total positive work (i.e., concentric contraction) was not significantly associated with muscle fat replacement.

Eccentric contraction during gait helps explain the differential progression of muscle fat replacement seen among leg muscles of DMD patients. The results of this study generate more insight regarding a mechanical role in the pathophysiology of DMD, and may potentially help in generating or improving therapies that focus on prolonged muscle function preservation.

Background
Gait retraining strategies are used to reduce medial compartment load in people with medial knee osteoarthritis. Two key gait retraining strategies are based on changing the foot progression angle (FPA). The FPA can be measured using a pressure sensitive walkways (PSW), but inertial measurement units (IMUs) are considered more suitable for routine clinical use.
Research question
The purpose of this study was to evaluate the reliability and validity of an IMU system to measure FPA under different gait retraining strategies in a potential clinical setting.
Methods
Twenty healthy participants (14 females, 6 males, mean age=33.7 years, SD=10.3 years) walked along a ± 8.5 m long path using different gait strategies (2x natural gait, 1x toe-out -and 1x toe-in gait) during four 90 second trials. FPA was measured simultaneously with the IMUs (Opal, APDM, Portland, USA) and a PSW (Zeno™ Walkway, ProtoKinetics, Havertown, USA), the latter considered the reference standard.
Results
Test-retest intraclass correlations (ICCs) for the IMUs and the PSW were indicative of good and excellent reliability respectively (IMU ICC=0.89; PSW ICC=0.97). This difference in reliability was also reflected by a higher standard error of measurement (SEM) for IMUs compared to the PSW (IMUs SEM=1.6°, PSW SEM=0.96°). Minimal detectable change (MDC) was 4.5° for the IMUs and 2.7° for the PSW. The repeated measures ANOVA indicated a significant effect of gait type on FPA (p<.001), whereas the measurement instrument did not affect FPA (p=.875). Bland-Altman plots indicate good agreement of both systems for the baseline condition, though the IMUs seem to consistently overestimate the FPA value compared to the PSW. We conclude that IMUs are reliable and valid measurement systems for measuring FPA in natural gait, toe-out and toe-in gait. Differences between the systems are significant for all gait strategies, so systems should not be used interchangeably.
Significance
The IMUs provide a promising tool for clinicians and researchers aiming to quantify FPA for gait retraining.

Duchenne Muscular Dystrophy (DMD) patients suffer from a severe form of progressive muscular weakness. Consequently, as the disease progresses these patients become more and more dependent on assistive devices for their daily activities. For instance lifting their arms against gravity already becomes challenging. So far, a considerable amount of effort has been put in the development of assistive devices. However, compensating the weight of the hand remains challenging as the required balancing torques are dependent on the position of the hand and the orientation of the forearm.

In this research a solution is proposed to passively compensate the weight of the hand by making use of a simplified torque profile (a constant torque). The effectiveness of this profile was assessed experimentally in a group of healthy subjects. For this the wrist muscle activity required to lift the hand against gravity was measured through surface electromyography, for several types of compensation. From this experiment the conclusion can be drawn that a constant torque profile performs similar to the theoretically ideal type of balancing, showing a similar reduction in the anti-gravity muscle activity.

Based on these findings, a mechanism has been developed capable of providing an adjustable constant force, by making use of a combination of positive and negative stiffness springs, for implementation in a wrist support for DMD patients.