Title Promoter Affiliations Abstract "Computational biomechanics as a tool for personalised medicine" "Charlotte Debbaut" "Department of Electronics and information systems" "Throughout history, medicine has been largely built on statistical grounds, treating individual patients as members of (potentially heterogeneous) groups, which may result in suboptimal treatment outcomes. Ideally, the general focus should be shifted from the general approach towards a more personalised medicine. This research project’s ambition is to take part in this revolution by using computational biomechanics as a tool for personalised medicine in two main research areas, being cancer and minimally invasive procedures. More specifically, the objectives are: (i) Optimisation and personalisation of targeted drug delivery for cancer treatment (i.e. transarterial drug delivery for liver cancer, intraperitoneal chemotherapy for peritoneal carcinomatosis, and lymphatic delivery), (ii) Development of planning tools for minimally invasive interventions (i.e. robot-assisted partial nephrectomies and neuro-interventional procedures), and (iii) Unravelling the role of biomechanics in diverse other applications (e.g. Fontan-related liver pathologies)." "Characterizing a rupture-prone mouse model of aortic aneurysm: the road to post-mortem validation of AAA rupture risk predicted by biomechanical computational models" "Patrick Segers" "Department of Electronics and information systems" "Abdominal aortic aneurysm (AAA) is a local dilatation of the aorta that can lead to sudden death when it ruptures. Patients are currently operated when the aneurysmatic diameter exceeds 5.5 cm. In this project, we want to investigate whether numerical techniques can characterize and predict the actual rupture incidence and location in a novel, rupture-prone mouse model of the disease." Biomechanics "Pascal Verdonck" "Department of Electronics and information systems, Department of Civil engineering" "The AOG Biomechanics is doing experimental and computational research on (1) biofluid flows in the cardiovascular system, the pulmonary airways and artificial organs, (2) structural mechanics (musculoskeletal system or stent inflation in an artery) and (3) mechanical interaction between fluids and structures (e.g. heart valve dynamics). The research unit aims to optimize diagnostic methods and therapies, all for the benefit of human health." "Computational models to investigate cerebrospinal fluid dynamics under normal conditions and in Chiari type 1 malformation" "Patrick Segers" "Department of Electronics and information systems" "The objective is to gain more insight into the impact of a disruption of the flow of cerebrospinal fluid in patients with Chiari type 1 malformation. Therefore, we develop computational models, which can realistically simulate cerebrospinal fluid and in turn can be applied to study cerebrospinal fluid pressure and flow under normal conditions and in Chiari type 1 malformation." "Decision support system for objective nasal airway obstruction assessment using computational fluid dynamics" "Joris Dirckx" "Vision lab, Ziekenhuisnetwerk Antwerpen (ZNA), GZA Hospitals, Biophysics and Biomedical Physics" "Surgery is often treatment of choice for nasal airway obstruction caused by anatomic abnormalities. Objective measures for nasal patency, such as rhinometry, correlate poorly with patient's symptoms and long-term satisfaction rates are low. In this project we develop a decision support system using patient-specific computational fluid dynamics models as an objective assessment tool in clinics. Model geometry is based on statistical shape models fitted to tomographic data." "In silico geneeskunde voor de behandeling van thoracale aorta aneurysmata op basis van integratieve multischaal mechanobiologische modellen" "Nele Famaey" "BioMechanics (BMe)" "Een aneurysma van de thoracale aorta is een levensbedreigende ziekte. Huidig onderzoek dat ernaar streeft de behandelingsmethodes te verbeteren is versnipperd en verdeeld over verschillende onderzoeksgebieden. Dit project is gericht op het overbruggen van de kloof tussen biomechanische modellen die zelden biologisch gevalideerd zijn en inzichten van vasculaire biologen die zeer nauwkeurige signaalprocessen bestuderen met een beperkte globale kijk. Om in silico geneeskunde mogelijk te maken, ontwikkelen we een computationeel instrument voor het voorspellen van aneurysmagroei op basis van een systeembiologisch geïnspireerd regulatiemodel op celniveau, in combinatie met een model op weefselniveau van de adaptatie van extracellulaire matrix doorheen de tijd. In combinatie met patiëntspecifieke eindige elementenmodellen van de thoracale aorta, zal dit een gepersonaliseerde behandeling en risicopreventie mogelijk maken." "Cone-beam Computed Tomography is a Fast and Promising Technique for Microstructural Imaging in Clinical Practice" "Harry van Lenthe" "Development and Regeneration, Kulak Kortrijk Campus, Biomechanics Section" "Due to the rising life expectancy, bone and joint diseases (e.g., osteoporosis, osteoarthritis and rheumatoid arthritis) have become an important socioeconomic burden. For these diseases, the importance of assessing the bone’s microarchitecture make-up in clinical practice has been emphasized in basic science. However, it remains challenging to assess it in clinical practice.High-resolution in vivo imaging became possible with the advent of a highresolution peripheral computed tomography (HR-pQCT) scanner. Two systems are currently on the market, XTremeCT-I and XTremeCT-II (Scanco Medical AG, Switzerland) which provide a voxel size of down to 82µm and down to 60.7µm, respectively. So far, a breakthrough of the scanner for widespread clinical applications is still lacking. The two main disadvantages of the scanner are the slow scanning time (2 à 3min. for a stack of 0.9 à 1cm), which makes scanning of a large volume of interest challenging in vivo, and the dedicated nature of the scanner which does not allow routine clinical use for standard musculoskeletal diagnostics.A promising alternative is high-resolution cone-beam computed tomography (CBCT), which is already the gold standard in many dental and maxillofacial applications. The top high-resolution CBCT scanners on the market, e.g. CBCT Newtom 5G (Cefla, Italy), feature a fast scanning time (18 à 31s.), a large field of view (12x12x8cm3) and a low radiation dosage, in addition to a high resolution (voxel size down to 75µm). Yet, CBCT is impaired by the presence of image artefacts that reduce image contrast, leading to it being currently used for qualitative evaluation only.The overarching aim of this PhD is to determine whether CBCT can be enhanced by means of artefact correction algorithms and advanced segmentation techniques in order to be used to visualize and quantify bone microstructure and to quantify bone mechanical parameters in clinical practice.To attain this main aim, four sub aims were formulated and worked out in this thesis. The first sub aim was to identify CBCT artefacts and to enhance CBCT images. In literature, scattering is addressed as the main detrimental factor in CBCT imaging and beam hardening is another often mentioned important artefact. To address these artefacts, a Monte Carlo simulation, as well as a C++ program was developed. In contrast to what is often assumed in literature, our simulations demonstrated that scattering is limited when scanning a wrist with a normal gantry and that the impact of beam hardening, rather than scattering, is more pronounced in CBCT images. The development of a beam hardening correction technique, which took into account the high bone content of extremities, was able to enhance the images significantly. Next to beam hardening correction, an in-house reconstruction and projection processing program was developed which enhanced the images already significantly, compared to the standard reconstruction of the scanner.The second sub aim of this thesis was to evaluate the accuracy of CBCT images in quantifying bone microstructural parameters. To enable quantification of the bone microstructural parameters, the images had to be segmented and a trabecular volume of interest had to be selected. For the segmentation, an adaptive segmentation technique was proposed in this thesis. This adaptive segmentation technique was a key element to enhance accuracy of the quantified bone microstructural parameters, because it enabled segmentation of not completely homogeneous images. To select the trabecular volume of interest automatically, the technique of Buie et al. was extended. Two ex vivo validations were performed in this thesis, one on 19 trapezia and another on 19 distal radii. Both validations demonstrated that our enhanced CBCT images were able to quantify bone microstructural parameters with high accuracy.The third sub aim was to evaluate the accuracy of CBCT images in quantifying bone mechanical parameters. Thus far, simple-flat surface boundary conditions have been mostly applied on sections of a bone, such as a section of the distal radius. To apply boundary conditions on entire bones or multiple bones, more advanced boundary conditions are needed. Therefore, a software technique was developed to apply more general loading conditions. Afterwards, the accuracy of CBCT to quantify bone mechanical parameters was tested on the previously mentioned 19 trapezia and 19 distal radii. Both validations demonstrated that the enhanced CBCT images had an adequate accuracy even when quantifying bone mechanical parameters.The last sub aim was to compare the accuracy of CBCT to HRpQCT, the current standard for in vivo high-resolution scanning of extremities. Although CBCT is visually less sharp, it provides a very similar, albeit slightly lower, accuracy in quantifying bone microstructural and mechanical parameters when compared with XTremeCT-II, the newest generation HR-pQCT scanner.In conclusion, it can be stated that our enhanced CBCT images are able to quantify bone microstructural and mechanical parameters with high accuracy. Hence, high-resolution CBCT, which features fast scanning of large FOV at high resolution and low radiation dosage, is a promising scanner for high-resolution imaging in clinical practice." "Development of a functional outcome prediction strategy for the design of orthoses." "Jos Vander Sloten" "Biomechanics Section, BioMechanics (BMe), Human Movement Biomechanics Research Group" "Approximately 200 million European citizens suffer from a disorder to the ankle or foot, which is accompanied by a decreased functionality of and/or pain in the foot, ankle joint of knee joint. Due to the aging of the population the number of people suffering this disorder increases. Mostly ankle foot ortheses (AFO) are described in order to recover the gait function of the patients. AFOs are external aids to correct the movement of the foot. The large variety of ankle disorders call for a personalized approach. The design of these aids currently relies largely on the personal experience and knowledge of the orthopaedist, movement registration and plantar pressure measurements. This subjectivity leads to a large uncertainty in the reliability and functionality of the orthosis. Themodern computer technology would allow, in principle, a fully digital design process. This has as advantages: flexibility in production, high speed of production and consistency in quality. Gait analysis software, such as ‘OpenSim’, ‘AnyBody’ and ‘SIMM’, are used to analyze the gait pattern of patient with orthosis. The use of predictive simulations is currently strongly limited by the lack of a validated contact model, which is also computational efficient, in order to predict the contact forces between both the body and the environment (AFO/footwear/ground). This research aims at designing, implementing and validating a simulation platform that allows to define design parameters for an optimal AFO, on the basis of forward simulations which predict the effect of design changes ofthe AFO on the motion and the forces of the body.The overall objective of this project will be achieved by improving the current simulation software. As a first operation, the force of the AFO on the body ischaracterized by means of a finite-element modeling. Then a contact model is defined, implemented and validated, which generally describes the contact between the body (foot/leg), the external fittings (shoe/AFO) and the ground. The computational efficiency is increased by the evolutionfrom this contact model to a surrogate model, where the force transmission of the AFO on the body segments are simplified by analytical expressions. Finally, this surrogate model is used in the fully predictive simulation, where the gait of patients with orthosis is simulated, starting from the experimentally measured pathological gait. This provides the necessary information to compare the different designs of orthosis quantitatively. Through optimization of an evaluation criterion, such as for example the step length or the energy cost, design parameters are defined for an optimal design of AFO, adapted to the patient's specific functional needs." "Prediction of gait neuromechanics following orthopedic interventions in children with cerebral palsy using computer simulations based on personalized models" "Ilse Jonkers" "Research Group for Neurorehabilitation (eNRGy), Human Movement Biomechanics Research Group" "Children with cerebral palsy (CP) suffer from a brain lesion that leads to impaired motor control, spasticity and muscle weakness. All these factors undermine the subjects' gait performance and, with time, will pose limitation to their mobility, independence and self-care. Orthopedic interventions aim at improving the walking performance. However, functional outcomes are not always as expected and, often, follow up surgery is needed to correct the treatment outcome, with an important socio-economic impact. My PhD will be part of the SimCP project, which aims at developing a computational platform that will support clinical decision making by allowing clinicians to a priori compare the functional outcome of orthopedic treatments based on subject-specific neuro-musculoskeletal models and predictive simulations. Specifically, I will quantify the lack of selective motor control expressed by CP subjects, characterized by a reduced number of independent motor modules. The modules will be determined by decomposing the experimental electromyography signals or computed muscle activations that reproduce observed joint torques, with the use of Non Negative Matrix Factorization. I will also analyze the effect of the detail of the musculoskeletal models on the extracted motor controls. I will then use these motor modules to drive subject-specific models during predictive simulations of the walking pattern after surgical intervention. To support the translation of these activities to the clinic, I will develop a Graphic User Interface that allows clinicians to directly interact with the computational models by translating information about an orthopedic treatment into changes in the models' parameters and the predicted outcome." "A Combined Multibody and Plantar Pressure Approach to Estimate and Predict Foot Kinematics Applied to 3D-printed Insoles" "Jos Vander Sloten" "BioMechanics (BMe), Human Movement Biomechanics Research Group" "In Europe, over 200 million people suffer from disabling foot and ankle pain caused by a variety of pathologies as overloading injuries, degenerative joint disorders and systemic diseases (e.g. diabetes). Foot orthoses (FOs) or insoles are a popular conservative treatment to alleviate pain and prevent further deterioration of the pathological condition; the goal is to optimize a patient’s foot function by relieving symptoms and slow down or even arrest the progression of the pathology (e.g., rearranging pressure distribution in diabetic patients to prevent foot ulcers). Currently, the process of patient assessment for insole design and manufacturing relies on subjective decision making and time-consuming handicraft work by the clinician. The design of these orthoses is primarily based on the capture of the foot shape using traditional techniques such as plaster casting.3D-printed insoles reduce the manufacturing time and allow efficient production of subject-specific insoles. It allows for the local adjustment of mechanical properties so that the insole can optimally guide the movement of the foot. Therefore, it is crucial to understand the biomechanical effect of the insole on the foot. The overall aim of this thesis was to develop the different steps necessary for the creation of a fully objective and automated digital workflow that goes from foot biomechanics assessment to the production of subject-specific insoles.Computer multibody models can describe the causal relations between input parameters (i.e., kinetics) and model response (i.e., kinematics) given a known geometrical structure. Only a limited number of detailed musculoskeletal foot models for use in dynamic simulations were described in literature. However, the number of accessible detailed musculoskeletal foot models is limited, this is a major limitation to reproduce results or to use the reported models in different studies. In the present work, two detailed OpenSim 3D multibody foot-ankle models generated based on CT scans using a semi-automatic tool, are described. The proposed models consist of five rigid segments (talus, calcaneus, midfoot, forefoot, and toes), connected by five joints (ankle, subtalar, midtarsal, tarsometatarsal and metatarsophalangeal), one with 15 DOF and the other with 8 DOF. The calculated kinematics of both models were evaluated using motion capture and compared against literature, both presenting realistic results. An inverse dynamic analysis was performed for the 8 DOF model, again presenting dynamic results similar to literature.The 8 DOF foot model was then used with in-vivo gait analysis measurements of flat feet and control subjects using different footwear while walking. The differences in kinematic and kinetic parameters between control and flat feet subjects were estimated in barefoot and shoe walking. In parallel, the influence of subject-specific 3D-printed insoles on kinematics and kinetics of flat feet subjects was compared to the influence of a subject-specific Ethylene-Vinyl Acetate (EVA) molded insole. The flat feet subjects presented an increase in forefoot dorsiflexion and abduction while walking barefoot. The use of EVA and 3D-printed insoles corrected the aberrant flat feet-related kinematics and kinetics presented during the minimalistic shoe condition: arch height increased, as reflected by the decreased forefoot dorsiflexion and abduction. Both insoles provided similar correction, thereby confirming the suitability of 3D-printed insoles in the correction of flat feet kinematics and kinetics.The use of plantar pressure measurement systems to evaluate foot and ankle pathologies is well established in clinical practice. Although relevant to detect local tissue (over-)loading, to date, plantar pressure data cannot be used to evaluate ankle-foot kinematics. In this thesis, we present a least squares optimization algorithm that minimizes the weighted difference between simulated and measured plantar pressure using different marker-sets data. Both, marker positions and plantar pressures are simulated in OpenSim using the previously described 8 DOF foot model coupled with an ellipsoid based elastic foundation contact model. It was concluded that a minimum of four markers combined with pressure data was needed to estimate the kinematics with accuracy comparable to the full marker approach.  The ability of estimating full foot kinematics using a simplified set-up that relies on a limited number of reflective markers combined with plantar pressure measurements has significant time and economic implications for both research and clinical applications. It will allow a more accessible, objective clinical evaluation of foot pathologies.With the introduction of 3D-printed insoles came the ability to manufacture insoles with mechanical properties that are tailored to specific subjects in a time efficient manner. However, our understanding of how mechanical insole properties influence the dynamic behaviour of the foot during movement is limited. So, a torque driven forward simulation framework was developed to evaluate the effect of different insoles’ properties on the kinematics of the foot.  In this thesis the effect of different insole stiffnesses on foot kinematics during walking was evaluated. The torque driven forward simulations were computed in OpenSim again using the 8 DOF foot model. The model was coupled with an elastic foundation foot-ground contact model. The insoles were modeled using bushing forces connecting the calcaneus to the forefoot. Increased bending stiffness mostly independent from torsional stiffness led to kinematic adaptations that have the potential to partially correct low foot longitudinal by increasing forefoot adduction.This thesis demonstrates the potential of detailed foot musculoskeletal models to be used for kinematic acquisition in a clinical environment and for the improvement of insoles design. These advances can lead to improved orthopaedic patient care, improving both the evaluation as well as the treatment prescription process."