Browsing by Author "Franz, Thomas"
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- ItemOpen Access4D flow and displacement sensitive MR imaging of upper arm arterio-venous connections for haemodialysis(2016) Jermy, Stephen; Meintjes, Ernesta M; Franz, Thomas; Auger, Daniel AChronic Kidney Disease (CKD) is a disease that causes kidney damage, often leading to the patient requiring haemodialysis treatment. Haemodialysis treatment requires a vascular access method, commonly Arteriovenous (AV) fistulae and grafts. These access methods must be regularly assessed to ensure the access remains unblocked and the flow rate is normal. Phase Contrast MRA (PC-MRA) is a versatile Magnetic Resonance Imaging (MRI) modality which is capable of imaging and quantifying blood flow in vivo. It is for this reason that this imaging technique was used to image blood flow in the vasculature of the upper arm of volunteers and haemodialysis patients with either an AV fistula or graft. This imaging technique is capable of producing temporally resolved Three-dimensional (3D) datasets (known as "Four-dimensional (4D)" flow) of blood flow in major vessels. Velocities are phase encoded between -π and π based on the chosen Velocity Encoding Constant (venc). To successfully characterise all velocities in the volume it is necessary to set the venc to be approximately equal to the highest velocity found in the vessel. Any lower venc value will cause phase wrapping, an imaging artefact causing all higher velocities to be wrapped by a multiple of 2 π. However, the increase in sensitivity to high velocities reduces the overall specificity of the velocities, especially for low velocities. Due to the pulsatile nature of blood flow in arterial vessels, a large range of velocities are encountered, while venous flow is more constant but lower than the peak arterial flow value. For this reason and due to the length of the 4D flow scans, 20-30 minutes, it would be preferable to perform one scan at a relatively low venc and correct any phase wrapping during post-processing. In this study, we performed both Two-dimensional (2D) PC-MRA scans at various locations in the upper arm and 4D PC-MRA scaans with similar venc settings. The purpose of the study was to implement and test several methods of phase unwrapping to remove phase wrapping artefacts from affected areas within the PC-MRA datasets.
- ItemOpen AccessCancer Cell Mechanics in Chemoresistance and Chemotherapeutic Drug Exposure(2019) Smith, Rochelle; Franz, Thomas; Zaman, M; Prince, SCancer remains a problem worldwide as one of the leading causes of morbidity and mortality. Many cancer patients experience recurrence and ultimately death due to treatment failure or the development of chemoresistance. The concept of chemoresistance however is complex, recent studies have highlighted that cellular structure and extra-cellular composition, mechanics and structure play a role in the development of chemoresistance. The mechanical properties of cells impact their architecture, migration patterns, intracellular trafficking and many other cellular functions. Studies have also revealed that cellular mechanical properties are modified during cancer progression. We investigated these mechanical properties and changes to them by using a malignant melanoma cell line (WM1158) and a chemoresistant malignant melanoma cell line (SK-MEL29). Malignant melanoma was the cell line of choice as it is one of the most prominent types of cancer known to develop chemoresistance. The aim of this study was to identify the effects of chemotherapeutic drug exposure on the mechanical properties and cytoskeletal composition of drug sensitive and drug resistant malignant melanoma cells. To achieve this, a combination of Multiple particle tracking microrheology (MPTM), quantitative RT-PCR and Western blotting techniques were utilised to demonstrate changes in cytoskeletal elements that are responsible for cellular mechanics. MPTM was developed as an approach to map intracellular mechanical properties of living cells and track the intracellular particles by Brownian motion to establish a viscoelastic model and compare it with the power-law approach. A quantification of the MPTM allowed capturing of the cell stiffness using the mean squared displacement (MSD) of cell under different conditions. The cytoskeletal elements actin and β-tubulin were analysed in qRT-PCR and Western blot as they form the key elements governing a cell’s mechanical stability and response to mechanical stimuli. The findings from this study revealed cell stiffness decreases as cancer progress, thereby cells become stiffer. The same pattern was evident for chemoresistant malignant cells and revealed that they had a loss of elasticity in comparison to their counter non-resistant malignant cells. With regards to protein levels and mRNA expression, the chemotherapeutic drug affected the cytoskeleton causing cells to undergo morphological changes which, however, was not seen in chemoresistant cells. The results from this study indicated that measuring mechanical properties of cells provides an efficient marker for cancer diagnosis and deeper understanding of cancer mechanobiology.
- ItemOpen AccessComputational biomechanics of acute myocardial infarction and its treatment(2015) Sirry, Mazin Salaheldin; Franz, Thomas; Davies, NeilThe intramyocardial injection of biomaterials is an emerging therapy for myocardial infarction. Computational methods can help to study the mechanical effect s of biomaterial injectates on the infarcted heart s and can contribute to advance and optimise the concept of this therapy. The distribution of polyethylene glycol hydrogel injectate delivered immediately after the infarct induction was studied using rat infarct model. A micro-structural three-dimensional geometrical model of the entire injectate was reconstructed from histological micro graphs. The model provides a realistic representation of biomaterial injectates in computational models at macroscopic and microscopic level. Biaxial and compression mechanical testing was conducted for healing rat myocardial infarcted tissue at immediate (0 day), 7, 14 and 28 days after infarction onset. Infarcts were found to be mechanically anisotropic with the tissue being stiffer in circumferential direction than in longitudinal direction. The 0, 7, 14 and 28 days infarcts showed 443, 670, 857 and 1218 kPa circumferential tensile moduli. The 28 day infarct group showed a significantly higher compressive modulus compared to the other infarct groups (p= 0.0055, 0.028, and 0.018 for 0, 7 and 14 days groups). The biaxial mechanical data were utilized to establish material constitutive models of rat healing infarcts. Finite element model s and genetic algorithms were employed to identify the parameters of Fung orthotropic hyperelastic strain energy function for the healing infarcts. The provided infarct mechanical data and the identified constitutive parameters offer a platform for investigations of mechanical aspects of myocardial infarction and therapies in the rat, an experimental model extensively used in the development of infarct therapies. Micro-structurally detailed finite element model of a hydrogel injectate in an infarct was developed to provide an insight into the micromechanics of a hydrogel injectate and infarct during the diastolic filling. The injectate caused the end-diastolic fibre stresses in the infarct zone to decrease from 22.1 to 7.7 kPa in the 7 day infarct and from 35.7 to 9.7 kPa in the 28 day infarct. This stress reduction effect declined as the stiffness of the biomaterial increased. It is suggested that the gel works as a force attenuating system through micromechanical mechanisms reducing the force acting on tissue layers during the passive diastolic dilation of the left ventricle and thus reducing the stress induced in these tissue layers.
- ItemOpen AccessA computational study of post-infarct mechanical effects of injected biomaterial into ischaemic myocardium(2012) Miller, Renee; Franz, Thomas; Davies, NeilCardiovascular diseases account for one third of all deaths worldwide, more than 33% of which are related to ischaemic heart disease, involving a myocardial infarction (MI). Emerging MI therapies involving biomaterial injections have shown some benefits; the underlying mechanisms of which remain unclear. Computational models offer considerable potential to study the biomechanics of a myocardial infarction and novel therapies. Geometrical data of a healthy human left ventricle (LV) obtained from magnetic resonance images (MRI) was used to create a finite element (FE) mesh of the LV at the end-systolic time point using Continuity® 6.3 (University of California in San Diego, US). A mesh of 96 hexahedral elements with high order basis functions was employed to adequately describe the geometry of the LV. Simulations of diastolic filling and systolic contraction were performed using a transversely isotropic exponential strain energy function and a model for active stress based on contraction at the cellular level. An anterior apical, transmural MI was modelled in the LV encompassing 16% of the LV wall volume. The infarct was modelled at acute and fibrotic stages of post-infarct LV remodelling by altering the constitutive and active stress models to best describe passive and active behaviour of the ischaemic myocardium at each time point. The geometry of the LV with the fibrotic infarct was adjusted to represent the wall thinning that occurs during LV post-MI remodelling. Hydrogel injection was modelled as layers with material properties differing from those of the surrounding myocardium while accounting for thickening of the LV wall at the injection site. The study design comprised a healthy case and two infarcted cases with and without hydrogel injection. The end-diastolic volume (EDV) increased in the acute infarct model compared to the healthy case due to the reduced stiffness in the infarct wall. An EDV increase was not observed in the fibrotic infarct model compared to the healthy case. This was partially attributed to the increase in infarct stiffness and partially due to the fact that remodelling-related dilation of the LV was not implemented in the model. Inclusion of hydrogel lowered EDV in both the acute and fibrotic models. The predicted ejection fraction (EF) decreased from 41.2% for the healthy case to 28.5% and 33.0% for the acute and fibrotic infarct models, respectively. Inclusion of hydrogel layers caused an improvement in EF in the acute model only.
- ItemOpen AccessDetermination of Cross-Directional and Cross-Wall Variations of Passive Biaxial Mechanical Properties of Rat Myocardia(2022-03-24) Ngwangwa, Harry; Nemavhola, Fulufhelo; Pandelani, Thanyani; Msibi, Makhosasana; Mabuda, Israel; Davies, Neil; Franz, ThomasHeart myocardia are critical to the facilitation of heart pumping and blood circulating around the body. The biaxial mechanical testing of the left ventricle (LV) has been extensively utilised to build the computational model of the whole heart with little importance given to the unique mechanical properties of the right ventricle (RV) and cardiac septum (SPW). Most of those studies focussed on the LV of the heart and then applied the obtained characteristics with a few modifications to the right side of the heart. However, the assumption that the LV characteristics applies to the RV has been contested over time with the realisation that the right side of the heart possesses its own unique mechanical properties that are widely distinct from that of the left side of the heart. This paper evaluates the passive mechanical property differences in the three main walls of the rat heart based on biaxial tensile test data. Fifteen mature Wistar rats weighing 225 ± 25 g were euthanised by inhalation of 5% halothane. The hearts were excised after which all the top chambers comprising the two atria, pulmonary and vena cava trunks, aorta, and valves were all dissected out. Then, 5 × 5 mm sections from the middle of each wall were carefully dissected with a surgical knife to avoid overly pre-straining the specimens. The specimens were subjected to tensile testing. The elastic moduli, peak stresses in the toe region and stresses at 40% strain, anisotropy indices, as well as the stored strain energy in the toe and linear region of up to 40% strain were used for statistical significance tests. The main findings of this study are: (1) LV and SPW tissues have relatively shorter toe regions of 10–15% strain as compared to RV tissue, whose toe region extends up to twice as much as that; (2) LV tissues have a higher strain energy storage in the linear region despite being lower in stiffness than the RV; and (3) the SPW has the highest strain energy storage along both directions, which might be directly related to its high level of anisotropy. These findings, though for a specific animal species at similar age and around the same body mass, emphasise the importance of the application of wall-specific material parameters to obtain accurate ventricular hyperelastic models. The findings further enhance our understanding of the desired mechanical behaviour of the different ventricle walls.
- ItemOpen AccessDevelopment and Validation of Experimental Protocol and Guidelines for Non-Invasive Superficial and Deep Muscle Electromyography in the Forearm(2018) Brijlal, Yasheen; Albertus, Yumna; de Jager, Kylie; Franz, ThomasThe present study investigated a novel non-invasive superficial and deep surface electromyography (sdEMG) technique to detect and isolate extrinsic muscles of the hand with the aim of developing experimental guidelines to aid future studies. The sdEMG technique comprises of two or more surface electrode arrays encircling the limb under investigation set up in a monopolar EMG recording modality and a blind source separation (BSS) algorithm to decompose the recorded mixed monopolar EMG signals into their constituent components, which is proposed to reflect the underlying EMG activity of each muscle. Three experimental parameters linked to the finger movement protocol (MP) were investigated that varied the effects of timing, randomisation and movement anticipation on the ability of the sdEMG technique to detect and isolate the superficial muscles flexor digitorum superficialis (FDS) and extensor digitorum (ED), and the deep muscles extensor indicis (EI), extensor pollicis longus (EPL), flexor digitorum profundus (FDP) and flexor pollicis longus (FPL). FDS and FDP were split into FDS-Index, FDS-Ring, FDP-Index and FDP-Ring bands resulting in a total of eight muscles investigated. A standard movement protocol consisting of 12 dynamic movements was designed to target the activation of the investigated muscles during each experimental run. The Timing experiments varied the movement window duration to 3, 5 and 7 seconds using the standard MP sequence. The Randomisation experiment consisted of a randomised MP sequence. The Anticipation experiment presented participants with the current, and next movement instruction in the standard MP sequence. The developed sdEMG system implemented 64 custom-made surface electrodes arranged in three bands positioned around the distal third of the forearm. An OT Bioelettronica® EMG-USB2 256-channel biopotential amplifier was used, set up in a referenced monopolar EMG configuration. Contraction detection apparatus was built consisting of finger exoskeletons and flex sensors to record when finger movements occurred. A forearm testing platform was built to secure the participant’s forearm during experimental testing and a visual participant instruction system was developed to convey the timed movement instructions. Five healthy, right-hand dominant male participants (mean ± SD; age: 24 ± 3 years) without any history of neuromuscular diseases or disabilities were recruited for the study. Each participant completed five experimental runs of the five MP variations while the EMG and flex sensor data was recorded. Independent Component Analysis (ICA) was used as the BSS algorithm and the EMG recordings were decomposed into Independent Components (ICs) which were further processed with a windowed 250ms root mean square (RMS) smoothing filter as well as signal normalisation. The flex sensor data was used to generate synchronised literature-informed predicted EMG (pEMG) waveforms, representing the ideal EMG activation signals for each muscle. The muscle-specific pEMG waveforms were also processed with a 250ms RMS filter and signal normalisation before signal comparisons were made using Pearson’s correlation against all pICs. In each experimental run, the pIC with the highest calculated Pearson’s correlation coefficient (r) value for each pEMG waveform was initially selected as the representative IC (rIC) for that muscle. A rIC selection algorithm was also developed which reassigned pICs that were selected to represent multiple muscles to ensure each muscle was assigned a unique rIC. A case study was conducted to evaluate the effects of the investigated movement protocol parameters upon which experimental guidelines were formed. Fisher-corrected mean population correlation coefficients (ρ) and 95% confidence intervals were calculated to evaluate the effects of timing, randomisation and anticipation of movements. Using an amalgamated population of all the experiments and experimental runs combined, the eight muscles investigated were isolated with ρ values greater than 0.65 indicating moderate isolation (defined as 0.60 ≤ ρ < 0.80), with the exception FDS-Index Band which was poorly isolated (ρ < 0.60) with a ρ value of 0.59. The data did, however, show high variability in all experiments indicating that the sample population was too small and was possibly influenced by poor performing participants. The Timing, Randomisation and Anticipation experiments showed no discernible effects across all participants on the ability of the sdEMG technique to detect and isolate the deep and superficial forearm muscles investigated. The Anticipation experiment also showed that participant reaction delays on average increased steadily during each experimental run suggesting the anticipated visual cues were too complex and potentially confused participants. Concise experimental sdEMG guidelines were developed in which the sdEMG technique was found to be robust to variations of the three movement protocol parameters investigated.
- ItemOpen AccessDevelopment of a device for multi-modal mechanical manipulation of cells in 2D and 3D engineering environment(2018) Sam, Jerry; Franz, ThomasAll organisms from bacteria to cells within the human body experience some form of mechanical stimuli. The biochemical response from mechanical stimuli is known as mechanotransduction. Cell manipulation devices provide an understanding of mechanotransduction and the various signalling mechanisms that take place. The objective of this Master’s thesis was to develop a device for multi-modal mechanical manipulation of cells in 2D and 3D environments. The device is to mimic the stress conditions or the mechanical environment of the cells in vitro. The mechanical cell loading device will be used to perform cellular mechanical experiments to assist in other future biophysical research and investigate the mechanics of cells under various degrees of tension, compression and shear so that a better understanding of mechanotransduction can be obtained. Cells are seeded in a biocompatible medium and their force response is observed. The incorporation of tension, compression and shear stress in a single device constitutes the uniqueness of this designed device. A cell manipulator device was designed and assembled with different modular attachments for the various kinds of stress loading. The dimensions of the device were selected in a manner to enable the device to be mountable on a microscope for live cell imaging. The Carl Zeiss LSM510 Confocal Microscope was the microscope available for the experimentation. In this project, live cell imaging is only possible with tensile strain. Thus, the tension system was the predominant focus. Live cell imaging during tension provides accurate information about cellular morphology. Three different types of PDMS membranes were designed, manufactured and tested by applying a tensile load from the designed device. The three types of PDMS membranes produced were: 20 mm x 20 mm, 20 mm x 20 mm with 1mm thickness dividers (dividers divided the PDMS membrane into 4 even sized quadrants), and 10 mm x 10 mm. Strain characterisation of the three types of PDMS membrane was performed. The PDMS membranes are marked with ink from a permanent marker which serves as a frame of reference for strain measurement. Using the permanent marker, dots were marked in grid format. The PDMS membranes were subjected to tensile stress from the designed device under a confocal microscope. Length deformation of the markers along the stretch axis was measured and recorded during the practical experimentation. Using FEA software, FEA models of each type of PDMS membrane was simulated. The purpose of the FEA models is to facilitate the future studies of researchers. FEA simulations provide feedback to guide actual cellular experimentation for researchers. The FEA models of the various types of PDMS membranes were validated against the practical experimentation of strain characterisation. From the analysis and discussion of the results of FEA and practical experimentation, the designed device satisfies the objectives of this project. The device was most successful with the 20 mm x 20 mm PDMS membrane type since it showed close correlation to the ideal strain output. FEA simulation of the 20 mm x 20 mm PDMS membrane also showed close correlation to the experimental results. But, in the instance of the 10 mm x 10 mm PDMS membrane, experimental results of the strain output did not correspond with the user strain due to the clamping mechanism unable to grapple PDMS membrane appropriately. Thus, validation of the FEA 10 mm x 10 mm PDMS membrane was not successful.
- ItemOpen AccessDevelopment of a numerical tool for the optimisation of vascular prosthesis towards physiological compliance(2007) Van der Merwe, Helena; Franz, Thomas; Reddy, B Daya; Zilla, PeterIt has been proposed that if a vascular prosthesis is to more closely approximate the mechanical behaviour of a native vessel, it should similarly feature a multi-component structure. One of the components could be a metal support structure, similar to an endovascular stent. The objective of the project was to develop a numerical tool, using the Finite Element Method (FEM) to aid in the development and optimization of such a metallic support structure. This tool was used to simulate the behaviour of different designs under the simulated in vivo conditions. The numerical results of the predicted mechanical behaviour are then analysed.
- ItemOpen AccessDevelopment of a Physiological flow loop simulator for graft compliance testing(2010) Reddy, Jordi; Franz, Thomas
- ItemOpen AccessDevelopment of a tissue-regenerative vascular graft: Structural and Mechanical Aspects(2010) Sirry, Mazin Salaheldin; Franz, ThomasIn attempt to prevent graft failure, the tissue-regeneration field offered the porous vascular scaffolds as promising solution for the lack of endothelialization seen in the small-calibre synthetic vascular graft. Another cause of graft failure was reported to be the mechanical mismatch between the graft and the host vessel. This study concerned the investigation and optimization of structural designs of tissue-regenerative vascular grafts, comprising ingrowth permissible porous polyurethane (PPU) foam and knitted reinforcement wire mesh, with the aim of providing vascular prostheses that mimic arterial mechanics. A 3D geometry of a knitted eight-loop wire mesh was imported into Abaqus CAE® 6.8-2 and assembled with a PPU tube geometry such that the wire mesh acted as external reinforcement (EX) or embedded reinforcement (EM) to the PPU tube. A 45°-section assembly was meshed using 8-node linear brick elements. Nitinol (NITI) and polyurethane (PU) material models were used for the knitted mesh. Material parameters obtained in experimental tests were implemented in hyperfoam (PPU), shape memory alloy (NITI) and linear elastic (PU) constitutive models. The luminal grafts surfaces were subjected to uniformly distributed pressure load ramping from 0 to 200mmHg. Models were compared in terms of predicted maximum stress and strain, wall compression, strain energy, radial displacement and compliance. The predicted radial compliance ranged between 1.2 and 15.6%/100mmHg in the reinforced grafts, compared to 106.4 and 65.1%/100mmHg for the non-reinforced grafts. The maximum stress in the Nitinol remained safe at 33 % of stress associated with start of austenite-martensite phase transformation (i.e. 483MPa). The maximum stress and strain values detected in the PPU tube indicated recoverable elastic deformation. The reinforcement enhanced the mechanical performance of the graft without affecting its tissue-regenerating characteristics, as the predicted maximum wall compression indicated that the reduction in size of pore windows would still allow ingrowth of capillaries and arterioles.
- ItemOpen AccessDrug eluting electrospun scaffolds for tissue regeneration(2018) Van den Bergh, Willem Johannes Wian; Bezuidenhout, Deon; Franz, ThomasThe desired healing response to electrospun scaffolds in tissue engineering is often limited by poor ingrowth due to insufficient porosity, thrombogenicity, lack of vascularisation and/or excessive inflammation. This study aimed at increasing structural porosity and incorporating/delivering anti-thrombotic/angiogenic (heparin) and anti-inflammatory (dexamethasone) agents. Porosity enhancement techniques were explored using two different approaches i) electrospinning of biostable polymer (Pellethane® , Pel) with concomitant electrospraying of soluble microparticles, which were subsequently removed to increase scaffold interconnectivity and ii) electrospinning of biodegradable polymer (DegraPol® , DP) at low collecting temperatures. Dexamethasone (Dex) was incorporated by simple admixture, while heparin (Hep) required chemical modification (heparin tributylammonium, HepTBA) to achieve solubility. Release rates were determined in vitro, followed by thrombogenicity (thromboelastography) and cytotoxicity (cell viability) assessments of modified/unmodified heparin prior to incorporation and after elution. Finally, in vivo responses were evaluated in a subcutaneous model (24 rats) for up to 12 weeks. Porosity was enhanced (P0.1). At 12 weeks of implantation, high-porosity Pel scaffolds allowed for full tissue ingrowth (>98%) while conventional scaffolds were limited (0.3). High-porosity scaffolds produced by combined electrospinning/spraying have the potential to enhance healing. Dex or HepTBA can be incorporated and eluted from degradable electrospun scaffolds, and localised delivery of HepTBA improves implant vascularisation. This study may contribute towards tissue engineered vascular graft development where anti-thrombogenicity and increased vascularisation are desired.
- ItemOpen AccessEfficient and robust partitioned solution schemes for fluid-structure interactions(2015) Bogaers, Alfred Edward Jules; Reddy, B Daya; Kok, Schalk; Franz, ThomasIn this thesis, the development of a strongly coupled, partitioned fluid-structure interactions (FSI) solver is outlined. Well established methods are analysed and new methods are proposed to provide robust, accurate and efficient FSI solutions. All the methods introduced and analysed are primarily geared towards the solution of incompressible, transient FSI problems, which facilitate the use of black-box sub-domain field solvers. In the first part of the thesis, radial basis function (RBF) interpolation is introduced for interface information transfer. RBF interpolation requires no grid connectivity information, and therefore presents an elegant means by which to transfer information across a non-matching and non-conforming interface to couple finite element to finite volume based discretisation schemes. The transfer scheme is analysed, with particular emphasis on a comparison between consistent and conservative formulations. The primary aim is to demonstrate that the widely used conservative formulation is a zero order method. Furthermore, while the consistent formulation is not provably conservative, it yields errors well within acceptable levels and converges within the limit of mesh refinement. A newly developed multi-vector update quasi-Newton (MVQN) method for implicit coupling of black-box partitioned solvers is proposed. The new coupling scheme, under certain conditions, can be demonstrated to provide near Newton-like convergence behaviour. The superior convergence properties and robust nature of the MVQN method are shown in comparison to other well-known quasi-Newton coupling schemes, including the least squares reduced order modelling (IBQN-LS) scheme, the classical rank-1 update Broyden's method, and fixed point iterations with dynamic relaxation. Partitioned, incompressible FSI, based on Dirichlet-Neumann domain decomposition solution schemes, cannot be applied to problems where the fluid domain is fully enclosed. A simple example often provided in the literature is that of balloon inflation with a prescribed inflow velocity. In this context, artificial compressibility (AC) will be shown to be a useful method to relax the incompressibility constraint, by including a source term within the fluid continuity equation. The attractiveness of AC stems from the fact that this source term can readily be added to almost any fluid field solver, including most commercial solvers. AC/FSI is however limited in the range of problems it can effectively be applied to. To this end, the combination of the newly developed MVQN method with AC/FSI is proposed. In so doing, the AC modified fluid field solver can continue to be treated as a black-box solver, while the overall robustness and performance are significantly improved. The study concludes with a demonstration of the modularity offered by partitioned FSI solvers. The analysis of the coupled environment is extended to include steady state FSI, FSI with free surfaces and an FSI problem with solid-body contact.
- ItemOpen AccessExperimental and computational study of the mechanics of chikungunya(2021) Matseke, Thabang Ofentse; Franz, ThomasDiseases outbreaks caused by infections from microorganisms like human immunodeficiency virus (HIV), influenza virus, Ebola virus, Zika virus, dengue virus, and malaria have infected millions of people in Africa. In Africa, viruses with a viral envelope, i.e. enveloped viruses, like HIV and influenza, cause thousands of deaths each year yet no cure exists. It has been proposed that the mechanical properties of enveloped viruses may play a role in viral entry into host cells. This dissertation aimed to study experimentally and computationally the mechanical properties of chikungunya virus to enable mechanobiological investigations of interactions between the chikungunya virus, and other enveloped viruses, and host cells involved in the infection process. The chikungunya virus strain used was the S27-African prototype and the virions underwent nanoindentation using atomic force microscopy (AFM). Tests were conducted in pH = 7.4 and 6.0 representing neutral extracellular and acidic endosomal environments, respectively, the latter promoting viral fusion. The height of the virion was recorded using AFM tapping mode before and after the indentation. The indentation tests were performed using AFM force spectroscopy mode. The spring constant of the virus was determined from the force-displacement data for an indentation force between 0.1 and 0.4 nN. The height and spring constant of the virions were considerably larger in the neutral extracellular environment (hᵥ = 57.8 ± 0.6 nm; kᵥ = 0.035 ± 0.003 N/m) than in the acidic endosomal environment (hᵥ = 46.0 ± 0.8 nm; kᵥ = 0.047 ± 0.003 N/m). It is proposed that the acidification of the environment caused partial or full dissociation of the glycoproteins from the membrane. Due to the hydrophobicity of the membrane and the way the glycoproteins are embedded, the membrane may also have dissociated from the capsid. A computational three-dimensional geometry of a chikungunya virus-like particle (VLP) was generated from cryogenic electron microscope (cryo-EM) images and developed into a finite element (FE) model to simulate nanoindentation tests. The VLP was represented as linear-elastic material. The calibration of the model using data from the indentation experiments in neutral extracellular environment predicted an elastic modulus of the chikungunya VLP of E = 2.9, 3.5 and 4.0 MPa for a Poisson's ratio of ᵥ = 0.4, 0.35 and 0.3, respectively. The experimental part of this dissertation provides new information on the mechanical properties of chikungunya virus and on possible mechanical and conformational changes of the virus during the infection process. The microstructural FE model, combined with the experimental data, can facilitate future studies into the mechanics and mechanobiology of virion-host cell interactions during infection.
- ItemOpen AccessFlow velocity measurement in haemodialysis access using 4D MRI(2016) Downs, Jennifer; Kahn, Delawir; Franz, ThomasTreatment of renal failure while awaiting transplant requires vascular access, which comes with both complications and failure rates. In order to improve this, information about the AVF or AVG itself, as well as the haemodynamics is required. This data will then be used for computer modelling techniques and computational flow dynamics. Previously, the required imaging was provided by contrasted MRI, contraindicated in renal failure. Haemodynamic data was prvided by, amongst other things, duplex Doppler. New MRI software that provides imaging data as well as haemodynamic information without using contrast could be used to provide new high-quality data for modelling. Methods: This was a prospective pilot study. Six control cases (with no history of vascular illness or surgery of any kind to the right upper arm), as well as three grafts and five fistulae underwent phase contrast MR angiography of the right upper arm with a Siemens Magnetom Symphony 1.5T MRI Scanner. Images were then processed using Supertool in Matlab, and flow velocities at predetermined points on the brachial artery and cephalic vein, graft and fistula were calculated. Results: Velocities ranged from 5.8 cm/sec in a volunteer's brachial artery to 85.5 cm/sec in an arteriovenous fistula patient's brachial artery. Flow volumes in the cephalic vein or access varied from 6.9 ml/min. in a volunteer and up to 4398.1 ml/min. in an arteriovenous fistula. Graphical representations show marked haemodynamic changes throughout the imaged vessels. Conclusion: This technique provides good imaging and quantitative data about small vessel haemodynamics.
- ItemOpen AccessHigh porosity electrospun scaffolds for small diameter vascular graft applications(2015) Voorneveld, Jason Dirk; Bezuidenhout, Deon; Bezuidenhout, Deon; Franz, ThomasPorosity, pore size and pore interconnectivity have been shown to be critical factors for cellular infiltration into vascular grafts. While electrospinning has been shown to produce many promising characteristics for the fabrication of vascular graft scaffolds, it has yet to create sufficient porosity for transmural endothelial in-growth. This study was aimed at using dual electrospinning with sacrificial fibre extraction to produce scaffolds with controllable porosity characteristics while maintaining sufficient structural strength to resist deformation during implantation. Scaffolds were subsequently covalently grafted with heparin, a known anti-coagulant with growth-factor binding properties.
- ItemOpen AccessIn vivo mechanical loading conditions of pectorally implanted cardiac pacemakers : feasibility of a force measurement system and concept of an animal-human transfer function(2009) De Vaal, Michael Hamman; Franz, ThomasThe objectives of this study were to assess the feasibility of this system for measuring in vivo mechanical loading on pectorally implanted pacemakers, to compare differences in mechanical loading experienced by pacemakers in different pectoral implant positions (i.e. sub-muscular and sub-coetaneous) and to formulate a concept of an interspecific transfer function for predicting the in vivo mechanical loads on sub-muscularly implanted pacemakers in humans, by using data obtained from baboons.
- ItemOpen AccessInvestigation of differences in cortical activation during wrist flexion and extension performed under real, passive and motor imagined paradigms(2016) Stoeckigt, Stefan; John, Lester; Franz, Thomas; Douglas, Tania SThe neuromuscular control comparison between flexion and extension of the upper extremities has been conducted in a number of studies. It has been speculated that differences in the corticospinal pathway between flexion and extension may play a role in the cortical difference detected between flexion and extension, resulting in higher cortical activation for extension. However, it is still unclear as to what roles these pathways play, and to what degree other factors (muscle force activation, sensory feedback, frequency of movement, structural and/or functional differences) might influence the cortical activation in the brain. It has been speculated that the difference in cortical muscular pathways is due to flexion movements being used more often in day to day activities, therefore requiring less cortical activation for that movement. Through the investigation of the cortical differences present during different movement types, a deeper understanding into the differences between flexion and extension may be obtained. No previous study has compared the cortical differences between flexion and extension of the upper extremities during different movement types. In this study, an offline investigation is conducted between wrist flexion and extension, during real, passive and motor imaginary movement with the help of a servo controlled hand device. Simultaneous recording of EEG, EMG and wrist dynamics (velocity, angle, strain) were made on fifteen healthy right handed subjects performing 60 randomized repartitions of right wrist flexion and extension, for kinaesthetic motor imaginary, passively moved, and voluntary real active movements. Real movements were conducted at 10% relative subject maximum voluntary contraction (MVC). A servo controlled hand device was used to regulate dynamic force applied for real movements, and provide motion during passive movements. The use of different movement types with the aid of a servo controlled hand device, may give a deeper understanding into the effects of muscle force activation, rate of movement and corticospinal pathway on flexion and extension. In order to investigate the cortical differences between flexion and extension, subjects perceived difficulty, movement dynamics, movement related cortical potential (MRCP), event related desynchronization and synchronization (ERD/ERS), and phase locking value (PLV) were measured. Each measurement examines a different aspect of the cortical activation present in the brain, during the different movement types. Although relative muscle force activation between wrist real flexion and extension was similar, the motor cortex activation during extension was higher than during flexion, by MRCP and mu-band ERD, with subjects also perceiving real wrist extension to be more difficult to perform. Passive movements found higher motor cortex activation for flexion (MRCP, beta-band ERD), however higher somatosensory cortical activation was present during extension, by mu-band ERS and PLV. Motor imagined wrist flexion showed higher cortical activation during wrist flexion, by MRCP and beta-band ERD. Although numerous variables were tested (each in difference frequency bands), with some being significant and others being non-significant, overall it can be suggested that there was higher cortical activation for extension. The higher cortical activation during wrist extension movements may be due to corticospinal and somatosensory motor control pathways to motor neuron and from sensory neuron pools for extensor/flexor muscle and muscle spindle of the upper extremities. This investigation contributes to the current literature relating to cortical differences between flexion and extension of the upper extremities, by including the real, passive and motor imaginary differences between flexion and extension.
- ItemOpen AccessLong-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner(2012) Saleh, Muhammad G; Sharp, Sarah-Kate; Alhamud, Alkathafi; Spottiswoode, Bruce S; van der Kouwe, André J W; Davies, Neil H; Franz, Thomas; Meintjes, Ernesta MPurpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI.
- ItemOpen AccessMathematical modelling of growth factor induced cell migration in 3D engineered matrices(2024) Ahmed, Riham K I; Franz, Thomas; Abdalrahman, Tamer; Davies, Neil H; Vermolen, FredCells mechanically interact with their environment to sense, for example, topography, elasticity, mechanical cues from other cells, and chemical signals. Multi-signalling stimuli have profound effects on cellular behaviour, including migration. The current study aims to develop a mathematical model for chemo-mechanically induced migration of individual cells in a collective in three-dimensional engineered extracellular matrices governed by the mechanical properties of the matrix and a growth factor gradient. In the developed model, each cell is assumed to transmit a traction force that locally deforms a planar elastic substrate, resulting in spatially varying strain energy density gradients. The magnitude and direction of strain energy density gradients define cell migration. Cell-substrate adhesion and partial random motion are included. Further, the Green function and Duhamel principle are used to solve the diffusion equation to describe the presence of a growth factor and represent chemo-mechanically induced deterministic collective cell migration on planar elastic substrates. Finally, three-dimensional strain energy density gradients due to local matrix deformation by embedded cells are obtained using finite element methods and implemented in the model to describe chemo-mechanically induced collective cell migration in extracellular matrices. Deterministic and random migration of up to 50 cells on planar substrates and threedimensional extracellular matrices with spatially uniform and varying stiffness is predicted. The effect of varying growth factor productivity and diffusivity is explored for cell migration on a planar substrate induced by a growth factor only and combined with mechanical cues. The model predicts that the maximum velocity of a cell migrating towards the growth factor source increases with increasing productivity and decreasing diffusivity of the growth factor. Collective cell migration due to mechanical cell interactions in the extracellular matrix is studied with sequential and non-sequential changes in matrix stiffness. The overall migration is directed towards the stiffest region for the sequential stiffness change and the softest region for the non-sequential stiffness change in the matrix. The chemo-mechanically induced cell migration is presented in three sequential extracellular matrices with an overall migration direction towards the growth factor in the softest region. The mathematical models can adequately simulate the chemo-mechanically induced collective cell migration in elastic planar substrates and three-dimensional extracellular matrices. The models provide qualitative results demonstrating collective cell migration in complex environments with several cues increasing the potential and capabilities to replace in vitro and in vivo experiments with in silico simulations in, for example, wound healing, cancer treatment, and regenerative medicine.
- ItemOpen AccessMethods and adaptations required to perform small-animal MRI scanning using a large bore clinical MRI(2012) Saleh, Muhammad G; Meintjies, Ernesta; Davies, Neil; Franz, ThomasSmall-animal imaging has been widely implemented to study succession of disease, therapeutic treatments and the effects of environmental insults. The gold standard noninvasive technique for following progression of heart failure in small-animal models is magnetic resonance imaging (MRI). The aim of this project was to adapt a clinical MRI system to perform small-animal cardiac MRI. The first part of the thesis describes the adaptations required, which included design and construction of a small-animal radiofrequency (RF) coil, physical support (cradle), a core body temperature regulation system, and optimization of pulse sequences. The system was validated using a phantom and in-vivo in 5 healthy rats. The signal-to-noise ratio (SNR) in the phantom was 91% higher using the small-animal coil compared to the standard head coil. SNRs of 7 ± 2 and 18.9 ± 0.6 were achieved in myocardium and blood, respectively, in healthy rats and MR left ventricular mass (LVM) was highly correlated with (r=0.87) with post-mortem mass. In the second part of the study, left ventricular remodeling (LVR) was investigated in a nonreperfused model of myocardial infarction (MI) in 5 sham and 7 infarcted rats. Rats were scanned at 2 and 4 weeks post surgery to allow for global and regional functional and structural analyses of the heart. Images were of sufficient quality to enable semi-automatic segmentation using Segment. Significant increase in end-systolic volume (ESV) was observed in MI rats at 2 weeks post surgery. At 4 weeks post surgery, end-diastolic volume (EDV) and ESV of MI rats were significantly higher than in sham rats. Ejection fraction (EF) of MI rats dropped significantly at 2 weeks and a further significant drop was observed at 4 weeks indicating contractile dysfunction. Wall thickness (WTh) analyses in MI rats at 4 weeks revealed significant reduction in end-diastolic (ED) wall thickness in the anterior region due to necrosis of myocytes. In the posterior region, WTh was significantly higher due to LV hypertrophy. At end-systole (ES), the MI rats revealed significant decrease in WTh in the anterior and lateral regions. MI rats suffered reduction in systolic wall thickening in all regions of the heart, indicating global contractile dysfunction.