Conduction of electrical excitation in cardiac tissue is mediated by multiple physiological factors. Abnormal conduction may lead to onset of arrhythmia, and is correlated experimentally and clinically with electrogram fractionation. In-silico modelling studies seek to characterise and predict the biophysical phenomena underlying electrical excitation and conduction, and thus inform experiment design, and diagnostic and treatment strategies. Existing models assume syncytial or continuum behaviour, which may not be an accurate assumption in the disease setting. The aim of this thesis is to correlate simple theoretical and experimental models of abnormal cardiac conduction, and investigate the limits of validity of the theoretical models under critical parameter choices. An experimental model of 1D continuum conduction is established in guinea pig pap- illary muscle to examine the relationship between mean tissue resistivity and electrical conduction velocity (CV). The relationship is compared with a monodomain tissue model coupled with the Luo Rudy I (LR1) guinea pig ventricular action potential, which obeys classical cable theory of conduction under pharmacological modulation. An experimental model of 1D discrete conduction is created via development of a micro-patterned culture model of the HL-1 atrial myocyte cell line on micro-electrode arrays, which has a lower baseline conduction velocity compared to conventional cardiomyocyte models. A novel 1D bidomain model of conduction of discrete cells coupled by gap junctions is proposed and validated, based on existing analytical and numerical studies, and coupled to the LR1 model. Simulation of slow conduction under modulation of physiological parameters reveal difference in the excitation conduction between continuum and discrete models. Electro- gram fractionation is observed in the discrete model, which may be a more realistic model of conduction in diseased myocardium. This work highlights possibilities and challenges in comparing and validating theoretical models with data from experiments, and the im- portance of choosing the appropriate modelling assumptions for the specific physiological question.

Modern advances in ultrasound imaging technology have led to the development of targeted microbubble contrast agents; micrometer sized encapsulated bubbles coated with binding agents. Their gas core gives them high echogenicity, scattering incident ultrasound and allowing them to oscillate to producing a detectible sound of their own. The binding agent allows them to be used for molecular imaging. The work in this thesis aims to provide a better understanding of the behaviour of microbubble contrast agents, but with a focus on their use as molecular imaging agents. The thesis starts with an introduction to microbubble contrast agents, stating their current clinical usage both as a normal contrast agent and for molecular imaging and highlighting their strengths and limitations. In the following chapter, the theory behind the modelling of microbubble motions is introduced, discussing modelling bubble oscillations using the Rayleigh-Plesset equation, and the translation of a bubble in an acoustic field through Bjerknes forces. The first piece of novel work to be presented in this thesis is in the form of a model for non-spherical oscillations in microbubble contrast agents, with the application of modelling the destruction of microbubble contrast agents. A Boussinesq-Scriven approach was taken, to adapt a pre-existing model for shell free bubbles by taking into account the viscoelastic effect of the shell. Results calculated using the developed model showed a significant difference in destruction threshold between the shelled and shell-free bubbles. The second piece of work focuses on the effects of an ultrasound field on adherent microbubbles including their detachment and deflation. Analysis of experimental results on targeted microbubbles adherent to a micro-tube with flow shows that the effects of ultrasound are significant even at relatively low acoustic pressure. As acoustic pressure is increased, the percentage of detached and/or deflated microbubbles does also. Four forces are identified which could be responsible for detachment, namely, shear, primary and secondary Bjerknes, and oscillations and their relative significance is investigated. The results from this work are then used to make suggestions about the clinical imaging for targeted contrast agents. The final novel piece of work presented is a dual transducer arrangement as a potential method of increasing targeted microbubble binding efficiency through the creation of a simple one-dimensional acoustic manipulator, capable of being implemented in any clinical ultrasound scanner with a phased array. Simulations and experimental investigations were carried out on the system in order to demonstrate the feasibility of such an acoustic manipulator and to gain understanding of its practicalities.

In this thesis we propose a framework for the detection and classification of colorectal polyps to assist endoscopists in bowel cancer screening. Such a system will help reduce not only the miss rate of possibly malignant polyps during screening but also reduce the number of unnecessary polypectomies where the histopathologic analysis could be spared. Our polyp detection scheme is based on a cascade filter to pre-process the incoming video frames, select a group of candidate polyp regions and then proceed to algorithmically isolate the most probable polyps based on their geometry. We also tested this system on a number of endoscopic and capsule endoscopy videos collected with the help of our clinical collaborators. Furthermore, we developed and tested a classification system for distinguishing cancerous colorectal polyps from non-cancerous ones. By analyzing the surface vasculature of high magnification polyp images from two endoscopic platforms we extracted a number of features based primarily on the vessel contrast, orientation and colour. The feature space was then filtered as to leave only the most relevant subset and this was subsequently used to train our classifier. In addition, we examined the scenario of splitting up the polyp surface into patches and including only the most feature rich areas into our classifier instead of the surface as a whole. The stability of our feature space relative to patch size was also examined to ensure reliable and robust classification. In addition, we devised a scale selection strategy to minimize the effect of inconsistencies in magnification and geometric polyp size between samples. Lastly, several techniques were also employed to ensure that our results will generalise well in real world practise. We believe this to be a solid step in forming a toolbox designed to aid endoscopists not only in the detection but also in the optical biopsy of colorectal polyps during in vivo colonoscopy.

The improvised explosive device (IED) has been the characteristic weapon of conflicts in Iraq and Afghanistan. Under-vehicle explosions result in rapid floor deformation, transmitting short duration, high amplitude loading to the occupant's foot and ankle. Current operational vehicles are subjected to full-scale explosions to assess the level of protection they offer their occupants. The decision to pass or fail a vehicle design is made through assessing the axial force transmitted through the lower extremity of a 'dummy' which has been designed to behave like a human. This thesis investigates the ability of combat boots to reduce the severity of injuries during under-vehicle explosions. Both experimental and numerical techniques were used to gain a better understanding of the behaviour of the combat boot under high rate loading. Initially, drop rig experiments were conducted to assess the shock absorbing capacity of the two combat boot designs most commonly used by UK troops. Following on, more complex experiments were conducted using an anti-vehicle under-belly injury simulator (AnUBIS) which was designed, developed and characterised to simulate floor displacement during an under-vehicle explosion. AnUBIS was used to compare the response of cadaveric specimens against two dummy designs; the Hybrid-III and the MiL-Lx. The MiL-Lx was found to be more biofidelic than the Hybrid-III. Finite element models of both the MiL-Lx and a combat boot were developed and used to investigate the sensitivity of the materials and geometry of the combat boots in reducing the force transmitted to the MiL-Lx during an under-vehicle explosion. Finally, two commercially available blast mat designs were assessed using AnUBIS and both the MiL-Lx and Hybrid-III. The two ATDs ranked the mats in the same order; however, the percentage reduction in peak force was different. The experimental and numerical approach used in this thesis has developed a greater understanding of both the biofidelity of current ATDs and the capacity of current mitigating technologies. This approach can be used to develop and assess mitigation technologies for use in future conflicts where under-vehicle explosions are a significant threat.

Total Hip Replacement (THR) is considered one of the commonest, mechanically effective and cost effective orthopaedic procedures performed. Routinely patients are discharged from follow-up at 1-year after surgery and little is known about hip and lumbar spine movement during function after this time. Twenty four participants, two years after uncomplicated primary THR were compared with 24 matched healthy adults during 4 functional activities and clinical assessment of hip and lumbar spine movement. The clinical tests and hip, pelvis and lumbar spine motion during gait are presented. A6 camera, Kinemetrix Motion Analysis system(50Hz) (MIE Ltd., UK) and a single 0.4 x 0.6m Bertec force platform (300Hz) (MIE Ltd., UK) were used. Reliability testing of dynamic and clinical measures was undertaken and all data were tested for normality. Mean range and peak data were tested using Analysis of variance and post hoc t-tests. Data were analysed in three groups: Those after THR both the operated (THR op) and non-operated sides (THR non op) were investigated and compared to healthy individuals (THN). Alpha was set at p<0.05. All physiological hip movements were greater in the THN group but only lumbar spine flexion and lateral flexion were significantly larger with extension being less. During gait, the THR op side had significantly decreased mean hip range compared to the THR non op side and THN groups, whilst the THN side had significantly less mean range of lumbar spine motion in the sagittal plane. Sagittal plane peak hip moments were significantly larger in the THN group compared to the THR op. Considerable difference were identified in timing and range of the movement patterns in angle-time and angle-angle diagrams for the THN and THR groups. These findings highlight possible longer term spinal complications through abnormal mechanical use and question the effectiveness of current rehabilitation after THR.

No description available.

No description available.

No description available.

Regaining satisfactory functional ambulation is one of the main aims of post stroke rehabilitation. Ankle foot orthoses (AFOs) are nowadays prescribed for the management of lower limb impairments following stroke onset. Their prescription and design however, is mainly empirical due to a lack of evidence-based research on their effects on gait and on their mechanical characteristics. Scientific data are crucial if the effects of rehabilitation are to be maximized. The work presented in this thesis includes the investigation and development of methods that could be used to assess the effects of AFO on stroke survivors gait ability and, a feasibility study involving early stroke patients. The feasibility study aimed to evaluate the issues involved in a pilot randomised controlled trial (RCT) and when using a variety of outcome measures. The study also aimed to investigate, in a small group of stroke patients, the effect the provision of a solid polypropylene AFO has on gait biomechanics during the acute rehabilitation phase over a follow-up period of six months and, to measure the loads transmitted by the orthosis during gait. Two gait analysis protocols, one allowing a full 3-D kinematics and kinetics evaluation of human gait and one for spatiotemporal parameters measurements, were introduced and their reliability explored. The feasibility of strain gauging an AFO for measuring orthotic loads was ascertained and the use of the uncontrolled manifold (UCM) approach to verify centre of mass (CM) control during gait was investigated. These methods were validated with tests on able-bodied subjects. The application of such methodologies on stroke patients was successful. A comprehensive set of data collected was able to differentiate outcomes between walking with and without an AFO. Beneficial effects were shown when the subjects walked with the AFO at the ankle but also at the hip and knee level. Spatiotemporal parameters also improved when walking with an AFO. Gait strategy was clarified with the UCM approach with respect to CM position and the contribution of the AFO to the dorsiflexor moment was shown during early stance. The methods proposed were capable of producing reliable results and being applied to early stroke patient to assess their walking capability. Conducting research exploiting such methodologies will allow a better understanding of AFO properties and effects on gait, to promote recovery after stroke. Difficulties were encountered in recruiting subjects and these are discussed along with suggestions for future studies.

A comprehensive system for investigation of biomechanical and neuromuscular processes involved with producing handwriting and drawing was developed. The system included a pen-like grip measuring device that enabled the variations of finger grip force associated with writing and drawing to be measured while holding the pen in tripod grip. The pen was integrated with a digitiser tablet for recording x,ycoordinates and pressure of the nib and a motion analysis system for recording the limb and hand kinematics. It was observed that for line drawing in the y-direction of the tablet, finger forces were directly related to pen tip movement and finger forces were modulated in a repeatable and predictable fashion, while this was not the case for line drawing in the x-direction. This was evidence for longstanding assumptions. Wrist rotation was required for production of lines in the x-direction without excessive deviation. For writing tasks, it was observed that no two tasks performed by one subject share an identical writing process, not even when the writing results are (nearly) identical. The neuromuscular control apparatus is highly flexible and works in a coordinated fashion that allows production of nearly equal end-results by means of different mechanical and therefore neuromuscular processes. For spiral drawing, tremor that originates from the fingers, hand and arm was quantified with the transducer pen. Limb joint kinematics were displayed in three dimensions with colour coding of coordinate sample numbers. This method can reveal the origin of some forms of limb tremor. Pen grip force patterns during signature writing were found to be characteristic for subjects, which relate to their individual pen-hand interaction, resulting from fine control of distal joints. Variation between trials of the same subject was observed, revealing adaptations of the computational processes during writing. The potential for signature verification by means of finger force recording was explored.