Diffusion magnetic resonance imaging (dmri) is a technique that can be used to examine the diffusion characteristics of water in the living brain. A recently developed application of this technique is tractography, in which information from brain images obtained using dmri is used to reconstruct the pathways which connect regions of the brain together. Proxy measures for the integrity, or coherence, of these pathways have also been defined using dmri-derived information. The disconnection hypothesis suggests that specific neurological impairments can arise from damage to these pathways as a consequence of the resulting interruption of information flow between relevant areas of cortex. The development of dmri and tractography have generated a considerable amount of renewed interest in the disconnectionist thesis, since they promise a means for testing the hypothesis in vivo in any number of pathological scenarios. However, in order to investigate the effects of pathology on particular pathways, it is necessary to be able to reliably locate them in three-dimensional dmri images. The aim of the work described in this thesis is to improve upon the robustness of existing methods for segmenting specific white matter tracts from image data, using tractography, and to demonstrate the utility of the novel methods for the comparative analysis of white matter integrity in groups of subjects. The thesis begins with an overview of probability theory, which will be a recurring theme throughout what follows, and its application to machine learning. After reviewing the principles of magnetic resonance in general, and dmri and tractography in particular, we then describe existing methods for segmenting particular tracts from group data, and introduce a novel approach. Our innovation is to use a reference tract to define the topological characteristics of the tract of interest, and then search a group of candidate tracts in the target brain volume for the best match to this reference. In order to assess how well two tracts match we define a heuristic but quantitative tract similarity measure. In later chapters we demonstrate that this method is capable of successfully segmenting tracts of interest in both young and old, healthy and unhealthy brains; and then describe a formalised version of the approach which uses machine learning methods to match tracts from different subjects. In this case the similarity between tracts is represented as a matching probability under an explicit model of topological variability between equivalent tracts in different brains. Finally, we examine the possibility of comparing the integrity of groups of white matter structures at a level more fine-grained than a whole tract.

This work is focussed on the analysis of breast tumour physiology by pharmacokinetic modelling of dynamic contrast enhanced MRI (DCE-MRI) data. DCEMRI consists of the intravenous bolus injection of a small molecular weight contrast agent into the patient followed by the rapid acquisition of MR images across both breasts. Due to the leaky nature of the lesion microvasculature there is a greater uptake of contrast agent within the tumour than in the surrounding tissues. The dynamic contrast enhanced MR signal curve can be fitted by compartmental analysis providing information linked to the tumour’s permeability and flow. The effect of the DCE-MRI acquisition parameters on the accuracy of the estimated pharmacokinetic quantities was investigated together with the assumptions lying behind the pharmacokinetic model used for the fitting. Contrast enhanced MRI data were also examined using a fractal measure of tumour heterogeneity with the aim of assessing whether this could be a potential predictor of the tumour response to chemotherapy. Among the factors believed to play an important role in terms of tumour treatment is an increased interstitial fluid pressure (IFP) in the central areas of some large tumours. Here DCE-MRI data were analyzed in a way to see whether it could provide any information related to IFP distribution across tumour volumes. Finally, when performing quantitative DCE-MRI, particular care needs to be taken in the choice of an arterial input function (AIF) which accurately describes the passage of the contrast agent bolus at the lesion location. Here a new approach was proposed and demonstrated for the estimation of a tumour capillary input function together with lesion pharmacokinetic parameters. This was achieved by optimizing the capillary input function with a measure of the patient’s cardiac output, a parameter which is expected to vary depending on the patient’s pathology/physiology.

Brain maturation is an important factor in cognitive, emotional, behavioural and motor development during childhood and adolescence. This study uses multi-modal magnetic resonance imaging (MRI) techniques to assess neural representations of devel opment in both healthy and abnormally developing populations. A novel face emotion stimulus set, designed to assess distinct dimensions of facial emotion, particularly to assess the e ect of averted faces, is introduced in a pilot functional MRI study of an adult cohort. Results from this pilot study show that interactions between face direction and emotion can infuence which brain areas are recruited for emo- tion processing, suggesting that the neural correlates of judging facial emotion content are modulated by face direction. Facial emotion perception was assessed as a neural task to investigate dimensions of emotion processing, and emotion processing development, in a group of children and adolescents. A number of correlations were found between dimensions of the task and developmental measures such as age, pubertal development and intelligence. In particular, intelligence was shown to be positively associated with the increasing utilization of regions associated with cognitive control, such as the prefrontal cortex. A voxel-based morphometry (VBM) study explored potential structural correlates of adolescent development. Age was found to correlate with changes in local brain regions, however pubertal development was shown to be a more accurate measure of those changes. A diusion tensor imaging assessment of white matter using fractional anisotropy has demonstrated important developmental di erences in white matter be- tween males and females over childhood and adolescence. Findings also suggest diff erent relationships between intelligence and white matter for males and females. Developmental Coordination Disorder, a common childhood disorder characterised by deficits in learning and automating motor skills, was assessed as an example of ab normal brain development. VBM was used to show that kinematic metrics of a simple visuomotor task correlated with regional grey matter volumes.

Depression and schizophrenia are common psychiatric disorders that can be disabling and chronic. This thesis aimed to further elucidate the underlying neural substrates using functional magnetic resonance imaging (fMRI) based studies. Hypothesized impairments in reinforcement learning in depression and schizophrenia were investigated, as were the neural correlates of abnormalities of social information processing in schizophrenia. Computational models of reinforcement learning are based on the concept of a 'prediction error' (PE, discrepancy between the expected and actual outcome) signal to update predictions of rewards and improve action selection. It has been argued that the firing of dopamine neurons encode a reward PE signal that mediates the learning of associations and the attribution of motivational salience to reward-related stimuli. Using model-based fMRI, the encoding of neural PE signals in patients with depression and schizophrenia were investigated. Consistent with hypotheses, patients exhibited different abnormalities in neural PE signals, with the degree of abnormality correlating with increased anhedonia/psychotic symptoms in depression/schizophrenia. These findings are consistent with the suggestion that a disruption in the encoding of PE signals contributes to anhedonia symptoms in depression by disrupting learning and the acquisition of salience of rewarding events. In schizophrenia, abnormal PE signals may contribute to psychosis by promoting aberrant perceptions and abnormal associations. In a different study, the neural responses to social exclusion in schizophrenia were investigated. Schizophrenia patients failed to modulate activity in the medial prefrontal cortex with the degree of exclusion, unlike controls. This highlights the neural substrates of putatively impaired social information processing in schizophrenia. Overall, these findings are consistent with proposals that psychiatric syndromes reflect different disorders of neural valuation. This perspective may help bridge the gap between the biological and phenomenological levels of understanding of depression and schizophrenia, hopefully contributing in the long term to the development of more effective treatments.

Individuals with Alcohol Related Neurodevelopmental Disorder (ARND) and Attention-Deficit/Hyperactivity Disorder (ADHD) display similar deficits in behavioural, cognitive, and executive dysfunction symptoms; however, the underlying impairment in brain function and attention pathways is thought to be different. This study compared these two clinical groups, and healthy controls, using psychological assessments and functional magnetic resonance imaging (fMRI). The two clinical groups had significantly different scores on measures of overall intellectual functioning, working memory, and the conjunction trials on the fMRI assessment but could not be differentiated on other measures from rating scales, standardized psychological assessments, and performance data from fMRI tasks. The fMRI task accuracy variables were strongly correlated with related standardized psychological measures. All groups demonstrated difficulties with response inhibition compared to attention, and the clinical groups demonstrated more difficulties with attention and variability compared to the control group on a computer-paced Go/No-Go task. The comparison of a self-paced and a computer-paced Go/No-Go task indicated that the computer-paced task would be more appropriate to use with fMRI to assess cortical activation in response inhibition. It was found that the ADHD group had higher levels of cortical activation (indicating that more cognitive effort was require to reach the same level of behavioural performance) compared to the ARND group during the visual-spatial attention tasks, whereas the ARND group had higher levels of activation during the response inhibition and working memory tasks. Despite no significant differences in behavioural performance, the fMRI tasks helped to demonstrate different activation patterns that could help distinguish and differentially diagnose these two similar groups. / October 2016

The purpose of this project was to assess techniques which could be implemented in clinical cardiac MRI using a moderate gradient performance imaging system in order to aid in the assessment of myocardial function. Possible improvements in image contrast were assessed using four different magnetisation preparation schemes applied prior to MR image acquisition in order to aid in the delineation of myocardial borders, and therefore improve cardiac image assessment quality. The usefulness of several novel T2*-weighted acquisition techniques were assessed in clinical cardiac applications in order to indirectly assess myocardial perfusion. Four magnetisation preparation schemes were applied in order to attempt to improve image contrast in short axis gradient-echo cardiac MRI; T2, T1, Magnetisation Transfer Contrast (MTC), and Double Inversion (DI). The T2, and preparation schemes proved to be the most effective, showing an initial improvement in image contrast by approximately 100% and proving effective in improving image contrast over the entire imaging duration {550 ms through the cardiac cycle). The MTC preparation scheme showed a 50% improvement in image contrast, again being effective over the entire imaging duration. The DI preparation scheme proved useful in creating a black blood gradient-echo image but showed no improvement in contrast throughout the imaging duration (since the DI preparation technique is essentially a 'snapshot' technique). Recent developments in cardiac MRI have moved towards assessment of myocardial perfusion, using first-pass contrast-enhancement imaging. This approach requires assessment of a large enough volume of the heart to allow assessment of perfusion as well as retaining a high temporal resolution of 7 or 2 seconds, and therefore a more modem high performance imaging system. For moderate performance gradient MR systems an alternative method of assessing myocardial perfusion is therefore required. Several novel techniques to assess myocardial T2* values in order to indirectly infer myocardial perfusion are introduced. The use of an original multi-echo gradient-echo imaging sequence to acquire T2* pixel-maps was investigated in phantoms and compared with commercially available sequences in order to validate its use.

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Original research submitted as partial fulfillment of the requirements for the Masters in Medicine degree in Orthopaedic surgery at the University of Witwatersrand, Johannesburg, April 2014 / Objectives 1. Assessment of radiological parameters of spinal stenosis using Magnetic Resonance imaging. 2. Clinical assessment of patients with Oswestry disability index and Neurogenic claudication outcome score questionnaires. 3. To assess correlation between clinical assessment questionnaires’ scores and radiological parameters. Background. Spinal stenosis is a common presentation in the elderly and a reason for surgical intervention. Diagnostic criteria are still inconclusive. There is poor correlation between clinical and radiological findings. New observations have been described and whether they improve diagnostic criteria remains to be seen. Methods. 30 patients with spinal stenosis were included in the study. The 2 questionnaires were administered and Magnetic Resonance Imaging copies were obtained. Questionnaires and images were analyzed. Osirix programme was used to analyze the images and do the measurements. Data was entered onto an excel sheet and analyzed using Statistica software. Frequencies and correlations were done. Results. The age range was between 41 and 85.There were 22 females and 8 males. L4/L5 was the commonest level involved in 23 patients. Multilevel involvement was 23% and those patients had a higher morphological grade, which was statistically insignificant. The commonest morphological grade was C. Sedimentation was positive in 93% of the patients. The Oswestry disability Index and Neurogenic Claudication Outcome score were negatively correlated, which was statistically significant, p = 0.0004. There was no correlation between clinical and radiological features. Conclusion. Spinal stenosis remains a clinical dilemma. There is variability within the population and lack of correlation between clinical and radiologic features. Radiological features however correlate with each other, but do not help with optimizing patient care.

Quadrupolar relaxation-based methods in Fast Field-Cycling MRI Nicholas R. Payne Aberdeen Biomedical Imaging Centre, University of Aberdeen, AB25 2ZD, Scotland, UK Fast Field-Cycling MRI (FFC-MRI) can access contrast based on the dependence of a sample's relaxation rate to the applied magnetic field strength. This technique can provide signal based on interactions with local quadrupolar nuclei through cross-relaxation, however, there are other so-called Nuclear Quadrupole Double Resonance (NQDR) techniques described in the literature. This work has been centred on efforts to apply these techniques to FFC-MRI and otherwise explore how interactions between protons and quadrupolar nuclei can be further exploited. Through this work two irradiation systems were designed and built for manual tuning, in the first instance, and automatic tuning. The latter was able to quickly retune to coil, however, it was limited in RF power handling capability. A second strand of work was concerned with the reduction in receiver deadtime required to detect signal from solid-state samples such as those previously used in NQDR experiments in the literature. However, circuitry designed to dampen coil ringing by temporarily reducing the resonator's Q-factor following a pulse, along with a novel method utilising field-cycling were not able to reduce the deadtime enough to detect signal from relevant samples. This, coupled with a lack of evidence of NQDR effects in gel-like samples, proved the ultimate stumbling block for NQDR in FFC-MRI. Success was seen in a third strand of work in which simulations were used to design custom experiments which could be used to provide large increases to the signal-to-noise ratio in some experiments. The simulated environment also allowed for fast testing and development of new post-process algorithms which could more accurately calculate relaxation rates. The work concluded that NQDR is unlikely to be useful in FFC-MRI due to the constraints on both the sample and the technique. However the information from quadrupolar nuclei can be improved with better post-processing and tailored pulse sequence parameters.

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