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Magnetic resonance imaging (MRI) is a widely employed imaging modality that allows observation of the interior of human body. Compared to other imaging modalities such as the computed tomography (CT), MRI features a relatively long scan time that gives rise to many potential issues. The advent of parallel MRI, which employs multiple receiver coils, has started a new era in speeding up the scan of MRI by reducing the number of data acquisitions. However, the finally recovered images from under-sampled data sets often suffer degraded image quality. This thesis explores methods that incorporate prior knowledge of the image to be reconstructed to achieve improved image recovery in parallel MRI, following the philosophy that ‘if some prior knowledge of the image to be recovered is known, the image could be recovered better than without’. Specifically, the prior knowledge of image sparsity is utilized. Image sparsity exists in different domains. Image sparsity in the image domain refers to the fact that the imaged object only occupies a portion of the imaging field of view; image sparsity may also exist in a transform domain for which there is a high level of energy concentration in the image transform. The use of both types of sparsity is considered in this thesis. There are three major contributions in this thesis. The first contribution is the development of ‘GUISE’. GUISE employs an adaptive sampling design method that achieves better exploitation of image domain sparsity in parallel MRI. Secondly, the development of ‘PBCS’ and ‘SENSECS’. PBCS achieves better exploitation of transform domain sparsity by incorporating a prior estimate of the image to be recovered. SENSECS is an application of PBCS that achieves better exploitation of transform domain sparsity in parallel MRI. The third contribution is the implementation of GUISE and PBCS in contrast enhanced MR angiography (CE MRA). In their applications in CE MRA, GUISE and PBCS share the common ground of exploiting the high sparsity of the contrast enhanced angiogram. The above developments are assessed in various ways using both simulated and experimental data. The potential extensions of these methods are also suggested.

This thesis addresses the much needed quantitative assessment of the physiological effects the magnetic fields used in MRI. MRI has a well-earned reputation for being a safe, non-ionising alternative imaging modality for both the patient and MR practioner alike. Although the operating environment can prove hazardous for inexperienced and untrained personnel, appropriate training and adoption of safe working practices can prevent adverse incidents.

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This work addresses the distortions in Functional Magnetic Resonance Images (FMRI) caused by subject motion. FMRI is a non-invasive technique which shows great promise in providing researchers and clinicians with neurological information both about healthy subjects and clinical patients by mapping functional activation within the brain using Echo Planar Imaging (EPI). If reliable information is to be obtained from these images, motion correction must be carried out in order to remove or suppress the artefacts arising from subject movement. This work begins by using exploratory data techniques to describe these artefacts so that they can be characterised according to their origin and spatio-temporal manifestation. Based on testing of the accuracy and consistency of existing rigid-body motion correction methods on FMRI data, a new registration algorithm Motion Correction using the FMRIB Linear Image Registration Tool (MCFLIRT) has been developed. It is shown that while MCFLIRT is both more accurate and more robust than previous methods, rigid-body registration schemes in general cannot completely remove the distortions associated with motion and so subsequent analysis of the images may still be inaccurate. Furthermore, it is demonstrated that failure to use a sufficiently detailed model of subject motion in FMRI can in fact lead to degradation of the images through the use of existing motion correction algorithms. Based on these findings, alternative schemes including non-rigid registration and adaptive real-time methods are evaluated. Leading on from this investigation, a framework for Temporally-Integrated Geometric EPI Realignment (TIGER), incorporating both spatial and temporal information about the images, is proposed. An implementation based on this novel modality-specific model is developed and tested against existing rigid-body registration methods. Results show that this new approach is able to achieve significantly more accurate results than previous methods. The quality of correction provided by this new approach brings more subtle artefacts in the data to the fore, suggesting a number of avenues of further research in this area. These are outlined in the final chapter of the thesis.

Accumulating evidence suggests that schizophrenia is associated with altered cerebral laterality secondary to a deviation from normal brain development. A number of findings suggest that age of onset of psychosis and gender may have a significant bearing on the nature and extent of the deviation. In order to examine this, early onset patients (12-19 years of age) were compared to healthy controls and later onset patients in a series of studies using standard neuropsychological techniques, experimental divided visual field (DVF) measures and magnetic resonance imaging (MRI). Specific attention was directed to examining the influence of sex and age of onset on hemispheric specialisation. In the neuropsychological studies, early onset patients (n=35) demonstrated significant impairment of intellectual functioning relative to normal adolescents (n=35) but no significant VIQ-PIQ discrepancy. Earlier age of onset was significantly correlated with reduced VIQ and FSIQ. Early onset patients showed significant reduction in hand skill, increased incidence of non-right eye preference and crossed hand-eye dominance. In addition, patients demonstrated reduced right ear advantage (REA) in dichotic listening and inability to modulate ear advantage by directing attention. In the DVF experiments, early onset patients (n=20) demonstrated normal lateralisation in phonological word recognition but sexually dimorphic anomalies in lexico-semantic processing relative to normal controls (n=20). Males showed impairment in imageable word recognition whereas females were more impaired in emotional word recognition. In both cases, the observed anomalies implicated a disturbance in the semantic network subserved by left hemisphere ventromedial and superior temporal heteromodal cortex. In MRI investigations, early onset patients (n=33) had smaller cerebral hemispheres and larger lateral ventricles than controls (n=32). Male patients showed reduction of leftward asymmetry in temporal lobe volume and female patients showed reversal of rightward asymmetry. Significant correlations were found between left ventricular brain ratio and reaction time to phonological word processing. Together, the combined results indicate that early onset schizophrenia is associated with a significant but selective alteration of cerebral laterality, that age of onset is likely to be a determinant of this alteration and that, to some extent, these changes are mediated by gender. The results are discussed within the context of neurodevelopmental aetiology.

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The gadolinium ((^153)Gd) complexes of 21 aza-phosphinic and aza-carboxylic acid macrocycles based on 1,4,7,10- tetraazacyclododecane were studied as possible contrast agents for magnetic resonance imaging. The acid dissociation rates and partition coefficients of gadolinium complexes were measured and related to their in vivo stability and route of elimination in mice. The anionic aza-phosphinic acids had low acid dissociation rates (24-78 x l0(^6) sec (^-1) at pH 1) which correlated with high in vivo stability (<0.025% dose in the skeleton at 24 hours). [Gd.l2N4P4Bz4]" shows potential as a gall bladder, bile duct contrast imaging agent at doses of 0.1 to 10 µmol/kg , and for tumour detection within the hepatobiliary system at doses of 100 to 200 µmol /kg .Macrocycles based on l,4,7,10-tetraazacyclododecane can be used to complex yttrium (90y) for tumour therapy. 90y complexes of aza-phosphinic and aza-carboxylic acid derivatives showed slow acid catalysed dissociation rates of 1-14 X 10"6 sec'l at pH 1, and rapid association kinetics of greater than 80% yttrium uptake within 30 minutes at 5 µM ligand. A tetraaza-carboxylic acid and a tri-phosphinic acid derivative modified with maleimide were linked to monoclonal antibodies and labelled with 90y. Both were highly stable in vivo with <0.0l% 90y dose in the mouse femur shaft at 48 hours.Seven aza-phosphinic and aza-carboxylic acid macrocycles based on i,4,7,-triazacyclononane were labelled with radioactive gallium or indium. Gallium complexes were generally more stable in vivo than the corresponding indium complexes. Three 67Ga and two min complexes showed potential as imaging agents and one gallium complex as a hepatobiliary imaging agent. Several complexes were examined as possible tumour localisation agents, [Ga.9N3] giving a tumour to blood ratio of 22:1 at 4 hours after injection.

The presence of white matter hyperintensities (WMH) and silent infarcts on magnetic resonance imaging is a common finding in elderly individuals. This subcortical ischemic vasculopathy is associated with age and cerebrovascular risk factors and can increase the risk of dementia, yet the contribution of subcortical vascular disease to the clinical profile and progression of Alzheimer’s disease patients is still relatively poorly understood. This study assessed the presence, severity and progression of WMH and lacunar infarcts and studied their relationship with measures of brain function and cognition in 64 patients with Alzheimer’s disease. Both a visual rating scale and volumetric tissue segmentation analysis were used to evaluate brain-behaviour relationships of WMH seen on T2-weighted and Proton Density MRI scans. In addition to describing the topographical distribution of WMH and lacunes, and examining sex differences, the volume and location of WMH were correlated with executive function, frontal lobe perfusion, and medial temporal lobe atrophy. The results confirm and extend previous findings suggesting that WMH are located primarily in the frontal and parietal regions and are associated with mild decline in tasks of executive function. WMH severity was not associated with a decrease in frontal lobe perfusion as measured by Single Photon Emission Computed Tomography. The investigation of different WMH subtypes revealed that lacunar infarcts were found most often within deep WMH. At one year follow-up, progression was seen in deep WMH, specifically in the frontal lobe and in lacunes found within the periventricular regions. Furthermore, progression in WMH was associated with a decline in cognition. Taken together, these studies indicate the utility of measuring WMH by subtype (periventricular and deep WMH and lacunes) in understanding progression patterns and brain-behavior relationships. Since, subcortical ischemic vasculopathy may be potentially preventable; this study underlines the need to study interventions that address risk factors for the development of small vessel cerebrovascular disease, which may be helpful in preventing disability in the elderly.

Whiplash-related injuries and manifestations, typically neck pain, following car collisions are known to potentially disable individuals with a high and increasing cost to society. There is limited knowledge regarding the temporomandibular joint (TMJ) sequelae following whiplash trauma. Previous studies are typically based on retrospective data and few follow-ups are prospective and controlled in design. Furthermore, previous follow-ups have not included magnetic resonance (MR) imaging, which is a prerequisite for verification of TMJ status. The aims of this prospective long-term study were (i) to determine frequency of inaccurate recall of TMJ symptoms in patients with a history of whiplash trauma, and (ii) to evaluate incidence, prevalence and progression of TMJ pathology, verified with MR imaging, and TMJ symptoms in patients after whiplash trauma, compared with the natural course in matched volunteers. We studied 60 consecutive patients who had neck symptoms following a rear-end car collision and were seen at a hospital emergency department. Bilateral TMJ MR imaging and clinical examination were performed at inception and at follow-up on average 15 years later. A self-administered questionnaire regarding TMJ symptoms (pain, dysfunction, or both) and a subsequent interview were performed at inception, at the one-year, and 15-year follow-up. Fifty-seven patients (95%) participated in all three examinations (85% for MR imaging examinations). Concurrently, 53 volunteers matched by age and sex followed the same protocol. Fifty volunteers (94%) participated in all three examinations (89% for MR imaging examinations). Ethics approval of the study protocol and informed consent from all participants was obtained. The calculated agreement between each patient’s inceptive and retrospective reports on TMJ symptoms yielded a kappa value of 0.41 (95% CI 0.18-0.64). Sixteen patients (40%) had inaccurate recall one year after whiplash trauma. There was no statistically significant difference in TMJ symptoms reported by the patients to be present before whiplash trauma compared with matched volunteers at inception. Prevalence of TMJ symptoms increased significantly with whiplash trauma and the increase remained stable throughout the 15-year study period, which contrasted to the natural course in volunteers. After one year the difference in prevalence between patients and volunteers was 54% versus 21% (p=0.0003) and after 15 years 49% versus 18% (p=0.0017). There was no statistically significant difference between patients and volunteers in prevalence of TMJ disc displacement either at inception (63% versus 53%) or at 15-year follow-up (63% versus 55%). TMJ disc displacement was significantly more prevalent in symptomatic volunteers compared with asymptomatic volunteers (89% versus 31%, p=0.0002). Incidence or progression of MR imaging verified TMJ pathology did not differ between patients and volunteers. This prospective 15-year follow-up concludes - that future studies on TMJ sequelae following whiplash trauma should be prospective in study design with examinations conducted in close proximity to whiplash trauma. This allows for reliable baseline status and potential bias of inaccurate recall of symptoms is minimized. - that future controlled studies on TMJ pathology in patients should include control groups of not only asymptomatic but also symptomatic volunteers in order to avoid potentially biased conclusions. - that one of three patients exposed to whiplash trauma can be expected to develop TMJ symptoms beyond that which corresponds to the natural course in volunteers. This finding and previously reported impairment of jaw function in patients with symptoms after whiplash trauma points to the need for including TMJs and related muscles in routine medical examinations of patients with symptoms following whiplash trauma. - that adult individuals presenting with no or mild TMJ symptoms seldom show development or aggravation of TMJ pathology and there is no or little indication for TMJ treatment of these adult individuals. This is in contrast to the higher progression of TMJ pathology previously reported for adult patients with TMJ symptoms, which requires treatment.