Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD

Functional neuroimaging in subjects at high genetic risk of schizophrenia

Schizophrenia is an incapacitating psychiatric disorder characterized by hallucinations and delusions with a lifetime risk of around 1% worldwide. It is a highly heritable disorder which generally becomes manifest in early adult life. The established condition has been associated with structural and functional brain abnormalities, principally in prefrontal and temporal lobes, but it is unclear whether such abnormalities are related to inherited vulnerability, medication effects, or the presence of symptoms. Furthermore, the mechanisms by which the pre-morbid state switches into florid psychosis are unknown. The Edinburgh High Risk Study is designed to address these issues. The first phase (1994-1999) employed repeated clinical, neuropsychological assessments and structural imaging. In the current phase (1999-2004) functional magnetic resonance imaging (fMRI) has been added to the tests used previously.As part of the Edinburgh High Risk Study, this study used a covert verbal initiation fMRI task (the Hayling Sentence Completion Test) known to elicit frontal and temporal activation, to examine a large number of young participants at high risk of developing schizophrenia for genetic reasons, in comparison with a matched group of healthy controls. Subjects were scanned at baseline, and after approximately one year. At the time of the baseline scan none of the participants met criteria for any psychiatric disorder, however, a number of subjects reported isolated psychotic symptoms on direct questioning. Over the course of the entire study (1994-2004), 21 individuals developed schizophrenia according to standard diagnostic criteria. Four of these subjects made the transition over the course of the current study (1999-2004), i.e. subsequent to the baseline functional scanThere were three main aims of the current study (i) to use fMRI to identify the neural correlates of state and trait effects in high risk individuals, (ii) to determine ifit is possible to distinguish those who subsequently become ill from those who remain well using functional imaging, and (iii) to determine if patterns of brain activity change with the transition to illness, or vary with changes in symptomatic status of these individuals.Regarding the first aim, group differences of apparent genetic origin were found in prefrontal, thalamic, cerebellar regions, and differences in activation in those with symptoms were found in the parietal lobe. Functional connectivity analysis examining interactions between these regions also indicated similar abnormalities. These results may therefore reflect inherited deficits, and the earliest changes associated with the psychotic state, respectively. Although only a small number of subjects became ill over the course of the current study («=4), initial findings suggested abnormalities in medial prefrontal and medial temporal regions (with an indication of parietal lobe dysfunction) were able to distinguish those who later became ill versus those that remained well. Finally, there were also indications of changes in activation patterns over time in a subgroup of subjects with varying symptomatic status.To conclude, these results are consistent with previous findings in the Edinburgh High Risk Study - what is inherited by the high risk individuals is a state of heightened vulnerability manifesting, in the case of functional imaging, as abnormalities in activation and/or connectivity in preffontal-thalamiccerebellar and prefrontal-parietal regions. These finding also suggest that there are additional differences seen in those with psychotic symptoms, and to some extent in those who subsequently go on to develop the disorder. These results are not confounded by anti-psychotic medication since all subjects were anti-psychotic naive at the time of assessment. The lack of findings traditionally associated with the established illness (dorsolateral prefrontal cortex and lateral temporal lobe) indicate these may be specifically associated with the established state, or when performance differences become manifest. Overall therefore these findings reveal information regarding the pathophysiology of the state of vulnerability to the disorder and about the mechanisms involved in the development of schizophrenia or schizophrenic symptomatology