Thesis (M.D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 194-207).

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 126-140).

Thesis (M.S.)--University of Florida, 2004. / Title from title page of source document. Document formatted into pages; contains 83 pages. Includes vita. Includes bibliographical references.

Thesis (PhD) - Swinburne University of Technology, Faculty of Life and Social Sciences, Brain Sciences Institute, 2008. / A thesis for Doctorate of Philosophy, Brain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology - 2008. Typescript. Includes bibliographical references (p. 193-250).

Thesis (M.D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 194-207) Also available in print.

Medical imaging plays an essential role in current clinical research and practice. Among the wealth of available imaging modalities, Positron Tomography Emission (PET) reveals functional processes in vivo by providing information on the interaction between a biological target and its tracer at the molecular level. A time series of PET images obtained from a dynamic scan depicts the spatio-temporal distribution of the PET tracer. Analysing the dynamic PET data then enables the quantification of the functional processes of interest for disease understanding and drug development. Given the time duration of a dynamic PET scan, which is usually 1-2 hours, any subject motion inevitably corrupts the tissue-tovoxel mapping during PET imaging, resulting in an unreliable analysis of the data for clinical decision making. Image registration has been applied to perform motion correction on misaligned dynamic PET frames, however, the current methods are solely based on spatial similarity. By ignoring the temporal changes due to PET tracer kinetics they can lead to inaccurate registration. In this thesis, a spatio-temporal registration framework of dynamic PET data is developed to overcome such limits. There are three scientific contributions made in this thesis. Firstly, the likelihood of dynamic PET data is formulated based on the generative model with both tracer kinetics and subject motion, providing a novel objective function. Secondly, the solution to the optimisation based on the generic plasma-input model is given, leading to the availability of a variety of biological targets. Thirdly, reference-input models are also incorporated to avoid blood sampling and thus extend the coverage of PET studies of the proposed framework. In the simulation-based validation, the proposed method achieves sub-voxel accuracy and its impact on clinical studies is evaluated on dopamine receptor data from an occupancy study, as well as breast cancer data from a reproducibility study. By successfully eliminating the motion artifacts as shown by visual inspection, the proposed method reduces the variability in clinical PET data and improves the confidence of deriving outcome measures on a study level. The motion correction algorithms developed in this thesis do not require any additional computational resources for a PET research centre, and they facilitate cost reduction by eliminating the need of acquiring extra PET scans in cases of motion corruption.

Structural changes in the frontal and temporal lobes and in subcortical white matter tracts often occur following closed head injury (CHI). In contrast to this well delineated structural pathology, the post-traumatic cognitively-related functional changes in these and other brain regions have not been adequately described. To characterize the long-term functional neuroanatomy of CHI, the present study compared regional cerebral blood flow (rCBF) patterns in 13 severely-injured, well-recovered, unmedicated patients to those from 13 well-matched healthy controls. rCBF was measured using oxygen-15 water intravenous bolus positron emission tomography (PET) while subjects performed the Wisconsin Card Sorting Test (WCST), an indicator of prefrontal lobe functioning that involves matching stimuli to a changing sorting principle based on external feedback, and a Cued Recall Memory Test (CRMT), which involves remembering semantically-related word pairs. The neuropsychological tasks were used to provoke specific neural systems believed to be important in task performance (the prefrontal cortex in the former, the hippocampus in the latter). Subjects also performed two specially designed sensorimotor control tasks to provide measures of baseline rCBF. Given the controversy regarding the statistical analysis of PET data, a two-pronged method was utilized: 1) Statistical Parametric Mapping, the state-of-the-art technique that examines rCBF throughout the entire brain, and 2) region of interest analysis, an anatomically-based method for examining rCBF in a limited set of brain regions. Between-group rCBF differences were tested in the four tasks separately and also in the two neuropsychological tasks after subtracting baseline rCBF (i.e., rCBF activation). To characterize the relationship between cerebral perfusion and behavior, correlations were performed between performance and rCBF activation (i.e., task-control) for each group separately, and between rCBF activation and an index of current neuropsychological functioning for the CHI patients. Analyses of each task separately revealed that, compared to controls, CHI patients showed lower rCBF in anterior cingulate cortex (ACC) and subcortical areas. Analyses of rCBF activation data revealed: 1) increases in left inferior frontal gyrus (including Broca's area) and left hippocampus of CHI patients relative to control subjects during the WCST, 2) a negative correlation between task performance and the right hippocampus during the WCST in CHI patients, and 3) correlations between the hippocampus and performance during the CRMT in the CHI patients that were in the opposite direction to those found in the control subjects. These neurofunctional changes are compatible with the structural and cognitive sequelae of CHI First, given a hypothesized role of the ACC in attentional processes, reduced rCBF in this region of CHI patients may relate to the persistent and often subtle difficulties in attention after CHI, whereas rCBF diminutions in subcortical regions may relate to diffuse damage to or deafferentation of subcortical regions in this CHI sample. Second, given similar (although slightly, but not significantly, poorer) performance on the WCST by the CHI patients, increased left prefrontal cortical activity may partially reflect behavioral compensation (e.g., subvocalization to aid memory during the task) and also physiological compensation for inefficiencies in other brain areas (e.g., subcortical regions). Finally, in light of the relatively poorer task performance of CHI patients (non-significant tendency in the WCST but highly significant in the CRMT), differences between the groups in the direction of the correlations between performance/cognition and hippocampal activation may suggest disorganization of hippocampal functioning in CHI patients. This exploratory and descriptive investigation identifies brain structures with post-traumatic changes that may be important to cognition. These results may provide evidence of both behavioral and neurophysiological compensation in patients with severe CHI. / Graduate

A short report submitted to the Faculty of Medicine, University of the Witwatersrand in partial fulfilment of the requirements for the degree of Master of Medicine in Nuclear Medicine / 19 patients were selected, from the patients screened, for investigation within 48 hours of the onset of an ischaemic cerebrovascular accident. Clinical neurulogical scoring, computerized tomography lCT) scans and single photon emission computed tomography (SPECT) scans were performed on day 1, day 10 and day 30. SPECT scan data was analysed by 5 semi-quantitative methods, and findings were compared with neuroloyical clinical scores on each respective day. It was found that day 1 SPECT scans are of value for early localization of the acute ischaemic infarction. A multiple regression model was developed using both the day 30 Defect Volume index and segmental analysis score which related to the day 30 clinical scores. The day 1 model was unsatisfactory and no such model was found relating day 10 SPECT semi-quantitative methods to day 10 clinical scoring. Changes in semi-quantitative scores from day 1 to day 30 did not correlate with clinical changes. Longer follow up may be required for there to be value in performing SPECT scans in stroke trials. A prognostic equation was derived by multiple regression analysis of day 1 SPECT scan scores and day 30 clinical scores. / Andrew Chakane 2019

published_or_final_version / Medicine / Master / Doctor of Medicine

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