Radiology - Theses
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ItemThe associations between physical activity and magnetic resonance imaging in people at risk of Alzheimer's disease( 2016)The world’s ageing population is growing rapidly, and although longevity is a positive development, this involves an increasing prevalence of neurodegenerative diseases including dementias such as Alzheimer’s Disease (AD). This disease cannot be cured and the burgeoning proportion of the population that is aged leads to an urgent need to identify people who are at risk of developing AD in the future. Cerebrovascular disease (CVD) is a known risk factor for AD and modifiable CVD risk factors, which may delay the onset of AD, include diabetes, obesity, smoking or hypertension and the level of physical activity (PA). Magnetic resonance imaging (MRI) measures CVD by assessing white matter lesions that can be detected as T2-signal white matter hyperintensities. Additionally, hippocampal volumes, also assessed by MRI, are an important biomarker in the context of cognitive decline and AD. This thesis examines cross-sectional baseline data from older participants from the AIBL Active (AA) study in Melbourne, Australia. This randomised clinical trial is a longitudinal sub-study of the Australian Imaging Biomarkers and Lifestyle (AIBL) flagship study. The AA study aims to assess the effect of PA on the possible delay of CVD progression. All the participants have either subjective memory complaints or mild cognitive impairment and at least one vascular risk factor including diabetes, hypertension, obesity, dyslipidaemia or smoking.
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ItemAcute stroke imaging: predicting response to therapy( 2012)Acute ischemic stroke is caused by a blocked blood vessel in the cerebral circulation. It is the most common form of stroke worldwide and a major cause of disability and death. Treatments to re-open the blocked blood vessel and reperfuse the brain are available but their effectiveness, when applied to all patients, rapidly decreases over the first few hours after stroke onset. However, there is significant pathophysiological heterogeneity within acute stroke patients which can be revealed using advanced MRI and CT techniques. The principle of “ischemic penumbra” – hypoperfused and often non-functioning brain that will, nonetheless, potentially recover if reperfused – underlies all therapies aiming to restore blood flow in acute ischemic stroke. Perfusion-diffusion mismatch using MRI is a surrogate marker of ischemic penumbra that has been refined over the last decade. This thesis examines the validity of the mismatch paradigm and confirms the use of diffusion imaging as a reliable indicator of irreversibly damaged brain. Diffusion imaging at 24 hours (a commonly used timepoint to assess reperfusion and hemorrhage) is also established as an accurate measure of final infarct volume. This allows calculation of infarct growth as a surrogate outcome whilst minimising loss to follow-up and is a strong predictor of clinical recovery. A less predictable outcome is the proportion of hypoperfused brain that will proceed to infarction in the absence of reperfusion. Collateral blood flow is shown to be a dynamic phenomenon with alterations correlating with infarct growth. The relationship between collateral flow and perfusion-diffusion mismatch is explored. The mismatch paradigm is then translated to CT perfusion which is more widely accessible in most centres but has, until recently, lacked thorough validation. Perfusion thresholds such as Tmax>6sec translate directly to CT. The best correlate of diffusion imaging for infarct core is shown to be relative cerebral blood flow (relCBF), with the exact threshold highly dependent on the software used in the analysis. This is a shift from previous work which had suggested cerebral blood volume (CBV) was the optimal parameter. Applying mismatch-based treatment decisions in clinical practice is also examined with a comparison of simple visual assessment of mismatch with fully automated volumetric software and manual volumetric calculation. The risk of bleeding after reperfusion (hemorrhagic transformation) is the chief concern when considering reperfusion therapies. This thesis examines predictors of hemorrhage and how they may be applied in clinical practice. The ultimate aim is to move beyond simple time-based windows for treatment to an individualized treatment decision based on the particular pathophysiology revealed by imaging. The amount of potentially salvageable brain tissue can be weighed against the risk of hemorrhage to make an informed treatment decision.