Radiology - Theses
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ItemThe preoperative MRI assessment of adult intracranial diffuse gliomas( 2018)MRI (Magnetic Resonance Imaging), is an integral part of the management of intracranial diffuse gliomas, consisting of both astrocytomas and oligodendrogliomas, and ongoing improvements in MRI technology continually enhance its value. While advanced MRI techniques are adding to the functional information available, standard sequences remain the mainstay of the assessment, and are also being improved. Initially, MRI provides critical diagnostic information and aids neurosurgical planning, but its role is expanding beyond these primary functions, as outlined in this thesis. Improved identification and delineation of the tumour allows optimal management by surgical resection and adjuvant radiotherapy. MRI is also important for prognostication, by identifying features that may convey a better or worse prognosis. The addition of MRI information to clinical data and the histopathological assessment thus provides the most comprehensive assessment of the individual patient. The recent 2016 update to the WHO classification of central nervous system tumours has led to significant changes in the histological characterisation of gliomas, now providing an integrated genotypic and phenotypic classification1. The two steps in the genotypic classification of gliomas is testing for an isocitrate dehydrogenase (IDH) mutation, and if present, determination of 1p/19q status1. There are logistic and cost issues, however, and MRI can aid decision-making. The value of MRI in this context is greatest when access to definitive testing methods is limited, and the focus on the molecular phenotype in the new WHO classification increases the potential for a combined histologic-MRI assessment method at such centres. Due to its ability to assess the entire tumour and provide non-invasive characterisation over time, MRI also has the potential to overcome some of the limitations of both the phenotypic and genotypic assessment, including sampling error, intra-tumoural heterogeneity and monoallelic gene expression. Information obtained by MRI is also increasing our understanding of the disease, well demonstrated by the growing interest in the non-enhancing component of tumour. Gliomas are essentially incurable, with recurrence almost inevitable despite optimal therapy. There is thus growing interest in advanced surgical techniques aimed at more aggressive management, and accurate delineation of the tumour by MRI provides a critical guide to the surgeon.
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ItemEffect of physical activity on progression of cerebrovascular disease in older adults at risk or alzheimer's disease( 2017)Objective: Alzheimer's disease (AD) is a form of dementia without cure. Dementias are the only condition out of the top 10 causes of mortality worldwide without cure and represent a significant health burden. White matter hyperintensities (WMH) are a biomarker of brain white matter disease, and are associated with a number of neuropsychiatric disorders including dementia. WMH progression has been shown to be reduced by vascular risk factor (VRF) control. Physical activity (PA) has also been shown to slow the progression of WMH, control VRF related disease and has also been shown to reduce cognitive decline. It is therefore postulated that PA can slow WMH progression and could perhaps be a lifestyle related treatment that slows cognitive decline, which would have great public health implications. Conventional manual segmentation (CMS) is the current gold standard in WMH volumetry. Side-by-side (SBS) segmentation has shown promise in WMH visual rating scales and other areas in radiology but has not yet been applied to manual segmentation of WMH lesions. We hypothesise that PA slows WMH progression, and this progression is slower in ApoE ε4 and PET Amyloid beta status negative patients. We also hypothesise that there is a concomitant positive association between baseline cognition measures and WMH progression. Finally, we hypothesise that side by side segmentation will give WMH volumes with more significant clinical associations than the traditional segmentation methods. Method: Data was obtained as part of the AIBL Active trial. Participants are older adults at risk of AD with at least one VRF. Imaging data was obtained on a Siemens 3T Tim Trio scanner. Images were processed according to accepted standards, with FLAIR images used for WMH volumetry, and MPRAGE images used to obtain estimated total intracranial volume (ETIV). WMH were manually segmented under expert neuroradiologist guidance (A/Prof P. Phal), firstly obtaining CMS volumes and then SBS volumes. These volumes were corrected for ETIV and log transformed, then compared against age, gender, VRF, baseline functional fitness, Years of education, cognitive group (SMC/MCI) and baseline neurocognitive assessments using correlations, and subsequently general linear models. Results: In older adults at risk of AD with at least one VRF, exercise over a 24 month period was not associated with a slowing of WMH progression. There was also no association between baseline functional fitness assessment and WMH progression. ApoE ε4 and PET Amyloid beta status were also not associated with a slowing of WMH progression. We did find correlations between WMH volume and age with both methods, with baseline WMH significantly predicting progression. Systolic blood pressure was also associated with WMH progression in correlations in the CMS general linear model. Anxiety was inversely associated with WMH progression while other cognitive measures were not. Side-by-side manual segmentation did not result in significant clinical differences compared to conventional manual segmentation. Conclusion: Based on our results we were unable to show effectiveness of physical activity in older adults at risk of AD in slowing WMH progression. We also cannot conclude that SBS WMH segmentation is more effective than accepted methods.
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ItemLongitudinal volumetric analysis of white matter hyperintensities on magnetic resonance imaging in aging and Alzheimer’s dementia( 2014)The experience of neurocognitive aging can be highly variable between individuals, with some passing into their twilight years with intact and healthy cognition while others find their mental faculties perceptibly dimmed or even impaired to the point of debilitation, with dementias such as Alzheimer’s dementia (AD) seated at this extremity of the spectrum. The burgeoning proportion of the population that is aged makes the identification of biological factors that influence cognitive trajectory with advancing age a high priority. White matter changes, evident as T2 signal hyperintensities on magnetic resonance imaging (MRI) and reflective of small vessel damage and disease, occur with increasing frequency with age and are common in the elderly, including those with dementia. Shown to be associated with cognitive impairment and AD, their relationship to vascular risk factors (VRF), association to other structural brain changes and influence on cognition remains to be clarified. A combination of manual and automated segmentation methods were applied to brain MRI from elderly patients being followed longitudinally in the Australian Imaging, Biomarkers and Lifestyles (AIBL) flagship study, yielding quantitative values for WMH, cerebral cortex and cortical structures selectively susceptible in AD. Age is a well-established risk factor for WMH, while the vascular changes underpinning white matter lesions has lead to a number of VRFs evaluated and suggested as risk factors. In this study, of the participant demographics only age was significantly associated with WMH measured both at baseline and longitudinally, while hypertension and smoking were the only VRFs found to have a significant effect in models of WMH volume. Cognitive decline and impairment is strongly related to hippocampal volume, particularly in AD patients. Amyloid is also a hallmark of AD pathology and is believed to mediate disease by its direct neurotoxic effects. In the presence of the neuropathological changes of AD the contribution of white matter lesions on cognition is not clear. This study did not find a direct relationship between WMH and cognitive decline or impairment, which were instead associated with amyloid burden and ApoE allele status. However, there was a higher burden of WMH in subjects with a significant amyloid burden and in particular in AD patients. WMH burden and rate of increase was also related to the lower cortical, hippocampal and amygdala volumes. WMH are a surrogate of microvascular damage, which can lead to impairment of vascular drainage and consequently reduced clearance of amyloid. Overall this study found that while the strength of the relationship between VRFs and WMH were not as strong in this study population, there was a significant association with cortical change and amyloid pathology, which in turn are factors in cognitive decline and impairment. This provides further evidence to support a role for cerebrovascular pathology in the pathogenesis of AD.