10 research outputs found
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A Novel Approach for the Visualisation and Progression Tracking of Metastatic Bone Disease
Metastatic bone disease (MBD) is a common secondary feature of cancer that can cause significant complications, including severe pain and death. Current methods of diagnosis require a highly trained radiologist capable of interpreting medical images and recognising the sites of MBD. These medical images are often noisy, two dimensional, greyscale and usually have a poor resolution.
In order to help assist with these issues, several studies have shown that computer aided methods can locate MBD within medical images. However these methods are limited in scope, accuracy, sensitivity, explainability and do not improve upon the poor visualisations of the underlying medical imaging data.
To address these limitations, I have developed a novel method of automatic MBD assessment and visualisation using computed tomography (CT) imaging data as the input. The method is fully automated and does not require any human interaction -- although users can interact with a viewer that visualises the results. This method has been tested on CT data from prostate cancer patients as prostate cancer is one of the most common sources of MBD.
The method described in this thesis has a sensitivity of 0.871 when detecting sclerotic and lytic lesions within a single data set. This sensitivity is comparable to existing methods, however the scope in detecting these lesions was limited to the vertebrae in previous studies. My method significantly expands this scope to include the ribs, vertebrae, pelvis and proximal femurs.
The work in this thesis also provides novel visualisations of the disease and does not suffer from explainability issues that plague modern machine learning algorithms.
In addition, I developed a novel method of tracking the spread of MBD at multiple time points using longitudinal CT data. This method is capable of calculating the change in lesion volume size across multiple time points, providing a novel numerical assessment.The Armstrong Trus
Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer
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Transcriptional landscape of the prenatal human brain.
The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development
Transcriptional landscape of the prenatal human brain
The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development
A comprehensive transcriptional map of primate brain development
The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny