Since its inception around 1975, Positron Emission Tomography (PET) has proved to be an important tool in medical research as it allows imaging of the brain function in vivo with high sensitivity. It has been widely used in clinical dementia research with [18F]2-Fluoro-2-Deoxy-D-Glucose (FDG) and amyloid tracers as imaging biomarkers in Alzheimer's Disease (AD). The high resolution offered by modern scanner technology has the potential to provide new insight into the interaction of structural and functional changes in AD. However, the high resolution of PET is currently limited by movement and resolution (even for high resolution dedicated brain PET scanner) which results in partial volume effects, the undersampling of activity within small structures. A modified frame-by-frame (FBF) realignment algorithm has been developed that uses estimates of the centroid of activity within the brain to detect movement and subsequently reframe data to correct for intra-frame movement. The ability of the centroid to detect motion was assessed and the added benefit of reframing data for real clinical scans with patient motion was evaluated through comparison with existing FBF algorithms. Visual qualitative analysis on 6 FDG PET scans from 4 blinded observers demonstrated notable improvements (ANOVA with Tukey test, p < 0.001) and time-activity curves were found to deliver biologically more plausible activity concentrations. A new method for Partial Volume Correction (PVC) is also proposed, PARtially-Segmented Lucy-Richardson (PARSLR),that combines the strength of image based deconvolution approach of the Lucy-Richardson (LR) Iterative Deconvolution Algorithm with a partial segmentation of homogenous regions. Such an approach is of value where reliable segmentation is possible for part but not all of the image volume or sub-volume. Its superior performance with respect to region-based methods like Rousset or voxel-based methods like LR was successfully demonstrated via simulations and measured phantom data. The approach is of particular importance for studies with pathological abnormalities where complete and accurate segmentation across or with a sub-volume of the image volume is challenging and for regions of the brain containing heterogeneous structures which cannot be accurately segmented from co-registered images. The developed methods have been shown to recover radioactivity concentrations from small structures in the presence of motion and limited resolution with higher accuracy when compared to existing methods. It is expected that they will contribute significantly to future PET studies where accurate quantitation in small or atrophic brain structures is essential.

[pt] O objetivo desta dissertação é quantificar e analisar as possíveis diferenças oriundas de métodos de correção de volume de diferentes normas na medição de derivados líquidos de petróleo. Essas correções são necessárias pois variações na temperatura e pressão a que esses fluidos estão submetidos geram variações de volume que podem levar a grandes diferenças entre os volumes medidos por clientes e fornecedores, em virtude de variações nas condições operacionais. De forma a minimizar a influência dessas variações nos volumes a serem considerados, estabeleceu-se uma condição padrão (20 graus Celsius e 101,325 kPa) para a qual todos os volumes medidos nas transações realizadas no Brasil devem ser corrigidos. A motivação deste trabalho advém do fato da regulamentação brasileira que rege essas correções ser muito antiga (anos 1970). Esse trabalho é uma oportunidade para analisar métodos de correção de volume mais recentes. Esses métodos podem gerar erros menores nas suas correções a depender das hipóteses adotadas em seus desenvolvimentos. Além disso, uma análise do impacto econômico da adoção desses métodos é realizada. Para estudar estas possíveis diferenças, a metodologia aplicada utiliza distribuições que modelam a variação da massa específica dos produtos ao longo do processo produtivo e, para outros, dados coletados ao longo de certos períodos especificados. São, então, obtidas massas específicas resultantes da aplicação de cada método. De posse das massas específicas calculadas nos resultados, são verificadas diferenças estatisticamente relevantes entre as correções efetuadas por cada método. As conclusões demonstram que essas diferenças justificam a atualização da regulamentação com os métodos contidos nos padrões mais atuais. / [en] The aim of this dissertation is to quantify and analyze the possible differences caused by the application of the correction methods defined on different standards for the measurement of the volume of liquid petroleum derivatives. This correction is necessary because pressure and temperature variations can cause considerable differences between measurements made by customer and supplier, due to operational conditions variations. To standardize this measurement, it was established that all volumes used on transactions in Brazil should be corrected to a base condition (in Brazil, 20 degrees Celsius and 101.325 kPa). This work s motivation comes from the fact that the Brazilian regulation is quite old (from the 1970s). This work is an opportunity to analyze more recent correction methods. These methods can give smaller errors depending on the hypothesis adopted in its developments. Besides that, an economic impact analysis of these methods adoption in realized. To study these possible differences, the applied methodology uses statistical distributions that model the specific gravity of the products during the productive process and, in other cases, uses data collected during certain periods. Corrected specific gravity values are, then, obtained for each method. With these values at hand, some statistically relevant differences are verified. Conclusions demonstrate that these differences justify the update of Brazilian regulation with the methods contained in standards that are more recent.

Hurricane is one of the most destructive and costly natural hazard to the built environment and its impact on low-rise buildings, particularity, is beyond acceptable. The major objective of this research was to perform a parametric evaluation of internal pressure (IP) for wind-resistant design of low-rise buildings and wind-driven natural ventilation applications. For this purpose, a multi-scale experimental, i.e. full-scale at Wall of Wind (WoW) and small-scale at Boundary Layer Wind Tunnel (BLWT), and a Computational Fluid Dynamics (CFD) approach was adopted. This provided new capability to assess wind pressures realistically on internal volumes ranging from small spaces formed between roof tiles and its deck to attic to room partitions. Effects of sudden breaching, existing dominant openings on building envelopes as well as compartmentalization of building interior on the IP were systematically investigated. Results of this research indicated: (i) for sudden breaching of dominant openings, the transient overshooting response was lower than the subsequent steady state peak IP and internal volume correction for low-wind-speed testing facilities was necessary. For example a building without volume correction experienced a response four times faster and exhibited 30-40% lower mean and peak IP; (ii) for existing openings, vent openings uniformly distributed along the roof alleviated, whereas one sided openings aggravated the IP; (iii) larger dominant openings exhibited a higher IP on the building envelope, and an off-center opening on the wall exhibited (30-40%) higher IP than center located openings; (iv) compartmentalization amplified the intensity of IP and; (v) significant underneath pressure was measured for field tiles, warranting its consideration during net pressure evaluations. The study aimed at wind driven natural ventilation indicated: (i) the IP due to cross ventilation was 1.5 to 2.5 times higher for Ainlet/Aoutlet>1 compared to cases where Ainlet/AoutletCFD based IP responses. Comparisons with ASCE 7-10 consistently demonstrated that the code underestimated peak positive and suction IP.

In translational medicine, complementary functional and morphological imaging techniques are used extensively to observe physiological processes in vivo and to assess structural changes as a result of disease progression. The combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides excellent soft tissue contrast from MRI with exceptional sensitivity and specificity from PET. This thesis explores the use of sequentially acquired PET and MR images to improve the quantification of small animal PET data. The primary focus was to improve image-based estimates of the arterial input function (AIF), which defines the amount of PET tracer within blood plasma over time. The AIF is required to produce physiological parameters quantifying key processes such as metabolism or perfusion from dynamic PET images. The gold standard for AIF measurement, however, requires serial blood sampling over the course of a PET scan, which is invasive in rat studies but prohibitive in mice due to small total blood volumes. To address this issue, the geometric transfer matrix (GTM) and recovery coefficient (RC) techniques were applied using anatomical MR images to enable the extraction of partial volume corrected image based AIFs from mouse PET images. A non-invasive AIF extraction method was also developed for rats, beginning with the optimization of an automated voxel selection algorithm to assist in extracting MR contrast agent signal time courses from dynamic susceptibility contrast (DSC) MRI data. This procedure was then combined with dynamic contrast enhanced (DCE) MRI to track a combined injection of Gadolinium-based contrast agent and PET tracer through the rat brain. By comparison with gold standard tracer blood sample data, it was found that normalized MRI-based AIFs could be successfully converted into PET tracer AIFs in the first pass phase when fitted with gamma variate functions. Finally, a MR image segmentation method used to provide PET attenuation correction in mice was validated using the Cambridge split magnet PET/MR scanner?s transmission scanning capabilities. This work recommends that contributions from MR hardware in the PET field of view must be accounted forto gain accurate estimates of tracer uptake and standard uptake values (SUVs). This thesis concludes that small animal MR data taken in the same imaging session can provide non-invasive methods to improve PET image quantification, giving added value to combined PET/MR studies over those conducted using PET alone.

In ischaemic stroke a disruption of cerebral blood flow leads to impaired metabolism and the formation of an ischaemic penumbra in which tissue at risk of infarction is sought for clinical intervention. In stroke trials, therapeutic intervention has largely been based on perfusion-weighted measures, but these have not been shown to be good predictors of tissue outcome. The aim of this thesis was to develop analysis techniques for magnetic resonance imaging (MRI) of chemical exchange saturation transfer (CEST) in order to quantify metabolic signals associated with tissue fate in patients with acute ischaemic stroke. This included addressing robustness for clinical application, and developing quantitative tools that allow exploration of the in-vivo complexity. Tissue-level analyses were performed on a dataset of 12 patients who had been admitted to the John Radcliffe Hospital in Oxford with acute ischaemic stroke and recruited into a clinical imaging study. Further characterisation of signals was performed on stroke models and tissue phantoms. A comparative study of CEST analysis techniques established a model-based approach, Bloch-McConnell model analysis, as the most robust for measuring pH-weighted signals in a clinical setting. Repeatability was improved by isolating non-CEST effects which attenuate signals of interest. The Bloch-McConnell model was developed further to explore whether more biologically-precise quantification of CEST effects was both possible and necessary. The additional model complexity, whilst more reflective of tissue biology, diminished contrast that distinguishes tissue fate, implying the biology is more complex than pH alone. The same model complexity could be used reveal signal patterns associated with tissue outcome that were otherwise obscured by competing CEST processes when observed through simpler models. Improved quantification techniques were demonstrated which were sufficiently robust to be used on clinical data, but also provided insight into the different biological processes at work in ischaemic tissue in the early stages of the disease. The complex array of competing processes in pathological tissue has underscored a need for analysis tools adequate for investigating these effects in the context of human imaging. The trends herein identified at the tissue level support the use of quantitative CEST MRI analysis as a clinical metabolic imaging tool in the investigation of ischaemic stroke.