Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2002. / Title from first page of PDF file. Document formatted into pages; contains xx, 143 p.; also contains graphics. Includes abstract and vita. Advisor: L. Stanley Durkin, Dept. of Physics. Includes bibliographical references (p. 137-143).

published_or_final_version / Physics / Master / Master of Philosophy

The criteria for diagnosing Alzheimer’s disease (AD) have recently been revised to include the use of biomarkers for the in vivo presence of β-amyloid, one of the neuropathological hallmarks of AD. Examples of such biomarkers are positron emission tomography (PET) β-amyloid specific ligands, including [18F]flutemetamol. The aim of this thesis was to characterize the binding properties of [18F]flutemetamol from a tracer kinetic perspective as well as by validating binding measures through comparison with tissue pathology assessments. The applicability of previously developed kinetic models of tracer binding for voxel-based analysis was examined and compared to arterial input compartment modelling, the “gold standard” for PET quantification. Several voxel-based methods were found to exhibit high correlations with compartment modelling, including the semi-quantitative standardized uptake value ratio (SUVR). The kinetic components of [18F]flutemetamol uptake were also investigated without model assumptions using the data driven method spectral analysis, with binding to β-amyloid shown to relate to a slow kinetic component. The same component was also found to predominate in the uptake of white matter, known to be free of β-amyloid accumulation. White matter uptake was however possible to separate from β-amyloid binding based on the relative contribution of the slow component to the total volume of distribution. Uptake of [18F]flutemetamol as quantified using SUVR or assessed visually was found to correlate well with tissue pathology assessments. Classifying the brains of 68 deceased subjects who had undergone [18F]flutemetamol PET scanning ante mortem, based on the spatial distribution of β-amyloid according to pre-defined phases, revealed that abnormal uptake patterns of [18F]flutemetamol were only certain to be found in the last phase of β-amyloid accumulation. In the same cohort however, [18F]flutemetamol was also shown to accurately distinguish between subjects with AD and non-AD dementia. While this supports the use of [18F]flutemetamol in clinical settings for ruling out AD, the association of abnormal [18F]flutemetamol uptake to late phases of β-amyloid accumulation may limit the detection of early accumulation and pre-clinical stages of AD. It remains to be investigated whether application of voxel-based methods and slow component filtering may increase sensitivity, particularly in the context of clinical trials.

published_or_final_version / Physics / Master / Master of Philosophy

published_or_final_version / Physics / Master / Master of Philosophy

published_or_final_version / Physics / Doctoral / Doctor of Philosophy

In 3D positron emission tomography the scatter effect is a significant physical factor degrading image quality. The advancements in computing that occurred the last decades al lowed us to simulate the scatter coincidences fast and ef ficiently. The main concern now is how accurately do we simulate the scatter events. The scope of this project is the implementation and the evaluation of a scatter simulation algorithm that would be able to simulate the scat ter ef fect more precisely than the existing ones. One way to simulate the scatter distribut ion is with an algorithm, first published by Watson and Ollinger, that is based on the Klein-Nishina formula. These methods have been implemented taking into account only the single scatter events (where a photon scatters once in the at tenuation medium). Multiple scatter is generally taken into account by some scaling or filtering procedure. Their main advantages are short computational time and relatively good precision compared to previous more heuristical methods. Although these single scatter algorithms have been effective there are cases where their results are not that accurate. For low energy thresholds and large at tenuation mediums multiple scatter is increased. Given that a significant percentage of people are over -weight (thus the at tenuation medium has large volume) we should consider introducing multiple scatter events in our simulations. Moreover, the distribut ion of all scatter events is broader than the one of single scatter events therefore even if the single scatter distribution is scaled it will not match the total scatter one. In previous work by C. Tsoumpas et al, a new scatter simulation algorithm was developed that attempts to approximate the total scatter distribution by taking into account the case where the one annihilated photon is scattered twice and the case where both annihilated photons are scattered once. These two cases describe the double scatter events and by introducing them into our scatter simulation algorithm we aim to obtain a better approximation of the total scatter distribution. In this thesis we have improved this double scatter simulation algorithm in two important ways. When both annihilated photons scatter they acquire a favourable polarization direction with respect to each other and this influences thei r detect ion probabilities, especially when low energy photons are detected. In the algorithm that we implemented we considered this effect by using the polarized Klein-Nishina formula for this case. In addition, we investigated and validated the need to introduce extra solid angle factors in the implementation. The whole implementation is based on the STIR library (Software for Tomographic Image Reconstruction) written in the C++ programming language. Scatter events can also be simulated by Monte Carlo simulation packages such as SimSET. SimSET is a public domain package designed to simulate positron emission tomography (PET) (and Single Photon Emission Tomography) and was used extensively in this project. Monte Carlo packages because of their ability to exclude any unknown physical parameter they can simulate physical processes like the ones that take place in PET very accurately. Thus they were essential for the evaluation of our scatter correction algorithm. The reason why Monte Carlo packages are not used inclinical practice instead of the model-based methods is that they demand a large computational time. Besides Monte Carlo packages we also per formed a series of experimental scans in order to evaluate our scatter simulation algorithm. The tomograph used for the experiments was the ECAT 962 used in a 3D mode. / -

Objective: To characterize the association between longitudinal changes in fasting serum glucose and changes in flourodeoxyglucose Positron Emission Tomography (FDG PET) measurements of regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer's disease (AD). A secondary objective was to investigate whether higher fasting serum glucose levels are associated with lower rCMRgl in younger adults within these same AD relevant brain areas. Methods: For the primary study, baseline, interim, and 4.4 ± 1.0-year follow-up fasting serum glucose and PET CMRgl were analyzed in 80 cognitively unimpaired, non-diabetic, 61.5 ± 5 year-old persons with a first-degree family history of AD, including 38 carriers and 42 non-carriers of the apolipoprotein E (APOE) ε 4 allele. An automated brain-mapping algorithm was used to characterize associations between changes in fasting serum glucose levels and changes in rCMRgl. Longitudinal changes in fasting serum glucose levels and their correlation with changes in six pre-selected neuropsychological test measures of memory, attention and processing speed were also assessed with linear regression. The secondary study included a cross sectional sample of 31 cognitively unimpaired, non-diabetic participants, 31.2 ±5.4 years of age. General linear model-based voxel-wise analyses were performed to examine the correlation between fasting serum glucose and rCMRgl. Results: In the primary study of older adults, average fasting serum glucose levels increased over longitudinal measurement, and changes in these levels were inversely associated with longitudinal CMRgl changes in the vicinity of brain regions preferentially affected by AD (p<0.05, corrected for multiple comparisons). Fasting serum glucose was also inversely associated with performance on a measure of visuospatial memory (p<0.05, corrected for multiple comparisons). In the younger sample, fasting serum glucose levels were inversely associated with rCMRgl in left frontal pole and right primary visual cortex regions (p<.05, corrected for multiple comparisons).Conclusions: In older adults, fasting serum glucose increases across time and is inversely related to rCMRgl in AD relevant regions and to visual memory test scores. This relationship between serum glucose and regional brain metabolism may begin in metabolically sensitive areas at a younger age.

The magnetosphere of pulsars is thought to consist of an electron-positron plasma rotating in the pulsar magnetic field (Beskin, Gurevich & Istomin 1983; Lominadze, Melikidze & Pataraya 1984; Gurevich & Istomin 1985). A finite, and indeed large, longitudinal electric field exists outside the star, and may accelerate particles, stripped from the surface, to high energies (Goldreich & Julian 1969; Beskin 1993). These particles may leave the magnetosphere via open magnetic field lines at the poles of the pulsar. This depletion of particles causes a vacuum gap to arise, a double layer of substantial potential difference. The primary particles, extracted from the star's surface, are accelerated in the double layer, along the pulsar magnetic field lines, and so produce curvature radiation. The curvature photons, having travelled the distance of the double layer may produce electron-positron pairs above the vacuum gap. These first-generation secondary particles, although no longer accelerating, may synchroradiate, generating photons which may then produce further electron-positron pairs. These synchrophoton produced pairs will be at energies lower than curvature photon produced pairs, since synchrophoton energies are approximately an order of magnitude less than that of the parent curvature photon. An attempt to model the electron-positron pulsar magnetosphere is made. A four component fluid electron-positron plasma is considered, consisting of a hot electron and positron species, at temperature Th , and a cool electron and positron species at temperature Tc . The hot components represent the parent first-generation curvature-born pairs, and the cooler components represent the second-generation pairs, born of synchrophotons. The hot components are assumed to be highly mobile, and are thus described by a Boltzmann density distribution. The cool components are more sluggish and are thus described as adiabatic fluids. The model is symmetric in accordance with pair production mechanisms, so that both species of hot(cool) electrons and positrons have the same temperature Th(Tc, and number density Nh(Nc ) . In the interests of completeness, linear electrostatic waves in five different types of electron-positron plasmas are considered. The dispersion relations for electrostatic waves arising in these unmagnetized plasmas are derived. Single species electron-positron plasmas are investigated, considering the constituents to be: both Boltzmann distributed; both adiabatic fluids; and finally, one species of each type. Linear electrostatic acoustic waves in multi-component electron-positron plasmas are then considered, under the four component model and a three component model (Srinivas, Popel & Shukla 1996). Small amplitude nonlinear electron-positron acoustic waves are investigated, under the four component electron-positron plasma model. Reductive perturbation techniques (Washimi & Taniuti 1966) and a derivation of the Korteweg-de Vries equation result in a zero nonlinear coefficient, and a purely dispersive governing wave equation. Higher order nonlinearity is included, leading to a modified Korteweg-de Vries equation (Watanabe 1984; Verheest 1988), which yields stationary soliton solutions with a sech dependence rather than the more familiar sech2. Arbitrary amplitude solitons are then considered via both numerical and analytical (Chatterjee & Roychoudhury 1995) analysis of the Sagdeev potential. The symmetric nature of the model leads to the existence of purely symmetrical compressive and rarefactive soliton solutions. Small and arbitrary amplitude soliton solutions are compared, and show good correlation. Under the assumption of Boltzmann distributed hot particles, severe restrictions are imposed on the existence domains of arbitrary amplitude soliton solutions. The Boltzmann assumption places a stringent upper limit on the cool species number density, in order for the solutions to be physical. An investigation is made of results obtained for an asymmetric electronpositron plasma (Pillay & Bharuthram 1992), consisting of cold electrons and positrons, and hot Boltzmann electrons and positrons at different temperatures Teh and Tph , and number density Neh and Nph . It is found that the assumption of Boltzmann particles again places restrictions on the acoustic soliton existence space, and that the results obtained may be physically invalid. Valid solutions are obtained numerically, within the boundaries of allowed cool species density values. / Thesis (M.Sc.)-University of Natal, Durban, 1998.