The investigation of hippocampal and hippocampal subfield volumetry, morphology and metabolites using 3T MRI

A detailed account of the hippocampal anatomy has been provided. This thesis will explore and exploit the use of 3T MRI and the latest developments in image processing techniques to measure hippocampal and hippocampal subfield volumes, hippocampal metabolites and morphology. In chapter two a protocol for segmenting the hippocampus was created. The protocol was assessed in two groups of subjects with differing socioeconomic status (SES). This was a novel, community based sample in which hippocampal volumes have yet to be assessed in the literature. Manual and automated hippocampal segmentation measurements were compared on the two distinct SES groups. The mean volumes and also the variance in these measurements were comparable between two methods. The Dice overlapping metric comparing the two methods was 0.81. In chapter three voxel based morphometry (VBM) was used to compare local volume differences in grey matter volume between the two SES groups. Two approaches to VBM were compared. DARTEL-VBM results were found to be superior to the earlier ’optimised’ VBM method. Following a small volume correction, DARTEL-VBM results were suggesitive of focal GM volumes reductions in both the right and left hippocampi of the lower SES group. In chapter four an MR spectroscopy protocol was implemented to assess hippocampal metabolites in the two differing SES groups. Interpretable spectra were obtained in 73% of the 42 subjects. The poorer socioeconomic group were considered to have been exposed to chronic stress and therefore via inflammatory processes it was anticipated that the NAA/Cr metabolite ratio would be reduced in this group when compared to the more affluent group. Both NAA/Cr and Cho/Cr hippocampal metabolite ratios were not significantly different between the two groups. The aim of chapter 5 was to implement the protocol and methodology developed in chapter 2 to determine a normal range for hippocampal volumes at 3T MRI. 3D T1-weighted IR-FSPGR images were acquired in 39 healthy, normal volunteers in the age range from 19 to 64. Following the automated procedure hippocampal volumes were manually inspected and edited. The mean and standard deviation of the left and right hippocampal volumes were determined to be: 3421mm3 ± 399mm3 and 3487mm3 ± 431mm3 respectively. After correcting for total ICV the volumes were: 0.22% ± 0.03% and 0.23% ± 0.03% for the left and right hippocampi respectively. Thus, a normative database of hippocampal volumes was established. The normative data here will in future act as a baseline on which other methods of determining hippocampal volumes may be compared. The utility of using the normative dataset to compare other groups of subjects will be limited as a result of the lack of a comprehensive assessment of IQ or education level of the normal volunteers which may affect the volume of the hippocampus. In chapter six Incomplete hippocampal inversion (IHI) was assessed. Few studies have assessed the normal incidence of IHI and of those studies the analysis of IHI extended only to a radiological assessment. Here we present a comprehensive and quantitative assessment of IHI. IHI was found on 31 of the 84 normal subjects assessed (37%). ICV corrected IHI left-sided hippocampal volumes were compared against ICV corrected normal left-sided hippocampal volumes (25 vs. 52 hippocampi). The IHI hippocampal volumes were determined to be smaller than the normal hippocampal volumes (p<< 0.05). However, on further inspection it was observed that the ICV of the IHI was significantly smaller than the ICV of the normal group, confounding the previous result. In chapter seven a pilot study was performed on patients with Rheumatoid Arthritis (RA). The aim was to exploit the improved image quality offered by the 3T MRI to create a protocol for assessing the CA4/ dentate volume and to compare the volume of this subfield of the hippocampus before and after treatment. Two methodologies were implemented. In the first method a protocol was produced to manually segment the CA4/dentate region of the hippocampus from coronal T2-weighted FSE images. Given that few studies have assessed hippocampal subfields, an assessment of study power and sample size was conducted to inform future work. In the second method, the data the DARTEL-VBM image processing pipeline was applied. Statistical nonparametric mapping was applied in the final statistical interpretation of the VBM data. Following an FDR correction, a single GM voxel in the hippocampus was deemed to be statistically significant, this was suggestive of small GM volume increase following antiinflammatory treatment. Finally, in chapter eight, the manual segmentation protocol for the CA4/dentate hippocampal subfield developed in chapter seven was extended to include a complete set of hippocampal subfields. This is one of the first attempts to segment the entire hippocampus into its subfields using 3T MRI and as such, it was important to assess the quality of the measurement procedure. Furthermore, given the subfield volumes and the variability in these measurements, power and sample size calculations were also estimated to inform further work. Seventeen healthy volunteers were scanned using 3T MRI. A detailed manual segmentation protocol was created to guide two independent operators to measure the hippocampal subfield volumes. Repeat measures were made by a single operator for intra-operator variability and inter-operator variability was also assessed. The results of the intra-operator comparison proved reasonably successful where values compared well but were typically slightly poorer than similar attempts in the literature. This was likely to be the result of the additional complication of trying to segment subfields in the head and tail of the hippocampus where previous studies have focused only on the body of the hippocampus. Inter-rater agreement measures for subfield volumes were generally poorer than would be acceptable if full exchangeability of the data between the raters was necessary. This would indicate that further refinements to the manual segmentation protocol are necessary. Future work should seek to improve the methodology to reduce the variability and improve the reproducibility in these measures

Alien Registration- Mclean, John (Milo, Piscataquis County)

https://digitalmaine.com/alien_docs/8576/thumbnail.jp

The environments of Markarian galaxies

The extensively studied Markarian sample of 1500 ultraviolet excess galaxies contains many Seyfert, starburst, and peculiar galaxies. Using the 20 minute V plates obtained for the construction of the Hubble Space Telescope Guide Star Catalog, the authors investigated the morphologies of the Markarian galaxies and the environments in which they are located. The relationship between the types of nuclear activity and the morphologies and environments of the Markarian galaxies is discussed. The authors conclude that the type of nuclear activity present in the galaxies of the Markarian sample is not dependent on either the morphology or the local environment of the galaxy. This is not to imply that nuclear activity per se is not influenced by the environment in which the nucleus is located. Rather the type of nuclear activity (at least in the Markarian population) does not appear to be determined by the environment

Integrating genealogical and dynamical modelling to infer escape and reversion rates in HIV epitopes

The rates of escape and reversion in response to selection pressure arising from the host immune system, notably the cytotoxic T-lymphocyte (CTL) response, are key factors determining the evolution of HIV. Existing methods for estimating these parameters from cross-sectional population data using ordinary differential equations (ODE) ignore information about the genealogy of sampled HIV sequences, which has the potential to cause systematic bias and over-estimate certainty. Here, we describe an integrated approach, validated through extensive simulations, which combines genealogical inference and epidemiological modelling, to estimate rates of CTL escape and reversion in HIV epitopes. We show that there is substantial uncertainty about rates of viral escape and reversion from cross-sectional data, which arises from the inherent stochasticity in the evolutionary process. By application to empirical data, we find that point estimates of rates from a previously published ODE model and the integrated approach presented here are often similar, but can also differ several-fold depending on the structure of the genealogy. The model-based approach we apply provides a framework for the statistical analysis of escape and reversion in population data and highlights the need for longitudinal and denser cross-sectional sampling to enable accurate estimate of these key parameters

The Application of Resonance Ionisation Spectroscopy to III-V Semiconductor Surface and Depth Analysis

Resonance Ionisation Spectroscopy (RIS) is a relatively new analytical technique which is gaining increasing significance in the field of quantitative trace analysis. This work is principally concerned with the particular application of Resonance Ionisation Spectroscopy to surface and depth analysis of semiconductor material. For any new technique to succeed amidst a plethora of competing, proven technologies, it must offer some added advantage. The introductory chapter assesses some of the common electron, ion and laser based techniques already in existence, with which RIS is in direct competition, stressing fundamental problems in use which limit their degree of success. As a preamble to Chapter 2, the process of Resonance Ionisation Spectroscopy is also introduced at this stage. Chapter 2 deals with the physical principles behind RIS and its mass analysis derivative, RIMS, introducing the concept of atomically selective ionisation schemes used to discriminate between elements. A rate equation model, restricted to a three level system, allows determination of the necessary experimental conditions for efficient implementation of the process. In its most common form, with regards to its application to solid sample analysis, RIS is applied in a post-ionisation mode, in which case ion sputtering or laser ablation are employed in the sample vaporisation process. Of the two methods, ion sputtering is by far the more versatile and better understood. Chapter 3 introduces the physical concepts of ion sputtering and erosion and includes the necessary theory for modelling of the experimental conditions. With regard to depth profiling in particular, the factors contributing to the broadening of known concentration profiles are described in detail. A prerequisite for such analysis, is the ability to detect and recognise the species being analysed. To this end, a major portion of the project was devoted to the design and construction of a time-of-flight mass spectrometer, responsibility for which was placed solely upon the author. Chapter 4 deals specifically with the instrumentation aspect of the project, detailing the operational principles of a time-of-flight mass spectrometer, the various components of the analysis system constructed, the vacuum and laser systems, the ion optical assembly and the sputter ion gun to name but a few. Chapter 5 is the first relating to actual experiments, and provides the basis for an estimate of the operational usefulness of the instrument. Both pulsed secondary ion (SIMS) and resonant ion (RIMS) analyses were carried out on Aluminium and Gallium by the author. The wavelength spectra allow an investigation of the effects of experimental parameters on the resonant process. Chapter 6 describes attempts at depth profiling of aluminium concentration through multilayered structures of GaAs and AlGaAs. During the design stage, familiarity with the problems associated with the secondary ion background prevalent in these experiments, led the author to devise a novel approach to experimental procedure and ion optical design. Chapter 7 discusses the solution in detail, and produces experimental data and computer simulation as confirmation of the usefulness of the method. Recent investigations by the author have led to the development of what has been termed Resonant Laser Ablation (RLA). Chapter 8 introduces this new concept which is derived from the combined mechanisms of laser ablation and resonant ionisation to offer enhancements in sensitivity and selectivity. The technique has generated a great deal of interest due to the possibilities it offers in the field of surface analysis. Experiments, carried out initially by the author and at a later stage in collaboration with Dr. Wang Li of the Department of Physics and Astronomy, on semiconductor and metal samples indicate that RLA may prove to be an interesting alternative technique to existing forms of laser spectrometry. Consequently RLA has become a subject for further investigations within the group. Finally, Chapter 9 discusses briefly the project as a whole and describes some interesting future developments which should enhance the position of RIS/RIMS in the fields of spectrometry and surface analysis

Alien Registration- Mclean, John J. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/21579/thumbnail.jp

Smart Grids in the City: Splintering Urbanism in a Smart Urban Future

This thesis examines how the emergence of smart grids is changing urban development practices and shifting the power relations between the government, private industry and end consumers. The research was undertaken as part of the Customer Led Network Revolution – a UK smart grid research project investigating a shift towards a low carbon economy. This thesis is just one outcome of the project and examines the ways in which smart grids are being produced internationally across a variety of different contexts, conducted with qualitative research with the aim to understand the implications for public responses to new energy technologies. The study first surveyed the development of smart grids projects internationally before selecting the case of the Pecan Street Project in Austin, Texas, to examine the drivers and barriers to the development of smart grids in detail. Drawing on the concepts of splintering urbanism and using the literature of large technical systems, the thesis argues that there are three critical dynamics to the emergence of the smart grid in Austin – the energy discourse that allows a smart grid to emerge; state backing of the project for economic development purposes; and changes in urban planning structures to facilitate smart growth. This study suggests that the growth of smart grids can be tailored to benefit a wide variety of stakeholders, but could “splinter” urban environments with potential risks for rising inequality. The research offers a valuable contribution to how smart grids can be produced in the UK and how they should be managed

Alien Registration- Mclean, John T. (Milo, Piscataquis County)

https://digitalmaine.com/alien_docs/8577/thumbnail.jp