Development & optimization of diffusion tensor imaging at high field strengths in translational research

Ever since the inception of Diffusion Tensor Imaging (DTI), unabated advancements in its capabilities and applications have been spearheaded by a vibrant research effort to devise dedicated acquisition sequences, protocols and hardware. In translational research, however, the transition of these innovations into the arenas of biomedical research, and ultimately clinical practice is frequently hampered by practical considerations. These include the availability of appropriate expertise, time and resources for their implementation, and considerations of compatibility with established techniques and results reported in literature. Such concerns provide the impetus to maximize the utility of existing protocols before attempting the development of novel dedicated techniques. In this thesis, three investigations, each targeting a different DTI application, are presented. The strategy implemented throughout involves assessing the suitability of existing sequences for the intended task, and determining any limiting factors, evaluating whether appropriate modifications of the acquisition protocols used are capable of alleviating limitations, and developing novel, dedicated protocols wherever necessary. The value and, importantly, the wide scope of this approach in answering important research questions is exemplified through the breadth of the studies presented. The first study presents, for the first time, a quantitative evaluation of the effects of cardiac pulsation on prevalent DTI metrics acquired with a specific acquisition protocol used routinely in clinical practice. Findings inform the on-going debate on whether the investment in cardiac gating is merited by improvements in data quality. Effects were observed during only 6 % of the cardiac cycle, and not 20 % as previously reported. The impact of cardiac pulsation on selected diffusion Tensor indices was minimal in group studies, but of potential practical relevance in individual cases. Methods to predict which individuals may benefit from gating have also been suggested. Secondly, the feasibility of post-mortem DTI was established through the successful acquisition, also for the first time, of DTI data on a chemically fixed whole human post-mortem brain using a clinical sequence. Previous failed attempts have been attributed to insufficient SNR. In this study scanner stability and distortion are found to be the main limiting factors, and mitigated using appropriate averaging and co-registration strategies. The third study assessed the potential of ultra-high field strength DTI by identifying and optimizing the potential strengths of DTI at 7T. Subsequent to optimization with respect to SNR, the main sources of artefact were found to be B1 inhomogeneity and inadequate fat suppression. Both were alleviated by modification of the available acquisition protocol, resulting in higher SNR and data quality than previously reported. Finally, in developing appropriate data quality measures, the ‘Difference method’, commonly used for the quantification of SNR, was found to be unsuitable for in vivo DTI acquisitions at 7 T, leading to the proposal, and successful implementation and validation of an alternative

Development & optimization of diffusion tensor imaging at high field strengths in translational research

Ever since the inception of Diffusion Tensor Imaging (DTI), unabated advancements in its capabilities and applications have been spearheaded by a vibrant research effort to devise dedicated acquisition sequences, protocols and hardware. In translational research, however, the transition of these innovations into the arenas of biomedical research, and ultimately clinical practice is frequently hampered by practical considerations. These include the availability of appropriate expertise, time and resources for their implementation, and considerations of compatibility with established techniques and results reported in literature. Such concerns provide the impetus to maximize the utility of existing protocols before attempting the development of novel dedicated techniques. In this thesis, three investigations, each targeting a different DTI application, are presented. The strategy implemented throughout involves assessing the suitability of existing sequences for the intended task, and determining any limiting factors, evaluating whether appropriate modifications of the acquisition protocols used are capable of alleviating limitations, and developing novel, dedicated protocols wherever necessary. The value and, importantly, the wide scope of this approach in answering important research questions is exemplified through the breadth of the studies presented. The first study presents, for the first time, a quantitative evaluation of the effects of cardiac pulsation on prevalent DTI metrics acquired with a specific acquisition protocol used routinely in clinical practice. Findings inform the on-going debate on whether the investment in cardiac gating is merited by improvements in data quality. Effects were observed during only 6 % of the cardiac cycle, and not 20 % as previously reported. The impact of cardiac pulsation on selected diffusion Tensor indices was minimal in group studies, but of potential practical relevance in individual cases. Methods to predict which individuals may benefit from gating have also been suggested. Secondly, the feasibility of post-mortem DTI was established through the successful acquisition, also for the first time, of DTI data on a chemically fixed whole human post-mortem brain using a clinical sequence. Previous failed attempts have been attributed to insufficient SNR. In this study scanner stability and distortion are found to be the main limiting factors, and mitigated using appropriate averaging and co-registration strategies. The third study assessed the potential of ultra-high field strength DTI by identifying and optimizing the potential strengths of DTI at 7T. Subsequent to optimization with respect to SNR, the main sources of artefact were found to be B1 inhomogeneity and inadequate fat suppression. Both were alleviated by modification of the available acquisition protocol, resulting in higher SNR and data quality than previously reported. Finally, in developing appropriate data quality measures, the ‘Difference method’, commonly used for the quantification of SNR, was found to be unsuitable for in vivo DTI acquisitions at 7 T, leading to the proposal, and successful implementation and validation of an alternative

In vivo mapping of vascular inflammation using the translocator protein tracer 18F-FEDAA1106

YesNon-invasive imaging methods are required to monitor the inflammatory content of atherosclerotic plaques. FEDAA1106 (N-(5-fluoro-2-phenoxyphenyl)-N-(2-(2-fluoroethoxy)-5- methoxybenzyl) acetamide) is a selective ligand for TSPO-18kDa (also known as peripheral benzodiazepine receptor), which is expressed by activated macrophages. We compared 18F- FEDAA1106 and 18F-FDG (a marker of glucose metabolism) for PET imaging of vascular inflammation. This was tested using a murine model where focal inflammation was induced in the carotid artery via placement of a constrictive cuff. Immunostaining revealed CD68-positive cells (macrophages) at a disturbed flow site located downstream from the cuff. Dynamic PET imaging using 18F-FEDAA1106 or 18F-FDG was registered to anatomical data generated by CT/CT angiography. Standardized uptake values (SUV) were significantly increased at cuffed compared to contralateral arteries using either 18F-FEDAA1106 (p<0.01) or FDG (p<0.05). However, the 18F-FEDAA1106 signal was significantly higher at the inflamed disturbed flow region compared to the non-inflamed uniform flow regions, whereas differences in FDG uptake were less distinct. We conclude that 18F-FEDAA1106 can be used in vivo for detection of vascular inflammation. Moreover, the signal pattern of 18F-FEDAA1106 correlated with vascular inflammation more specifically than FDG uptake.: This study was funded by the British Heart Foundation and through a grant from the Swiss National Science Foundation (310030_143343/1 to B.R.K.

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe