The introduction of mobile communications has undoubtedly altered our physical and social world. Like the Internet, it has changed the way we interact with each other allowing for communication using a variety of communication mediums by means of a magnitude of interactive mobile devices. The context, content, persons communicating, situation and timing all have a varying degree of influence on the sensitivity of information being shared. The individual's awareness of exposure of their private information on the Internet has filtered through into the mobile communications space. It is commonly held in current mobile communication network literature that as privacy-sensitive information travels through a network, it may be exposed to privacy infringement at various stages along its journey. Much of the concern from the individual's perspective, though, stems from a fear of the unknown. In the presence of these threats and vulnerabilities it is justified to wonder whether current mobile communications networks (and indeed future networks) provides sufficient privacy for users with very valuable information to communicate. In this thesis, I develop a systematic approach to identifying areas of privacy concern in a current mobile communication networks in an effort to outline mobile communication privacy principles and how applicable they are in Next Generation Networks. With a privacy stance, the objective of my work is through technical examination and sometimes theoretical undertaking to identify acceptable solutions which restrict the flow of private information and ultimately confirm, through privacy analyses, the benefits gained in doing so. The results show that, given the current situation and technological configuration, there are commonalities which extend beyond a mere concern within a mobile communications network's requirement for privacy enhancement. In a perfect world, the idea is to articulate towards a system of privacy by design rather than as an uttered afterthought. It is no longer inconceivable to think there is an opportunity to deliver a privacy-conscious network, if careful consideration is given to all parties and aspects that govern a mobile communications network and the correct privacy-enhancing technologies are administered correctly. Throughout my thesis, although each privacy solution is segmented and may have a specific privacy application, the results attested contribute largely to a converged prospectus for privacy-aware future generation communication networks. The significance of this lies in the study of past privacy pitfalls in order to better manage the potential for future privacy problems. The rationalisation is if privacy principles are identified (in existing networks) and adhered and applied to (in next generation networks), then we converge towards a network infrastructure that possesses a desirable level of privacy protection. / Thesis (PhD)--University of Pretoria, 2011. / Computer Science / unrestricted

The placebo effect represents a fascinating example of how cognition can influence the physiology of the brain and body. The expectation of therapeutic benefit elicited by a placebo given in the guise of active medication has been proposed to be a form of reward expectation, and is associated with activation of brain reward circuitry. Prominent placebo effects occur in Parkinson’s disease (PD), where the expectation of symptom improvement stimulates dopamine release in the striatum. In the work described in this dissertation, positron emission tomography with [¹¹C] raclopride was used to investigate the relationship between the strength of expectation of benefit and the degree of dopamine release in PD, and how this relationship corresponds to current models of dopamine function in reward. Chapter 3 describes a pilot study conducted in patients who had undergone subthalamic nucleus deep-brain stimulation (STN-DBS) in which we examined how awareness of stimulator status (ON or OFF) affected synaptic dopamine levels compared to when subjects were blind. No difference was detected between conditions; however, it proved to be difficult to maintain blinding due to the profound effects of STN-DBS. Chapter 4 describes the development of the methodology for the analysis of high-resolution PET data, in which we utilized the combined efforts of neuroscience and imaging physics to optimize the analysis of [¹¹C] raclopride PET data. In Chapter 5, I describe the use of verbal instructions to manipulate patients’ expectations in order to investigate how the likelihood of receiving levodopa influenced dopamine release when the patients were in fact given placebo. Placebo-induced dopamine release was differentially modulated by expectation in the dorsal and ventral striatum: dopamine release in the putamen was related monotonically to expected reward value, whereas dopamine released in the ventral striatum reflected the uncertainty of benefit or the salience of the expectation. The placebo effect in PD therefore involves at least two related but separate mechanisms: the expectation of benefit itself, which is scaled to reflect the value of the drug to the patient and is mediated by nigrostriatal dopamine, and the uncertainty or salience of benefit that is mediated by mesolimbic dopamine. / Medicine, Faculty of / Graduate

Small animal positron emission tomography (PET) image analysis can be particularly challenging with heavily-lesioned animal disease models with limited tracer uptake such as the 6-hydroxydopamine (OHDA) lesioned rat model of Parkinson's disease. Methodology-related variations in measured values of 10% or 15% can obscure meaningful biological differences, so accurate analysis methods are essential. However, placing regions of interest (ROIs) on these images without additional guidance is unreliable, and can lead to significant errors in results. To address this problem, this work develops a partly atlas-guided method place ROIs on structures that lack specific binding with presynaptic dopaminergic tracers. The method is tested by correlation of PET binding potential (BP) with autoradiographic binding measurements, and with repeated PET scans of the same subjects, both with the presynaptic tracer ¹¹C-dihydrotetrabenazine (DTBZ). The method is found to produce reliable results. When directly comparing PET images of the same subject to detect changes, it is essential to minimize variations due to analysis method. To this end, a masking method for automated image registration (AIR) of PET images with dopaminergic tracer rat images is developed. Coregistration with AIR and separate ROI placement are compared and tested with repeated scans of the same rat with DTBZ, and are found to be equivalent. Kinetic modelling algorithms may also introduce bias or scatter to binding potentials (BP) calculated from TACs or in parametric images. To determine the optimal method for this step, algorithms for dopaminergic tracers are compared for small animal DTBZ, ¹¹C-methylphenidate (MP), and ¹¹C-raclopride (Rac) data. Among the tested methods is a new variant of the Logan graphical kinetic modelling method, developed in this work, that issignificantly less biased by target tissue TAC noise than the standard Logan approach. The modified graphical method is further compared with the Logan graphical algorithms with added-noise simulations. The simplified reference tissue model (SRTM) is found to have the best method for ROI TAC data, while the modified graphical algorithm may be preferred when generating parametric images. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

Elevated sympathetic nervous system (SNS) tone contributes to excess cardiac mortality associated with type 2 diabetes mellitus (T2DM). Chronic SNS stimulation has detrimental effects to the heart, in particular, with its cell signaling abilities. (R)-[11C]Rolipram small animal positron emission tomography (PET), an noninvasive nuclear imaging modality, was used to assess phosphodiesterase-4 (PDE4) alterations in a high fat diet (HFD), streptozotocin (STZ) induced model of hyperglycemia in rats. Prior to investigation in the animal model, characterization of (R)-[11C]rolipram small animal PET was completed. (R)-[11C]Rolipram binds specifically to PDE4 in the rat heart demonstrated by competitive blockade with (R)-rolipram with the PDE4 enzyme susceptible to saturation with increasing injected masses of unlabeled rolipram. (R)-[11C]Rolipram cardiac retention was elevated by acute norepinephrine stimulation via desipramine pharmacologic challenge. Quantitative (R)-[11C]rolipram PET was highly reproducible in the heart and presents an ideal avenue to investigate PDE4 alterations. (R)-[11C]rolipram small animal PET did not reveal changes in PDE4 expression and activity in STZ-treated hyperglycemic animals compared to STZ-treated euglycemic and control groups. In vitro measures of PDE4 enzyme expression and activity, with or without desipramine, were also not altered between treatment groups. Although (R)-[11C]rolipram small animal PET does not reveal PDE4 alterations in this animal model of diabetes, its utility to assess PDE4 alterations in other over active SNS pathologies, such as heart failure and obesity, remains.

Die therapeutischen Möglichkeiten des metastasierten Prostatakarzinoms (Pca) haben sich durch die neuen Substanzen Docetaxel und Abirateron deutlich verbessert. Das prostataspezifische Membranantigen (PSMA) stellt für die Diagnose und Therapie des Pca´s einen vielversprechenden Angriffspunkt dar. PSMA wird in Prostatakarzinomzellen überexprimiert und dient als Zielstruktur für nicht-invasives bildgebendes Verfahren und Lutetium-177-PSMA-Radioligandentherapie als Therapieoption. Der CXCR4-Rezeptor wird an unterschiedlichen Zelltypen und Organen exprimiert. Seine Überexpression wird mit einer Metastasierung und schlechter Prognose assoziiert. Gallium-68-PSMA PET/CT liefert genaue Kenntnisse bezüglich Ausbreitung und Fortschreiten des Tumorgeschehens. Die vorliegende Arbeit untersucht die Zusammenhänge zwischen Expression von PSMA und CXCR4 in Verbindung mit etablierten Therapeutika und versucht Wege aufzuzeichnen, welche durch Erhöhung der PSMA-Expression zur verbesserten Sensitivität des PSMA PET/CT führen könnten, wodurch der personalisierte Therapieansatz weiter optimiert werden kann. / Novel therapeutic agents such as docetaxel and abiraterone have significantly improved treatment strategies for metastatic prostate cancer in recent years. Prostate-specific membrane antigen (PSMA) represents a promising target for diagnosis and therapy of prostate cancer. PSMA is over expressed in prostate cancer cells providing a target structure for non-invasive imaging and Lutetium-177-PSMA radioligand therapy. The CXCR4-receptor is expressed on different cell types and organs. Its over expression is associated with metastasis and poor prognosis. PET/CT imaging with Gallium-68-labelled PSMA ligands provide relevant information regarding tumor staging and progression. The present study investigates the interaction between expression of PSMA and CXCR4 considering established therapeutic agents to improve sensitivity of PSMA PET/CT imaging and optimize personalized cancer medicine.

Die Positronen-Emissions-Tomographie (PET) ist eine etablierte Methode zur Untersuchung von Stoffwechselvorgängen im Menschen. Sie wird als Werkzeug in der medizinischen Forschung ebenso wie klinisch als Diagnoseverfahren zur Erkennung von Metastasen eingesetzt. Dieses Projekt beschäftigt sich mit einer nichtmedizinischen Anwendung dieses bildgebenden Verfahrens – dem Aufbau und der Anwendung eines PET-Tomographen zur Untersuchung des Verhaltens von Schaum in Blasensäulen, dem Versuchsstand SCHAUMPET. Insbesondere wird auf die technische Realisierung des Projektes und die angewendeten Verfahren zur Bildgewinnung eingegangen. Am Beispiel von Natriumcapronat wird gezeigt, dass sich die Anreicherung eines Tensids in einer Schaumschicht mit Hilfe der Positronen-Emissions-Tomographie nachweisen lässt.

Die Kombination von Positronen-Emissions-Tomographie (PET) und Röntgen-Computertomographie (CT) in Form moderner PET/CT-Geräte ermöglicht die Nutzung der CT-Information zur Korrektur der Photonenschwächung in der PET. Allerdings können Bewegungen, die zum Beispiel durch die Atmung hervorgerufen werden können, zu einer fehlerhaften Schwächungskorrektur führen. Die Einführung von zeitlich aufgelöster Bildgebung für beide Modalitäten (4D-PET/4D-CT) ermöglicht nicht nur die Auflösung von periodischen Bewegungen, sondern auch die Reduktion dieser Fehler in der Schwächungskorrektur. Dazu werden die einzelnen Datensätze des 4D-PET, die jeweils einer bestimmten Bewegungsphase entsprechen, mit dem entsprechenden CT-Datensatz dieser Atemphase schwächungskorrigiert. In der vorliegenden Arbeit wurde diese phasenkorrelierte Schwächungskorrektur des 4D-PET mit dem 4D-CT am Universitästsklinikum Dresden installierten PET/CT ermöglicht und anhand von Phantomexperimenten mit anderen Schwächungskorrekturmethoden für 4D-PET verglichen. Dazu musste zunächst die Aufnahme von 4D-CT an dem verwendeten PET/CT ermöglicht und dessen Synchronität mit dem 4D-PET hergestellt werden. Außerdem wurde ein vorhandenes Atemphantom so modifiziert, dass es typische Bewegungen von Bronchialkarzinomen in zwei Dimensionen und mit zwei möglichen Atemmustern simuliert. Die phasenkorrelierte Schwächungskorrektur führte zu einer quantitativ korrekten Wiederherstellung des Aktivitätsvolumens, der darin enthaltenen Aktivität sowie der Bewegungsamplitude und stellt somit die beste der hier verglichenen 4D-PET-Schwächungskorrekturmethoden dar. Diese Ergebnisse lassen vermuten, dass die phasenkorrelierte Schwächungskorrektur auch bei klinischer Anwendung eine signifikante Verbesserung in oben genannten Punkten darstellt. Dies sollte in Zukunft an Patientendaten überprüft werden. / The combination of Positron Emission Tomography (PET) and Computed Tomography (CT) in one device allows the use of CT-information for attenuation correction in PET. Though motion, for example induced by respiration, can cause inaccurate attenuation correction. The implementation of time-resolved imaging methods for both modalities (4D-PET/4D-CT) enables not only the resolution of motion but also the reduction of artifacts caused by attenuation correction. Therefore, the single datasets of the 4D-PET that are related to a individual respiratory phase, are attenuation corrected with the corresponding dataset of the 4D-CT. This phase correlated attenuation correction of the 4D-PET with the 4D-CT was implemented at the PET/CT installed at the Universitätsklinikum Dresden. For that purpose the acquisition of 4D-CT was implemented at the PET/CT and its synchronisation with the 4D-PET was verified. Furthermore the new attenuation correction method was compared with other attenuation correction methods by performing phantom experiments. Therefore an exisisting respiratory phantom had to be modified to perform typical lung tumor motion in two dimensions with two possible patterns of respiration. The phase correlated attenuation correction leads to a quantitatively correct restauration of the activity volume, its total activity and its motion amplitude. Compared with other correction methods, the phase correlated attenuation correction shows the best results in all examined criteria. This findings suggest that the clinical application of the phase correlated attenuation correction will also lead to a significant improvement in all mentioned points. This has to be verified by analyzing patient data.

This thesis deals with a new low-energy method of chemical recycling of poly(ethylene terephthalate) (PET) using natural oils as reagents and microwave irradiation to accelerate depolymerization. The results of experiments with PET waste and castor oil, when the reaction mixture was heated in microwave reactor, showed that a complete depolymerization of PET chain has occured. Optimal conditions for the depolymerization PET were established: wt. ratio of PET / castor oil = 1 / 9.7, when the molar ratio of ester bonds of PET / hydroxyl groups of castor oil = 1 / 2.7, catalyst : zinc acetate at wt 1% from the PET mass, reaction temperature ranging from 235 to 245řC and the reaction time 60 min. Decomposition experiments also showed, that microwave irradiation accelerated decomposition of PET. Depolymerization reactionin MW reactor was complete at 6x shorter reaction time than the decomposition in the classically heated reactor. The results of analysis showed that the resulting product,the recyclate, was composed of unreacted castor oil and polyol products, that contained partially or fully esterified structural unit of PET, which were ended by ester-linked units of castor oil.

Title: Gallium Complexes for Molecular Imaging of Bone Tissue Author: Bc. Jan Holub Department of Inorganic Chemistry, Faculty of Science, Charles University Supervisor: RNDr. Vojtěch Kubíček, PhD. Supervisor's Email address: kubicek@natur.cuni.cz ABSTRACT This thesis is focused on preparing new ligands for selective complexation of gallium, which might serve as potential radiopharmaceuticals for 68 Ga-PET bone imaging. Two new ligands were prepared, combining 1,4,7-triazacyclonone-1,4-diacetic acid macrocyclic skeleton and bis(phosphonate) pendant arm, bound to the remaining free nitrogen atom on the macrocycle. Macrocyclic skeleton is responsible for high kinetic and thermodynamic stability of the Ga3+ complex and the bis(phosphonate) pendant arm insures selective delivery of the complex to the bone tissue. Both new ligands were fully characterized by NMR and mass spectroscopy. Complexation of Ga3+ was studied by 31 P and 71 Ga NMR spectroscopy. Binding to bone tissue was simulated by adsorption of the complexes to hydroxoapatite. Radiochemical experiments including study of 68 Ga complexation kinetics and basic in-vivo experiments including biodistribution studies and PET examination were done in cooperation with Johannes-Gutenberg Universität Mainz in Germany. Data obtained from these experiments were...

Every year more than fourteen-thousand adults in the United States are diagnosed with glioma, the most common malignant tumor of the central nervous system. Gliomas arise from glue like glial cells and present with a range of grade and prognosis. Glioblastoma multiforme (GBM), a grade IV glioma, is the most common glioma subtype and carries dismal prognosis with fewer than one half of patients surviving one year after diagnosis. The standard treatment for GBM is resection followed by a cocktail of chemo and radiation therapy. Unfortunately, complete surgical resection is impossible for GBM, and intra-tumor heterogeneity, a GBM hallmark, negatively impacts chemo and radiation therapy efficacy. This thesis contains six chapters that evaluate advanced imaging and statistical methods that may be used to improve glioma management. Chapter one presents background information to establish the relationship of four subsequent studies with ranging topics on advanced imaging techniques, biopsy sampling, and radiomic analysis. In chapter two, a case report is presented that demonstrates the importance of advanced magnetic resonance imaging (MRI) such as arterial spin labeled (ASL) perfusion sequences. In this case, a patient with a benign cerebral lesion presents with receptive aphasia and of the imaging data acquired, only ASL showed decrease cerebral aphasia. Chapter three describes the impact biopsy selection has on correlation between prognostic and histologic features in 35 patients with GBM. Multiple biopsy selection methods were compared, resulting in a wide range in correlation significance. Chapter four presents different voxel-wise radiomic models in adult glioma patients. From one voxel-wise radiomic model, predicted disease compositions (PDC) were computed in 17 glioma patients and were able to significantly (α = 0.05) predict overall survival, tumor grade, and endothelial proliferation. Chapter five describes the feasibility and hardware constraints of simultaneous PET/MR imaging protocols. A dynamic infusion of fluorodeoxyglucose (FDG) was administered with simultaneous MR imaging including echo planar imaging (EPI) based sequences used for functional MRI (fMRI). Heat from the EPI sequences deposited in the PET detector hardware and resulted in significant hardware failure. Finally, chapter six provides outlook and application to glioma clinical management considering the methods and findings presented in each study.<br>