Positron emission tomography (PET) and single photon emission tomography (SPECT) are two nuclear emission-imaging modalities that rely on the detection of high-energy photons emitted from radiotracers administered to the subject. The majority of these photons are attenuated (absorbed or scattered) in the body, resulting in count losses or deviations from true detection, which in turn degrades the accuracy of images. In clinical emission tomography, sophisticated correction methods are often required employing additional x-ray CT or radionuclide transmission scans. Having proven their potential in both clinical and research areas, both PET and SPECT are being adapted for small animal imaging. However, despite the growing interest in small animal emission tomography, little scientific information exists about the accuracy of these correction methods on smaller size objects, and what level of correction is required. The purpose of this work is to determine the role of attenuation and scatter corrections as a function of object size through simulations. The simulations were performed using Interactive Data Language (IDL) and a Monte Carlo based package, Geant4 application for emission tomography (GATE). In IDL simulations, PET and SPECT data acquisition were modeled in the presence of attenuation. A mathematical emission and attenuation phantom approximating a thorax slice and slices from real PET/CT data were scaled to 5 different sizes (i.e., human, dog, rabbit, rat and mouse). The simulated emission data collected from these objects were reconstructed. The reconstructed images, with and without attenuation correction, were compared to the ideal (i.e., non-attenuated) reconstruction. Next, using GATE, scatter fraction values (the ratio of the scatter counts to the total counts) of PET and SPECT scanners were measured for various sizes of NEMA (cylindrical phantoms representing small animals and human), MOBY (realistic mouse/rat model) and XCAT (realistic human model) digital phantoms. In addition, PET projection files for different sizes of MOBY phantoms were reconstructed in 6 different conditions including attenuation and scatter corrections. Selected regions were analyzed for these different reconstruction conditions and object sizes. Finally, real mouse data from the real version of the same small animal PET scanner we modeled in our simulations were analyzed for similar reconstruction conditions. Both our IDL and GATE simulations showed that, for small animal PET and SPECT, even the smallest size objects (~2 cm diameter) showed ~15% error when both attenuation and scatter were not corrected. However, a simple attenuation correction using a uniform attenuation map and object boundary obtained from emission data significantly reduces this error (~1% for smallest size and ~6% for largest size, in non-lung regions). In addition, we did not observe any significant improvement between the uses of uniform or actual attenuation map (e.g., only ~0.5% for largest size in PET studies). The scatter correction was not significant for smaller size objects, but became increasingly important for larger sizes objects. These results suggest that for all mouse sizes and most rat sizes, uniform attenuation correction can be performed using emission data only. For smaller sizes up to ~ 4 cm, scatter correction is not required even in lung regions. For larger sizes if accurate quantization needed, additional transmission scan may be required to estimate an accurate attenuation map for both attenuation and scatter corrections.

Purpose: The purpose of this thesis is to contribute to knowledge of customers’ buying behaviour toward premium dog food by examining their brand associations and how these are shaped by using Bozita Robur as a case study. Background: Market for dog food has increased heavily during the last decades what made knowledge of underlying driving forces of dog food consumption crucial for dog food producers. Quite peculiar is a phenomenon of purchasing behaviour towards a product purchased but not consumed turning it into a more complex and dynamic object of study. Lack of coherent and conclusive research that offer an understanding of primary behavioural drivers and preferences of Swedish dog food customers makes it a good opportunity to continue investigating the dog food industry. Method: The study is conducted in the form of a single case study. A survey instrument is used to collect data on awareness and to identify behavioural beliefs and subjective norms of consumers, followed by phone interviews that uncover their attitudes towards dog food brands. Lantmännen Doggy’s brand Bozita Robur is used for this purpose. Data collected is further analyzed with the application of consumer behaviour related theories. Findings: The study has found that Swedish customers have built a positive image associated with premium dog food brands, where superior quality is the primary association. On the brand schema level, each of the premium dog food brands investigated holds specific associations in consumer minds, whereas the strength of these associations depends much on brand recognition levels. Bozita Robur, though less familiar among respondents, was found to have a positive brand schema and is associated with Swedishness and high quality. Customers of premium dog food brand actively search for information when making a purchasing decision towards a dog feed brand. In a product, they do value high nutrition content. Dog owners are influenced by various social groups, among which breeders and specialty store staff have the strongest influence when it comes to purchasing advice of the dog food brands.

Several cardiac diseases, including hypertrophy, cardiomyopathy, and myocardial infarction, result in the upregulation of cardiac angiotensin II type-1 receptors (AT1R). Imaging the AT1R in vivo via PET provides the potential to monitor disease progression and guide therapy accordingly. The aim of this research was to develop a novel F-18 labeled losartan analog as an AT1R PET tracer and begin evaluation in rats. Due to the longer half-life and shorter positron range of F-18, we presume that an F-18 labeled tracer will be more beneficial than current C-11 labeled tracers. Prior structure-activity relationship (SAR) studies suggested the addition of substituents to the hydroxyl group of losartan would minimally affect AT1R binding affinity. [18F]Fluoropyridine losartan ([18F]FPyrLos) was synthesized in an automated module through conjugation of [18F]fluoro-3-pent-4-yn-1-yloxypyridine ([18F]FPyKYNE) to azide-modified losartan via the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) ‘click’ reaction. [18F]FPyrLos was produced in approximately 10% yield (decay-corrected) with > 97.5% purity and specific activities up to 4,200 mCi/µmol. MicroPET (Siemens Inveon) images of normal Sprague Dawley rats displayed high uptake in the kidneys (ratio of 8.3 compared to surrounding tissue at 10 min). Metabolite analysis in the kidneys and plasma by column-switch HPLC revealed that roughly two-thirds of the tracer was unchanged 10 min post-injection and that one labeled hydrophilic metabolite exists, accounting for roughly 6% of the total activity. Both microPET and metabolism studies displayed a dose-dependent reduction in renal uptake upon co-injection with AT1R blocker candesartan indicating specific binding. Further work in rat disease models is required to evaluate the potential of this tracer for imaging cardiac AT1R.

<p><strong>Purpose: </strong>The purpose of this thesis is to contribute to knowledge of customers’ buying behaviour toward premium dog food by examining their brand associations and how these are shaped by using Bozita Robur as a case study.<strong></strong></p><p><strong>Background:</strong> Market for dog food has increased heavily during the last decades what made knowledge of underlying driving forces of dog food consumption crucial for dog food producers. Quite peculiar is a phenomenon of purchasing behaviour towards a product purchased but not consumed turning it into a more complex and dynamic object of study. Lack of coherent and conclusive research that offer an understanding of primary behavioural drivers and preferences of Swedish dog food customers makes it a good opportunity to continue investigating the dog food industry.</p><p><strong>Method:</strong> The study is conducted in the form of a single case study. A survey instrument is used to collect data on awareness and to identify behavioural beliefs and subjective norms of consumers, followed by phone interviews that uncover their attitudes towards dog food brands. Lantmännen Doggy’s brand Bozita Robur is used for this purpose. Data collected is further analyzed with the application of consumer behaviour related theories.</p><p><strong>Findings: </strong>The study has found that Swedish customers have built a positive image associated with premium dog food brands, where superior quality is the primary association. On the brand schema level, each of the premium dog food brands investigated holds specific associations in consumer minds, whereas the strength of these associations depends much on brand recognition levels. Bozita Robur, though less familiar among respondents, was found to have a positive brand schema and is associated with Swedishness and high quality.</p><p><strong> </strong>Customers of premium dog food brand actively search for information when making a purchasing decision towards a dog feed brand. In a product, they do value high nutrition content. Dog owners are influenced by various social groups, among which breeders and specialty store staff have the strongest influence when it comes to purchasing advice of the dog food brands.</p>

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.

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Die Positronen-Emissions-Tomographie (PET) bei der Schwerionentherapie ist eine wichtige Methode zur Qualitätskontrolle in der Tumortherapie mit Kohlenstoffionen. Die vorliegende Arbeit beschreibt die Verbesserungen des PET-Verfahrens, wodurch sich in der Folge präzisere Aussagen zur Dosisapplikation treffen lassen. Aufbauend auf den Grundlagen (Kap. 2) werden die Neuentwicklungen in den drei darauf folgenden Abschnitten (Modellierung des Abbildungsprozesses bei der PET, Streukorrektur für PET bei der Schwerionentherapie, Verarbeitung der rekonstruierten PET-Daten) beschrieben. Die PET-Methode bei der Schwerionentherapie basiert auf dem Vergleich zwischen den gemessenen und vorausberechneten Aktivitätsverteilungen. Die verwendeten Modelle in der Simulation (Erzeugung der Positronenemitter, deren Ausbreitung, der Transport und der Nachweis der Annihilationsquanten) sollten so präzise wie möglich sein, damit ein aussagekräftiger Vergleich möglich wird. Die Genauigkeit der Beschreibung der physikalischen Prozesse wurde verbessert und zeiteffiziente Algorithmen angewendet, die zu einer erheblichen Verkürzung der Rechenzeit führen. Die erwarteten bzw. die gemessenen räumlichen Radioaktivitätsverteilungen werden mit einem iterativen Verfahren rekonstruiert [Lau99]. Die gemessenen Daten müssen hinsichtlich der im Messobjekt auftretenden Comptonstreuung der Annihilationsphotonen korrigiert werden. Es wird ein geeignetes Verfahren zur Streukorrektur für die Therapieüberwachung vorgeschlagen und dessen Realisierung beschrieben. Zur Einschätzung der Güte der Behandlung wird die gemessene und die simulierte Aktivitätsverteilung verglichen. Dazu wurde im Rahmen der vorliegenden Arbeit eine Software entwickelt, das die rekonstruierten PET-Daten visualisiert und die anatomischen Informationen des Röntgentomogramms mit einbezieht. Nur durch dieses Auswerteverfahren war es möglich, Fehler im physikalischen Strahlmodell aufzudecken und somit die Bestrahlungsplanung zu verbessern.

Today tumour diseases are the second most cause of death in Western countries. But only 45 percent of the patients can be cured by the established treatment methods. The further improvement of the these forms of therapy and the development of new therapeutical approaches is urgent. A substantial proportion of the patients could benefit from particle therapy with heavy ions. Beams of accelerated heavy ions (e.g. carbon, nitrogen or oxygen) with an energy between 70 and 500 AMeV are characterised by physical and biological properties superior to the radiation used in conventional radiotherapy (photons, electrons, neutrons). They form a sharp dose maximum (Bragg peak) shortly before coming to rest and are scarcely scattered while penetrating tissue. Because of the increased relative biological efficiency of these ions in the Bragg peak region they are suitable for precision therapy of deeply seated, compact, radioresistant tumours near to organs at risk. For a safe application of heavy ions close to radiosensitive structures (brain stem, optical nerves, eyes) an in situ monitoring of the therapy is desirable. This can be accomplished by positron emission tomography (PET), since fragmentation reactions between the stable ions of the therapy beam and the atomic nuclei of the tissue generate a dynamic spatial distribution of positron emitters (ß+-emitters) that can be observed by a positron camera. At the Gesellschaft für Schwerionenforschung in Darmstadt a medical treatment site for heavy ion therapy has been established in co-operation with the Radiologische Universitätsklinik Heidelberg, the Deutsches Krebsforschungszentrum Heidelberg and the Forschungszentrum Rossendorf. The fast variation of the beam energy in conjunction with the vertical and horizontal beam deflection by dipole magnets (raster scanning) allows the three-dimensional, strictly tumour shape conformed irradiations. The dual head positron camera BASTEI has been installed at the treatment place in order to measure the decay of the ß+-emitters during the irradiation and a few minutes after. Two ways to verify the treatment plan by PET are possible. # In critical situations when the beam has to pass very heterogeneous structures and radiosensitive organs are situated in the direction of the beam behind the Bragg peak, a monoenergetic low dose beam pulse can be applied to the patient. The range of the particles can be derived from the simultaneous PET scan, so that the correct range calculation of the treatment plan is ensured before the therapeutical irradiations are started. # During each fraction of the heavy ion therapy the ß+-activity distributions are measured routinely. Based on the time course of every individual therapy fraction the expected ß+-emitter distribution is computed. By comparing the simulated with the measured data the precision of the dose deposition of this single therapy fraction is assessed. If a considerable disagreement between these two distributions is revealed by this comparison the treatment plan has to be modified before proceeding with the following therapy fraction. The PET data are recorded in list mode, together with a protocol of important accelerator parameters of the irradiation. Because of the half-lives of the most abundant ß+-emitters 11C and 15O it is on principle impossible to obtain the precise position of the 12C therapy beam by PET during the irradiation. …

Positron emission tomography (PET) is a powerful, non-invasive in vivo imaging technique used for diagnostics and drug development. The synthesis of \(^{18}F\)-PET tracers is challenging due to the short half-life of the unnatural isotope that necessitates late-stage fluorination, and the limited reactivity of nucleophilic fluoride, the preferred and widely accessible form of \(^{18}F\). This thesis describes the development of an electrophilic fluorination reagent derived from fluoride. The reagent can be employed in a late-stage fluorination reaction of palladium aryl complexes to give access to small molecule aryl fluorides. The reagent can be made from \([^{18}F]\)fluoride and used to synthesize radiolabeled small molecules for PET imaging experiments. Two small molecules known to interact with the serotonergic system were synthesized, radiolabeled, and imaged in rats and non-human primates and evaluated for use as PET tracers. / Chemistry and Chemical Biology

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