Background: The 18 kDa translocator protein (TSPO), expressed at a low level in the healthy human central nervous system (CNS), is upregulated in inflammatory brain diseases by activated microglia and other immune cells. Using positron emission tomography (PET) radioligands targeting TSPO, it is possible to localise this signal and map the course of microglial activation and its effects on disease progression. Here, a newly developed second generation TSPO PET ligand, [18F]GE-180, was evaluated in different models of preclinical and clinical neuroinflammatory disease. Methods: A preclinical model of low-level inflammation with lipopolysaccharide (LPS) was designed. Rats were scanned with the first generation TSPO ligand [11C]- (R)-PK11195 and either [18F]GE-180 or [18F]DPA-714, with dual scanning enabling the direct comparison of second generation tracers with [11C]-(R)-PK11195. An arterial blood sampling system for rodent imaging with [18F]DPA-714 was set up and characterised. The performance of [18F]GE-180 was assessed in a clinical study in nine relapsing-remitting multiple sclerosis patients (RRMS) and ten healthy volunteers (HV). A comparison of kinetic modelling approaches for [18F]GE-180 human brain PET data was performed, as well as a longitudinal analysis with intervention using the disease-modifying treatment, natalizumab to evaluate the potential of [18F]GE-180 as a biomarker for therapy monitoring in MS subjects. Finally, the plasma-protein binding behaviour of [18F]GE-180 was evaluated in vitro using ultrafiltration. Results: In LPS animals, [18F]GE-180 produced a significantly higher ipsi- to contralateral uptake ratio and binding potential () than [11C]-(R)-PK11195 (p = 0.03), but [18F]DPA-714 did not. There was no significant difference between animals scanned with [18F]GE-180 and [18F]DPA-714, suggesting no overall superiority of the former. Characterisation of an arterial sampling system for rodent studies with [18F]DPA-714 allowed correction for dispersion effects. A comparison of reference regions showed that a novel externally derived tissue estimated with lower bias than a contralateral reference region. In human [18F]GE-180 brain PET data, the unconstrained two-tissue compartment model (2TCM) best described tracer behaviour in RRMS and HV subjects. Normal appearing white matter (NAWM) in patients was elevated over that of HVs. Standardised uptake values (SUVs) for the tracer in rodents were 0.28±0.12 and 0.84±0.31 in healthy tissue and LPS lesions respectively, and in humans were 0.36±0.04 (HV) and 0.58 (in a gadolinium- enhancing MS lesion). [18F]GE-180 uptake was also significantly reduced in the brains of RRMS subjects treated with natalizumab, correlating with clinically-identified improvement. [18F]GE-180 has a free fraction of between 1 and 8%.Conclusions: [18F]GE-180 shows good brain uptake in the rodent brain and produces superior signal to [11C]-(R)-PK11195, but not to [18F]DPA-714. The 2TCM fits human [18F]GE-180 PET data well, and the tracer is able to identify an elevated signal in RRMS patients compared to healthy subjects. [18F]GE-180 shows a large fraction of non-displaceable binding in human blood, thus further optimisation of kinetic modelling approaches is suggested.

Positron emission tomography (PET) is a powerful and highly specialised imaging modality that has the inherent ability to detect and quantify changes in the bio-distribution of an intravenously administered radio-labelled tracer, through dynamic image acquisition of the system under study. By modelling the temporal distribution of the tracer, parameters of interest regarding specific biological processes can be derived. Traditionally parameter estimation is done by first reconstructing a set of dynamic images independently, followed by kinetic modelling, leading to parameters of reduced accuracy and precision. Furthermore only simple geometrical models are used during image reconstruction to model the mapping between the image space and the data space, leading to images of reduced resolution. This thesis attempts to address some of the problems associated with the current methodology, by implementing and evaluating new spatiotemporal image reconstruction strategies in oncology PET/CT imaging, with simulated, phantom and real data. More specifically this thesis is concerned with iterative reconstruction techniques, the incorporation of resolution recovery and kinetic modelling strategies within the image reconstruction process and the application of such methods in perfusion [15O]H2O imaging. This work is mainly based upon 2 whole body PET/CT scanners, the Siemens Biograph 6 B-HiRez and TruePoint TrueV, but some aspects of this work were also implemented for the High resolution research tomograph (HRRT).

Positron emission tomography (PET) is a widely used molecular imaging modality,which offers quantitative information about many biochemical processes in vivo. In particular, the dynamic PET data provide physiologically meaningful parametricimages after the estimation of the parameters of a model that best describes thekinetic behaviour of the injected radiotracer. Spatiotemporal 4D image reconstructionalgorithms estimate these physiological parameters directly from the raw sinogramdata, where the noise distribution can be more accurately modelled and thus leading tostatistically more reliable parameter estimates. In this thesis a novel direct parametricimage reconstruction algorithm is introduced, which is based on the expectationmaximisation (EM) framework and is applicable to any spatiotemporal model. Themethod is evaluated for the spectral analysis model, which is a linear temporal modeland a two-tissue compartment model, which is a nonlinear temporal model. Inaddition, the method is evaluated for a linear spatial model and in particular the modelthat is normally used to describe the blurring components in image-based resolutionmodelling. Finally, the performance of gradient-based 3D reconstruction algorithmswas also assessed as an alternative to the well-established EM-based algorithms.

Parkinson’s disease (PD) is the second most common neurodegenerative condition to affect humans, and is characterised by the loss of dopaminergic neurons from the substantia nigra pars compacta (SNpc) in the midbrain along with the deposition of abnormal aggregates of alpha-synuclein protein in the brain which are in the form of Lewy bodies. Dopaminergic neurons from the SNpc project into a large subcortical structure known as the striatum, and positron emission tomography (PET) studies have demonstrated the dysfunction of the dopaminergic system in the striatum of patients with PD. Furthermore, immunohistochemistry studies of the striatum have identified the degeneration of dopaminergic nerve terminals and inclusions of alpha-synuclein. An aggressive and early onset form of familial PD is caused by the G51D point mutation in alpha-synuclein (G51D/+). Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has been used to generate a novel and precise rat model of PD which has the G51D mutation in rat alpha-synuclein. Wild-type (WT) and G51D/+ rats were analysed over the course of ageing (5, 10/11 and 16/17 months of age) using histological experiments and L-3,4-dihydroxy-6-18F-fluorophenylalanine (18FDOPA) PET imaging in order to determine if G51D/+ rats have abnormalities of histological staining and dopaminergic function analogous to those identified in patients with PD. Histological experiments were optimised using WT rat tissue and then used immunohistochemistry for tyrosine hydroxylase (an enzyme involved in the synthesis of dopamine) to evaluate dopamine nerve terminal integrity in the striatum of WT and G51D/+ rats. In addition, immunohistochemistry for alpha-synuclein was used to evaluate staining for alpha-synuclein in cell bodies and the neuropil within the striatum of WT and G51D/+ rats. 18F-DOPA is a well validated PET radiotracer and has been used to investigate dopaminergic function in the striatum of rats. The enzyme aromatic L-amino acid decarboxylase converts 18F-DOPA to 6-18F-fluorodopamine, which is in turn incorporated into presynaptic vesicles, and then released into the synaptic cleft following neuronal activation. PET imaging experiments were first optimised using phantoms and WT rats, then the optimised protocols were applied to studies of WT and G51D/+ rats. Results from tyrosine hydroxylase immunohistochemistry at Bregma 0.00 mm identified a trend for decreased optical density of tyrosine hydroxylase staining in the striatum of 5 month G51D/+ rats compared with age-matched WT controls (p=0.15), and in 17 month G51D/+ rats compared with age-matched WT controls (p=0.10). Semi-quantitative analysis of alpha-synuclein immunohistochemistry indicated an increased abundance of alpha-synuclein positive cell somata in the striatum, and decreased punctate terminal staining in the neuropil of G51D/+ rats compared with age-matched WT rats. 18F-DOPA PET imaging experiments indicated a trend for decreased influx rate constant (Ki) of 18F-DOPA in the striatum of 5 month old G51D/+ rats compared with age-matched WT controls (p=0.08), and a trend for decreased distribution volume ratio (DVR) of 18F-DOPA in the striatum relative to the cerebellum of 16 month old G51D/+ rats when compared with age-matched WT controls (p=0.09). 18F-DOPA PET imaging experiments also identified a trend for a decreased effective distribution volume ratio (EDVR) of 18F-DOPA in the striatum relative to the cerebellum (p=0.09) and in turn indicated increased effective dopamine turnover (EDT) (p=0.13) in the striatum of 16 month old G51D/+ rats compared with age-matched WT rats. Therefore, the results indicated abnormalities of dopaminergic function, as well as tyrosine hydroxylase and alpha-synuclein staining in G51D/+ rats compared with age-matched WT controls, and this appeared to have some features of PD in humans. Indices of EDT indicated compensatory changes in dopaminergic function in the striatum of 16 month old G51D/+ rats compared with age-matched WT rats. Additional compensatory changes in dopaminergic terminal function and tyrosine hydroxylase protein expression may be evident in 11 and 10 month old G51D/+ rats respectively compared with age-matched WT rats. The G51D/+ rat model represents an interesting model for further studies such as the underlying pathophysiology of PD. However, the phenotype observed in G51D/+ rats appeared to be less severe than that which has been observed in humans with G51D type PD.

Made available in DSpace on 2014-06-11T19:26:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-10Bitstream added on 2014-06-13T18:54:26Z : No. of bitstreams: 1 coelho_tm_me_bauru.pdf: 479749 bytes, checksum: b9c4aa0add23a730f10f9d3ed7c6bde9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Este trabalho apresenta a descrição do panorama brasileiro em relação à reciclagem de garrafas PET e aos processos envolvidos na recuperação de valor do produto, por meio da aplicação da logistica reversa. A relevância do estudo consiste no levantamento de informações sobre os desafios e oportunidades do setor. Em nível mundial, o Brasil é um dos maiores consumidores de PET em garrafa e os baixos custos industriais da embalagem pós-consumo aliados à falta de estrutura do canal reverso proporcionam um aumento significativo desse resíduo no meio ambiente. Buscou-se mostrar as ações realizadas no Brasil, bem como em outros Países elencados pela Associação Brasileira dos Fabricantes de Embalagens PET - ABIPET. Foi realizada uma pesquisa exploratória que consistiu no levantamento das informações junto a associações referentes ao setor de PET no Brasil. Os resultados, após a análise dos aspectos ambientais, econômicos e sociais, mostram os desafios e oportunidades para retorno de embalagens PET pós-consumo no Brasil e descrevem a necessidade de conscientizar os envolvidos direta e indiretamente; de estruturar as cadeias reversas pós-consumo; de reduzir o consumo a fim de diminuir os resíduos gerados e de envolver os setores industriais para a busca de tecnologias mais limpas junto à cadeia produtiva do PET, a responsabilidade estendida do fabricante, bem como o poder público com o objetivo de auxiliar o processo por meio de políticas públicas / This work presents a description of the Brazilian panorama over the recycling of PET bottles and the processes involved in the recovery of product value through the application of reverse logistics. The relevance of the study is a survey of information on the challenges and opportunities in the industry. Globally, Brazil is one of the largest consumers of PET bottles and the low manufacturing costs of post-consumer packaging coupled with lak of structure of the reverse channel provides a significant increase of this residue in the environment. We tried to show the actions performed in Brazil and other countries listed by the Brazilian Association of Manufacturers of PET Packaging - ABIPET. We performed an exploratory study consisted of getting information from association for the PET industry in Brazil. The results, after analysis of the environemental, economic and social aspects, show the challenges and oportunities for return of post-consumer PET in Brazil and describe the need to educate those involved directly and indirectly, to structure the post-consumer reverse; to reduce consumption in order to reduce the waste generated and to involve industries in the search for cleaner technologies along the production chain of PET, the extended manufacture's responsability and the government in order to assist the process through public policies

Master of Science / Grain Science and Industry / Sajid Alavi / The U.S. pet food market was approximately worth $22 billion in 2013. Further growth is predicted at a pace faster than most major human food product categories. More than 60% of pet food products are processed using extrusion, and a significant proportion is produced using baking. However, research is lacking on fundamental process and product differences between extrusion and baking. The current study focuses on this aspect and also in-depth characterization of process and product quality. Three iso-nutritional diets were formulated for dry expanded dog food using 0%, 7% and 15% fresh meat inclusion. Major variations between diets were inclusion rates of mechanically deboned chicken, cereal grains, and poultry fat. Each diet was processed with a single screw extruder using various thermal and/or mechanical energy inputs (obtained by varying pre-conditioner stem injection and/or extruder screw speeds). Diets were also processed by baking using a 30 foot experimental oven at 425°F, although the fresh meat inclusion was at 0%, 10% and 20% levels. Proximate analysis of products was conducted. Products were also characterized for physico-chemical properties such as bulk density, piece density, expansion ratio, degree of gelatinization and textural attributes. As fresh meat inclusion increased (0–15%), expansion ratio (4.1–3.5) decreased irrespective of extrusion treatment. Expansion was not evident in the baked kibbles, and bulk and piece densities were up to 56% higher for baked versus extruded kibbles. Textural analysis of extruded kibbles revealed serrated force-deformation response, typical of cellular products, with peak hardness of 2.9–1.5 kgf. On the other hand, baked products had a ‘smooth’ force-deformation response with higher peak hardness than extruded products (up to 3 kgf). Microbial counts for baked products were higher than extruded products, and rancidity profiles as obtained from gas chromatography also had marked differences. The extrusion process was characterized by detailed mass and energy balance analyses, and compared with baking that lacks mechanical energy input. Results from this study provide a useful bench-mark for dry expanded pet food product quality and commonly used processing technologies.

Orientador: Rosani de Castro / Banca: Jorge Henrique Caldeira de Oliveira / Banca: José Alcides Gobbo Junior / Resumo: Este trabalho apresenta a descrição do panorama brasileiro em relação à reciclagem de garrafas PET e aos processos envolvidos na recuperação de valor do produto, por meio da aplicação da logistica reversa. A relevância do estudo consiste no levantamento de informações sobre os desafios e oportunidades do setor. Em nível mundial, o Brasil é um dos maiores consumidores de PET em garrafa e os baixos custos industriais da embalagem pós-consumo aliados à falta de estrutura do canal reverso proporcionam um aumento significativo desse resíduo no meio ambiente. Buscou-se mostrar as ações realizadas no Brasil, bem como em outros Países elencados pela Associação Brasileira dos Fabricantes de Embalagens PET - ABIPET. Foi realizada uma pesquisa exploratória que consistiu no levantamento das informações junto a associações referentes ao setor de PET no Brasil. Os resultados, após a análise dos aspectos ambientais, econômicos e sociais, mostram os desafios e oportunidades para retorno de embalagens PET pós-consumo no Brasil e descrevem a necessidade de conscientizar os envolvidos direta e indiretamente; de estruturar as cadeias reversas pós-consumo; de reduzir o consumo a fim de diminuir os resíduos gerados e de envolver os setores industriais para a busca de tecnologias mais limpas junto à cadeia produtiva do PET, a responsabilidade estendida do fabricante, bem como o poder público com o objetivo de auxiliar o processo por meio de políticas públicas / Abstract: This work presents a description of the Brazilian panorama over the recycling of PET bottles and the processes involved in the recovery of product value through the application of reverse logistics. The relevance of the study is a survey of information on the challenges and opportunities in the industry. Globally, Brazil is one of the largest consumers of PET bottles and the low manufacturing costs of post-consumer packaging coupled with lak of structure of the reverse channel provides a significant increase of this residue in the environment. We tried to show the actions performed in Brazil and other countries listed by the Brazilian Association of Manufacturers of PET Packaging - ABIPET. We performed an exploratory study consisted of getting information from association for the PET industry in Brazil. The results, after analysis of the environemental, economic and social aspects, show the challenges and oportunities for return of post-consumer PET in Brazil and describe the need to educate those involved directly and indirectly, to structure the post-consumer reverse; to reduce consumption in order to reduce the waste generated and to involve industries in the search for cleaner technologies along the production chain of PET, the extended manufacture's responsability and the government in order to assist the process through public policies / Mestre

Made available in DSpace on 2016-06-02T19:12:24Z (GMT). No. of bitstreams: 1 4689.pdf: 1138367 bytes, checksum: 36a09c831467eb93c2b6105a45d2c99d (MD5) Previous issue date: 2003-12-04 / Universidade Federal de Sao Carlos / The increasing requirement of Ply(ethylene terephtalate) PET from the package market has made this available to the public discarded, quickly, since the technology of multi way package hasn t been possible due to high cost on the plant and it s inadequate reuse. In the PET mechanical recycling, the most used way worldwide to recovery this material, the features obtained after the many steps of reprocessing determine its final application. One of the biggest challenges in the recycling business is how to make the return of consumer residues in blown mouding package for carbonated soft drinks, as for recoverying original molecular weight features, always reduced with the manufacturing process, time of use and recycling reprocess. The reactions of solid state polymerization has been used success to attend polymers network. However, SSP available technologies in the market act in the virgin PET s manufacture with continuous process in large scale and high investment. Nothing has been doing for PET post consumer and if we consider that had to develop a low cost SSP system and a low scale where many of the companies would have access. Then the proposed work had for objective to develop a system compact pilot reactor for drying, crystallization and post condensation in order to increase PET s molecular weight and study the influence of its variables process about several features of recycled PET. The results obtained to show for objective was reached, however only laboratory scale and the most efficiency to process using vacuum system. / O crescente aumento da demanda do Poli(tereftalato de etileno) PET vindo do nicho de mercado de embalagens para líquidos carbonatados fez com que esse produto ficasse disponível ao publico após o descarte, muito rapidamente. A tecnologia de embalagens retornáveis (multi way) não foi viável devido ao custo (embalagem, envasamento) e a sua reutilização inadequada. Na reciclagem mecânica do PET, que e a forma mais utilizada mundialmente para recuperação deste material, as características obtidas após as diversas etapas do processamento determinam a sua aplicação final. Um dos grandes desafios nesta área e a viabilização técnica de retorno dos resíduos pós-consumo as suas aplicações em embalagens sopradas para bebidas carbonatadas, quanto a recuperação das características de peso molecular original sempre diminuídas com o processo de fabricação, com o tempo de uso e com os reprocessamentos na reciclagem. As reações de polimerização no estado solido (SSP) tem sido utilizadas com sucesso para atender a cadeia do polímero. Entretanto, tecnologias de SSP disponíveis no mercado atuam na fabricação de PET virgem com processos contínuos de grande escala e alto investimento. Pouco se tem feito para o PET pós-consumo, principalmente na forma de flakes . Considerando que este mercado e pulverizado com numerosos fornecedores e diversificadas empresas, propôs-se desenvolver um sistema de SSP de baixo custo e pequena escala onde a maioria das empresas teria acesso. Assim, o trabalho proposto teve por objetivo desenvolver um sistema piloto de reator único para desumidificação, cristalização e pós condensação, operando com diferentes gases inertes ou vácuo de modo a aumentar o peso molecular do PET em flakes e estudar a influência das suas variáveis de processo sobre diversas características de PET reciclado. Os resultados obtidos mostraram que o objetivo foi alcançado, porém escala laboratorial de bancada, com eficiência maior para o processo utilizando o sistema de vácuo.

Dans le cadre du projet européen ENVISION (2010-2014) et en collaboration avec l'équipe CAS-PHABIO de l'IPNL, cette thèse constitue une contribution méthodologique et technique dans le domaine de la dosimétrie et de l'imagerie de contrôle par émission des positons (TEP) pour les organes en mouvement. Les méthodes actuelles utilisent le recalage déformable d'images CT pour estimer le mouvement des organes internes. Le recalage déformable permet d'estimer le déplacement de chaque voxel d'une image à une autre. La dose radio-thérapeutique ainsi que l'activité TEP sont accumulées sur des voxels. Ces approches ont des difficultés quand il s'agit de prendre en compte la variation de densité à l'intérieur des organes et l'aspect non-répétitif du mouvement respiratoire. Les travaux antérieurs de l'équipe ont permis de développer un premier modèle biomécanique complet du système respiratoire qui, corrélé avec des signaux externes, pourrait prendre en compte la variabilité du mouvement respiratoire. Cette thèse présente une approche qui permet d'intégrer un tel modèle biomécanique dans un système de planification de traitement pour l'hadronthérapie. Dans cette thèse, nous avons choisi d'investiguer de près l'utilisation des maillages tétraédriques déformables dans la dosimétrie et la reconstruction d'images TEP afin d'estimer les avantages et inconvénients de ce type de géométrie. En conclusion, notre approche peut être utilisée avec n'importe quel modèle de déformation basé sur une géométrie tétraédrique et dont le mouvement est décrit par le déplacement des nœuds des maillages et donc contrairement aux méthodes basés images, notre approche n'est pas nécessairement dépendante de l'existence des images internes à tout moment. Dans le futur, les méthodes développées dans cette thèse pourraient être utilisées avec un modèle biomécanique complet du système respiratoire afin de quantifier, par exemple, les effets de la variabilité de la respiration sur le dépôt de dose / Respiratory-induced organ motion is a technical challenge to nuclear imaging and to charged particle therapy dose calculations for lung cancer treatment in particular. Internal organ tissue displacements and deformations induced by breathing need to be taken into account when calculating Monte Carlo dose distributions as well as when performing tomographic reconstructions for PET imaging. Current techniques based on Deformable Image Registration (DIR) cannot fully take into account the density variations of the tissues nor the fact that respiratory motion is not reproducible. As part of the ENVISION (2010-2014) European project, in collaboration with the CAS-PHABIO team from IPNL (the Nuclear Physics Institute from Lyon), this PhD project presents a methodological contribution to physical dose calculations and PET-based treatment verification for hadron therapy in the case of moving tumours. Contrary to DIR-based methods where motion is described by relative voxel displacement, each organ is represented as a deformable grid of tetrahedra where internal motion is described by mesh vertex transformations calculated using continuum mechanics. First, this PhD project proposes a new method to calculate four dimensional dose distribution over tetrahedral meshes, which are deformed using biomechanical modeling based on Finite Element Analysis (FEA). The second part of the PhD is focused on motion compensation for PET image reconstruction using deformable tetrahedral meshes

The aim of this work is the assessment of the diagnostic accuracy in parathyroid glands (PG) detection by various scintigraphic methods and to propose the optimal examination procedure for successful localization of hyperfunctional PG. The patients were divided into 3 groups with individual types of hyperparathyroidism (HPT): group I. primary PHPT (253 patients), group II. normocalcemic NPHPT (75 patients) and group III. secondary SHPT (61 patients). For all the patients protocol A was performed: one day a two-phase SPECT/CT scan using 99mTc-MIBI (technetium 2-methoxyisobutylisonitrile) depicted simultaneously thyroid gland and PG, and another day thyroid SPECT using 99mTc-NaTcO4 (pertechnetate) for 3D subtraction analysis. In case of 44 patients from group I with negative or unclear results of the protocol A also protocol B was performed: PET/CT using 18F-FCH (fluorocholine). The results of surgery and histology served as a "gold standard" for the assessment of the accuracy of scintigraphic findings. In group I. 209/253 patients had a positive finding on scintigraphy using protocol A and 44 patients with an unclear or negative finding of protocol A underwent protocol B examination. In total, 253 patients were operated. The results of the diagnostic accuracy: sensitivity, specificity, positive...