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Assessment of abdominal aortic aneurysm biology using magnetic resonance imaging and positron emission tomography-computed tomographyForsythe, Rachael Olivia January 2018 (has links)
Background Although abdominal aortic aneurysm (AAA) growth is non-linear, serial measurements of aneurysm diameter are the mainstay of aneurysm surveillance and contribute to decisions on timing of intervention. Aneurysm biology plays a key part in disease evolution but is not currently routinely assessed in clinical practice. Magnetic Resonance Imaging (MRI) and Positron Emission Tomography-Computed Tomography (PET-CT) provide insight into disease processes on a cellular or molecular level, and represent exciting new imaging biomarkers of disease activity. Macrophage-mediated inflammation may be assessed using ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and the PET radiotracer 18FSodium Fluoride (18F-NaF) identifies microcalcification which is a response to underlying necrotic inflammation. The central aim of this thesis was to investigate these imaging modalities in patients with AAA. Methods and Results USPIO MRI: MULTI-CENTRE STUDY In a prospective multi-centre observational cohort study, 342 patients (85.4% male, mean age 73.1±7.2 years, mean AAA diameter 49.6±7.7mm) with asymptomatic AAA ≥4 cm anteroposterior diameter underwent MRI before and 24-36 hours after intravenous administration of USPIO. Colour maps (depicting the change in T2* caused by USPIO) were used to classify aneurysms on the basis of the presence of USPIO uptake in the aneurysm wall, representing mural inflammation. Intra- and inter-observer agreement were found to be very good, with proportional agreement of 0.91 (kappa 0.82) and 0.83 (kappa 0.66), respectively. At 1 year, there was 29.3% discordant classification of aneurysms on repeated USPIO MRI and at 2 years, discordance was 65%, suggesting that inflammation evolves over time. In the observational study, after a mean of 1005±280 days of follow up, there were 126 (36.8%) aneurysm repairs and 17 (5.0%) ruptures. Participants with USPIO enhancement (42.7%) had increased aneurysm expansion rates (3·1±2·5 versus 2·5±2·4 mm/year; difference 0·6 [95% confidence intervals (CI), 0·02 to 1·2] mm/year, p=0·0424) and had higher rates of aneurysm rupture or repair (69/146=47·3% versus 68/191=35·6%; difference 11·7%, 95% CI 1·1 to 22·2%, p=0·0308). USPIO MRI was therefore shown to predict AAA expansion and the composite of rupture or repair, however this was not independent of aneurysm diameter (c-statistic, 0·7924 to 0·7926; unconditional net reclassification -13·5%, 95% confidence intervals -36·4% to 9·3%). 18F-NaF PET-CT: SINGLE-CENTRE STUDY A sub-group of 76 patients also underwent 18F-NaF PET-CT, which was evaluated using the maximum tissue-to-background ratio (TBRmax) in the most diseased segment (MDS), a technique that showed very good intra- (ICC 0.70-0.89) and inter-observer (ICC 0.637-0.856) agreement. Aneurysm tracer uptake was compared firstly in a case-control study, with 20 patients matched to 20 control patients for age, sex and smoking status. 18F-NaF uptake was higher in aneurysm when compared to control aorta (log2TBRmax 1.712±0.560 vs. 1.314±0.489; difference 0.398 (95% CI 0.057, 0.739), p=0.023), or to non-aneurysmal aorta in patients with AAA (log2TBRmax 1.647±0.537 vs. 1.332±0.497; difference 0.314 (95% CI 0.0685, 0.560), p=0.004). An ex vivo study was performed on aneurysm and control tissue, which demonstrated that 18F-NaF uptake on microPET-CT was higher in the aneurysm hotspots and higher in aneurysm tissue compared to control tissue. Histological analysis suggested that 18F-NaF was highest in areas of focal calcification and necrosis. In an observational cohort study, aneurysms were stratified by tertiles of TBRmax in the MDS and followed up for 510±196 days, with 6 monthly serial ultrasound measurements of diameter. Those in the highest tertile of tracer uptake expanded more than 2.5 times more rapidly than those in the lowest tertile (3.10 [3.58] mm/year vs. 1.24 [2.41] mm/year, p=0.008) and were also more likely to experience repair or rupture (15.3% vs. 5.6%, log-rank p=0.043). In multivariable analyses, 18F-NaF uptake on PET-CT emerged as an independent predictor of AAA expansion (p=0.042) and rupture or repair (HR 2.49, 95% CI1.07, 5.78; p=0.034), even when adjusted for age, sex, body mass index, systolic blood pressure, current smoking and, crucially, aneurysm diameter. Conclusion These are the largest USPIO MRI and PET-CT studies in AAA disease to date and the first to investigate 18F-NaF. Both USPIO MRI and 18F-NaF PET-CT are able to predict AAA expansion and the composite of rupture and repair, with 18F-NaF PETCT emerging as the first imaging biomarker that independently predicts expansion and AAA events, even after adjustment for aneurysm diameter. This represents an exciting new predictor of disease progression that adds incremental value to standard clinical assessments. Feasibility and randomised clinical trials are now required to assess the potential of this technique to change the management and outcome of patients with AAA.
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Avaliação dos níveis de radiação ambiental no laboratório de tomografia por emissão de pósitrons acoplada a tomografia computadorizada, microPET/CT / Evaluation of ambient radiation levels in positron emission tomography/computed tomography in microPET/CT laboratorySarmento, Daniele Martins 24 May 2016 (has links)
O sistema microPET/CT é um importante equipamento utilizado nas pesquisas de imagem diagnóstica em pequenos animais. O radiofármaco mais usado nesta tecnologia é o fluordeoxiglicose marcado com flúor-18. Este estudo tem como objetivo efetuar o controle radiológico no laboratório de pesquisa microPET/CT do Centro de Radiofarmácia do IPEN-CNEN/SP, de forma a satisfazer tanto as normas nacionais como as recomendações internacionais. O laboratório está classificado pela equipe de radioproteção da instalação como área supervisionada, nas quais embora não seja obrigatória a adoção de medidas específicas de proteção e segurança, devem ser submetidas reavaliações regulares das condições do ambiente de trabalho. Visando assegurar a proteção radiológica dos trabalhadores diretamente envolvidos no manuseio do equipamento, realizou-se o monitoramento do local de trabalho e a avaliação do controle de dose individual. Inicialmente foi feito o monitoramento pré-operacional, isto é, o levantamento radiométrico no laboratório. Além disso, mediu-se nível de radiação externa nas instalações do laboratório e suas adjacências, por meio da colocação de nove dosímetros termoluminescentes (TL) de CaSO4:Dy, em locais previamente selecionados. Os indivíduos ocupacionalmente expostos foram avaliados mensalmente por meio do uso de dosímetros TL posicionados no tórax e por medidas de corpo inteiro, tomadas a cada seis meses. O período do estudo foi de dois anos, com início em abril de 2014. Para o controle do microPET/CT realizou-se testes de desempenho de acordo com o protocolo padrão do equipamento e em conformidade com a norma desenvolvida pela força tarefa para estudos com PET em animais Animal PET Standard Task Force. O presente estudo permitiu demonstrar que os níveis de radiação das áreas (estimativas de dose ambiente e dose efetiva), assim como a blindagem do equipamento estão adequados de acordo com os limites da exposição ocupacional. Ressalta-se a importância de se seguir rigorosamente os princípios de radioproteção, já que se trata de pesquisas com fontes radioativas não seladas. / Micro PET/CT scanner is an essential tool generally used for small animal molecular imaging. Fluorine-18-labeled fluorodeoxyglucose is the most widely used radioisotope in this technique. The present study aimed to evaluate the radiation levels in a micro PET/CT research laboratory of the Radiopharmacy Center at IPEN-CNEN / SP, in order to accomplish both national standards and international recommendations. The radioprotection team has classified the laboratory as supervised area; even this laboratory does not require the adoption of specific measures for protection and safety, should be done regular re-evaluation of the conditions of occupational exposures. Workplace monitoring and individual control assessment were carried out to ensure the radiological protection of all workers directly involved in handling the scanner. Initially, there was conducted a radiometric survey, as well as measurements of the external radiation level in the workplace and its surroundings. To achieve this goal, there were placed nine thermoluminescent dosimeters of CaSO4:Dy in preselected locations. Monthly evaluations of the occupationally exposed individuals were carried out through the use of TL dosimeters, ported in the workers´ chest. Moreover, whole body measurements were performed every six months. The study period was about two-years which started in April 2014. All tests to evaluate micro PET/CT performance were based on the standard protocol of the equipment in accordance with the standard developed by the Animal PET Standard Task Force. Present study\'s results demonstrated that the ambient radiation levels (ambient and effective estimated radiation dose), as well as the effective shielding equipment are both adequate. This study emphasizes that it is essential to strictly follow the principles of radioprotection in workplace, whenever researches involve radioactive unsealed sources.
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Avaliação dos níveis de radiação ambiental no laboratório de tomografia por emissão de pósitrons acoplada a tomografia computadorizada, microPET/CT / Evaluation of ambient radiation levels in positron emission tomography/computed tomography in microPET/CT laboratoryDaniele Martins Sarmento 24 May 2016 (has links)
O sistema microPET/CT é um importante equipamento utilizado nas pesquisas de imagem diagnóstica em pequenos animais. O radiofármaco mais usado nesta tecnologia é o fluordeoxiglicose marcado com flúor-18. Este estudo tem como objetivo efetuar o controle radiológico no laboratório de pesquisa microPET/CT do Centro de Radiofarmácia do IPEN-CNEN/SP, de forma a satisfazer tanto as normas nacionais como as recomendações internacionais. O laboratório está classificado pela equipe de radioproteção da instalação como área supervisionada, nas quais embora não seja obrigatória a adoção de medidas específicas de proteção e segurança, devem ser submetidas reavaliações regulares das condições do ambiente de trabalho. Visando assegurar a proteção radiológica dos trabalhadores diretamente envolvidos no manuseio do equipamento, realizou-se o monitoramento do local de trabalho e a avaliação do controle de dose individual. Inicialmente foi feito o monitoramento pré-operacional, isto é, o levantamento radiométrico no laboratório. Além disso, mediu-se nível de radiação externa nas instalações do laboratório e suas adjacências, por meio da colocação de nove dosímetros termoluminescentes (TL) de CaSO4:Dy, em locais previamente selecionados. Os indivíduos ocupacionalmente expostos foram avaliados mensalmente por meio do uso de dosímetros TL posicionados no tórax e por medidas de corpo inteiro, tomadas a cada seis meses. O período do estudo foi de dois anos, com início em abril de 2014. Para o controle do microPET/CT realizou-se testes de desempenho de acordo com o protocolo padrão do equipamento e em conformidade com a norma desenvolvida pela força tarefa para estudos com PET em animais Animal PET Standard Task Force. O presente estudo permitiu demonstrar que os níveis de radiação das áreas (estimativas de dose ambiente e dose efetiva), assim como a blindagem do equipamento estão adequados de acordo com os limites da exposição ocupacional. Ressalta-se a importância de se seguir rigorosamente os princípios de radioproteção, já que se trata de pesquisas com fontes radioativas não seladas. / Micro PET/CT scanner is an essential tool generally used for small animal molecular imaging. Fluorine-18-labeled fluorodeoxyglucose is the most widely used radioisotope in this technique. The present study aimed to evaluate the radiation levels in a micro PET/CT research laboratory of the Radiopharmacy Center at IPEN-CNEN / SP, in order to accomplish both national standards and international recommendations. The radioprotection team has classified the laboratory as supervised area; even this laboratory does not require the adoption of specific measures for protection and safety, should be done regular re-evaluation of the conditions of occupational exposures. Workplace monitoring and individual control assessment were carried out to ensure the radiological protection of all workers directly involved in handling the scanner. Initially, there was conducted a radiometric survey, as well as measurements of the external radiation level in the workplace and its surroundings. To achieve this goal, there were placed nine thermoluminescent dosimeters of CaSO4:Dy in preselected locations. Monthly evaluations of the occupationally exposed individuals were carried out through the use of TL dosimeters, ported in the workers´ chest. Moreover, whole body measurements were performed every six months. The study period was about two-years which started in April 2014. All tests to evaluate micro PET/CT performance were based on the standard protocol of the equipment in accordance with the standard developed by the Animal PET Standard Task Force. Present study\'s results demonstrated that the ambient radiation levels (ambient and effective estimated radiation dose), as well as the effective shielding equipment are both adequate. This study emphasizes that it is essential to strictly follow the principles of radioprotection in workplace, whenever researches involve radioactive unsealed sources.
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