Orientador: Diana Rodrigues de Pina / Resumo: A tomografia computadorizada (TC) é amplamente utilizada no diagnóstico e estadiamento de patologias da região de abdômen-pelve devido a sua alta sensibilidade e especificidade. A possibilidade de adquirir maior número de imagens em menor tempo e a maior disponibilidade de equipamentos levaram a um aumento significativo dos exames de TC e consequente aumento das doses efetivas globais fornecidas por esta modalidade. Desta forma, foram desenvolvidas ferramentas que buscam reduzir as doses de radiação dos exames sem perda da qualidade da imagem. Uma destas ferramentas é a modulação automática da corrente do tubo (automatic tube current modulation – ATCM), que permite a obtenção de exames que concordam com o princípio ALARA (as low as reasonably achievable). O objetivo deste estudo foi avaliar a qualidade da imagem e as doses de radiação de diferentes protocolos de TC de abdômen-pelve com a ferramenta ATCM. Foram avaliados cinco protocolos de TC de abdômen-pelve com a ferramenta ATCM em dois tomógrafos distintos, um 16-canais e um 64 canais. Foi utilizado um fantoma antropomórfico para avaliações dosimétricas e um fantoma analítico para avaliações objetivas de qualidade da imagem. Para a análise subjetiva da qualidade da imagem, foram utilizados 15 exames retrospectivos de pacientes submetidos a TC de abdômen-pelve. Estes exames foram avaliados por um radiologista com experiência na área de tomografia de abdômen. As três análises forneceram informações que possibilitaram a escol... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13270号 / 論医博第2184号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科内科系専攻 / (主査)教授 溝脇 尚志, 教授 平井 豊博, 教授 伊達 洋至 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduction Neutropenia is a life-threatening and dose-limiting toxicity of palliative lung cancer chemotherapy. Whilst some neutropenias are inevitable, evidence suggests that patients with a previous neutropenic event are 50% more likely to have a further neutropenic event. The aim of this research is to evaluate the variables associated with the risk of secondary neutropenic events and the role of chemotherapy dose reductions. Methods A retrospective analysis was carried out on 361 biochemical neutropenic events in palliative lung cancer patients across 5 sites in South Yorkshire and Bassetlaw. Predictors for a secondary neutropenic event were investigated in univariate and multivariate logistic regression analysis. The predictive model was validated through discrimination statistics, described by Receiver Operating Characteristic Area Under Curve (ROC-AUC). Results The incident rate for secondary neutropenic events was 32.7%. Patients with a successful intervention received a higher mean Relative Dose Intensity (RDI) of 75.65% compared to 65.05%, across the 2 chemotherapy cycles. The univariate analysis found that the biochemical type of neutropenia (depth and length of suppression) (p=0.003), dose reduction of drug 1 (p=0.042), average dose reduction (p=0.019), and cumulative dose reduction (p=0.018) were significant at reducing the risk of secondary neutropenia. Granulocyte-Colony Stimulating Factor did not offer a protective effect. The final logistic regression model evaluated 357 events and included all variables due to significant interrelationship. The model had a ROC-AUC of 0.76 (0.71-0.81) (p= 0.0021), explaining 27% of the variance. Conclusion Appropriate dose reductions play a vital role in preventing secondary neutropenic events and delivering optimal RDIs. The results of this study can aid in identifying high-risk patients.

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Yes / Digital image processing used in modern cardiac interventional x-ray systems may have the potential to enhance image quality such that it allows for lower radiation doses. The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. Incremental amounts of image noise were added to five PCI patient angiograms, simulating the angiogram having been acquired at corresponding lower dose levels (by 10-89% dose reduction). Sixteen observers with relevant and experience scored the image quality of these angiograms in three states - with no image processing and with two different modern image processing algorithms applied; these algorithms are used on state-of-the-art and previous generation cardiac interventional x-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction allowed for by the processing algorithms, for equivalent image quality scores. The dose reductions [with 95% confidence interval] from the state-of-the-art and previous generation image processing relative to no processing were 24.9% [18.8- 31.0%] and 15.6% [9.4-21.9%] respectively. The dose reduction enabled by the state-of-the-art image processing relative to previous generation processing was 10.3% [4.4-16.2%]. This demonstrates that statistically significant dose reduction can be facilitated with no loss in perceived image quality using modern image enhancement; the most recent processing algorithm was more effective in preserving image quality at lower doses. / The study was funded by Philips Healthcare (the Netherlands).

A recente inserção e forte avanço da mamografia digital no Brasil como ferramenta de rastreamento do câncer mamário e as evidências de outras condições de otimização, quando comparadas à mamografia convencional (tela filme), requerem que novos parâmetros de qualidade sejam incluídos e estudados, bem como que as condições de otimização sejam revistas. O objetivo deste trabalho foi determinar a técnica radiográfica otimizada para dois sistemas de detecção (CR e DR) em uso em três unidades de mamografia: Mammomat 3000 Nova (Siemens), Senographe DMR (GE) e Senographe 2000D (GE). A otimização foi conduzida para uma variedade de combinações de fatores técnicos e configurações de simuladores de mama, tais como valores de kilovoltagem (26 a 32 kV), combinações anodo/filtro (Mo/Mo, Mo/Rh e Rh/Rh), material simulador de mama de várias espessuras (2 a 8 cm) e lesões simuladas como massas e calcificações, usando uma figura de mérito (FOM) como parâmetro. Verificou-se que o uso da combinação anodo/filtro que gera os espectros mais energéticos em cada equipamento proporcionou os maiores valores de FOM para todas as espessuras de simulador de mama e voltagens, devido a redução da dose. As combinações anodo/filtro que deram esses resultados foram Mo/Rh para o equipamento da marca Siemens e Rh/Rh para ambos os equipamentos da marca GE, correspondentes aos espectros mais energéticos de cada unidade. Foi observada ainda uma tendência de aumento do kV que maximiza FOM com o aumento da espessura. / The recent introduction and intense advance of digital mammography in Brazil as a tool in breast cancer screening and the evidences of new optimization conditions when compared to conventional mammography (screen-film) require adding and studying novel quality parameters, as well as revisiting optimization conditions. The objective of this work was to determine optimized radiographic technique for two detection systems (CR and DR) in use in three mammography units: Mammomat 3000 Nova (Siemens), Senographe DMR (GE) and Senographe 2000D (GE). Optimization was conducted for various combinations of technique factors and breast phantom configurations, such as kilovoltage settings (26 to 32 kV), target/filter combinations (Mo/Mo, Mo/Rh and Rh/Rh), breast equivalent material in various thicknesses (2 to 8 cm) and simulated mass and calcification lesions, using a figure of merit (FOM) as a parameter. When using anode/filter combination which generates higher energy spectra in each equipment, it was verified that higher FOM values were achieved for all voltages and phantom thicknesses, due to dose reduction. Anode/filter combinations which led to those results were Mo/Rh for Siemens equipment and Rh/Rh for both GE equipments, corresponding to the higher energy spectra in each unity. It was also observed an increasing tendency of kV which maximizes FOM with the increase of thickness.

A recente inserção e forte avanço da mamografia digital no Brasil como ferramenta de rastreamento do câncer mamário e as evidências de outras condições de otimização, quando comparadas à mamografia convencional (tela filme), requerem que novos parâmetros de qualidade sejam incluídos e estudados, bem como que as condições de otimização sejam revistas. O objetivo deste trabalho foi determinar a técnica radiográfica otimizada para dois sistemas de detecção (CR e DR) em uso em três unidades de mamografia: Mammomat 3000 Nova (Siemens), Senographe DMR (GE) e Senographe 2000D (GE). A otimização foi conduzida para uma variedade de combinações de fatores técnicos e configurações de simuladores de mama, tais como valores de kilovoltagem (26 a 32 kV), combinações anodo/filtro (Mo/Mo, Mo/Rh e Rh/Rh), material simulador de mama de várias espessuras (2 a 8 cm) e lesões simuladas como massas e calcificações, usando uma figura de mérito (FOM) como parâmetro. Verificou-se que o uso da combinação anodo/filtro que gera os espectros mais energéticos em cada equipamento proporcionou os maiores valores de FOM para todas as espessuras de simulador de mama e voltagens, devido a redução da dose. As combinações anodo/filtro que deram esses resultados foram Mo/Rh para o equipamento da marca Siemens e Rh/Rh para ambos os equipamentos da marca GE, correspondentes aos espectros mais energéticos de cada unidade. Foi observada ainda uma tendência de aumento do kV que maximiza FOM com o aumento da espessura. / The recent introduction and intense advance of digital mammography in Brazil as a tool in breast cancer screening and the evidences of new optimization conditions when compared to conventional mammography (screen-film) require adding and studying novel quality parameters, as well as revisiting optimization conditions. The objective of this work was to determine optimized radiographic technique for two detection systems (CR and DR) in use in three mammography units: Mammomat 3000 Nova (Siemens), Senographe DMR (GE) and Senographe 2000D (GE). Optimization was conducted for various combinations of technique factors and breast phantom configurations, such as kilovoltage settings (26 to 32 kV), target/filter combinations (Mo/Mo, Mo/Rh and Rh/Rh), breast equivalent material in various thicknesses (2 to 8 cm) and simulated mass and calcification lesions, using a figure of merit (FOM) as a parameter. When using anode/filter combination which generates higher energy spectra in each equipment, it was verified that higher FOM values were achieved for all voltages and phantom thicknesses, due to dose reduction. Anode/filter combinations which led to those results were Mo/Rh for Siemens equipment and Rh/Rh for both GE equipments, corresponding to the higher energy spectra in each unity. It was also observed an increasing tendency of kV which maximizes FOM with the increase of thickness.

Automatic exposure control (AEC) is effective at reducing potentially harmful radiation doses without sacrificing image quality for many types of computed tomography (CT) scans. However, there is a need for more information regarding the use of AEC for CT head scans. This study was conducted at Johnson County Community Hospital in Mountain City, TN. Preexisting adult CT head scans (n)60 were randomly selected to form 2 stratified samples, (n)30 each. One sample used a standard protocol, and the other used a protocol with a mA-modulated AEC system, Siemens CARE Dose 4D. Causal-comparative analyses were conducted, and it was determined that AEC was effective at maintaining subjective image quality while reducing radiation doses an average of 38% for adult CT head scans. It was concluded that using AEC was an effective tool to optimize radiation doses for adult CT head scans in one particular setting, but more research on this topic is needed.

OBJECTIF : L’objectif de cette étude a été de valider le potentiel des méthodes de reconstruction itérative nouvellement développées en imageries CT à faisceau conique, afin de réduire la dose d’exposition dans le cadre des bilans de localisation des canines incluses. MÉTHODOLOGIE : Quarante examens par imagerie volumétrique à faisceau conique de canines incluses ont été reconstruits à pleine dose (D), demi-dose (D2) et quart de dose (D4). Ces examens ont été analysés par un radiologiste maxillo-facial et par un résident en orthodontie. La cohérence entre les évaluations des critères radiologiques retenus a été évaluée avec les tests de Kappa Cohen. RÉSULTATS : Les résultats de cette étude ont montré de fortes valeurs de Kappa concernant l'évaluation inter-examinateur de la position de la canine impactée avec des scores compris entre 0.606 – 0.839. Les valeurs de Kappa déterminées pour la résorption, l'ankylose et les lésions associées étaient beaucoup plus faibles avec des scores compris entre 0.000 et 0.529. CONCLUSION : Cette étude a permis de montrer que la localisation des canines incluses pourrait potentiellement être possible à faible dose (1/4 dose), comparativement à un dosage conventionnel. Toutefois, le diagnostic de la résorption, de l'ankylose ou encore de certaines lésions associées nécessitent de la haute résolution et donc des acquisitions à pleine dose. / AIM : The aim of this study was to validate the potential of newly developed iterative reconstruction methods in cone beam CT imaging to reduce the exposure dose for localization assessments of impacted canines. METHODS : Forty Cone beam CT examinations of impacted canines were reconstructed at full dose (D), half dose (D2) and quarter dose (D4). These examinations were analyzed by a maxillofacial radiologist and by an orthodontic resident. Consistency between the assessments of the selected radiological criteria was evaluated with Kappa Cohen tests. RESULTS : The results of this study showed high Kappa values regarding the inter-examiner assessment of the impacted canine position with scores ranging from 0.606 - 0.839. The Kappa values determined for resorption, ankylosis and associated lesions were lower with scores between 0.000 and 0.529. CONCLUSION : This study showed that the localization of impacted canines could potentially be possible at low dose (1/4 dose), compared to a conventional assay. However, the diagnosis of resorption, ankylosis or certain associated lesions requires high resolution and therefore full dose acquisitions.

Recent clinical findings in chronic myeloid leukemia (CML) patients suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitor (TKI) treatment substantially depends on an individual’s leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will remain in treatment-free remission (TFR). Here, we used an ordinary differential equation (ODE) model for CML, which explicitly includes an anti-leukemic immunological effect and applied it to 21 CML patients for whom BCR-ABL1/ABL1 time courses had been quantified before and after TKI cessation. Immunological control was conceptually necessary to explain TFR as observed in about half of the patients. Fitting the model simulations to data, we identified patient-specific parameters and classified patients into three different groups according to their predicted immune system configuration ('immunological landscapes”). While one class of patients required complete CML eradication to achieve TFR, other patients were able to control residual leukemia levels after treatment cessation. Among them were a third class of patients, that maintained TFR only if an optimal balance between leukemia abundance and immunological activation was achieved before treatment cessation. Model simulations further suggested that changes in the BCR-ABL1 dynamics resulting from TKI dose reduction convey information about the patient-specific immune system and allow prediction of outcome after treatment cessation. This inference of individual immunological configurations based on treatment alterations can also be applied to other cancer types in which the endogenous immune system supports maintenance therapy, long-term disease control or even cure.