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In recent years, computer tomography (CT) has become an increasingly important tool in the clinical diagnosis, mainly because of the advent of fast scanning techniques and high spatial resolution of the vision hardware. In addition to the detailed information of morphology, functional CT also gives the physiologic information, such as perfusion. It can help doctors to make better decision. Our goal in this paper is to evaluate lung perfusion by comparing pre and post contrast-enhanced CT images. After the contrast agent is injected, it flows with blood stream and causes the temporal changes in CT values. Therefore, we can quantize perfusion values from the changes of CT values between pre and post contrast-enhanced CT images. Then guided by color -coded maps, a quantitative analysis for the assessment of lung perfusion can be performed. As a result, it is easier for observer to determinate the lung perfusion distribution. Moreover, we can use color - coded images to visualize pulmonary embolism and monitor therapeutic efficacy.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19173号 / 医博第4015号 / 新制||医||1010(附属図書館) / 32165 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 福田 和彦, 教授 小池 薫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19556号 / 医博第4063号 / 新制||医||1012(附属図書館) / 32592 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小池 薫, 教授 福田 和彦, 教授 三嶋 理晃 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-21T19:41:07Z No. of bitstreams: 1 Renata Kelly da Palma.pdf: 5650038 bytes, checksum: 27a64e62c897fb5ab5e43cf7a98e3250 (MD5) / Made available in DSpace on 2018-06-21T19:41:07Z (GMT). No. of bitstreams: 1 Renata Kelly da Palma.pdf: 5650038 bytes, checksum: 27a64e62c897fb5ab5e43cf7a98e3250 (MD5) Previous issue date: 2015-10-07 / Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. The decellularizing agent perfusion technique via the pulmonary artery (PA) has been shown very effective in the process however; vascular perfusion pressure and flow vary along the pulmonary decellularization process. These factors are not fully understood it being very important in the optimization process, ensuring the integrity of the scaffold. The objectives were to characterize the pressure / pulmonary vascular flow associated with variation in vascular resistance (VR), according to the control of the infusion (pressure or flow) at the time of the infusion of different decellularizing agents in PA and determine the VR's behavior in relation to different pressures of lung inflation (tracheal pressure) and perfusion (pulmonary artery). For the first study, were used 43 lungs of the healthy mice (C57/BL6) with 7–8 weeks old and in the second study, lungs of the 5 healthy rat (Sprague- Dawley) with 7-8 weeks old. In the first study, after excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization process being perfused through PA. For the second study, the decellularized lungs were subjected to variations in tracheal pressure (0 to 15 cmH2O) and vascular pressure (5 to 30 cmH2O). Pressure (PPA) and flow (V’PA) at the pulmonary artery were continuously measured. The VR (VR=PPA/V’PA) considerably varied throughout lung decellularization, particularly for pressure controlled perfusion, as compared with flow-controlled perfusion. This study shows that monitoring perfusion mechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity. Moreover, arterial lung pressure has more influence on behavior of vascular resistance in decellularized lungs than positive airway pressure, providing information that could be relevant for future cell repopulation by using the vascular resistance as a facilitator cell distribution throughout pulmonary circuit. / A geração artificial de órgãos é uma alternativa potencial na obtenção de órgãos viáveis para o transplante humano. Obter scaffolds perfeitos para serem recelularizados é um grande desafio e um passo fundamental na bioengenharia de pulmões. A técnica de perfusão de agentes descelularizantes através da artéria pulmonar (AP) tem se apresentado muito eficaz no processo entretanto, a pressão e o fluxo de perfusão vascular variam ao longo do processo de descelularização pulmonar. Estes fatores ainda não se encontram totalmente compreendidos, sendo muito importantes na otimização do processo, assegurando a integridade dos scaffolds. Os objetivos foram caracterizar a relação pressão/fluxo vascular pulmonar associado a variação de resistência vascular (RV), de acordo com o controle da perfusão (pressão ou fluxo) no momento da infusão de diferentes agentes descelularizantes na AP e determinar o comportamento da RV em relação a diferentes pressões de insuflação pulmonar (pressão traqueal) e de perfusão (artéria pulmonar). Para o primeiro estudo, foram utilizados 43 pulmões de camundongos machos saudáveis (C57/BL6) com idade de 7-8 semanas e no segundo estudo, pulmões de 5 ratos machos saudavéis (Sprague- Dawley) com idade de 7-8 semanas. No primeiro estudo, após excisão e canulação da traqueia e da artéria pulmonar, os pulmões foram insuflados a uma pressão de 10 cmH2O na via aérea e submetidos ao processo convencional de descelularização sendo perfundidos através da AP. Para o segundo estudo, os pulmões descelularizados foram submetidos a variações de pressão traqueal (0 à 15 cmH2O) e pressão vascular (5 à 30 cmH2O). A pressão na artéria pulmonar (PPA) e o fluxo da artéria pulmonar (V’PA) foram continuamente mensurados. A RV (Rv=PPA/V`PA.Rv) variou consideravelmente ao longo do processo de descelularização pulmonar, particularmente na perfusão por pressão controlada, quando comparado a perfusão controlada por fluxo. Concluimos que o monitoramento da mecânica de perfusão ao longo do processo de descelularização fornece informações relevantes na otimização do processo, assegurando um limite para pressão vascular, preservando a integridade do scaffold. Somado a estes achados um resultado relevante demonstrou que a pressão arterial pulmonar tem mais influência no comportamento da RV nos pulmões descelularizados do que pressão positiva nas vias aéreas, fornecendo informações importantes para futuro manejo no processo de recelularização utilizando a RV como um facilitador na distribuição celular através do arcabouço celular pulmonar.

A Tomografia de Impedância Elétrica (TIE) é um método de imagem que está sendo desenvolvido para uso em medicina, especialmente na terapia intensiva. Visando uma melhoria da resolução anatômica das imagens de TIE, foi desenvolvido um modelo fuzzy que leva em consideração a alta resolução temporal e as informações funcionais, contidas nos sinais de perfusão pulmonar e ventilação pulmonar. Foram elaborados três modelos fuzzy: modelagem fuzzy do mapa cardíaco, do mapa de ventilação pulmonar e do mapa de perfusão pulmonar. Um mapa comparativo de ventilação e perfusão foi gerado através de uma segmentação das imagens, segundo notas de corte sobre os valores dos pixels. As imagens de perfusão fuzzy foram comparadas com as imagens de perfusão obtidas pelo método de injeção de uma solução hipertônica, considerada como padrão-ouro das imagens de perfusão. O desempenho do modelo foi avaliado através da análise das imagens de TIE obtidas em experimentos animais com treze porcos. Os animais foram submetidos a diferentes condições fisiológicas através de lesão pulmonar, recrutamento pulmonar e intubação seletiva. O modelo global foi capaz de identificar a região cardíaca e pulmonar em todos os porcos, independentemente das condições fisiológicas a que foram submetidos. Os resultados foram bastante expressivos tanto em termos qualitativos (a imagem obtida pelo modelo foi bastante similar a da tomografia computadorizada) quanto em termos quantitativos (a área média da curva ROC foi de 0,84). Os resultados do estudo poderão servir de base para o desenvolvimento de ferramentas clínicas, baseadas em TIE, para diagnósticos de algumas patologias e situações críticas, tais como distúrbio entre ventilação e perfusão, pneumotórax e tromboembolismo pulmonar. / Electrical Impedance Tomography (EIT) is an image method that has been developed for use in medicine, specially in critical care medicine. Aiming at improving the anatomical resolution of EIT images a fuzzy model was developed based on EIT high temporal resolution and the functional information contained in the pulmonary perfusion and ventilation signals. Fuzzy models were elaborated for heart map modeling, ventilation and perfusion map modeling. Image segmentation was performed using a threshold method and a ventilation/perfusion map was generated. Fuzzy EIT perfusion map was compared with the hypertonic saline injection method, considered as the gold-standard for EIT perfusion image. The model performance was evaluated through analysis of EIT images obtained from animal experiment with thirteen pigs. The animals were submitted to different physiological conditions, such as ventilation induced lung injury, selective intubations and lung recruitment maneuver. The global model was able to identify both the cardiac and pulmonary regions in all animals. The results were expressive for both qualitative (the image obtained by the model was very similar to that of the CT-scan) and quantitative (the ROC curve area average was 0.84) analysis. These achievements could serve as the base to develop EIT diagnosis system for some critical diseases, such as ventilation to perfusion mismatch, pneumothorax and pulmonary thromboembolism.

<p>The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first group consists of the general degrading factors inherent to the physical interaction processes of radiation with matter, such as scatter and attenuation processes which are common to all three detectors The second group consists of specific factors inherent to the particular radiation detection properties of the used detector which have to be separately studied for each detector system. Therefore, the aim of this thesis was devoted to the development of computational methods to enable quantitative molecular imaging in PET, SPET and in vivo patient dosimetry with CMOS image sensors.</p><p>The first task was to develop a novel quantitative dual isotope method for simultaneous assessments of regional lung ventilation and perfusion using a SPET technique. This method included correction routines for photon scattering, non uniform attenuation at two different photon energies (140 and 392 keV) and organ outline. This quantitative method was validated both with phantom experiments and physiological studies on healthy subjects.</p><p>The second task was to develop and clinically apply a quantitative method for tumour to background activity uptake measurements using planar mammo-scintigraphy, with partial volume compensation.</p><p>The third stage was to produce several computational models to assess the spatial resolution limitations in PET from the positron range, the annihilation photon non-collineairy and the photon depth of interaction.</p><p>Finally, a quantitative image processing method for a CMOS image sensor for applications in ion beam therapy dosimetry was developed.</p><p>From the obtained phantom and physiological results it was concluded that the methodologies developed for the simultaneous measurement of the lung ventilation and perfusion and for the quantification of the tumour malignancy grade in breast carcinoma were both accurate. Further, the obtained models for the influence that the positron range in various human tissues, and the photon emission non-collinearity and depth of interaction have on PET image spatial resolution, could be used both to optimise future PET camera designs and spatial resolution recovery algorithms. Finally, it was shown that the proton fluence rate in a proton therapy beam could be monitored and visualised by using a simple and inexpensive CMOS image sensor.</p>

The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first group consists of the general degrading factors inherent to the physical interaction processes of radiation with matter, such as scatter and attenuation processes which are common to all three detectors The second group consists of specific factors inherent to the particular radiation detection properties of the used detector which have to be separately studied for each detector system. Therefore, the aim of this thesis was devoted to the development of computational methods to enable quantitative molecular imaging in PET, SPET and in vivo patient dosimetry with CMOS image sensors. The first task was to develop a novel quantitative dual isotope method for simultaneous assessments of regional lung ventilation and perfusion using a SPET technique. This method included correction routines for photon scattering, non uniform attenuation at two different photon energies (140 and 392 keV) and organ outline. This quantitative method was validated both with phantom experiments and physiological studies on healthy subjects. The second task was to develop and clinically apply a quantitative method for tumour to background activity uptake measurements using planar mammo-scintigraphy, with partial volume compensation. The third stage was to produce several computational models to assess the spatial resolution limitations in PET from the positron range, the annihilation photon non-collineairy and the photon depth of interaction. Finally, a quantitative image processing method for a CMOS image sensor for applications in ion beam therapy dosimetry was developed. From the obtained phantom and physiological results it was concluded that the methodologies developed for the simultaneous measurement of the lung ventilation and perfusion and for the quantification of the tumour malignancy grade in breast carcinoma were both accurate. Further, the obtained models for the influence that the positron range in various human tissues, and the photon emission non-collinearity and depth of interaction have on PET image spatial resolution, could be used both to optimise future PET camera designs and spatial resolution recovery algorithms. Finally, it was shown that the proton fluence rate in a proton therapy beam could be monitored and visualised by using a simple and inexpensive CMOS image sensor.

A Tomografia de Impedância Elétrica (TIE) é um método de imagem que está sendo desenvolvido para uso em medicina, especialmente na terapia intensiva. Visando uma melhoria da resolução anatômica das imagens de TIE, foi desenvolvido um modelo fuzzy que leva em consideração a alta resolução temporal e as informações funcionais, contidas nos sinais de perfusão pulmonar e ventilação pulmonar. Foram elaborados três modelos fuzzy: modelagem fuzzy do mapa cardíaco, do mapa de ventilação pulmonar e do mapa de perfusão pulmonar. Um mapa comparativo de ventilação e perfusão foi gerado através de uma segmentação das imagens, segundo notas de corte sobre os valores dos pixels. As imagens de perfusão fuzzy foram comparadas com as imagens de perfusão obtidas pelo método de injeção de uma solução hipertônica, considerada como padrão-ouro das imagens de perfusão. O desempenho do modelo foi avaliado através da análise das imagens de TIE obtidas em experimentos animais com treze porcos. Os animais foram submetidos a diferentes condições fisiológicas através de lesão pulmonar, recrutamento pulmonar e intubação seletiva. O modelo global foi capaz de identificar a região cardíaca e pulmonar em todos os porcos, independentemente das condições fisiológicas a que foram submetidos. Os resultados foram bastante expressivos tanto em termos qualitativos (a imagem obtida pelo modelo foi bastante similar a da tomografia computadorizada) quanto em termos quantitativos (a área média da curva ROC foi de 0,84). Os resultados do estudo poderão servir de base para o desenvolvimento de ferramentas clínicas, baseadas em TIE, para diagnósticos de algumas patologias e situações críticas, tais como distúrbio entre ventilação e perfusão, pneumotórax e tromboembolismo pulmonar. / Electrical Impedance Tomography (EIT) is an image method that has been developed for use in medicine, specially in critical care medicine. Aiming at improving the anatomical resolution of EIT images a fuzzy model was developed based on EIT high temporal resolution and the functional information contained in the pulmonary perfusion and ventilation signals. Fuzzy models were elaborated for heart map modeling, ventilation and perfusion map modeling. Image segmentation was performed using a threshold method and a ventilation/perfusion map was generated. Fuzzy EIT perfusion map was compared with the hypertonic saline injection method, considered as the gold-standard for EIT perfusion image. The model performance was evaluated through analysis of EIT images obtained from animal experiment with thirteen pigs. The animals were submitted to different physiological conditions, such as ventilation induced lung injury, selective intubations and lung recruitment maneuver. The global model was able to identify both the cardiac and pulmonary regions in all animals. The results were expressive for both qualitative (the image obtained by the model was very similar to that of the CT-scan) and quantitative (the ROC curve area average was 0.84) analysis. These achievements could serve as the base to develop EIT diagnosis system for some critical diseases, such as ventilation to perfusion mismatch, pneumothorax and pulmonary thromboembolism.