Parkinson's disease (PD) is a neurodegenerative disease that causes degeneration of nigral dopaminergic terminals in the caudate and the putamen regions of the striatum in the basal ganglia. According to current practice, when an unequivocal clinical diagnosis of PD cannot be made, a single-photon emission computed tomography scan using the DaTscan radionuclide (SPECT DaT scan) is ordered. However, the assessment of SPECT DaT scans in the diagnosis of PD depends on the subjective judgment of a radiologist, which can pose problems for the accuracy of the diagnosis. Furthermore, as research studies generally do not quantify SPECT DaT scans when using them, their conclusions are not based on standardized data. The aim of this paper is to propose a method of quantification for SPECT DaT scans, to be employed in diagnostic and research environments. The methodology proposed in this thesis project will eventually be used for a much larger multimodal imaging project investigating the connectivity changes in the brain related to cognitive and affective symptoms in PD patients. Each of the 4 subjects in this project underwent a SPECT DaT scan and an MPRAGE scan (Magnetization Prepared Rapid Gradient Echo), an anatomical MRI (magnetic resonance image). The SPECT DaT scans and the MPRAGEs were coregistered, and then a voxel-based quantification of the caudate and the putamen in the left and the right hemispheres was performed in every subject. First, the percentages of voxels with intensities exceeding various pericalcarine baselines were calculated. A pericalcarine baseline was used because the pericalcarine gyrus in the occipital lobe has been shown to have little to no dopaminergic activity, particularly on SPECT DaT scans. Next, asymmetry indices (AI) were calculated for two of the thresholds whereby the ratio of the percentage of voxels in the right to the left hemispheric region was taken. Wilcoxon Signed-Rank tests and bootstrapping analyses were performed on both the caudate and the putamen in all four subjects to determine the significance of any detected asymmetry. The quantification of the data and the AI values revealed asymmetries in the voxel intensities between the left and right hemispheres. This asymmetry was consistent with each subject's side of physical symptom onset. According to the bootstrapping analyses, this asymmetry was significant in five of the eight comparisons. In summary, this methodology has potential to bring greater objectivity to the use of SPECT DaT scans in the diagnosis of PD and in research through its anatomically accurate, voxel-based quantification.

A tomografia computadorizada por emissão de fóton único (SPECT) é uma das modalidades de diagnóstico na Medicina Nuclear em que se detecta a radiação emitida por um radiofármaco previamente administrado ao paciente. Visto que osfótons emitidos sofrem interações com o corpo do paciente, fazem-se necessárias as correções de atenuação e de espalhamento a fim de melhor representar a distribuição do radiofármaco, e assimresultar em imagens mais precisas. O objetivo deste trabalho é avaliar os parâmetros anotados como padrão para reconstruções de imagens tomográficas e as correções de atenuação e de espalhamento em imagens SPECT do Hospital de Clínicas da Faculdade de Medicina da Universidade de São Paulo, por meio de análises qualitativas e quantitativas das imagens reconstruída a partir das aquisições tomográficas. Sob um protocolo de SPECT-CT cerebral modificado para duas janelas de aquisição, foram adquiridas imagens SPECT e SPECT-CT (BrightView XCT, Philips) utilizando fantomaJaszczak e reconstruídas pelos métodos FBP, MLEM e OSEM. Os resultados mostram que o método FBP apresenta imagens de baixa precisão devido à baixa SNR. A avaliação sugere o uso dos métodos iterativos MLEM e OSEM com correção de atenuação como método padrão de reconstrução de imagens de perfusão cerebral. De acordo com a avaliação de imagens do fantomaJaszczak e análise do contraste entre esfera fria ebackground,propõe-se análise observacional e avaliação das imagens clínicas reconstruídas pelo método OSEM com os parâmetros 3 iterações, 16 subsets, filtro Butterworth com frequência de corte 0,34 e potencia 1, como novos parâmetros padrão de reconstrução de imagens. / Single Photon Emission Computed Tomography (SPECT) is one of the diagnostic modalities in nuclear medicine, it detects the radiation emitted by a radioisotope previously administered to the patient. Since the photons undergo interactions with the patient\'s body,attenuationand scatteringcorrections are necessary in order to best represent the distribution of the radiopharmaceutical, and thus result in more accurate images. The aim of this study is to evaluate the standard parameters for tomographic imagesreconstruction, and attenuation and scatter corrections ofSPECT images, from Hospital das Clínicas da Faculdade de Medicina de RibeirãoPreto, Universidade de São Paulo, through qualitativeand quantitative analysis of the reconstructed image obtained from SPECT aquisitions. Though a modified to two windows of acquisition protocol for cerebral SPECT-CT, we acquired SPECT and SPECT-CT images (BrightView XCT, Philips) using phantom Jaszczak and the ones were reconstructed by FBP, MLEM and OSEM methods. The results show that the FBP method has poor image precision due to low SNR. The review suggests the use of iterative methods MLEM and OSEM with attenuation correction as a standard method of image reconstruction of cerebral perfusion. According to the images the phantom Jaszczak and contrast analysis between cold sphere and background, we propose observational analysis and evaluations of clinical images reconstructed by OSEM method with parameters 3 iterations, 16 subsets, Butterworth filter with cutoff frequency 0.34 and order 1, as newstandard parameters for image reconstruction parameters.

Made available in DSpace on 2014-06-12T23:13:34Z (GMT). No. of bitstreams: 2 arquivo2649_1.pdf: 1468078 bytes, checksum: ce4d110c6332d8130a6b30314d29a3d4 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / O objetivo deste trabalho foi avaliar as incertezas e limitações de ambos os métodos de quantificação de imagens, planar e SPECT, e propor correções para melhorar a exatidão na quantificação de atividade baseada no uso de imagens com o propósito de realizar cálculos de dosimetria interna também mais exatos. Neste trabalho, três fantomas que representaram geometrias de diferentes graus de complexidade (esferas, região do miocárdio e região do torso), foram usados para estudar as incertezas e as limitações de cada método com respeito ao tamanho, ao volume, à atividade contida no objeto, à presença de background, entre outras variáveis. O desempenho da quantificação foi avaliado para as imagens realizadas com três importantes radionuclídeos usados na rotina clinica : o 99mTc, o 111In e o 131I. Os resultados mostraram que, apesar do efeito do volume parcial constituir um importante fator para a subestimação da atividade quantificada com as imagens SPECT, a quantificação de atividade realizada com este método apresentou as menores variações dos valores conhecidos de atividade através dos diferentes níveis de background e das diferentes concentrações usadas quando comparados aos valores apresentados pelo método planar. Quando todas as correções são aplicadas à imagem SPECT, a subtração de background passa a ser o fator que causa a maior incerteza na quantificação da atividade e o erro associado a este fator pode ser reduzido realizando-se uma caracterização da sua influência na quantificação da atividade em função do tamanho do objeto. Os resultados sugerem que o uso de imagens SPECT deve ser preferido ao de imagem planar para a quantificação de atividade quando estudos dosimétricos envolvendo pequenos objetos (<11 ml) são realizados, pois fornece resultados mais confiáveis

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18866号 / 医博第3977号 / 新制||医||1008(附属図書館) / 31817 / 京都大学大学院医学研究科医学専攻 / (主査)教授 戸井 雅和, 教授 平岡 眞寛, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Parkinson’s disease (PD) is a common neurodegenerative disorder associated with dysfunction of the basal ganglia, which contributes to a range of motor, cognitive, and affective symptoms. Striatal dopaminergic deficits are one of the core pathological mechanisms thought to contribute to the extra-motor (i.e., cognitive and affective) symptoms in early PD. The present study investigated the relationship between striatal dopaminergic integrity and cognition in 21 patients with PD and 21 age and education matched controls. Each individual underwent dopamine transporter (DaT) imaging with single photon emission computed tomography (SPECT) (i.e., DaTscan) and standardized neuropsychological testing. Strong positive associations were found between DaT availability in the striatum and verbal memory (r = .52-.61) and problem solving/set-shifting (r = .55) in patients with PD. Additional moderate to strong positive associations (r = .49-.56) between DaT concentrations and visuospatial functions in patients with PD were found. However, similar significant associations between DaT and cognition were observed in age and education matched controls. Clinically, it is important for health care professionals to consider the role of both striatal and extra-striatal mechanisms as they relate to cognition in PD. Future studies examining the full range of pathological mechanisms that contribute to cognitive dysfunction in PD over time are warranted in order to inform more effective and targeted interventions.

Programa de Formación de Especialista en Medicina Nuclear / La actividad cerebral presente en las imágenes de SPECT con radiofármacos tecneciados como el etilen cisteína dímero (ECD) u oximas (HMPAO) representa el flujo al momento de inyección y de algunos minutos posteriores. La interpretación visual requiere entrenamiento, especialmente al comparar la evolución en el mismo paciente; el uso de softwares puede facilitar la evaluación individual y permite el análisis grupal y comparativo. Existen programas complejos que requieren modificar la morfología cerebral siguiendo un modelo predefinido estandarizado con plantillas normalizadas. / Fondecyt Regular 1160885

Emphysema is a condition of the lung characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by a destruction of their walls. The primary pathogenesis of emphysema is poorly understood. One of the major issues of COPD is that no diagnostic tests are sensitive enough to detect early disease. Standard pulmonary function tests (PFTs) do not explain the underlying pathophysiology of airflow limitation, nor do they provide information on how COPD may be affecting pulmonary blood flow. Functional imaging, specifically ventilation and perfusion (V/Q) Single Photon Emission Computed Tomography (SPECT), is a sensitive tool that can provide information on pulmonary function in different lung regions. When V/Q images are co-registered to CT, regional analysis can be coupled to structural information. The objective of this study was to examine how emphysematous change identified and localized by CT density based thresholds affects lung function as measured by V/Q SPECT in a mouse model of the disease. A dose response study was conducted where Female BALB/c mice were exposed intranasally to 0.0, 0.5, 2.5 and 5.0 units (U) of porcine pancreatic elastase (PPE). V/Q SPECT/CT scanning was performed 45 days post exposure, followed by measurement of lung compliance using the Flexivent® rodent ventilator 46 days post exposure. Whole lung slice analysis software was used to quantify airspace enlargement and alveolar capillary density from histological sections of the lung. CT pulmonary angiography (CTPA) was also performed on controls and mice exposed to 5 U PPE to examine vascular density. In this mouse model of emphysema, V/Q SPECT was useful in quantitatively examining how ventilation and perfusion is affected in mild and severe emphysema while providing evidence of low log(V/Q) ratio in otherwise normal lung densities. This could be caused by airflow obstruction as a result of widespread narrowing or loss of small conducting airways. Low log(V/Q) ratio is caused by mild emphysema indicating airflow obstruction or dysfunctional hypoxic vasoconstriction in underventilated regions of the lung. The majority of severely emphysematous regions of the lung have matched but equally reduced log(V/Q), although low log(V/Q) is also present. Pulmonary hypertension in response to chronic hypoxia may explain our finding of reduced perfusion activity and vascular density in emphysematous lung, but further research is required to investigate the presence of this pathology. V/Q SPECT was also shown to be superior in the detection of emphysema compared to CT and Flexivent measured lung compliance providing evidence towards shifting the current assessment and monitoring paradigms. Due to the widespread availability of this imaging technique, it could be used to screen asymptomatic smokers for early disease and identify and locate pathology so therapies targeting the appropriate disease pathway can be prescribed. This will inevitably improve patient care. / Thesis / Master of Science (MSc)

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24519号 / 医博第4961号 / 新制||医||1065(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 辻川 明孝, 教授 大鶴 繁 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24200号 / 医博第4894号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 中本 裕士, 教授 江木 盛時 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Despite recent advances, radiopharmaceuticals to detect and characterize bacterial infections have a number of limitations. Many of the clinically approved radiopharmaceutical agents are not specific to bacterial infections and accumulate at lesions of inflammation. Hence, new approaches are necessary to detect bacteria with high specificity and selectivity. A library of desferrioxamine B (DFO) derivatives were prepared to create radiolabeled siderophores to create a bacteria-specific imaging probe by exploiting the mechanism bacteria use to scavenge iron, which plays a key role in bacterial growth and biofilm formation Compounds were synthesized using two convenient carbamate forming strategies in 30% to 92% yield. The cold and radioactive gallium (67Ga) complexes were prepared and characterized and their uptake by S. aureus bacteria were assessed in vitro and in vivo. In vivo studies revealed that 67GaDFOethoxycarbamate had uptake comparable to GaDFO that was blockable, showing the compound was actively taken up via the siderophore pathway. In vivo studies in a mouse model resulted in a good infected to non-infected thigh ratio (11:1) and non-specific uptake by the GI tract. Bioorthogonal chemistry was also explored as an approach for imaging infection using trans-cyclooctene (TCO) functionalized vancomycin and a tetrazine functionalized 67GaDFO (67GaDFO-Tz) complex.2,3 In vitro results revealed that allowing vancomycin-TCO to bind S. aureus prior to the addition of 67GaDFO-Tz (pretargeting) showed higher (63%) uptake than with a conjugate formed prior to incubation with the bacteria (direct targeting, 28%). For the bioorthogonal approach, the distribution of the 67GaDFO-Tz was assessed in a S. aureus infection murine model, which showed significant uptake of 67GaDFO-Tz in the GI tract 1 h post intravenous injection. However, uptake in the infected joint was evident at 71 h post infection. The data suggests targeting bacteria using TCO-labeled antibiotics and radiolabeled tetrazines is a feasible strategy, but that further optimization of the vancomycin injection dose and injection time are necessary. / Thesis / Master of Science (MSc)