<p>The overall goal of this dissertation is to optimize and evaluate the performance of the single photon emission computed tomography (SPECT) subsystem of a dedicated three-dimensional (3D) dual-modality breast imaging system for enhanced semi-automated, quantitative clinical imaging. This novel hybrid imaging system combines functional or molecular information obtained with a SPECT subsystem with high-resolution anatomical imaging obtained with a low dose x-ray Computed Tomography (CT) subsystem. In this new breast imaging paradigm, coined "mammotomography," the subject is imaged lying prone while the individual subsystems sweep 3-dimensionally about her uncompressed, pendant breast, providing patient comfort compared to traditional compression-based imaging modalities along with high fidelity and information rich images for the clinician. </p><p> System evaluation includes a direct comparison between dedicated 3D SPECT and dedicated 2D scintimammography imaging using the same high performance, semi-conductor gamma camera. Due to the greater positioning flexibility of the SPECT system gantry, under a wide range of measurement conditions, statistically significantly (p<0.05) more lesions and smaller lesion sizes were detected with dedicated breast SPECT than with compressed breast scintimammography. The importance of good energy resolution for uncompressed SPECT breast imaging was also investigated. Results clearly illustrate both visual and quantitative differences between the various energy windows, with energy windows slightly wider than the system resolution having the best image contrast and quality.</p><p> An observer-based contrast-detail study was performed in an effort to evaluate the limits of object detectability under various imaging conditions. The smallest object detail was observed using a 45-degree tilted trajectory acquisition. The complex 3D projected sine wave acquisition, however, had the most consistent combined intra and inter-observer results, making it potentially the best imaging approach for consistent clinical imaging.</p><p> Automatic ROR contouring is implemented using a dual-layer light curtain design, ensuring that an arbitrarily shaped breast is within ~1 cm of the camera face, but no closer than 0.5 cm at every projection angle of a scan. Autocontouring enables simplified routine scanning using complex 3D trajectories, and yields improved image quality. Absolute quantification capabilities are also integrated into the SPECT system, allowing the calculation of in vivo total lesion activity. Initial feasibility studies in controlled low noise experiments show promising results with total activity agreement within 10% of the dose calibrator values.</p><p> The SPECT system is integrated with a CT scanner for added diagnostic power. Initial human subject studies demonstrate the clinical potential of the hybrid SPECT-CT breast imaging system. The reconstructed SPECT-CT images illustrate the power of fusing functional SPECT information to localize lesions not easily seen in the anatomical CT images. Enhanced quantitative 3D SPECT-CT breast imaging, now with the ability to dynamically contour any sized breast, has high potential to improve detection, diagnosis, and characterization of breast cancer in upcoming larger-scale clinical testing.</p> / Dissertation

<p>This work investigates phantom and subject positioning as well as collecting data with a variety of angular sampling and acquisition trajectories. The overall goal of this work has been to utilize the dedicated, breast SPECT-CT system to acquire the best possible images. A large portion of this work has been to apply corrections to the system for quantitative imaging. The system has been shown to provide high quality images with minimal out-of-field signal contribution. Additionally, the quantification procedure has been shown to be within 10% of the known activity concentration present at the time of imaging for both VAOR and PROJSINE trajectories.</p> / Dissertation

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...

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

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

Os distúrbios da articulação temporomandibulares (DTM) apresentam um impacto negativo na qualidade de vida de seus portadores. A diversidade de sinais e sintomas apresentados pelos pacientes, como dores musculares, cefaléias (difusa ou localizada), dores na região da articulação temporomandibular (ATM), limitações ou excessos de abertura da boca e ruídos articulares dificultam o diagnóstico clínico. Para isso, há necessidade de uma investigação clínica minuciosa e de exames complementares. Os exames radiográficos convencionais e tomografias mostram a anatomia da região sem demonstrar alterações funcionais locais. A técnica de imagens tomográficas em Medicina Nuclear, SPECT (Single Photon Emission Computed Tomography) com 99m Tc-MDP (radiofármaco composto de Tecnécio 99 metaestável e Metileno Difosfonato), demonstra o metabolismo da região, e associada à fusão de imagens co-registradas com a tomografia computadorizada (CT), permite a localização anatômica das alterações ósseas funcionais existentes nas estruturas envolvidas. É um exame com baixa dose de radiação que possibilita a observação conjunta estrutural anatômica e metabólica. Neste trabalho avaliamos, retrospectivamente, exames SPECT/CT de 33 pacientes realizados no Setor de Medicina Nuclear do Departamento de Imagem do Centro de Tratamento e Pesquisa - Hospital do Câncer A. C. Camargo, que apresentavam sinais e sintomas de provável DTM. Os resultados dos exames foram relacionados aos dados existentes nos prontuários dos pacientes, como sexo, idade, anamnese e exame clínico. Por meio de análise descritiva, utilizando as freqüências e porcentagens das variáveis de interesse, pudemos avaliar a confiabilidade do exame. Concluímos que o SPECT/CT, quando aplicado em pacientes portadores de sinais e sintomas de DTM, apresentou alta sensibilidade (100%), especificidade (90,9%) e acurácia (96,9%), demonstrando que é um método de diagnóstico por imagem de relevância, útil e de grande valia, podendo ser um dos métodos de escolha indicados para diagnóstico de DTM. / Temporomandibular joint dysfunction play a negative role on patient life quality standard. A diversity of signs and symptoms such us muscular pain, headaches (focal or diffuse), temporomandibular joint localized pain, limitation or excessive mandibular opening and joint noise may lead to difficulties of correct diagnosis. Clinical investigation and complementary exams are necessary in these cases. Conventional radiographic and tomographic exams exactilly indicates local anatomy but do not demonstrate functional metabolic changes. Tomographic images on Nuclear Medicine, SPECT (Single Photon Emission Computed Tomography) with 99m Tc-MDP (methylene diphosphonate) a radiopharmaceutical labeled with Technetium 99m demonstrate regional metabolism changes. The association to co-registered computed tomography (CT) and image fusion allows the anatomic placement of bone functional alteration into the involved structures. SPECT/CT is a low dose radiation procedure that makes simultaneous anatomic and metabolic observation possible. This assignment was retrospectively analyzed, SPECT/CT of 33 patients from the Nuclear Medicine Sector of the Image Department of the Research and Treatment Center of the Cancer Hospital A. C. Camargo, that presented sings and symptoms of probable temporomandibular joint dysfunction. The results of the exams were related with the patient data that were on their file like sex, age, anamnesis and clinical exam. The assessment of the reliability of the exam was evaluated by descriptive analysis using frequencies and percentages of the interest variables. We conclude that SPEC/CT showed high sensitivity (100%), specificity (90,9%) and accuracy (96,9%); demonstrating that it is an important and useful diagnostic method, that may be an exam of choice to the diagnostic features of temporomandibular joint disfunction.

Os distúrbios da articulação temporomandibulares (DTM) apresentam um impacto negativo na qualidade de vida de seus portadores. A diversidade de sinais e sintomas apresentados pelos pacientes, como dores musculares, cefaléias (difusa ou localizada), dores na região da articulação temporomandibular (ATM), limitações ou excessos de abertura da boca e ruídos articulares dificultam o diagnóstico clínico. Para isso, há necessidade de uma investigação clínica minuciosa e de exames complementares. Os exames radiográficos convencionais e tomografias mostram a anatomia da região sem demonstrar alterações funcionais locais. A técnica de imagens tomográficas em Medicina Nuclear, SPECT (Single Photon Emission Computed Tomography) com 99m Tc-MDP (radiofármaco composto de Tecnécio 99 metaestável e Metileno Difosfonato), demonstra o metabolismo da região, e associada à fusão de imagens co-registradas com a tomografia computadorizada (CT), permite a localização anatômica das alterações ósseas funcionais existentes nas estruturas envolvidas. É um exame com baixa dose de radiação que possibilita a observação conjunta estrutural anatômica e metabólica. Neste trabalho avaliamos, retrospectivamente, exames SPECT/CT de 33 pacientes realizados no Setor de Medicina Nuclear do Departamento de Imagem do Centro de Tratamento e Pesquisa - Hospital do Câncer A. C. Camargo, que apresentavam sinais e sintomas de provável DTM. Os resultados dos exames foram relacionados aos dados existentes nos prontuários dos pacientes, como sexo, idade, anamnese e exame clínico. Por meio de análise descritiva, utilizando as freqüências e porcentagens das variáveis de interesse, pudemos avaliar a confiabilidade do exame. Concluímos que o SPECT/CT, quando aplicado em pacientes portadores de sinais e sintomas de DTM, apresentou alta sensibilidade (100%), especificidade (90,9%) e acurácia (96,9%), demonstrando que é um método de diagnóstico por imagem de relevância, útil e de grande valia, podendo ser um dos métodos de escolha indicados para diagnóstico de DTM. / Temporomandibular joint dysfunction play a negative role on patient life quality standard. A diversity of signs and symptoms such us muscular pain, headaches (focal or diffuse), temporomandibular joint localized pain, limitation or excessive mandibular opening and joint noise may lead to difficulties of correct diagnosis. Clinical investigation and complementary exams are necessary in these cases. Conventional radiographic and tomographic exams exactilly indicates local anatomy but do not demonstrate functional metabolic changes. Tomographic images on Nuclear Medicine, SPECT (Single Photon Emission Computed Tomography) with 99m Tc-MDP (methylene diphosphonate) a radiopharmaceutical labeled with Technetium 99m demonstrate regional metabolism changes. The association to co-registered computed tomography (CT) and image fusion allows the anatomic placement of bone functional alteration into the involved structures. SPECT/CT is a low dose radiation procedure that makes simultaneous anatomic and metabolic observation possible. This assignment was retrospectively analyzed, SPECT/CT of 33 patients from the Nuclear Medicine Sector of the Image Department of the Research and Treatment Center of the Cancer Hospital A. C. Camargo, that presented sings and symptoms of probable temporomandibular joint dysfunction. The results of the exams were related with the patient data that were on their file like sex, age, anamnesis and clinical exam. The assessment of the reliability of the exam was evaluated by descriptive analysis using frequencies and percentages of the interest variables. We conclude that SPEC/CT showed high sensitivity (100%), specificity (90,9%) and accuracy (96,9%); demonstrating that it is an important and useful diagnostic method, that may be an exam of choice to the diagnostic features of temporomandibular joint disfunction.

Ce travail de thèse réalisé à l’Institut de Chimie Moléculaire de l’Université de Bourgogne porte dans un premier temps sur la synthèse d’agents chélatants bifonctionnels adaptés à la chélation de radiométaux trivalents, notamment l’indium-111. La plus grande partie de ce travail a ensuite consisté à réaliser le greffage d’un agent chélatant bifonctionnel dérivé du DOTA sur différents anticorps ou fragments d’anticorps monoclonaux : le trastuzumab (anti HER2, traitement de cancers du sein), le cétuximab (anti EGFR, traitement de nombreux cancers, dont le cancer colorectal) et l’abciximab (antiagrégant plaquettaire). Une attention particulière a été apportée à la caractérisation des différents immunoconjugués. La dernière étape de ce travail de thèse porte sur le radiomarquage à l’indium-111 de deux immunoconjugués préparés : le trastuzumab et le cétuximab. Ces étapes de radiomarquage nous ont permis de déterminer la fraction immunoréactive et l’affinité de chaque radiotraceur. Nous avons ainsi pu étudier la biodistribution in vivo de ces radiotraceurs chez la souris par imagerie SPECT-CT. Nous avons également développé une méthode de greffage originale pour le marquage d’un fragment d’anticorps de type Fab, l’abciximab, dans le but de suivre la biodistribution de cet antiagrégant plaquettaire. Enfin, nous avons également validé le concept d’imagerie multimodale à travers le greffage et le radiomarquage d’un agent bimodal pour l’imagerie optique et la SPECT sur des lipopolysaccharides bactériens. Les travaux réalisés nous ont permis d’acquérir un savoir faire en matière de greffage d’anticorps et de radiomarquage. Les résultats obtenus permettent d’envisager le greffage d’autres anticorps ou biomolécules, ainsi que l’utilisation d’autres radionucléides pour l’imagerie PET ou la radioimmunothérapie / This work conducted at the “Institut de Chimie Moléculaire de l’Université de Bourgogne” carries at first on the synthesis of bifunctional chelating agents suitable for the chelation of trivalent radiometals, including indium-111. The greater part of this work was then dedicated to the grafting of a DOTA derivative bifunctional chelating agent on different antibodies or fragments of monoclonal antibodies: trastuzumab (anti-HER2 treatment of breast cancer), cetuximab (anti EGFR, treatment of many cancers, including colorectal cancer) and abciximab (antiplatelet). Particular attention was paid to the characterization of various immunoconjugates. The critical step of this thesis consisted in the indium-111 radiolabeling of two previously prepared immunoconjugates: trastuzumab and cetuximab. These steps of radiolabelling allowed us to determine the immunoreactive fraction and affinity of each radiotracer. Thus, we were able to study the in vivo biodistribution of the radiotracers in tumour-bearing mice by SPECT-CT. We also developed an original method for the labeling of a Fab antibody fragment in order to monitor the biodistribution of the antiplatelet agent (abciximab). Finally, we also validated the concept of multimodal imaging through grafting and radiolabeling of a bimodal agent for optical and SPECT imaging on bacterial lipopolysaccharide. Thank’s to this work, we gained an expertise in antibodies radiolabeling. The results obtained allow to consider the labeling of antibodies or other biomolecules, and the use of other radionuclides for PET imaging and radioimmunotherapy

99mTecknetium-tetrofosmin är ett radiofarmaceutiskt medel som används vid myokardscintigrafi för att bedöma myokardperfusionen genom att avbilda vänsterkammarens blodflöde. Radiofarmakat uppvisar ett lågt myokardiellt upptag på endast 1,2%, där majoriteten av resterande radiofarmaka rensas ut genom levern och utsöndras via gallsystemet. Det extrakardiella upptaget i buken kan minska bildkvalitén, dölja defekter och försämra diagnostisk noggrannhet. GE StarGuide är en SPECT/CT-kamera utrustad med avancerad detektorteknologi som möjliggör fokuserad fotoninsamling, vilket bidrar till högre bildupplösning. Syftet med den här studien var att undersöka effekten av bukupptag vid bedömning av vänsterkammarens blodfördelning vid myokardscintigrafi med hjälp av SPECT/CT-kameran StarGuide. För att uppnå detta användes en thoraxmodell med ett fantomhjärta och en slang som simulerade bukupptag. Slangen fylldes med varierande aktivitetskoncentrationer och avståndet mellan slangen och fantomhjärtat varierades systematiskt. Vårdpersonal inom området bedömde sedan om bildomtagning var nödvändig, baserat på bildkvalitén och effekten av bukupptaget. Resultatet från studien indikerar en kvalitativ och kvantitativ påverkan av bukupptag vid bedömning av blodfördelningen i vänsterkammaren för de olika undersökta aktivitetskoncentrationerna och avstånden. Däremot observerades ingen statistisk signifikant skillnad mellan aktivitetskoncentrationerna vad gäller den kvantitativt påverkan. Vidare studier krävs för att validera dessa fynd och ge nya riktlinjer för att optimera användningen av StarGuide inom den nuklearmedicinska verksamheten. / 99mTechnetium-tetrofosmin is a radiopharmaceutical agent used for myocardial perfusion scintigraphy to assess myocardial perfusion by imaging the left ventricular bloodflow. The agent exhibits a low myocardial uptake of only 1,2%, with the majority of the agent being cleared through the liver and excreted via the biliary system. The extracardiac uptake in the abdomen can reduce image quality, conceal defects, and compromise diagnostic accuracy. The GE StarGuide is a SPECT/CT-camera equipped with advanced detector technology that allows for focused photon collection, thus contributing to improved image resolution. The objective of the present phantomstudy was to investigate the effect of abdominal uptake on the assessment of blood distribution in the left ventricle during myocardial perfusion scintigraphy using the SPECT/CT-camera StarGuide. To acieve this, a thorax model containing a phantomheart was used, with a tube simulating abdominal uptake. The tube was filled with varying activity concentrations, and the distance between the tube and the phantomheart was systematically varied. Healthcare professionals within the field then assessed whether image retakes were necessary based on the image quality and the impact of the abdominal uptake. The results of the study indicated that there is a qualitative and quantitative effect of extracardiac uptake on the assessment of left ventricular blood distribution for the different activity concentrations and distances examined, however, no statistically significant difference was observed between the activity concentrations quantitatively. Further investigations are needed to validate these findings and provide guidance for optimizing the use of the StarGuide camera in nuclear medicine practice.