Cardiovascular disease remains the commonest cause of death worldwide. The majority of deaths are caused by atherosclerotic plaque rupture with resultant myocardial infarction or stroke, or rupture of abdominal aortic aneurysms. Conventional imaging modalities have consistently failed to identify atherosclerotic plaques or aneurysms with high-risk pathological features that are at highest risk of rupture or progression. The development of modern molecular imaging techniques targeted at these features could lead to the identification of such high-risk plaques and aneurysms in vivo and guide the development of novel treatment strategies. The aim of this thesis was to evaluate whether novel molecular modalities have a role in providing new insights into biological disease processes, and identify high-risk plaques and aneurysms. Using positron emission tomography-computed tomography (PET-CT), 18F-fluorodeoxyglucose and 18F-fluoride were utilised as markers of metabolic inflammation and active calcification. Cellular inflammation was assessed using ultrasmall superparamagnetic particles of iron oxide (USPIO) enhanced magnetic resonance imaging (MRI). In a prospective trial, 80 patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-fluoride and 18F-fluorodeoxyglucose PET-CT, and invasive coronary angiography (Chapter 3). Intense 18F-fluoride uptake localised to recently ruptured plaque in patients with acute myocardial infarction. In patients with stable coronary artery disease, 18F-fluoride uptake identified coronary plaques with high-risk features on intravascular ultrasound. 18F-fluoride PET-CT is the first noninvasive imaging method to identify and localise ruptured and high-risk coronary plaques. Aortic vascular uptake of 18F- fluorodeoxyglucose was studied in patients with myocardial infarction and stable angina (Chapter 4). In a separate outcome of 1,003 patients enrolled in the Global Registry of Acute Coronary Events, we further evaluated whether infarct size predicted recurrent coronary events. Patients with myocardial infarction had higher remote atherosclerotic tracer uptake that correlated with the degree of myocardial necrosis, and exceeded that observed in patients with stable coronary disease. The outcome cohort demonstrated that patients with higher degree of myocardial necrosis had the highest risk of early recurrent myocardial infarction. This supports the hypothesis that acute myocardial infarction exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: myocardial infarction begets myocardial infarction. In a prospective imaging cohort, the role inflammation and calcification was assessed in 63 patients with abdominal aortic aneurysms and 19 age and sex matched patients with atherosclerosis (Chapter 5). Compared to non-aneurysmal segments, enhanced inflammation and calcification was observed within the wall of aortic aneurysmal segments. In comparison to matched controls with atherosclerosis, the entire aorta in those with aortic aneurysm appears more highly inflamed, suggesting presence of a global aortopathy rather than a disease confined only to the abdominal region of the aorta. Aortic aneurysms have greater active inflammation and calcification than atherosclerotic controls suggesting a more intense, destructive and transmural pathological process. A subgroup of fifteen patients with aortic aneurysms underwent imaging with both PET-CT with 18F-fluorodeoxyglucose, and T2*- weighted MRI before and 24 h after administration of USPIO (Chapter 6). Whilst there was a moderate correlation between the two tracers, there were distinct differences in the pattern and distribution of uptake suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively. These studies provide novel insights into vascular biological processes involved in the initiation, progression and rupture of atherosclerotic plaques and aortic aneurysms. Future longitudinal studies are needed to establish whether these techniques have a role in improving the clinical management and treatment of patients with coronary artery disease and aortic aneurysms.

Submitted by Fernanda Rodrigues de Lima (fernanda.rlima@ufpe.br) on 2018-07-20T22:10:35Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Marcos Antônio Dórea Machado.pdf: 2233914 bytes, checksum: b98eee9403ebcdd88d55481bc0692500 (MD5) / Approved for entry into archive by Alice Araujo (alice.caraujo@ufpe.br) on 2018-07-23T17:59:48Z (GMT) No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Marcos Antônio Dórea Machado.pdf: 2233914 bytes, checksum: b98eee9403ebcdd88d55481bc0692500 (MD5) / Made available in DSpace on 2018-07-23T17:59:48Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Marcos Antônio Dórea Machado.pdf: 2233914 bytes, checksum: b98eee9403ebcdd88d55481bc0692500 (MD5) Previous issue date: 2017-02-10 / O equipamento PET, os parâmetros de aquisição e a reconstrução de imagens em exames oncológicos de PET têm impacto tanto na qualidade das imagens quanto na quantificação da atividade metabólica dos tumores. Neste trabalho é apresentado um método para otimizar os parâmetros de aquisição de imagens em exames FDG-F18 PET/CT de tumores sólidos, a partir do ruído no simulador IEC/NEMA e na região do fígado de 88 pacientes. O algoritmo de reconstrução Point Spread Function (PSF), harmonizado de acordo com os critérios da European Association of Nuclear Medicine (EANM), foi usado para gerar imagens superiores em termos de ruído. Assim, as medidas de ruído no simulador IEC/NEMA foram correlacionadas às quantificações dos coeficientes de recuperação de contraste máximos (CRCmax), em que os limites adotados pela EANM para CRCmax foram usados como critérios de qualidade que definem a relação ótima entre parâmetros de aquisição, ruído e quantificações. Adicionalmente, o ruído na região do fígado de 48 pacientes foi caracterizado para as reconstruções OSEM e PSF (CRCmáx harmonizados) com densidades de contagens tipicamente usadas em uma rotina clínica. Outro conjunto de 40 imagens em modo lista da região do fígado de pacientes foi usado para gerar 160 imagens com um amplo espectro de densidade de contagens, a fim de compreender o ruído em diferentes contextos de densidade de contagens. Aquisição de imagens com aproximadamente 350 MBq.s/kg no simulador IEC/NEMA apresentou variabilidade da quantificação em conformidade aos limites da EANM, que corresponde a um ruído no simulador de CV = 8,7%. Este mesmo parâmetro de aquisição quando aplicado a um paciente, resulta em um ruído de CV = 7,1% na região do fígado, que pode ser usado como uma medida de garantia da qualidade na rotina de exames. Entretanto, a região entre 200-320 MBq.s/kg sugere oferecer quantificações de SUVmáx reprodutíveis pois o ruído no fígado mostrou-se controlado nesta região de densidade de contagens. O uso do SUVpeak mostrou-se ainda mais reprodutível, incluindo a região entre 100-200 MBq.s/kg. Este método representa a base para um estudo que possa identificar o protocolo de aquisição otimizado, para vários equipamentos e tipos de reconstrução, a fim de executar exames de PET/CT com baixa posologia atendendo aos critérios de harmonização da EANM. / The PET/CT scanner, the image acquisition and the reconstruction parameters in oncological PET affect the image quality and the quantification of tumor activity. In this work, we presented a method for image acquisition optimization of FDG-F18 PET/CT examinations in solid tumors by using noise metrics in the IEC/NEMA phantom and in the liver of 88 subjects. The Point Spread Function (PSF) reconstruction algorithm, harmonized according to he European Association of Nuclear Medicine (EANM), was used to generate superior images in terms of noise. Then, we used the IEC/NEMA phantom to correlate noise and maximum contrast recovery coefficient (CRCmáx) quantitation measurements which the EANM CRCmáx limits were adopted as criteria to define the optimal relations among acquisition parameters, noise and quantification. Additionally, the noise in the liver of 48 subjects was characterized for OSEM and PSF reconstructions (CRCmáx harmonized) by using clinical count densities typically used in clinical routine. Another set of 40 list mode images from the liver was used to generate 160 images with a wide range count density spectrum in order to understand the noise characteristics in different count density context. Image acquisitions of about 350 MBq.s/kg in the IEC/NEMA phantom presented CRCmáx variability within EANM limits, which corresponds to 8.7% noise in phantom. Such image acquisition parameter provides 7.1% noise in the liver, which might be used as a quality assurance measurement in clinical routine. However, the 200-320 MBq.s/kg range may pose reproducible SUVmáx quantitation since noise in liver was satisfactorily controlled for such count density spectrum. When SUVpeak was used, it presented even better reproducibility, including the 100-200 MBq.s/kg spectrum. The presented method provides the basis to more robust studies to identify the optimal acquisition parameter for different scanners and reconstructions in order to perform low-dose FDF-F18 PET/CT according to EANM harmonization criteria.

Die therapeutischen Möglichkeiten des metastasierten Prostatakarzinoms (Pca) haben sich durch die neuen Substanzen Docetaxel und Abirateron deutlich verbessert. Das prostataspezifische Membranantigen (PSMA) stellt für die Diagnose und Therapie des Pca´s einen vielversprechenden Angriffspunkt dar. PSMA wird in Prostatakarzinomzellen überexprimiert und dient als Zielstruktur für nicht-invasives bildgebendes Verfahren und Lutetium-177-PSMA-Radioligandentherapie als Therapieoption. Der CXCR4-Rezeptor wird an unterschiedlichen Zelltypen und Organen exprimiert. Seine Überexpression wird mit einer Metastasierung und schlechter Prognose assoziiert. Gallium-68-PSMA PET/CT liefert genaue Kenntnisse bezüglich Ausbreitung und Fortschreiten des Tumorgeschehens. Die vorliegende Arbeit untersucht die Zusammenhänge zwischen Expression von PSMA und CXCR4 in Verbindung mit etablierten Therapeutika und versucht Wege aufzuzeichnen, welche durch Erhöhung der PSMA-Expression zur verbesserten Sensitivität des PSMA PET/CT führen könnten, wodurch der personalisierte Therapieansatz weiter optimiert werden kann. / Novel therapeutic agents such as docetaxel and abiraterone have significantly improved treatment strategies for metastatic prostate cancer in recent years. Prostate-specific membrane antigen (PSMA) represents a promising target for diagnosis and therapy of prostate cancer. PSMA is over expressed in prostate cancer cells providing a target structure for non-invasive imaging and Lutetium-177-PSMA radioligand therapy. The CXCR4-receptor is expressed on different cell types and organs. Its over expression is associated with metastasis and poor prognosis. PET/CT imaging with Gallium-68-labelled PSMA ligands provide relevant information regarding tumor staging and progression. The present study investigates the interaction between expression of PSMA and CXCR4 considering established therapeutic agents to improve sensitivity of PSMA PET/CT imaging and optimize personalized cancer medicine.

Indiana University-Purdue University Indianapolis (IUPUI) / The advances in health care technology help physicians make more accurate diagnoses about the health conditions of their patients. Positron Emission Tomography/Computed Tomography (PET/CT) is one of the many tools currently used to diagnose health and disease in patients. PET/CT explorations are typically used to detect: cancer, heart diseases, disorders in the central nervous system. Since PET/CT studies can take up to 60 minutes or more, it is impossible for patients to remain motionless throughout the scanning process. This movements create motion-related artifacts which alter the quantitative and qualitative results produced by the scanning process. The patient's motion results in image blurring, reduction in the image signal to noise ratio, and reduced image contrast, which could lead to misdiagnoses. In the literature, software and hardware-based techniques have been studied to implement motion correction over medical files. Techniques based on the use of an external motion tracking system are preferred by researchers because they present a better accuracy. This thesis proposes a motion correction system that uses 3D affine registrations using particle swarm optimization and an off-the-shelf Microsoft Kinect camera to eliminate or reduce errors caused by the patient's motion during a medical imaging study.

Made available in DSpace on 2015-07-22T20:49:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-10-27 / Objetivo: Comparar a sobrevida de pacientes com recidiva de câncer de ovário que realizaram estudo com 18F FDG PET-CT não dedicado, tomografia computadorizada e marcador CA-125 com as enfermas que se submeteram ao tratamento e seguimento usual com tomografia computadorizada e o marcador CA-125. Metodologia: Estudaram-se pacientes com neoplasia ovariana epitelial maligna no Hospital do Câncer AC Camargo- São Paulo, no período compreendido entre janeiro de 1996 à dezembro de 2003, as quais apresentaram recidiva, comprovada pela cirurgia. Avaliaram-se 44 pacientes (grupo A) que efetuaram exame 18F-FDG em PET-CT não dedicado e 31 doentes (grupo B) que efetuaram o seguimento habitual. Excluíram-se as pacientes em vigência de quimioterapia (menos de 48 horas) da data da realização do exame 18F-FDG em PET-CT não dedicado. Resultados: Pacientes com exames de PET-CT não dedicado (grupo A) apresentaram significante aumento da sobrevida em comparação com o grupo B (p=0.0200). Outrossim, 11 pacientes com estudo anátomopatológico “borderline” apresentaram apenas um exame falso negativo (implantes peritoneais), 10 verdadeiro negativos e 18 verdadeiro positivos. Conclusão: O emprego do FDG-PET-CT não dedicado na avaliação de pacientes com neoplasia ovariana maligna mostrou ser procedimento que resultou em benefícios, interferindo na atitude dos cirurgiões, mormente na recidiva subclínica. Verificou-se maior sobrevida das enfermas após o tratamento da recidiva quando foi identificado pelo FDG-PET-CT não dedicado seja por sítios ou locais insuspeitos ou mesmo pela completa ausência de sintomas e sinais clínicos. / Purpose The aim of this study was to compare the impact of the survival in patients with ovarian cancer recurrence undergoing non-dedicated [18F]FDG PET-CT, CT and serum CA-125 (group A) and patients that were submitted to conventional follow-up with CT and serum CA-125. Methods Patients diagnosed with epithelial ovarian cancer at the AC Camargo Cancer Hospital from January 1996 to December 2003 who presented recurrence (checked by surgery), and performed [18F]FDG PET-CT on a total of 44 patients- group A, and 31 patients -group B undergoing conventional follow up. Patients undergoing chemotherapy less than 48 hours before non-dedicated PET-CT were excluded from the research. Results Patients of Group A presented an increase on their survival rate of 5.94 in comparison with group B (p=0.0200). The 11 borderline patients in group A performed 29 [18F]FDG PET-CT studies with 1 false negative (peritoneal implants), 10 true negatives and 18 true positives. Conclusion Oncologists are used to test several markers in order to perform diagnosis, staging and prognosis, but their real benefit in the treatment is still uncertain. The use of [18F]FDG PET-CT in the evaluation of subclinical ovarian cancer recurrence has been shown to be accurate and presented a rewarding cost-benefit relationship, interfering in the surgeons conduct facing a subclinical recurrence. / TEDE / BV UNIFESP: Teses e dissertações

Thesis (M.A.)--Boston University / The standardized uptake value (SUV) is increasingly being used for diagnosis, staging, and monitoring disease in clinical oncology. Comparing tumor SUV to background SUV is an attractive way to minimize variability and ensure the quality of scans across different institutions. The liver has been identified as a potential source for background normalization, however no studies have compared the liver to other background sites for a variety of cancers. The purpose of this study was to evaluate the use of liver uptake for the standardization of FDG PET/CT imaging. Scans from 145 patients were prospectively reviewed under the supervision of a radiologist with board certification in nuclear medicine (R.M.S. , 3 years of experience). Liver SUV values were correlated to mediastinum SUV values in lung and breast cancer patients, and internal jugular vein (IJV) SUV values in head and neck cancer patients. The independent t-test was used to determine if there was a statistically significant affect of the amount of incubation time or use of intravenous contrast on the SUV. For the lung and breast cancer patients, a strong correlation was observed between the mediastinum SUVmean and liver SUVmean (r = 0.89), whereas for the head and neck cancer patients, a weaker correlation was observed between the IJV SUVmean and the liver SUVmean (r = 0.69). Neither the amount of incubation time nor the use of IV contrast demonstrated a significant affect on the SUV. We conclude that liver SUVmean may be used to standardize FOG PET/CT studies in cancers of the lung, breast and head and neck. However, additional studies in other cancers as well as the affects of age, gender, benign disease and use of chemotherapy are still desired before widespread adoption of this standard.

Background: Surgical treatment of colorectal liver metastases (CLRM) depends on resectability that is currently based on the CT scan. With the PET/CT scan, a more accurate pre-operative assessment of resectability may be possible. Methods: A Cochrane-based diagnostic test systematic review and a systematic review of cost-effectiveness studies on PET scans were conducted. Lastly, a diagnostic decision analysis model was created to assess the cost-effectiveness of the technology. Results: PET/CT scans was equally sensitive for hepatic metastases and more sensitive for extra-hepatic metastases compared to CT scans. A cost-savings of PET scans for CRLM is identified; with decision modelling demonstrating a cost-savings with the addition of PET/CT scans to the current clinical algorithm. Conclusion: There is cautious support for the addition of PET/CT scans to the pre-operative assessment in CRLM. Unnecessary surgery may be prevented, thus decreasing wait times. Future endeavours include finding, evaluating and validating methodology for appropriate effectiveness measures. / Health Technology Assessement

A novel Y-90 liquid brachytherapy strategy is currently being studied for the treatment of osteosarcoma using a preclinical translational model in dogs to assess its potential efficacy and toxicity. In this study, dosimetry calculations are performed for Y-90 liquid brachytherapy in a dog with osteosarcoma using the Geant4 Monte Carlo code. A total of 611.83 MBq Y-90 radiopharmaceutical is administered via direct injections, and the in vivo distribution of Y-90 is assessed using a time-of-flight (TOF) PET/CT scanner. A patient-specific geometry is built using anatomical data obtained from CT images. The material properties of tumor and surrounding tissues are calculated based on a CT number - electron density calibration. The Y-90 distribution is sampled in Geant4 from PET images using a collapsing 3-D rejection technique to determine the decay sites. Dose distributions in the tumor bed and surrounding tissues are calculated demonstrating significant heterogeneity with multiple hot spots at the injection sites. Dose volume histograms show about 33.9 percent of bone and tumor and 70.2 percent of bone marrow and trabecular bone receive a total dose over 200 Gy; about 3.2 percent of bone and tumor and 31.0 percent of bone marrow and trabecular bone receive a total dose of over 1000 Gy. Y-90 liquid brachytherapy has the potential to be used as an adjuvant therapy or for palliation purposes. Future work includes evaluation of pharmacokinetics of the Y-90 radiopharmaceutical, calibration of PET/CT scanners for the direct quantitative assessment of Y-90 activity concentration, and assessment of efficacy of the Y-90 liquid brachytherapy strategy.

No description available.

Positron emission tomography (PET) is a powerful and highly specialised imaging modality that has the inherent ability to detect and quantify changes in the bio-distribution of an intravenously administered radio-labelled tracer, through dynamic image acquisition of the system under study. By modelling the temporal distribution of the tracer, parameters of interest regarding specific biological processes can be derived. Traditionally parameter estimation is done by first reconstructing a set of dynamic images independently, followed by kinetic modelling, leading to parameters of reduced accuracy and precision. Furthermore only simple geometrical models are used during image reconstruction to model the mapping between the image space and the data space, leading to images of reduced resolution. This thesis attempts to address some of the problems associated with the current methodology, by implementing and evaluating new spatiotemporal image reconstruction strategies in oncology PET/CT imaging, with simulated, phantom and real data. More specifically this thesis is concerned with iterative reconstruction techniques, the incorporation of resolution recovery and kinetic modelling strategies within the image reconstruction process and the application of such methods in perfusion [15O]H2O imaging. This work is mainly based upon 2 whole body PET/CT scanners, the Siemens Biograph 6 B-HiRez and TruePoint TrueV, but some aspects of this work were also implemented for the High resolution research tomograph (HRRT).