As doenças cardiovasculares são a principal causa de mortalidade no mundo. A aterosclerose é a base fisiopatológica dessas doenças, sendo definida como um processo crônico-inflamatório multifatorial, resultando da interação de diferentes células como linfócitos, macrófagos, células endoteliais e células musculares lisas na parede arterial. A lipoproteína de baixa densidade eletronegativa [LDL(-)], uma subfração modificada da LDL nativa, desempenha um papel-chave na aterosclerose, uma vez que as modificações sofridas por esta partícula são capazes de induzir o acúmulo de ésteres de colesterol em macrófagos e a subsequente formação de células espumosas. O sistema imunológico é crucial no processo aterogênico e estratégias terapêuticas direcionadas à imunoregulação deste processo têm sido utilizadas como novas alternativas tanto na prevenção do desenvolvimento quanto da progressão desta doença. Dentre essas estratégias, destaca-se o uso de fragmentos de anticorpos como o scFv (do inglês, single chain fragment variable), que podem ainda estar conjugados a nanopartículas com o intuito de aumentar sua eficiência de ação no organismo. Diante do papel da LDL(-) na aterosclerose, este projeto objetivou avaliar os efeitos in vitro e in vivo de um sistema nanoestruturado contendo fragmentos scFv anti-LDL(-) derivatizados na superfície de nanocápsulas sobre macrófagos murinos e humanos primários e em camundongos knockout para o gene do receptor da LDL (Ldlr-/-) no desenvolvimento e na progressão dessa doença. Demonstrou-se que o tratamento de macrófagos com a formulação scFv anti-LDL(-)-MCMN-Zn diminuiu de forma significativa a captação de LDL(-), assim como a expressão de IL-1β (mRNA e proteína) e MCP-1 (mRNA). Foi demonstrada a internalização da nanoformulação pelos macrófagos via diferentes mecanismos de endocitose, demonstrando seu potencial uso como carreador de fármacos. In vivo, a nanoformulação diminuiu de forma significativa a área da lesão aterosclerótica em camundongos Ldlr-/- submetidos à avaliação pela técnica de tomografia por emissão de pósitrons (do inglês, PET), utilizando o radiotraçador 18F-FDG (18F-desoxiglicose), associada à tomografia computadorizada (CT) com agente de contraste iodado, além da análise morfométrica das lesões no arco aórtico. O conjunto dos resultados obtidos evidenciou a ação ateroprotetora da formulação scFv anti-LDL(-)-MCMN-Zn, reforçando seu potencial como estratégia terapêutica na aterosclerose. / Cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerosis is the pathophysiological basis of these diseases, defined as a chronic inflammatory multifactorial process, resulting from the interaction of several cells such as lymphocytes macrophages, endothelial cells and smooth muscle cells within the arterial wall. The electronegative low-density lipoprotein [LDL(-)], a modified subfraction of native LDL, plays a key role in atherosclerosis, since its modifications are capable of inducing the accumulation of cholesteryl esters in macrophages and the subsequent foam cells formation. The immune system is crucial in atherogenic process and therapeutic strategies directed to the immunoregulation of this process have been used as a new alternative in the prevention of the development as well as the progression of this disease. Among these strategies, it is the use of antibody fragments such as scFv (single chain fragment variable), which may be also conjugated to nanoparticles in order to increase their efficiency in the body. Given the role of LDL(-) in atherosclerosis, the aim of this project was to evaluate the in vitro and in vivo effects of a nanostructured system containing scFv anti-LDL(-) fragments derivatized on the surface of nanocapsules on murine and human primary macrophages and in the development and progression of the disease in LDL receptor knockout mice (Ldlr-/-). It was demonstrated that the treatment of macrophages with scFv anti-LDL(-)-MCMN-Zn formulation significantly decreases the uptake of LDL(-) and the expression IL-1β (mRNA and protein) and MCP-1 (mRNA). Moreover, the internalization of the nanoformulation by macrophages through different endocytosis mechanisms was shown, demonstrating its potential use as a nanocarrier. In vivo, the nanoformulation decreased the area of atherosclerotic lesions in Ldlr-/- mice evaluated by positron emission tomography with 18F-FDG associated with computed tomography with iodinated contrast agent (PET/CT), besides the lesion morphometric analysis at the aortic arch Thus, these data provide evidence of the atheroprotection action of the ateroprotection action of the scFv anti-LDL(-)-MCMN-Zn formulation, suggesting its promising use as a therapeutic strategy for atherosclerosis.

L’imagerie multi-modale Tomographie par émission de positons (TEP)/ Tomodensitométrie(TDM) est la modalité d’imagerie la plus utilisée pour le diagnostic et le suivi des patients en oncologie. Les images obtenues par cette méthode offrent une cartographie à la fois de la densité des tissus (modalité TDM) mais également une information sur l’activité métabolique des lésions tumorales (modalité TEP). L’analyse plus approfondie de ces images acquises en routine clinique a permis d’extraire des informations supplémentaires quant à la survie du patient ou à la réponse au(x) traitement(s). Toutes ces nouvelles données permettent de décrire le phénotype d’une lésion de façon non invasive et sont regroupées sous le terme de Radiomics. Cependant, le nombre de paramètres caractérisant la forme ou la texture des lésions n’a cessé d’augmenter ces dernières années et ces données peuvent être sensibles à la méthode d’extraction ou encore à la modalité d’imagerie employée. Pour ces travaux de thèse, la variabilité de ces caractéristiques a donc été évaluée sur les images TDM et TEP à l’aide d’une cohorte test-retest : pour chaque patient, deux examens effectués dans les mêmes conditions, espacés d’un intervalle de l’ordre de quelques jours sont disponibles. Les métriques reconnues comme fiables à la suite de cette analyse sont exploitées pour l’étude de la survie des patients dans le cadre du cancer du poumon. La construction d’un modèle pronostique à l’aide de ces métriques a permis, dans un premier temps, d’étudier la complémentarité des informations fournies par les deux modalités. Ce nomogramme a cependant été généré par simple addition des facteurs de risque. Dans un second temps, les mêmes données ont été exploitées afin de construire un modèle pronostique à l’aide d’une méthode d’apprentissage reconnue comme robuste : les machines à vecteurs de support ou SVM (support vector machine). Les modèles ainsi générés ont ensuite été testés sur une cohorte prospective en cours de recrutement afin d’obtenir des résultats préliminaires sur la robustesse de ces nomogrammes. / Positron emission tomography (PET) / Computed tomography (CT) multi-modality imaging is the most commonly used imaging technique to diagnose and monitor patients in oncology. PET/CT images provide a global tissue density description (CT images) and a characterization of tumor metabolic activity (PET images). Further analysis of those images acquired in clinical routine supplied additional data as regards patient survival or treatment response. All those new data allow to describe the tumor phenotype and are generally grouped under the generic name of Radiomics. Nevertheless, the number of shape descriptors and texture features characterising tumors have significantly increased in recent years and those parameters can be sensitive to exctraction method or whether to imaging modality. During this thesis, parameters variability, computed on PET and CT images, was assessed thanks to a test-retest cohort : for each patient, two groups of PET/CT images, acquired under the same conditions but generated with an interval of few minutes, were available. Parameters classified as reliable after this analysis were exploited for survival analysis of patients in the context of non-small cell lug cancer (NSCLC).The construction of a prognostic model with those metrics permitted first to study the complementarity of PET and CT texture features. However, this nomogram has been generated by simply adding risk factors and not with a robust multi-parametric analysis method. In the second part, the same data were exploited to build a prognostic model using support vector machine (SVM) algorithm. The models thus generated were then tested on a prospective cohort currently being recruited to obtain preliminary results as regards the robustness of those nomograms.

Die Kombination von Positronen-Emissions-Tomographie (PET) und Röntgen-Computertomographie (CT) in Form moderner PET/CT-Geräte ermöglicht die Nutzung der CT-Information zur Korrektur der Photonenschwächung in der PET. Allerdings können Bewegungen, die zum Beispiel durch die Atmung hervorgerufen werden können, zu einer fehlerhaften Schwächungskorrektur führen. Die Einführung von zeitlich aufgelöster Bildgebung für beide Modalitäten (4D-PET/4D-CT) ermöglicht nicht nur die Auflösung von periodischen Bewegungen, sondern auch die Reduktion dieser Fehler in der Schwächungskorrektur. Dazu werden die einzelnen Datensätze des 4D-PET, die jeweils einer bestimmten Bewegungsphase entsprechen, mit dem entsprechenden CT-Datensatz dieser Atemphase schwächungskorrigiert. In der vorliegenden Arbeit wurde diese phasenkorrelierte Schwächungskorrektur des 4D-PET mit dem 4D-CT am Universitästsklinikum Dresden installierten PET/CT ermöglicht und anhand von Phantomexperimenten mit anderen Schwächungskorrekturmethoden für 4D-PET verglichen. Dazu musste zunächst die Aufnahme von 4D-CT an dem verwendeten PET/CT ermöglicht und dessen Synchronität mit dem 4D-PET hergestellt werden. Außerdem wurde ein vorhandenes Atemphantom so modifiziert, dass es typische Bewegungen von Bronchialkarzinomen in zwei Dimensionen und mit zwei möglichen Atemmustern simuliert. Die phasenkorrelierte Schwächungskorrektur führte zu einer quantitativ korrekten Wiederherstellung des Aktivitätsvolumens, der darin enthaltenen Aktivität sowie der Bewegungsamplitude und stellt somit die beste der hier verglichenen 4D-PET-Schwächungskorrekturmethoden dar. Diese Ergebnisse lassen vermuten, dass die phasenkorrelierte Schwächungskorrektur auch bei klinischer Anwendung eine signifikante Verbesserung in oben genannten Punkten darstellt. Dies sollte in Zukunft an Patientendaten überprüft werden. / The combination of Positron Emission Tomography (PET) and Computed Tomography (CT) in one device allows the use of CT-information for attenuation correction in PET. Though motion, for example induced by respiration, can cause inaccurate attenuation correction. The implementation of time-resolved imaging methods for both modalities (4D-PET/4D-CT) enables not only the resolution of motion but also the reduction of artifacts caused by attenuation correction. Therefore, the single datasets of the 4D-PET that are related to a individual respiratory phase, are attenuation corrected with the corresponding dataset of the 4D-CT. This phase correlated attenuation correction of the 4D-PET with the 4D-CT was implemented at the PET/CT installed at the Universitätsklinikum Dresden. For that purpose the acquisition of 4D-CT was implemented at the PET/CT and its synchronisation with the 4D-PET was verified. Furthermore the new attenuation correction method was compared with other attenuation correction methods by performing phantom experiments. Therefore an exisisting respiratory phantom had to be modified to perform typical lung tumor motion in two dimensions with two possible patterns of respiration. The phase correlated attenuation correction leads to a quantitatively correct restauration of the activity volume, its total activity and its motion amplitude. Compared with other correction methods, the phase correlated attenuation correction shows the best results in all examined criteria. This findings suggest that the clinical application of the phase correlated attenuation correction will also lead to a significant improvement in all mentioned points. This has to be verified by analyzing patient data.

Positron Emission Tomography (PET) is pivotal in medical imaging but is prone to artifactsfrom physiological movements, notably respiration. These motion artifacts both degradeimage quality and compromise precise attenuation correction. To counteract this, gatingstrategies partition PET data in synchronization with respiratory cycles, ensuring each gatenearly represents a static phase. Additionally, a 3D deep learning image registration modelcan be used for inter-gate motion correction, maximizing the use of the full acquired data. Thisstudy aimed to implement and evaluate two gating strategies: an external device-based approachand a data-driven centroid-of-distribution (COD) trace algorithm, and assess their impact on theperformance of the registration model. Analysis of clinical data from four subjects indicated thatthe external device approach outperformed its data-driven counterpart, which faced challengesin real-patient settings. Post motion compensation, both methods achieved results comparableto state-of-the-art reconstructions, suggesting the deep learning model addressed some data-driven method limitations. However, the motion corrected outputs did not exhibit significantimprovements in image quality over state-of-the-art standards. / Positronemissionstomografi (PET) är fundamentalt inom medicinsk avbildning men påverkasav artefakter orsakade av fysiologiska rörelser, framför allt andning. Dessa artefakter påverkarbildkvaliteten negativt och försvårar korrekt attenueringskorrigering. För att motverka dettakan tekniker för rörelsekorrigering tillämpas. Dessa innefattar gating-tekniker där PET-dataförst synkroniseras med andningscykeln för att därefter segmenterateras i olika så kalladegater som representerar en specifick respiratorisk fas. Vidare kan en 3D djupinlärningsmodellanvändas för att korrigera för rörelserna mellan gaterna, vilket optimerar användningen av allinsamlad data. Denna studie implementerade och undersökte två gating-tekniker: en externenhetsbaserad metod och en datadriven ”centroid-of-distribution (COD)” spår-algoritm, samtanalyserade hur dessa tekniker påverkar prestandan av bildregistreringsmodellen. Utifrånanalysen av kliniska data från fyra patienter visade sig metoden med den externa enhetenvara överlägsen den datadrivna metoden, som hade svårigheter i verkliga patient-situationer.Trots detta visade bildregistreringsmodellen potential att delvis kompensera för den datadrivnametodens begränsningar, då resultatet från båda strategeierna var jämförbara med befintligaklinisk bildrekonstruktion. Dock kunde ingen markant förbättring i bildkvalitet urskiljas av derörelsekorrigerade bilderna jämfört med nuvarande toppstandard.

Cancer is one of the major causes of worldwide mortality. Imaging plays a vital role in the staging, follow-up, and evaluation of therapeutic response in cancer patients. Whole-body (WB) magnetic resonance imaging (MRI), as a non-ionizing imaging technique, is a promising procedure to assess tumor spreading in a single examination. New MRI technological developments now enable the application of diffusion-weighted imaging (DWI) of the entire body. DWI reflects the random motion of water molecules and provides functional information of body tissues. DWI can be quantified with the use of the apparent diffusion coefficient (ADC). The aim of this dissertation was to demonstrate the value of WB MRI including DWI in cancer patients. WB MRI including DWI, 18F-NaF PET/CT, and bone scintigraphy was performed on 49 patients with newly diagnosed, high-risk prostate cancer, for the purpose of detecting bone metastases. WB DWI showed higher specificity, but lower sensitivity compared to 18F-NaF PET/CT. In addition, WB MRI including DWI, and CT of the chest and abdomen was performed in 23 patients with malignant melanoma. We concluded that WB MRI could not completely supplant CT for the staging of malignant melanoma, especially with respect to the detection of lesions in the chest region. In this study, WB MRI and DWI were able to detect more bone lesions compared to CT, and showed several lesions outside the CT field of view, reinforcing the advantage of whole-body examination. WB MRI, including DWI, was performed in 71 patients with testicular cancer. This modality demonstrated its feasibility for use in the follow-up of such patients. WB MRI, including DWI, and 18F-FDG PET-CT, were carried out in 50 patients with malignant lymphoma. Both these imaging modalities proved to be promising approaches for predicting clinical outcomes and discriminating between different subtypes of lymphomas. In conclusion, WB MRI, including DWI, is an evolving technique that is continuing to undergo technical refinement. Standardization of image acquisition and analysis will be invaluable, allowing for more accurate comparison between studies, and widespread application of this technique in clinical practice. Both WB MRI, including DWI and PET/CT, have their particular strengths and weaknesses in the evaluation of metastatic disease. DWI and PET/CT are different functional techniques, so that combinations of these techniques may provide complementary and more comprehensive information of tumor tissue.

Introduction. Fused Positron Emission Tomography and Computed Tomography (PET/CT) is an emerging investigative tool in cardiovascular disease that provides an imaging-based quantification of pathophysiological processes of interest. The purpose of this thesis was to study the application of PET to identify fundamental pathophysiological processes driving 3 forms of cardiovascular disease: aortic stenosis, myocardial infarction, and atherosclerosis. Methods. Aortic Stenosis. Patients with a spectrum of calcific aortic valve disease (n=121) who underwent PET-CT imaging for the identification of valvular calcification (18Ffluoride) and inflammation (18F-fluorodeoxyglucose, 18F-FDG) underwent serial imaging and clinical follow-up over 2 years. Baseline imaging findings were compared with echocardiographic and CT markers of disease progression and clinical outcome. Myocardial Infarction. Patients underwent PET-CT imaging with 18F-fluciclatide (a novel αvβ3-selective radiotracer highlighting active angiogenesis, inflammation and fibrosis) after ST-segment elevation MI (n=21), alongside stable patients with chronic total occlusion (CTO) of a major coronary vessel (n=7), and healthy volunteers (n=9). Myocardial radiotracer uptake was compared with clinical and cardiac magnetic resonance imaging (CMR) markers of infarction and remodeling. Atherosclerosis. Patients with a spectrum of atherosclerotic disease categorized as stable or unstable (recent MI) underwent PET/CT imaging with 18F-fluciclatide (n=46). Thoracic aortic 18F-fluciclatide uptake was compared with aortic atherosclerotic burden quantified by CT plaque thickness, plaque volume and calcium scoring. Histological validation. Tissue from the aortic valve, myocardium and carotid arteries of study subjects was acquired and examined ex vivo using histology and autoradiography. Results. Aortic Stenosis. Baseline valvular 18F-fluoride uptake correlated strongly with the rate of progression in AVC (r=0.80, p < 0.001) and with haemodynamic progression (mean aortic valve gradient r=0.32, p=0.001). It emerged as independently associated with clinical outcome after age and sex-adjustment (HR 1.55 [1.33-1.81], p < 0.001). 18F-FDG demonstrated moderate correlations with disease progression as assessed by CT (r=0.43, p=0.001) and echocardiography (18F-FDG r=0.30, p=0.001), and was associated with clinical outcomes independent of age and sex (HR 1.35 [1.16-1.58], p < 0.001). Valvular 18F-fluoride uptake correlated with immunohistochemical markers of calcification activity. There was no correlation between 18F-FDG uptake and inflammation. Myocardial Infarction. 18F-Fluciclatide binding was demonstrated in ex vivo peri-infarct myocardium and uptake was increased in vivo at sites of acute infarction compared to remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17 respectively, p < 0.001) and myocardium of healthy volunteers (TBRmean 1.34±0.22 vs 0.70±0.03; p < 0.001). There was no 18F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with myocardial activity similar to healthy volunteers (TBRmean 0.71±0.06 vs. 0.70±0.03,p=0.83). 18F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index ≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, p < 0.001), was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery. Atherosclerosis. 18F-Fluciclatide vascular binding ex vivo co-localised with regions of increased αvβ3 integrin expression, and markers of inflammation and angiogenesis. 18F-Fluciclatide uptake in vivo correlated with measures of aortic atherosclerotic burden: plaque thickness (r=0.57, p=0.001), total plaque volume (r=0.56, p=0.001) and the CT aortic calcium score (r=0.37, p=0.01). Patients with recent MI had greater aortic 18F-fluciclatide uptake than those with stable disease (TBRmax 1.33 vs 1.21, p=0.01). Conclusions. In a range of cardiovascular diseases, PET-CT can provide insights into key pathophysiological processes, guide patient risk stratification and prognosis, and identify important biomarkers of disease activity that can be used for the development of future therapeutic interventions.

Cervical cancer remains the third most commonly diagnosed gynecological malignancy in the United States and throughout the world despite being potentially preventable. Patients diagnosed with cervical cancer may develop local recurrence in the cervix and surrounding structures (vaginal apex, parametrial, or paracervical), regional recurrence in pelvic lymph nodes, distant metastasis, or a combination of all. The management of such treatment outcomes has not been subject to rigorous investigation. Therefore, there is a need for studies and clinical trials that focus on decision making to support the choice of the best treatment modality that leads to the minimal number of adverse treatment outcomes. Medical imaging plays a vital role in the initial diagnosis, staging, and guiding treatment decisions for cancer patients. Positron Emission Tomography-Computed Tomography (PET/CT) hybrid scanner has proven to be a primary functional imaging modality in the oncology clinic. A typical oncological application of PET/CT aims to examine the whole body for high tracer uptake as a sign of tumorous lesions or metastasis using 18F-Fluoro-2-deoxy-D-glucose (18F-FDG). This radiopharmaceutical has been proven to be useful for the quantitative determination of regional glucose metabolism localized in the brain, heart, bladder, and, fortunately, in tumors. Currently, 18F-FDG measured on PET is the prominent radiotracer in cancer staging and follow-up imaging. In the –omics1 era, mining data to derive inherent information about a system has influenced the medical field, especially oncological imaging. The process of radiomics involves high throughput analysis of medical images to extract a large number of quantified features that are presented as a decision supporting tool for clinicians in terms of various clinical tasks such as staging, prediction, and prognosis. In recent studies, the focus of radiomics has exceeded the whole-tumor analysis to include the quantification of habitats, sub-regions within the tumor volume defined based on specific criteria, with the intent to investigate the diversity extent of the intratumor heterogeneity as robust descriptors and predictors of clinicopathological factors. The presented work is a retrospective analysis of a cohort consisting of pretreatment Positron Emission Tomography and Computed Tomography (PET/CT) hybrid scans of cervical cancer patients consecutively treated with radiochemotherapy. We extracted radiomic features from the primary cervical tumor volumes, and voxel intensity-based features from tumor habitats to analyze the tumors’ heterogeneity based on 18Flourodeoxyglocuse (18F-FDG) uptake of PET, and Hounsfield Units (HU) of CT to obtain useful tumor information, which might be associated with treatment outcomes. To our knowledge, a limited number of studies have focused on investigating the potential role of radiomic features on cervical cancer PET/CT images. Briefly, the workflow of this study consisted of investigating parameters that might affect radiomic features predictive performance by evaluating the reproducibility of radiomic features extracted from 18F-FDG PET images for segmentation methods, gray levels discretization, and PET reconstruction algorithms. Afterward, we used these features to predict cervical treatment outcomes after radiochemotherapy. Due to the use of human data, this research study acquired the approval of the institutional review board (IRB) at the University of South Florida.

Background: In an ongoing study conducted at Karolinska Institutet &amp; Karolinska University Hospital, Positron Emission Tomography (PET)/Computed Tomography (CT) scans are performed on patients with tibia fractures and deformations treated with Taylor Spatial Frames (TSFs) in order to monitor their bone remodeling progress. Each patients receive an administration of approximately 2 MBq/kg bodyweight of Na18F associated with PET scans on two sessions, six and twelve weeks after the attachment of the TSF. These PET/CT scans provide information about the progress of the healing bone and can be used to estimate the optimal time point for de-attachment of the TSF. The Standardized Uptake Value (SUV) is used as a measure of the rate of bone remodeling for these patients, however, there is a need for verification of this practice by a method independent of the PET scanner. Furthermore, information regarding the biodistribution of the Na18F throughout the body of these patients and the effects of the TSF on the CT scan X‑rays is required. Additionally, an investigation of alternative methods that have the potential to provide similar information with a lower absorbed dose to the patients is desirable. Materials and methods: Thermoluminescent Dosimeters (TLDs) were attached on the skin at the position of the heart, urinary bladder, femurs, fracture, and the contralateral tibia of twelve patients during the first one hour and five minutes after the administration of the Na18F. Additional TLD measurements were performed during the CT scan of two of these patients. From the PET scan images, SUVs at the fracture site of these patients were collected. An investigation of the possibility of exploiting the “naturally” occurring bone seeking radionuclide Strontium-90 (90Sr) in the human body to gain information about the fracture site was undertaken. Using a 90Sr source, three different detection techniques were evaluated and a practical methodology for in vivo measurements on the tibia fracture patients was developed. As it was concluded that TLD based measurements were the most suitable technique for this purpose, and it was tested on five patients with tibia fractures. Results: From the collected TLD data, it was concluded that for these patients the urinary bladder is the organ receiving the greatest amount of absorbed dose and the organ most affected as the administered activity exceeds 2 MBq/kg. On average, a three times higher surface dose was measured on the tibia fracture compared to the un-fractured tibia. A linear relationship between the surface dose and SUVmax was shown. A strong positive correlation between the activity concentration at the fracture site and the amount of injected activity was found, and it was demonstrated that this also affects the SUVs. For patients who were administered different amounts of Na18F for the two PET scans, maximum activity concentrationwas less affected than mean activity concentration. It was concluded that TSF’s effect on the scatter of the X-rays to organs higher up in the body is negligible. Regarding “naturally” occurring 90Sr in the human body, no higher activity at the fractured tibia compared to the non‑fractured tibia could be found. Conclusions: This project assessed the accumulation of Na18F in the fracture site of patients treated with TSF by a method independent of the PET scanner. The methodology of using SUVs as an indicator for bone remodeling was verified. It was shown that the uptake of Na18F by the fracture site is strongly correlated to the amount of injected activity. The importance of considering the amount of injected activity when evaluating and comparing SUVs was highlighted. In vivo measurements using LiF:Mn TLDs did not indicate any quantifiable higher concentration of 90Sr at the fracture in the tibia bone.

The present thesis is focused on the development and application of narrow scanned high energy photon beam for radiation therapy. The introduction of physically and biologically optimized intensity modulated radiation therapy (IMRT) requires a flexible and accurate dose delivery method to maximize the treatment outcome. Narrow scanned photon beams is a fast option for IMRT since it is not dependent on mechanically moving heavy collimator leafs and largely independent of the complexity of the desired dose distribution. Scanned photon beams can be produced by scanning an electron beam of low emittance, incident on a thin bremsstrahlung target of low atomic number. The large fraction of high energy electrons that are transmitted through the target has to be removed by a strong purging magnet. In the thesis a strong purging magnet, coupled with a magnetic scanning magnet, is presented for an intrinsic electron energy of 50 - 75 MeV and a source to isocenter distance of 75 cm. The available scan area at isocenter can be as large as 43 x 40 cm2 for an incident electron energy of 50 MeV and 28 x 40 cm2 at 75 MeV. By modifying the existing treatment head of the racetrack microtron MM50, it was possible to experimentally produce relevant dose distributions with interesting properties from 50 MV scanned narrow photon beams while deflecting the transmitted electrons onto a simplified electron stopper. The deflection of the transmitted electrons was studied both experimentally and by the Monte Carlo method. With high energy photons, treatment verification is possible through PET-CT imaging of the positron annihilations induced by photonuclear reactions in the patient. Narrow scanned high energy photon beams is the ideal beam quality since the activation efficiency and the effective photon energy will be more uniform than the filtered photon beam from a full range bremsstrahlung target. The induced 11C activity 50 MV by scanned narrow photon beams was measured using PET-CT imaging and compared with Monte Carlo simulations. The combination of fast flexible dose delivery with treatment verification using PET-CT imaging makes narrow high energy scanned photon beams a very interesting treatment modality for biologically optimized adaptive radiation therapy. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Submitted.

Submitted by Renorbio (renorbioba@ufba.br) on 2017-07-06T14:52:02Z No. of bitstreams: 1 DEFINIÇÃO DE PROTOCOLOS DE PET-CT (defesa) (FINAL-crip).pdf: 2587129 bytes, checksum: ee0e1f775d6ec22cc7dc9aead962cb89 (MD5) / Approved for entry into archive by Uillis de Assis Santos (uillis.assis@ufba.br) on 2017-07-06T15:21:56Z (GMT) No. of bitstreams: 1 DEFINIÇÃO DE PROTOCOLOS DE PET-CT (defesa) (FINAL-crip).pdf: 2587129 bytes, checksum: ee0e1f775d6ec22cc7dc9aead962cb89 (MD5) / Made available in DSpace on 2017-07-06T15:21:56Z (GMT). No. of bitstreams: 1 DEFINIÇÃO DE PROTOCOLOS DE PET-CT (defesa) (FINAL-crip).pdf: 2587129 bytes, checksum: ee0e1f775d6ec22cc7dc9aead962cb89 (MD5) / A crescente disponibilidade de equipamentos de alta performance, software de reconstrução e métodos quantitativos tem proporcionado novas oportunidades para a melhoria das imagens e gestão dos pacientes. A busca por estratégias eficazes de redução da dose, sem comprometer o diagnóstico, tem se tornado uma parte essencial para otimização de protocolos. Este estudo descreve um método para se obter alta qualidade das imagens clínicas com aquisições de PET/CT com FDG-F18 relacionando a geometria do paciente, regime de dose, protocolos de aquisição de imagens e técnicas de processamento. Dados de aquisição de 58 indivíduos adultos de ambos os sexos foram avaliados retrospectivamente. Imagens do fígado foram adquiridas em modo-lista durante 360 s em um equipamento de PET/CT de alto desempenho. As imagens foram reconstruídas com intervalo de 30s. Foram avaliadas as relações entre os diferentes parâmetros indivíduo-dependentes, qualidade dos dados e da imagem. A taxa de ruído equivalente e o coeficiente de variação foram utilizados como métricas. Com base nas relações mais fortes entre estes parâmetros, foram identificados protocolos de aquisição otimizados e regimes de administração de atividade para diferentes métodos de reconstrução. Foi encontrada a relação mais forte da qualidade dos dados entre NECR e a massa corpórea, sendo o aumento da massa corpórea capaz de causar uma redução exponencial do NECR (R² = 0,72). Encontramos também uma relação entre qualidade de imagem e massa corpórea (R² = 0,82 para reconstruções OSEM3D e R² = 0,86 nas reconstruções PSF, p <0,001). Se um regime linear dose é utilizado, aumentando FDG- F18 proporcionalmente a massa, a qualidade da imagem degrada com o aumento da massa corpórea do paciente quando um mesmo tempo de aquisição é usado. A adoção de protocolos diferentes para três faixas de massa corporal (<60 kg, 60-90 kg, > 90 kg) na rotina clínica permite melhor qualidade de imagem com tanto PSF e métodos de reconstrução OSEM3D. Em conclusão, foi demonstrada neste estudo uma metodologia para determinar o tempo de aquisição das imagens, a partir da atividade de FDG-F18 administrada, a fim de obter imagens de alto padrão de qualidade. Este método oferece uma oportunidade para se realizar procedimentos de PET/CT mais custo-eficazes e com redução da dose de radiação. / The increasing availability of high performance equipment, reconstruction software and quantitative methods have provided new opportunities to improve image capturing and management of patients. Currently, new and effective strategies that reduce dose exposure, yet do not compromise diagnostics are underway and have become essential to protocol optimization. This study describes a method to achieve consistent clinical image quality in 18F-FDG scans accounting for patient habitus, dose regimen, image acquisition and processing techniques. Data was acquired from 58 adults, male and female, which were evaluated retrospectively. Images of the liver were acquired in list-mode during 360 s on a high-performance PET/CT scanner. The scans were reconstructed at incremental 30 s intervals and correlations between different patient-dependent parameters (PDP) and image and data quality were evaluated. Patient Noise Equivalent Count Rate (NECR) and coefficient of variation (CV) were used as metrics in our analysis. Based on the strongest PDP correlations, optimized acquisition protocols and dose regimens were identified for different reconstruction methods. Results: The strongest correlation of patient data quality was found between NECR per unit activity (NECRN) and body mass (BM): increasing BM causes NECRN to decrease exponentially (R² = 0.72). Patient body mass was also found to be the strongest PDP determinant of image quality (R² = 0.82 in OSEM3D and R² = 0.86 in PSF, p < 0.001). If a linear dose regimen is used, increasing 18F-FDG proportionally to BM, image quality degrades with increasing patient body mass when standard acquisition time is used. The adoption of different schemes for three body mass ranges (< 60 kg, 60–90 kg, > 90 kg) in clinical routine allows improved image quality with both PSF and OSEM3D reconstruction methods. In conclusion, this study has demonstrated a methodology for determining the time of image acquisition from FDG- F18 activity administered in order to obtain high quality standard images. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures, and achieve better patient management and cost-effective operations and at a reduced radiation dose.