Дисертації з теми "PET/CT Scan"

Orientadores: Gustavo Antonio de Souza, Sophie Françoise Mauricette Derchain
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O exame PET/CT com FDG-18F é um método de diagnóstico por imagem, útil em oncologia. O câncer de ovário é o câncer ginecológico de maior letalidade, sendo a terceira neoplasia mais freqüente do trato genital feminino no Brasil. O objetivo deste estudo foi avaliar o PET/CT com FDG-18F em pacientes com suspeita de recidiva de carcinoma de ovário e descrever a distribuição das lesões encontradas. Sujeitos e Métodos: Foram incluídas neste estudo retrospectivo 45 mulheres com suspeita de recidiva de câncer de ovário. As pacientes foram encaminhadas para clínica PET/CT Campinas de novembro 2006 até novembro de 2010, por aumento do CA-125, sintomas clínicos e/ou alterações na ultrassonografia (US), tomografia (TC) ou ressonância (RM). Para a confirmação da recidiva, 15 pacientes foram submetidas à cirurgia e 30 foram acompanhadas por um período mínimo de seis meses. Resultados: Quarenta e duas pacientes foram diagnosticadas com recidiva e três não apresentaram evidência de doença durante o período de acompanhamento. O CA-125 estava aumentado em 34 pacientes, 14 apresentavam sintomas clínicos e 23 tinham alterações em US, TC ou RM. Trinta e oito pacientes apresentaram o exame PET/CT positivo, todas com recidiva confirmada. Três pacientes apresentaram achados inconclusivos na PET/CT, todas com doença. Quatro exames de PET/CT eram negativos, sendo que uma paciente teve recidiva confirmada e as demais permaneceram sem evidências de doença durante o acompanhamento. Onze pacientes com CA-125 elevado apresentavam resultados de US, TC ou RM normais. Todas tiveram doença confirmada, sendo que a PET/CT detectou recidiva em nove e foi inconclusiva em duas. Entre as onze pacientes com CA- 125 normal, foram detectadas metástases na PET/CT em oito. As metástases mais freqüentes foram diagnosticadas em linfonodos, sendo localizados na região pélvica e abdominal em 30 pacientes, na região torácica em 16 e em sete pacientes, na região cervical. Implantes pélvicos e abdominais foram detectados em 27 pacientes. Outros locais de metástases foram fígado (n=7), baço (n=2), pleura (n=2), pulmão (n=2) e osso (n=2). O exame PET/CT detectou lesões não suspeitas em 20 das 45 pacientes (44,4%). A PET/CT detectou um novo tumor primário de tireoide numa paciente sem recidiva de carcinoma de ovário. Conclusão: O exame PET/CT foi útil para avaliação da extensão da recidiva de carcinoma de ovário. A recidiva acometeu mais freqüentemente os linfonodos, sendo a maioria localizada na região pélvica e abdominal. Metástases em linfonodos torácicos foram um achado freqüente nesta população estudada
Abstract: 18F-FDG PET/CT is a diagnostic method useful in oncology. Ovarian cancer is the third most frequent cancer of the female genital tract in Brazil, however, it has the highest mortality of all gynecological cancers. The aim of this study was to evaluate the use of 18F-FDG PET/CT in patients with suspected ovarian cancer recurrence and describe the distribution of metastasis. Methods: Fortyfive female patients with suspicion of ovarian cancer recurrence were included in this retrospective study. They were referred to PET/CT Campinas clinic from November 2006 to November 2010, because of elevated CA-125, clinical suspicion of ovarian cancer recurrence, or alterations detected on ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI). PET/CT results were compared with histologic findings (n=15) or clinical followup for at least six months (n=30). Results: Forty-two patients were confirmed with ovarian cancer recurrence. Three patients remained free of disease during clinical follow-up. CA-125 was elevated in a total of 34 patients, 14 patients had clinical symptoms of disease and 23 presented with alterations on US, CT and MRI. Thirty eight patients had positive PET/CT scan, all with confirmed disease. Three patients had equivocal PET/CT findings and in all three, recurrence was confirmed. Four patients had negative PET/CT scan: one with confirmed recurrence and three free from disease during follow-up. Nine out of 11 patients with elevated CA-125 and normal conventional imaging had positive PET/CT scan and two had equivocal findings. There were eleven patients with normal CA-125 levels, eight presented with positive PET/CT scan. Lymph nodes were the most frequent site of relapse of disease, most being in the pelvic/abdominal region (n=30) and others in thoracic (n=16) or cervical region (n=7). Peritoneal implants were found in 27 patients. Distant sites of metastasis included liver (n=6), spleen (n=2), pleura (n=2), lung (n=2) and bone (n=2). PET/CT detected unsuspected lesions in 20/45 patients (44.4%). One patient with PET/CT negative for ovarian cancer recurrence was diagnosed with primary papillary carcinoma of the thyroid. Conclusion: 18F-FDG PET/CT was a useful tool for evaluation of the extension of ovarian cancer recurrence. In the current series, lymph nodes were the most frequent site of relapse of disease, with supradiaphragmatic lymph node metastasis in large number of cases
Mestrado
Oncologia Ginecológica e Mamária
Mestre em Ciências da Saúde

Establece la relación del valor de la eficiencia de los cristales con la cuantificación del SUV. El estudio es de tipo observacional, cuantitativo, longitudinal, prospectivo y de nivel relacional. Se realizaron 50 controles de calidad obteniendo el ECF diario, así como el SUVmáx., temperatura ambiental, temperatura del gantry y humedad relativa en la mañana, medio día y tarde diariamente. Proceso realizado en PET SCAN PERÚ – CAMN durante el año 2018. Los valores del Factor de la Eficiencia de los Cristales (ECF) están entre 2,775 y 2,803. El Valor de Captación Estándar (SUVmáx.) varía entre 0,9921 y 1,0869. La temperatura ambiental se localiza en el rango de 17,67 °C y 21, 07 °C. Los valores de la temperatura del gantry se ubican entre 34,67 y 36,67. Mientras que la humedad relativa está entre 39,33% y 52%. Se concluye que existe correlación inversamente proporcional entre el Factor de la Eficiencia de los Cristales (ECF) y el Valor de Captación Estándar (SUVmáx.), por lo cual, se sugiere continuar con los controles de calidad diario. Además, la temperatura influye indirectamente al SUV máx.
Tesis

The elderly population (those aged 65 years or older) in Hong Kong is expected to increase from approximately 13% in 2009 to 28% by 2039. With this rapid growth of elders, it raises attention to prevent and treat chronic diseases of aging. Dementia is particularly concerned because the short term memory loss and other cognitive malfunctions lead to a loss of independent function that has a extensive impact on individuals, families, health and social welfare systems. Currently over 70,000 people endure dementia in Hong Kong and expect quadruple rises by 2036. In order to cope with these diseases, accurate diagnosis is very useful, particular at early stage when treatment outcomes are most effective. Numerous studies have found that AD and other dementias could alter brain metabolism significantly. AD patients usually present the posterior cingulated and parietotemporal cortices hypometabolism and spread into the frontal lobes in advanced disease. In contrast, FTD patients show manifestly hypometabolism in the frontal and anterior temporal cortices, while DLB patients present hypometabolism in the posterior brain comprising primarily the parietoocipital regions. Theoretically, 18F-FDG PET scan can help in the early diagnosis of AD and other dementias by highlighting these decreased FDG uptake cortex regions before MRI or CT scans can detect any structural damage. This is a retrospective chart review study. Patients who had received FDG brain PET-CT scan previously had their regional brain metabolism quantitated using a software call Cortex-ID and clinical laboratory tests. The study is * To develop a Neural Network (NN) that can diagnose the various types of dementia using Brain PET-CT scan, testing accuracy of NN versus an expert and, * To see if the NN can correlate with the clinical severity of the disease as reflected by MMSE score. Finally, three neural networks have been designed and they all fulfill all the required specifications.
published_or_final_version
Diagnostic Radiology
Master
Master of Medical Sciences

Abstract Introduction Knowledge about the oncologic status of pelvic lymph nodes forms an essential and integral part in the management of women with uterine cancer. Lymph node status is part of endometrial cancer staging and plays an important role in primary treatment and adjuvant treatment planning and prognosis in women with cervical cancer. Current practice in the management of uterine cancers involves systematic full pelvic lymphadenectomy, mainly to determine the oncological status of the nodes, as there is no high-quality evidence suggesting a therapeutic effect attributable to lymphadenectomy. Imaging in the form of computed tomography (CT) scans and magnetic resonance (MRI) scan is not accurate to determine pelvic lymph node status in women with uterine cancer. Functional scans such as 18Fluoro-deoxy-glucose positron emission/computed tomography (FDG-PET/CT) scan might provide better access in this setting. Sentinel lymph node biopsy (SLNB) procedures, specifically the SLNB algorithm, have been proposed as a safe and accurate alternative procedure to full systematic lymphadenectomy in women with uterine cancers. It has also been proposed as a better alternative than complete omission of lymphadenectomy in women with presumed low risk early stage endometrial cancer. SLNB procedures might also be able to detect higher rates of lymph node metastases with the detection of micro metastases following pathological ultrastaging The presence or absence of high risk human papilloma virus (hrHPV) DNA in sentinel lymph nodes of women with cervical cancer has also been suggested to be a useful adjunct to frozen section examination (FSE) in assisting with determination of the status of the non-sentinel nodes. Some data suggest the combination of negative FSE and absence of hrHPV accurately predict the absence of metastases. South African women have high prevalence of human immunodeficiency virus infection, tuberculosis (TB) and pelvic inflammatory disease (PID). All these infections involve the lymphatic system. Data on SLNB procedures are form well-developed countries with different disease burdens and socioeconomic profiles, and there is no data from women living in low-resource settings. Aims This study aimed to determine the efficacy of and performance of FDG-PET/CT scan and SLNB and SLNB algorithm in accurately predicting the regional lymph node status of the pelvis in women with early stage cervical cancer and presumed early stage endometrial cancer. It also aimed to investigate the usefulness of HPV DNA testing of sentinel nodes in women with cervical cancer. Population and setting This was a prospective observational study performed in the Gynaecologic Oncology Unit at the Kalafong Provincial Tertiary Hospital and Steve Biko Academic Hospital. Patients aged 18 years and older, with operable stages cervical cancer and presumed early stage endometrial cancer willing and able to provide informed consent were eligible for inclusion. Materials and methods Sentinel node mapping was done using methylene blue (MB) and indocyanine green (ICG) injected into the cervix after induction of anaesthesia at the time of primary surgery. 99Technetium nanocolloid (99Tc) was administered one day pre-operatively followed by lymphoscintigram. FDG-PET/CT scans were performed prior to surgery. Following mapping and removal, FSE, HPV DNA typing, haematoxylin and eosin (H&E) examination with ultrastaging on H&E negative specimens were performed on the SLNs. All patients underwent systematic full pelvic lymphadenectomy and appropriate cancer surgery. Results One hundred patients were prospectively recruited to the study and results of 94 patients were available for analysis. SNL detection rate of the whole group was 60.6% with bilateral detection 29.2%. Twenty-four patients (25.5%) had pelvic metastases. Sixty-five percent of women with cervical cancer in this study were HIV positive, and the SLN detection rate in this group was 65% with bilateral detection rate of 30%. The detection rate was significantly higher in women without nodal metastases, those with stage IA2 – IB2 disease, with tumour less than 2 cm and women with BMI less than 25 kg/m2. HIV status, history of TB, PID and the presence of adhesions did not influence the SLN detection rate. The sentinel lymph node biopsy algorithm has a sensitivity of 100%, NPV of 100% and a false negative rate of 0% in this study. The SLNB procedure identified two women with only micro metastases (15.4%). These women would not have been identified with systematic lymphadenectomy and H&E examination. Indocyanine green and the combination of methylene blue and 99Technetium nanocolloid had significantly better sentinel node detection rates compared to methylene blue alone FDG-PET/CT scan was performed in 28 women. The sensitivity, specificity, positive and negative predictive values of FDG-PET/CT scans to accurately predict nodal status, were 66.67%, 82%, 30.77% and 95.38% respectively. The false negative rate of FDG-PET/CT scans was 33.3%. The sensitivity, specificity, PPV and NPV for FSE in this cohort was 66.67%, 100%, 100% and 96.05% respectively. The FNR for FSE was 23.1%. Thirty-two patients with cervical cancer had tumour and SLN hrHPV DNA data. The sensitivity, specificity, PPV and NPV of sentinel lymph node HPV DNA to predict metastases was 50%, 69.6%, 30 and 84.2% respectively with a false negative rate of 42.8%. Conclusions Although the SLN detection rate was lower compared to the published literature, the SLNB algorithm performed excellently in this group of patients of which the majority were HIV-infected. The SLNB procedure can be considered as a treatment option in selected cases in the management of women with early stage endometrial and cervical cancer. PET/CT should not be used as part of the primary diagnosis and staging investigations in women with uterine cancer, and is recommended only in selected cases for initial staging of locally advanced cervical cancer being considered for radical chemoradiation therapy. In this study, testing for the presence of hrHPV DNA in the sentinel lymph nodes was not useful as a predictor of pelvic lymph node status. The combination of negative FSE and negative hrHPV in the SLNs did not have a reliable negative predictive value for the absence of pelvic nodal metastases.
Thesis (PhD)--University of Pretoria, 2017.
Obstetrics and Gynaecology
PhD
Unrestricted

L’objectif du travail de cette thèse est la contribution au développement de nouvelles techniques dans le domaine dessystèmes de détection sans marqueur pour une utilisation dans trois domaines vitaux de la santé en utilisant des capteursinnovants et peu coûteux. Pour la réalisation de nos objectifs nous avons eu recours principalement à de l’électroniqueembarquées et du traitement du signal en utilisant le capteur Kinect. Des résultats encourageants ont été obtenus et sontprésentés tout au long de cette thèse. Dans la première partie de ce travail, nous présentons un nouveau système desurveillance visuelle sans marqueur en temps réel pour détecter et suivre les personnes âgées et surveiller leurs activitésdans leur environnement intérieur en utilisant un réseau de capteurs Kinect. Le système identifie également l’événementde chute des personnes âgées sous surveillance. Dans la deuxième partie nous utilisons également le capteur Kinectmais cette fois ci pour la détection sans marqueur des mouvements de la tête d’un patient lors d’un examen utilisant LaTomographie par Emission de Positons (CT/PET) du cerveau. Ce travail est basé sur la compensation de la dégradationde l’image TEP due aux mouvements de la tête du patient. Pour nos essais un cobaye dit « fantôme » a été réalisé,les résultats sur le fantôme sont prometteur ce qui a donné lieu à un test sur un vrai patient volontaire. Les résultatsfinaux montrent l’efficacité de ce nouveau système. La troisième partie du travail présente la mise en oeuvre d’un nouveausystème intelligent pour contrôler un fauteuil roulant électrique par des mouvements spéciaux de la tête toujours sansmarqueur. Un algorithme adapté est conçu pour détecter en continu les degrés des mouvements du visage en utilisant lecapteur Kinect. Fautes de fauteuil roulant électrique, le système a été testé sur un véhicule radio commandé
The objective of the work of this thesis is the contribution in developing novel technical methods in the field of marker-lesssensing systems for use in three vital health areas by using new inexpensive sensors. Several scientific areas are involvedin achieving our objective such as; electronics and signal processing by using the Kinect sensor. Encouraging results wereachieved as presented throughout this thesis. In the first part of this work we present a new real-time marker-less visualsurveillance system for detecting and tracking seniors and monitoring their activities in the indoor environment by usingnetwork of Kinect sensors. The system also identifies the fall event with the elderly. In the second part, we present anew approach for a marker-less movement detection system for influential head movements in the brain Positron EmissionTomography imaging (CT/PET) by employing the Kinect sensor. This work addresses the compensation of the PET imagedegradation due to subject’s head movements. A developed particular phantom and volunteer studies were carried out.The experimental results show the effectiveness of this new system. The third part of the work presents the design andimplementation of a new smart system for controlling an electric wheelchair by special mark-less head movements. Anadaptable algorithm is designed to continuously detect the rotation degrees of the face pose using the Kinect sensor inreal-time that are interpreted as controlling signals through a hardware interface for the electric wheelchair actuators

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.

A characteristic feature of Chronic Obstructive Pulmonary Disease (COPD) is an abnormal inflammatory response in the lungs to inhaled particles or gases. The ability to assess and monitor this response in the lungs of COPD patients is important for understanding the pathogenic mechanisms, but also provides a measure of the activity of the disease. Disease activity is more likely to relate to lung inflammation rather than the degree of airflow limitation as measured by the FEV1. Preliminary studies have shown the 18F fluorodeoxyglucose positron emission tomography (18F FDG-PET) signal, as a measure of lung inflammation, is quantifiable in the lungs and is increased in COPD patients compared to controls. However, the methodology requires standardisation and any further enhancement of the methodology would improve its application to assess inflammation in the lungs. I investigated various methods of assessing FDG uptake in the lungs and assessed the reproducibility of these methods, and particularly evaluated whether the data was reproducible or not in the COPD patients (smokers and ex-smokers). This data was then compared with a group of healthy controls to assess the role of dynamic 18F FDG-PET scanning as a surrogate marker of lung inflammation. My data showed a good reproducibility of all methods of assessing FDG lung uptake. However, using conventional Patlak analysis, the uptake was not statistically different between COPD and the control group. Encouraging results in favour of COPD patients were nonetheless shown using compartmental methods of assessing the FDG lung uptake, suggesting the need to correct for the effect of air and blood (tissue fraction effect) when assessing this in a highly vascular organ like the lungs. A prospective study analysis involving a bigger cohort of COPD patients would be desirable to investigate this further.

L’objectif global de cette thèse était d’étudier, à partir de la cohorte des patients du centre de référence PXE du CHU d’Angers, différente aspects du phénotype cardiovasculaire (CV) du PXE. Ainsi, dans un premier travail, nous avons pu montrer dans l’étude GOCAPXE, que les calcifications ectopiques seraient un processus actif pouvant être détecté par une imagerie moléculaire utilisant un traceur spécifique de l’activité ostéoblastique, le 18-Fluorure de Sodium (18F-NaF); que ce processus était détectable avant même que ces calcifications ne soient visibles par les techniques d’imageries classiques; que ce processus était localisé aux zones habituellement lésées dans le PXE : les plis de flexion et le cou pour la peau et l’artère fémorale superficielle pour le vaisseau. Cette technique mériterait d’être validée dans une étude longitudinale et son rôle en tant biomarqueur diagnostique et de suivi serait ainsi envisageable. Le deuxième travail de cette thèse a été d’étudier les conséquences morphologiques et fonctionnelles d’une augmentation chronique de la pression artérielle chez les patients PXE. Cette question était pertinente car dans la littérature, la question d’une hypertension artérielle (HTA) chez les PXE reste controversée. Nous avons ainsi montré pour la première fois que dans un modèle d’HTA induite par le Deoxycorticostérone (DOCA)-Salt chez la souris Abcc6-/- cette augmentation de la pression artérielle induisait un remodelage CV avec à la fois de la fibrose et des calcifications dystrophiques. Les résultats de cette étude suggèrent la nécessité d’un contrôle optimal de la pression artérielle chez les patients PXE. Le troisième travail de cette thèse a été de caractériser une lésion de la carotide interne détectée avec une fréquence élevée dans la cohorte angevine. Nous avons pu montrer que cette anomalie était une hypoplasie de la carotide interne d’origine probablement congénitale. Chez les patients de la cohorte angevine, cette lésion était associée à des anévrismes intracrâniens mais nous n’avons pas retrouvé d’association avec la survenue d’accident vasculaire cérébral. Ainsi, les résultats de cette étude invitent les praticiens prenant en charge des patients PXE à la rechercher systématiquement dans le bilan vasculaire d’un patient PXE. Si une telle lésion est retrouvée, une imagerie vasculaire intracrânienne devrait être proposée à la recherche d’anévrismes et leur prise en charge discuté en concertation multidisciplinaire. Enfin, le dernier travail a permis de montrer qu’un traitement systémique par le Thiosulfate de Sodium (STS), utilisé dans la calciphylaxie rénale, était efficace sur la régression des calcifications artérielles et cutanées chez une jeune garçon ayant un phénotype CV gravissime résultant de la combinaison délétères de plusieurs gènes pathogènes du spectre PXE Ce traitement mériterait d’être validé dans un essai thérapeutique chez l’humain mais aussi la démonstration de ses mécanismes d’action dans le modèle murin Abcc6-/-. Nous suggérons d’utiliser ce traitement en cas de PXE sévère et rapidement progressif notamment sur le plan vasculaire. Au terme de ce travail de thèse, nous avons montré que le gène ABCC6 était impliqué dans le remodelage vasculaire à la fois au niveau développemental (Hypoplasie Carotidienne) mais aussi acquis (Fibrose, Calcification Cardiaque Dystrophique). Nous avons montré aussi que les calcifications dans le PXE étaient tissus et localisations spécifiques, que ces calcifications étaient actives. Enfin nous avons ouvert la porte à un traitement des formes graves du PXE avec le Thiosulfate de Sodium. Une approche thérapeutique multimodale ciblant plusieurs mécanismes concourant aux calcifications seraient judicieux à évaluer dans les futurs essais cliniques
Since the discovery of the ABCC6 gene in 2000, mutations are at the origin of PseudoxanthomeElastic (PXE), knowledge of genetics, pathophysiology, phenotypic characterizations have has mademajor advances, notably with the Discovery in 2013 of the fundamental role of Pyrophosphateinorganic (PPi) as a deficient anti‐calcifying factor in patients. The overall goal of this thesis was tostudy, from the cohort of patients at the center of PXE reference of the CHU d'Angers, differentaspects of cardiovascular phenotype (CV) of PXE. Thus, in a first work, we were able to show in thestudy GOCAPXE, that ectopic calcifications would be a active process that can be detected by imagingUsing a specific activity tracer Osteoblastic, 18‐sodium fluoride (18F‐NaF); that this process wasdetectable even before these calcifications are not visible by conventional imaging techniques; thatthis process was localized to areas usually injured in the PXE: flexion folds and neck for skin and thesuperficial femoral artery for the vessel. This technique should be validated in a study longitudinaland its role as a diagnostic biomarker In this way, monitoring and monitoring could be considered.The second work of this thesis was to study the morphological consequences and functional of achronic increase in blood pressure in PXE patients. This question was relevant because in theliterature, the question of a high blood pressure (hypertension) in PXE remains controversial. Wehave thus shown for the first time that in a model of HTA induced by the Deoxycorticosterone(DOCA)‐Salt in Abcc6‐/‐ this increase in blood pressure led to a CV remodeling with both fibrosis andcalcifications dystrophic. The results of this study suggest need for optimal control of blood pressurein patients. The third work of this thesis was to characterize a lesion of the internal carotid detectedwith high frequency in the Angevine cohort. We have could show that this abnormality washypoplasia of the Probably congenital internal carotid. In the patients of the angevine cohort, thislesion was associated with intracranial aneurysms but we have not found in association with theoccurrence of vascular accident brain. Thus, the results of this study invite practitioners supportingPXE patients to search for it systematically in the vascular balance of a PXE patient. If such a lesion isfound, vascular imaging Intracranial should be proposed to research Aneurysms and theirmanagement discussed in consultation multidisciplinary. Finally, the latest work has made it possibleto show that systemic treatment with Thiosulphate Sodium (STS), used in renal calciphylaxia, waseffective on the regression of arterial calcifications and skin in a young boy with a phenotype CVGravel resulting from the deleterious combination of several pathogenic genes of the PXE spectrumThis treatment would deserve be validated in a human therapeutic trial but also the demonstrationof its mechanisms of action in the Abcc6‐/‐murin model. We suggest using this treatment for severeand rapidly progressive PXE especially on the vascular plane.At the end of this thesis work, we showed that the ABCC6 gene was involved in vascular remodelingat both at the developmental level (Carotid Hypoplasia) but also acquired (Fibrosis, CardiacCalcification Dystrophic). We also showed that calcifications in PXE were tissues and locationsspecific, that these calcifications were active. Finally we have opened the door to a treatment ofsevere forms of PXE with Sodium Thiosulphate. An approach multimodal therapy targeting multiplemechanisms this would be useful to evaluate in future clinical trials

Nowadays, lung cancer assessment is a complex and tedious task mainly per- formed by radiological visual inspection of suspicious pulmonary nodules, using computed tomography (CT) scan images taken to patients over time. Several computational tools relying on conventional artificial intelligence and computer vision algorithms have been proposed for supporting lung cancer de- tection and classification. These solutions mostly rely on the analysis of indi- vidual lung CT images of patients and on the use of hand-crafted image de- scriptors. Unfortunately, this makes them unable to cope with the complexity and variability of the problem. Recently, the advent of deep learning has led to a major breakthrough in the medical image domain, outperforming conven- tional approaches. Despite recent promising achievements in nodule detection, segmentation, and lung cancer classification, radiologists are still reluctant to use these solutions in their day-to-day clinical practice. One of the main rea- sons is that current solutions do not provide support to automatic analysis of the temporal evolution of lung tumours. The difficulty to collect and annotate longitudinal lung CT cases to train models may partially explain the lack of deep learning studies that address this issue. In this dissertation, we investigate how to automatically provide lung can- cer assessment through deep learning algorithms and computer vision pipelines, especially taking into consideration the temporal evolution of the pulmonary nodules. To this end, our first goal consisted on obtaining accurate methods for lung cancer assessment (diagnostic ground truth) based on individual lung CT images. Since these types of labels are expensive and difficult to collect (e.g. usually after biopsy), we proposed to train different deep learning models, based on 3D convolutional neural networks (CNN), to predict nodule malig- nancy based on radiologist visual inspection annotations (which are reasonable to obtain). These classifiers were built based on ground truth consisting of the nodule malignancy, the position and the size of the nodules to classify. Next, we evaluated different ways of synthesizing the knowledge embedded by the nodule malignancy neural network, into an end-to-end pipeline aimed to detect pul- monary nodules and predict lung cancer at the patient level, given a lung CT image. The positive results confirmed the convenience of using CNNs for mod- elling nodule malignancy, according to radiologists, for the automatic prediction of lung cancer. Next, we focused on the analysis of lung CT image series. Thus, we first faced the problem of automatically re-identifying pulmonary nodules from dif- ferent lung CT scans of the same patient. To do this, we present a novel method based on a Siamese neural network (SNN) to rank similarity between nodules, overpassing the need for image registration. This change of paradigm avoided introducing potentially erroneous image deformations and provided computa- tionally faster results. Different configurations of the SNN were examined, in- cluding the application of transfer learning, using different loss functions, and the combination of several feature maps of different network levels. This method obtained state-of-the-art performances for nodule matching both in an isolated manner and embedded in an end-to-end nodule growth detection pipeline. Afterwards, we moved to the core problem of supporting radiologists in the longitudinal management of lung cancer. For this purpose, we created a novel end-to-end deep learning pipeline, composed of four stages that completely au- tomatize from the detection of nodules to the classification of cancer, through the detection of growth in the nodules. In addition, the pipeline integrated a novel approach for nodule growth detection, which relies on a recent hierarchi- cal probabilistic segmentation network adapted to report uncertainty estimates. Also, a second novel method was introduced for lung cancer nodule classification, integrating into a two stream 3D-CNN the estimated nodule malignancy prob- abilities derived from a pre-trained nodule malignancy network. The pipeline was evaluated in a longitudinal cohort and the reported outcomes (i.e. nodule detection, re-identification, growth quantification, and malignancy prediction) were comparable with state-of-the-art work, focused on solving one or a few of the functionalities of our pipeline. Thereafter, we also investigated how to help clinicians to prescribe more accurate tumour treatments and surgical planning. Thus, we created a novel method to forecast nodule growth given a single image of the nodule. Partic- ularly, the method relied on a hierarchical, probabilistic and generative deep neural network able to produce multiple consistent future segmentations of the nodule at a given time. To do this, the network learned to model the mul- timodal posterior distribution of future lung tumour segmentations by using variational inference and injecting the posterior latent features. Eventually, by applying Monte-Carlo sampling on the outputs of the trained network, we esti- mated the expected tumour growth mean and the uncertainty associated with the prediction. Although further evaluation in a larger cohort would be highly recommended, the proposed methods reported accurate results to adequately support the ra- diological workflow of pulmonary nodule follow-up. Beyond this specific appli- cation, the outlined innovations, such as the methods for integrating CNNs into computer vision pipelines, the re-identification of suspicious regions over time based on SNNs, without the need to warp the inherent image structure, or the proposed deep generative and probabilistic network to model tumour growth considering ambiguous images and label uncertainty, they could be easily appli- cable to other types of cancer (e.g. pancreas), clinical diseases (e.g. Covid-19) or medical applications (e.g. therapy follow-up).
Avui en dia, l’avaluació del càncer de pulmó ´es una tasca complexa i tediosa, principalment realitzada per inspecció visual radiològica de nòduls pulmonars sospitosos, mitjançant imatges de tomografia computada (TC) preses als pacients al llarg del temps. Actualment, existeixen diverses eines computacionals basades en intel·ligència artificial i algorismes de visió per computador per donar suport a la detecció i classificació del càncer de pulmó. Aquestes solucions es basen majoritàriament en l’anàlisi d’imatges individuals de TC pulmonar dels pacients i en l’ús de descriptors d’imatges fets a mà. Malauradament, això les fa incapaces d’afrontar completament la complexitat i la variabilitat del problema. Recentment, l’aparició de l’aprenentatge profund ha permès un gran avenc¸ en el camp de la imatge mèdica. Malgrat els prometedors assoliments en detecció de nòduls, segmentació i classificació del càncer de pulmó, els radiòlegs encara són reticents a utilitzar aquestes solucions en el seu dia a dia. Un dels principals motius ´es que les solucions actuals no proporcionen suport automàtic per analitzar l’evolució temporal dels tumors pulmonars. La dificultat de recopilar i anotar cohorts longitudinals de TC pulmonar poden explicar la manca de treballs d’aprenentatge profund que aborden aquest problema. En aquesta tesi investiguem com abordar el suport automàtic a l’avaluació del càncer de pulmó, construint algoritmes d’aprenentatge profund i pipelines de visió per ordinador que, especialment, tenen en compte l’evolució temporal dels nòduls pulmonars. Així doncs, el nostre primer objectiu va consistir a obtenir mètodes precisos per a l’avaluació del càncer de pulmó basats en imatges de CT pulmonar individuals. Atès que aquests tipus d’etiquetes són costoses i difícils d’obtenir (per exemple, després d’una biòpsia), vam dissenyar diferents xarxes neuronals profundes, basades en xarxes de convolució 3D (CNN), per predir la malignitat dels nòduls basada en la inspecció visual dels radiòlegs (més senzilles de recol.lectar). A continuació, vàrem avaluar diferents maneres de sintetitzar aquest coneixement representat en la xarxa neuronal de malignitat, en una pipeline destinada a proporcionar predicció del càncer de pulmó a nivell de pacient, donada una imatge de TC pulmonar. Els resultats positius van confirmar la conveniència d’utilitzar CNN per modelar la malignitat dels nòduls, segons els radiòlegs, per a la predicció automàtica del càncer de pulmó. Seguidament, vam dirigir la nostra investigació cap a l’anàlisi de sèries d’imatges de TC pulmonar. Per tant, ens vam enfrontar primer a la reidentificació automàtica de nòduls pulmonars de diferents tomografies pulmonars. Per fer-ho, vam proposar utilitzar xarxes neuronals siameses (SNN) per classificar la similitud entre nòduls, superant la necessitat de registre d’imatges. Aquest canvi de paradigma va evitar possibles pertorbacions de la imatge i va proporcionar resultats computacionalment més ràpids. Es van examinar diferents configuracions del SNN convencional, que van des de l’aplicació de l’aprenentatge de transferència, utilitzant diferents funcions de pèrdua, fins a la combinació de diversos mapes de característiques de diferents nivells de xarxa. Aquest mètode va obtenir resultats d’estat de la tècnica per reidentificar nòduls de manera aïllada, i de forma integrada en una pipeline per a la quantificació de creixement de nòduls. A més, vam abordar el problema de donar suport als radiòlegs en la gestió longitudinal del càncer de pulmó. Amb aquesta finalitat, vam proposar una nova pipeline d’aprenentatge profund, composta de quatre etapes que s’automatitzen completament i que van des de la detecció de nòduls fins a la classificació del càncer, passant per la detecció del creixement dels nòduls. A més, la pipeline va integrar un nou enfocament per a la detecció del creixement dels nòduls, que es basava en una recent xarxa de segmentació probabilística jeràrquica adaptada per informar estimacions d’incertesa. A més, es va introduir un segon mètode per a la classificació dels nòduls del càncer de pulmó, que integrava en una xarxa 3D-CNN de dos fluxos les probabilitats estimades de malignitat dels nòduls derivades de la xarxa pre-entrenada de malignitat dels nòduls. La pipeline es va avaluar en una cohort longitudinal i va informar rendiments comparables a l’estat de la tècnica utilitzats individualment o en pipelines però amb menys components que la proposada. Finalment, també vam investigar com ajudar els metges a prescriure de forma més acurada tractaments tumorals i planificacions quirúrgiques més precises. Amb aquesta finalitat, hem realitzat un nou mètode per predir el creixement dels nòduls donada una única imatge del nòdul. Particularment, el mètode es basa en una xarxa neuronal profunda jeràrquica, probabilística i generativa capaç de produir múltiples segmentacions de nòduls futurs consistents del nòdul en un moment determinat. Per fer-ho, la xarxa aprèn a modelar la distribució posterior multimodal de futures segmentacions de tumors pulmonars mitjançant la utilització d’inferència variacional i la injecció de les característiques latents posteriors. Finalment, aplicant el mostreig de Monte-Carlo a les sortides de la xarxa, podem estimar la mitjana de creixement del tumor i la incertesa associada a la predicció. Tot i que es recomanable una avaluació posterior en una cohort més gran, els mètodes proposats en aquest treball han informat resultats prou precisos per donar suport adequadament al flux de treball radiològic del seguiment dels nòduls pulmonars. Més enllà d’aquesta aplicació especifica, les innovacions presentades com, per exemple, els mètodes per integrar les xarxes CNN a pipelines de visió per ordinador, la reidentificació de regions sospitoses al llarg del temps basades en SNN, sense la necessitat de deformar l’estructura de la imatge inherent o la xarxa probabilística per modelar el creixement del tumor tenint en compte imatges ambigües i la incertesa en les prediccions, podrien ser fàcilment aplicables a altres tipus de càncer (per exemple, pàncrees), malalties clíniques (per exemple, Covid-19) o aplicacions mèdiques (per exemple, seguiment de la teràpia).

碩士
東海大學
工業工程與經營資訊學系
102
Positron molecular imaging (FDG-PET) is an important diagnostic tool for the diagnosis of cancer, heart disease and neurological disorders and other mental disorders. However, the domestic hospitals usually only have one positron molecular imaging scanner. With increased numbers of people with cancer, relaxation of the scope of national health insurance, and more robust concept of public health screening molecular imaging positron demand will be doubled. Clinically, the procedure take at least 2-3 hours to 5-6 hours. The Inspection schedule, waiting time and machine utilization will affect the satisfaction of patient and the profits of medical institutes. In this study, through the use of Lean tools to identify value-added and non-value added time; collect all patients of the time record of examination from January 2013 to January 2014. Then analyze data and draw VSM (Value Stream Mapping) by group to find controlled factors and uncontrolled factors. Not only clarify factors which associated with value-added and non-value added time, but also investigate the factors and the suggestion of improvement. We obtained four factors which wasted time ranged from 64 to 85 minutes via analysis of Value stream mapping, and check if physician attributes and disease positions extremely affect the chance of secondary imaging positron or not. The average exam time of patients receive one more scanning will increase 85 minutes.

Fluorine-18 Fluorodeoxyglucose positron emission tomography-computed tomography (F-18 FDG PET-CT) is now established in the staging, restaging and therapy response monitoring of Hodgkin’s lymphoma (HL) and high grade Non-Hodgkin’s lymphoma (HG NHL), specifically for nodal disease and extra-nodal disease excluding the bone marrow. The role of FDG PET-CT for evaluating bone marrow involvement in HL and HG NHL has not been established yet. There are however several publications on this subject but no consensus has been reached. Bone marrow trephine biopsy (BMB) is the gold standard for bone marrow assessment in lymphoma. Although the occurrence of adverse effects is uncommon, BMB is an invasive procedure that may induce anxiety in patients. A retrospective review of FDG PET-CT bone marrow findings of HL patients referred for a staging scan from June 2008 to January 2014 was done, these findings were compared to the BMB findings also done as part of initial staging. The findings of 55 patients were reviewed analysed.

碩士
國立高雄大學
資訊工程學系碩士班
100
In recent years, as stereoscopic display technology is applied more and more widely, more images tend to use it to provide the depth information that 2D images cannot bring. In this thesis, we present stereoscopic images using perspective projection of lung and display 3D effect on active shutter glasses system. Stereoscopic images are created by a calculation of standardized uptake value (SUV) on positron emission tomography (PET) and overlapped with computer tomography (CT). Than shown the difference with traditional 2D MIP image. Stereoscopic image using perspective and the others works. Applied stereoscopic technology to medical image processing to expend our vision from 2D to 3D and helpful for diagnosis such as improve diagnosis efficiency or surgical path planning.

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 study was done at Steve Biko Academic hospital to determine the influence that respiratory gating will have on target volumes used in radiotherapy treatment planning. The primary objective was to compare target volumes of respiratory gated scans to ungated scans and to determine whether it will be meaningful to permanently implement a 4D respiratory gating system on CT scanners in the South African public health sector and to use these images for target volume delineation in radiotherapy planning. The study consisted of three sections. In the first section, 4D respiratory gated CT images were obtained and delineated with 4D software. The full-inspiration and full-expiration phases of the gated scans were then fused to obtain ungated images which were also delineated. The gross tumor volumes (GTVs) of the gated phases were compared to the ungated GTVs, and found that on average the volumes decreased by 14.63% with a standard deviation of 7.96% when gating was applied. Yet another aim was to determine the influence that 4D imaging will have on radiotherapy treatment planning. One of the 4D study sets was imported to the XIO treatment planning system where IMRT treatment plans were created on both the gated and ungated scans. The plans conformed to the treatment aims and restrictions when clinical parameters such as DVHs were used to evaluate it. The planned target volume coverage differed by less than 1% between the gated and the ungated plans, but significant dose reductions to the OARs of up to 32.65% to the contralateral lung were recorded on the gated plan. In the second section of this study, respiratory gated CT scans were simulated by applying the breath-hold technique to lung cancer patients. The technique was applied during full-inspiration which fundamentally represents the maximum peak of the sinusoidal respiratory waveform. An ungated scan was also acquired during normal respiration. The clinical target volumes (CTVs) were identified on both scans by three oncologists and the average CTVs were compared. It was found that the CTVs decreased significantly by an average of 14.33%. Palliative patients receive parallel opposing field therapy which is planned from 2D films. It is very unlikely that these opposing field sizes will differ when gating is applied. It was therefore concluded that only radical lung patients, which was estimated to be a mere 0.03% of the total radiation therapy patient population, will benefit by implementing respiratory gating or any motion-reduction technique. For the third section of the study, respiratory gated PET scans were acquired on a PET/CT scanner to evaluate external, non-technical parameters that will influence respiratory gating. The results indicated that time and patient participation were not limiting factors. The biggest concerns however were the effectiveness of the gating system, software limitations and the gated results. These problems might be minimized with thorough training on the system. All three sections as well as the financial implications were considered to conclude that it will not be meaningful to implement 4D respiratory gating techniques in the South African public health sector Copyright
Dissertation (MSc)--University of Pretoria, 2013.
Medical Oncology
unrestricted

The quality of the image of 18F-FDG PET/CT scans in overweight patients is commonly degraded. This study evaluates, retrospectively, the relation between SNR, weight and dose injected in 65 patients, with a range of weights from 35 to 120 kg, with scans performed using the Biograph mCT using a standardized protocol in the Nuclear Medicine Department at Radboud University Medical Centre in Nijmegen, The Netherlands. Five ROI’s were made in the liver, assumed to be an organ of homogenous metabolism, at the same location, in five consecutive slices of the PET/CT scans to obtain the mean uptake (signal) values and its standard deviation (noise). The ratio of both gave us the Signal-to- Noise Ratio in the liver. With the help of a spreadsheet, weight, height, SNR and Body Mass Index were calculated and graphs were designed in order to obtain the relation between these factors. The graphs showed that SNR decreases as the body weight and/or BMI increased and also showed that, even though the dose injected increased, the SNR also decreased. This is due to the fact that heavier patients receive higher dose and, as reported, heavier patients have less SNR. These findings suggest that the quality of the images, measured by SNR, that were acquired in heavier patients are worst than thinner patients, even though higher FDG doses are given. With all this taken in consideration, it was necessary to make a new formula to calculate a new dose to give to patients and having a good and constant SNR in every patient. Through mathematic calculations, it was possible to reach to two new equations (power and exponential), which would lead to a SNR from a scan made with a specific reference weight (86 kg was the considered one) which was independent of body mass. The study implies that with these new formulas, patients heavier than the reference weight will receive higher doses and lighter patients will receive less doses. With the median being 86 kg, the new dose and new SNR was calculated and concluded that the quality of the image remains almost constant as the weight increases and the quantity of the necessary FDG remains almost the same, without increasing the costs for the total amount of FDG used in all these patients.

Introduction: Targeted pharmaceuticals for labelling with radio-isotopes for very specific imaging (and possibly later for targeted therapy) play a major role in Theranostics which is currently an important topic in Nuclear Medicine as well as personalised medicine. There was a need for a very specific lung cancer radiopharmaceutical that would specifically be uptaken in integrin 3 expression cells to image patients using a Positron Emission Tomography- Computed Tomography (PET-CT) scanner. Background and problem statement: Cold kits of c (RGDyK)–SCN-Bz-NOTA were kindly donated by Seoul National University (SNU) to help meet Steve Biko Hospital’s need for this type of imaging. These cold kits showed great results internationally in labelling with a 0.1 M 68Ge/68Ga generator (t1/2 of 68Ge and 68Ga are 270.8 days and 67.6 min, respectively). However the same cold kits failed to show reproducible radiolabeling with the 0.6 M generator manufactured under cGMP conditions at iThemba LABS, Cape Town and distributed by IDB Holland, the Netherlands. Materials and methods: There was therefore a need for producing an in-house NOTA-RGD kit that would enable production of clinical 68Ga-NOTA-RGD in high yields from the IDB Holland/iThemba LABS generator. Quality control included ITLC in citric acid to observe labelling efficiency as well as in sodium carbonate to evaluate colloid formation. HPLC was also performed at iThemba LABS as well as Necsa (South African Nuclear Energy Corporation). RGD was obtained from Futurechem, Korea. Kit mass integrity was determined by testing labelling efficiency of 10, 30 and 60 μg of RGD per cold kit. The RGD was buffered with sodium acetate trihydrate. The original kits were dried in a desiccator and in later studies only freeze dried. Manual labelling was also tested. The radiolabelled in-house kit’s ex vivo biodistribution in healthy versus tumour mice were examined by obtaining xenografts. The normal biodistribution was investigated in three vervet monkeys by doing PET-CT scans on a Siemens Biograph TP 40 slice scanner. Results: Cold kit formulation radiolabeling and purification methods were established successfully and SOPs (standard operating procedures) created. HPLC results showed highest radiochemical purity in 60 μg cold kit vials. 68Ga-NOTA-RGD showed increased uptake in tumours of tumour bearing mouse. The cold kit also showed normal distribution according to literature with fast blood clearance and excretion through kidneys into urine, therefore making it a suitable radiopharmaceutical for clinical studies. Conclusion: The in-house prepared cold kit with a 4 month shelf-life was successfully tested in mice and monkeys.
MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014