Caractérisation des tumeurs et de leur évolution en TEP/TDM au F-FDG pour le suivi thérapeutique

La Tomographie par Emission de Positons (TEP) au Fluoro-déoxyglucose marqué au Fluor 18 ( F-FDG), analogue du glucose, permet d'obtenir une image de la consommation de glucose dans l'organisme. La plupart des foyers tumoraux présentant une consommation excessive de glucose, son utilisation en oncologie permet d'améliorer la prise en charge des patients en diminuant le temps nécessaire pour évaluer l'efficacité des traitements tels que la chimiothérapie et la radiothérapie. Mon projet de recherche visait à proposer et améliorer des méthodes de quantification en TEP au F-FDG afin de caractériser au mieux l'évolution métabolique des volumes tumoraux.De nombreux facteurs biaisent la quantification en TEP. Parmi eux, l'Effet de Volume Partiel (EVP) reste difficile à corriger, notamment à cause de la faible résolution spatiale des images TEP. Afin de déterminer l'impact de la correction de l EVP sur l évaluation des réponses des tumeurs, une étude sur données simulées par Monte Carlo a tout d abord été effectuée. Cette étude a été complétée par l analyse de données TEP/TDM (Tomodensitométrie) acquises chez 40 patients atteints de cancers colorectaux métastatiques (CCM), traités par chimiothérapie à l'Institut Jules Bordet (Bruxelles). L analyse de 101 tumeurs a montré que les critères tels que le SUV, n incluant pas de correction de l'EVP, et qui reflètent alors le volume tumoral et son activité, prédisaient mieux l évolution tumorale que les critères corrigés de l EVP. Compte tenus des résultats prometteurs récents de méthodes de caractérisation de l hétérogénéité de la fixation du FDG dans les tumeurs, un second volet de notre travail a consisté à étudier l intérêt de la prise en compte de la texture dans le cadre du suivi thérapeutique. L application de l analyse de texture aux cas de CCM étudiés précédemment n a pas permis de démontrer une valeur ajoutée des indices de texture par rapport aux index quantitatifs couramment employés en clinique. Nous avons montré que cette conclusion s expliquait en partie par la non-robustesse des indices de texture vis-à-vis des paramètres impliqués dans leur mesure. Nous avons enfin cherché à évaluer une méthode d Analyse Factorielle de Séquences d Images Médicales (AFSIM), appliquée au contexte du suivi thérapeutique, pour caractériser l évolution tumorale tout au long du traitement. Cette étude a porté sur 9 séries de 4 à 6 examens TEP/TDM de patients traités par radiothérapie au Centre Hospitalier Universitaire Henri Becquerel de Rouen. Outre l information visuelle globale apportée par cette méthode, l analyse quantitative des résultats obtenus a permis de caractériser l hétérogénéité de la réponse vue par l AFSIM. L échec des index classiques, provenant entre autres de leur incapacité à distinguer les processus inflammatoires de l activité métabolique tumorale, a permis de monter la valeur ajoutée de l AFSIM par rapport aux index tels que le SUV maximal ou moyen.Positron Emission Tomography (PET) using F-FluoroDeoxyGlucose ( F-FDG), a radiolabelled analogue of the glucose, is used to get an image of the glucose consumption in the body. As most tumor masses show a high glucose consumption, PET is widely used in oncology for diagnosis and patient monitoring. In the context of patient monitoring, the motivation is to decrease the time interval needed to assess treatment (radiotherapy or chemotherapy efficieny) compared to therapeutic follow-up based only on anatomic imaging only (Computed Tomography or Magnetic Resonance Imaging). My research project aimed at proposing and improving quantitative methods in FDG-PET to better characterize tumor evolution.In PET, many factors affect the accuracy of parameters estimated from the images. Among them, Partial Volume Effect (PVE) remains difficult to correct, mainly due to the low spatial resolution of PET images. To determine the impact of PVE on treatment response evaluation, a preliminary study was performed using Monte Carlo simulated PET scans. An additional study was conducted based on the analysis of the PET/CT (Computed Tomography) data of 40 Metastatic Colorectal Cancer (MCC) patients treated with chemotherapy at the Jules Bordet Institute (Brussels, Belgium). The analysis of the 101 tumors showed that criteria such as the Standardized Uptake Value (SUV), which does not include PVE correction, were better predictors of tumors evolutions than PVE corrected criteria. This is because without PVE correction, SUV includes information on both metabolic volume and metabolic activity, which are two relevant pieces of information to characterize the tumor. A second part of our work was to study the potential of tumor texture analysis in patient monitoring, following promising results reported in the literature. Texture analysis was applied to the MMC patients data previously mentioned but did allow to a better segregation of tumors responses as compared to indices currently used in the clinics. We found that this was partly due to the lack of robustness of the textures indices.Finally, we evaluated a Factor Analysis in Medical Images Series (FAMIS) method to characterize tumor evolution during treatment. This study focused on 9 series of 4 to 6 PET/CT scans acquired all along the radiotherapy/radio-chemotherapy of patients treated at the Centre Hospitalier Universitaire Henri Becquerel (Rouen, France). In addition to the rich visual information brought by this method, a quantitative analysis of the results made it possible to characterize response heterogeneity as seen using FAMIS. In particular, FAMIS clearly demonstrated the occurrence of inflammatory processes. In addition, due to the low metabolic activity of the tumors at the end of the treatment, many conventional indices could not describe the tumor changes, while FAMIS gave a full assessment of the tumor change over time.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

A critical analysis of the role of testosterone in erectile function: From pathophysiology to treatment - A systematic review

Context: Androgen modulation of erectile function (EF) is widely accepted. However, the use of testosterone replacement therapy (TRT) in men with erectile dysfunction (ED) has generated an unprecedented debate. Objective: To summarize the relevant data on the incidence, diagnosis, and management of ED coexisting with hypogonadism and to develop a pathophysiology-based treatment algorithm. Evidence acquisition: We reviewed the relevant medical literature, with a particular emphasis on original molecular studies, prospective observational data, and randomized controlled trials performed in the past 20 yr. Evidence synthesis: Testosterone modulates nearly every component involved in EF, from pelvic ganglions to smooth muscle and the endothelial cells of the corpora cavernosa. It also regulates the timing of the erectile process as a function of sexual desire, coordinating penile erection with sex. Epidemiologic studies confirm the significant overlap of hypogonadism and ED; however, most guidelines do not consider the differential diagnosis of hypogonadism or the relevance of subclinical disease. Various clinical tools can help the physician to assess and restore androgen levels in men with ED. Special attention is given to fertility-sparing treatments, due to the increasing number of older men desiring fatherhood. The simultaneous use of phosphodiesterase type 5 inhibitors (PDE5-Is) and TRT has recently been questioned. Originally proposed as a salvage therapy for nonresponders to PDE5-Is, this approach has been inappropriately transformed into a combination therapy. Clinical data are consistent when reinterpreted in the proper framework, whereas molecular evidence remains controversial. Conclusions: A body of molecular and clinical evidence supports the use of TRT in hypogonadal patients with ED, although the benefit-risk ratio is uncertain in advanced age. Critical appraisal of this evidence enabled the development of a pathophysiology-oriented algorithm designed to avoid inappropriate treatments and support whether to start with TRT, PDE5-I only, or both. Apparently divergent findings are reconciled when TRT is correctly indicated. An improved diagnosis and individualized management is desirable in light of the many available options. © 2013 European Association of Urology

Description de la femelle de Stomopteryx flavipalpella Jaeckh, 1959 (Lepidoptera, Gelechiidae)

Buvat Roger, Nel Jacques. Description de la femelle de Stomopteryx flavipalpella Jaeckh, 1959 (Lepidoptera, Gelechiidae). In: Bulletin de la Société entomologique de France, volume 99 (2), juin 1994. p. 126