La notion de cluster désigne l'agrégation dans le temps et/ou l'espace d'évènements. Dans de nombreux domaines, les experts observent certaines agrégations d'évènements et la question se pose de savoir si ces agrégations peuvent être considérées comme normales (le fruit du hasard) ou non. D'un point de vue probabiliste, la normalité peut être décrite par une hypothèse nulle de répartition aléatoire des évènements. La détection de clusters d'évènements est un domaine de la statistique qui s'est particulièrement étendu au cours des dernières décennies. En premier lieu, la communauté scientifique s'est attachée à développer des méthodes dans le cadre unidimensionnel (ex : le temps) puis, par la suite, a étendu ces méthodes au cas multidimensionnel, et notamment bidimensionnel (l'espace). Parmi l'ensemble des méthodes de détection de clusters d'évènements, trois grands types de tests peuvent être distingués. Le premier concerne les tests globaux qui permettent de détecter une tendance globale à l'agrégation, sans pour autant localiser les clusters éventuels. Le deuxième type correspond aux tests focalisés qui sont utilisés lorsque des connaissances a priori permettent de définir un point source (date ou localisation spatiale) et de tester l'agrégation autour de ce dernier. Le troisième type englobe les tests de détection de cluster (ou sans point source défini) qui permettent la localisation, sans connaissance a priori, de clusters d'évènements et le test de leur significativité statistique. Au sein de cette thèse, nous nous sommes focalisés sur cette dernière catégorie et plus particulièrement aux méthodes basées sur les statistiques de scan (ou de balayage). Ces méthodes sont apparues au début des années 1960 et permettent de détecter des clusters d'évènements et de déterminer leur aspect "normal" (le fruit du hasard) ou "anormal". L'étape de détection est réalisée par le balayage (scan) par une fenêtre, dite fenêtre de scan, du domaine d'étude (discret ou continu) dans lequel sont observés les évènements (ex: le temps, l'espace,…). Cette phase de détection conduit à un ensemble de fenêtres définissant chacune un cluster potentiel. Une statistique de scan est une variable aléatoire définie comme la fenêtre comportant le nombre maximum d'évènements observés. Les statistiques de scan sont utilisées comme statistique de test pour vérifier l'indépendance et l'appartenance à une distribution donnée des observations, contre une hypothèse alternative privilégiant l'existence de cluster au sein de la région étudiée. Par ailleurs, la principale difficulté réside dans la détermination de la distribution, sous l'hypothèse nulle, de la statistique de scan. En effet, puisqu'elle est définie comme le maximum d'une suite de variables aléatoires dépendantes, la dépendance étant due au recouvrement des différentes fenêtres de scan, il n'existe que dans de très rares cas de figure des solutions explicites. Aussi, un pan de la littérature est axé sur le développement de méthodes (formules exactes et surtout approximations) permettant de déterminer la distribution des statistiques de scan. Par ailleurs, dans le cadre bidimensionnel, la fenêtre de scan peut prendre différentes formes géométriques (rectangulaire, circulaire,…) qui pourraient avoir une influence sur l'approximation de la distribution de la statistique de scan. Cependant, à notre connaissance, aucune étude n'a évalué cette influence. Dans le cadre spatial, les statistiques de scan spatiales développées par M. Kulldorff s'imposent comme étant, de loin, les méthodes les plus utilisées par la communauté scientifique. Le principe de ces méthodes résident dans le fait de scanner le domaine d'étude avec des fenêtres de forme circulaire et de sélectionner le cluster le plus probable comme celui maximisant un test de rapport de vraisemblance. [...] / The concept of cluster means the aggregation of events in time and / or space. In many areas, experts observe certain aggregations of events and the question arises whether these aggregations can be considered normal (by chance) or not. From a probabilistic point of view, normality can be described by a null hypothesis of random distribution of events.The detection of clusters of events is an area of statistics that has particularly spread over the past decades. First, the scientific community has focused on developing methods for the one-dimensional framework (eg time) and then subsequently extended these methods to the multidimensional case, especially two-dimensional (space). Of all the methods for detecting clusters of events, three major types of tests can be distinguished. The first type concerns global tests that detect an overall tendency to aggregation, without locating any clusters. The second type corresponds to the focused tests that are used when a priori knowledge is used to define a point source (date or spatial location) and to test the aggregation around it. The third type includes the cluster detection tests that allow localization, without a priori, cluster of events and test their statistical significance. In this thesis, we focused on the latter category, especially to methods based on scan statistics.These methods have emerged in the early 1960s and can detect clusters of events and determine their \"normal" appearance (coincidence) or "abnormal". The detection step is performed by scanning through a window, namely scanning window, the studied area (discrete or continuous, time, space), in which the events are observed. This detection step leads to a set of windows, each defining a potential cluster. A scan statistic is a random variable defined as the window with the maximum number of events observed.Scan statistics are used as a test statistic to check the independence and belonging to a given distribution of observations, against an alternative hypothesis supporting the existence of cluster within the studied region. Moreover, the main difficulty lies in determining the distribution of scan statistics under the null hypothesis. Indeed, since it is defined as the maximum of a sequence of dependent random variables, the dependence is due to the recovery of different windows scan, it exists only in very rare cases explicit solutions. Also, a piece of literature is focused on the development of methods (exact formulas and approximations) to determine the distribution of scan statistics. Moreover, in the two-dimensional framework, the scanning window can take various geometric shapes (rectangular, circular, ...) that could have an influence on the approximation of the distribution of the scan statistic. However, to our knowledge, no study has evaluated this influence. In the spatial context, the spatial scan statistics developed by M. Kulldorff are the most commonly used methods for spatial cluster detection. The principle of these methods lies in scanning the studied area with circular windows and selecting the most likely cluster maximizing a likelihood ratio test statistic. Statistical inference of the latter is achieved through Monte Carlo simulations. However, in the case of huge databases and / or when important accuracy of the critical probability associated with the detected cluster is required, Monte Carlo simulations are extremely time-consuming.First , we evaluated the influence of the scanning window shape on the distribution of two dimensional discrete scan statistics. A simulation study performed with squared, rectangular and discrete circle scanning windows has highlighted the fact that the distributions of the associated scan statistics are very close each to other but significantly different. The power of the scan statistics is related to the shape of the scanning window and that of the existing cluster under alternative hypothesis through out a simulation study. [...]

No description available.

La dysplasie cérébelleuse est une anomalie du développement tissulaire intéressant principalement le cervelet et résultant en une anomalie focale ou diffuse de son architecture macroscopique et microscopique. Plusieurs travaux antérieurs ont bien documenté sa caractérisation morphologique à l'imagerie par résonance magnétique (IRM). Cependant, le retentissement de cette malformation, parfois associée à d'autres anomalies développementales du système nerveux central (SNC), sur le développement et le fonctionnement cognitifs est mal connu et peu documenté. Dans le but d'étudier les corrélations anatomo-fonctionnelles de cette pathologie constitutionnelle du cervelet, par le biais de l'approche des altérations neuropsychologiques, génétiques et, fonctionnelles associées, ainsi que par l'approche neuroanatomique, nous avons dirigé nos travaux dans quatre axes principaux et sur trois types de population distinctes. Le premier axe a concerné l'évaluation du profil neuropsychologique et du suivi chez dix enfants porteurs d'une dysplasie cérébelleuse isolée (DCI). Nous avons pu observer chez ces enfants une grande diversité de l'expression neuropsychologique de la DCI, depuis l'efficience normale jusqu'au retard mental sévère, sans corrélation avec le degré de dysplasie. D'autre part, au cours du suivi de ces enfants, nous avons observé une hétérogénéité d'évolution à caractère imprédictible, avec l'émergence des certaines fonctions dans l'axe du langage notamment. Le deuxième axe a porté sur l'investigation fonctionnelle du SNC par l'étude de la consommation cérébrale du fluorodeoxyglucose par Tomographie à émission de positons (TEP-FDG) chez six enfants porteurs d'une DCI. Les résultats ont montré, au sein du cervelet, un aspect normal dans les dysplasies mineures (limitées au vermis), un hypométabolisme des zones dysplasiques (corrélé à l'extension anatomique), et un isométabolisme au cortex dans les hétérotopies. Toutefois, ces anomalies de captation du glucose n'étaient pas corrélées au dysfonctionnement cognitif. Le troisième axe était d'approcher les corrélations génétiques, dans l'hypothèse d'un lien physiopathologique embryologique entre le cerveau et le cervelet, dans les dysplasies cérébelleuses associées (DCA) aux Lissencéphalies (cerveaux lisses). La caractérisation génétique relativement bien définie des Lissencéphalies nous a permis d'identifier des gènes de la migration neuronale et axonale (RELN et VLDRL) comme étant significativement associés aux dysplasies cérébelleuses, en dehors des dystrophies musculaires congénitales impliquant les gènes de la O-glycosylation. Le quatrième axe a été de rechercher chez des volontaires sains les marqueurs neuroanatomiques potentiels des altérations cognitives dans les dysplasies cérébelleuses, partant de l'hypothèse selon laquelle, une malformation isolée du cervelet induirait des anomalies anatomiques détectables en imagerie par tenseur de diffusion (DTI), sur les voies de projections cérébello-corticales, vraisemblablement impliquées dans la contribution du cervelet au développement et à l'exécution des fonctions supérieures. Ce travail nous a permis d'individualiser et de quantifier les projections cérébello-corticales préfrontales et pariétales chez tous les sujets sains. Ainsi, nos travaux nous ont permis: (i) de mieux établir les anomalies neuropsychologiques propres aux DCI et leur caractère hétérogène, tant au diagnostic qu'à l'évolution, (ii) de corréler la dysplasie cérébelleuse à des anomalies de la consommation cérébrale du glucose et par conséquent de son fonctionnement, (iii) de suggérer d'axer chez ces patients la recherche d'anomalies génétiques sous-jacentes vers les gènes impliqués dans la migration neuronale et axonale, et enfin, (iv) d'obtenir des marqueurs neuroanatomiques que nous pourrons appliquer aux patients pour étudier la possibilité de l'altération des vois de projections cérébello-corticales. De nombreuses perspectives d'imagerie avancée anatomique et fonctionnelle du SNC appliquées aux dysplasies cérébelleuses ont été ainsi ouvertes. / Cerebellar dysplasia is a developmental anomaly involving mainly the cerebellum, resulting in a focal or diffuse macroscopic and microscopic disruption of the tissue architecture. Previous studies have well documented the magnetic resonance imaging (MRI) features of this malformation. However, the impact of cerebellar dysplasia, which may be associated with other developmental anomalies of the central nervous system (CNS), on the cognitive development and function, is ill known and poorly documented. We aimed to study the structural functional correlations in this cerebellar malformation, by investigating the neuropsychological, genetic and, functional disturbances associated as well as the neuroanatomical approach. Our work was conducted in 4 directions including 3 different populations. First, we assessed the neuropsychological profile and the follow-up of children with isolated cerebellar dysplasia (ICD). We observed I this population a wide range of neuropsychological expression of ICD, from normal efficiency to severe mental retardation, without no correlation with the degree of dysplasia. Moreover, during the follow-up of these children, we noticed the unpredictable heterogeneity of the cognitive evolution with the emergence in some cases of certain function such as language. Secondly, we investigated the CNS function using fluorodeoxyglucose positron emission tomography (FDG-PET) in six children with ICD. The results showed within the cerebellum a normal aspect in patients with minor dysplasia (restricted to the vermis), a hypometabolism in dysplastic zones (correlating with the anatomical extent), and a metabolism similar to that of the cortex in heterotopias. Nevertheless, these functional disturbances were not correlated with neuropsychological impairement. Thirdly, we attempted to investigate the genetic abnormalities leading to the embryology physiopathology basis of cerebellar dysplasias associated (CDA) with Lissencephalies (smooth brain). The quite well characterized genetics of human brain lissencephalies have allowed us to identify some genes involved in the neuronal and axonal migration process (RELN and VLDLR) to be significantly associated with cerebellar dysplasia, not including CDA in muscular dystrophy syndromes related to O-glycosylation defects. Fourthly, we aimed to find in normal volunteers the neuroanatomical potential markers of cognitive disturbances associated with cerebellar dysplasia, on the hypothesis that an isolated cerebellar malformation could induce some anomalies on the pathways of cerebello-cortical projections, detectable by diffusion tensor imaging (DTI). These pathways are presumably involved in the cerebellar implication in higher functions. This work has allowed us to visualize and quantify selectively the cerebello-cortical projections to the prefrontal and parietal cortices in the normal human brain. Thus, our overall results have permitted: (i) to clearly assess the neuropsychological disturbances associated with ICD and their heterogeneity, both at the time of diagnosis and at the follow-up, (ii) to correlate the cerebellar dysplasia to brain glucose uptake differences and subsequently to brain dysfunction, (iii) to suggest some precise genetic analyses in neuronal and axonal migration pathways, and eventually, (iv) to obtain some anatomical markers which we can apply to dysplastic patients in order to assess the putative disruption of cerebello-cortical projections. Thereby, our results have opened numerous perspectives in applying advanced anatomical and functional neuroimaging techniques to the cerebellar dysplastic patients.

No description available.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Radiation Therapy has been one of the most common techniques to treat various types of cancers, in particular is Head and Neck Cancer (HNC) which accounts for three percent of all cancers in the United States. During the treatment procedure, the patient is immobilized using immobilization devices such as the full head face mask, bite blocks, stereotactic frame, etc. to get accurate location of tumor. The disadvantage of these devices is that they are very uncomfortable to the patient especially people suffering from Post-Traumatic Stress Disorder (PTSD) and claustrophobia who cannot wear any confined masked system such as the full head mask or bite block during the treatment procedure. To mitigate this problem, there has been a lot of research in modifying such immobilizing devices without neglecting the accurate location of tumor. To this end, the research presented in this thesis focuses on developing a mask less system with accurately locating the position of tumor using the technique of coordinate transformation at the same time fulfilling the three important characteristics: • Comfort • Accuracy • Low price Such a system is comfortable to the patient because no confining mask system is used and we choose minimal contact points on the patient for fixing the patient. Traditionally, such type of cancer treatment is carried out in two stages: Diagnosis stage, which identifies the location of the tumor and the external markers and the Treatment stage where the tumor is treated with immobilization device being common in both the stages. In the new system, the immobilization devices vary at the two stages. The head position is monitored by using pressure sensor assembly where spring and pressure sensor setup detects the amount and direction of head deviation. We also prepare a customized 3D printed nose bridge part for extra referencing in the treatment room. Also, it is important that we use material for our immobilization devices which does not contain any metal and MRI compatible. Once the patient lies down on the treatment couch and is immobilized using the immobilization devices, then tumor location is calculated using the theory of coordinate transformation and transformation matrix in the Diagnosis and Treatment Stage. To validate the system, simulation of immobilization devices used in the new design was carried out using ANSYS Workbench 15.0 and LS-Dyna software’s Explicit Dynamics method. The simulation for the head-fixing device showed a deflection of ±0.1974 mm with respect to machine isocenter with a load of 60 N, which is lower than the customer requirement of ±3 mm with respect to machine isocenter of head deviation. The material used for the external markers for patient positioning was selected to be polyetheretherketone (PEEK) which is a radiolucent and widely used MRI compatible material. The system also takes into consideration the effect of weight loss, which is one of the drawbacks of the current systems. Although still in the development stage, this mask less system holds to be the next new variety of immobilization devices that are comfortable to the patient and less expensive to be implemented in future cancer treatment practices.

Neste trabalho investigamos o comportamento da técnica de varredura z no caso onde a fase do campo elétrico se afasta do perfil Gaussiano devido a saturação da não-linearidade óptica. A teoria usual da varredura z, baseada no método da decomposição Gaussiana, não pode descrever os resultados obtidos com os bem caracterizados absorvedores saturáveis com tempos lentos de resposta (milisegundos): Al2O3:Cr3+ (rubí), Beal2O4:Cr3+ (alexandrita) e GdAlO3: Cr3+ (aluminato de gadolínio dopado com cromo). Este objetivo pode ser alcançado por meio de uma teoria baseada na transformada de Hankel do campo elétrico que se propaga através da amostra e pela inclusão da saturação da fase nesta teoria. O formalismo alternativo também permite a inclusão de outros efeitos como por exemplo, térmico. Como no caso do meio Kerr, o índice de refração não-linear pode ser obtido da medida da diferença entre o pico e o vale da transmitância, na determinação da refração não-linear, ou da transmitância de pico, na determinação da absorção não-linear. Em relação a parte experimental, é introduzida uma técnica de varredura z com um único feixe resolvida no tempo para caracterizar, com radiação cw, a refração não-linear dos materiais citados. Devido a eliminação dos efeitos lineares parasíticos, a técnica é capaz de medir distorções de frente de onda tão pequenas quanto N104. A demonstração experimental da técnica alternativa é realizada com um laser de Ar+ com baixa potência e um laser de He-Ne / In this work we investigated the behavior of the Z-scan technique in the case where the phase of the electric field departs from Gaussian due to the saturation of the optical nonlinearity. The usual theory of Z-scan, based on Gaussian decomposition method, cannot describe experimental results obtained with well-characterized chromium-doped saturable absorbers of slow (milisecond) response: Al2O3:Cr3+ (ruby), Beal2O4:Cr3+ (alexandrite) e GdAlO3: Cr3+ (chromium doped gadolinium aluminate). This aim can be accomplished by means of a theory based on the Hankel transform of the electric field passing through the sample and the inclusion of the phase saturation. The alternative formalism also allows the inclusion of thermal effects. As in the case of Kerr media, the nonlinear refractive index can be obtained from the measurement of the transmittance difference between peak and valley, in the refractive case, or of the transmittance peak, in the absorptive case. Concerning to experimental part, a single-beam time-resolved Z-scan is introduced to characterize the nonlinear refraction of the above materials. Owing to the elimination of parasitic linear effects, the technique is able to measure induced wave front as small as N104. We demonstrate this method on several materials using low power Ar+ and He-Ne lasers

Αρχικά μελετήσαμε την μη-γραμμική οπτική και τα βασικά μη-γραμμικά φαινόμενα, όπως για παράδειγμα τον οπτικό περιορισμό, τη γένεση δεύτερης αρμονικής, τη γένεση τρίτης αρμονικής, την αυτοεστίαση, το οπτικό φαινόμενο kerr και το συνεχές φαινόμενο kerr. Eπιπλέον περιγράψαμε την τεχνική z-scan και εκτιμήσαμε τις μη-γραμμικές οπτικές ιδιότητες του C60 και C120. / First of all, research the nonlinear optics and basic nonlinear phenomena, for example, optical limiting, second harmonic generation, third harmonic generation, self-focusing, optical kerr effect and DC kerr effect. In addition description technique z-scan and estimate the nonlinear optical properties C60 and C120

Neste trabalho investigamos o comportamento da técnica de varredura z no caso onde a fase do campo elétrico se afasta do perfil Gaussiano devido a saturação da não-linearidade óptica. A teoria usual da varredura z, baseada no método da decomposição Gaussiana, não pode descrever os resultados obtidos com os bem caracterizados absorvedores saturáveis com tempos lentos de resposta (milisegundos): Al2O3:Cr3+ (rubí), Beal2O4:Cr3+ (alexandrita) e GdAlO3: Cr3+ (aluminato de gadolínio dopado com cromo). Este objetivo pode ser alcançado por meio de uma teoria baseada na transformada de Hankel do campo elétrico que se propaga através da amostra e pela inclusão da saturação da fase nesta teoria. O formalismo alternativo também permite a inclusão de outros efeitos como por exemplo, térmico. Como no caso do meio Kerr, o índice de refração não-linear pode ser obtido da medida da diferença entre o pico e o vale da transmitância, na determinação da refração não-linear, ou da transmitância de pico, na determinação da absorção não-linear. Em relação a parte experimental, é introduzida uma técnica de varredura z com um único feixe resolvida no tempo para caracterizar, com radiação cw, a refração não-linear dos materiais citados. Devido a eliminação dos efeitos lineares parasíticos, a técnica é capaz de medir distorções de frente de onda tão pequenas quanto N104. A demonstração experimental da técnica alternativa é realizada com um laser de Ar+ com baixa potência e um laser de He-Ne / In this work we investigated the behavior of the Z-scan technique in the case where the phase of the electric field departs from Gaussian due to the saturation of the optical nonlinearity. The usual theory of Z-scan, based on Gaussian decomposition method, cannot describe experimental results obtained with well-characterized chromium-doped saturable absorbers of slow (milisecond) response: Al2O3:Cr3+ (ruby), Beal2O4:Cr3+ (alexandrite) e GdAlO3: Cr3+ (chromium doped gadolinium aluminate). This aim can be accomplished by means of a theory based on the Hankel transform of the electric field passing through the sample and the inclusion of the phase saturation. The alternative formalism also allows the inclusion of thermal effects. As in the case of Kerr media, the nonlinear refractive index can be obtained from the measurement of the transmittance difference between peak and valley, in the refractive case, or of the transmittance peak, in the absorptive case. Concerning to experimental part, a single-beam time-resolved Z-scan is introduced to characterize the nonlinear refraction of the above materials. Owing to the elimination of parasitic linear effects, the technique is able to measure induced wave front as small as N104. We demonstrate this method on several materials using low power Ar+ and He-Ne lasers

INTRODUCTION: Pulmonary embolism (PE) is a major cause of mortality during pregnancy. It is estimated that about 20% of maternal deaths in north america are due to PE. A lung V/Q study in a standard (non-gravid) patient typically consists of a low dosage ventilation study followed by a higher dosage perfusion study. In some centers however, perfusion-only imaging, without accompanying ventilation imaging has been employed. In this method, a several-fold lower dose of radioactivity is used. Perfusion-only imaging has multiple advantages. In addition to reduction of radiation dose to the mother and the fetus, there is decreased cost to the health-care system as well as improved patient convenience and shortened hospital workflow. OBJECTIVES: The present study aimed at assessing the negative predictive value (among other diagnostic accuracy measures) of perfusion-only imaging in a large group of pregnant patients with suspected pulmonary embolism. METHODS: This study was a retrospective cohort study of the entire pregnant patients with suspected PE who underwent V/Q scan at The Ottawa Hospital and their V/Q scans were available in the PACS system. After acquiring REB approval, a comprehensive search in the PACS (Picture Archiving and Communication System) was conducted to find pregnant patients who were assessed for PE in our division since 2004 (the earliest date the V/Q images were available in our system). A statistical consultation was made before the initiation of data collection and at the time of data analysis. All patients who met the inclusion criteria were included. Initially a nuclear medicine resident with 2 years of experience read all the perfusion- only images. The PISAPED criteria were used for image interpretation. Then the results were compared against the reports made by nuclear medicine staffs that were available to us in our electronic system and a final interpretation was made after such comparison. The follow-up clinical notes were used as the gold standard to make a final diagnosis of PE. Finally, diagnostic accuracy measures were calculated. RESULTS: A total of 364 patients were included. Mean maternal age at the time of lung V/Q scan was 30.3 years-old (SD=5.8) ranging from 16 to 51 years-old. From a total of 362 lung perfusion scans, 316/362 (87.3%) scans interpreted as normal, 17/362 (4.7%) scans were interpreted as high probability and 29/362 (8.0%) scans were interpreted as non-diagnostic. Pulmonary embolism was diagnosed in a total of 15 patients directly after performing lung scan. None of the patients with normal perfusion-only scans were diagnosed later with PE, proving a negative predictive value of 100%. The sensitivity and specificity of perfusion-only imaging after including the non-diagnostic studies were 100% (100% to 100%) and 99.1% (88.1% to 94.1%), respectively with a negative predictive value of 100% (100% to 100%) and a positive predictive value of 32.6% (19.1% to 46.2%). Conclusion: The results of the current study show that perfusion-only imaging has a very high negative predictive value for PE in pregnant population and therefore can exclude PE with a very high degree of accuracy.