Au cours des dix dernières années, l’utilisation de l’imagerie par tomographie par émission de positrons (TEP) s’est rapidement développée en oncologie. Certaines tumeurs non visibles en imagerie anatomique conventionnelle sont détectables en mesurant l'activité métabolique dans le corps humain par TEP. L’imagerie TEP est utilisée pour guider la délivrance de traitements locaux tels que par rayonnement ionisants ou ablation thermique. Pour la délivrance de ces traitements, segmenter la zone tumorale avec précision est primordial. Cependant, la faible résolution spatiale des images TEP rend la segmentation difficile. Plusieurs études ont démontré que la segmentation manuelle est sujette à une grande variabilité inter- et intra- individuelle et est fastidieuse. Pour ces raisons, de nombreux algorithmes de segmentation automatiques ont été développés. Cependant, peu de données fiables, avec des résultats histopathologiques existent pour valider ces algorithmes car il est expérimentalement difficile de les produire. Le travail méthodologique mis en place durant cette thèse a eu pour but de développer une méthode permettant de comparer les données histopathologiques aux données obtenue par TEP pour tester et valider des algorithmes de segmentation automatiques. Cette méthode consiste à réaliser des autoradiographies quantitatives de spécimens prélevés lors de biopsies guidées par TEP/tomodensitométrie (TDM); l’autoradiographie permettant d’imager la distribution du radiotraceur dans les échantillons avec une haute résolution spatiale. Les échantillons de tissus sont ensuite finement tranchés pour pouvoir être étudiés à l’aide d’un microscope. L’autoradiographie et les photomicrographes de l’échantillon de tissus sont ensuite recalés à l’image TEP, premièrement en les alignant avec l’aiguille à biopsie visible sur l’image TDM, puis en les transférant sur l’image TEP. Nous avons ensuite cherché à utiliser ces données pour tester deux algorithmes de segmentation automatique d'images TEP, le Fuzzy Locally Adaptive Bayesian (FLAB) développé au Laboratoire de Traitement de l'Information Médicale (LaTIM) à Brest, ainsi qu’une méthode de segmentation par seuillage. Cependant, la qualité de ces données repose sur la précision du recalage des images TEP, autoradiographiques et des micrographes. La principale source d’erreur dans le recalage de ces images venant de la fusion des images TEP/TDM, une méthode a été développée afin de quantifier la précision du recalage. Les résultats obtenus pour les patients inclus dans cette étude montrent que la précision de la fusion varie de 1.1 à 10.9 mm. En se basant sur ces résultats, les données ont été triées, pour finalement sélectionner les données acquises sur 4 patients jugées satisfaisantes pour tester les algorithmes de segmentation. Les résultats montrent qu’au point de la biopsie, les contours obtenus avec FLAB concordent davantage avec le bord de la lésion observé sur les micrographes. Cependant les deux méthodes de segmentation donnent des contours similaires, les lésions étant peu hétérogènes. / During the last decade, positron emission tomography (PET) has been finding broader application in oncology. Some tumors that are non-visible in standard anatomic imaging like computerized tomography (CT) or ultrasounds, can be detected by measuring in 3D the metabolic activity of the body, using PET imaging. PET images can also be used to deliver localized therapy like radiation therapy or ablation. In order to deliver localized therapy, the tumor border has to be delineated with very high accuracy. However, the poor spatial resolution of PET images makes the segmentation challenging. Studies have shown that manual segmentation introduces a large inter- and intra- variability, and is very time consuming. For these reasons, many automatic segmentation algorithms have been developed. However, few datasets with histopathological information are available to test and validate these algorithms since it is experimentally difficult to produce them. The aim of the method developed was to evaluate PET segmentation algorithms against the underlying histopathology. This method consists in acquiring quantitative autoradiography of biopsy specimen extracted under PET/CT guidance. The autoradiography allows imaging the radiotracer distribution in the biopsy specimen with a very high spatial accuracy. Histopathological sections of the specimen can then obtained and observed under the microscope. The autoradiography and the micrograph of the histological sections can then be registered with the PET image, by aligning them first with the biopsy needle seen on the CT image and then transferring them onto the PET image. The next step was to use this dataset to test two PET automatic segmentation algorithms: the Fuzzy Locally Adaptive Bayesian (FLAB) developed at the Laboratory of Medical Information Processing (LaTIM) in Brest, France, as well as a fix threshold segmentation method. However, the reliability of the dataset produced depends on the accuracy of the registration of the PET, autoradiography and micrograph images. The main source of uncertainty in the registration of these images comes from the registration between the CT and the PET. In order to evaluate the accuracy of the registration, a method was developed. The results obtained with this method showed that the registration error ranges from 1.1 to 10.9mm. Based on those results, the dataset obtained from 4 patients was judged satisfying to test the segmentation algorithms. The comparison of the contours obtained with FLAB and with the fixed threshold method shows that at the point of biopsy, the FLAB contour is closer than that to the histopathology contour. However, the two segmentation methods give similar contours, because the lesions were homogeneous.

Made available in DSpace on 2016-01-26T18:55:38Z (GMT). No. of bitstreams: 1 Ana Maria Silva Camargo.pdf: 475946 bytes, checksum: 6019edcfebc4f243e71350aa8bdb6438 (MD5) Previous issue date: 2013-08-05 / Snakebites with Caudisona durissa terrifica are of great importance for the high mortality rate in humans and animals. Neurotoxicity, myotoxicity, abnormal coagulation, hepato and nephrotoxicity are the most commonly observed clinical signs. The present study aimed to evaluate by histopathology the kidney of Wistar rats experimentally intoxicated crotalic venom at different doses. Ninety rats were divided into three groups as follows: control group (CG) - received solution of sodium chloride 0.9% intramuscular (IM); Group 4 (G4) - received 4mg/kg of crotalic venom IM; Group 8 (G8) -received 8mg/kg of crotalic venom IM. Histopathological examination of the kidney was performed in 6 hours time (M6) and 24 hours (M24) after the inoculation of the venom (AV). Moderate renal congestion was observed in both groups, hydropic degeneration and acute tubular necrosis little to G4 in M6 and high incidence of acute tubular necrosis in M24, however, acute tubular necrosis was predominant in the G8 at both times. It is concluded that in Wistar rats using doses of 4 and 8mg/Kg after 24 hours intoxication, crotalic venom causes histological changes in the kidney characterized by congestion, hydropic degeneration and acute tubular necrosis, and the signal strength dose dependent. Further studies are needed to evaluate the causes that lead to the installation of histological renal changes in this species. / Acidentes ofídicos com a Caudisona durissa terrifica são de grande importância pelo alto índice de mortalidade em humanos e animais. Neurotoxicidade, miotoxicidade, alteração de coagulação, hepato e nefrotoxicidade são os sinais clínicos mais comumente observados. O presente estudo teve como objetivo avaliar por meio de exame histopatológico o rim de ratos Wistar experimentalmente intoxicados com veneno crotálico em diferentes doses. Noventa ratos foram distribuídos em três grupos sendo: Grupo controle (GC): receberam solução de cloreto de sódio 0,9% intramuscular (IM); Grupo 4 (G4) - receberam 4mg/Kg do veneno crotálico IM; Grupo 8 (G8)-receberam 8mg/Kg de veneno crotálico IM. A histopatologia do rim foi realizada nos momentos 6 horas (M6) e 24 horas (M24) após a inoculação do veneno (AV). Foi observada congestão renal moderada nos dois grupos, degeneração hidrópica e pouca necrose tubular aguda para o G4 no M6 e alta incidência de necrose tubular aguda no M24, no entanto, a necrose tubular aguda foi predominante no G8 nos dois momentos. Conclui-se que em ratos wistar utilizando-se as doses de 4 e 8mg/Kg em 24 horas após intoxicação, o veneno crotálico provoca alterações histológicas em rim caracterizadas por congestão, degeneração hidrópica e necrose tubular aguda, sendo a intensidade dos sinais dose dependente. Novos estudos são necessários para avaliação das causas que levam a instalação das alterações histológicas renais nesta espécie animal.

Made available in DSpace on 2016-07-18T17:53:12Z (GMT). No. of bitstreams: 1 Ana Maria Silva Camargo.pdf: 475946 bytes, checksum: 6019edcfebc4f243e71350aa8bdb6438 (MD5) Previous issue date: 2013-08-05 / Snakebites with Caudisona durissa terrifica are of great importance for the high mortality rate in humans and animals. Neurotoxicity, myotoxicity, abnormal coagulation, hepato and nephrotoxicity are the most commonly observed clinical signs. The present study aimed to evaluate by histopathology the kidney of Wistar rats experimentally intoxicated crotalic venom at different doses. Ninety rats were divided into three groups as follows: control group (CG) - received solution of sodium chloride 0.9% intramuscular (IM); Group 4 (G4) - received 4mg/kg of crotalic venom IM; Group 8 (G8) -received 8mg/kg of crotalic venom IM. Histopathological examination of the kidney was performed in 6 hours time (M6) and 24 hours (M24) after the inoculation of the venom (AV). Moderate renal congestion was observed in both groups, hydropic degeneration and acute tubular necrosis little to G4 in M6 and high incidence of acute tubular necrosis in M24, however, acute tubular necrosis was predominant in the G8 at both times. It is concluded that in Wistar rats using doses of 4 and 8mg/Kg after 24 hours intoxication, crotalic venom causes histological changes in the kidney characterized by congestion, hydropic degeneration and acute tubular necrosis, and the signal strength dose dependent. Further studies are needed to evaluate the causes that lead to the installation of histological renal changes in this species. / Acidentes ofídicos com a Caudisona durissa terrifica são de grande importância pelo alto índice de mortalidade em humanos e animais. Neurotoxicidade, miotoxicidade, alteração de coagulação, hepato e nefrotoxicidade são os sinais clínicos mais comumente observados. O presente estudo teve como objetivo avaliar por meio de exame histopatológico o rim de ratos Wistar experimentalmente intoxicados com veneno crotálico em diferentes doses. Noventa ratos foram distribuídos em três grupos sendo: Grupo controle (GC): receberam solução de cloreto de sódio 0,9% intramuscular (IM); Grupo 4 (G4) - receberam 4mg/Kg do veneno crotálico IM; Grupo 8 (G8)-receberam 8mg/Kg de veneno crotálico IM. A histopatologia do rim foi realizada nos momentos 6 horas (M6) e 24 horas (M24) após a inoculação do veneno (AV). Foi observada congestão renal moderada nos dois grupos, degeneração hidrópica e pouca necrose tubular aguda para o G4 no M6 e alta incidência de necrose tubular aguda no M24, no entanto, a necrose tubular aguda foi predominante no G8 nos dois momentos. Conclui-se que em ratos wistar utilizando-se as doses de 4 e 8mg/Kg em 24 horas após intoxicação, o veneno crotálico provoca alterações histológicas em rim caracterizadas por congestão, degeneração hidrópica e necrose tubular aguda, sendo a intensidade dos sinais dose dependente. Novos estudos são necessários para avaliação das causas que levam a instalação das alterações histológicas renais nesta espécie animal.

West Nile virus (WNV) is a widespread emerging zoonotic neurotropic flavivirus cycling naturally between mosquitos and birds. WNV causes disease in 20% of infections in the most susceptible incidental hosts which are horses and humans. Up to 40% of affected horses and 1- to approximately 50% of affected humans develop neurological signs and/or flaccid paralysis, in some cases fatal or severely debilitating, due to variable encephalitis, meningitis and poliomyelitis. Two predominant genetic lineages exist, 1 and 2, with neurovirulent lineage 1 strains recorded in the northern and western hemispheres, the milder lineage 1 Kunjin strain in Australia, and the lineage 2 strain endemic to southern Africa and Madagascar and considered, until recently, to have mainly mildly pathogenic strains. Since 2002 investigations into South African lineage 2 WNV strains showed that they resulted in severe neurological disease in horses and humans. From 2004 lineage 2 strains were recorded for the first time in southern Europe as a cause of neurological signs and death in birds, and increasingly, in horses and humans. In 2011 the mild lineage 1 Kunjin strain mutated to an equine neurovirulent strain in New South Wales, Australia, and in 2010 the first South African case of lineage 1 WNV was reported from the western Cape in a mare which showed severe neurological signs, abortion and death. Laboratory strains of mice are extremely susceptible to WNV and have been mostly used in experimental studies since the 1937 discovery of the virus in Uganda. In the early 2000s studies in mice showed that field strains of lineage 1 and 2 WNV ranged from mildly pathogenic to highly neurovirulent, however, the associated pathology of the lineage 2 infections was not studied. In the current study, the macroscopic and microscopic pathology of a South African human-neurovirulent field strain of lineage 2 WNV (SPU93/01) and the neurovirulent lineage 1 (NY99/385) strain were investigated and compared in mice used as controls in 2 WNV vaccine studies. The clinical signs, CNS and extra-CNS pathology were indistinguishable between the lineages and some lesions were comparable to those previously reported. Lineage 1 WNV equine pathology has been well described but that of lineage 2 only briefly previously described. The pathology in 6 naturally-occurring fatal lineage 2 WNV-infected horses with severe neurological signs, was investigated and compared with that of the single South African lineage 1 WNV field infection. Diagnoses were confirmed by real-time RT-PCR. Similarities and some slight differences in lesions were found in both mouse and horse studies when compared with lineage 1 pathology cases and with previous reports, and the neurovirulence of the lineage 2 field strains was confirmed. WNV immunohistochemistry (IHC) of all mouse tissues allowed speculation as to pathogenesis of intestinal lesions, but in equine CNS lesions was mostly negative. Ultrastructure of IHC positive cells showed rare WNV particles. In the horse cases rabies, equine herpes virus, and other arboviral co-infections were excluded and similarities and implications of gross lesions of African horsesickness to those often seen in WNV infections were discussed. / Dissertation (MSc)--University of Pretoria, 2014. / gm2014 / Medical Virology / unrestricted

Brain and nervous system tumors were responsible for around 250,000 deaths in 2020 worldwide. Correctly identifying different tumors is very important, because treatment options largely depend on the diagnosis. This is an expert task, but recently machine learning, and especially deep learning models have shown huge potential in tumor classification problems, and can provide fast and reliable support for pathologists in the decision making process. This thesis investigates classification of two brain tumors, glioblastoma multiforme and lower grade glioma in high-resolution H&E-stained histology images using deep learning. The dataset is publicly available from TCGA, and 220 whole slide images were used in this study. Ground truth labels were only available on whole slide level, but due to their large size, they could not be processed by convolutional neural networks. Therefore, patches were extracted from the whole slide images in two sizes and fed into separate networks for training. Preprocessing steps ensured that irrelevant information about the background was excluded, and that the images were stain normalized. The patch-level predictions were then combined to slide level, and the classification performance was measured on a test set. Experiments were conducted about the usefulness of pre-trained CNN models and data augmentation techniques, and the best method was selected after statistical comparisons. Following the patch-level training, five slide aggregation approaches were studied, and compared to build a whole slide classifier model. Best performance was achieved when using small patches (336 x 336 pixels), pre-trained CNN model without frozen layers, and mirroring data augmentation. The majority voting slide aggregation method resulted in the best whole slide classifier with 91.7% test accuracy and 100% sensitivity. In many comparisons, however, statistical significance could not be shown because of the relatively small size of the test set.

Mammary cancer is a serious health issue in pet rabbits; prognostic factors are unknown. In a normal mammary gland, glandular secretory cells are surrounded by a single continuous layer of myoepithelial cells. In non-invasive mammary carcinomas, tumor cells are delineated by an intact myoepithelial layer, which is gradually lost to invasive carcinomas. The main aim of this study was to determine in rabbit mammary carcinomas (n = 119) the expression of myoepithelial markers that have prognostic significance in human cancer. Results show that all cases contained some retained myoepithelial cells. In 93% of the tumors, neoplastic cells expressed the myoepithelial marker calponin. There was a statistically significant association between higher percentages of calponin-containing cancer cells and histological features indicative of a better tumor differentiation, i.e., a lower proliferation of tumor cells, an increased percentage of tubular growth within the tumor, and a lower tumor grade, respectively. These results suggest that rabbit mammary carcinomas develop from progression of non-invasive cancer forms, and that calponin expression in cancer cells likely represents a favorable prognostic factor. The latter hypothesis has to be confirmed in long-term follow-up studies.

Extensive use of the organophosphate diazinon has led to its accumulation in aquatic environments and negative effects on fish health. Most studies focus on the effects of short term exposure to high levels of organophosphate pesticides. This research was conducted to assess the effect of chronic sub-lethal exposure to 0, 0.01, and 0.1 mg/L diazinon for 15 and 30 days on blood parameters and histopathological damage in alligator gar, Atractosteus spatula. Fish exposed to either concentration were motionless, produced excess mucous, had lighter skin color, and had skin lesions. Blood indices of red blood cells, leukocytes and hematocrit values significantly decreased but there was no significant change in mean cell volume. Hemoglobin values significantly increased in fish exposed to the low dose for 15 days, but significantly decreased for the other exposure doses and times. On the contrary, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration values significantly increased in fish exposed to both concentrations and duration times. Leukocyte differentials showed significant decreases in lymphocytes with significant increases of monocytes in fish exposed to the high dose in both exposure times. The most frequent biomarker for exposure to organophosphate pesticides is the inhibition of cholinesterase (ChE). Diazinon significantly reduced plasma ChE activity in a dose-dependent manner, with 62% and 72% in the low and high concentrations for 30 days, respectively. Plasma ChE could be determined from peripheral blood samples and did not require sacrifice of the fish. Fish exposed to either diazinon concentration or duration time developed histopathological changes in skin, gills, liver, and kidney tissues. The skin lesions were on the head and body, and progressed into deep ulcerations. The histopathological changes in the liver included hepatic vacuoles, swollen hepatocytes, steatosis, aggregation of macrophages, necrosis, and hepatic fibrosis. Also, exposed fish demonstrated vacuolar degeneration in the hematopoietic tissues of the kidney. Gills showed epithelial hyperplasia in the secondary lamellae. In conclusion, long term exposure to sub-lethal concentrations of diazinon induced significant changes in hematological indices and histopathological alteration in various tissues. Plasma ChE can be used to monitor diazinon exposure in wild gar populations.

No description available.

L'otite moyenne est une condition fréquente chez le veau et peut parfois être subclinique, rendant difficile son diagnostic à la ferme. L'objectif de cette étude est d’estimer la sensibilité et la spécificité de l'échographie des bulles tympaniques pour le diagnostic d'otite moyenne clinique et subclinique et de déterminer sa répétabilité. Quarante veaux âgés entre 19 et 50 jours ont été sélectionnés dans une ferme de veaux de grain, en fonction des résultats de l'échographie réalisée à la ferme (A). L'échographie a été réalisée une seconde fois par le même échographiste (A') et par un second échographiste (B), et le diagnostic noté pour chaque bulle tympanique comme étant négatif, suspect ou positif. Les images ont été enregistrées pour relecture et le diagnostic noté. Les veaux ont été euthanasiés, soumis en nécropsie et l'histologie a été utilisée comme méthode de référence. À l'histologie, 45 bulles tympaniques étaient atteintes d'otite moyenne et 35 bulles tympaniques étaient saines. Selon l'échographiste et la classification des bulles tympaniques suspectes, la sensibilité de l'échographie variait de 32% à 63% et la spécificité variait de 84% à 100%. La répétabilité était modérée, avec des valeurs de kappa de 0,53 entre A' et B, de 0,48 entre A et A', et de 0,58 et 0,75 pour la relecture de leurs images par A' et B respectivement. / Otitis media is a common disease in calves but can remain subclinical, making diagnosis challenging on the farm. The objective of this study is to estimate the sensitivity and specificity of the ultrasound imaging technique of tympanic bulla for the diagnosis of clinical and subclinical otitis media, and to determine its repeatability. Forty calves 19-50 days of age were selected from a veal calf farm, on the basis of results of ultrasound examination performed on the farm (A). Ultrasound examination was performed a second time by the same ultrasonographer (A') and by another ultrasonographer (B), and diagnosis was recorded for both tympanic bulla as negative, suspicious or positive. Images were recorded for further re-reading. Calves were euthanized and submitted for necropsy, and histopathologic diagnosis was used as gold standard. Based upon histology, 45 bullae were affected with otitis media and 35 bullae were unaffected. Depending on ultrasonographer and on classification of suspicious bullae, sensitivity varies from 32% to 63% and specificity varies from 84% to 100%. Repeatability is moderate, with kappa values of 0.53 for A'-B, 0.48 for A-A', and 0.58 and 0.75 for re-reading of A' and B, respectively.

Karenia brevis, le dinoflagellé produisant des brevetoxines (PbTx), est la principale espèce d’efflorescences d’algues toxiques dans le Golfe du Mexique. Les effets de cette algue sur Mercenaria mercenaria et Crassostrea virginica sont méconnus tandis que les efflorescences coïncident avec la période de reproduction de ces espèces. Ce projet avait pour but de déterminer les effets i) d’une exposition à K. brevis en laboratoire et naturelle de terrain sur les processus physiologiques associés à la reproduction de M. mercenaria et C. virginica, et ii) d’une exposition à K.brevis sur la qualité et le développement des gamètes, embryons et larve de ces espèces. Suite à l'exposition des adultes de clams et d’huîtres à K. brevis, les paramètres physiologiques de la reproduction ont été affectés. La présence de PbTx dans les tissus des gamètes et le potentiel transfert maternel de PbTx à la progénie via les ovocytes, pourraient avoir entraîné les effets négatifs observés lors du développement larvaire.Les effets négatifs similaires causés par l'exposition des stades précoces à différentes préparations de cellules de K. brevis suggèrent que d'autres composés toxiques, en plus de PbTx, pourraient être impliqués dans la toxicité et, que la majorité des effets délétères se produisent durant les divisions embryonnaires.Le clam et l’huître américaine sont sensibles à K. brevis. Les effets négatifs sur les adultes et jeunes stades de vie, combinés à une exposition quasi-annuelle aux efflorescences de K. brevis, pourraient engendrer des perturbations majeures sur le recrutement des populations de ces espèces importantes, et avoir des répercussions environnementales et économiques. / The brevetoxin (PbTx) producing dinoflagellate, Karenia brevis is the most prevalent harmful algal bloom species in the Gulf of Mexico. The effects of this alga on Mercenaria mercenaria and Crassostrea virginica are poorly understood yet, blooms typically overlap with periods of reproduction and spawning in these species.The aims of this project were to determine the effects of i) laboratory and field exposure of K. brevis on the reproductive and related physiological processes of adult M. mercenaria and C. virginica and the quality of the offspring that were produced and ii) K. brevis exposure on gamete, embryo and larval development in these species.Following exposure of adult clams and oysters to K. brevis, negative effects were recorded on reproductive and physiological parameters. PbTx was recorded in gamete tissues, and maternal transfer of this PbTx to the offspring via the oocytes, may have resulted in the significant negative effects recorded on larval development up to the end of the lecithotrophic phase.The similar dose-dependent negative effects caused by direct exposure of gamete and early life stages to different cell preparations of K. brevis suggests that other toxic compounds in addition to PbTx may be involved in toxicity and, that the majority of negative effects occur during embryonic divisions.Hard clams and eastern oysters are susceptible to K. brevis exposure. The negative effects on adult and early life stages combined with the near- annual exposure to blooms of K. brevis could cause significant bottle-necks on the recruitment and population dynamics of these important species and, have wider reaching environmental and economic impacts.