We have developed a simulation of the AdaptiSPECT small-animal Single Photon Emission Computed Tomography (SPECT) imaging system. The simulation system is entitled SimAdaptiSPECT and is written in C, NVIDIA CUDA, and Matlab. Using this simulation, we have accomplished an analysis of the Scanning Linear Estimation (SLE) technique for estimating tumor parameters, and calculated sensitivity information for AdaptiSPECT configurations.SimAdaptiSPECT takes, as input, simulated mouse phantoms (generated by MOBY) contained in binary files and AdaptiSPECT configuration geometry contained in ASCII text files. SimAdaptiSPECT utilizes GPU parallel processing to simulate AdaptiSPECT images. SimAdaptiSPECT also utilizes GPU parallel processing to perform 3-D image reconstruction from 2-D AdaptiSPECT camera images (real or simulated), using a novel variant of the Ordered Subsets Expectation Maximization (OSEM) algorithm. Methods for generating the inputs, such as a population of randomly varying numerical mouse phantoms with randomly varying hepatic lesions, are also discussed.

L’imagerie in vivo du petit animal est de plus en plus utilisée en pharmacologie pour identifier et caractériser l’activité de nouveaux agents anticancéreux.La première partie de ma thèse a consisté à développer des outils pour améliorer la quantification enbioluminescence. Une méthode, basée sur les caractéristiques spectrales des photons émis, a été établie pour corriger l’absorption tissulaire. La seconde, faisant appel aux méthodes de restauration d’images, avait pour but de corriger la diffusion pour augmenter la résolution. Dans un second temps, j’ai mis en place des modèles in vivo de tumeurs expérimentales bioluminescentes (un glioblastome intracérébral, un lymphome anaplasique à grandes cellules et un neuroblastome métastatique) en utilisant les méthodes d’imagerie décrites précédemment. Ces études ont permis d’étendre la caractérisation de l’activité préclinique d’un nouvel agent anticancéreux. L’objectif de la dernière partie de mon travail était de développer des sondes d’imagerie. La première sonde, un anticorps monoclonal anti-CD45 marqué avec un fluorochrome a permis la détection de cellules leucémiques humaines implantées chez la souris en utilisant l’imagerie de fluorescence. La seconde a été développée pour prédire l’entrée d’un agent anticancéreux, un conjugué spermine-podophyllotoxin, dans les cellules tumorales via les transporteurs des polyamines. La sonde synthétisée est une spermine à laquelle un groupement HYNIC a été ajouté afin de pouvoir lier un radioisotope : le Technétium 99m et ainsi réaliser un examen scintigraphique. Les résultats ont démontré la faisabilité d’une application préclinique de cette sonde. Ainsi à l’issu de cette thèse, les méthodes de traitement des signaux de bioluminescence développées sont disponibles pour améliorer l’application de l’imagerie optique en pharmacologie. Bien sûr des études supplémentaires sont encore nécessaires pour définir précisément dans quel contexte ces corrections seront les plus appropriées. / Small animal imaging is more and more used in pharmacology to identify and to characterize the activities of new antitumor agents. The first part of my thesis consisted in the development of new tools to improve the quantitation in bioluminescence. A method, based on spectral characteristics of emitted photons, has been established to correct tissue absorption. The second, using methods of image restoration had for objective to correct tissue scattering to increase the resolution. In a second part, I developed in vivo models of bioluminescent tumors (intracranial glioblastoma, a large cell anaplastic lymphoma and a metastatic neuroblastoma) using the imaging methods described previously. These studies allowed the characterization of the activity of a new antitumor agent. The aim of the last part was to develop imaging probes. The first, a monoclonal antibody antiCD45 labeled with a fluorochrome allowed the detection of human leukemic cells implanted in the mice using fluorescence imaging. The second was developed to predict the uptake of a antitumor agent, a spermine-podophyllotoxin conjugate, in tumor cells via the polyamine transport system. The synthesized probe is a spermine conjugated to a HYNIC group to bind a radioisotope: the Technetium 99m and to realize a scintigraphic examination. The results showed the feasibility of a preclinical use of this probe. So, at this end of this thesis, the developed methods of bioluminescent signal processing are available to improve the use of optical imaging in pharmacology. Of course, supplementary studies are necessary to define precisely in which context these corrections will be the most appropriate.

The Internet which is also known as ‘Information Superhighway’, ‘Global Information Infrastructure’, ‘Cyberspace’, ‘Hyperspace’ etc., connects millions of computers in a web and makes almost immediate communication possible, irrespective of the location of its users. The Internet provides huge resources that are useful for veterinary and animal science professionals and the amount of accessible veterinary medicine information is increasing rapidly. Ideally, this could provide a formidable opportunity for Veterinarians to exchange and process veterinary medicine information with colleagues around the world from their desktop. Though the Internet offers virtually unlimited amount of information related to small animal medicine and surgery and provides a number of tools to access, it is useful in at least three aspects related to veterinary medicine and surgery viz., communication, education and research. This paper attempts to profile such important digital knowledge resources useful for small animal veterinary medicine professionals.

Small-animal x-ray imaging is an important tool for medical research. The penetration power of x-rays makes it possible to investigate the 3D structure of small animals and other thick biological samples by computed tomography (CT). However, small-animal x-ray imaging often requires high resolution due to the small structures involved, and short exposure times due to sample movement. This constitutes a challenge, since these two properties require compact x-ray sources with parameters that are not widely available. In this Thesis we present the first application of liquid-metal-jet sources for small-animal imaging. This source concept was invented at KTH just over ten years ago. The use of a high-speed metal jet as electron-beam target, instead of a solid anode, enables higher x-ray flux while maintaining a small x-ray spot for high-resolution imaging. In the present work, a liquid-metal jet source with a higher-energy spectrum has been developed. It has stronger 24 keV radiation compared to previous sources, which makes it more suitable for imaging of small animals and other few-cm-thick objects, which require the higher penetration of 20-35 keV x-rays. We have applied the liquid-metal-jet x-ray sources for whole-body imaging of sacrificed mice and zebrafish. With high-resolution absorption-contrast CT we have visualized fine bone details of mice. We have also used phase contrast, a new method that can considerably improve imaging of, e.g., soft tissue, for demarcation of mm-sized tumors inside a full mouse and for mouse cartilage imaging. In zebrafish imaging, we have exploited the greatly enhanced contrast of phase-imaging to resolve single muscle fibers (and possibly even myofibrils) in whole zebrafish in a laboratory setting for the first time. The muscle structures have diameters in the 5-7 μm range and extremely low contrast, which makes them difficult to observe. With phase contrast, we have demonstrated low-dose and high-resolution angiography of mouse and rat organs and tissues ex vivo. We show detection of blood vessels with diameters below 10 μm with radiation doses compatible with living small animals, which is not possible with absorption contrast and iodinated contrast agents. In addition, we have investigated the vascular network of tumors in mouse ears and visualized the chaotic arrangement of newly-formed blood vessels. Finally, we present the first results from a new high-power liquid-metal-jet x-ray source prototype, operating at 10× the power of our previous sources, with the same x-ray spot size. This source constitutes an important step towards future in-vivo small-animal laboratory imaging with high resolution. / Röntgenavbildning av små försöksdjur är en viktig metod inom medicinsk forskning. Röntgenstrålar penetrerar material, vilket gör det möjligt att undersöka 3D-strukturen hos försöksdjur och andra tjocka biologiska prov med hjälp av datortomografi (CT). Tyvärr kräver smådjursavbildning ofta dels hög upplösning, eftersom de relevanta strukturerna är små, dels korta exponeringstider, eftersom objektet tenderar att röra sig. Detta är en utmaning, då båda egenskaperna kräver kompakta röntgenkällor med speciella egenskaper som inte är brett tillgängliga. I denna avhandling visar vi den första användningen av metallstråleröntgenkällor för avbildning av hela smådjur. Den här typen av röntgenkälla uppfanns vid KTH för drygt tio år sedan. Genom att låta elektronerna träffa en stråle av flytande metall, istället för en solid metallanod, kan vi generera mer röntgenstrålning men samtidigt behålla en liten källpunkt, vilket behövs för avbildning med hög upplösning. En ny metallstrålekälla utvecklades som en del av denna avhandling. Den ger ett röntgenspektrum med högre energier, vilket gör källan mer lämpad än tidigare källor för avbildning av små försöksdjur och andra centimetertjocka biologiska objekt. Vi har använt metallstrålekällor för att avbilda intakta, avlivade möss och zebrafiskar. Med högupplöst absorptions-CT har vi detekterat små bendetaljer inuti möss. Vi har även använt faskontrastavbildning, en ny metod som avsevärt kan förbättra avbildning av mjukvävnad, till att demarkera millimeterstora tumörer inuti en hel mus, samt för avbildning av brosk i leder hos möss. Faskontrast ger en kraftig förstärkning av kontrasten i bilden, vilket även har använts för att för första gången detektera individuella muskelfibrer (och eventuellt även myofibriller) inuti zebrafiskar med en kompakt röntgenkälla. Muskelstrukturerna har diametrar på 5-7 μm och låg kontrast, vilket gör dem svåra att observera. Med hjälp av faskontrast har vi utvecklat en metod för att avbilda blodkärl med diametrar under 10 μm inuti organ och vävnader från möss och råttor ex vivo, med stråldoser som är kompatibla med studier av levande smådjur. Detta är inte möjligt med konventionell absorptionskontrast och jod-baserade kontrastmedel. Vi har dessutom avbildat nyformade blodkärl kring tumörer i musöron och observerat kärlens kaotiska struktur. Slutligen presenterar vi de första resultaten från en prototyp av en ny högeffektskälla. Källan har tio gånger högre effekt än tidigare metallstrålekällor, men bibehåller samma storlek på källpunkten. Den här högeffektskällan är ett viktigt steg mot framtida laboratoriebaserad avbildning av levande små försöksdjur med hög upplösning. / <p>QC 20150331</p>

No description available.

Cette thèse est consacrée au traitement d’images de bioluminescence chez le petit animal. Ce type d’imagerie, bien qu'utilisé en routine pour la recherche en cancérologie par exemple, présente néanmoins des problèmes liés aux phénomènes de diffusion et d'absorption par les tissus internes à l'animal. Il s'ajoute à cela le bruit du système d'acquisition ainsi que le bruit lié aux rayonnements cosmiques. Ceci influe sur la qualité des images acquises et rend leur exploitation délicate. Le but de cette thèse est de compenser ces effets perturbateurs. Les travaux menés ont abouti à la proposition d’un modèle de formation des images de bioluminescence ainsi qu’à une chaîne de traitement adaptée composée d’une étape de filtrage suivie d’une étape de déconvolution. Après étude de la nature des différents bruits liés à l'acquisition, nous avons mis au point un nouveau filtre médian pour la suppression du bruit impulsionnel aléatoire présent sur les images acquises ; ce filtre représente le premier bloc de la chaîne proposée. Pour l'étape de déconvolution, nous avons mené une étude comparative de différents algorithmes de déconvolution. Cela a conduit à choisir un algorithme de déconvolution aveugle initialisé avec la réponse impulsionnelle estimée du système d'acquisition. Nous avons validé notre approche globale en comparant les résultats à la réalité terrain. Au travers de différents essais cliniques, nous avons montré que le traitement que nous proposons permet une amélioration significative de la mesure des sources bioluminescentes et une meilleure distinction de sources très proches, ce qui représente un apport non négligeable pour les utilisateurs d'images de bioluminescence. / This thesis is devoted to the analysis of bioluminescence images applied to the small animal. This kind of imaging modality is used in cancerology studies. Nevertheless, some problems are related to the diffusion and the absorption of the tissues of the light of internal bioluminescent sources. In addition, system noise and the cosmic rays noise are present. This influences the quality of the images and makes it difficult to analyze. The purpose of this thesis is to overcome these disturbing effects. We first have proposed an image formation model for the bioluminescence images. The processing chain is constituted by a filtering stage followed by a deconvolution stage. We have proposed a new median filter to suppress the random value impulsive noise which corrupts the acquired images; this filter represents the first block of the proposed chain. For the deconvolution stage, we have performed a comparative study of various deconvolution algorithms. It allowed us to choose a blind deconvolution algorithm initialized with the estimated point spread function of the acquisition system. At first, we have validated our global approach by comparing our obtained results with the ground truth. Through various clinical tests, we have shown that the processing chain allows a significant improvement of the spatial resolution and a better distinction of very close tumor sources, what represents considerable contribution for the users of bioluminescence images.

Introduction Cutaneous scars represent a common surgical complication, yet no effective drug therapy for scar treatment currently exists despite huge patient and physician demand. A connexin 43 (Cx43) carboxyl terminus (CT) mimetic peptide, alpha Connexin Carboxy-Terminus 1 (αCT1), has demonstrated efficacy in improving long-term scar appearance in pre-clinical and clinical trials. However, current understanding of the mechanism-of-action by which αCT1 improves long-term scar appearance with early intervention treatment is not well understood. Methods In vivo: Scar biopsies from 1) human, 2) Sprague-Dawley rat, and 3) IAF Hairless guinea pig trials of αCT1 were examined for collagen matrix structure at 4 weeks (all models), and 2 and 6 weeks (rat and guinea pig models only). Collagen matrix variables examined included local disorganization of the fibers, a variable that is higher in unwounded skin compared to scar tissue, and density of the fibers, which is higher in scar tissue but can also be used as an early temporal marker of the rate of healing. In vitro: Primary murine dermal fibroblasts were isolated from the whole dermis of 3-4 week old transgenic mice expressing collagen 1(α2) GFP-tpz. Cells were sorted for expression via FACS and plated on prealigned collagen substrate for 7 days under conditions favorable to generating extracellular matrix. Results: All in vivo scar biopsies demonstrated some level of altered collagen matrix structure with αCT1 treatment. Treated scars had higher local disorganization of the collagen fibers within the wound, and an increase in collagen matrix density compared to control at certain earlier timepoints that tended to decrease or disappear at later timepoints. The IAF Hairless guinea pig, a novel splinted wound healing model presented herein, was found to closely replicate the human dermal collagen profile and changes in collagen profile spurred by αCT1, significantly outperforming the traditional rat model. Primary dermal murine fibroblasts treated in vitro with αCT1 significantly increased synthesis of procollagen 1, the precursor of collagen 1 necessary for constructing the extracellular matrix, suggesting that at least part of the reason for higher collagen density at early in vivo timepoints is due to increased collagen synthesis by fibroblasts. Conclusion: αCT1 treatment in the early stages of wound healing prompts individual fibroblasts to increase their output of collagen and create a more disorganized early collagen matrix. These early changes potentially spur the long-term scar appearance improvements seen in clinical trials, and provide a basis for future work to discover the cellular pathways to alter in order to improve wound healing and cutaneous scarring outcomes. / Doctor of Philosophy / Skin wounds frequently result in scars that can range from barely visible to enormous eyesores. Almost everyone will experience at least one skin wound in their lifetime leading to a scar that they wish were less visible, feeding the multi-billion dollar market for anti-scarring agents. However, many of the products on store shelves that claim to reduce scar appearance have not proven those claims. Most of the therapies that do have some degree of scientific evidence to support their claims are difficult to use properly, such as silicone sheeting, and often result in only minor improvements to scar appearance. Alpha Connexin Carboxy-Terminus 1 (αCT1), marketed in clinical trials as Granexin® gel, is a protein-based therapy that works on the cellular level to fundamentally alter the skin's initial reaction to wounding and improving long-term scar appearance. This dissertation explores the link between cellular processes altered by αCT1 and long-term clinical improvements in scar appearance by studying both the extracellular matrix present in the scar in human and animal models and the creation of that extracellular matrix by dermal fibroblasts. In both human and animal models, topical application of αCT1 had no effect on skin surface appearance at early timepoints of 2-6 weeks, correlating with previous research that found scar appearance only improved at 3+ months post-injury. However, deep within the newly constructed tissue of the scar, these studies show the collagen organizational structure of αCT1-treated scars is more similar to unwounded skin and slightly more dense at early timepoints, suggesting αCT1 marginally improved the speed of healing. These findings in humans and animals were also verified in part in cell culture experiments that found dermal fibroblasts increased collagen output in response to αCT1 treatment. A novel wound healing model in the hairless guinea pig, superior at replicating human skin than established models like the rat, is also presented and shown to have effects strongly similar to the human with αCT1 treatment. These results provide a fundamental insight into the mode-of-action by which αCT1 may improve long term scar appearance and identifies early collagen structure as a target for future therapeutics to modify, as well as a new animal model in which to test them.

Objective: The aims of this prospective clinical cohort study were to determine the prevalence of asymptomatic bacteriuria in dogs with cranial cruciate ligament disease and to determine which clinical parameters and clinicopathologic data are associated with asymptomatic bacteriuria. Another aim was to determine the incidence of surgical site infections in dogs with and without asymptomatic bacteriuria. Results: In 156 dogs with cruciate ligament disease, the prevalence of asymptomatic bacteriuria was 7.1%. Furthermore, the prevalence was 12.4% in female dogs and 0% in male dogs. The most common bacterial isolate was Escherichia coli. Patient sex, urine white blood cells/ high-powered field, and microscopic bacteriuria were significantly different between dogs with and without asymptomatic bacteriuria. Only 60% of dogs with microscopic bacteriuria had growth on urine aerobic culture. No significant difference was found in age, body weight, body condition score, duration of lameness, limb affected, or other urinalysis values between dogs with and without asymptomatic bacteriuria. Of the dogs that had 8-week repeat cultures, 2/3 dogs with asymptomatic bacteriuria had negative urine cultures and 3/43 without asymptomatic bacteriuria had positive urine cultures. Of 57 dogs that received surgery and had sufficient follow-up, 15 developed surgical site infection. All surgical site infections occurred in dogs without AB. The incidence of surgical site infection in this population was 26.3% (15/57). Conclusions: Prevalence of asymptomatic bacteriuria in dogs presenting with cranial cruciate ligament disease was similar to previously reported values in male and female dogs. This suggests that dogs with cranial cruciate ligament disease are not more prone to asymptomatic bacteriuria than dogs in previously studied populations. Preliminary data suggests that AB does not predispose dogs to SSI however further research and continued data collection is warranted. / Master of Science / Asymptomatic bacteriuria is defined as having bacteria in the urine without signs of lower urinary tract disease. The aim of this study was to determine the prevalence asymptomatic bacteriuria in dogs with cranial cruciate ligament disease. Additionally, another aim was to determine the incidence of surgical site infections after cranial cruciate ligament surgery in dogs with and without asymptomatic bacteriuria. Prevalence of asymptomatic bacteriuria in dogs presenting with cranial cruciate ligament disease was found to be similar to previously reported values in male and female dogs. This suggests that dogs with cranial cruciate ligament disease are not more prone to asymptomatic bacteriuria than dogs in previously studied populations. Preliminary data suggests that dogs with bacteria in the urine does not predispose dogs to SSI however further research and continued data collection is warranted.

Orientador: Vânia Maria de Vasconcelos Machado / Resumo: A ressonância magnética é um método diagnóstico primordial na avaliação de enfermidades intracranianas na medicina e na medicina veterinária para a investigação, elaboração e realização de tratamentos, planejamento cirúrgico e controle. Por meio dessa modalidade diagnóstica pode-se pesquisar muitas enfermidades intracranianas: congênitas, malformações, inflamatórias, infecciosas, vasculares, neoplásicas dentre outras. Ressonância magnética é um exame não invasivo, baseado em princípios físicos complexos que formam imagens em múltiplos planos de uma determinada região. O objetivo deste trabalho é fornecer um estudo retrospectivo das enfermidades neurológicas presentes na rotina de exames de ressonância magnética da região crânio -encefálica e sua casuística na Faculdade de Medicina Veterinária e Zootecnia da Universidade Estadual Paulista, campus de Botucatu nos anos de 2012 a 2017. Realizou-se uma análise retrospectiva dos exames de ressonância magnética de pequenos animais da região crânio- encefálica. Os dados foram compilados e classificados segundo a região de exame, diferentes áreas de encaminhamento, casuística das enfermidades intracranianas segundo a espécie durante o período de 2012 a 2017. Dentre os 420 animais, sendo eles 340 canídeos e 80 felídeos observou-se dentre as regiões de exame o encéfalo com 95%; maioria dos encaminhamentos para a realização do exame de ressonância magnética são recebidos do serviço de neurologia veterinária 58%; a casuística das suspeita... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Magnetic resonance imaging is a primordial diagnostic method in the evaluation of intracranial diseases in medicine and veterinary medicine for investigation, elaboration and realization of treatments, surgical planning and control. By means of this diagnostic modality, one can investigate many intracranial diseases: congenital, malformations, inflammatory, infectious, vascular, and neoplastic among others. Magnetic resonance imaging is a non-invasive examination based on complex physical principles that form multi-plane imaging of a region. The goal of this work is to provide a retrospective study of the neurological diseases present in routine magnetic resonance imaging of the cranioencephalic region and its casuistry at the Faculty of Veterinary Medicine and Animal Science of the Universidade Estadual Paulista, Campus Botucatu, from 2012 to 2017. Was made a retrospective analysis of magnetic resonance imaging of small animals of the craniocephalic region. The data were compiled and classified according to the region of examination, different routing areas, and the number of intracranial diseases according to the species during the period from 2012 to 2017. Among the 420 animals, of which 340 canines and 80 felids were observed among the regions examination of the brain with 95%; most referrals for performing the MRI are received from the Veterinary Neurology Service 58%; the casuistry of the diagnostic suspicions of the diseases with 54 animals with convulsion, 49 animals ... (Complete abstract click electronic access below) / Doutor

Research involved in modeling human lung disease conditions has provided insight into disease development, progression, and treatment. In particular, mouse models of human pulmonary disease are increasingly utilized to characterize lung disease conditions. With advancements in small animal imaging it is now possible to investigate the phenotypic differences expressed in inbred mouse strains in vivo to investigate specific disease conditions that affect the lung. In this thesis our aim was to generate a comprehensive characterization of the normative mouse lung phenotypes in three of the most utilized strains of mice, C57BL/6, A/J, and BALB/c, through imaging techniques. The imaging techniques that we utilized in this research included micro-CT, a custom Large Image Microscope Array (LIMA) system for 3D microscopy, and classical histology. Micro-CT provided a non-destructive technique for acquiring in vivo and fixed lung images. The LIMA 3D microscopy system was utilized for direct correspondence of the gold standard histology images as well as to validate the anatomical structures and measurements that were extracted from the micro-CT images. Finally, complete lung histology slices were utilized for assessment of the peripheral airspace structures that were not resolvable using the micro-CT imaging system. Through our developed imaging acquisition and processing strategies we have been able to successful characterize important phenotypes in the mouse lung that have not previously been known as well as identify strain variations. These findings will provide the scientific community with valuable information to be better equipped and capable of pursuing new avenues of research in investigating pulmonary disease conditions that can be modeled in the mouse.