Dissertations / Theses on the topic 'Morphological diagnostic'

>Magister Scientiae - MSc
In this study PbSe quantum dots (QDs) were successfully synthesized via the organometallic and aqueous routes. Optical characterization was carried out using photoluminescence (PL) spectroscopy, structural and morphological characterization were carried out using X-ray diffraction (XRD) and transmission electron microscopy (TEM). Energy-dispersive X-ray spectroscopy (EDS) was used to determine the composition of the QDs. All the synthesized QDs were found to have emissions within the near-infrared region of the spectrum (≥1000 nm) with most of them being less than 5 nm in size. The aqueous synthesized QDs had a perfect Gaussian emission spectrum with a FWHM of ~23 nm indicating pure band gap emission and narrow size distribution respectively. The QDs were determined to have a cubic rock-salt crystal structure consistent with bulk PbSe. The aqueous synthesized QDs were however not stable in solution with the QDs precipitating after approximately 48 h. The organometallic synthesized QDs were transferred into the aqueous phase by exchanging the surface oleic acid ligands with 11-mercaptoundecanoic acid ligands. The ligand exchanged QDs were however stable in solution for over two weeks. The effects of reaction parameters on the optical and structural properties of the organometallic synthesized QDs were investigated by varying the reaction time, temperature, ligand purity, lead and selenium sources. It was observed that larger QDs were formed with longer reaction times, with reactions proceeding faster at higher reaction temperatures than at lower temperatures. Varying the ligand purity was found to have minimal effects on the properties of the synthesized QDs. The lead and selenium sources contributed largely to the properties of the QDs with lead oxide producing spherical QDs which were smaller compared to the cubic QDs produced from lead acetate. TBPSe was seen to produce smaller QDs as compared to TOPSe. The cytotoxity of the synthesized QDs was determined following the WST-1 cell viability assay with the QDs being found to be non-toxic at all the tested concentrations

One of the current problems among women’s reproductive system diseases is ovarian tumors. Each year the risk of this disease shows a tendency to increase. The pathognomonic feature of the morphological diagnostic of ovarian cancer is Psammoma bodies (PBs), which are represented by plasticized calcium structures and are placed in the form of concentration circles. Should be noted, that the process of pathological biomineralization is most common in serous papillary carcinoma, but the mechanism of PBs formation is not fully understood yet.

There have been phenomenal advances in the field of reproductive medicine and success rates following in vitro fertilisation have improved dramatically in recent years. The aim of this project was to improve our understanding of human preimplantation embryo development by identifying potential markers of viability that may aid us in selecting the best embryo for uterine transfer in the clinical embryology laboratory. Investigations into the distribution of cytoskeletal F-actin in human embryos demonstrated that a highly organised actin cortex is important for embryo cleavage and continued development to the blastocyst stage. Whilst they are polarised in the mouse from the oocyte to the blastocyst, the regulatory proteins leptin and STAT3 are co-localised only at the oocyte stage in humans, and are distributed within different cytoplasmic domains in human cleavage stage embryos and blastocysts. Whether polarity in humans is predetermined in the oocyte remains elusive, but none of the evidence generated in this thesis supports this idea. Leptin transiently activates STAT3 via the long form of the leptin receptor, and most significantly in the ICM of human day 6 blastocysts. Morphological features of blastocysts that can be visualised microscopically, such as a double ICM and cytoplasmic projections connecting the ICM to the TE, provide clues to their viability and may help us to choose the most suitable embryo from a cohort when deciding which to transfer. Nuclear volumes may in future contribute to this selection. Using time lapse technology to study cleavage patterns is now a routine occurrence in the clinical embryology laboratory. The results in this thesis show that distinctive patterns of divisions and the site at which blastocysts hatch can provide us with more information than a snap-shot morphological evaluation. Finally, contributing to the development of modelling software and predictive algorithms for the study of human embryos, particularly in time lapse imaging, means that our understanding of this fascinating area of medicine will continue to progress.

Background: Bone metastases occur in most patients with advanced hormone-refractory prostate cancer causing pain, pathologic fractures, and spinal cord compression. Few studies specifically address surgical treatment of metastatic spinal cord compression (MSCC) in prostate cancer. Criteria for identifying patients who may benefit from surgery are poorly defined. Most of the current knowledge regarding tumor biology in prostate cancer is based on studies of primary tumors or soft tissue metastases. The mechanisms regulating growth of bone metastases are not fully established. Aims: a) to evaluate outcome after surgery for MSCC in prostate cancer and to identify prognostic factors for survival and functional recovery; b) to evaluate current practice for referral of prostate cancer patients with MSCC; c) to analyze expression of androgen receptor (AR), cell proliferation, apoptosis, and prostate-specific antigen (PSA) in bone metastases with regard to survival after surgery for complications of bone metastases. Patients and Methods: We retrospectively evaluated the hospital records of 68 consecutive patients operated for metastatic spinal cord compression. Tumor tissue from bone metastases was obtained on spinal surgery (54 patients), fracture surgery (4 patients) and biopsy (2 patients), and analyzed by immunohistochemistry. Results: Study I: Mortality and complication rate after surgery was high. Patients with hormone-naïve disease and those with hormone-refractory disease with good performance status and without visceral metastases had more favorable survival. The ability to walk after surgery was related to better survival. Study II: A new score for prognosis of survival after surgery for spinal cord compression includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The score is simple, tumor specific, and easy to apply in clinical practice. Study III: Our results suggest that delays in diagnosis and treatment may have negative impact on functional outcome. Pretreatment ability to walk, hormone status of prostate cancer, and time from loss of ambulation influenced neurological recovery after surgery for spinal cord compression. Study IV: High nuclear AR immunostaining in bone metastases and high preoperative serum PSA were associated with a poor outcome after metastasis surgery in patients with hormone-refractory prostate cancer. Short-term effect of castration therapy disclosed that nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected. Conclusion:  Prostate cancer patients with metastatic spinal cord compression represent a heterogeneous group. We identified prognostic factors for survival and functional outcome, which may help clinicians in making decisions about treatment. Our results also implicate the need for development of local and regional guidelines for treatment of patients with spinal cord compression, as well as the importance of information to patients at risk.

Sinonasal and dental diseases can be a serious disorder in horses due to the persistence of the former and the common extension of the latter to the supporting bones of the skull. The diagnosis of equine sinonasal and dental disease can be challenging due to the complexity of these and adjacent anatomical structures, and therefore the use of advanced imaging, including computed tomography (CT) has greatly increased recently. A major aim of this study was to improve the morphological characterization of the sinuses and cheek teeth in normal horses of different ages. These studies defined the volumes of the 7 different sinus compartments; showed that the volume of the different compartments increase with age; that in contrast to accepted findings, the Triadan 09 alveoli is located in the caudal maxillary sinus (CMS) in 13% of the youngest group and the Triadan 10 alveoli is fully within the rostral maxillary sinus (RMS) in 53% of cases. The infraorbital canal was found to be susceptible to apical infection-related damage in horses < 2 years of age (< 2 y.o.) due to the intimate relationship of this canal and the medial aspect of the maxillary cheek teeth alveoli. The mean positions of the clinical crowns and apices of the maxillary Triadan 11s were 2.48 cm (adjusted 5.2% of head height) and 2.83 cm (adjusted 6.2% of head height) more rostral, respectively in horses >16 y.o. compared to horses < 6 y.o., consistent with rostral dental drift. Measurements of dental drift could provide further objective radiographic guidelines on ageing horses by dental imaging and also help our understanding of the aetiopathogenesis of cheek teeth diastemata. This study also found that the reserve crown length decreased from a mean of 4.7 cm (adjusted 19.7% of head height) in the youngest (< 6y.o.) group of horses to a mean of 2.9 cm (adjusted 10.5% of head height) in the oldest group (>15y.o.), with the 06s and 09s having the shortest reserve crowns. These data are useful reference information for clinicians and radiologists in the diagnosis and treatment of equine sinonasal and dental disease. Morphological characterization of the ventral and dorsal conchal bullae in horses of different age using CT described the age-related difference in sizes of these structures (smaller in younger horses). In the ventral conchal bulla, this reduction in volume was probably related to protrusion of the large dental alveoli in young horses into the nasal cavity and bulla. Bullae linear measurements and volumes were also associated with head size. The anatomical position of both bullae was associated with specific maxillary cheek teeth, thus increasing the diagnostic value of conventional radiography in the investigation of bulla disease and providing landmarks for the surgical treatment of this disorder. Skull shape analyzed with the use of Procrustes statistical analysis showed landmark variability between different age groups and in particular, high landmark variability between young (< 5y.o.) and old (>16y.o.) horses and less landmark variability between adult (6-15y.o.) and old horses. Future studies could investigate changes in the equine skull in relation to genotype to characterize breed-related diseases affecting teeth and sinonasal compartments. In the second part of the study, 32 infected maxillary cheek teeth extracted from clinical cases were evaluated grossly and histologically and these pathological results were compared to the pre-extraction radiographic and CT imaging findings. This study showed a high sensitivity (97%) of CT in detecting changes in teeth affected by apical infection. In the third part of the study, 30 cheek teeth assessed as being abnormal based on oral, radiographic and CT examinations were extracted along with their alveoli from 27 cadaver heads. Gross and histological examination findings from these teeth and alveoli were compared to the pre-extraction imaging findings, again showed high sensitivity (96.4%) of CT in diagnosing cheek teeth apical infection. Additionally, CT showed a high correlation with histology in detecting dental infection related alveolar bone changes including alveolar bone lysis, sclerosis and bone thickening. This aspect of the study was also the second largest pathological study of equine apical infection published to date and thus has also improved our understanding of the pathogenesis of this disorder. In conclusion, CT was shown to be an excellent imaging modality for improving the morphological characterization of the sinuses and teeth in normal horses of different ages, and thus also improving the value of this modality in diagnosis and treatment of disease affecting sinonasal and dental structures. This study also objectively showed the high sensitivity of CT in detecting cheek teeth apical infection in horses as compared to radiography, including by assessment of alveolar bone changes. Overall, the results of this project improve morphological knowledge of the equine skull and teeth and will have direct clinical benefits by improving the diagnosis and thus the treatment of equine sinonasal and dental disease.

Assisted reproductive technology procedures has become a more complex treatment over the years after implementation of preimplantation genetic diagnostics and cryopreservation methods such as slow freeze and vitrification. When embryos undergo these methods they are exposed to external damage that threaten to affect their quality and thereby lead to lower survival rates and lower pregnancy rates. The aim of this study was to document blastocysts quality after vitrification, re-vitrification and preimplantation genetic diagnosis with subsequent vitrification. A total of 126 blastocysts were collected, of which 119 blastocysts were documented with the help of an experienced embryologists and the remaining seven blastocysts were from a new series of re-vitrified embryos. The 126 collected blastocyst were allocated into groups depending on their degree of preimplantation genetic diagnosis and vitrification. The gathered data was scoring according to morphology, expansion and proportion of necrotic cells at 2 and 4 hours of the expansion phase. Fisher exact test was used for statistical evaluation. There were no significant difference when comparing data before and after vitrification and preimplantation diagnosis, which indicates that these methods do not cause morphological damage to the blastocyst.

Актуальність: Проблема діагностики захворювань передміхурової залози є на сьогоднішній день надзвичайно актуальною. В Україні рак передміхурової залози (РПЗ) посідає 4 місце після раку легень, шлунку, шкіри. Мета: Дослідити основні методи ранньої діагностики РПЗ в світовій практиці та прогноз в залежності від морфологічної будови пухлини.

Akutni respiratorni distres sindrom (ARDS) predstavlja klinički sindrom koji se manifestuje teškom respiratornom insuficijencijom sa razvojem akutnog edema pluća u odsustvu znakova popuštanja leve polovine srca. S obzirom da ovaj sindrom ima heterogenu etiologiju, progresivan tok i visoku stopu mortaliteta, pravovremena i tačna dijagnoza esencijalna je u primeni efektivne i rane terapije, a samim tim i u poboljšanju prognoze bolesti. Cilj ove doktorske disertacije bio je da se ispita povezanost kliničke i patohistološke dijagnoze ovog sindroma, kao i da se analiziraju i uporede vrednosti kliničkih parametara neophodnih za postavljanje dijagnoze ARDS-a sa patohistološkim parametrima oštećenja plućnog tkiva. Studija je obuhvatila 67 pacijenata Instituta za plućne bolesti Vojvodine koji su umrli pod kliničkom slikom ARDS-a i/ili kod kojih je na obdukciji patohistološki dokazan ARDS. Za postavljanje kliničke dijagnoze ARDS-a korišćeni su kriterijumi The American-European Consensus Conference iz 1994. Nakon semikvantitativne analize patohistoloških parametara difuznog alveolarnog oštećenja određivan je histološki stadijum ARDS-a i svi pacijenti podeljeni su u dve grupe: I grupa - pacijenti u eksudativnoj fazi i II grupa - pacijenti u proliferativnoj fazi difuznog alveolarnog oštećenja. Formirane grupe pacijenata upoređivane su u odnosu na vrednosti kliničkih parametara 12h pre smrtnog ishoda. U cilju procene prisustva komorbiditeta analizirani su indeks telesne mase (engl. body mass index- BMI) i podaci o prethodno dijagnostikovanoj arterijskoj hipertenziji. Kod svih pacijenata uključenih u studiju upoređivane su kliničke dijagnoze sa obdukcionim nalazom. Za klasifikaciju autopsijskih dijagnoza korišćena je Goldman-ova klasifikacija. Na osnovu provedenog istraživanja, došlo se do zaključka da slaganje klinički dijagnostikovanih i patohistološki potvrđenih slučajeva ARDS-a iznosi 68%. Senzitivnost kliničke dijagnoze ARDS-a iznosi 82%, a pozitivna prediktivna vrednost 80%. Pacijenti sa nalazom eksudativne faze DAD-a u plućnom tkivu su u najvećem procentu imali klinički težak ARDS, dok su se pacijenti sa nalazom proliferativne faze sindroma češće manifestovali pod kliničkom slikom srednje teškog ARDS-a, odnosno utvrđeno je da postoji statistička povezanost između nižih vrednosti PaO2/FiO2 i teže faze ARDSa. Patohistološkom analizom promena u plućnom tkivu nađeno je da najvažnija obeležja eksudativne faze ARDS-a predstavljaju: hijaline membrane, edem i krvarenje, dok su se kao najvažnija obeležja proliferativne faze ARDS-a izdvojili: proliferacija pneumocita tipa II, intersticijalna i mutilantna fibroza i organizirajuća pneumonija. Kod pacijenata sa kliničkom dijagnozom ARDS-a kod kojih ARDS nije i patohistološki dokazan, najčešći nalaz na plućima bila je fibrinozno-purulentna bronhopneumonija. Analizom etioloških faktora koji doprinose razvoju ovog sindroma otkriveno je da je ARDS najčešće nastao kao posledica delovanja direktnih/pulmonalnih činilaca: pneumonije i virusa gripa H1N1. Najzastupljeniji komorbiditeti prisutni kod pacijenata sa ARDS-om bili su sistemska hipertenzija i gojaznost. Najzad, kod svih pacijenata uključenih u istraživanje upoređivane su kliničke dijagnoze sa obdukcionim nalazom i na osnovu Goldman-ove klasifikacije kliničke dijagnoze i obdukcioni nalaz slažu se u 72% slučajeva. Rezultati ove studije mogli bi se upotrebiti u daljim istraživanjima kako bi omogućili bolji dijagnostički pristup ovom problemu, a samim tim i bolji terapijski pristup i smanjivanje stope mortaliteta.
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by severe respiratory failure with development of acute pulmonary edema in the absence of left heart failure signs. Since this syndrome has a heterogeneous etiology, progressive course and high mortality, timely and accurate diagnosis is essential in the implementation of effective and early treatment, and therefore in improving the prognosis of the disease. The aim of this PhD thesis was to examine the association between clinical and pathohistological diagnosis of this syndrome, as well as to analyze and compare the values of clinical parameters necessary for the diagnosis of ARDS with pathohistological parameters of diffuse alveolar damage. The study included 67 patients of the Institute for Lung Diseases who died under clinical picture of ARDS and / or in which, at the autopsy, pathohistological diagnosis of ARDS was set. To set up a clinical diagnosis of ARDS the criteria of the American-European Consensus Conference in 1994 were used. After a semi-quantitative analysis of histopathological parameters of diffuse alveolar damage, all patients were divided into two groups: Group I - patients in the exudative stage and Group II - patients in the proliferative phase of diffuse alveolar damage. Formed groups of patients were compared with respect to clinical parameters values 12 h before death. In order to assess the presence of comorbidities body mass index (BMI) and data on previously diagnosed arterial hypertension were analyzed. In all patients included in the study the clinical diagnosis were compared with autopsy findings according to Goldman's classification. According to this study, agreement of clinically diagnosed and histologically confirmed cases of ARDS is 68%. The sensitivity of clinical diagnosis of ARDS is 82%, and positive predictive value is 80%. Patients with exudative phase of DAD most frequently had a severe form of ARDS, whereas patients with proliferative phase often manifested with moderate form of ARDS, ie it was found that there is a statistical association between lower values PaO2 / FiO2 and more severe phase of ARDS. Pathological analysis of changes in lung tissue revealed that the most important characteristics of exudative phase of ARDS are: hyaline membrane, edema and bleeding, while the most important features of the proliferative phase of ARDS are: the proliferation of type II pneumocytes, interstitial fibrosis and mutilating and organizing pneumonia. In patients with a clinical diagnosis of ARDS in which ARDS was not pathohistologically proven, the most common finding in the lungs was fibrinous-purulent bronchopneumonia. The analysis of etiological factors that contribute to the development of this syndrome discovered that ARDS usually develop as a result of pulmonary factors: pneumonia and influenza virus H1N1. The most common comorbidities present in patients with ARDS were systemic hypertension and obesity. Finally, in all patients included in the study clinical diagnosis and autopsy findings were compared and based on Goldman's classification clinical diagnosis and autopsy findings are in agreement in 72% of cases. The results of this study could be used in further research to enable better diagnostic approach to this problem, and therefore a better therapeutic approach and reducing mortality rates.

La réussite d'un programme de lutte biologique ou intégrée est fortement liée à l'agent de lutte impliqué, à ses caractéristiques intrinsèques et à ses différentes interactions avec le milieu cible d'introduction. Une juste identification de l'ennemi naturel, une connaissance approfondie de sa biologie, son écologie, son potentiel de gestion des populations de nuisibles et même, de sa génétique sont indispensables avant son implication dans un tel programme. Ce travail de thèse s'insère dans le cadre de la problématique de limitation des risques sanitaires et environnementaux liés aux productions de fruits et légumes au niveau du bassin méditerranéen. Plus spécifiquement, il s'agit de limiter les impacts phytosanitaires et économiques de certains ravageurs s'attaquant à la tomate (Solanum lycopersicum L.), culture méditerranéenne par excellence. Depuis une vingtaine d'années, la protection biologique et intégrée a considérablement évoluée en mettant en jeu une large gamme d'agents de lutte pour une gestion satisfaisante des principales invasions parasitaires (les deux aleurodes Bemisia tabaci (Gennadius, 1889) et Trialeurodes vaporariorum (Westwood, 1856), et plus récemment le lépidoptère Tuta absoluta (Meyrick, 1917) ). Parmi les auxiliaires utilisés en région méditerranéenne, une punaise zoophytophage appartenant au genre Macrolophus (Hemiptera: Miridae) s'est imposée comme la pierre angulaire du contrôle biologique des ravageurs de la tomate. Bien que commercialisé depuis les années 90 sous le nom de Macrolophgus caliginosus, son identité spécifique porte encore à confusion. Ceci est du à la présence dans la zone d'origine (bassin méditerranéen) de deux espèces morphologiquement très proches : Macrolophus caliginosus/melanotoma et Macrolophus pygmaeus. La première partie de la thèse a permis de clarifier ce problème d'identification par une double approche morphologique et moléculaire, et de proposer une nouvelle clé d'identification de toutes les espèces paléarctiques du genre Macrolophus. La deuxième partie s'est focalisée sur des aspects de la bio-écologie de l'espèce commercialisée identifiée dans cette thèse comme M. pygmaeus. L'influence des ressources trophiques sur sa capacité de survie a été d'abord étudiée puis le caractère cannibale de cet agent de lutte a été mis en évidence. L'étroite relation entre sa phytophagie et sa zoophagie a été démontrée et enfin l'impact de la température sur sa réponse fonctionnelle a été caractérisé. Les résultats montrent l'importance de tous ces paramètres sur le potentiel de prédation de M. pygmaeus et soulignent leur contribution à la réussite ou à l'échec de son rôle dans la protection biologique intégrée de la tomate
The success of a biological or integrated pest management control program is deeply dependant of the involved biological control agent as well as its intrinsic characteristics and its various interactions with the target introduction area. Before any implication in such a program an accurate/correct identification, a detailed knowledge of its biology, ecology, potential in pest control are necessary. This work was developed in a context of the sanitary and environmental fruits and vegetables production limitation risk problems. It consists, more specifically, in the phytosanitary and environmental impact limitations of some tomato (Solanum lycopersicum L.) pests. In the last twenty years, the biological and integrated pest management has considerably changed by involving a large scale of biological control agents for a successful control of the main parasitic invasions (the two whiteflies, Bemisia tabaci [Gennadius, 1889) and Trialeurodes vaporariorum (Westwood, 1856), more recently the moth Tuta absoluta (Meyrick, 1917)]. Among the natural enemies used on the Mediterranean region, one finds a zoophytophagous bug belonging to the Macrolophus genus (Hemiptera: Miridae. In spite of its marketing since the 1990s under the name Macrolophgus caliginosus, its specific identity still remains unclear. This is due to the presence in the origin zone (Mediterranean area) of two morphologically closed species: Macrolophus caliginosus/melanotoma and Macrolophus pygmaeus. The first part of this thesis shed light on the identification problem through a double morphological and molecular approach. It also provided a new identification key of all the Palaearctic species belonging to the genus Macrolophus. The second part focused on some bio-ecological traits of the commercialised species, identified in this work as M. pygmaeus. The influence of trophic/feeding resources on the survival capacity has been studied and a cannibalistic behaviour has been demonstrated. The close relationship between phytophagy and zoophagy was characterized; finally the impact of temperature on its functional response was described. The results showed the importance of all these parameters on M. pygmaeus predation potential and emphasized their contribution on the success or failure in tomato pest management

Fulminant myocarditis is rare but a potentially life-threatening disease. Acute or mild myocarditis following acute ischemia is generally associated with a profound activation of the host’s immune system. On one hand this is mandatory to protect the host’s heart by fighting the invading agents (i.e., bacteria, viruses or other microbial agents) and/or to induce healing and repair processes in the damaged myocardium. On other hand, uncontrolled activation of the immune system may result in the generation of auto-reactive (not always beneficial) immune cells. Myocarditis or inflammatory cardiomyopathy is characterized by focal or diffuse infiltrates, myocyte necrosis and/or apoptosis and subsequent fibrotic replacement of the heart muscle. In humans, about 30% of the myocarditis-patients develop dilated cardiomyopathy. As the clinical picture of myocarditis is multifaceted, it is difficult to diagnose the disease. Therefore, the main goal of the present work was to test and further develop novel non-invasive methods for the detection of myocardial inflammation by employing both contrast enhanced MRI techniques as well as novel nuclear tracers that are suitable for in vivo PET/ SPECT imaging. As a part of this thesis, a pre-clinical animal model was successfully established by immunizing female Lewis rats with whole-porcine cardiac myosin (CM). Induction of Experimental Autoimmune Myocarditis (EAM) is considered successful when anti-myosin antibody titers are increased more than 100-fold over control animals and pericardial effusion develops. In addition, cardiac tissues from EAM-rats versus controls were analyzed for the expression of various pro-inflammatory and fibrosis markers. To further exploit non-invasive MRI techniques for the detection of myocarditis, our EAM-rats were injected either with (1) ultra-small Paramagnetic iron oxide particles (USPIO’s; Feraheme®), allowing for in vivo imaging , (2) micron sized paramagnetic iron oxide particles (MPIO) for ex vivo inflammatory cell-tracking by cMRI, or (3) with different radioactive nuclear tracers (67gallium citrate, 68gallium-labeled somatostatin analogue, and 68gallium-labeled cyclic RGD-peptide) which in the present work have been employed for autoradiographic imaging, but in principle are also suitable for in vivo nuclear imaging (PET/SPECT). In order to compare imaging results with histology, consecutive heart sections were stained with hematoxylin & eosin (HE, for cell infiltrates) and Masson Goldner trichrome (MGT, for fibrosis); in addition, immuno-stainings were performed with anti-CD68 (macrophages), anti-SSRT2A (somatostatin receptor type 2A), anti-CD61 (β3-integrins) and anti-CD31 (platelet endothelial cell adhesion molecule 1). Sera from immunized rats strongly reacted with cardiac myosin. In immunized rats, echocardiography and subsequent MRI revealed huge amounts of pericardial effusion (days 18-21). Analysis of the kinetics of myocardial infiltrates revealed maximal macrophage invasion between days 14 and 28. Disappearance of macrophages resulted in replacement-fibrosis in formerly cell-infiltrated myocardial areas. This finding was confirmed by the time-dependent differential expression of corresponding cytokines in the myocardium. Immunized animals reacted either with an early or a late pattern of post-inflammation fibrosis. Areas with massive cellular infiltrates were easily detectible in autoradiograms showing a high focal uptake of 67gallium-citrate and 68gallium labeled somatostatin analogues (68Ga DOTA-TATE). Myocardium with a loss of cardiomyocytes presented a high uptake of 68gallium labeled cyclic RGD-peptide (68Ga NOTA-RGD). MRI cell tracking experiments with Feraheme® as the contrast-agent were inconclusive; however, strikingly better results were obtained when MPIOs were used as a contrast-agent: histological findings correlated well with in vivo and ex vivo MPIO-enhanced MRI images. Imaging of myocardial inflammatory processes including the kinetics of macrophage invasion after microbial or ischemic damage is still a major challenge in, both animal models and in human patients. By applying a broad panel of biochemical, histological, molecular and imaging methods, we show here that different patterns of reactivity may occur upon induction of myocarditis using one and the same rat strain. In particular, immunized Lewis rats may react either with an early or a late pattern of macrophage invasion and subsequent post-inflammation fibrosis. Imaging results achieved in the acute inflammatory phase of the myocarditis with MPIOs, 67gallium citrate and 68gallium linked to somatostatin will stimulate further development of contrast agents and radioactive-nuclear tracers for the non-invasive detection of acute myocarditis and in the near future perhaps even in human patients
Eine fulminant verlaufende Myokarditis ist eine seltene aber potentiell lebensbedrohliche Erkrankung. Akute oder chronische Myokarditis gehen generell mit einer starken Aktivierung des Immunsystems der Betroffenen einher. Zum einen ist dies notwendig, um das Herz durch Bekämpfung der Eindringlinge (z.B. Bakterien, Viren oder andere mikrobielle Erreger) zu schützen und/oder Heilungs- und Reparaturprozesse im geschädigten Myokard einzuleiten. Zum anderen kann eine unkontrollierte Aktivierung des Immunsystems aber auch zur Entstehung von (nicht immer vorteilhaften) auto-reaktiven Immunzellen führen. Eine Myokarditis oder entzündliche Kardiomyopathie ist charakterisiert durch fokale oder diffuse Infiltrate, Nekrose und/oder Apoptose der Myozyten und einen fortschreitenden fibrotischen Ersatz des Herzmuskelgewebes. Beim Menschen entwickeln etwa 30% der Myokarditis-Patienten eine dilatative Kardiomyopathie. Da das klinische Bild der Myokarditis sehr vielfältig sein kann, ist die Diagnosestellung dieser Erkrankung schwierig. Deshalb war es das Kernziel dieser Arbeit, nicht-invasive Methoden zum Nachweis myokardialer Entzündungen zu testen, und dabei neue Bildgebungsverfahren unter Einsatz von neuen MRT-Kontrastmitteln sowie neuen nuklearen Tracern, die auch für PET/SPECT geeignet wären, zu entwickeln. Diese Verfahren wurden von uns zunächst an einem human-analogen Ratten-Modell evaluiert, mit dem Ziel später evtl. auch einmal beim Menschen eingesetzt werden zu können. Für unser präklinisches Tiermodell wurden weibliche Lewis-Ratten mit kardialem Myosin aus Schweinen immunisiert. Die erfolgreiche Induktion einer „Experimentellen Autoimmunen Myokarditis (EAM)“ wurde durch einen signifikanten Anstieg der Anti-Myosin Antikörpertiter in immunisierten Tieren und die Ausbildung eines Perikardergusses (Echokardiographie) bestätigt. Zusätzlich wurde aus apikalem kardialem Gewebe RNA isoliert und die Expression verschiedener pro-inflammatorischer und pro-fibrotischer molekularer Marker untersucht. Um die Bildgebung mittels kontrast-verstärktem cMRT zu optimieren, wurden den Tieren entweder kleine Eisenoxid-Nanopartikel (Ultra small paramagnetic iron oxide particles, USPIO; Feraheme®), oder sog. ,,Micronsized paramagnetic iron oxide particles (MPIO)‘‘ für das Tracking inflammatorischer Zellen injiziert. Im daraufolgenden Schritt wurden radioaktive nukleare Tracer (67Gallium-Citrat, 68Gallium-markierte Somatostatin-Analoga und 68Gallium-markierte zyklische RGD-Peptide) injiziert, um dann Autoradiogramme von Herzschnitten zu gewinnen

碩士
中原大學
醫學工程研究所
91
Lung cancer becomes one of worldwide deadly diseases growing with each passing day. Using high resolution Computed Tomography images due to complex lung pathological changes can help to find lurk nidus on chest X-ray images. This study developed a set of utilizing computer assistant quantification analysis and diagnosis system in order to help doctors distinguish lung nodules and provide patients with condition track. This study directly caught lung DICOM images to analyze which where aimed at tissues interesting applying window/level to modulate. Using image process technology, for example, image enhance, semi-automated edge selection, Gaussian smoothing, curvatures calculation, circularity and texture count, etc. the shapes of lung nodules were analyzed and diagnosed. Furthermore, combining OpenGL and Marching cube algorithms could show 3-dimension images of chest and nodules and provide the observation in morphology. During study processing, image simulation nodule phantoms including different sections of thickness spherical phantom CT images and different appearance spherical phantoms were used to test parameters accuracy of system and precede actual diagnostic differentiation and conference for clinical lung cancer cases. Besides, with assistance of clinical doctors, the differences between this system and traditional artificial distinguishing the benignancy and malignant nodules were compared. Preliminary results showed that the accuracy of system and the error of curvatures calculation in different sections of thickness in phantom test evaluating which due to insert-value technology in reconstruction. In clinical cases analysis, two different sections of thickness 3mm and 5mm were evaluated. The results showed that the accuracy was 0.67, sensitivity was 1 and Kappa is 0.378 for 3mm section thickness lung nodules testing cases. The reasons of low accuracy and Kappa were the testing data size were too small and the great part in benign cases which were inflammation type and fibered nodules, its each characteristics, were similar to malignant nodules. For 5mm section thickness lung nodules testing cases, accuracy was 0.833, specificity was 1 and Kappa was 0.515. For the results, we found that the characteristics of the calcification nodes of benign nodules, bacterial affection and fibered types were similar to malignant nodules, hence, this lower accuracy were got in this system. The accomplishment of system can provide texture analysis and diagnoses in lung nodules, and help differential diagnosis in clinical lung nodules actually. It also supported the evaluation in lung cancer before and after of treatment. In the future, we will increase the clinical cases collections and feature parameters of other nodules which will perfect the trainings in Back Propagation Neural Network and raise the accuracy of system. To add automatic edge detection function also can improve the efficiency of this system.

博士
國立陽明大學
醫學工程研究所
98
With technique improvement, sonography has been widely employed in the development of the computer-aided diagnosis system. In recent years, the main researches of computer-aided diagnosis system have focused on the common tumors, such as the breast cancer, lung cancer, and etc., and most of them have been approved for the usefulness in clinic. Some uncommon tumors–like soft-tissue tumors, is difficult for the physicians to accumulate the diagnostic experiences. The study is based on the collection of various types of soft-tissue tumors to develop a computer-aided diagnosis as second opinion in clinical use. In this dissertation, the morphological features and texture features of soft-tissue tumors were extracted for the tumor classification. Generally, the natures of morphological features accorded with the malignant tumors are directly spreading into local invasion to the pseudocapsule and peripheral structural tissues. In comparison with the benign tumors sonograpghically, shapes with malignant tumors are appearing to irregularity and protrusion. Furthermore, texture features which can be regarded as another feature for the tumor diagnosis are retrieved from the visual perception for representing the characteristics of smooth and homogeneous echogenecity for benign tumors; in the other hand, the characteristics of high echogenecity and high contrast for malignant tumors. Last, the clinical evaluation by the physicians was added to evaluate the effectiveness and reliability of the system for the validation of diagnostic model which was capable of providing the valuable reference in the tumor diagnosis.

Dissertação de mestrado em Evolução e Biologia Humanas apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra
O estudo da dentição surge na Antiguidade Clássica, desenvolvendo-se para a análise da anatomia (formação e estudo histológico dentário) nos séculos XVIII e XIX (Alt et al., 1998). Os caracteres discretos começam a considerar-se na pesquisa de relações biológicas entre populações a partir do século XIX (Silva, 2002), surgindo a apreciação dos caracteres fenotípicos dentários a partir do trabalho de Lasker (1950, in Irish e Nelson, 2008). A consideração por graus da variação discreta dos caracteres identificados surge sistematicamente com o método ASUDAS (Turner et al., 1991). O presente trabalho teve como objectivos estudar os caracteres discretos de 163 mandíbulas e da dentição presente em 104 destas, caracterizando uma população de origem portuguesa, alojada no Museu de História Natural da FC-UP. Além disso, pretendeu-se caracterizar biologicamente essa amostra através do padrão estabelecido, quando comparado com o de outras populações mundiais e ibéricas. O sistema ASUDAS (Tuner et al., 1991), a que se acresceu um carácter sugerido por Weets (2009), foi usado para a caracterização morfológica dentária. Hauser e De Stefano (1989), Movsesjan et al. (1975 in Galera et al., 1995) e Albuquerque (1952) sugeriram metodologias de observação dos caracteres anatómicos mandibulares, aqui adoptadas. A diagnose sexual mandibular recorreu, ainda, a vários métodos complementares (Loth e Henneberg [1996], adaptado por Balci et al. [2005]; Buikstra et al., 1994; Ferenbach et al., 1980; Giles, 1964). As frequências de caracteres não-métricos dentários permitiram denotar a proximidade da população estudada com as populações europeias e, em menor grau, norte-africanas. A comparação com amostras ibéricas mostrou uma semelhança entre estas e o presente material, indiciando alguma proximidade com populações de território português. Os dados referentes a caracteres mandibulares corroboram a ligação biológica a populações europeias, o que era esperado. Este trabalho contribuiu assim para a caracterização de uma amostra que se presumia portuguesa , através da dentição inferior e da morfologia mandibular. O autor sugere investimento da investigação na caracterização da morfologia dentária das amostras portuguesas, recentes e de passados mais remotos, que contribuam para a interpretação da história ibérica, sublinhando a necessidade de garantir resultados completos e inequívocos.
The study of human dentition began in the Classical Era, developing towards the analysis of anatomy (dental formation and histology) in the 18th and 19th centuries (Alt et al., 1998). Discrete trais were used in the search for biological relationships between populations from the 19th century onwards (Silva, 2002), and the consideration of fenotypical dental traits was brought on by Lasker.s work (Lasker, 1950, in Irish e Nelson, 2008). The recording by degrees of expression was systematized by the ASUDAS method (Turner et al., 1991). The present work has the objective of studying the discrete traits of 163 mandibles and the dentition present in 104 of these, to characterize a population of portuguese origin, located at the Museu de Historia Natural da FC-UP. As well as this, there was the intention of biologically characterizing such sample, by comparing the established pattern with the ones found in world and iberian samples. The ASUDAS system, to which a trait suggested by Weets (2009) was added, was used to characterize the dental morphology. Hauser and De Stefano (1989), Movsesjan et al. (1975 in Galera et al., 1995) and Albuquerque (1952) suggested methods of recording mandibular non-metric traits, adopted herein. The mandibular sexual diagnosis was established through a multiplicity of complementary methodologies (Loth and Henneberg [1996], adapted by Balci et al. [2005]; Buikstra et al., 1994; Ferenbach et al., 1980; Giles, 1964). The frequencies of non-metric dental traits allowed the identification of the proximity of european samples and, to a lesser degree, of north African samples, to the present population. The comparison of iberian samples showed likeness between these and the present material, underlining some proximity with the populations in the current xv portuguese territory. The data referring to mandibular traits corroborate the biological link to european populations, which was expected. This work thus contributes to characterize a sample that was assumed to be Portuguese and natural of Oporto, through the inferior dentition and the mandibular traits. The author suggests that future researchers should invest in characterizing the portuguese samples, recent and otherwise, contributing to a greater knowledge of iberian history, also emphasizing the need to acquire complete and unequivocal results.