The maintenance and regulation of cellular NAD(P)(H) content and its influence on cell function involves in many metabolic pathways which are poorly understood. Niacin deficiency in humans, which leads to low NAD status, causes sun sensitivity in skin, indicative of DNA repair deficiencies. Animal models of niacin deficiency demonstrate genomic instability and increased cancer development in sensitive tissues including skin. Therefore, we have developed a cell culture model that allows assessment of pathways regulated by NAD(P) content as a way to identify NAD-dependent signaling events that may be critical in early skin carcinogenesis. Using our model, we showed that niacin restriction, and consequent NAD depletion, reversibly alters NAD(P)(H) pools, increases apoptosis, induces G2/M cell cycle arrest, and decreases DNA stability. These alterations are affected by increased expression and activity of NOX leading to an accumulation of ROS, which may provide a survival mechanism as has been shown in cancer cells. Our data also support the hypothesis that glutamine is a likely alternative energy source during niacin deficiency. Here, we also identified the expression of all seven NAD-dependent deacetylase (SIRT) family members in skin cells. We showed that in response to photodamage, the expression of several SIRTs is altered in keratinocytes. Furthermore, we showed that SIRTs responses to photodamage differ between normal and immortalized keratinocytes, which may be indicative of alterations potentially important in skin carcinogenesis. In addition, we have shown that NAD-depleted HaCaT keratinocytes are more sensitive to photodamage. We observed that both poly(ADP-ribose) polymerases (PARPs) and SIRTs are inhibited by the unavailability of their substrate, NAD+, leading to unrepaired DNA damage upon photodamage and subsequent increase in cell death. Our data demonstrate that both SIRTs and PARPs are critical following DNA damage and identify which SIRTs are essential. Finally, we identified for the first time the expression of the nicotinic acid receptor in human skin keratinocytes, mainly in the differentiating keratinocytes of the stratum corneum in the epidermis. This study identifies new roles for niacin as a potential skin cancer prevention agent and demonstrates that niacin status is a critical resistance factor for UV damaged skin cells.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-05-04T19:02:47Z No. of bitstreams: 1 CHRISTINA_PIMENTEL_OPPERMANN_KUSSLER.pdf: 1245692 bytes, checksum: dfe118de17f82c070a6bae2300e41933 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-05-14T12:19:33Z (GMT) No. of bitstreams: 1 CHRISTINA_PIMENTEL_OPPERMANN_KUSSLER.pdf: 1245692 bytes, checksum: dfe118de17f82c070a6bae2300e41933 (MD5) / Made available in DSpace on 2018-05-14T12:22:46Z (GMT). No. of bitstreams: 1 CHRISTINA_PIMENTEL_OPPERMANN_KUSSLER.pdf: 1245692 bytes, checksum: dfe118de17f82c070a6bae2300e41933 (MD5) Previous issue date: 2017-12-26 / Introduction: endometrial cancer is the most prevalent gynecological neoplasm in developed countries and the second most prevalent in Brazil, second only to cervical cancer. It corresponds to 5% of cancers in women worldwide. The majority of cases present as initial disease, and surgical treatment is curative. Few treatment options exist for patients with poor prognostic factors and advanced disease, and the process of carcinogenesis in endometrial cancer has not been fully elucidated. Sirtuins are proteins involved in several cellular processes. The family of these proteins is composed of seven sirtuins (SIRT1-SIRT7). They present specific cell locations, acting in a variety of processes, including regulation of gene transcription, genomic stability, metabolic control, cell cycle regulation, and cell survival. Few studies have evaluated the role of sirtuins in endometrial cancer as well as its association with prognostic factors. Objective: to evaluate the expression of SIRT1 and SIRT7 enzymes in histological samples of endometrial carcinoma of patients operated at Hospital S?o Lucas (Pontif?cia Universidade Cat?lica) between January 2000 and December 2015 and associate the expression of these proteins with the pathological staging and prognostic factors. Materials and Methods: we performed a retrospective study evaluating 66 samples of patients with endometrial cancer from January 2000 to December 2015. The expression of SIRT1 and SIRT7 proteins was identified by the immunohistochemical technique and quantified by the Allred score. The expression of these proteins in cancer samples was correlated with the prognostic factors: age, tumor grade, tumor size, myometrial invasion, lymphovascular invasion and pathological staging. Results: SIRT 1 expression was positive in 40.9% of samples and SIRT7 expression in 24.1% of cases. Expression of these proteins did not present a statistically significant association with any of the adverse prognostic factors in endometrial cancer. Conclusions: endometrial cancer samples were positive for both SIRT1 and SIRT7, but without correlation in the study with prognostic factors. Expression of these proteins in samples of endometrial cancer may represent a possible therapeutic target to be developed in future studies. / Introdu??o: O c?ncer de endom?trio ? a neoplasia maligna ginecol?gica mais prevalente nos pa?ses desenvolvidos e a segunda mais prevalente no Brasil, menos freq?ente apenas do que o c?ncer de colo uterino. Corresponde a 5% dos c?nceres em mulheres no mundo. A maioria dos casos se apresenta como doen?a inicial, sendo o tratamento cir?rgico curativo. Existem poucas op??es de tratamento para pacientes com fatores progn?sticos adversos e com doen?a avan?ada, sendo ainda pouco elucidado o processo de carcinog?nese no c?ncer de endom?trio. As sirtu?nas s?o prote?nas envolvidas em diversos processos celulares. Sua fam?lia ? composta por sete sirtu?nas (SIRT1-SIRT7). Apresentam localiza??es celulares espec?ficas, atuando em uma s?rie de processos, incluindo a regula??o da transcri??o g?nica, estabilidade gen?mica, controle metab?lico, regula??o do ciclo celular e sobreviv?ncia celular. Poucos estudos avaliaram o papel das sirtu?nas no c?ncer de endom?trio, bem como a sua associa??o com fatores progn?sticos. Objetivo: avaliar a express?o das enzimas SIRT1 e SIRT7 em amostras histol?gicas de carcinoma de endom?trio de pacientes operadas no Hospital S?o Lucas da Pontif?cia Universidade Cat?lica do Rio Grande do Sul (PUCRS) no per?odo de janeiro de 2000 a dezembro de 2015 e associar a express?o dessas prote?nas com o estadiamento patol?gico e fatores progn?sticos. M?todos: foi realizado um estudo retrospectivo com a avalia??o de 66 amostras de pacientes com c?ncer de endom?trio no per?odo de janeiro de 2000 at? dezembro de 2015. A express?o das prote?nas SIRT1 e SIRT7 foi identificada pela t?cnica de imunohistoqu?mica e quantificada pelo escore de Allred. A express?o dessas prote?nas nas amostras de neoplasia foi correlacionada com os fatores progn?sticos: idade, grau tumoral, tamanho do tumor, invas?o miometrial, invas?o linfovascular e estadiamento patol?gico. Resultados: a express?o de SIRT1 foi positiva em 40.9% das amostras e a de SIRT7 em 24.1% dos casos. A express?o dessas prote?nas n?o apresentou associa??o estatisticamente significativa com nenhum dos fatores progn?sticos adversos no c?ncer de endom?trio. Conclus?es: as amostras de c?ncer de endom?trio apresentaram positividade, tanto para SIRT1 quanto para SIRT7, mas sem correla??o com fatores progn?sticos. A express?o dessas prote?nas em amostras de neoplasia de endom?trio pode significar um poss?vel alvo terap?utico a ser estudado e desenvolvido em estudos futuros.

Radioembolization (also called selective internal radiation therapy, SIRT) with yttrium-90 (90Y)-loaded microspheres has been broadly adopted as a locoregional therapy for primary and metastatic liver cancers. Although radioembolization is a well-established therapy, efforts to personalise and refine the planning and administration of therapy are ongoing. The ability to accurately predict, plan and deliver optimal doses to tumour and non-tumour tissues, including final validation of dose distribution, is essential for successful radiotherapy. Determining the true dose absorbed by tissue compartments is the primary way to safely individualise therapy for maximal response while respecting normal tissue tolerances. The overarching objective of this work was to expand our knowledge of dosimetry in 90Y-resin-microsphere radioembolization, with the ultimate goal of improving the clinical outcomes in our patients. Initially we sought to identify the patient- and treatment-related variables that predict radioembolization outcome in patients with intrahepatic cholangiocarcinoma (Chapter 2). Then, as a step toward personalised radioembolization in liver metastases from colorectal cancer patients, we evaluated the relationship between radioembolization real absorbed dose, as determined by 90Y positron emission tomography, and outcome (lesion-based and patient-based) (Chapter 3). In the work described in Chapter 4, we compared predictive (simulated) and post-treatment (real) dosimetry in liver metastases from colorectal cancer patients to pursue radioembolization personalisation. Finally, based on experience accumulated in previous studies and advances reported in the literature, we generated state-of-the-art recommendations to assist practitioners in performing personalised radioembolization with 90Y-resin microspheres in patients with primary and metastatic liver tumours (Chapter 5). / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

One of the biggest challenges facing geoscientists is the ability to accurately predict failure within a rock mass. Conventionally, numerical modeling is performed to predict the response of the rock mass due to excavation. However, numerical modeling relies heavily on the estimated physical characteristics of the rock mass. Unless dense, costly sampling of the rock mass has been performed, the results of the modeling are not robust. Seismic tomography offers a unique advantage of monitoring the rock mass response over conventional numerical modeling because it is able to measure the true alteration in response to excavation (Westman, 2003). This paper utilizes a tomographic inversion scheme using the Fast Marching Method for raypath tracing and the Simultaneous Iterative Reconstruction Technique to solve the p-wave velocity model of an underground mine and surrounding rock mass. The inversion scheme presented is tested using a data set from Creighton Mine in Sudbury, Ontario, Canada and includes 9,270 distinct events over 62 days. A total of 53 geophones recorded 191,856 p-waves that are able to be used for inversion. Temporal monitoring of the seismic p-wave velocity in the vicinity of a known Mw 2.6 fault-slip event that occurred on March 14th is performed by creating tomograms of the axial plane at the depth of the event and of an oblique plane where a dense distribution of events occurred including the March 14th event. Tomograms are produced on a weekly basis leading up to the event and also on a daily basis three days before the event. The weekly tomograms reveal a decrease in p-wave velocity in the vicinity of the Mw 2.6 event as time approaches the event and then a significant increase 1,600 ft/sec larger than the background velocity the week of the event. The daily tomograms reveal a 1,200 ft/sec velocity increase in the same area from March 13th to March 14th, however, no trends in the daily or weekly tomograms prior to the date of the March 14th event suggest the known event is imminent. / Master of Science / One of the biggest challenges facing geoscientists is the ability to accurately predict failure within a rock mass. Conventionally, numerical modeling is performed to predict the response of the rock mass due to excavation. However, numerical modeling relies heavily on the estimated physical characteristics of the rock mass. Unless dense, costly sampling of the rock mass has been performed, the results of the modeling are not robust. Seismic tomography offers a unique advantage of monitoring the rock mass response over conventional numerical modeling because it is able to measure the true alteration in response to excavation (Westman, 2003). This paper utilizes a tomographic inversion scheme using the Fast Marching Method for raypath tracing and the Simultaneous Iterative Reconstruction Technique to solve the p-wave velocity model of an underground mine and surrounding rock mass. The inversion scheme presented is tested using a data set from Creighton Mine in Sudbury, Ontario, Canada and includes 9,270 distinct events over 62 days. A total of 53 geophones recorded 191,856 p-waves that are able to be used for inversion. Temporal monitoring of the seismic p-wave velocity in the vicinity of a known M_w 2.6 fault-slip event that occurred on March 14th is performed by creating tomograms of the axial plane at the depth of the event and of an oblique plane where a dense distribution of events occurred including the March 14th event. Tomograms are produced on a weekly basis leading up to the event and also on a daily basis three days before the event. The weekly tomograms reveal a decrease in p-wave velocity in the vicinity of the M_w 2.6 event as time approaches the event and then a significant increase 1,600 ft/sec larger than the background velocity the week of the event. The daily tomograms reveal a 1,200 ft/sec velocity increase in the same area from March 13th to March 14th, however, no trends in the daily or weekly tomograms prior to the date of the March 14th event suggest the known event is imminent.

Dissertation in der sich mit dem Thema der Selektiven Internen Radiotherapie auseinandergesetzt wurde. Der Titel der Doktorarbeit lautet: Langzeit-Follow-Up von Patienten mit malignen primären und sekundären Lebertumoren nach Selektiver Interner Radiotherapie, Ziel war es das Überleben der Patienten nach Selektiver Interner Radiotherapie zu untersuchen. Hierbei standen insbesondere Patienten mit hepatocellulärem Karzinom im Fokus. Interessant war, dass bei ca. 66% der Patienten mit hepatocellulärem Karzinom keine Vortherapien vor dem Verfahren durchgeführt wurden. Des Weiteren wurde auch das Ansprechen auf die Therapie näher betrachtet. Die Auswertung erfolgte mittels Vergleich von MRT Aufnahmen vor und nach der Selektiven Internen Radiotherapie.:Inhaltsverzeichnis Tabellenverzeichnis 6 Abbildungsverzeichnis 7 Abkürzungsverzeichnis 9 1 Einleitung 11 1.1 Die Selektive Interne Radiotherapie (SIRT) 11 1.1.1 Medizinhistorische Aspekte der SIRT 11 1.1.2 SIRT­Verfahren 12 1.1.2.1 Indikationen 14 1.1.2.2 Kontraindikationen 14 1.1.2.3 Erfordernisse und Vorgehen vor der Therapiedurchführung 14 1.1.2.4 Komplikationen 15 1.2 Das hepatozelluläre Karzinom (HCC) 16 1.2.1 Epidemiologie in Deutschland 16 1.2.2 Risikofaktoren 16 1.2.3 Therapie 16 1.2.4 Prognose 18 1.3 Das cholangiozelluläre Karzinom (CCC) 18 1.3.1 Epidemiologie 18 1.3.2 Risikofaktoren 19 1.3.3 Therapie 19 1.3.4 Prognose 19 1.4 Das hepatisch metastasierte kolorektale Karzinom (hmCRC) 21 1.4.1 Epidemiologie 21 1.4.2 Therapie 21 1.4.3 Prognose 23 1.5 Zum Forschungsstand der SIRT beim HCC 23 1.6 REILD und Betrachtung von Leberparametern im zeitlichen Verlauf 23 1.7 Fragestellungen und Ziele der vorliegenden Studie 24 2 Material und Methoden 25 2.1 Art, Ort und Zeitraum der Studie 25 2.2 Probanden/ Stichprobe 25 2.3 Durchführung der SIRT 28 2.3.1 Berechnungsmodell für die Therapieaktivität 28 2.4 Analyseparameter 30 3 Ergebnisse 32 3.1 Deskriptive Charakterisierung der Stichprobe 32 3.1.1 Deskriptive Charakterisierung der Studienteilnehmer 32 3.1.2 Deskriptive Charakterisierung der Tumorentitäten 33 3.1.3 Deskriptive Charakterisierung von Studienteilnehmern ohne SIRT 34 3.2 Tumorgrößen und Therapieaktivitäten 35 3.3 Zeitintervall zwischen der Diagnosestellung des Lebertumors und dem Therapiebeginn 37 3.4 Ansprechen auf SIRT 38 3.5 Überleben 43 3.5.1 Todesursachen 43 3.5.2 Überlebenszeit 45 3.5.3 Einflussfaktoren auf das Überleben (Korrelationen) 48 3.5.3.1 Zusammenhang von Tumorgröße und Überleben 48 3.5.3.2 Zusammenhang von Therapieaktivität und Überleben 52 3.5.3.3 Zusammenhang zwischen SIRT und Überleben bei Studienteilnehmern mit monolobärem und bilobärem Leberbefall 54 3.6 Auswertung der Leberwerte (Leberparameter) 57 4 Diskussion 63 4.1 Deskription der Studienteilnehmer 63 4.2 Diskussion und Interpretation der eigenen Ergebnisse 63 4.2.1 Tumorgrößen und Tumoraktivitäten 63 4.2.2 Zeitintervall zwischen Diagnosestellung des Lebertumors und dem Therapiebeginn 64 4.2.3 Ansprechen auf SIRT 65 4.2.4 Auswertung der Überlebenszeiten 66 4.2.4.1 Vergleich von Studienteilnehmern mit und ohne SIRT in Bezug auf die Überlebenszeit 66 4.2.4.2 Vergleich von Studienteilnehmern mit HCC und der Gruppe „anderer hepatisch metastasierter Tumor“ bezüglich der Ansprechrate nach SIRT und der Überlebenszeit 67 4.2.4.3 Vergleich von Überlebenszeiten bei den unterschiedlichen Tumorentitäten nach SIRT 67 4.2.4.4 Diskussion der Ergebnisse von Patienten mit HCC 69 4.2.4.5 Diskussion über den Einfluss des Tumorvolumens auf die Überlebenszeit 69 4.2.4.6 Zusammenhang zwischen Therapieaktivität und Überleben 69 4.2.4.7 Mono­ oder bilobäre Leberbeteiligung bei Studienteilnehmern mit HCC 70 4.2.4.8 Nähere Betrachtung der Studienteilnehmer mit geringerem Überleben und einem Tumorvolumen >0 bis 500 ml nach SIRT 70 4.2.4.9 Auswertung der Leberparameter 71 4.3 Vergleich der Daten mit anderen Studien 72 4.3.1 SARAH­Studie 72 4.3.2 SIRveNIB­Studie 73 4.3.3 LEGACY­ Studie 74 5 Zusammenfassung 76 6 Summary 79 7 Literaturverzeichnis 83 8 Anhang (Tabelle 2­5) 103 Anlage 1: Erklärungen zur Eröffnung des Promotionsverfahrens 115 Anlage 2: Erklärung über die Einhaltung der gesetzlichen Vorgaben 116

Liver metastases are the most common cause of death in colorectal cancer patients. The standard of care and potential for cure for colorectal liver metastases is resection, but often times disease it too extensive for this treatment. Over the years, cancer research has made way for advances in treating progressive disease through immunotherapy. By genetically modifying an individual’s immune system using virally transduced chimeric antigen receptor T cells (CAR-T), patients are better able to receive exquisitely specific T cells to target specific tumors. Furthermore, selective delivery strategies may enhance efficacy while limiting detrimental, systemic adverse effects. Not only this, CAR-Ts have also lead to complete remission in some liquid tumors while maintaining the potential for remission in solid tumors as well. This literature review takes readers through the emergence of the different generations of CAR-T and the various studies including clinical trials that have demonstrated the safety and efficacy of CAR-T. The second portion of this paper will outline the design for a phase II clinical trial using intrahepatic CAR-T therapy in addition to selective internal radiation therapy (SIRT) for refractory CEA+ colorectal liver metastases. Benefits and limitations of using these therapies are further discussed.

No description available.

Le Carcinome Hépatocellulaire a une incidence mondiale élevée et est associé à un mauvais pronostic. Les traitements curatifs existants ne sont applicables qu’à une minorité de patients. La radiothérapie sélective interne (SIRT) est un traitement palliatif de plus en plus utilisé. Elle consiste à l’injection sélective intra-tumorale de microsphères d’yttrium-90 par infusion intra-artérielle, et repose sur deux étapes : une étape pré-thérapeutique de simulation du traitement avec l’injection de macroagrégats d’albumines marqués au 99mTc et le traitement en lui-même. Cependant les caractéristiques de ces deux vecteurs diffèrent et peuvent conduire à des variations de biodistribution et à une dosimétrie approximative. Ce travail a pour but de développer un vecteur radiothéranostique unique pour la SIRT : les microparticules à base d’amidon (SBMP), afin de pallier aux différents problèmes rencontrés en clinique. L’optimisation du radiomarquage par le 68Ga et le 188Re sous forme de kits lyophilisés prêts-à-l’emploi, a permis d’obtenir une pureté radiochimique > 98 % et > 95 % respectivement. Une étude préliminaire par imagerie TEP/TDM in vivo chez le rat, suite à l’injection intraartérielle des 68Ga-SBMP a montré une biodistribution spécifique des microparticules avec plus de 95 % de l’activité retrouvée dans le foie et plus particulièrement dans les tumeurs. Les SBMP offrent plusieurs avantages répondant à différents problèmes actuels et constituent un agent théranostique prometteur pour la SIRT. Une présentation de la SIRT, des différentes microparticules en développement pour la SIRT et des modèles animaux de tumeur hépatique existants seront également développées dans ce travail. / The Hepatocellular Carcinoma has a high incidence worldwide and is associated with a bad prognostic. The existing curative treatments can only be apply in a minority of cases. The selective internal radiation therapy (SIRT) is a palliative treatment that is increasingly used. This technique is define by the selective intratumoral injection of yttrium-90microspheres via intra-arterial infusion. It involves two steps : a pre-therapeutic one for treatment simulation purpose with the injection of serum albumin macroaggregates radiolabeled with 99mTc and the treatment itself. However the characteristics of these two vectors are different and can lead to variations in biodistribution and approximate dosimetry. This works aims to develop a unique radiotheranostic vector for the SIRT: the starch-basedmicroparticles (SBMP), in order to overcome the different currents clinical problems. The optimization of the radiolabeling by the 68Ga and the 188Re in the form of ready-to-use radiolabeling kits allowed to obtain a radiochemical purity > 98 % and > 95 % respectively. A preliminary in vivo study by PET/CT imaging in rat, following the intra-arterial injection of 68Ga-SBMP displayed a specific biodistribution of the microparticles with more than 95 % of the activity found in the liver and mostly in the tumors. The SBMP offer several advantages that answer different current issues and area promising theranostic agent for the SIRT. A presentation of the SIRT, the different microparticles in development and the existing animal models of hepatic tumor will also be developed in this work.

Με την τομογραφία επιχειρείται η δημιουργία μιας εικόνας-τομής των ιδιοτήτων ενός αντικειμένου χρησιμοποιώντας μετρήσεις της ενέργειας που διαδόθηκε μέσω του αντικειμένου, σε δέκτες στην περιφέρειά του. Έχει αποδειχθεί ότι ένα αντικείμενο είναι δυνατόν να απεικονισθεί με ακρίβεια από ένα πλήρες σύνολο περιμετρικών προβολών του. Η τομογραφική ανάλυση είναι δυνατό να γίνει αξιοποιώντας κυματική ενέργεια που έχει διαδοθεί μέσω του υπό μελέτη αντικειμένου (ακτινική τομογραφία) ή προέρχεται από ανάκλαση, περίθλαση κ.ο.κ. σε ανομοιογενή τμήματα του αντικειμένου (περιθλαστική τομογραφία). Στην παρούσα εργασία γίνεται πειραματική εφαρμογή της μεθόδου της σεισμικής τομογραφικής απεικόνισης σε αρχαιολογικά προβλήματα, όπως στην ανίχνευση αρχαιολογικών αντικειμένων στο υπέδαφος ή σε περιβάλλον τεχνητών λόφων (τύμβων -ταφικών μνημείων). Η εφαρμογή αυτή συνιστά ενδιαφέρουσα πρόκληση λόγω του ιδιαίτερα ανομοιογενούς περιβάλλοντος στο οποίο επιχειρείται η ανίχνευση των αντικειμένων καθώς και των μικρών γενικά, αλλά και συχνά απροσδιόριστων, διαστάσεων των αντικειμένων αυτών. Ο μη καταστρεπτικός χαρακτήρας της εφαρμογής είναι ιδιαίτερα ευνοϊκός και αποδεκτός στην αρχαιολογική έρευνα, τόσο σε αναγνωριστικό όσο και σε ανασκαφικό/ σωστικό επίπεδο. Παρουσιάζονται αναλυτικά οι αρχές και το θεωρητικό μέρος της τομογραφικής μεθοδολογίας, με ιδιαίτερη αναλυτική αναφορά στις δύο κύριες μεθόδους ανασύνθεσης των χαρακτηριστικών του εσωτερικού του ερευνώμενου μέσου (χώρου), την ακτινική τομογραφία και περίθλασης, καθώς και τις σχετικές τεχνικές και αλγόριθμους αντιστροφής. Τέλος γίνεται εφαρμογή της ακτινικής τομογραφίας σε 3 διαστάσεις, σε σεισμικές καταγραφές από αρχαιολογικούς-μνημειακούς χώρους, με τη χρήση του αλγόριθμου SIRT (τεχνική ταυτόχρονης επαναληπτικής ανασύνθεσης). Τα δεδομένα ήταν χρόνοι πρώτης άφιξης καθώς και πλάτη σε μια περίπτωση. Kατά την εφαρμογή της ακτινικής τομογραφίας, γίνονται δοκιμές ρύθμισης των παραμέτρων και μεταβλητών κατά τη διαδικασία της αντιστροφής, ώστε να διερευνηθεί η επίδρασή τους στο αποτέλεσμα. Επίσης, διερευνάται η αποτελεσματικότητα της μεθόδου με κατασκευή μοντέλων με βάση πληροφορίες για τους χώρους έρευνας, υπολογισμό συνθετικών χρόνων και αντιστροφή των συνθετικών χρόνων για σύγκριση με τα αποτελέσματα των πραγματικών χρόνων και εξαγωγή συμπερασμάτων. Λαμβάνοντας υπόψη τα στοιχεία από τις ανωτέρω δοκιμές, επιλέγονται τελικές τιμές παραμέτρων για την αντιστροφή των πραγματικών δεδομένων και γίνεται αξιολόγηση και ερμηνεία των αποτελεσμάτων. Γίνεται επίσης δοκιμαστική εφαρμογή τεχνικών επεξεργασίας / ενίσχυσης εικόνας στα αποτελέσματα της αντιστροφής, για την ενίσχυση κυρίως των μικρών, τοπικών, μεταβολών της σεισμικής ταχύτητας και την πληρέστερη απεικόνιση των χώρων έρευνας. Παρουσιάζονται τα αποτελέσματα από την έρευνα του προϊστορικού οικισμού Παλαμαρίου Σκύρου, του χώρου θεμελίωσης του Καθολικού (Ναού) της Ι.Μ. Δαφνίου Αττικής, του εσωτερικού του τεχνητού λόφου – πιθανού τύμβου Καστά Μεσολακκιάς Σερρών και των νεκροταφείων της περιοχής Chatby της Αλεξάνδρειας Αιγύπτου. / With tomography is attempted the creation of an image – slice of the internal properties of a medium / object with use of measurements of the energy which was transmitted through the medium, at receivers on the outside of it. It has been proved that a medium can be imaged with precision by a set of perimetric projections. Tomographic analysis is possible by employing wave energy that has been transmitted through the medium under investigation (ray tomography) or has been reflected or diffracted at various inhomegeneities within the medium (diffraction tomography). In the present study, an experimental application of the seismic tomographic imaging method is made in the field of archaeological exploration, such as detection of archaeological remains in the subsurface or in artificial hills (tumuli). The application poses an interesting challenge, because of the highly inhomogeneous environment where the detection is tried and the small and unknown, in general, dimensions of the target objects. The non-destructive character of the application makes it quite attractive and acceptable in archaeological exploration, both at reconnaissance and later stages of excavation. The principles and theoretical foundations of the tomographic methodology are presented, with particular reference to the two main methods of reconstruction of the internal character of the investigated medium and included objects, that is ray and diffraction tomography, as well as the relevant inversion techniques and algorithms. Finally, an application of ray tomography on seismic recordings from archaeological / monumental sites is made, with use of the simultaneous iterative reconstruction technique (SIRT). In the application of ray tomography, adjustment tests of inversion parameters and variables are made, in order to study their effect on the inversion result. The effectiveness of the method and of the algorithm is investigated with the aid of synthetic models based on possible information from the test sites and the bibliography. Using the models as starting models, synthetic travel times are calculated and are then inverted, while the resulting image is compared with the synthetic starting model and conclusions are drawn. Based on the results of the above tests, final parameter values are set for the inversion of real field data and an assessment and an interpretation of the results is made. Image processing and enhancement is applied to the resulting tomograms, in order to enhance and clarify the small (hidden) variations of seismic velocity, which may reflect important subsurface information, mainly related to particular archaeological targets. There are presented the results from the investigation of the subsurface of a part of the prehistoric settlement of Palamari (Skyros isl., Greece) of the foundations of the church of Dafni Monastery (Attica, Greece), of the interior of the artificial hill / possible tumulus at Kasta Messolakia (Serrae, Greece) and of the subsurface of the cemeteries of Chatby area (Alexandria, Egypt).

Phase-contrast imaging (PCI) is a modality of medical x-ray imaging that can solve one of the main limitations with conventional attenuation-based imaging: the imaging of materials with low attenuation coefficients, such as soft tissues. A modality of PCI, Propagation-based phase-contrast imaging (PBI), was used in this project. This method does not require any optical elements than those used in the conventional imaging; it does, however, require more processing compared to other kinds of PCI. In addition to the reduced image quality, the required image reconstruction process, with PCI, also requires several manual adjustments, which in turn results in a lot of time consuming. In order to achieve that, a simple iterative image reconstruction method that combines Simultaneous Iterative Reconstruction Technique (SIRT) and propagation-based phase-contrast imaging was developed. The proposed method was compared with another commonly used phase-retrieval method, Paganin's algorithm. The obtained results showed higher resolution and reduced blur artefacts compared with Paganin's method. The developed method also appeared to be less sensitive to error in the input parameters, such as the attenuation coefficient, but also more time-consumption than the non-iterative Paganin's method, due to the higher data processing. / Faskontrastavbildning är en ny medicinsk röntgenavbildningsteknik, som har utvecklats för att ge bättre kontrast än konventionell röntgenavbildning, särskilt för objekt med låg attenuationskoefficient, såsom mjuk vävnad. I detta projekt användes s.k. propagationsbaserad faskonstrantavbildning, som är en av de enkla metoder som möjliggör faskontrastavbildningen, utan extra optiska element än det som ingår i en konventionell avbildning. Metoden kräver dock mer avancerad bildbehandling. Två av de huvudsakliga problemen som oftast uppstår vid faskontrastavbildning är minskad bildkvalité efter den väsentliga bildrekonstruktionen, samt att den är tidskrävande p.g.a. manuella justeringar som måste göras. I det här projektet implementerades en enkel metod baserad på en kombination av den iterativa algoritmen för bildrekonstruktion, Simultaneous Iterative Reconstruction Technique (SIRT), med propagationsbaserad faskonstrantavbildning. Resultaten jämfördes med en annan fasåterhämtningsmetod, som är välkänd och ofta används inom detta område, Paganinsmetod. Efter jämförelsen konstaterades att upplösningen blev högre och artefakter som suddighet reducerades. Det noterades också att den utvecklade metoden var mindre känslig för manuell inmatning av parametern för attenuationskoefficient. Metoden visade sig dock vara mer tidskrävande än Paganin-metoden.