The proteinase activities of the L1210 and L5178Y murine lymphocytic leukemias have been measured and characterized in order to determine whether a correlation exists between proteinase activity and metastatic potential. Such a correlation would be expected if proteinases promote invasion and metastasis by degrading host tissue. These lines were chosen for study because they are very similar in most respects, but differ dramatically in their ability to metastasize. The kinetics of tumor cell proliferation, death, and metastasis for these lines are the best currently available. / Tumor cell suspensions and supernatants were assayed for activity against basement membrane, elastin, Type I collagen, hemoglobin, casein, benzoyl-Arg-napthylamide, and N-acetyl-(Ala)(,3)-p-nitroanilide. Since no quantitative assay for the hydrolysis of intact basement membranes existed prior to these studies, a sensitive new one based on the hydrolysis of bovine lens capsule membranes has been developed. Significant levels of proteinase activities were detected in suspensions of both tumor lines against all the substrates tested, and it is clear that the spectrum of activities found is capable of facilitating metastasis. Two membrane-associated proteinases have been found in both tumor lines, one active against both basement membranes and benzoyl-Arg-napthylamide and the other against N-acetyl-(Ala)(,3)-p-nitroanilide. Host cells were primarily responsible for the hydrolysis of the other substrates, although there was some cathepsin D activity attributable to tumor cell death. / No significant differences in proteinase activity levels were detected between the two lines. hence, while these proteinase activities may assist in the metastasis of these two cell lines, some other factor must also be involved. The ability of the two tumor lines to bind to intact basement membranes was examined and no differences in binding capacity were detected. Thus, some other additional factor, such as the capacity for directional motility, is probably involved. / Source: Dissertation Abstracts International, Volume: 45-06, Section: B, page: 1662. / Thesis (Ph.D.)--The Florida State University, 1984.

Source: Dissertation Abstracts International, Volume: 41-09, Section: B, page: 3289. / Thesis (Ph.D.)--The Florida State University, 1980.

The cytocidal and radiosensitizing effects of two newly developed 2-nitroimidazole derivatives (Ro 03-8799 and RSU-1164) were evaluated with the original compound, misonidazole, serving as a reference agent. More specifically, euoxic and hypoxic BP-8 murine sarcoma cells were exposed for up to 3 hours to various concentrations of the three nitroimidazole derivatives, with or without irradiation, and the resulting cell lethality was monitored with the $\sp{125}$IUdR prelabeling assay. When cell death was evaluated as a function of drug molarity, the three nitroimidazoles displayed widely different toxicities, but when expressed in terms of toxicity ratio between euoxic and hypoxic cells, all three drugs showed nearly identical toxicity differentials of 16 to 18 in 1 hour drug incubation experiments. Prolonging the treatment period to 3 hours with RSU-1164, the toxicity ratio was increased significantly from 16 to 73. This increase was attributed to the bifunctional action of RSU-1164 as a combined electron-affinic and alkylating agent, with the alkylation component of hypoxic cell killing becoming more pronounced after prolonged drug incubation. Combined administration of hyperthermia and nitroimidazoles increased drug-induced cell lethality for all three agents, but did not materially change the relative toxicity differential between euoxic and hypoxic cells. / The radiosensitizing effects of the three compounds were studied at sublethal drug doses, with the drug concentrations adjusted to provide equitoxic (isosurvival)treatment conditions. Under thse experimental conditions, all three drugs displayed equal radiosensitizing effects in short term drug exposures which measure mainly the so-called "oxygen-mimetic" component of radiosensitization. However, with longer drug incubation periods a second component of sensitization known as "preincubation effect" or "damage interaction" became apparent. The magnitude of this damage interaction effect at equitoxic doses for RSU-1164 produced significantly higher damage interaction than the other two agents. / In conclusion, based on cellular toxicity and radiosensitization data, Ro 03-8799 appears to offer no advantage over misonidazole as a selective cytocidal and radiosensitizing agent for hypoxic cells, but RSU-1164 does provide a moderate therapeutic advantage. Additional factors operating in intact animals could further enhance the potential of RSU-1164 and could also serve to make Ro 03-8799 more effective than misonidazole as an adjuvant to chemotherapy and radiotherapy of cancers. (Abstract shortened with permission of author.) / Source: Dissertation Abstracts International, Volume: 49-10, Section: B, page: 4126. / Major Professor: Kurt G. Holer. / Thesis (Ph.D.)--The Florida State University, 1988.

Source: Dissertation Abstracts International, Volume: 36-12, Section: B, page: 5935. / Thesis (Ph.D.)--The Florida State University, 1975.

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Changes in cerebral venous blood volume (DCBVv) is a critical component of the BOLD fMRI signal (instead of total DCBV), but its role has remained relatively unexplored, predominantly because measuring CBVv non-invasively is challenging. Motivated by this challenge, this thesis focuses on the development and use of the venous refocusing for volume estimation (VERVE) technique to non-invasively measure DCBVv. Driven by the substantial signal-to-noise (SNR) gain at high field, VERVE was re-designed for 3 T. This technique is strongly field-dependent through its reliance on venous blood transverse relaxation (T2) variations as a function of the Carr-Purcell Meiboom-Gill (CPMG) refocusing interval and blood oxygenation. To characterize this dependence, human whole blood T2 relaxometry was performed at 3 T. The results reveal significantly enhanced blood T2 dependence relative to 1.5 T, one best modelled as a diffusion process. In addition, human grey and white matter T2 relaxometry results support venous blood T2 variation being the predominant source of VERVE contrast at 3 T. The subsequent design of VERVE was based on the blood relaxometry results. Also, to minimize signal biases due to gradient-echo BOLD effects, greatly amplified at 3 T, a turbo spin-echo approach was adopted, further boosting SNR. VERVE was then used with arterial spin labeling (ASL) to assess the steady-state venous flow-volume relationship in humans under visual and sensorimotor stimulation. The results demonstrated a spatially-invariant flow-volume relationship characterized by a power-law coefficient (a) of 0.23, significantly lower than Grubb’s value of 0.38 (derived using total DCBV). The assumption of the latter in calibrated BOLD introduced a significant underestimation in cerebral oxygen metabolism changes (DCMRO2). Finally, the interactions giving rise to the controversial BOLD post-stimulus undershoot were examined with respect to the prevalent biomechanical, metabolic and neuron / Les changements du volume sanguin cérébral veineux (DCBVv) est un élément essentiel du signal BOLD (par opposition à l’ensemble de DCBV). Pourtant, jusqu'ici le rôle du CBVv est resté relativement inexploré, et ce du aux difficultés liées aux mesures non-invasives du CBVv. Motivée par ce défi, cette thèse se rapporte sur le développement et l'utilisation de la méthode VERVE (refocalisation veineuse pour l’estimation du volume), qui permet l’estimation non-invasive de DCBVv. D’abord, l’augmentation importante du rapport signal-sur-bruit (SNR) aux champs magnétiques élevés a mené à réviser VERVE pour 3 T. Le contraste VERVE est basé sur les variations du temps de relaxation transversale (T2) sanguin veineux en fonction de l’intervalle de refocalisation Carr-Purcell Meiboom-Gill (CPMG) et de l’oxygénation sanguine. Pour caractériser cette dépendance, qui dépend fortement du champ magnétique, une étude relaxométrique du sang humain a été réalisé à 3 T. Les résultats indiquent que la dépendance du T2 sanguin est amplifiée de façon importante entre 1.5 T et 3 T. Un modèle de diffusion décrit le mieux cette dépendance. D’autre part, une étude relaxométrique de la matière grise et blanche a été réalisée, confirmant la dominance de l’effet T2 sanguin dans le contraste VERVE. La composition de VERVE se rapporte aux résultats relaxométriques sanguins. En plus, afin de minimiser l’effet de l’écho de gradient, amplifié à 3 T, une approche turbo spin-écho a été adoptée. VERVE est ensuite utilisée avec le marquage des spins artériels (ASL) pour mesurer les changements du CBVv et du débit sanguin cérébral (CBF) chez les sujets sains lors de stimulations visuelles et sensorimotrices. Les résultats démontrent une relation débit-volume invariante à travers le cortex, caractérisée par a = 0.23, inférieure à la valeur de Grubb (0.38, calculée a partir du CBV total). En employant cett

A protocol of establishing radiochromic film based reference dosimetry for high dose rate Ir-192 brachytherapy source was assessed and described. A comparison between calibration curves created in water and Solid Water are provided. Solid Water was shown to be a viable alternative to water in establishing calibration curve for Ir-192 radiation beam. A Monte Carlo correction factor was calculated to convert the dose to water into dose to Solid Water and the experimental methods that we performed agreed with the Monte Carlo results where the ratio (DSW/DW)Ir-192 was found to be 0.9808 ± 0.14% (1σ). EBT-2 GAFCHROMIC film model was also investigated for absorption properties and found to be a less sensitive than its predecessor (EBT-1) in terms of net change of absorbance, but that did not affect the dosimetric value that this film possesses. A dose error assessment method has been described for EBT-2 film model (and is applicable to other types as well) that can establish the time error constraints on the post-irradiation scanning time that will still provide an acceptable dose error for clinical applications if the protocol employing the shorter post-irradiation scanning time is implemented in the clinic. We show that for two post-irradiation scanning times of 30 minutes and 24 hours the 1% dose error can be granted if the scanning time window is less than ± 5 minutes and ± 2 hours, respectively. Performance of EBT-2 model was also evaluated in water and it was concluded that a suggested correction protocol is necessary for immersion times that exceed 2 hours. This correction was tested with the calibration curve created from water setup and found to be effective when compared to the dose-corrected calibration curve in Solid Water. / Un protocole d'établir film radiochromique dosimétrie de référence en fonction de débit de dose élevé source Ir-192 curiethérapie été évalués et décrits. Une comparaison entre les courbes d'étalonnage créé dans l'eau et Solid WaterTM sont fournis. Solid WaterTM s'est révélée être une alternative viable à l'eau dans l'établissement de la courbe d'étalonnage pour les Ir-192 faisceau de rayonnement. Un facteur de correction de Monte Carlo a été calculé pour convertir la dose à l'eau en dose à Solid WaterTM et les méthodes expérimentales que nous avons réalisé d'accord avec les résultats de Monte Carlo où le ratio (DSW/DW)Ir-192 a été trouvé à 0.9808 ± 0.14% (1σ). EBT-2 modèle GAFCHROMICTM film a également été étudiée pour les propriétés d'absorption et jugé être un moins sensible que son prédécesseur (EBT-1) en termes de variation nette de l'absorbance, mais cela n'a pas d'incidence sur la valeur dosimétrique que ce film possède. Une méthode d'évaluation des doses d'erreur a été décrit pour le modèle EBT-2 film (et est applicable à d'autres types ainsi) qui permet d'établir les contraintes de temps d'erreur sur le post-irradiation temps de balayage, qui va encore donner une erreur de dose acceptable pour des applications cliniques, si le protocole emploie le plus court post-irradiation de numérisation temps est mis en œuvre dans la clinique. Nous montrons que pour deux post-irradiation de numérisation fois de 30 minutes et 24 heures, la dose d'erreur de 1% peut être accordée si la fenêtre de temps de balayage est inférieure à ± 5 minutes et de ± 2 heures, respectivement. Performance de la EBT-2 modèle a également été évaluée dans l'eau et il a été conclu un protocole de correction proposé est nécessaire pour que les temps d'immersion supérieure à 2 heures. Cette correction a été testé avec la courbe de calibration créée à partir d'installation de l'eau et ont été jugés effic

Photoneutrons generated in the linac head are a byproduct of the radiotherapy process and can be potentially harmful to clinical personnel. The lack of accuracy associated with analytical photoneutron shielding methods has generated much interest in the Monte-Carlo (MC) method as a more flexible and precise tool for radiotherapy bunker design. The purpose of this work was to use MC simulations to characterize photoneutron fluence, dose, and spectrum throughout various radiotherapy bunker configurations and for various room design features, such as the presence of a maze, a bulkhead, and the addition of borated polyethylene on the maze walls. Three existing rooms at the MUHC and two hypothetical doorless rooms were modelled with the MCNP5 code and using the Visual Editor GUI. The analytical spectrum of an 18 MV linac served as the point source of photoneutrons and was surrounded with a 10 cm radius tungsten sphere placed 100 cm above the isocenter. The next-event estimator variance reduction technique was used and simulations were performed with 20 million particle histories yielding un- certainties under 1%. Physical measurements were also attempted with bubble detectors and a He-3 neutron spectrometer. The latter was unsuccessful because of pulse pile-up caused by the Linac's pulsed mode of operation, whereas the former gave us qualitative information on neutron equivalent dose distribution in the maze and around the linac. Simulation results showed a marked decrease in neutron equivalent dose near the bunker entrance when maze walls are lined with BPE and when a bulk-head is added in the inner maze passage. It was found that the high thermal neutron cross-section of BPE was key in reducing the portion of thermal photoneutrons in the spectrum along the maze. The bulkhead was also useful in reducing photoneutron fluence entering the maze and hence reducing overall photoneutron dose near the entrance of the bunker. Future work will focus on validating simulations with accurate physical measurements and refining the MC code to make it more user friendly and flexible in reproducing bunker geometry. / Les photoneutrons générés par le linac sont un produit secondaire de la radiothérapie et peuvent être nuisibles au personnel médical. Le manque de précision des équations analytiques pour le blindage contre les photoneutrons a accéléré le développement des méthodes Monte-Carlo (MC), qui sont considérées plus flexibles et précises pour le design des salles de radiothérapie. L'objectif de cette étude est d'utiliser les simulations MC afin de caractériser le flux, la dose, et le spectre des photoneutrons pour différentes configurations de salles de radiothérapie, telles que la présence d'un corridor, d'un bloc d'atténuation, et l'addition de borate de polyéthyléne sur les murs du corridor. Trois chambres du MUHC et deux chambres hypothétiques ont été modélisées avec le code MCNP5 et le logiciel Visual Editor. Le spectre d'énergie analytique d'un linac opérant à 18 MV a été utilisée comme source ponctuelle de photoneutrons. Ce point est entouré d'une sphére de Tungsténe de 10 cm de rayon positionnée 100 cm au dessus de l'isocentre. L'estimateur du prochain événement est la technique de réduction de variance qui a été utilisée et les simulations ont été effectuées avec 20 millions de particules résultant en des incertitudes inférieures à 1%. Des mesures physiques ont aussi été tentées à l'aide de compteurs à bulles et un spectrométre de neutrons à He-3. Ce dernier n'a pas eu de succés à cause de l'effet d'accumulation du signal pulsé. Les tests avec compteurs de bulles ont permis d'avoir une idée qualitative sur la distribution de la dose équivalente dans le corridor et autour du linac. Les résultats des simulations ont montré une diminution de la dose équivalente de neutron prés de l'entrée de la chambre quand les murs du corridor sont couverts de borate de polyéthyléne et quand un bloc d'atténuation est présent dans le passage de la chambre centrale vers le corridor. Il a été confirmé que la haute probabilité d'interaction des neutrons de basses énergies avec le borate de polyéthyléne est essentiel à la réduction de la portion de photoneutrons à basses énergies à travers le corridor. Le bloc atténuateur contribue aussi à la réduction du flux de photoneutrons entrant dans le corridor et réduit ainsi la dose totale à l'entrée de la chambre. La suite des travaux vise à mettre l'emphase sur la validation des simulations à l'aide de mesures expérimentales et sur le perfectionnement du code MC pour donner plus de flexibilité à l'utilisateur dans la reproduction des salles de radiothérapie.