In its latest neurotoxicity guidelines released by the US EPA Office of Prevention, Pesticides and Toxic Substances (OPPTS) in 1998, it is recommended that in a neurobehavioral testing, at a minimum, for acute studies, observations and activity testing should be made before the initiation of exposure, at the estimated TOPE (time of peak effects) within 8 hrs of dosing, and at 7 and 14 days after dosing. It is recommended that estimation of TOPE be made by dosing pairs of rats across a range of doses and making regular observations of gait and arousal. However it is well known that TOPE may vary with end points or exposure conditions. In order to derive quantitative safety measures such as the benchmark doses (BMD), dose-time-response modeling must be done first and a model-based estimate is then implied. In many cases, the overall BMD corresponds to a TOPE estimate. In such cases a substantial variation in the TOPE estimate in turn may result in substantial variation in BMD estimate. Therefore a reliable statistical estimate of TOPE is crucial to the correct determination of BMD. We therefore performed simulation studies to assess the impact of the experiment-based TOPE on the statistical estimation of the true TOPE on the basis of a fitted dose-time-response model. The simulation allows for the determination of the optimal timing range for the 2nd testing. The results indicated that given only four repeated observations, the optimal second testing time was at about midway between time zero and the true TOPE. Choosing the second testing time at the TOPE may not generate statistical estimates closer to the true TOPE.

La radiothérapie interne sélective (RTIS), en plein développement ces dernières années, constitue une alternative thérapeutique pour les cancers primaires et secondaires inopérables du foie. Le principe repose sur l’administration intra-artérielle de microsphères chargées d’yttrium-90 avec pour objectif la destruction des cellules tumorales par l’irradiation.L’activité d’yttrium-90 à administrer au patient est actuellement généralement prescrite à partir d’approches semi-empiriques ou peu personnalisées, faciles à mettre en place cliniquement. De nouveaux outils sont aujourd'hui disponibles semblables à ceux utilisés en radiothérapie externe. Leur utilisation encore peu répandue nécessite un retour d'expérience clinique pour mettre en avant leurs bénéfices et guider l'application clinique. Par ailleurs, le traitement RTIS est précédé d'une étape de simulation. Des différences inhérentes à cette procédure en deux temps (type de particules utilisées, modalité d’imagerie, modifications de flux vasculaires, etc.) existent et pourraient potentiellement conduire à des écarts dosimétriques entre la planification et le traitement. C’est dans ce contexte que s’inscrit le projet de cette thèse qui porte sur l'optimisation de la dosimétrie pour le traitement du carcinome hépatocellulaire par RTIS.Les doses délivrées au cours de 42 traitements par microsphères de résine réalisés entre 2012 et 2015 au CHU de Montpellier, ont été rétrospectivement calculées à l’échelle du voxel sur un logiciel de dosimétrie dédié (PLANET Dose, DOSIsoft, Cachan). Les doses délivrées ont été calculées pour le volume tumoral et le volume de foie sain définis anatomiquement, à partir de l’imagerie post-traitement TEP aux microsphères d’yttrium-90. Ce travail a mené à deux études complémentaires. La première analyse a consisté à confronter les données dosimétriques recueillies (doses moyennes, histogrammes dose-volume) à la réponse tumorale, la toxicité hépatique et la survie du patient. Les résultats obtenus, en accord avec ceux de la littérature, ont confirmé l’existence d’une relation dose-effet en RTIS. La deuxième étude a mis en évidence les limites du modèle BSA (body surface area pour surface corporelle) qui avait été utilisé pour planifier l’activité à administrer, à prédire la dose délivrée et par conséquent l’efficacité du traitement. L’absence de considérations dosimétriques et de prise en compte de l’hétérogénéité de distribution, de ce modèle ont notamment été discutées. Ces deux études ont ainsi souligné l'intérêt de planifier l'activité d'yttrium-90 à administrer en se basant sur des données dosimétriques individualisées.Une troisième étude a été conduite sur une population de 23 patients atteints de CHC, traités par microsphères de verre traités entre 2015 et 2018 au CHU de Montpellier. L’objectif a été de comparer les dosimétries prédictives et post-traitement calculées à l’échelle du voxel. Les résultats cliniques obtenus ont été appuyés par des expérimentations sur fantômes physiques (simple et anthropomorphique). Une bonne corrélation a été montrée, mettant en avant la valeur prédictive de la dosimétrie de planification. En revanche, un écart significatif a été observé et semble lié en partie à la quantification de l’imagerie TEP à l’yttrium-90. De plus, il a été montré que le geste radiologique peut influencer la distribution de particules et donc de dose, d’où la nécessité d’une reproductibilité aussi parfaite que possible entre les deux étapes. / Selective internal radiation therapy (SIRT) is a growing therapeutic alternative for unresectable primary and secondary liver cancer. The principle is based on the intra-arterial administration of yttrium-90 loaded microspheres for tumor cell destruction through irradiation.Yttrium-90 activity to be administered to the patient is, at the moment, usually prescribed using semi-empirical or barely personalized approaches that can be easily clinically implemented. New tools, similar to the ones used in external beam radiotherapy, are available today. These tools, which are not yet widely spread, require clinical feedback to show their benefits and guide the clinical application. Besides, a simulation stage is always performed before SIRT treatment itself. This two-step procedure implies differences (in terms of particles used, imaging modality, vascular flow modifications, etc.) that could potentially lead to dose deviations between planning and treatment. The thesis project comes within this scope, dealing with dosimetry optimization for hepatocellular carcinoma SIRT.Delivered doses during 42 treatment procedures performed between 2012 and 2015 at Montpellier University Hospital, were retrospectively calculated at the voxel level using a dosimetry dedicated software (PLANET Dose, DOSIsoft, Cachan). Two complementary studies were carried out from this work. The first one analyzed dose data (average dose, dose volume histograms) versus patient follow-up including tumor response, liver toxicity and patient survival. The results obtained are consistent with the other teams, confirming the dose-effect relationship in SIRT. The second study highlighted the limitations of the BSA (body surface area) model that was used for activity planning. In particular, the limitations of this model to predict delivered dose and consequently treatment efficiency were quantitatively demonstrated. The lack of dosimetry and heterogeneity distribution considerations were also discussed. These two studies emphasized the interest for yttrium-90 activity planning based on individualized dose data.A third study was conducted on a population of 23 patients treated between 2015 and 2018 at Montpellier University Hospital. The aim was to compare predictive and post-treatment dosimetry calculated at the voxel level. The clinical results were supported by phantom (simple and anthropomorphic) experimentations. A good correlation was observed highlighting the predictive value of dosimetry planning. However, a significant deviation was noticed and seems to be partly related to yttrium-90 TEP quantification. In addition, it was also noted that the radiological gesture can affect particle distribution and consequently dose distribution, this is why reproducibility as perfect as possible is required between the two stages.

<p>Interventional radiological procedures often require long fluoroscopic exposure times and high levels of radiation exposure to patients, which often are higher than most radiological examinations except for computed tomography (CT) whose effective doses can be higher, and in addition to having radiation risks that are higher for both patient and medical staff. Therefore it is important to monitor and map the radiation entrance exposure to the patients, to minimize the probability of skin injury, and to detect areas of overlapping radiation fields. The aim of this thesis is to evaluate patient doses in interventional radiology procedures using a new GAFCHROMIC-XR TYPE R DOSIMETER MEDIA X-ray Dosimetry film, which allows mapping of the skin dose distribution, when placed closer to the skin. These radiochromic films can be characterized by a power response dose function when plotting pixel value versus air kerma and have been calibrated up to 5 Gy when using a flatbed scanner. Image analysis was performed using the red channel component of standard the RGB (Red, Green, and Blue) color space image. The association between the Maximum Entrance Skin Doses (MESD) and Dose Area Product (DAP) values for two interventional procedures; coronary angiography (CA), and percutaneous transluminal coronary angiography (PTCA) is investigated.</p>

Interventional radiological procedures often require long fluoroscopic exposure times and high levels of radiation exposure to patients, which often are higher than most radiological examinations except for computed tomography (CT) whose effective doses can be higher, and in addition to having radiation risks that are higher for both patient and medical staff. Therefore it is important to monitor and map the radiation entrance exposure to the patients, to minimize the probability of skin injury, and to detect areas of overlapping radiation fields. The aim of this thesis is to evaluate patient doses in interventional radiology procedures using a new GAFCHROMIC-XR TYPE R DOSIMETER MEDIA X-ray Dosimetry film, which allows mapping of the skin dose distribution, when placed closer to the skin. These radiochromic films can be characterized by a power response dose function when plotting pixel value versus air kerma and have been calibrated up to 5 Gy when using a flatbed scanner. Image analysis was performed using the red channel component of standard the RGB (Red, Green, and Blue) color space image. The association between the Maximum Entrance Skin Doses (MESD) and Dose Area Product (DAP) values for two interventional procedures; coronary angiography (CA), and percutaneous transluminal coronary angiography (PTCA) is investigated.

No description available.

Brachytherapy is a form of radiotherapy in which radioactive sources are placed at short distances from, or even inside the target volume. The use of high dose rate brachytherapy is a widely accepted and clinically proven treatment for some stages of prostate cancer. The aim of this project was to investigate potential improvements on two of the most important aspects of high dose rate (HDR) and pulsed dose rate (PDR) prostate brachytherapy - prostate definition and treatment delivery verification. The use of magnetic resonance (MR) imaging in addition to the conventional computed tomography (CT) imaging methods currently used routinely for brachytherapy planning may provide some benefit in accurately defining the prostate and surrounding critical structures. The methods used in this project involved analysis of data sets provided by two Radiation Oncologists. The results presented showed inter-observer and intra-observer variations in the size and shape of the prostate, as well as analysis of the dosimetric differences that may be reported due to the differences in prostate size and shape. The results also included analysis of critical structure dosimetry - dose to the surrounding radio-sensitive rectum and urethra. In summary, the results showed that the prostate was defined to be smaller using MR imaging than CT, however the consistency between Oncologists was not significantly improved using MR imaging. MR imaging may be useful in reducing the dose to normal tissue surrounding the prostate and in obtaining better coverage of the smaller target volume, without compromising the critical structures. The use of LiF:Mg,Ti thermoluminescent dosimeters (TLDs) is a potential avenue for in vivo dose verification of an HDR or PDR prostate brachytherapy treatment plan. This project included a phantom study of these TLDs with the aim to determine their feasibility for clinical use. Cylindrical TLD rods (6 mm length x 1 mm diameter) were used, as these fit inside the brachytherapy needles implanted into the prostate, and therefore had potential to be used clinically to verify the dose delivered in the prostate. This study was extended to include determination of a correction factor to allow an independent radiation source (6 MV photon beam from a linear accelerator) to be used to obtain control readings for this relative dosimetric method. The results showed these TLDs to be a promising in vivo dosimeter for prostate brachytherapy with potential errors in the order of 4%. Their potential lies in the fact that they could detect and flag significant calculation errors in treatment plans, and they utilise equipment used routinely for external beam radiotherapy dosimetry in many treatment facilities, reducing the cost of implementing such a procedure.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Made available in DSpace on 2014-06-11T19:35:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-23Bitstream added on 2014-06-13T21:07:59Z : No. of bitstreams: 1 pereira_am_dr_rcla.pdf: 830341 bytes, checksum: de8af8468e88b6f5c5cf902007f24ed7 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / As abelhas Apis mellifera são insetos ecologicamente e economicamente importantes. Elas asseguram a polinização de diversas plantas contribuindo para a manutenção da biodiversidade. Seu valor econômico resulta não somente de seus produtos diretos mas também pela ativa polinização que exercem em culturas. A polinização feita por animais é importante para a reprodução sexuada de muitas culturas e para a maioria das plantas nativas, as quais também podem ser importantes como fonte de calorias e micronutrientes para os seres humanos. Além do mais, o declínio no número de polinizadores pode acarretar uma redução concomitante no número de espécies vegetais. A abelha A. mellifera, destaca-se como polinizador economicamente mais valioso para culturas em todo o mundo. Por outro lado, a agricultura moderna cada vez mais depende do uso de produtos químicos para controlar plantas daninhas, fungos e insetos-praga para assegurar a produtividade. Abelhas melíferas podem entrar em contato com tais agentes químicos devido suas atividades de coleta de água, resinas vegetais, pólen e néctar. A intoxicação resultante desta exposição pode ser letal, o que é facilmente identificável, ou causar efeitos na fisiologia e no comportamento do inseto. Tais efeitos, ocasionados por doses subletais, são difíceis de serem mensurados, como paralisia, desorientação ou mudanças comportamentais; porém, podem comprometer toda a estrutura social da colônia. Visando um melhor conhecimento dos efeitos de doses subletais de inseticidas em abelhas, estudou-se a ação dos ingredientes ativos Acetamiprido, Tiametoxam e Fipronil na sobrevivência e nos comportamentos de reflexo de extensão da probóscide e da atividade locomotora em operárias de A. mellifera. Preliminarmente, observou-se a DL50 vinte e quatro horas após o tratamento tópico do Acetamiprido Tiametoxam e Fipronil foram registrados... / the pollination of many wild flowers, and thus contributing to plant biodiversity. Their economic value derives not only from their direct products but also from their pollinating activity in crop plants. Animal pollination is important to sexual reproduction of many crops and the majority of wild plants, which can also be important for providing calories and micronutrients for humans. Furthermore, the decline of pollinating species can lead to a parallel decline in number of plant species. A. mellifera stands out as the most economically valuable crop pollinator in the world. Modern agriculture increasingly depends on the use of chemicals substances to control weeds, fungi and insect pests to ensure high yields. Honey bees may frequently become exposed to such chemicals as a consequence of their foraging activities collecting water, natural resins, pollen and nectar. Intoxication resulting from this exposure can be lethal, which is easily identifiable, or cause effects on the physiology and insect behavior. These effects, caused by sublethal doses are difficult to measure (such as paralysis, disorientation or behavioral changes), and can compromise the entire social structure of the colony. To improve the knowledge about the effects of insecticides sublethal doses effects in honey bees, we studied the action of the active ingredients Acetamiprid, Thiamethoxam and Fipronil on survival and behavior of the proboscis extension reflex (PER) and locomotor activity in workers of A. mellifera. Twenty-four hours after topic application, the LD50 values of Acetamiprid, Thiamethoxam and Fipronil were 9,3 μg/bee, 17 ng/bee and 1,9 ng/bee, respectively. We also estimated a LT50 with values of 1,4 hours, 3,8 hours and 19,8 hours to Acetamiprid, Thiamethoxam and Fipronil respectively. The behaviors were analyzed 1, 4 and 24 hours after topical application of active ingredients at doses corresponding... (Complete abstract click electronic access below)

Profissionais da área aeronáutica, como pilotos e comissários de bordo, são submetidos a doses de radiação de origem cósmica, que podem ser maiores do que as doses médias dos trabalhadores da indústria nuclear. A diversidade de partículas de altas energias presentes no campo de radiação a bordo das aeronaves torna complexa a mensuração da dose e requer cuidados especiais em relação aos sistemas de dosimetria a serem empregados nesta área. A Força Aérea Brasileira, por meio de seu Instituto de Estudos Avançados (IEAv /DCTA), em conjunto com o Instituto de Pesquisas Energéticas e Nucleares (IPEN / CNEN -SP) vem estudando o assunto desde 2008. Um protótipo de detector de radiação passivo para medições em aeronaves foi previamente construído e testado em condições de voo e de laboratório. O detector é capaz de medir a grandeza dosimétrica conhecida como dose absorvida (usando dosímetros passivos), que serão posteriormente correlacionados ao equivalente de dose ambiente e à dose efetiva recebidos por profissionais da área aeronáutica. Neste contexto, uma abordagem teórica por meio de simulações Monte Carlo com os códigos computacionais MCNP5 e MCNPX, foi usada para modelar e caracterizar a resposta do detector em determinadas condições experimentais. Este trabalho apresenta os resultados preliminares da modelagem computacional, com ênfase especial na comparação entre a grandeza fundamental dose absorvida (mensurada e simulada) e sua relação com o equivalente de dose ambiente e dose efetiva para este detector. / Aircrews, as pilots and flight attendants, are subjected to cosmic ray doses which can be higher than the average doses on workers from the nuclear industry. The diversity of particles of high energies present in the radiation field on board of aircrafts, turns the determination of the incident dose and requires special care regarding dosimetric systems to be used in this kind of field. The Brazilian Air Force, through the Institute for Advanced Studies (Instituto de Estudos Avançados, IEAv/DCTA) in conjunction with the Institute of Energetic and Nuclear Research (Instituto de Pesquisas Energéticas e Nucleares IPEN/CNEN-SP) are working on this subject since 2008. A prototype of a radiation detector for aircraft measurements was previously built and tested in flight and laboratory conditions. The detector is able of measuring a quantity known as absorbed dose (using passive dosimeters), which will subsequently be correlated to the ambient dose equivalent and the effective dose received by aircrews. In this context, a theoretical approach through Monte Carlo simulations with the computational codes MCNP5 and MCNPX was used to model and characterize the detector response at such experimental conditions. This work presents the preliminary results of the computational modeling, with special emphasis on the comparison between the absorbed dose quantity (measured and simulated) and its relationship with the ambient dose equivalent and the effective Dose for this detector.

O objetivo principal deste estudo foi analisar, na Gerência de Aceleradores Cíclotron do IPEN, o controle das doses de radiação ionizante e sua distribuição, comparando seus valores com as exigências regulamentares. A análise do controle das taxas de dose por meio do monitoramento de área foi realizada a partir de dados obtidos durante as produções de Flúor-18 no período de janeiro de 2010 a dezembro de 2011, totalizando 1011 medidas em cada ponto monitorado. A análise das doses provenientes de exposições ocupacionais foi realizada por meio de consulta aos históricos de dose individual. Durante os anos de 2007 a 2011 foram analisados os registros individuais das doses efetivas, totalizando 91 registros e de 2009 a 2011 foram analisados os registros de dose equivalente (nas mãos), totalizando 49 registros. Os indivíduos ocupacionalmente expostos envolvidos no estudo foram classificados, de acordo com a tarefa, em três grupos: alvos, radioproteção e operação e manutenção. Os resultados obtidos dos níveis de exposição ocupacional da radiação foram analisados e comparados com os limites estabelecidos pela autoridade regulatória nacional e com as recomendações internacionais. Com base nos resultados registrados do monitoramento de área e das doses recebidas, os procedimentos de radioproteção aplicados na instalação durante o período estudado foram averiguados e sugestões de melhorias foram dadas sob o ponto de vista da proteção radiológica. / The main purpose of this study was to analyze, at the Gerência de Aceleradores Cíclotron (Management of Cyclotron Accelerators) at IPEN, the control of ionizing radiation doses and their distribution by comparing their values with regulatory requirements. The analysis of the dose rate for the area monitoring was carried out from the data obtained during the production of Fluorine-18 from January 2010 to December 2011, totalizing 1011 measurements at each monitored spot. The doses analysis was performed through consultation of the individual dose records. During the years 2007 to 2011 the records of individual effective doses were analyzed, adding up to 91 records; from 2009 to 2011 the records of equivalent dose (hands) were analyzed, totalizing 49 records. The occupationally exposed individuals involved in the study were classified in three groups according to their task: targets, radioprotection and operation and maintenance. The results of occupational exposure levels of radiation were analyzed and compared with values established in national standards and international recommendations. Based on the results of the area monitoring and the doses received and recorded, radiation protection procedures implemented at the facility during the study period were checked and suggestions for improvements were given from the point of view of radiological protection.