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1
Hollis, Kevin John. "Microbeam design in radiobiological research." Thesis, Brunel University, 1995. http://bura.brunel.ac.uk/handle/2438/4824.
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Recent work using low-doses of ionising radiations, both in vitro and in ViVO, has suggested that the responses of biological systems in the region of less than 1 Gray may not be predicted by simple extrapolation from the responses at higher doses. Additional experiments, using high-LET radiations at doses of much less than one alpha particle traversal per cell nucleus, have shown responses in a greater number of cells than have received a radiation dose. These findings, and increased concern over the effects of the exposure of the general population to low-levels of background radiation, for example due to radon daughters in the lungs, have stimulated the investigation of the response of mammalian cells to ionising radiations in the extreme low-dose region. In all broad field exposures to particulate radiations at low-dose levels an inherent dose uncertainty exists due to random counting statistics. This dose variation produces a range of values for the measured biological effect within the irradiated population, therefore making the elucidation of the dose-effect relationship extremely difficult. The use of the microbeam irradiation technique will allow the delivery of a controlled number of particles to specific targets within an individual cell with a high degree of accuracy. This approach will considerably reduce the level of variation of biological effect within the irradiated cell population and will allow low-dose responses of cellular systems to be determined. In addition, the proposed high spatial resolution of the microbeam developed will allow the investigation of the distribution of radiation sensitivity within the cell, to provide a better understanding of the mechanisms of radiation action. The target parameters for the microbeam at the Gray Laboratory are a spatial resolution of less than 1 urn and a detection efficiency of better than 99 %. The work of this thesis was to develop a method of collimation, in order to produce a microbeam of 3.5 MeV protons, and to develop a detector to be used in conjunction with the collimation system. In order to determine the optimum design of collimator necessary to produce a proton microbeam, a computer simulation based upon a Monte-Carlo simulation code, written by Dr S J Watts, was developed. This programme was then used to determine the optimum collimator length and the effects of misalignment and divergence of the incident proton beam upon the quality of the collimated beam produced. Designs for silicon collimators were produced, based upon the results of these simulations, and collimators were subsequently produced for us using techniques of micro-manufacturing developed in the semiconductor industry. Other collimator designs were also produced both in-house and commercially, using a range of materials. These collimators were tested to determine both the energy and spatial resolutions of the transmitted proton beam produced. The best results were obtained using 1.6 mm lengths of 1.5 µm diameter bore fused silica tubing. This system produced a collimated beam having a spatial resolution with 90 % of the transmitted beam lying within a diameter of 2.3 ± 0.9 µm and with an energy spectrum having 75 % of the transmitted protons within a Gaussian fit to the full-energy peak. Detection of the transmitted protons was achieved by the use of a scintillation transmission detector mounted over the exit aperture of the collimator. An approximately 10 urn thick ZnS(Ag) crystal was mounted between two 30 urn diameter optical fibres and the light emitted from the crystal transmitted along the fibres to two photomultiplier tubes. The signals from the tubes were analyzed, using coincidence counting techniques, by means of electronics designed by Dr B Vojnovic. The lowest counting inefficiencies obtained using this approach were a false positive count level of 0.8 ± 0.1 % and an uncounted proton level of 0.9 ± 0.3 %. The elements of collimation and detection were then combined in a rugged microbeam assembly, using a fused silica collimator having a bore diameter of 5 urn and a scintillator crystal having a thickness of - 15 µm. The microbeam produced by this initial assembly had a spatial resolution with 90 % of the transmitted protons lying within a diameter of 5.8 ± 1.6 µm, and counting inefficiencies of 0.27 ± 0.22 % and 1.7 ± 0.4 % for the levels of false positive and missed counts respectively. The detector system in this assembly achieves the design parameter of 99 % efficiency, however, the spatial resolution of the beam is not at the desired I urn level. The diameter of the microbeam beam produced is less than the nuclear diameter of many cell lines and so the beam may be used to good effect in the low-dose irradiation of single cells. In order to investigate the variation in sensitivity within a cell the spatial resolution of the beam would require improvement. Proposed methods by which this may be achieved are described.
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Coghill, Matthew Taylor. "Radiobiological modeling using track structure analysis." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44731.
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The purpose of this thesis is to present data pertinent to and propose conclusions regarding the coordination
of radiobiologic effectiveness (RBE) and linear energy transfer (LET). RBE is a quantity relating the effectiveness
of different radiations in causing cell death. LET is a measure of the rate of energy transferred to material by an
ionizing particle. This relationship of these values varies for different particles. The reason for this is still inconclusive. The petitioner has made use of a toolkit for Geant4, known as Geant4-DNA, to perform track-structure analysis on a chromosome model. Geant4 is an object-oriented program for the "simulation of the passage of particles through matter" developed by CERN that makes use of Monte Carlo methods and is expanded by Geant4-DNA to handle low-energy electron physics as well as physic-chemical effects. The chromosome model, in this case, has been developed by the petitioner as a nucleus with a basic, uniform distribution of chromatin. Radiation damage to DNA, in the form of aberrations, lesions and strand breaks, can be coordinated to energy deposited or number of ionizations occurring in the target (in this case DNA or chromatin fiber). Certain threshold values have been established as indicate of different types of DNA damage. The ultimate goal of this work is to score these clusters of events against the threshold values to determine the severity of DNA damage. The final comparison of the results for different particles will provide for a better understanding of the RBE-LET relationships by improving the understanding of the underlying nanodosimetric qualities.
3
Weeks, Amanda. "Radiobiological Effects of internalised Radiopharmaceuticals in Human Cells." Thesis, University of Kent, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499642.
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Sandström, Helena. "Contouring variability in radiosurgery - dosimetric and radiobiological implications." Licentiate thesis, Stockholms universitet, Fysikum, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-123252.
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The use of Stereotactic Radiation Therapy (SRT) employing one large fraction of radiation, as in stereotactic radiosurgery (SRS), or few fractions of high doses, has continuously increased due to the technical development and the progress in dose delivery complemented by the positive clinical experience. The success of stereotactic radiation therapy depends on many clinical, dosimetric and radiobiological factors. For SRS in particular, the delivery of a highly conformal dose distribution to the target in one fraction allowing at the same time the sparing of the normal tissue and the critical structures is part of the basic concept of the technique. Provided that the highly accurate radiosurgical equipment available today is used, planning and delivering the prescribed dose distribution is an achievable goal, and therefore the main issue to be solved is the definition of the target. As the target volume in radiosurgery is usually defined without margins, the success of the stereotactic approach critically depends on the accurate delineation of the target which could be identified as a factor of key importance. In addition, the delineation of the Organs At Risk (OAR) is also critical. The purpose of this work was to evaluate the current degree of variability for target and OAR contouring and to establish methods for analysing multi-observer data regarding structure delineation variability. A multi-center target and OAR delineation study was initiated. Two complex and six common cases to be treated with SRS were selected and subsequently distributed to centers around the world performing Gamma Knife® radiosurgery for delineation and treatment planning. The resulting treatment plans and the corresponding delineated structures were collected and analysed. Results showed a very high variability in contouring for four complex radiosurgery targets. Similar results indicating high variability in delineating the OAR and reporting the doses delivered to them were also reported. For the common radiosurgery targets however, a higher agreement in the delineation was observed, although lower than expected. The assessment of the quality of treatment planning for radiosurgery is usually performed with respect to the coverage of the target, the planning specificity, and dose to the sensitive structures and organs close to the target. However, physical dose conformity to the target does not guarantee the success of the treatment. The assessment of the plan quality should also be performed with respect to the clinical outcome expressed as probability of controlling the target that should be irradiated. In this respect, this study also aimed to create the framework for assessing the impact of the inaccuracy in delineating the target on the predicted treatment outcome for radiosurgery targets known for their high potential to invade the neighbouring normal tissue, using radiobiological models. In addition, radiobiological models have also been used to determine the tumour control probability accounting for the oxygenation for stereotactic radiation therapy targets. The results suggest that radiobiological modelling has the potential to add to the current knowledge in SRS by theoretically assessing the key factors that might influence the treatment outcome.
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Bertrand, Olivier F. "Prevention of coronary restenosis using a radioactive stent : radiobiological studies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ64515.pdf.
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Falk, Jennie. "Robust Optimization for Uncertain Radiobiological Parameters in Inverse Dose Planning." Thesis, KTH, Optimeringslära och systemteori, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-160135.
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Cancer is a common cause of death worldwide with radiotherapy as one of the most used treatments. Radiation treatment plans are normally optimized using constraints on the maximum dose to tumours and minimum dose to surrounding healthy structures. It has been suggested that utilizing biological models in the radiation plan optimization process could improve outcome significantly. Such treatment plans depend not only on the accuracy of the biological models, describing the dose response relations of different tumours and other structures, but also on the accuracy of tissue specific parameters in these models. Different sets of biological model parameters lead to different treatment plans and thus, uncertainties in these parameters may compromise the quality of the treatments. In this thesis, several radiobiological optimization models have been developed, including either the concepts of Tumour Control Probability (TCP) and Normal Tissue Complication Probability (NTCP), or Equivalent Uniform Dose (EUD). The uncertainties of model parameters are expressed by probability density functions included in the dose optimization process. Robust optimization methods that account for the uncertainties have been developed and implemented in a MATLAB GUI created for Gamma Knife surgery. The robust optimized dose plans have been compared to non-robust plans using fixed parameter values. The results suggest that the final dose distribution strongly depend on the distribution functions and that the robust treatment plans are less dependent on variations in the model parametersCancer är en av de största dödsorsakerna i världen idag, och strålningsterapi är en vanligt förekommande behandlingsform. Vanligtvis optimeras behandlingsplaner för strålningsbehandlingar genom att sätta villkor på en minimal dos till tumörer och en maximal dos till omkringliggande vävnad. Biologiska modeller har utvecklats som ett alternativ till dessa villkor, för att användas i optimeringen av behandlingsplaner. Resultatet av sådan radiobiologisk dosoptimering beror inte endast av kvaliteten på de biologiska modellerna, utan även på noggrannheten i de vävnadsspecifika parametrar som finns i modellerna. Olika val av parametervärden leder till olika resultat och därför kommer osäkerheter i dessa parametrar att äventyra kvaliteten på strålningsbehandlingar. Radiobiologiska optimeringsmodeller som inkluderar koncepten Tumour Control Probability (TCP) och Normal Tissue Complication Probability (NTCP), eller Equivalent Uniform Dose (EUD) har utvecklats i detta examensarbete. De osäkra modellparametrar har uttryckts med sannolikhetsfördelningar och inkluderats i optimeringsmodellen. Robusta optimeringsmetoder som tar hänsyn till osäkerheter har utvecklats och implementerats i ett grafiskt användargrässnitt i MATLAB, med syftet att kunna användas i Gammaknivs- kirurgi. De optimerade robusta dosplanerna har jämförts med icke-robusta optimerade dosplaner där värden på de osäkra parametrarna är konstanta. Resultaten pekar på att dosplanerna starkt beror på de olika fördelningar av parametrar som använts och att robusta optimeringsmetoder ger behandlingsplaner som är mindre känsliga för variationer i de biologiska parametrarna.
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Mavroidis, Panayiotis. "Determination and use of radiobiological response parameters in radiation therapy optimization /." Stockholm : Karolinska Univ. Press, 2001. http://diss.kib.ki.se/2001/91-7349-092-X/.
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Iori, Mauro. "Rotational intensity modulated radiation therapy : dosimetric, treatment planning, and radiobiological aspects." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569581.
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The introduction in Radiation Oncology of x-ray beams fluence modulation, the treatment technique known as Intensity Modulated Radiation Therapy (IMRT), is leading to the flourishing of new and increasingly sophisticated treatments. It is within this context that delivery systems have been evolving from static to rotational IMRT techniques through which significant advantages have occurred in terms of treatment plan quality, delivery efficiency and accuracy, although paying the price of longer calculation times for the plan optimization. The point has been reached where the perceived advantages of rotational IMRT techniques, for which some companies have marketed therapy systems with different architecture from that of conventional linear accelerators, have led users to question whether the established and more conventional systems are becoming obsolete. However, the newly available methods of delivering Intensity Modulated Arc Therapies (IMAT) using conventional accelerators, an advanced form of rotational IMRT that combines multiple arcs with variable fluence and gantry speed, seem to have provided a preliminary answer to this concern. Although it is difficult to know which of these treatment modalities will be discontinued in the near future, it is clear that the rotational IMR T is expected to become increasingly important. Therefore, the problem of understanding which are the strengths of these techniques, or the most effective methods (forward or inverse-planning based) of their treatment planning procedures, as well as the most robust and effective systems for verifying dosimetrically such rotational deliveries can be considered current research topics. As a results, different aspects of rotational IMRT techniques have been investigated in this work, starting with the pre-clinical dosimetry of IMAT therapies, passing through the planning procedures also in comparison with static IMR T, and advancing to a special application of 'rotational IMRT': the simulation of radiobiologically optimised, voxel-based dose-painting, guided by the metabolic tumour imaging. In particular we have worked on: two methods for the pre-clinical dosimetry of IMA T treatments using a matrix detector of ionization-chambers and an electronic portal imaging device, a forward and an inverse-planning approach for simulating IMAT treatments, a ranking of plans simulated with static and rotational IMRT modalities on prostate tumour. The high conformality achievable by rotational IMRT, as well as its potential to deliver selectively different doses inside a heterogeneous target volume, together with the image guidance capabilities of the newest therapy units, makes arc modulation the most appropriate and suitable instrument for assessing future "dose painting" treatments. In this regard, two radiobiological objective functions for guiding the dose redistribution inside a group of prostate tumours according to their estimated clonogenic density distribution (based on Position Emission Tomography imaging) were developed, compared and analysed.
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Fernandez, Alejandro Carabe. "A theoretical investigation of the radiobiological rationale for high-LET radiotherapy." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487551.
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Conere, Thomas James. "The radiobiological effects of gas mixtures under ambient and hyperbaric conditions." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292290.
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Chung, Yoonsun. "Radiobiological evaluation of new boron delivery agents for boron neutron capture therapy." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/44784.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2008.Includes bibliographical references (p. 123-132).
This thesis evaluates the radiobiological effectiveness of three new boron compounds namely a boronated porphyrin (BOPP) and two liposome formulations for neutron capture therapy (BNCT). The methodology utilizes in vitro and in vivo comparisons that characterize compounds relative to boric acid and boronophenylalanine (BPA). In vitro evaluations utilized a colorimetric assay and 96-well plates to minimize the quantities of compound required for testing. The assay was optimized for the murine SCCVII, squamous cell carcinoma to determine the chemical toxicity and relative cellular uptake of a compound. BOPP was toxic at low concentrations and comparisons between the different compounds for thermal neutron irradiations were performed with approximately 5 [mu]g 10B/ml in the culture medium to allow radiation induced effects to govern the observed response. Using less than 300 [mu]g of compound and 250 kVp X-rays as control irradiations, a compound biological effectiveness (CBE) of 3.3 ± 0.7 was determined for BOPP that is comparable to the result for boric acid (3.5 ± 0.5) indicating a non-selective intracellular accumulation of 10B. BPA has a significantly higher CBE of 6.1 + 0.7. Boronated liposomes (MAC-16 and MAC+TAC) were evaluated with the EMT-6 murine mammary carcinoma. Biodistribution studies showed high 10B uptake in tumor (20-40 [mu]g 10B/g) 30 hours after a single i.v. injection (dose 6-20 [mu]g 10B per gram of body weight). Tumor control experiments were performed using thermal neutrons to study the efficacy of the boron delivered by liposomes and BPA. The MAC-16 produced a 16 % tumor control and BPA (dose 43 [mu]g 10B/gbw) 63 % for tumor boron concentrations of approximately 20 [mu]g 10B/g and the same neutron fluence.
(cont.) Liposome doses were limited by injection volume and so two injections were tried 2-hours apart that doubled the boron concentration in tumor compared to a single administration. This improved the therapeutic response to 67 % with less apparent skin damage than with BPA. Microscopic studies using fluorescent labeled liposomes revealed 10B was nonuniformly distributed and concentrated at the edge of the tumor. Based on these studies in the tumor cell lines chosen neither of the compounds appear superior to BPA.
by Yoonsun Chung.
Ph.D.
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Folkert, Michael R. (Michael Ryan) 1975. "Development, characterization, and application of a charged particle microbeam for radiobiological research." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/34434.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 2005."September 2005."
Includes bibliographical references (leaves 194-197).
The goal of this work is to develop a charged-particle microbeam for use in radiobiological research at the MIT Laboratory for Accelerator Beam Applications (LABA). The purpose of this device is to precisely explore the radiation response of biological systems on a cellular and subcellular level, particularly in the area of temporal and spatial effects of radiation on in vitro systems. An accelerator-based 750 keV proton source was characterized and integrated into a laboratory-scale device that includes a deflection/gating system, single-particle detection system, imaging and positioning system, and a collimation system with two designed modes: a "charged-particle microslit" for delivering a -3 micron by 1 mm dose profile; and a pinhole aperture for delivering a -3 micron diameter pattern of radiation. The entire device measures less than 4 m, requires minimal radiation shielding, and utilizes a dedicated ion source. The charged particle microslit has been fully characterized and used to deliver a radiation pattern to a series of mammalian fibroblast cell monolayers that have subsequently been assayed for direct and indirect chemical effects of radiation, double-stranded DNA damage, and DNA repair protein localization. These studies will contribute to the understanding of the radiation-induced bystander effect, which is generally defined as the induction of biological effects in cells that are not directly traversed by ionizing radiation.
(cont.) Analysis of the range of assays performed on the microbeam-irradiated cells demonstrates that even though the physical radiation dose is confined to a subnuclear width (< 5 microns), in many cases the biological effects of the radiation extend for many cell widths (> 40 microns) and show dependence on the initial radiation dose delivered to the directly irradiated cells. As an experimental system, the LABA Microbeam was designed to be practically turn-key, and most applications require only one operator to perform. The LABA Microbeam represents a significant step towards a cost-effective and easily operated charged-particle microbeam appropriate for use as a standard laboratory research tool. Further work remains in automation of the microbeam subsystems and optimization/characterization of the pinhole-aperture collimator, as well as expanding the scope of the radiobiological assays performed using the charged-particle microslit.
by Michael R. Folkert.
Ph.D.
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AlDahlawi, Ismail. "Calibration of a radiobiological irradiator : the Faxitron cabinet X-ray system model CP160." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112370.
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Radiobiological irradiation can be performed using appropriately collimated sealed source radioisotope machines such as Co-60 units, as well with X-ray tubes and linear accelerators. The increasing research interest in delivering organ-specific or whole body animal external irradiation has led to the introduction of dedicated X-ray units for research purposes. In this work, the proprieties of a kilovoltage X-ray biological irradiator, the Faxitron cabinet X-ray system model CP160, are investigated and dosimetrically characterized. Calculation formalisms for everyday use of the radiobiological irradiator in laboratory conditions, specifically for cell cultures and small animals total body irradiation, were developed following the AAPM TG-61 protocol. The quality of the X-ray beams generated by this irradiator was found to range between HVL 0.7 mm Cu for a 160 kVp 0.5 mm Cu filtered beam, and HVL 0.07 mm Al for a 20 kVp non-filtered beam. Our calculation formalisms for cell cultures and small animal irradiations were found to be valid within +/-5%.
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Cole, Aidan. "Investigation of the radiobiological and dosimetric implications of respiratory motion in advanced radiotherapy." Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.673797.
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The primary aim of radiotherapy is to deliver sufficient dose to eradicate a tumour whilst sparing normal tissue. This balance in tumour control probability (TCP) and normal tissue complication probability (NTCP) can be influenced by a number of factors, one of which is respiratory motion. This thesis investigates the potential dosimetric and radiobiological differences as a result of respiratory motion in lung cancer radiotherapy. It demonstrates significant dosimetric improvements by using advanced motion management techniques (4DCT and respiratory gating) and modulated radiotherapy (VMAT), in regi~ns of lung tumour motion. These techniques confer improvements in NTCP and can allow for dose escalation. However, when patient characteristics and tumour characteristics are included in clinical modelling algorithms, the potential gain may not be as clinically relevant as anticipated. Many advanced techniques currently used in radiotherapy departments, have been implemented without a clear understanding of potential differences in radiobiological response compared with previous techniques. This thesis demonstrates significant differences in the radiation induced bystander effect (RISE), in the presence of respiratory motion and modulated radiotherapy. In vitro studies of respiratory gating indicate a trend towards increased survival as treatment delivery time increases. There is an increased dependence on the use of these radiotherapy techniques which introduce complex spatiotemporal dose modulation. The data presented in this thesis indicates that radiobiological consequences may not be fully explained by existing theories. These findings may be of particular relevance for modulated radiotherapy in NSCLC radiotherapy.
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Caceres, Maria Alejandra. "A dosimetry and radiobiological model for intravascular brachytherapy treatment planning with radioisotope emitting stents." FIU Digital Commons, 2003. http://digitalcommons.fiu.edu/etd/1961.
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The aim of this study was to develop a practical, versatile and fast dosimetry and radiobiological model for calculation of the 3D dose distribution and radiobiological effectiveness of radioactive stents. The algorithm was written in Matlab 6.5 programming language and is based on the dose point kernel convolution. The dosimetry and radiobiological model was applied for evaluation of the 3D dose distribution of 32P, 90Y, 188Re and 177Lu stents. Of the four, 32P delivers the highest dose, while 90Y, 188Re and 177Lu require high levels of activity to deliver a significant therapeutic dose in the range of 15-30 Gy. Results of the radiobiological model demonstrated that the same physical dose delivered by different radioisotopes produces significantly different radiobiological effects. This type of theoretical dose calculation can be useful in the development of new stent designs, the planning of animal studies and clinical trials, and clinical decisions involving individualized treatment plans.
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Beyreuther, Elke. "Realization of radiobiological in vitro cell experiments at conventional X-ray tubes and unconventional radiation sources." Forschungszentrum Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:d120-qucosa-62621.
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More than hundred years after the discovery of X-rays different kinds of ionizing radiation are ubiquitous in medicine, applied to clinical diagnostics and cancer treatment as well. Irrespective of their nature, the widespread application of radiation implies its precise dosimetric characterization and detailed knowledge of the radiobiological effects induced in cancerous and normal tissue. Starting with in vitro cell irradiation experiments, which define basic parameters for the subsequent tissue and animal studies, the whole multi-stage process is completed by clinical trials that translate the results of fundamental research into clinical application. In this context, the present dissertation focuses on the establishment of radiobiological in vitro cell experiments at unconventional, but clinical relevant radiation qualities.
In the first part of the present work the energy dependent biological effectiveness of photons was studied examining low-energy X-rays (≤ 50 keV), as used for mammography, and high-energy photons (≥ 20 MeV) as proposed for future radiotherapy. Cell irradiation experiments have been performed at conventional X-ray tubes providing low-energy photons and 200 kV reference radiation as well. In parallel, unconventional quasi-monochromatic channeling X-rays and high-energy bremsstrahlung available at the radiation source ELBE of the Forschungszentrum Dresden-Rossendorf were considered for radiobiological experimentation. For their precise dosimetric characterization dosimeters based on the thermally stimulated emission of exoelectrons and on radiochromic films were evaluated, whereas just the latter was found to be suitable for the determination of absolute doses and spatial dose distributions at cell position. Standard ionization chambers were deployed for the online control of cell irradiation experiments. Radiobiological effects were analyzed in human mammary epithelial cells on different subcellular levels revealing an increasing amount of damage for decreasing photon energy. For this reason, the assumed photon energy dependence was reconfirmed for a cell line other than human lymphocytes, an important finding that was discussed on the 2007 Retreat of the German Commission on Radiological Protection.
After successful finalization of the photon experiments the focus of the present dissertation was directed to the realization of in vitro cell irradiation experiments with laser-accelerated electrons. This research was carried out in the frame of the project onCOOPtics that aims on the development of laser-based particle accelerators, which promise accelerators of potentially compact size and more cost-effectiveness suitable for a widespread medical application, especially for high precision hadron therapy. The unique properties, i.e., the ultrashort bunch length and resultant ultrahigh pulse dose rate, of these unconventional particle accelerators demand for extensive investigations with respect to potential effects on the dosimetric and radiobiological characterization. Based on the experiences gained at ELBE first experiments on the radiobiological characterization of laser-accelerated electrons have been performed at the Jena Titanium:Sapphire laser system. After beam optimization, a sophisticated dosimetry system was established that allow for the online control of the beam parameters and for the controlled delivery of dose to the cell sample. Finally, worldwide first systematic in vitro cell irradiation experiments were carried out resulting in a reduced biological effectiveness for laser-accelerated electrons relative to the 200 kV X-ray reference, irrespectively on the biological effect and cell lines examined. These successful results are the basis for future in vivo studies and experiments with laser-accelerated protons.
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Fager, Marcus. "Radiobiological plan optimization in Proton therapy for Prostate tumors using a Patched Integrated Edge [PIE] technique." Thesis, Stockholms universitet, Fysikum, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-96203.
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Purpose: A novel treatment planning technique using proton pencil beam scanning (PBS) is proposed that takes advantage of the increased Linear Energy Transfer (LET) at the distal edge of proton beams to deposit the increased biological effective dose related to the elevated LET protons within prostate tumors. Background: The availability of proton treatment for cancer has increased the latest decade and will continue to increase rapidly in the coming decade. The Relative Biological Effectiveness (RBE) of protons earlier considered to be 1.10 has started to be questioned in the latest decade. This thesis investigates what would be the effect of a variable RBE on the effective dose to the target. Method: Uniform dose distributions were planned using two different beam arrangements: (1) Full-Target Plans (FTP), with two lateral fields, each field targeting the entire target; (2) Patched Integrated Edge (PIE) plans, with 2, 4, and 7 fields, each field targeting only the respective proximal segment of the target. Dose distributions were calculated and optimized with Eclipse in order to deliver the same dose to the target as well as to maintain the same OARs dose constrains for all the plans. Beam properties (range, modulation, spot map and weights) were used to calculate dose and dose averaged LET distributions with Monte Carlo. The RBE for each plan was calculated using radiobiological models taking into account the dose and LETd distribution as well as published values of for the irradiated tissues as input parameters. The RBE weighted dose (DRBE) was calculated for each planning approach and evaluated with respect to three different aims. Results: An increase of the number of fields using PIE increased the LETd within the target. The increased LETd resulted in an increase of the RBE weighted dose, DRBE, of up to 12.7 Gy (RBE) to the target, which is a 14% increase. However, if the same DRBE is to be delivered to the target with FTP and PIE the increase of LETd in the target implied a decrease of dose per fraction, d, of up to 0.21 Gy, a decrease of 13 %. Conclusions: A modified distribution of proton’s linear energy transfer in PBS allows to deposit highly effective biological dose by the elevated-LET protons within the target, which might help to increase the effectiveness of prostate radiotherapy. This might also serve as a platform to investigate how the physical prescribed dose can be reduced by increasing the LETd in the target in order to maintain a constant DRBE in the prostate.
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Kjellsson, Lindblom Emely. "Time, dose and fractionation: accounting for hypoxia in the search for optimal radiotherapy treatment parameters." Doctoral thesis, Stockholms universitet, Fysikum, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-148301.
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The search for the optimal choice of treatment time, dose and fractionation regimen is one of the major challenges in radiation therapy. Several aspects of the radiation response of tumours and normal tissues give different indications of how the parameters defining a fractionation schedule should be altered relative to each other which often results in contradictory conclusions. For example, the increased sensitivity to fractionation in late-reacting as opposed to early-reacting tissues indicates that a large number of fractions is beneficial, while the issue of accelerated repopulation of tumour cells starting at about three weeks into a radiotherapy treatment would suggest as short overall treatment time as possible. Another tumour-to-normal tissue differential relevant to the sensitivity as well as the fractionation and overall treatment time is the issue of tumour hypoxia and reoxygenation. The tumour oxygenation is one of the most influential factors impacting on the outcome of many types of treatment modalities. Hypoxic cells are up to three times as resistant to radiation as well-oxygenated cells, presenting a significant obstacle to overcome in radiotherapy as solid tumours often contain hypoxic areas as a result of their poorly functioning vasculature. Furthermore, the oxygenation is highly dynamic, with changes being observed both from fraction to fraction and over a time period of weeks as a result of fast and slow reoxygenation of acute and chronic hypoxia. With an increasing number of patients treated with hypofractionated stereotactic body radiotherapy (SBRT), the clinical implications of a substantially reduced number of fractions and hence also treatment time thus have to be evaluated with respect to the oxygenation status of the tumour. One of the most promising tools available for the type of study aiming at determining the optimal radiotherapy approach with respect to fractionation is radiobiological modelling. With clinically validated in vitro-derived tissue-specific radiobiological parameters and well-established survival models, in silico modelling offers a wide range of opportunities to test various hypotheses with respect to time, dose, fractionation and details of the tumour microenvironment. Any type of radiobiological modelling study intended to provide a realistic representation of a clinical tumour should therefore take into account details of both the spatial and temporal tumour oxygenation. This thesis presents the results of three-dimensional radiobiological modelling of the response of tumours with heterogeneous oxygenation to various fractionation schemes, and oxygenation levels and dynamics using different survival models. The results of this work indicate that hypoxia and its dynamics play a major role in the outcome of radiotherapy, and that neglecting the oxygenation status of tumours treated with e.g. SBRT may compromise the treatment outcome substantially. Furthermore, the possibilities offered by incorporating modelling into the clinical routine are explored and demonstrated by the development of a new calibration function for converting the uptake of the hypoxia-PET tracer 18F-HX4 to oxygen partial pressure, and applying it for calculations of the doses needed to overcome hypoxia-induced radiation resistance. By hence demonstrating how the clinical impact of hypoxia on dose prescription and the choice of fractionation schedule can be investigated, this project will hopefully advance the evolution towards routinely incorporating functional imaging of hypoxia into treatment planning. This is ultimately expected to result in increased levels of local control with more patients being cured from their cancer.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 6: Manuscript.
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Wilkins, David E. Carleton University Dissertation Physics. "Radiobiological and magnetic resonance studies of combined radiation and cisplatin therapy in the 9L rat brain tumour model." Ottawa, 1993.
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Chandrasekaran, Mekala. "The effect of photon dose calculation algorithms on the clinical outcome of radiotherapy as assessed by radiobiological models." Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/9373/.
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The accuracy of dose calculation algorithms used for radiotherapy treatment planning play a significant role in the clinical outcome of various treatment regimens. Heterogeneities in human anatomy such as lung, air cavities, bone, soft tissue and fat present challenges to the dose calculation algorithms as they are prone to disrupt the charged-particle equilibrium. Monte Carlo (MC) based dose calculation algorithms are proven to be superior to all the current analytical algorithms owing to their ability to account for all the physical interactions that are involved in radiation transport. Numerous publications have examined the differences in physical doses calculated by analytical algorithms when compared to MC in dealing with heterogeneities. However, before this work the clinical significance of these differences in physical dose has never been investigated in detail. An EGSnrc, BEAMnrc and DOSXYZnrc based MC dose calculation engine was set up in a parallel computing environment to simulate three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiation therapy (IMRT). A Varian 2100 C/D accelerator head was modeled and validated to match measurements of open and dynamic wedged fields in a homogeneous water phantom which was found to be in good agreement with measurements within 2%/2mm and 3%/3mm respectively. In addition, MC calculated doses in a heterogeneous lung phantom were compared to radiochromic film measurements. Overall, there was good agreement between the two, although large differences of upto 16% were found in some cases. This dose calculation system was used to perform MC simulations on computed tomography (CT) images. The clinical impact of the differences in absolute doses calculated by various photon dose calculation algorithms for two clinical tumour sites was investigated. The tumour control probability (TCP) and normal tissue complication probability (NTCP) were estimated using well established bio-mathematical radiobiological models. This work includes the analysis of 7 convolution (i.e. pencil-beam) and convolution-superposition (CS) based photon dose algorithms available in commercial treatment planning systems (TPSs) as well as MC, in treatment plans of non-small cell lung carcinoma (NSCLC) and nasopharyngeal carcinoma (NPC). In both NSCLC and NPC, the convolution algorithms overestimate the dose to the tumour and hence overestimate the TCP to up to 45%. Some of the CS algorithms were comparable to MC though others exhibit significant differences. In NSCLC, the absolute differences in the NTCP values with radiation pneumonitis and rib fracture as end points were not as large as the differences found in the TCPs. On the other hand, in NPC, the overestimation of probability of occurrence of xerostomia by some TPS algorithms may be preventing dose escalation. Parameters for the TCP model were derived by fitting the TCP predictions to published outcome for four widely varying dose-fractionation regimens for a patient cohort undergoing radical radiotherapy treatment for NSCLC. The derived parameter sets strongly depend on the accuracy of the dose calculation algorithm involved. Parameters derived based on dose-distribution data sets obtained using one particular dose calculation algorithm may not hold good when evaluating treatment plans calculated with a different algorithm. In this sub-study, the influence of dose calculation algorithms on TCP model parameters was evaluated. Significant differences were found in TCPs when calculated with inconsistent parameters. Hence, the choice of dose calculation algorithm is crucial and although some algorithms generally perform close to MC in handling inhomogeneities, it is necessary to understand how the underlying differences affect the predicted clinical outcome.
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Shin, Wook Geun. "Development and application of the Geant4-DNA toolkit for the simulation of radiobiological effects at the sub-cellular scale." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0310.
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Prévoir les effets biologiques induits par les rayonnements ionisants est un défi scientifique majeur de la radiobiologie actuelle, en particulier pour essayer de mieux comprendre les effets des faibles doses sur le milieu vivant ainsi que la cancérogénèse. L'approche computationnelle basée sur les codes de simulation des structures de traces dans le milieu biologique par la technique Monte Carlo est aujourd'hui la méthode la plus fiable pour calculer les effets précoces des radiations ionisantes sur l'ADN, la cible cellulaire principale des effets des radiations. Parmi les codes existants, l'extension Geant4-DNA de la boîte à outils généraliste Geant4 est la première entièrement ouverte et librement accessible à la communauté. Geant4-DNA peut simuler non seulement l'étape physique mais aussi les étapes physico-chimique et chimique de la radiolyse de l'eau. Ces étapes peuvent être combinées avec des modèles géométriques simplifiés de l'ADN afin d'évaluer les dommages précoces directs et indirects à l'ADN. Dans cette thèse, je propose (1) d'améliorer dans Geant4-DNA la modélisation de la diffusion élastique des électrons dans l'eau liquide pour simuler plus précisément la distribution spatiale des dépôts d'énergie et des espèces radicalaires. Ensuite, (2) l'étape physico-chimique de la radiolyse de l'eau est également améliorée en se basant sur des approches décrites dans la littérature (modélisation, mesures), cette étape affectant fortement l'étape chimique en modifiant les rendements initiaux et la concentration des espèces radicalaires. (3) La méthode du temps de réaction indépendant (IRT) est en outre implémentée dans Geant4-DNA afin de réduire le temps de calcul pour simuler la cinétique chimique de la radiolyse de l'eau. Enfin, j'évalue (4) les dommages biologiques induits à l'échelle subcellulaire en utilisant une géométrie de l'ADN cellulaire développée dans une étude précédente, en incluant dans la simulation toutes les améliorations développées au cours de cette thèse, jusqu'à la réparation des dommages précoces. Ces développements sont regroupés au sein d'une chaine de simulation complète destinée aux utilisateurs de Geant4 et de son extension Geant4-DNAPredicting the biological effects induced by ionizing radiation is a major scientific challenge of current radiobiology, in particular to try to better understand the effects of low doses on living beings as well as carcinogenesis. The computational approach based on codes to simulate trace structures in the biological medium using the Monte Carlo technique is today the most reliable method to calculate the early effects of ionizing radiation on DNA, the main cellular target of radiation effects. Among the existing codes, the Geant4-DNA extension of the Geant4 general purpose simulation toolkit is the first one fully open and freely available to the community. Geant4-DNA can simulate not only the physical but also the physico-chemical and chemical stages of water radiolysis. These stages can be combined with simplified geometric models of DNA to assess direct and indirect early DNA damage. In this thesis, I propose (1) to improve in Geant4-DNA the modeling of the elastic scattering of electrons in liquid water in order to simulate more precisely the spatial distribution of energy deposits and radical species. Then, (2) the physico-chemical stage of water radiolysis is also improved based on approaches described in the literature (modeling, measurements), this step strongly affecting the chemical stage by modifying the initial yields and the concentration of radical species. (3) In addition, the Independent Reaction Time (IRT) method is implemented in Geant4-DNA to reduce the computational time to simulate the chemical kinetics of water radiolysis. Finally, I evaluate (4) the biological damage induced at the subcellular scale using a cellular DNA geometry developed in a previous study, including in the simulation all the improvements developed during this thesis, up to the repair of early DNA damage. These developments are grouped in a complete simulation chain for users of the Geant4-DNA extension of Geant4
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Frese, Malte Christian [Verfasser], and Uwe [Akademischer Betreuer] Oelfke. "Potentials and Risks of Advanced Radiobiological Treatment Planning for Proton and Carbon Ion Therapy / Malte Christian Frese ; Betreuer: Uwe Oelfke." Heidelberg : Universitätsbibliothek Heidelberg, 2011. http://d-nb.info/1179229266/34.
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Laura, Antonovic. "Radiobiological end-points for the theoretical evaluation of the effectiveness of carbon ions and photons in treating tumours with dynamic hypoxia." Doctoral thesis, Stockholms universitet, Fysikum, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-102731.
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Tumours are characterised by unorganised vasculature, which often results in hypoxic regions. Hypoxia is a common cause for photon radiotherapy (RT) treatment failure, as hypoxic cells require up to 2-3 times higher doses compared to well-oxygenated cells for the same effect in terms of cell kill. The increase in dose that would be required to treat the tumours of cancer patients is limited by the radiation sensitivity of surrounding normal tissues. Using carbon ions instead of photons, the radiation dose can be conformed to the tumour to a much higher degree, resulting in an improved sparing of normal tissues. In addition, carbon ions have a much higher radiobiological effectiveness near the end of their range, which is positioned in the tumour. Also, the radiation modes of action leading to cell death when carbon ions interact with living tissues, are less sensitive to the oxygen status compared with the action modes of photons. The focus of this thesis lies in the development of models for the computation of the cell surviving fraction and tumour control probability (TCP) in hypoxic tumours after photon and carbon ion RT. The impact of fractionation was evaluated with regard to possible spatial changes in oxygenation, both for stereotactic body RT and for carbon ion RT. The feasibility of a method to determine and deliver the optimal photon dose for achieving a high TCP according to spatial variations in radiation sensitivity was evaluated in a treatment planning study. The radiobiological models were finally used for the theoretical quantification of the gain in using carbon ions instead of photons. The results show that there are great possibilities to increase the number of positive outcomes of radiation treatment of tumours if the key influential factors are taken into account, such as level and distribution of hypoxia, radiation quality and choice of fractionation schedule.At the time of the doctoral defence the following papers were unpublished and had a status as follows; Paper 3: Manuscript; Paper 4: Epubl ahead of print; Paper 5: Manuscript
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Sandström, Helena. "Variability in target delineation instereotactic radiosurgery withLeksell Gamma Knife® Perfexion™ and a perspective on radiobiological outcome: A multiobserver study." Thesis, Stockholms universitet, Medicinsk strålningsfysik (tills m KI), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-100429.
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Petrigliano, Maria Stefania. "Comparison of radiobiological effects induced by ultra-high and standard dose rate of x-rays on a radio-resistant cell line." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/10813/.
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Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a ultra-high dose rate comparing them with standard dose rate.
In this regard, a radioresistant SK-MEL-28 cell line were irradiated with x-ray in order to have a total dose of 2 and 4 Gy, at two different dose rate. The ultra-high dose rate is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles, in this case, we focused our study on the influence of X-rays. While a low dose rate is obtained with conventional X-ray tube.
In this study it results that a ultra-high dose rate enhances radiosensitivity of melanoma cells while reducing the adhesion, proliferation and migration ability of cells.
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Heller, Dennis P. Carleton University Dissertation Physics. "Radiobiological aspects of cellular recovery following high and low dose-rate irradiation with/without mild hyperthermia in a human glioma cell model." Ottawa, 1993.
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Smith, Debbie Michelle Carleton University Dissertation Physics. "The radiobiological equivalence of low dose rate irradiation and pulsed dose rate irradiation, as it relates to brachytherapy, using U-87MG blioblastoma cell line." Ottawa, 2000.
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Adamus-Górka, Magdalena. "Improved dose response modeling for normal tissue damage and therapy optimization." Doctoral thesis, Stockholm University, Medical Radiation Physics (together with KI), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7433.
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The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis overview part, some of the basic properties of the dose response relation are reviewed and the most common radiobiological dose-response models are compared with regard to their ability to describe experimental dose response data for rat spinal cord using the maximum likelihood method. For vascular damage the relative seriality model was clearly superior to the other models, whereas for white matter necrosis all models were quite good except possibly the inverse tumor and critical element models. The radiation sensitivity, seriality and steepness of the dose-response relation of the spinal cord is found to vary considerably along its length. The cervical region is more radiation sensitive, more parallel, expressing much steeper dose-response relation and more volume dependent probability of inducing radiation myelitis than the thoracic part. The higher number of functional subunits (FSUs) consistent with a higher amount of white matter close to the brain may be responsible for these phenomena. With strongly heterogeneous dose delivery and due to the random location of FSUs, the effective size of the FSU and the mean dose deposited in it are of key importance and the radiation sensitivity distribution of the FSU may be an even better descriptor for the response of the organ. An individual optimization of a radiation treatment has the potential to increase the therapeutic window and improve cure for a subgroup of patients.
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Smith, Debbie Michelle. "The radiobiological equivalence of low dose rate irradiation and pulsed dose rate irradiation, as it relates to brachytherapy, using the U-87MG glioblastoma cell line." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ57780.pdf.
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Milián, Félix Más. "Estudo in vitro dos efeitos radiobiológicos no DNA plasmidial com radiações ionizantes de baixo LET." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/43/43134/tde-04122006-150637/.
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O estudo da interação da radiação com moléculas de DNA tem se intensificado nos últimos anos, determinando avanços nas técnicas experimentais e na compreensão teórica desse fenômeno. No entanto, falta ainda um estudo sistemático e com boa precisão da interação de diferentes radiações com o DNA em condições controladas. Neste trabalho desenvolveu-se uma técnica experimental que permite o estudo daquela interação com diferentes radiações, permitindo uma análise quantitativa dos efeitos da radiação sobre o DNA, mais especificamente, da produção de single- e double strand breaks em moléculas de DNA plasmidial irradiados em solução aquosa com diferentes concentrações de scavengers. Para o desenvolvimento desse trabalho, foram realizados diversos testes para encontrar as condições ideais para se reduzir as incertezas na quantificação das diferentes quebras no DNA. Desenvolveu-se também um programa computacional que permite uma análise precisa da imagem da eletroforese, que oferece ferramentas úteis para a análise quantitativa. Com isso, reduziram-se as incertezas e flutuações experimentais, o que permitiu o estudo da interação radiação-DNA em condições de concentrações de scavengers muito baixas. Os resultados são compatíveis com os dados experimentais, nas condições onde estes já existiam, e compatíveis com o esperado teoricamente nas condições onde não existem dados experimentais para a comparaçãoThe interaction of radiation with DNA molecules has been intensively studied in the last years, allowing improvements on the experimental techniques and on the theoretical comprehension of the phenomena involved in that interaction under controlled conditions. In this work, a new experimental technique has been developed which enables one to study the radiation-DNA interaction for different radiations and with reduced uncertainties, allowing a quantitative analysis of single- and double-strand breaks on DNA in aqueous solutions with different scavenger concentrations. To this end, many experimental tests were performed in order to find the best experimental condition for reducing the uncertainties. A software was developed for quantitative analysis of the electrophorese image, offering the most important tools for accurate quantification of the DNA products. An important reduction on uncertainties was achieved, allowing the extension of experimental studies to the low scavenger concentration region. The results are in good agreement with experimental data at those conditions where these experiments were already performed, and in agreement with the theoretical model where there are no experimental results to compare with.
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Lindblom, Emely. "The impact of hypoxia on tumour control probability in the high-dose range used in stereotactic body radiation therapy." Thesis, Stockholms universitet, Fysikum, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-84518.
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The use of stereotactic body radiation therapy employing few large fractions of radiation dose for the treatment of non-small cell lung cancer has been proven very successful, high values of tumour control probability (TCP) being clinically achieved. In spite of the success of the fractionation schedules currently used, there is a tendency towards reducing the number of fractions for economical and practical reasons, and also for maximizing the comfort of the patients. It is therefore the main aim of this thesis to investigate the impact of a severely reduced number of fractions on the tumour control probability for tumours that contain hypoxic areas. The impact on TCP of other factors such as hypoxic fraction, distribution of the oxygen partial pressure and location of the hypoxic volume within the tumour were also investigated. The effect of tumour motion due to breathing was included and evaluated using Cone Beam Computed Tomography (CBCT) data from patients imaged with internal markers in the liver and pancreas. The results clearly showed that in the presence of hypoxia, TCP is seriously compromised if there is not enough time for reoxygenation between fractions. A reduction in the number of fractions of just one fraction may require an increase of several Gy per fraction to obtain a similar TCP. The diaphragmatic tumour motion range showed little influence on TCP provided that the PTV encompassed all tumour positions. The dose delivered to the PTV margin was found not to be the only factor that is significant for local control, the average dose correlated better with TCP. The agreement of the results of this work with clinical results also serve as a strong indicator that inter-fraction reoxygenation is an important process in real-life patients treated with stereotactic body radiotherapy.
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McKenna, Frederick W. "Studies of cell survival curve fitting, effective doses for radiobiological evaluation in SBRT treatment techniques and the dependence of optical density growth in Gafchromic EBT film used in IMRT." Oklahoma City : [s.n.], 2009.
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Keßler, Jaqueline Verfasser], Ralph [Akademischer Betreuer] Golbik, Dirk [Akademischer Betreuer] Vordermark, and Daniel [Akademischer Betreuer] [Zips. "Effect of molecular markers HIF-1α and IDH1 on the radiobiological behavior of human malignant glioma cell lines in normoxia and hypoxia / Jaqueline Keßler ; Ralph Golbik, Dirk Vordermark, Daniel Zips." Halle, 2016. http://d-nb.info/1118500555/34.
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Chanrion, Marie-Anne. "Study and development of physical models to evaluate biological effects of ion therapy : the study of local control of prostate cancer." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10304/document.
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La radiothérapie externe est un traitement anticancéreux locorégional efficace et curatif. Néanmoins, il y a toujours des malades qui meurent de tumeurs locales non-contrôlées. Les nouvelles techniques en radiothérapie visent toujours à trouver un moyen d'augmenter la dose à la tumeur tout en réduisant au minimum la dose aux tissus sains adjacents. Une des dernières techniques innovantes est l'hadronthérapie par ions carbone. Ces dix dernières années ont vu augmenter le nombre de nouveaux centres d hadronthérapie dans le monde avec des faisceaux d'ions carbone, forts des résultats promettant des projets pilotes Berkeley (USA), Chiba (Japon) et Darmstadt (Allemagne). Les avantages théoriques des ions carbone sont: une meilleure balistique et une meilleure efficacité dans la destruction des cellules tumorales. Ainsi cette technique a le potentiel d'augmenter le contrôle des tumeurs, particulièrement pour celles inopérables et radiorésistantes. Les effets biologiques varient le long de la trajectoire des ions de haut TEL (Transfert d'´Énergie Linéique) comme les ions carbone. Ainsi des modèles radiobiologiques sont nécessaires pour quantifier les effets biologiques. Il existe plusieurs modèles radiobiologiques qui reposent sur des approches et des approximations théoriques différentes. Ces modèles ont été développés au sein de chacune des institutions où se déroulaient les projets pilotes. Au stade actuel des connaissances, il semble peu probable d'atteindre une rapide convergence des résultats produits par ces différents modèles. Parmi les modèles radiobiologiques utilisés en clinique, il y a le Local Effect Model (LEM), développé en Allemagne et implémenté dans les systèmes de planification de traitement certifiés CE, le modèle de la National Institute of Radiological Science (NIRS), employé dans les centres japonais d'hadronthérapie possédant un système d'irradiation passif, et le Microdosimetric Kinetic Model (MKM) employé dans les centres japonais d'hadronthérapie possédant un système d'irradiation actif en mode pencil beam scanningExternal beam radiotherapy (EBRT) is a therapy technique aiming at treating locoregional tumors with high efficiency. However, many tumors remain uncontrolled. Newest EBRT techniques always aim at increasing the dose to the tumor while sparing the surrounding healthy tissues. Carbon-ion beam therapy is one of these promising techniques. The number of clinical centres offering carbon-ion beam radiotherapy has been increasing over the world for the last decade. This keen interest spread after very promising results from pilot projects at Berkeley (USA), Chiba (Japan) and Darmstadt (Germany). The theoretical advantages of carbon-ionsare better spatial selectivity in dose deposition and better efficiency in cell killing. They have thus the potential to increase the control of tumors, particularly for unresectable radioresistant tumors. In high linear-energy-transfer (LET) radiations, such as carbon-ion beams, biological effects vary along the ion track, hence, to quantify them, specific radiobiological models are needed. There exist several radiobiological models based on very different theoretical approaches and approximations. They were created and improved in each of the pilot institutions. At the current state of knowledge, no convergence between the model results seems to be possible in the very near future. Clinically employed radiobiological models are the Local Effect Model (LEM) developed in Germany and implemented in CE-certified treatment planning systems, the National Institute of Radiological Science (NIRS) model employed in Japanese centres with passive beam delivery systems and the microdosimetric kinetic model (MKM) in Japanese centres with active scanning beam delivery systems
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Qatarneh, Sharif. "Development of a Whole Body Atlas for Radiation Therapy Planning and Treatment Optimization." Doctoral thesis, Stockholm : Stockholm university & Karolinska institutet, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-803.
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Zackrisson, Björn. "Biological effects of high energy radiation and ultra high dose rates." Doctoral thesis, Umeå universitet, Onkologisk radiobiologi, 1991. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-96889.
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Recently a powerful electron accelerator, 50 MeV race-track microtron, has been taken into clinical use. This gives the opportunity to treat patients with higher x-ray and electron energies than before. Furthermore, treatments can be performed were the entire fractional dose can be delivered in parts of a second. The relative biological effectiveness (RBE) of high energy photons (up to 50 MV) was studied in vitro and in vivo. Oxygen enhancement ratio (OER) of 50 MV photons and RBE of 50 MeV electrons were investigated in vitro. Single-fraction experiments, in vitro, using V-79 Chinese hamster fibroblasts showed an RBE for 50 MV x-rays of approximately 1.1 at surviving fraction 0.01, with reference to the response to 4 MV x- rays. No significant difference in OER could be demonstrated. Fractionation experiments were carried out to establish the RBE at the clinically relevant dose level, 2 Gy. The RBE calculated for the 2 Gy/fraction experiments was 1.17. The RBEs for 20 MV x-rays and 50 MeV electrons were equal to one. In order to investigate the validity of these results, the jejunal crypt microcolony assay in mice was used to determine the RBE of 50 MV x-rays. The RBE for 50 MV x-rays in this case was estimated to be 1.06 at crypt surviving fraction 0.1. Photonuclear processes are proposed as one possible explanation to the higher RBE for 50 MV x-rays. Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. With the aim of investigating whether a difference in effect between irradiation at high dose rates and at conventional dose rates could be verified, pulsed 50 MeV electrons from a clinical accelerator were used for experiments with ultra high dose rates (mean dose rate: 3.8 x 10^ Gy/s) in comparison to conventional (mean dose rate: 9.6 x 10"^ Gy/s). V-79 cells were irradiated in vitro under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed for ultra high dose rates compared to conventional dose rates. A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data are dependent on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. This study shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes at the intracellular level.S. 1-44: sammanfattning, s. 47-130: 5 uppsatser
digitalisering@umu
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Hollmark, Malin. "Absorbed dose and biological effect in light ion therapy." Doctoral thesis, Stockholm : Medical Radiation Physics, Stockholm university together with KI, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7756.
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Alvares-Garcia, Rosana de Souza. "Efeitos da radiação gama sobre os fenotipos nucleares de alguns tipos celulares de Triatoma infestants klug(Hemiptera,reduviidae)." [s.n.], 1988. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317814.
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Orientador : Maria Luiza Silveira MelloDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Alterações induzidas por radiação gama em fenótipos nucleares definidos em termos de padrões de organização cromatínicos e de áreas nucleares e de heterocromatina foram estudadas em ninfas machos de 5º estádio de Triatoma infestans Os órgãos escolhidos para análise citológica foram túbulos de Malpighi, musculatura, traquéias e testículos. As doses de radiação gama empregadas para se realizar as análises citológicas foram escolhidas com base na construção de curvas de sobrevivência para as ninfas. Os preparados foram submetidos à reação de Feulgen e banda C e as áreas nucleares foram determinadas por cariometria. As curvas de sobrevivência dos insetos irradiados indicaram que a radiação induz redução na expectativa de vida desses Insetos; a dose de radiação que mais drasticamente afetou a sobrevida dos insetos foi 1220Gy (1220/GOmln) Este decréscimo na expectativa de vida pode ter tido como causa um envelhecimento precoce e o fator físico da radiação, que é a taxa de dose. Os resultados mostraram alterações nos fenótipos nucleares das células analisadas, sendo caracterizado como: vacuolizado, picnótico, de heterocromatina descompactada, com compactação da área eucromatica simultânea ou não à descompactação da heterocromatina, gigante e micronúcleos. Além disso, foram também constatados os fenótipos normais usuais. Com relação as alterações nos fenótipos nucleares encontrados nos insetos irradiados, seriam decorrentes de modificações na própria fisiologia cromatínica e/ou corresponderiam a etapas de um processo necrótico celular associado aos efeitos da radiação. A ação mais drástica observada a nível somático, correspondeu ao aparecimento do fenótipo vacuolizado, que afetou os núcleos poliplóides e foi produzido em condições de radiação que mais reduziram a sobrevivência dos insetos. Na linhagem germinativa, por outro lado, alterações sérias apareceram sob a forma de picnose e micronúcleos, a primeira em condições drásticas ou brandas de radiação e a segunda apenas em condições mais drásticas. As áreas eucromáticas mostraram-se mais susceptíveis aos efeitosda radiação que as áreas heterocromáticas, já que são regiões mais ativas da cromatina. Não se descarta a hipótese de que as alterações aparentemente mais brandas em compactação cromatínica nos vários tipos celulares possam induzir a prazo mais longo, alterações severas na sobrevivência dos insetos
Abstract: Alterations induced by gamma radiation in nuclear phenotypes as defined in terms of chromatin organization patterns and nuclear and heterochromatin areas, were studied in 5th instar male nymphs of Triatoma infestans. Malpighlan tubules, muscles, tracheae and testes were the organs chosen for cytological analyses. The choice of the gamma radiation doses used to carry out the cytological analyses was based on the surv1val curves constructed for the nymphs. The preparations were submitted to the C-banding technique and to the Feulgen reaction. The nuclear areas were determined by karyometry. The survival insects indicated that the radiation induced a decrease in the insect survival was that of 1220Gy (1220Gy/60min). The decrease in life expectant could have been caused by premature ageing and the physical factor of the radiation, which is the rete of dos age. The results showed alterations 1n the nuclear phenotypes of the cells analysed. New fenotypes appeared showing being characterized as: vacuolization, picknosis, unraveling of lhe heterochromatin, condensation of the euchromatin area either simullaneously with the unravellingof the heterochromatin. Giant nuclei and micronuclei were also detected. In addition, the usual normal phenotypas were also faund. With respect to the alterations of the nuclear phenotypes found in the irradtated insects, these would be a result of modifications in the actual chromatin physiology and/or would correspond to stages In a cellular necrotic process associated with the effects of Irradiation. At the somatic level, the most drastic action observed was the appearance at nuclear vacuolization, which affected the polyploid nuclei 8nd was produced under those conditions of radiation which most reduced Insect survival. On the other hand, in the male germinative cell line, serious alterations appeared in the forro of pycknosis and micronuclei, the former under both drastic and mild conditions of radiation and the latter under only the most drastic conditions. The euchromatic areas were shown to be more susceptlble to the effects of radiation than the heterochromatin areas, since the former are the more active chromatin regions. The hypothesis that the apparently milder alterations in ehromatin condensation of the various cellular types could induee severe alterations in insect survival on a long term basic, cannot be neglected.
Mestrado
Biologia Celular
Mestre em Ciências
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Cedioli, Alessandro. "Acquisizioni e archiviazioni d'immagini microscopiche di broncosfere in radiobiologia." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amslaurea.unibo.it/3562/.
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Nonostante l’oggettiva constatazione dei risultati positivi riscontrati a seguito dei trattamenti radioterapici a cui sono sottoposti i pazienti a cui è stato diagnosticato un tumore, al giorno d’oggi i processi biologici responsabili di tali effetti non sono ancora perfettamente compresi. Inseguendo l’obbiettivo di riuscire a definire tali processi è nata la branca delle scienze biomediche denominata radiobiologia, la quale appunto ha lo scopo di studiare gli effetti provocati dalle radiazioni quando esse interagiscono con un sistema biologico. Di particolare interesse risulta essere lo studio degli effetti dei trattamenti radioterapici nei pazienti con tumore del polmone che rappresentano la principale causa di morte dei paesi industrializzati. Purtroppo per via della scarsa reperibilità di materiale, non è stato finora possibile studiare nel dettaglio gli effetti delle cure radioterapiche nel caso di questo specifico tumore. Grazie alle ricerche di alcuni biologi dell’IRST sono stati creati in-vitro sferoidi composti da cellule staminali e tumorali di polmone, chiamate broncosfere, permettendo così di avere ottimi modelli tridimensionali di tessuto umano allo stato solido su cui eseguire esperimenti al fine di regolare i parametri dei trattamenti radioterapici, al fine di massimizzarne l’effetto di cura. In questo lavoro di Tesi sono state acquisite sequenze di immagini relative a broncosfere sottoposte a differenti tipologie di trattamenti radioterapici. Le immagini acquisite forniscono importanti indicazioni densitomorfometriche che correlate a dati clinoco-biologico potrebbero fornire importanti indicazioni per regolare parametri fondamentali dei trattamenti di cura. Risulta però difficile riuscire a confrontare immagini cellulari di pre e post-trattamento, e poter quindi effettuare delle correlazioni fra modalità di irraggiamento delle cellule e relative caratteristiche morfometriche, in particolare se le immagini non vengono acquisite con medesimi parametri e condizioni di cattura. Inoltre, le dimensioni degli sferoidi cellulari da acquisire risultano essere tipicamente maggiori del parametro depth of focus del sistema e questo implica che non è possibile acquisire una singola immagine completamente a fuoco di essi. Per ovviare a queste problematiche sono state acquisite sequenze di immagini relative allo stesso oggetto ma a diversi piani focali e sono state ricostruite le immagini completamente a fuoco utilizzando algoritmi per l’estensione della profondità di campo. Sono stati quindi formulati due protocolli operativi per fissare i procedimenti legati all’acquisizione di immagini di sferoidi cellulari e renderli ripetibili da più operatori. Il primo prende in esame le metodiche seguite per l’acquisizione di immagini microscopiche di broncosfere per permettere di comparare le immagini ottenute in diverse acquisizioni, con particolare attenzione agli aspetti critici di tale operazione. Il secondo è relativo alla metodica seguita nella archiviazione di tali immagini, seguendo una logica di classificazione basata sul numero di trattamenti subiti dal singolo sferoide. In questo lavoro di Tesi sono stati acquisiti e opportunamente archiviati complessivamente circa 6500 immagini di broncosfere riguardanti un totale di 85 sferoidi. I protocolli elaborati permetteranno di espandere il database contenente le immagini di broncosfere con futuri esperimenti, in modo da disporre di informazioni relative anche ai cambiamenti morfologici subiti dagli sferoidi in seguito a varie tipologie di radiotrattamenti e poter quindi studiare come parametri di frazionamento di dose influenzano la cura. Infine, grazie alle tecniche di elaborazioni delle immagini che stiamo sviluppando sarà inoltre possibile disporre di una ricostruzione della superficie degli sferoidi in tempo reale durante l’acquisizione.
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Ferreira, Rivea Ines. "Efeito da irradiação local por eletrons no processo de reparação tecidual, em ratos diabeticos." [s.n.], 2001. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290146.
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Orientador: Solange Maria de AlmeidaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: As radiações ionizantes e certos estados patológicos, como a diabetes mellitus, determinam alterações nos fenômenos biológicos do reparo tecidual. O presente trabalho experimental teve por finalidade pesquisar o efeito da irradiação por elétrons sobre os componentes do tecido de granulação, na pele de ratos diabéticos. Para tanto, 48 ratos da linhagem Wistar foram separados em 4 grupos: animais-controle, animais normais irradiados, animais diabéticos e animais diabéticos irradiados. Inicialmente, o estado diabético foi induzido por meio da administração intravenosa de estreptozotocina. Após 15 dias da indução, todos os animais foram submetidos a um ato cirúrgico para a realização de uma ferida excisional, na região dorsal anterior. No 3° dia pós-operatório, apenas uma área que compreendia cerca de 1cm, lateralmente a cada margem do ferimento, foi irradiada com uma dose única de 1,OGy, por feixes de elétrons com 6MeV de energia. A reparação tecidual foi estudada aos 4,7,13 e 21 dias que sucederam a cirurgia, por microscopias ópticas comum e de polarização. Empregou-se as técnicas de coloração por hematoxilina-eosina, visando à observação das características morfológicas do tecido de granulação, e, picrosirius, com a finalidade de identificar e avaliar a maturação do colágeno neoformado. Para a detecção do dicroísmo linear, que se relaciona à organização macromolecular dos feixes de fibras colágenas, uma parte das amostras teciduais foi submetida à reação histoquímica com o azul de toluidina a 0,025%, em pH 4,0. A avaliação, essencialmente qualitativa, das amostras teciduais permitiu concluir-se que: 1. A irradiação local causou um retardo na cicatrização, por atrasar os eventos proliferativos. Contudo, não impediu que o processo de reparo culminasse na restauração tecidual; 2. Os desequilíbrios metabólicos inerentes à diabetes atuaram em sinergismo com a irradiação no retardo da reparação tecidual, não somente por adiarem a fase proliferativa, mas também por condicionarem a persistência da fase inflamatória; 3. A irradiação e o estado diabético ocasionaram uma redução no conteúdo de colágeno, do tecido de granulação, que foi mais acentuada para os animais diabéticos irradiados
Abstract: Ionizing radiations and certain pathologic states, such as diabetes mellitus, have major impact on the biologic phenomena of tissue repair. The aim of the present experimental research was to investigate the effect of electron irradiation on skin granulation tissue components, in diabetic rats. In this study, 48 Wistar rats were divided into 4 groups: control animais; normal irradiated animais; diabetic animais and diabetic irradiated animais. First, diabetes mellitus was induced, in the last two groups, by a single intravenous injection of streptozotocin. Fifteen days later, ali the animais underwent a surgery in arder to make an excisional wound in the anterior dorsal skin. On the third day postoperation, only an area approximately 1cm wide around the wounds was exposed to 1Gy of 6MeV electron beam radiation, delivered in a single dose. Wound healing was examined at 4,7, 13, and 21 day time intervals after wounding by ordinary and polarized light microscopies. Hematoxylin and eosin staining was used for the study of morphological aspects of the newly formed granulation tissue. For specific identification and evaluation of collagen maturation, some tissue sections were stained with picrosirius red. In order to detect the linear dichroism, that is related to the macromolecular organization of collagen fibers, other tissue sections were stained with 0.025% toluidine-blue aqueous solution, at pH 4.0. Based upon the essentially qualitative evaluation of granulation tissue, it was possible to conclude that: 1. Local irradiation caused a delay in wound healing, as a consequence of the retardation in the proliferative events. However, ali the wounds ultimately have closed; 2. Diabetes associated dysfunctions and electron irradiation acted synergistically in delaying tissue repair, not only by postponing proliferative phase, but also by prolonging inflammatory phase; 3. Irradiation and diabetic state determined a decrease in collagen content, in the granulation tissue, which was more pronounced in diabetic irradiated animais
Mestrado
Radiologia Odontologica
Mestre em Radiologia Odontológica
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Tuji, Fabricio Mesquita. "Avaliação do efeito radioprotetor do selenito de sodio em glandulas parotidas de ratos." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290164.
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Orientadores: Solange Maria de Almeida, Silvana Pereira BarrosTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Doutorado
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Peixoto, Breno Cherfên [UNESP]. "Efeitos biológicos da radioterapia na expressão do fator de crescimento epidérmico (EGF) durante a odontotogênese em camundongos (Mus musculus)." Universidade Estadual Paulista (UNESP), 2006. http://hdl.handle.net/11449/105848.
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Pacientes portadores de câncer na região de cabeça e pescoço quando submetidos à radioterapia podem apresentar vários tipos de manifestações clínicas, dentre elas a diminuição dos níveis salivares do fator de crescimento epidérmico (EGF). O EGF é uma pequena proteína (53 aminoácidos) que estimula a proliferação de células dos mamíferos, sendo encontrada em vários órgãos em desenvolvimento. Pode também exercer um papel fisiológico na erupção dentária ao interagir com outras moléculas como o fator de crescimento transformante β (TGF-β), a interleucina 1 (IL-1) e do fator de estimulação de colônia 1 (CSF-1), aumentando a reabsorção óssea e estimulando a quimiotaxia de células mononucleares. O objetivo deste trabalho foi verificar, por meio de reações de imuno-histoquímica, se a expressão do fator de crescimento epidérmico (EGF) pode ser alterada na odontogênese do primeiro molar superior de camundongos Mus musculus, após exposição de fêmeas prenhes a radioterapia, na dose de 3 Gray (Gy) ao décimo dia de gestação. Foram avaliados os germes dentários dos embriões aos 14, 16 e 18 dias de desenvolvimento pré-natal. As análises morfológica microscópica óptica e histomorfométrica demonstraram que o número de células epiteliais periféricas do órgão do esmalte imunopositivas para o EGF foi significativamente menor no grupo 3 Gy em relação ao grupo controle nos períodos de 14o (P<0,0001), 16o (P<0,0001<0,05) e 18o (P<0,0008) dias pré-natais. Processo FAPESP no 2008/54534-8.
Malignant neoplasm orofacial patients when receiving radiation therapy can present several types of radiation injuries and clinical manifestations, such as decrease of the salivary epidermal growth factor (EGF) levels. EGF is a small protein (53 amino acids) that stimulates the proliferation of cells of the mammals, being found in several organs in development. EGF can exercise a physiological role in the dental eruption through the interaction with other molecules such as transforming growth factor beta (TGF-β), interleukin-1 (IL-1) and colony-stimulating factor-1 (CSF-1), which increases the bone reabsorption and stimulating the chemotaxis for mononuclear cells. The objective of this work was to verify through technique of immunohistochemistry, changes in the expression of the EGF in the odontogenesis of the first upper molar in Mus musculus mice embryos to the 14th, 16th and 18th days of intrauterine life. Pregnant mice was irradiated on the 10th gestacional day with a 3 Gray (Gy) dose. The microscopical mophological and histomorphometrical analysis showed a significant decrease in the number of EGF-positive dental epithelium cells in the 3 Gy group when compared with control group in 14th (P<0,0001), 16th (P<0,0001<0,05) and 18th (P<0,0008) intrauterine day periods. Supported by FAPESP no 2008/54534-8.
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Rangel, Araújo Sampaio Claudine. "Avaliação Eletromiográfica nos músculos masseter e temporal anterior após o uso de placa de Hawley modificada, em pacientes com DTM." Universidade Federal de Pernambuco, 2003. https://repositorio.ufpe.br/handle/123456789/5068.
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Previous issue date: 2003Este estudo foi realizado com treze voluntárias, entre dezesseis e trinta e quatro anos, que possuíam classificação de DTM de moderada a severa; selecionadas através de um questionário anamnésico de classificação de desordens temporomandibulares. Os registros foram realizados por meio de eletrodos bipolares de superfície, antes do uso da placa de Hawley modificada, com 14 dias de instalada e 28 dias após, usada 8 horas por noite. Com o objetivo de avaliar a atividade eletromiográfica dos músculos masseter e temporal anterior na condição de repouso e em contração isométrica máxima. Pretende-se relacionar as mudanças ocorridas na atividade eletromiográfica desses músculos com a evolução dos sinais e sintomas relatados nas diferentes aplicações do questionário anamnésico, a fim de quantificar a eficácia clínica do aparelho utilizado. A amplitude do sinal eletromiográfico foi quantificada pelo seu valor médio (Root Mean Square- RMS) e análise espectral de freqüência através da freqüência média, ambos os parâmetros calculados através de uma rotina do programa MatLab. Os dados foram analisados estatisticamente por meio dos testes não paramétricos de Friedman e Wilcoxon e as correlações foram testadas por meio do teste de Spearman, considerando-se para todos os testes, o nível de significância de 5%. Após a análise dos resultados, concluiu-se haver redução significativa da atividade eletromiográfica do temporal e masseter na posição de repouso, indicativa de relaxamento muscular. Observou-se também, que em contração isométrica voluntária máxima (CIVM) ocorreu correlação positiva entre as atividades eletromiográficas dos músculos masseter e temporal anterior direito e esquerdo, independentemente dos tempos da pesquisa. A partir dos resultados também concluiu-se que o aparelho promoveu significativa correlação na redução no grau de severidade de DTM e aumento na abertura bucal máxima à medida que o tratamento evoluiu
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Boas, Fabricio de Almeida Souza Vilas. "Avaliação do potencial radiossensibilizador de uma tiossemicarbazona derivada de N(4)-Metil-Toluil-2-acetilpiridina e seu complexo de cobre sobre linhagens celulares de tumores cerebrais." CNEN - Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, 2010. http://www.bdtd.cdtn.br//tde_busca/arquivo.php?codArquivo=161.
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Fundação de Amparo a Pesquisa do Estado de Minas GeraisA radioterapia é uma das principais abordagens terapêuticas utilizadas no tratamento do câncer e é indicada, principalmente, em casos onde as lesões são inoperáveis. No entanto, uma de suas limitações advém dos próprios efeitos biológicos da radiação, além de outros fatores tais como a radiorresistência inerente a alguns tipos tumorais, tais como os cerebrais. Então, a aplicação concomitante de agentes antineoplásicos com radioterapia vem sendo praticada na clínica de modo a maximizar o efeito benéfico do último e ao mesmo tempo minimizar os efeitos colaterais da exposição à radiação ionizante. Dentro deste contexto geral é importante a pesquisa de novos compostos que possam ser selecionados como protótipos para o desenvolvimento de agentes que possuam os menores efeitos adversos possíveis. As tiossemicarbazonas são uma classe de compostos sintéticos que apresenta um amplo perfil farmacológico e já demonstraram atividade antitumoral. Também já foi relatado que a complexação destes compostos com cátions metálicos pode ser capaz de torná-los mais eficazes. O objetivo do presente trabalho foi avaliar o potencial radiossensibilizador de uma tiossemicarbazona derivada de N(4)-metil-toluil-2-acetilpiridina e seu complexo com cobre sobre linhagens celulares de glioblastoma multiforme, o qual de todos os tumores cerebrais é o que apresenta a maior agressividade e o maior índice de morbidade. Foi avaliada a sensibilidade de linhagens celulares de glioblastoma com diferentes status de p53 RT2 e U87 (p53 selvagem) e T98 (p53 mutante) à radiação gama de uma fonte de 60Co. Os resultados de citotoxicidade indicaram que as linhagens em questão apresentam uma radiossensibilidade similar, p53-independente. Os efeitos citotóxicos da tiossemicarbazona Lac e seu complexo CuLac foram avaliados e os resultados indicaram que ambas possuem excelente efeito citotóxico na ordem de 10-8 M em todas as linhagens avaliadas, portanto menores que drogas como a hidroxiuréia, cisplatina e etoposídeo (IC50 entre 10-4 e 10-6 M em média). O tratamento com as tiossemicarbazonas seguido de 6 Gy de radiação gama se mostrou mais eficiente que o tratamento com radiação isolada em todas as linhagens. A complexação com cobre não alterou de modo significativo o efeito antitumoral da tiossemicarbazona livre sobre as linhagens testadas. Análises de fotomicrografias ópticas indicaram que todos os tratamentos ocasionaram alterações morfológicas, tais como arredondamento celular, redução do volume citoplasmático e surgimento de vesículas na membrana citoplasmática. O conjunto de dados indicam que a tiossemicarbazona Lac e seu complexo de cobre possuem potente efeito antitumoral e também induzem radiossensibilização nas linhagens testadas.
Radiation therapy is one of the main therapeutical approaches used for the treatment of cancer and is indicated, mostly, in cases which the lesions are inoperable. However, one of its limitations comes from its own biological effects, besides other factors such as the radioresistance inherent to some types of tumors like the cerebral ones. Therefore, the concurrent aplication of antineoplasic agentes with the radiation therapy has been used in the clinical pratice with the objective of maximize the benefical effects of the latter and at the same time minimize the side effects of the exposure to ionizing radiation. In this general context is important the research for new compounds that can be selected as prototypes for the development of agents that possess the least adverse effects as possible. The thiosemicarbazones are a class of synthetic compounds that present a broad pharmacological profile and have demonstrated antitumoral activity. Also has been reported that the coordination of these compounds to metallic cations may be capable of make them more effective. The objective of the present work was to evaluate the radiosensitizing potential of a thisemicarbazone derived from N(4)-methyl-tolyl-2-acetylpyridine and its copper complex against glioblastoma multiforme cell lines, which of all brain tumors types, are the most agressive and have the highest morbidity. The sensitivity of glioblastoma cell lines with different p53 status RT2 and U87 (p53 wild type) and T98 (p53 mutant) to gamma radiation from a 60Co source was assessed. Citotoxicity results indicated that the cell lines in study presented a similar radiosensitivity, p53-independent. The citotoxic effects of the thiosemicarbazone Lac and its complex CuLac were assayed and the results indicated that both possess na excelent effect at the order of 10-8 M in all cell lines evaluated, therefore smaller than drugs such as hydroxyurea, cisplatin and etoposide (IC50 between 10-4 and 10-6 M). The treatment with the thiosemicarbazones followed by a 6 Gy gamma radiation dose showed to be more effective than the radiation alone in all cell lines. Coordination to Cooper had not changed significantly the antitumoral effect of the free thiosemicarbazone agains the cell lines tested. Morphological analysis of optical photomicrographies indicated that all treatment caused alterations, such as cell rounding, diminishing of the cytoplasmic volume and rising of vesicles at the cytoplasmic membrane. Together these data indicate that the thiosemicarbazone Lac and its metallic complex possess potent antitimoral effect amd also induce radiosensitivity in the tested cell lines.
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Caiffa, Luigi. "Studio di classi di sferoidi multicellulari di carcinoma polmonare epidermoidale in radiobiologia." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amslaurea.unibo.it/5372/.
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Il tumore del polmone rappresenta la prima causa di morte nei paesi industrializzati. Le possibilità di trapianto ed intervento chirurgico risultano molto limitate pertanto lo standard di cura risulta essere la radioterapia, a volte abbinata alla chemioterapia. Sebbene trattando radioterapicamente il tumore si ottengano ottimi risultati, attualmente non esistono solide linee guida per la personalizzazione del trattamento al paziente.
Il poter eseguire in laboratorio test radioterapici su un elevato numero di campioni risulterebbe un valido approccio sperimentale d’indagine, ma la carenza di materiale su cui poter condurre gli esperimenti limita questa possibilità. Tipicamente, per ovviare al problema vengono utilizzati sferoidi multicellulari tridimensionali creati in laboratorio partendo da singole cellule del tumore in esame. In particolare, l’efficacia del trattamento viene tipicamente correlata alla riduzione volumetrica media stimata utilizzando un set di sferoidi teoricamente identici.
In questo studio vengono messe in discussione la validità delle affermazioni tipicamente sostenute attraverso l’analisi di volumi medi. Abbiamo utilizzando un set di circa 100 sferoidi creati in laboratorio partendo da singole cellule di carcinoma epidermoidale polmonare e trattati secondo sette differenti modalità di trattamento radioterapico (variando intensità di radiazione e numero di frazioni). In una prima fase abbiamo analizzato le singole immagini, acquisite al microscopio ottico circa ogni 48 ore, per identificare features morfometriche significative da affiancare all’analisi volumetrica. Sulla base dell’andamento temporale di queste features abbiamo suddiviso gli sferoidi in sottoclassi con evoluzioni completamente differenti che fanno supporre un differente “stato” biologico. Attraverso algoritmi di estrazione di features e classificazione e analizzando riduzione volumetrica, grado di frastagliatura del bordo e quantità di cellule liberate nel terreno di coltura abbiamo definito un protocollo per identificare in maniera automatica le sottopopolazioni di sferoidi. Infine, abbiamo ricercato con successo alcune features morfometriche in grado di predire, semplicemente analizzando immagini acquisite nei giorni seguenti all’ultimo trattamento, lo “stato di salute” del tumore a medio/lungo periodo.
Gli algoritmi realizzati e le features identificate se opportunamente validate potrebbero risultare un importante strumento non invasivo di ausilio per il radioterapista per valutare nel breve periodo gli effetti a lungo periodo del trattamento e quindi poter modificare parametri di cura al fine di raggiungere uno stato desiderato del tumore.
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Peixoto, Breno Cherfên. "Efeitos biológicos da radioterapia na expressão do fator de crescimento epidérmico (EGF) durante a odontotogênese em camundongos (Mus musculus) /." São José dos Campos : [s.n.], 2009. http://hdl.handle.net/11449/105848.
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Orientador: Luiz Cesar de MoraesBanca: João Luiz de Miranda
Banca: Luiz Cesar de Moraes
Banca: Miguel Angel Castilho Salgado
Banca: Yasmin Rodarte Carvalho
Banca: Marlene Fenyo Soeiro de Matos Pereira
Resumo: Pacientes portadores de câncer na região de cabeça e pescoço quando submetidos à radioterapia podem apresentar vários tipos de manifestações clínicas, dentre elas a diminuição dos níveis salivares do fator de crescimento epidérmico (EGF). O EGF é uma pequena proteína (53 aminoácidos) que estimula a proliferação de células dos mamíferos, sendo encontrada em vários órgãos em desenvolvimento. Pode também exercer um papel fisiológico na erupção dentária ao interagir com outras moléculas como o fator de crescimento transformante β (TGF-β), a interleucina 1 (IL-1) e do fator de estimulação de colônia 1 (CSF-1), aumentando a reabsorção óssea e estimulando a quimiotaxia de células mononucleares. O objetivo deste trabalho foi verificar, por meio de reações de imuno-histoquímica, se a expressão do fator de crescimento epidérmico (EGF) pode ser alterada na odontogênese do primeiro molar superior de camundongos Mus musculus, após exposição de fêmeas prenhes a radioterapia, na dose de 3 Gray (Gy) ao décimo dia de gestação. Foram avaliados os germes dentários dos embriões aos 14, 16 e 18 dias de desenvolvimento pré-natal. As análises morfológica microscópica óptica e histomorfométrica demonstraram que o número de células epiteliais periféricas do órgão do esmalte imunopositivas para o EGF foi significativamente menor no grupo 3 Gy em relação ao grupo controle nos períodos de 14o (P<0,0001), 16o (P<0,0001<0,05) e 18o (P<0,0008) dias pré-natais. Processo FAPESP no 2008/54534-8.
Abstract: Malignant neoplasm orofacial patients when receiving radiation therapy can present several types of radiation injuries and clinical manifestations, such as decrease of the salivary epidermal growth factor (EGF) levels. EGF is a small protein (53 amino acids) that stimulates the proliferation of cells of the mammals, being found in several organs in development. EGF can exercise a physiological role in the dental eruption through the interaction with other molecules such as transforming growth factor beta (TGF-β), interleukin-1 (IL-1) and colony-stimulating factor-1 (CSF-1), which increases the bone reabsorption and stimulating the chemotaxis for mononuclear cells. The objective of this work was to verify through technique of immunohistochemistry, changes in the expression of the EGF in the odontogenesis of the first upper molar in Mus musculus mice embryos to the 14th, 16th and 18th days of intrauterine life. Pregnant mice was irradiated on the 10th gestacional day with a 3 Gray (Gy) dose. The microscopical mophological and histomorphometrical analysis showed a significant decrease in the number of EGF-positive dental epithelium cells in the 3 Gy group when compared with control group in 14th (P<0,0001), 16th (P<0,0001<0,05) and 18th (P<0,0008) intrauterine day periods. Supported by FAPESP no 2008/54534-8.
Doutor
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Larocca, Samanta. "La risposta cellulare ai diversi tipi di radiazione tramite espressione genica e radiobiologia sistemica." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amslaurea.unibo.it/7832/.
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Questo progetto ha confrontato gli effetti indotti da diversi tipi di radiazioni, diversa intensità delle dosi, diverso rateo di dose su sistemi cellulari differenti. In particolare sono stati seguiti due studi differenti, finalizzati all’indagine degli effetti e dei meccanismi indotti da trattamenti radioterapici su cellule in coltura.
Nel primo studio -EXCALIBUR- sono stati investigati i meccanismi di induzione e trasmissione del danno a basse dosi di radiazioni, in funzione della qualità della radiazione (raggi gamma e protoni) e della dose.
Cellule di glioblastoma umano (T98G) sono state irraggiate con raggi gamma e protoni a due diverse dosi (0,25 Gy e 2 Gy); in questo studio è stata valutata e analizzata la variazione di espressione genica rilevata utilizzando la tecnologia dei microarray.
Per mezzo dell’analisi statistica, con due software diversi, si è osservato come nelle cellule irraggiate si attivino i geni legati alla senescenza cellulare; questo risultato è significativo, visto che potrebbe rappresentare una prospettiva terapeutica interessante per molte neoplasie.
Il secondo studio –Plasma Focus- ha lo scopo di ampliare le applicazioni nel settore medicale di una sorgente radiante che produce raggi X ad altissimo rateo di dose (plasma focus). In questo studio, l’attenzione è stata posta sulla preparazione dei campioni biologici per l’irraggiamento. Cellule di adenocarcinoma mammario (MCF7) sono state coltivate in laboratorio e posizionate all’interno di appositi portacampioni pronte per essere irraggiate con raggi X ad alto e a basso rateo di dose.
Per mezzo della microscopia ottica e della citometria a flusso in fluorescenza, si è osservato come un rateo di dose elevato provochi danni cellulari superiori. L’analisi quantitativa ha mostrato che, nelle cellule trattate con il plasma focus, il 18% risulti danneggiato rispetto al 7% delle cellule di controllo; con i raggi X convenzionali risulta danneggiato l'8% di cellule, rispetto al 3% delle cellule di controllo.
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Moreira, João Vítor de Almeida. "Radiobiologia: efeito das radiações ionizantes na célula e formas de protecção das radiações ionizantes." Master's thesis, Universidade da Beira Interior, 2011. http://hdl.handle.net/10400.6/987.
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A radiação ionizante é a radiação com energia suficiente para que durante uma interacção com um átomo, possa remover electrões fortemente vinculados à sua órbita, fazendo com que o átomo se torne carregado ou ionizado.
A radiação ionizante ocorre sob duas formas: ondas ou partículas. Ondas com maior comprimento, mas com frequência mais baixa (calor e rádio) têm menos energia do que aquelas com comprimentos mais curtos e frequência mais alta (radiação X e gama). Nem toda a radiação electromagnética é ionizante. Apenas a parte de alta frequência do espectro electromagnético, que inclui raios X e gama são ionizantes.
As formas específicas de radiação ionizante designam-se partículas de radiação, que consistem em partículas atómicas e subatómicas (electrões, protões, etc.) que transportam energia na forma de energia cinética ou de massa em movimento.
Desde sempre o Homem está exposto a radiação proveniente de fontes naturais (radiação de fundo) e, recentemente, de fontes artificiais.
Relativamente à radioactividade natural, há que ter em conta que existem pequenas quantidades de urânio, tório e outros elementos radioactivos que emitem baixos níveis de radiação ionizante. Outra fonte de exposição natural são os raios cósmicos. A grande maioria destes são filtrados pela atmosfera mas, em locais de grande altitude ou em voos comerciais, a exposição pode ser considerável, ao contrário do que sucede ao nível do mar. Os raios cósmicos podem também interagir com átomos na atmosfera terrestre criando isótopos radioactivos como é o caso do Carbono-14.
Os efeitos da radiação no corpo humano são complexos e dependem do tipo de radiação, mais concretamente da sua intensidade e energia.
A radiação ionizante, pela sua elevada energia, é capaz de penetrar na matéria, ionizar os átomos, romper ligações químicas e causar danos nos tecidos biológicos, como a presença de eritema, dermatite, lesão vascular e alopécia, cataratas e ainda alterações a nível dos sistemas hematopoiético, gastrointestinal, neuronal e vascular. A exposição a doses elevadas de radiação ionizante pode ainda resultar na destruição de células ou na indução de cancro.
No entanto, o uso de radiação ionizante tem inúmeras aplicações que apresentam largos benefícios para a sociedade e para os indivíduos. Um exemplo comum é o recurso à radiação ionizante em medicina, onde esta é largamente utilizada com fins diagnósticos (raio-X, TC e mamografia) e terapêuticos (radioterapia, braquiterapia e medicina nuclear).
No contexto industrial, as aplicações são igualmente vastas, destacando-se a radiografia industrial em ensaios não-destrutivos, esterilização por irradiação e os medidores nucleares de densidade, humidade, peso e nível de interface.
Devido aos efeitos deletérios da radiação ionizante no organismo humano, é necessário recorrer a diversos métodos para protecção, os quais estão devidamente regulamentados pelas diferentes entidades e devem ser conhecidos e utilizados, não só por profissionais experientes, mas também pelo público em geral, que está exposto a radiações. Nos diferentes métodos de protecção, há que ter em conta os métodos de barreira (óculos, protectores das gónadas, aventais e luvas de chumbo, entre outros), tempo de exposição e distância à fonte de radiação.
O objectivo desta dissertação de mestrado passa por efectuar uma pesquisa bibliográfica acerca dos seguintes aspectos ligados à radiação ionizante: efeitos a nível celular; fontes de exposição a radiação; limites máximos de radiação a que um indivíduo pode estar exposto; medidas de protecção radiológica e sua fiscalização.Ionizing radiation is a kind of radiation with enough energy so that during an interaction with an atom, it can remove electrons strongly tied to its orbit, causing the atom to become charged or ionized. Ionizing radiation occurs in two forms: waves or particles. Longer waves, but with lower frequency (heat and radio) have less energy than those with shorter lengths and higher frequency (X and gamma radiation). Not all electromagnetic radiation is ionizing. Only the high frequency part of the electromagnetic spectrum, which includes X-rays and gamma rays, is ionizing. Specific forms of ionizing radiation are called radiation particles, which consist of atomic and subatomic particles (electrons, protons, etc.) that transport energy as kinetic energy or mass in motion. Mankind has always been exposed to radiation from natural sources (background radiation) and recently, from artificial sources too. With regard to natural radioactivity, it must be remembered that there are small amounts of uranium, thorium and other radioactive elements that emit low levels of ionizing radiation. Another source of natural exposure are cosmic rays. Most of these are filtered through the atmosphere, but in high altitudes or on commercial flights, the exposure can be considerable, unlike what happens at sea level. Cosmic rays can also interact with atoms in Earth's atmosphere creating radioactive isotopes such as Carbon-14. The effects of radiation on the human body are complex and depend on the type of radiation, specifically its intensity and energy. Ionizing radiation, for their high energy, can penetrate matter, ionize the atoms, break chemical bonds and cause damage to biological tissues such as erythema, dermatitis, vascular lesions, alopecia, cataracts, and even changes in the hematopoietic, gastrointestinal, neuronal and vascular systems. Exposure to high doses of ionizing radiation may also result in the destruction of cells or even cancer induction. However, the use of ionizing radiation has many applications that have broad benefits for society and individuals. A common example is the use of ionizing radiation in medicine, where it is widely used for diagnostic purposes (X-ray, CT scans and mammography) and treatment (radiotherapy, brachytherapy and nuclear medicine). In the industrial setting, applications are similarly extensive, especially in industrial radiography in non-destructive tests, sterilization by radiation and nuclear gauges of density, humidity, weight and interface level. Due to the deleterious effects of ionizing radiation on the human body, it is necessary to use several methods for protection, which are properly regulated by different entities and should be known and used, not only by experienced professionals, but also by the general public exposed to radiation. The different protective methods that should be considered are: barrier methods (protective glasses, gonads protectors, lead aprons and gloves, among others); exposure time; distance to the source of radiation. The objective of this dissertation is to do a literature research on the following aspects of ionizing radiation: effects at cellular level; sources of radiation; maximum radiation dose that an individual can be exposed; radiation protection measures and its supervision.
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Finocchiaro, Domenico. "Ottimizzazione di un sistema di calcolo Voxel dosimetry e implementazione di grandezze radiobiologiche per MRT." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/12025/.
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Il presente lavoro di tesi nasce in seguito all’esperienza di tirocinio svolta presso l’Arcispedale Santa Maria Nuova di Reggio Emilia. Fulcro di questo lavoro è lo sviluppo di un sistema di pianificazione della dose per il trattamento dei pazienti sottoposti a Molecular Radionuclide Therapy (MRT). Presso tale struttura ospedaliera è già stato sviluppato uno strumento che si appoggia all’ambiente di lavoro Matlab per il calcolo dosimetrico. Tale programma è chiamato VoxelMed. Si tratta di uno strumento di calcolo che lavora al così detto voxel-level, tecnica di sviluppo recente che permette il calcolo della dose assorbita all’interno di un paziente in modo più dettagliato rispetto ai metodi di calcolo basati unicamente sulla stima media per organo, tipicamente impiegati in dosimetria tradizionale. Parte del lavoro di tesi consiste nell’implementare nuove modalità di calcolo ed aggiungere ulteriori accorgimenti all’attuale versione di VoxelMed. In VoxelMed è stata poi integrata ex-novo una componente di calcolo di misure radiobiologiche, in particolare della BED. La dose assorbita non è infatti un parametro sufficiente per valutare gli effetti della radiazione sui tessuti, a parità di tipo ed energia della radiazione gli effetti possono essere molto variabili. La BED è il parametro che tiene conto della risposta del tessuto sano o cancerogeno alla radiazione. Parte del lavoro è stato svolto sperimentalmente, tramite misure con fantocci acquisiti o preparati ad hoc. In particolare si sono utilizzati diverse tipologie di fantocci, per effettuare protocolli di calibrazione dei sistemi di acquisizione, misure di curve di effetto di volume parziale e test finali di verifica. Per un ulteriore verifica delle prestazioni di calcolo si sono effettuate misurazioni su un gruppo di pazienti e si sono confrontati i risultati con quelli ottenuti dal software maggiormente utilizzato nella pratica clinica, OLINDA/EXM.
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Fantigrossi, Ilaria. "Analisi temporale di caratteristiche morfometriche estratte da immagini di broncosfere sottoposte a differenti trattamenti radiobiologici." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amslaurea.unibo.it/4334/.
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