The purpose of this work is to investigate the influence of possible patient movement and anatomy alteration on the quality of delivered prostate US based HDR-brachytherapy. The effect of patient movement and anatomy change (after the needle implantation and 3D image set acquisition) on catheter and organ dislocation and the consequences that this generated on the DVHs, conformity index and on radiobiological parameters. Materials and methods: This work is based on 3D image sets and treatment plans of 48 patients obtained right after the needle implantation (clinical plan is based on this 3D image set) and before and after the irradiation. In our institution the 3D-US based pre-planning, the transperineal implantation of needles using template and the intraoperative planning and irradiation is realized using the real-time dynamic planning system Oncentra Prostate. All pre-plans and all the inverse optimization of clinical plans were based on HIPO using the modulation restriction option. The patient body/OARs/catheters movement are generated from the clinical, pre- and post- irradiation plans and its influence on DVH-, COIN and radiobiological parameters of PTV and OARs are calculated and presented. Results: It is observed a slight decrease of treatment plan quality with increase of time between the clinical image set acquisition and the patient irradiation. Also, we show that the patient body movement/anatomy alteration and/or catheters dislocation results in decreased plan quality; change of values of the COIN, DVH- and radiobiological parameters. Conclusion: The measured mean shift of anatomy and needles (beams) is as low as 1.0mm that is lower by an order of magnitude to values known from external beam irradiation. For high modulated plans as those in HDR Brachytherapy such small shifts result in dosimetric changes which are in general lower than 5%. Our results demonstrate that quality assurance procedures have to be clinically implemented to guarantee anatomy and implant stability of the order of 1mm. This can only be realized without any manipulation of the implant and anatomy as done, for instance in the case of removing the US-probe before treatment delivery or moving the patient from one bed to another for the irradiation purposes / Σκοπός της εργασίας αυτής είναι να διερευνήσει την επιδραση που έχει η πιθανή μετακίνηση του ασθενούς και η αλλαγή της ανατομίας στην ποιότητα της Βραχυθεραπείας. Η μετακίνηση του ασθενούς, οι αλλαγές της ανατομίας ( μετά την εμφύτευση των βελονών και την συλλογή των τρισδιάστατων 3D εικόνων), η μετακίνηση των καθετήρων και των οργάνων επιφέρουν αλλαγές που παρουσιάζονται μέσα από τα ιστογράμματα δόσης - όγκου (DVH), δείκτη συμμορφίας (conformity index) και των ραδιοβιολογικών παραμέτρων. Υλικά και Μέθοδοι: Η μελέτη αυτή βασίζεται στην συλλογή τρισδιάστατων εικόνων υπερήχων (3D set) και στους σχεδιασμούς θεραπείας (treatment plans) από 48 ασθενείς που συλλέχθηκαν σε τρείς φάσεις: μετά την εμφύτευση των καθετήρων (κλινικός σχεδιασμός θεραπείας (clinical plan) βασίζεται σε αυτή την συλλογή 3D εικόνων), πριν την ακτινοβόληση και μετά την ακτινοβόληση.Στην κλινική μας ο προσχεδιασμός της θεραπείας (pre-planing) που βασίζεται στο τρισδιάστατο υπερηχογράφημα (3D-US), η διαπερινεϊκή εμφύτευση των καθετήρων με την βοήθεια του οδηγού template, ο διεγχειρητικός σχεδιασμός της θεραπείας (intraoperative planning) και η ακτινοβόληση πραγματοποιούνται με την χρήση του Real-time dynamic planning system Oncentra Prostate. Όλα τα pre-plans και όλα τα inverse optimization clinical plans βασίζονται στο HIPO χρησιμοποιώντας την επιλογή του modulation restriction. Οι μετακινήσεις του σώματος του ασθενούς/ των ευαίσθητων σε κίνδυνο οργάνων (OARs)/ και των καθετήρων αναπαράγονται από τα clinical, pre και post- irradiation plans. Κατόπιν υπολογίζεται και παρουσιάζεται η επίδρασή τους στο DVH, COIN και στις ραδιοβιολογικές παραμέτρους του όγκου στόχου σχεδιασμού (PTV) και των (OARs). Αποτελέσματα: Παρατηρείται μια ελαφρά μείωση της ποιότητας του σχεδιασμού θεραπείας με την αύξηση του χρόνου μεταξύ του κλινικού σχεδιασμού και της ακτινοβόλησης του ασθενούς. Επίσης παρουσιάζουμε ότι η μετακίνηση του ασθενούς/ η αλλαγή στην ανατομία ή/ και η μετακίνηση των καθετήρων έχει ως αποτέλεσμα στην μείωση της ποιότητας του σχεδιασμού. Έχουμε αλλαγή στις αλλαγές στις τιμές του COIN, του DVH και των ραδιοβιολογικών παραμέτρων. Συμπέρασματα: Η μέση τιμή των μετρούμενων μετακινήσεων της ανατομίας και των βελονών είναι ιδιαίτερα μικρή περίπου 1.0mm σε σύγκριση με τις γνωστές τιμές από την εξωτερική ακτινοθεραπεία. Για τους υψηλής διαμόρφωσης σχεδιασμούς, όπως αυτοί της HDR βραχυθεραπείας, μικρές μετακινήσεις οδηγούν σε δοσιμετρικές αλλαγές γενικά μικρότερες από 5%. Τα αποτελέσματα μας παρουσιάζουν ότι λαμβάνοντας υπόψη τις διαδικασίες εξασφάλισης ποιότητας επιτυγχάνεται η ακινητοποίηση του εμφυτεύματος της τάξης του 1mm. Αυτό μπορεί να επιτευχθεί μόνο με ακινητοποίηση του εμφυτεύματος και της ανατομίας, για παράδειγμα στην περίπτωση όπου μετακινούμε την κεφαλή της συσκευής υπερήχων (US- probe) πριν την ακτινοβόληση ή μετακινώντας τον ασθενή από ένα κρεβάτι σε ένα άλλο για τις ανάγκες τις ακτινοβόλησης.

Τhe purpose of this study is to investigate and analyze the influence of the possible errors eventually occurring in a 3D-US based HDR Brachytherapy of prostate cancer on the quality of dose delivery. The influence of modulation restriction tool on the plan quality and sensitivity is also investigated. Materials: Twelve clinical implants for HDR Brachytherapy of prostate cancer have been selected out of the clinical routine. The range of the prostate volumes was 26-101 cm3. Due to the fact that the implanted needles are fixed on the template, the most probable error should be a systematic shift of the implanted catheters on the cranial-caudal direction caused by the movement of the patient relative to the template. The planning was done using HIPO which is implemented in the real time intraoperative planning system Oncentra Prostate (OcP). HIPO offers a unique modulation restriction option that limits the free modulation of dwell times. Firstly the reference plans, where no catheter shift has been simulated, the clinical with MR >0 and the theoretical with MR=0, for all 12 implants have been compared. Then for each of the 12 clinical implants, 10 systematic shifts of the implanted catheters in the range of [-5, +5] mm in step of 1mm were simulated. The influence of this systematic shift on DVH-, COIN, EI and radiobiological parameters of PTV and OARs is calculated and recorded. The analysis of the observed changes has been done firstly by addressing the quality of the implant. For this purpose the range of shift was estimated that the resulted 3D dose distributions keep fulfilling the clinical dosimetric protocol. Secondly, the focus was placed to the stability of the dose distribution. Here the range for the shift has been estimated which enables that the dosimetric, conformity and radiobiological parameters of the implant remain within ±5% or ±10% of the originally planned values. Results: The use of modulation restriction (MR>0) results in plans with more conformal dose distribution (COIN, EI) but slightly lower D90 and V100 , gEUD, EUD2,v and EUD2,s values. The quality analysis demonstrate that for the DVH based parameters values of prostate a maximal shift of ±1.0 mm can be tolerated, although in case of using the modulation restriction the sensitivity from the influence of the systematic shift is greater. Similar were the results for the DVH parameters for urethra, rectum and bladder. For the stability analysis in order to keep the dosimetric parameters within ±5% of the originally planned value for the prostate and OARs, a maximum shift of around ±0.5 mm can be tolerated and for the ±10% criterion this is -1.0/+0.5 mm. The same behavior applies for the radiobiological parameters. The analysis based on COIN considering only the target and also the OARs have shown a maximum shift range of ±1.5 mm. For the EI analysis this range is ±0.0 mm. For ±10% criterion this is ±2.5 mm and ±0.5 mm respectively. Conclusion: Our study has demonstrated that high modulated, high conformal Brachytherapy dose distributions for prostate HDR implants are sensitive to systematic catheter shift. The consequence of shift changes is not clear. We can generally speak about a required geometrical stability of the implant as high as ±1.0mm. Modulation restriction without improving this reduces significantly the total dwell time keeping the plan quality and increasing conformity (COIN, EI). / Ο σκοπός αυτής της μελέτης είναι να ερευνήσουμε και να αναλύσουμε την επιρροή που μπορεί να έχουν τα πιθανά λάθη που συμβαίνουν στην Υψηλού Ρυθμού Δόσης (HDR) Βραχυθεραπεία του καρκίνου του προστάτη, η οποία βασίζεται σε τρισδιάστατες εικόνες (3D) υπερήχου, στη ποιότητα εναπόθεσης δόσης. Επίσης διερευνάται η επίδραση του Modulation Restriction (MR) στην ποιότητα και ευαισθησία του πλάνου θεραπείας. Υλικά και Μέθοδοι: Επιλέχθηκαν 12 κλινικά εμφυτεύματα για την HDR Βραχυθεραπεία του καρκίνου του προστάτη από την κλινική ρουτίνα μας. Το εύρος του όγκου του προστάτη είναι 26-101 cm3. Επειδή οι βελόνες που εμφυτεύθηκαν στον προστάτη είναι σταθεροποιημένες πάνω στο template, το πιο πιθανό λάθος που μπορεί να συμβεί είναι η συστηματική μετατόπιση των εμφυτευμένων καθετήρων σε cranial – caudal (κρανιακή – ουραία ) διεύθυνση η οποία έχει προκληθεί από την κίνηση του ασθενούς σε σχέση με το template. Το πλάνο θεραπείας έγινε χρησιμοποιώντας την επιλογή HIPO του προγράμματος real time intraoperative planning system Oncentra Prostate (OcP). Το HIPO προσφέρει την δυνατότητα επιλογής του Modulation Restriction (MR) το οποίο περιορίζει την ελεύθερη διαμόρφωση των χρόνων παραμονής της πηγής στους καθετήρες. Στα αρχικά μας πλάνα θεραπείας (reference plans) δεν έχει γίνει προσομοίωση μετακίνησης του καθετήρα. Συγκρίνουμε τα κλινικά μας πλάνα (MR>0) και τα θεωρητικά μας (MR=0) και για τα 12 εμφυτεύματα. Στην συνέχεια για κάθε ένα από τα 12 εμφυτεύματα γίνεται η προσομοίωση 10 συστηματικών μετακινήσεων των εμφυτευμένων καθετήρων με εύρος [-5,+5]mm και με βήμα 1mm. Υπολογίζεται και καταγράφεται η επίδραση της συστηματικής μετακίνησης στα ιστογράμματα δόσης - όγκου (DVH), δείκτη συμμορφίας (conformity index- COIN), External Index (EI) και στις ραδιοβιολογικές παραμέτρους για τον όγκο στόχου (PTV) και των ευαίσθητων σε κίνδυνο οργάνων (OARs). Αρχικά η ανάλυση των παρατηρούμενων αλλαγών έχει γίνει σύμφωνα με την ποιότητα του εμφυτεύματος (quality analysis). Για αυτό τον λόγο το εύρος της μετακίνησης έχει υπολογιστεί έτσι ώστε τα αποτελέσματα από τις 3D κατανομές δόσεις να πληρούν το κλινικό δοσιμετρικό μας πρωτόκολλο. Στην συνέχεια εστιάσαμε στην σταθερότητα της κατανομής της δόσης (stability analysis). Σε αυτή την περίπτωση το εύρος μετακίνησης των καθετήρων έχει υπολογιστεί έτσι ώστε οι τιμές των DVH, COIN και ραδιοβιολογικών παραμέτρων των εμφυτευμάτων να παραμένουν μέσα στο ±5% ή στο ±10% των αρχικών πλάνων (reference). Αποτελέσματα: Χρησιμοποιώντας την επιλογή του Modulation Restriction (MR>0) προκύπτουν πλάνα με πιο ομοιόμορφη κατανομή της δόσης (COIN, EI) αλλά με ελαφρώς μικρότερες τιμές των D90, V100, gEUD, EUD2,v και EUD2,s. H “quality analysis” έδειξε ότι για τις δοσιμετρικές παραμέτρους του προστάτη η μέγιστη μετατόπιση που μπορούμε να έχουμε είναι ±1mm. Χρησιμοποιώντας την επιλογή του MR η μετατόπιση αυτή γίνεται ακόμα πιο ευαίσθητη. Παρόμοια ήταν τα αποτελέσματα μας για τις δοσιμετρικές παραμέτρους των OARs (ουρήθρα, κύστη και ορθό). Σύμφωνα με την “stability analysis” η μέγιστη μετατόπιση που μας επιτρέπεται έτσι ώστε να διατηρήσουμε τις τιμές των δοσιμετρικών παραμέτρων του προστάτη και των OARs μέσα στο ±5% της τιμής του αρχικού μας πλάνου είναι ±0.5mm ενώ για το ±10% το όριο αυτό είναι -1.0/+0.5 mm. Την ίδια συμπεριφορά παρατηρούμε και για τις ραδιοβιολογικές παραμέτρους. Η ανάλυση που βασίζεται στο COIN, συμπεριλαμβάνοντας αρχικά μόνο τον στόχο μας και στην συνέχεια και τα OARs έδειξε ότι η μέγιστη μετακίνηση μας έχει εύρος ±1.5mm . Για την ανάλυση που βασίζεται στο EI αυτό το εύρος είναι ±0.0 mm . Για το ±10% τα όρια είναι ±2.5mm και 0.5mm αντίστοιχα. Συμπεράσματα: Η μελέτη μας έδειξε ότι οι υψηλά διαμορφωμένες και οι υψηλά ομοιόμορφες κατανομές δόσης των εμφυτευμάτων της HDR βραχυθεραπείας του προστάτη είναι ευαίσθητες στις συστηματικές μετακινήσεις των καθετήρων. Οι συνέπειες από τις αλλαγές αυτών των μετακινήσεων δεν είναι ξεκάθαρες. Μπορούμε γενικά να μιλήσουμε για μια απαιτούμενη γεωμετρική σταθερότητα του εμφυτεύματος τόσο υψηλή όσο ±1.0mm. Η δυνατότητα επιλογής του MR χωρίς να βελτιώνει αυτό, μειώνει σημαντικά τον ολικό χρόνο παραμονής της πηγής στους καθετήρες διατηρώντας την ποιότητα του πλάνου θεραπείας και αυξάνοντας την ομοιομορφία στην κατανομή της δόσης (COIN, EI).

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.

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 comparação / The 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.

<p>The main objective of radiation therapy is to obtain the highest possible probability of tumor cure while minimizing adverse reactions in healthy tissues. A crucial step in the treatment process is to determine the location and extent of the primary tumor and its loco regional lymphatic spread in relation to adjacent radiosensitive anatomical structures and organs at risk. These volumes must also be accurately delineated with respect to external anatomic reference points, preferably on surrounding bony structures. At the same time, it is essential to have the best possible physical and radiobiological knowledge about the radiation responsiveness of the target tissues and organs at risk in order to achieve a more accurate optimization of the treatment outcome.</p><p>A computerized whole body Atlas has therefore been developed to serve as a dynamic database, with systematically integrated knowledge, comprising all necessary physical and radiobiological information about common target volumes and normal tissues. The Atlas also contains a database of segmented organs and a lymph node topography, which was based on the Visible Human dataset, to form standard reference geometry of organ systems. The reference knowledgebase and the standard organ dataset can be utilized for Atlas-based image processing and analysis in radiation therapy planning and for biological optimization of the treatment outcome. Atlas-based segmentation procedures were utilized to transform the reference organ dataset of the Atlas into the geometry of individual patients. The anatomic organs and target volumes of the database can be converted by elastic transformation into those of the individual patient for final treatment planning. Furthermore, a database of reference treatment plans was started by implementing state-of-the-art biologically based radiation therapy planning techniques such as conformal, intensity modulated, and radiobiologically optimized treatment planning.</p><p>The computerized Atlas can be viewed as a central framework that contains different forms of optimal treatment plans linked to all the essential information needed in treatment planning, which can be adapted to a given patient, in order to speed up treatment plan convergence. The Atlas also offers a platform to synthesize the results of imaging studies through its advanced geometric transformation and segmentation procedures. The whole body Atlas is anticipated to become a physical and biological knowledgebase that can facilitate, speed up and increase the accuracy in radiation therapy planning and treatment optimization.</p>

The main objective of radiation therapy is to obtain the highest possible probability of tumor cure while minimizing adverse reactions in healthy tissues. A crucial step in the treatment process is to determine the location and extent of the primary tumor and its loco regional lymphatic spread in relation to adjacent radiosensitive anatomical structures and organs at risk. These volumes must also be accurately delineated with respect to external anatomic reference points, preferably on surrounding bony structures. At the same time, it is essential to have the best possible physical and radiobiological knowledge about the radiation responsiveness of the target tissues and organs at risk in order to achieve a more accurate optimization of the treatment outcome. A computerized whole body Atlas has therefore been developed to serve as a dynamic database, with systematically integrated knowledge, comprising all necessary physical and radiobiological information about common target volumes and normal tissues. The Atlas also contains a database of segmented organs and a lymph node topography, which was based on the Visible Human dataset, to form standard reference geometry of organ systems. The reference knowledgebase and the standard organ dataset can be utilized for Atlas-based image processing and analysis in radiation therapy planning and for biological optimization of the treatment outcome. Atlas-based segmentation procedures were utilized to transform the reference organ dataset of the Atlas into the geometry of individual patients. The anatomic organs and target volumes of the database can be converted by elastic transformation into those of the individual patient for final treatment planning. Furthermore, a database of reference treatment plans was started by implementing state-of-the-art biologically based radiation therapy planning techniques such as conformal, intensity modulated, and radiobiologically optimized treatment planning. The computerized Atlas can be viewed as a central framework that contains different forms of optimal treatment plans linked to all the essential information needed in treatment planning, which can be adapted to a given patient, in order to speed up treatment plan convergence. The Atlas also offers a platform to synthesize the results of imaging studies through its advanced geometric transformation and segmentation procedures. The whole body Atlas is anticipated to become a physical and biological knowledgebase that can facilitate, speed up and increase the accuracy in radiation therapy planning and treatment optimization.

Radiation therapy with light ions improves treatment outcome for a number of tumor types. The advantageous dose distributions of light ion beams en-able exceptional target conformity, which assures high dose delivery to the tumor while minimizing the dose to surrounding normal tissues. The demand of high target conformity necessitates development of accurate methods to calculate absorbed dose distributions. This is especially important for heavy charged particle irradiation, where the patient is exposed to a complex radia-tion field of primary and secondary ions. The presented approach combines accurate Monte Carlo calculations using the SHIELD-HIT07 code with a fast analytical pencil beam model, to pro-vide dose distributions of light ions. The developed model allows for ana-lytical descriptions of multiple scattering and energy loss straggling proc-esses of both primary ions and fragments, transported in tissue equivalent media. By applied parameterization of the radial spread of fragments, im-proved description of radial dose distributions at every depth is obtained. The model provides a fast and accurate tool of practical value in clinical work. Compared to conventional radiation modalities, an enhanced tissue response is seen after light ion irradiation and biological optimization calls for accu-rate model description and prediction of the biological effects of ion expo-sure. In a joint study, the performance of some radiobiological models is compared for facilitating the development towards more robust and precise models. Specifically, cell survival after exposure to various ion species is modeled by a fast analytical cellular track structure approach in conjunction with a simple track-segment model of ion beam transport. Although the stud-ies show that descriptions of complex biological effects of ion beams, as given by simple radiobiological models, are approximate, the models may yet be useful in analyzing clinical results and designing new strategies for ion therapy.

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 comparação / The 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.

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. / <p>S. 1-44: sammanfattning, s. 47-130: 5 uppsatser</p> / digitalisering@umu

Active Particles at the Temelin NPP, Radiobiological Risks and Protective Precautions The term active particle (AC) was applied on Temelín NPP (ETE) in order to denominate small fragments of high radioactive matters, sized up to 1 millimeter, forming into primary circuit. In accordance with latest available know-how, the ACs major contains corrosion products, that were activated during passing through reactor core. After primary circuit opening, due to carry out outage works, the ACs will spread into ETE radiation controlled area. In proportion to their size, the ACs activity is relative high, so that the ACs can jeopard workers, who will contact them. This jeopardy is namely associated with AC penetration into organism - ingestion or inhalation. The main goal of this dissertation is to determine grounds of ACs occurence in Temelín NPP, to review ACs radiobiological risks and to evaluate procedures and protective aids, used for assurance of workers radiation protection. This dissertation is resuming actual know-how about ACs occured and occuring in Temelín NPP, including suggestions for radiation protection procedures and for protective aids utilization, that are to be used for reduction of above mentioned jeopardy. Next areas are concerned: - analysis of ACs forming and matters composition - description of ACs physical-radiation parameters - identification of main ACs sources in primary circuit - assesment and evaluation of radiobiological jeopardies, associated with ACs occurence in Temelín NPP radiation controlled area - assesment of procedures and protective aids used for protection of workers, who can be endangered by ACs