Dissertationen zum Thema „Radiation dosimetry“

Durch die Einführung von Synchrozyklotronen und Laser-Teilchenbeschleunigern, entwickelt mit dem Ziel günstigere und kompaktere Protonentherapieanlagen bereitzustellen, werden stark gepulste Strahlenfelder möglicherweise Anwendung in der Teletherapie finden. Darüber hinaus bergen stark gepulste Strahlenfelder das Potential klinischer Vorteile durch eine bessere Schonung gesunden Gewebes oder die verbesserte Behandlung bewegter Tumore. Allerdings ergeben sich neue Herausforderungen im Bereich der Dosimetrie, der Grundlage für eine präzise therapeutische Anwendung ionisierender Strahlung. Diese Herausforderungen betreffen sowohl den Bereich der klinischen Dosimetrie für die unmittelbare Strahlenanwendung als auch die Strahlenschutzdosimetrie zum Schutz von Umwelt und Personal. Luftgefüllte Ionisationskammern, die primären Messinstrumente der klinischen Dosimetrie, sind von einem zunehmenden Signalverlust aufgrund von Volumenrekombination betroffen, da stark gepulste Strahlenfelder eine hohe Ionisationsdichte innerhalb eines sehr kurzen Zeitraums erzeugen. Beschreibungen für diese Effekte sind zwar gut etabliert für die moderat gepulsten Felder im gegenwärtigen klinischen Einsatz (Boags Theorie), allerdings sind die dafür nötigen Näherung höchst wahrscheinlich unzureichend für die stark gepulsten Strahlenfelder zukünftiger Beschleuniger. Ferner sind Dosisleistungsmessgeräte, welche im Strahlenschutz als fest installierte oder mobile Überwachungsdosimeter eingesetzt werden, nur für kontinuierliche Strahlenfelder geprüft und bauartzugelassen, was Zweifel an ihrer Eignung für die Messung gepulster Felder eröffnet. In dieser Arbeit wurden beide Bereiche der Dosimetrie, sowohl Strahlenschutz als auch klinische Dosimetrie, untersucht, um die medizinische Anwendung stark gepulster Strahlung zu ermöglichen. Für ein möglichst umfassendes Verständnis wurden dabei experimentelle Untersuchungen mit theoretischen Überlegungen und Entwicklungen verzahnt. Mit dem ELBE-Forschungsbeschleuniger wurde ein gepulster 20 MeV Elektronenstrahl und somit ein gepulstes Strahlungsfeld erzeugt, welches eine systematische Untersuchung in einem großen Bereich in Bezug auf Pulsdosis und Pulsdauer erlaubte. Ionisationskammern für den klinischen Einsatz wurden mit diesem Elektronenstrahl direkt bestrahlt und ein Faraday-Becher diente als unabhängige Referenzmessung. Dosisleistungsmessgeräte hingegen wurden im, durch den Elektronenstrahl im Faraday-Becher erzeugten, Bremsstrahlungsfeld bestrahlt. Dabei fungierte die Ionisationskammer vor dem Faraday-Becher als Strahlmonitor und diente zur Bestimmung der Referenzdosis des Bremsstrahlungsfeldes über eine Querkalibrierung mit Thermolumineszenzdosimetern. Es wurden drei Dosisleistungsmessgeräte basierend auf unterschiedlichen Messprinzipien untersucht, die damit einen großen Teil der im Strahlenschutz eingesetzten Messprinzipien abdecken: Die Ionisationskammer RamION, das Proportionalzählrohr LB1236-H10 und der Szintillationsdetektor AD-b. Für die klinische Dosimetrie wurden zwei verbreitete Ionisationskammergeometrien untersucht: die Advanced Markus Kammer als Flachkammer und die PinPoint Kammer als Kompaktkammer. Zusätzlich zu der üblichen Luftfüllung wurde außerdem eine Füllung mit reinem Stickstoff und zwei Flüssigionisationskammern mit Isooctan und Tetramethylsilan untersucht. Ferner wurde eine numerische Berechnung der Volumenrekombination in Ionisationskammern durch die Beschreibung der Prozesse von Ladungsfreisetzung, Ladungstransport und Reaktion entwickelt, um eine Beschreibung zu erhalten, die ohne die für Boags Theorie notwendigen Näherungen auskommt. Insbesondere berücksichtigt diese Berechnung den Einfluss der freigesetzten Ladungen auf das elektrische Feld, der in Boags Theorie vernachlässigt wird. Von den drei untersuchten Dosisleistungsmessgeräten zeigte nur das RamION Messungen innerhalb der gegebenen Toleranzen in den untersuchten Strahlungsfeldern. Die unerwartet schlechte Präzision des AD-b Szintillationsdetektors, der keinen prinzipiellen Beschränkungen in gepulsten Feldern unterliegen sollte, wurde auf die Signalverarbeitung im Messgerät zurückgeführt, welche das prinzipielle Problem einer unbekannten Signalverarbeitung in kommerziellen Geräten hervorhebt. Das LB 1236-H10 Proportionalzählrohr andererseits maß den Erwartungen entsprechend. Dies unterstützt zwar die in DIN IEC/TS 62743 dargelegten Erwartungen für zählende Dosimeter, zeigt allerdings zugleich die allgemeine Unzulänglichkeit solcher Instrumente für die Messung stark gepulster Felder und demonstriert die Notwendigkeit für weitere normative Bestrebungen, um einheitliche Bedingungen für die Untersuchung nicht-zählender Dosimeter (wie das RamION) zu schaffen. Durch die Aufnahme dieser Ergebnisse in die Literatur der Strahlenschutzkommission wurde hier der Grundstein für eine solche Entwicklung gelegt. Die Untersuchung der Ionisationskammern für klinische Dosimetrie zeigte z.T. starke Abweichungen zwischen Boags Theorie und experimentellen Beobachtungen. Boags Theorie beschreibt Volumenrekombination hinreichend genau lediglich für die zwei Flüssigionisationskammern. Im Falle sämtlicher gasgefüllter Kammern waren effektive Parameter notwendig, deren Wert kaum einen Zusammenhang mit der ursprünglichen Definition besaß. Doch auch dieser Ansatz versagt jedoch für die Advanced Markus-Kammer bei Sammelspannungen ≥ 300 V und Pulsdosen ab ca. 100 mGy. Das entwickelte numerische Berechnungsverfahren lieferte eine deutlich passendere Berechnung der Volumenrekombination und ermöglichte es, die Ursache für die Unterschiede zu Boags Theorie in dem Einfluss der freigesetzten Ladungen auf das elektrische Feld zu identifizieren. Eine aufgrund der erhöhten Pulsdosis erhöhte positive Raumladung verlangsamt die Sammlung der normalerweise schnellen freien Elektronen, welche von Volumenrekombination zunächst unbeeinträchtigt sind. Aufgrund der längeren Verweildauer im Kammervolumen, lagert sich jedoch ein höherer Anteil der Elektronen an und bildet negative Ionen. Der daraus resultierende höhere Anteil an Ladungen die Volumenrekombination ausgesetzt sind, zusätzlich zu der erhöhten Ladungsmenge, bedingt eine Erhöhung der Volumenrekombination mit der Pulsdosis, die sich nicht durch Boags Theorie beschreiben lässt. Insbesondere von Bedeutung ist dieser Effekt bei hohen elektrischen Feldstärken und kleinen Elektrodenabständen, die in einem hohen Anteil freier Elektronen resultieren. Des Weiteren erlaubt das numerische Verfahren die Berechnung für beliebige Pulsdauern, wohingegen Boags Theorie auf verschwindend geringe Pulsdauern beschränkt ist. Im Allgemeinen ergab das numerische Berechnungsverfahren Ergebnisse in guter Übereinstimmung mit den experimentellen Beobachtungen für die sehr verschiedenartigen Füllungen von Luft, Stickstoff und Flüssigkeiten. Auch die geometrisch komplexere Kompaktkammer konnte prinzipiell damit beschrieben werden, wobei sich jedoch für die untersuchte PinPoint-Kammer einige Diskrepanzen zu den experimentellen Beobachtungen ergaben. Eine vielversprechende Weiterentwicklung der Berechnung wäre die verbesserte Beschreibung der Sammelspannungsabhängigkeit der Volumenrekombination. In ihrer derzeitigen Form erfordert die Berechnung eine Charakterisierung jeder Kammer und Spannung, was durch eine Weiterentwicklung der Berechnung möglicherweise eliminiert werden könnte. Nichtsdestotrotz stellt die entwickelte numerische Berechnung eine deutliche Verbesserung gegenüber Boag's Theorie durch die korrekte Beschreibung der Pulsdosis- und Pulsdauerabhängigkeit der Volumenrekombination in stark gepulsten Felder dar, was prinzipiell eine absolute Dosimetrie dieser Felder ermöglichen sollte
Synchrocyclotrons and laser based particle accelerators, developed with the goal to enable more compact particle therapy facilities, may bring highly pulsed radiation field to external beam radiation therapy. In addition, such highly pulsed fields may be desirable due to their potential clinical benefits regarding better healthy tissue sparing or improved gating for moving tumors. However, they pose new challenges for dosimetry, the corner stone of any application of ionizing radiation. These challenges affect both clinical and radiation protection dosimetry. Air-filled ionization chambers, which dominate clinical dosimetry, face the problem of increased signal loss due to volume recombination when a highly pulsed field liberates a large amount of charge in a short time in the chamber. While well established descriptions exist for this volume recombination for the moderately pulsed fields in current use (Boag's formulas), the assumptions on which those descriptions are based will most likely not hold in the prospective, highly pulsed fields of future accelerators. Furthermore, ambient dose rate meters used in radiation protection dosimetry as survey meters or fixed installations are generally only tested for continuous fields, casting doubt on their suitability to measure pulsed fields. This thesis investigated both these aspects of dosimetry - clinical as well as radiation protection - to enable the medical application of highly pulsed radiation fields. For a comprehensive understanding, experimental investigations were coupled with theoretical considerations and developments. Pulsed fields, varying in both dose-per-pulse and pulse duration over a wide range, were generated with the ELBE research accelerator, providing a 20 MeV pulsed electron beam. Ionization chambers for clinical dosimetry were investigated using this electron beam directly, with an aluminium Faraday cup providing the reference measurement. Whereas the dose rate meters were irradiated in the photon field generated from stopping the electron beam in the Faraday cup. In those measurements, the reference was calculated from the ionization chamber, then serving a an electron beam monitor, cross-calibrated to the photon field with thermoluminescent dosimeters. Three dose rate meters based on different operating principles were investigated, covering a large portion of the operating principles used in radiation protection: the ionization chamber based RamION, the proportional counter LB 1236-H10 and the scintillation detector AD-b. Regarding clinical dosimetry, measurements of two prominent ionization chamber geometries, plane-parallel (Advanced Markus chamber) and thimble type (PinPoint chamber), were performed. In addition to common air-filled chambers, chambers filled with pure nitrogen and two non-polar liquids, tetramethylsilane and isooctane, were investigated. In conjunction with the experiments, a numerical solution of the charge liberation, transport, and recombination processes in the ionization chamber was developed to calculate the volume recombination independent of the assumptions necessary to derive Boag's formulas. Most importantly, the influence of the liberated charges in the ionization chamber on the electric field, which is neglected in Boag's formulas, is included in the developed calculation. Out of the three investigated dose rate meters only the RamION could be identified as an instrument truly capable of measuring a pulsed field. The AD-b performed below expectations (principally, a scintillator is not limited in detecting pulsed radiation), which was attributed to the signal processing, emphasizing the problem of a typical black-box signal processing in commercial instruments. The LB 1236-H10, on the other hand, performed as expected of a counting detector. While this supports the recent effort to formalize these expectations and standardize testing for counting dosimeters in DIN IEC/TS 62743, it also highlights the insufficiency of counting detectors for highly pulsed fields in general and shows the need for additional normative work to establish requirements for dose rate meters not based on a counting signal (such as the RamION), for which no framework currently exists. With these results recognized by the German radiation protection commission (SSK) the first steps towards such a framework are taken. The investigation of the ionization chambers used in radiation therapy showed severe discrepancies between Boag's formulas and the experimentally observed volume recombination. Boag's formulas describe volume recombination truly correctly only in the two liquid-filled chambers. All the gas-filled chambers required the use of effective parameters, resulting in values for those parameters with little to no relation to their original meaning. Even this approach, however, failed in the case of the Advanced Markus chamber for collection voltages ≥ 300 V and beyond a dose-per-pulse of about 100 mGy. The developed numerical model enabled a much better calculation of volume recombination and allowed the identification of the root of the differences to Boag's formulas as the influence of the liberated charges on the electric field. Increased positive space charge due to increased dose-per-pulse slows the collection and reduces the fraction of fast, free electrons, which are unaffected by volume recombination. The resultant increase in the fraction of charge undergoing volume recombination, in addition to the increase in the total amount of charge, results in an increase in volume recombination with dose-per-pulse that is impossible to describe with Boag's formulas. It is particularly relevant in the case of high electric fields and small electrode distances, where the free electron fraction is large. In addition, the numerical calculation allows for arbitrary pulse durations, while Boag's formulas apply only to very short pulses. In general, the numerical calculation worked well for plane-parallel chambers, including those filled with the very diverse media of liquids, nitrogen and air. Despite its increased complexity, the thimble geometry could be implemented as well, although, in the case of the PinPoint chamber, some discrepancies to the experimental data remained, probably due to the required geometrical approximations. A possible future development of the numerical calculation would be an improved description of the voltage dependence of the volume recombination. At the moment it requires characterizing a chamber at each desired collection voltage, which could be eliminated by an improved modeling of the volume recombination's dependence on collection voltage. Nevertheless, the developed numerical calculation presents a marked improvement over Boag's formulas to describe the dose-per-pulse dependence and pulse duration dependence of volume recombination in ionization chambers, in principle enabling the application of ionization chambers in the absolute dosimetry of highly pulsed fields

Electron beam therapy planning and custom electron bolus design were identified as areas in which improvements in equipment and techniques could lead to significant improvements in treatment delivery and patient outcomes. The electron pencil beam algorithms used in conventional Treatment Planning Systems do not accurately model the dose distribution in irregularly shaped objects, near oblique surfaces or in inhomogeneous media. For this reason, at Christchurch Oncology Centre the TPS is not relied on for planning electron beam treatments. This project is an initial study of ways to improve the design of custom electron bolus, the planning of electron beam therapy, and other radiation therapy simulation tasks, by developing a system for the accurate assessment of dose distributions under irregular contours in clinically relevant situations. A shaped water phantom system and a diode array have been developed and tested. The design and construction of this water phantom dosimetry system are described, and its capabilities and limitations discussed. An EGS/BEAM Monte Carlo simulation system has been installed, and models of the Christchurch Oncology Centre linacs in 6MeV and 9MeV electron beam modes have been built and commissioned. A test was run comparing the EGS/BEAM Monte Carlo system and the CMS Xio conventional treatment planning system with the experimental measurement technique using the water phantom and the diode array. This test was successful as a proof of the concept of the experimental technique. At the conclusion of this project, the main limitation of the diode array system was the lack of data processing software. The array produces a large volume of raw data, but not enough processed data was produced during this project to match the spatial resolution of the computer models. An automated data processing system will be needed for clinical use of the array. It has been confirmed that Monte Carlo and pencil-beam algorithms predict significantly different dose distributions for an irregularly shaped object irradiated with megavoltage electron beams. The results from the diode array were consistent with the theoretical models. This project was an initial investigation. At the time of writing, the diode array and the water phantom systems were still at an early stage of development. The work reported here was performed to build, test and commission the equipment. Additional work will be needed to produce an instrument for clinical use. Research into electron beam therapy could be continued, or the equipment used to expand research into new areas.

A novel optical calorimetry approach is proposed for the dosimetry of therapeutic radiation, based on the optical technique of Digital Holographic Interferometry (DHI). This detector determines the radiation absorbed dose to water by measurement of the refractive index variations arising from radiation induced temperature increases. The output consists of a time series of high resolution, two dimensional images of the spatial distribution of the projected dose map across the water sample. This absorbed dose to water is measured directly, independently of radiation type, dose rate and energy, and without perturbation of the beam. These are key features which make DHI a promising technique for radiation dosimetry. A prototype DHI detector was developed, with the aim of providing proof-of-principle of the approach. The detector consists of an optical laser interferometer based on a lensless Fourier transform digital holography (LFTDH) system, and the associated mathematical reconstruction of the absorbed dose. The conceptual basis was introduced, and a full framework was established for the measurement and analysis of the results. Methods were developed for mathematical correction of the distortions introduced by heat di usion within the system. Pilot studies of the dosimetry of a high dose rate Ir-192 brachytherapy source and a small eld proton beam were conducted in order to investigate the dosimetric potential of the technique. Results were validated against independent models of the expected radiation dose distributions. Initial measurements of absorbed dose demonstrated the ability of the DHI detector to resolve the minuscule temperature changes produced by radiation in water to within experimental uncertainty. Spatial resolution of approximately 0.03 mm/pixel was achieved, and the dose distribution around the brachytherapy source was accurately measured for short irradiation times, to within the experimental uncertainty. The experimental noise for the prototype detector was relatively large and combined with the occurrence of heat di usion, means that the method is predominantly suitable for high dose rate applications. The initial proof-of-principle results con rm that DHI dosimetry is a promising technique, with a range of potential bene ts. Further development of the technique is warranted, to improve on the limitations of the current prototype. A comprehensive analysis of the system was conducted to determine key requirements for future development of the DHI detector to be a useful contribution to the dosimetric toolbox of a range of current and emerging applications. The sources of measurement uncertainty are considered, and methods suggested to mitigate these. Improvement of the signal-to-noise ratio, and further development of the heat transport corrections for high dose gradient regions are key areas of focus highlighted for future development.

The thesis gives an overview on the preclinical results in Microbeam Radiation Therapy (MRT), a novel radiation therapy using microscopically small beams. In the first chapter preclinical results and biological observations after Microbeam Radiation Therapy are presented, in particular the normal tissue tolerance is highlighted. A chapter based on theoretical Monte Carlo dose calculations is summarizing a set of data on peak to valley dose ratios (PVDR) and relative dose distributions for various parameter settings, providing some guideline for preclinical studies. The main part of the thesis is focusing on the experimental dosimetry, on one side to measure the high dose rate in the homogenous field proposing the necessary corrections to be applied for absolute dose measurements and on the other side, to measure peak and valley dose. For the high resolution dose measurements of the spatially fractionated beam, results using several types of detectors are presented and discussed. Various results using Gafchromic film dosimetry in combination with a microdensitometer show slightly higher (~10-15 %) valley dose than the MC calculated values. Results of theoretical calculations of output factors and their experimental verification are in very good agreement. The great potential of interlaced Microbeams in an anthropomorphic phantom with one single high dose delivery is discussed, including the technical challenges to be mastered in the future.

Thesis (M.S. in Electrical Engineering)--Naval Postgraduate School, September 2003.
Thesis advisor(s): Todd R. Weatherford, Andrew A. Parker. Includes bibliographical references (p. 39). Also available online.

The spin-lattice relaxation rate R$ sb1$ of irradiated Fricke solution was studied as a function of the absorbed dose D. The R$ sb1$ increases linearly with D up to a dose of $ sim$250 Gy after which the response saturates. A model describing the R$ sb1$ of a solution of either ferrous (Fe$ sp{2+})$ or ferric (Fe$ sp{3+})$ ions is presented; it is based on fast exchange between protons on water molecules in the bulk and protons on water molecules in the coordination shell of the ions. All inherent relaxation parameters of the different proton groups are determined. An extension of the model is made to describe the spin-lattice relaxation behaviour of irradiated Fricke solution. Good agreement between model predictions and experimental results is observed. The model relates the spin-lattice relaxation rate of a Fricke dosimeter to the chemical yield of ferric ion, thus creating an absolute dosimetry technique. Various practical aspects of the NMR-Fricke system are described.

The spin-spin and spin-lattice relaxation times of protons on polymers, T$ sb{ rm 1p}$ and T$ sb{ rm 2p}$, respectively, have been used to probe the absorbed dose of irradiated polymer solutions in which radiation-induced changes in polymer molecular weight, M$ sb{ rm n}$, occur. The M$ sb{ rm n}$ dependencies of T$ sb{ rm 1p}$ and T$ sb{ rm 2p}$, and of the water proton T$ sb{ rm 1w}$ for solutions of poly(ethylene oxide) (PEO) in D$ sb2$O and H$ sb2$O are presented. T$ sb{ rm 1p}$ and T$ sb{ rm 1w}$ are independent of M$ sb{ rm n},$ and T$ sb{ rm 2p}$ varies with M$ sb{ rm n}$ according to a specific inverse power dependence until low M$ sb{ rm n}$ when T$ sb2$ saturation occurs. The dose dependence of T$ sb{ rm 1p}$ and T$ sb{ rm 2p}$ measured for dilute solutions of PEO in D$ sb2$O reflects the dependence of M$ sb{ rm n}$ on dose. A novel semi-empirical model is proposed for the dose dependence of T$ sb{ rm 2p}$ which incorporates the measured M$ sb{ rm n}$ power dependence of T$ sb{ rm 2p}$ into a theoretical expression of the dose dependence of the M$ sb{ rm n}$. This expression is based on previous bulk polymer work and has been modified to hold for polymers in solution. The model can be fitted well to the T$ sb{ rm 2p}$ data measured for different doses, and the values of the fitting parameters agree with those expected from independent measurements. Practical aspects of the NMR/polymer dosimetry technique are also addressed.

ABSTRACT Intensity modulated beams use complicated computerized treatment planning systems; this makes a manual verification of the number of monitor units difficult to perform. Consequently, before treatment, patient-specific quality assurance must be done in order to ensure that the delivery agrees with the plan; this process involves a measurement of 2D dose distribution in a phantom. In this thesis, first, a photostimulable phosphor luminescence device (also referred to as computed radiography or CR) was evaluated for dosimetric purposes. The proposed protocol showed linearity response of the CR, but energy and field size dependence were discovered. Second, two widely used films for IMRT QA were compared: the radiological film, EDR2, and the radiochromic film, EBT, with the use of the scanner EPSON1680 and the software FILMQA. Results showed that in the relative dose mode, EDR2 gives higher number of pixels passing a chosen criterion compared to EBT. This fact is attributed to the highest contrast observed with EDR2; therefore, any change on pixel value due to scanner artifacts will have less impact on dose calculations with EDR2. Finally, the impact of scanner artifacts on dose assessment with EBT films, processed with FILMQA and a program written on MATLAB, was studied. A correction was introduced on MATLAB that proves the importance of taking scanner artifacts into account for the measurements with the scanner EPSON1680 and EBT films digitized in the portrait orientation. Comparison between FILMQA and MATLAB was performed on profile’s measurements and on fifteen head and neck IMRT QA cases. This comparison showed that one case out of fifteen was drastically improved with MATLAB, yet FILMQA gave inaccurate results of profiles compared with the correction applied on MATLAB.
ABRÉGÉDélivrer un traitement conforme à la planification est une des responsabilités duphysicien médical; ceci est relativement simple à vérifier en RadiothérapieConformationnelle. Cependant, la complexité des calculs en Radiothérapie avecModulation d’Intensité (RTMI) rend cette vérification moins évidente puisque larelation entre la dose et les unités moniteures est plus difficile à établir. Enconséquence, irradier un fantôme conformément au plan établi pour le patient estune étape effectuée avant chaque traitement. Cette irradiation s’accompagned’une mesure à l’aide d’une chambre d’ionisation et d’une mesure desdistributions de doses à 2D. Dans cette thèse trois points sont soulevés. Lepremier consiste à évaluer le Computed Radiography (CR) en dosimétrie; leprotocole proposé a mené à une réponse linéaire mais dépendante en énergie et enlargeur de champ. En second lieu, une comparaison de deux films (EDR2 et EBT)largement utilisés pour l’assurance qualité en RTMI a été effectuée. L’étude amontré qu’en dose relative, EDR2 donnent de meilleurs résultats que EBT. Ceciest attribuable au fait que le contraste enregistré avec EDR2 rend les artefacts descanners moins importants sur le calcul de dose comparativement à EBT. Latroisième partie de ce travail traite de l’importance des artefacts introduits lors dela lecture des EBT sur le scanner EPSON1680. Une correction de ces artefacts,effectuée sur MATLAB, a prouvé leur importance. Le logiciel FILMQA utilisé enclinique pour le traitement des films a montré une grande erreur sur la mesure desprofils, mais sur 15 plans d’RTMI étudiés, un seul cas a véritablement étéamélioré par la correction effectuée sur MATLAB.

Several dosimetric parameters were measured for three very small radiation fields (1.5, 3, and 5 mm diameter at the machine isocenter) with a small ionization chamber and a new type of radiochromic film. The experiments were carried out on a Clinac-18 linac and the fields were shaped by specially manufactured collimators. When measuring dose profiles, the ionization chamber measurements were first corrected for response variation in off-axis direction, and then deconvolved to eliminate the blur due to the poor resolution of the chamber. The measured data agreed with Monte Carlo simulations within the established statistical uncertainties.
Dynamic stereotactic radiosurgery was carried out on the same accelerator using the very small radiation beams. The dose distributions and their displacements from the laser-defined isocenter of the linac were measured and then compared to 3-D Monte Carlo calculations. The results proved that dynamic radiosurgery with very small beams has potential for clinical use.

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Dissertação (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Dosimetry is the methodology of determining the amount of radiation energy imparted in matter and volume. Although several techniques and devices are available for use in both laboratory and clinical settings, most rely on certain conditions, assumptions and approximations to convert the energy into radiation dose. The many uncertainties from current techniques are introduced due to the material differences between the sensitive detector volume and the phantom material, typically water. The aim of this thesis is to use the water sample itself to detect the amount of radiation energy that has been imparted upon it. Radiation energy absorbed by the sample is ultimately converted into heat, raising the temperature of the sample and changing the refractive index property. The refractive index change results in a shortening of the optical path length and as a result, light passing through the sample experiences a phase change. Phase information cannot be directly measured, as it is merely a property of light wave propagation, thus another technique must be used. Digital holographic interferometry was employed to capture snapshots of the sample’s changing state over time, and when compared with a reference, the interference phase information was extracted and used to calculate the refractive index change, which can then be related to radiation absorbed dose. The aim of this research was to design and build interferometry setups using holographic interferometry to determine the refractive index change induced by radiation and to explore the possibilities of using fibre optics. Experiments were conducted on the setups to determine the validity of the method and the accuracy of the system. With external heating sources in the forms of an open flame and infrared laser, we could see distinct heating patterns formed in the phase images. The phase allowed the calculation of the temperature and therefore energy from the change in refractive index, but was limited to phase differences within 2π between the images, due to wrapped phases. In the stability tests, we demonstrated the accuracy of the system and found it was heavily influenced by the amount of vibration in the vicinity. In the short term, a standard deviation of 0.015 degrees was recorded but a larger standard deviation of 0.078 degrees was measured in the longer term. We can be confident of the temperature measurements to within 0.1 of a degree, equal to hundreds of Grays in radiation dose, however this is not sufficiently accurate for dosimetry. Future work may include improving accuracy by reducing the vibration in the system.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
FAPESP:05/00258-1

L’utilisation de petits champs dans les techniques de radiothérapie a considérablement augmenté, en particulier dans les traitements stéréotaxiques et les grands champs uniformes ou non uniformes qui sont composés de petits champs tels que la radiothérapie à modulation d’intensité (IMRT) ou la radiothérapie par microfaisceaux. Pour ces champs d’irradiation, les erreurs dosimétriques ont augmenté par rapport aux faisceaux conventionnels. La raison principale en est qu’il n’existe pas de protocole dosimétrique standard. Dans le cas de la MRT, un protocole dédié a été développé sur la base d’une mesure de faisceau large avec une chambre d’ionisation PinPoint combinée à la multiplication avec un OF pour prédire la dose dans le pic. Ce protocole est pratique en ce sens qu’il permet de surmonter le manque de résolution spatiale du détecteur et de toute façon d’aller de l’avant avec les procédures pré-cliniques en permettant le calcul de la dose pic. La dose dans la vallée est ensuite récupérée à l’aide du PVDR, également basé sur des calculs MC.Au cours de la dernière décennie, des détecteurs à haute résolution spatiale permettant des mesures à l’échelle du micron sont devenus disponibles. Parmi eux, le détecteur de microdiamants PTW, les films HDV2 combinés avec le système de lecture approprié et le FNTD. Les mesures effectuées sur la ligne de lumière biomédical ID 17 avec ces trois dosimètres ont mis en évidence des divergences entre les valeurs simulées MC de OF et PVDR et les données expérimentales qui traitent d’un problème concernant la validité du protocole de dosimétrie actuel. En outre, il a été souligné que les valeurs OF et PVDR différent entre les différents codes MC, ce qui représente un problème lorsque ces valeurs sont associé au protocole de dosimétrie. Obtenir des valeurs fiables d’OF et de PVDR pour les mesures expérimentales et numériques représente le défi de ce travail.Dans ce travail, les écarts entre les simulations MC et les données mesurées sont attribués à un manque de détails dans les simulations MC et au fait que les caractéristiques spécifiques du détecteur peuvent influencer la mesure. Une série de simulations MC est mise au point pour quantifier chacun de ces effets. Le principal inconvénient d'une telle étude est le temps de simulation, de sorte que des astuces sont utilisées pour accélérer le calcul et néanmoins garder les résultats aussi précis que possible
The use of small fields in radiotherapy techniques has increased substantially, in particular in stereotactic treatments and large uniform or nonuniform fields that are composed of small fields such as for intensity modulated radiation therapy (IMRT) or Microbeam Radiation Therapy. For these irradiation fields, dosimetric errors have increased compared to conventional beams. The main reason for this is that no standard dosimetric protocol exists. In the case of MRT, a dedicated protocol has been developed based on a broad beam measurement with a PinPoint chamber combined with the multiplication with an OF to predict the peak dose. This protocol is handy in the sense that it allows to overcome the lack of spatial resolution of the detector and anyway move forward with pre-clinical procedures by enabling the calculation of the peak dose. The valley dose is then retrieved using the PVDR also based on MC calculations.Over the last decade, detectors with high spatial resolution allowing measurements at the micron scale became available. Among them, the PTW microDiamond detector, HDV2 films combined with the appropriate read-out system and FNTD. Measurements performed at the ID 17 biomedical beamline with these three dosimeters highlighted discrepancies between the MC simulated values of OF and PVDR and experimental data which addresses an issue regarding the validity of the current dosimetry protocol. Moreover, it has been highlighted that OF and PVDR values differ between the different MC codes which represents a problem when associated with the dosimetry protocol. Obtaining reliable values of OF and PVDR for both experimental and numerical measurement represents the challenge of this work.In this work, the discrepancies between the MC simulations and measured datas are assigned to a lack of details in the MC simulations and to the fact that detector specific characteristics can influence the measurement. A series of MC simulation is developed to quantify each of these effects. The major drawback of such study is the simulation time, so tricks are used to speed up the calculation and nevertheless keep the results as accurate as possible

Radiation therapy is a beneficial treatment for approximately half of all people diagnosed with cancer. This project improved the safety of radiation therapy for several vulnerable cohorts: pregnant patients, patients with electronic implants such as pacemakers, and young people at risk of developing secondary cancers later in life. In doing so, this research furthered equitable access to safe, high-quality health care.

The goal of the thesis was to investigate, and better define, what the requirements are for accurate small field relative dosimetry. Diode detector selection and experimental techniques were evaluated. EGSnrc Monte Carlo simulations were used to predict diode detector dosimetric parameters and assist in interpreting measured data. An emerging scintillator based detector technology was also tested and methods developed to standardize the reporting of small field dosimetric data. Using careful experimental methods the relative output uncertainty for the smallest square field size of side 0.5 cm was reduced to better than ±1.00% for all detector types. Monte Carlo simulation data revealed that for the same small field size the relative output measured using unshielded and shielded diodes will be 5% and 10% greater than the actual relative output in water. Further simulation work showed that simplified diode detector models are valid for use in small field dosimetry simulations. The diode detector over-response was also shown to be insensitive to variations in the electron energy and spot size incident on the Bremsstrahlung target. Experimental methods were refined to include the definition of an effective field size, which was shown to remove much of the ambiguity in reporting small field relative output data across a population of linear accelerators. Each of the for mentioned areas of investigation have been shown to be requirements for accurate small field relative.

Six radiation dosimetry and medical physics problems were analyzed using a beta version of MCNP 5 as part of an international intercomparison of radiation dosimetry computer codes, sponsored by the European Commission committee on the quality assurance of computational tools in radiation dosimetry. Results have been submitted to the committee, which will perform the inter-code comparison and publish the results independently. A comparison of the beta version of MCNP 5 with MCNP 4C2 is made, as well as a comparison of the new Doppler broadening feature. Comparisons are also made between the *F8 and F6 tallies, neutron tally results with and without the use of the S(a,b) cross sections, and analytically derived peak positions with pulse height distributions of a Ge detector obtained using the beta version of MCNP 5. The following problems from the study were examined: Problem 1 was modeled to determine the near-field angular anisotropy and dose distribution from a high dose rate 192Ir brachytherapy source in a surrounding spherical water phantom. Problem 2 was modeled to find radial and axial dose in an artery wall from an intravascular brachytherapy 32P source. Problem 4 was modeled to investigate the response of a four-element TLD-albedo personal dosimeter from neutrons and/or photons. Significant differences in neutron response with S(a,b) cross sections compared to results without these cross sections were found. Problem 5 was modeled to obtain air kerma backscatter profiles for 150 and 200 kVp X-rays upon a water phantom. Air kerma backscatter profiles were determined along the apothem and diagonal of the front face of the phantom. A comparison of experimental results is also made. Problem 6 was modeled to determine indirect spectral and energy fluences upon two neutron detectors within a calibration bunker. The largest indirect contribution was found to come from low energy neutrons with an average angle of 47o where 0o is a plane parallel to the floor. Problem 7 was modeled to obtain pulse height distributions for a germanium detector. Comparison of analytically derived peaks with peak positions in the spectra are made. An examination of the Doppler broadening feature is also included.

Laser-driven particle acceleration is an area of increasing research interest given the recent development of short pulse high intensity lasers. A significant difficulty in this field is given by the exceptionally large instantaneous dose rates which such particle beams can produce. This represents a challenge for standard dosimetry techniques and more sophisticated procedures need to be explored. In this thesis I present novel detection and characterisation methods using a combination of GafChromic films, TLD chips, nuclear activation and Monte Carlo simulations, applicable to laser-driven beams. Part of the work is focused on the detection of laserdriven protons used to irradiate V79 cells in order to determine the feasibility of laser-driven proton therapy. A dosimetry method involving GafChromic films and numerical simulations has been appositely developed and used to obtain cell survival results, which are in agreement with those obtained by conventionally accelerated proton beams. Another part is dedicated to the detection and characterisation of laser-driven electron and X-ray beams. An innovative simulation method to obtain the temperature of the electrons accelerated by the laser, and predict the subsequently generated X-ray beam, has been developed and compared with the acquired experimental data.

The measurement of radiation dose in radiotherapy is vital in ensuring the accuracy of treatments. As more advanced techniques using protons and ions emerge, they pose challenges to ensure the same level of accuracy of dosimetry is achieved as for conventional X-ray radiotherapy. A relatively new method of particle acceleration using ultra-high intensity lasers and thin metallic targets has sparked a large effort to investigate the possible application of this technology in radiotherapy, which in turn requires accurate methods of dosimetry to be carried out and is the main motivation for this work. Accurate dosimetry was initially performed here using an air ionisation chamber, various models of GafChromic film and a PMMA phantom in 15 and 29 MeV protons and 38 MeV \(\alpha\)-particles from the Birmingham cyclotron. In developing an accurate protocol for absorbed dose-to-water at these relatively low proton energies, new data was generated on the proton energy response of GafChromic films. This enabled accurate dosimetry of a prototype laser-particle source, and provided improvements to a method of spectroscopic measurement in the resultant mixed field of multi-energy protons, electrons and X-rays. Monte Carlo simulations using MCNPX but mainly FLUKA were performed throughout to support and verify experimental measurements.

There have been developments in radiation therapy treatment techiques, which lead to an increase in the complexity of these treatments. The aim is to deliver highly conformal three-dimensional (3D) dose distributions, such as stereotactic radiosurgery (SRS). Polymer gel dosimetry offers three-dimensional (3D) dosimetry techniques for dose verification of dose distributions. Nisopropyl- acrylamide (NIP AM) polymer gel was the latest to develop and can be prepared under a normal atmospheric environment and has lower toxicity compared with the highly toxic polymer gels used earlier. NIPAM polymer gel using X-ray computed tomography (CT) was experimentally investigated in terms of its X-ray CT dose response, sensitivity and dose resolution. The effect of radiation beam type, radiation beam energy and radiation beam dose rate on X-ray CT dose response have also been studied. The temporal stability of NIP AM polymer gel has been examined over several days post-irradiation. The change in the polymer gel dosimeter's physical and electron densities as a function of absorbed dose was also investigated. In ,this study two new prototype phantoms were designed and constructed for imaging and irradiation of polymer gel dosimeters to provide simplicity and practicality for clinical dosimetry. The dosimetric and water equivalence properties of four NIP AM based polymer gel dosimeter formulations have been studied by examining their physical properties, interaction probability, radiation transport parameters and performing Monte Carlo modelling of depth doses. NIP AM polymer gel dosimeter irradiated at different doses using 6 Me V photon beam and 400 MU min-1 dose rate were found to have higher CT dose response (up to 37.8% at 10 Gy dose point) than results reported in the literature for NIP AM gel using similar concentration. The CT dose sensitivity of NIPAM polymer gel was found to be 0.405±0.014 H Gi1 , which is 26.2% higher than the reported sensitivity of 0.32l±0.008 H Gy-l with similar NIPAM gel concentration. The maximum change in physical density as a function of absorbed dose for polymer gel dosimeters was found to be up to ~1.0% for an absorbed dose of 20 Gy. 111

Evidence that radiation-related cardiovascular disease and second primary cancers can occur in cancer survivors following radiation therapy (RT) has emerged from several independent sources. Cardiotoxicity and second cancers are of particular concern for patients with good prognosis, such as those with Hodgkin lymphoma (HL). HL patients are among the youngest to receive RT, which means that those who are cured of their cancer have decades-long natural life-expectancies during which treatment-related long-term toxicities may cause years of excess morbidity or premature mortality. A considerable amount of research has been conducted to investigate the risk of radiation-related cardiotoxicity and second cancers. However, there are still substantial gaps in knowledge. It is therefore important to improve our understanding regarding these risks and develop treatment approaches and survivorship care to minimise their impact on patients' quality of life. In this thesis, I have investigated the risk of congestive heart failure (CHF) in a cohort of 2619 HL survivors and presented, for the first time, dose-response relationships for risk of CHF versus cardiac radiation doses. I also validated the radiation dosimetry method used to estimate the cardiac doses in this study as well as for other reconstruction methods, versus a gold standard based on the patients' own computed tomography scans. Additionally, I investigated what effect the dose reconstruction errors had on the dose-response relationships. I then focused on modern RT methods and specifically on proton RT. Based on published dose-response relationships (including that developed in this thesis) I predicted cardiovascular and second cancer risks for patients treated with advanced RT. This thesis has provided new knowledge in the study of late effects in HL patients who were treated decades ago as well as for patients treated more recently with advanced RT methods. The results here can be used to facilitate progress towards personalised RT in terms of choosing the appropriate RT method by integrating individualised risk prediction in advanced RT treatment planning. The research here provides the basis for further work towards evidence-based case selection for HL patients for the first NHS proton therapy centres in the UK, opening in 2018-2021.

As the world's nuclear reactors approach the end of their originally planned lifetimes and seek license extensions, which would allow them to operate for another 20 years, accurate information regarding neutron radiation exposure is more important than ever. Structural components such as the reactor pressure vessel (RPV) become embrittled by neutron irradiation, reducing their capability to resist crack growth and increasing the risk of catastrophic failure. The current dosimetry approaches used in these high flux environments do not provide real-time information. Instead, radiation dose is calculated using computer simulations, which are checked against dose readings that are only available during refueling once every 1.5-2 years. These dose readings are also very expensive, requiring highly trained technicians to handle radioactive material and operate specialized characterization equipment. This dissertation describes the development of a novel neutron radiation dosimeter based on carbon nanotubes (CNTs) that not only provides accurate real-time dosimetry, but also does so at very low cost, without the need for complex instrumentation, highly trained operators, or handling of radioactive material. Furthermore, since this device is based on radiation damage rather than radioactivation, its readings are time-independent, which is beneficial for nuclear forensics. In addition to development of a novel dosimeter, this work also provides insight into the particularly under-investigated topic of the effects of neutron irradiation of carbon nanotubes. This work details the fabrication and characterization of carbon nanotube based neutron and gamma radiation dosimeters. They consist of a random network of CNTs, sealed under a layer of silicon dioxide, spanning the gap between two electrodes to form a conductive path. They were fabricated using conventional wafer processing techniques, making them intrinsically scalable and ready for mass production. Electrical properties were measured before and after irradiation at several doses, demonstrating a consistent repeatable trend that can be effectively used to measure dose. Changes to the microstructure were investigated using Raman spectroscopy, which confirmed that the changes to electrical properties are due to increasing defect concentration. The results outlined in this dissertation will have significant impacts on both the commercial nuclear industry and on the nanomaterials scientific community. The dosimeter design has been refined to the point where it is nearly ready to be deployed commercially. This device will significantly improve accuracy of RPV lifetime assessment while at the same time reducing costs. The insights into the behavior of CNTs in neutron and gamma radiation environments is of great interest to scientists and engineers studying these nanomaterials.
Ph. D.

Exposures to ionising radiation resulting from natural sources or medical diagnostics are generally very low. In contrast, exposures to therapeutic radiation, although, they are often partial exposures, represent much higher doses. Similar levels of exposure may also occur as a consequence of a radiological accident, where it would be necessary to quickly separate individuals requiring urgent medical attention from the “worried-well”. The well-established biodosimetry techniques based on cytogenetics, particularly scoring dicentric chromosomes, are accurate and sensitive, yet, they are unsuitable for mass screening due to limited capacity and the time required for providing dose estimates. Measuring gene expression changes following radiation exposure was suggested over a decade ago to be an alternative method for dose estimation, as it is a quick, sensitive and suitable technique for high throughput application. The qPCR protocol was extensively optimised for increased reproducibility and sensitivity in order to be suitable for biodosimetry purposes. Radiation-responsive transcripts were identified and characterised in terms of temporal- and dose-responses. Finally, candidate transcripts were validated in human blood irradiated ex vivo and in vivo in blood samples obtained from cancer patients undergoing radiotherapy treatment. The data generated here serve as a proof of principle that qPCR-based gene expression assays can be used for radiation biodosimetry purposes to aid classical cytogenetics tools in an event of mass causality.

Recent events have underscored the need for the United States government to provide streamlined emergency response procedures and subsequent dose estimations for personnel responding to incidents involving radioactive material. Indeed, the National Council on Radiation Protection and Measurements Report No. 138 (NCRP 2001) indicates that exposures received by first responders will be important for a number of reasons, including planning for the appropriate use of key personnel in an extended emergency situation. In response, the Department of Homeland Security has published Protective Action Guides (DHS 2006) to help minimize these exposures and associated risks. This research attempts to provide some additional radiological exposure knowledge so that an Incident Commander, with limited or no information, can make more informed decisions about evacuation, sheltering-in-place, relocation of the public, turn-back levels, defining radiation hazard boundaries, and in-field radiological dose assessments of the radiation workers, responders, and members of the public. A method to provide such insight begins with providing a model that describes the physics of radiation interactions, radiation source and geometry, collection of field measurements, and interpretation of the collected data. A Monte Carlo simulation of the model is performed so that calculated results can be compared to measured values. The results of this investigation indicate that measured organ absorbed doses inside a tissue equivalent phantom compared favorably to the derived organ absorbed doses measured by the Panasonic thermoluminescence dosimeters and with Monte Carlo ‘N’ Particle modeled results. Additionally, a Victoreen 450P pressurized ion chamber measured the integrated dose and these results compared well with the Panasonic right lateral TLD. This comparison indicates that the Victoreen 450P ionization chamber could potentially serve as an estimator of real-time effective dose and organ absorbed dose, if energy and angular dependence corrections could be taken into account. Finally, the data obtained in this investigation indicate that the MCNP model provided a reasonable method to determine organ absorbed dose and effective dose of a simulated Radiological Dispersal Device in an Inferior-Superior geometry with Na99mTcO4 as the source of radioactive material.

Diamond has long been the material of interest for radiotherapy dosimetry due to its high sensitivity, radiation hardness and near tissue equivalency. However natural diamond detector has not become a popular choice because of variability among detectors, high cost and response dependence on dose rate. The recent success in synthesizing single crystal diamond has reignited the interest. Synthetic diamond is highly reproducible in purity and electrical properties, combined with small size, it is a suitable candidate for small field dosimetry. A newly available synthetic single crystal diamond detector is being studied to determine the basic dosimetric characteristic and applicability in small field dosimetry. A series of measurements were made in comparison with a 0.125c.c ionization chamber, and two diode detectors. Response of the diamond detector is independent on dose, dose rate and energy. The output factors of small fields determined by the diamond detector is lower than that of the diode detectors and higher than that of the ionization chamber which are known to over response and under response respectively. In percentage depth dose and beam profile measurements, the diamond detector performs similarly with the two diode detectors. It is found that the diamond detector is suitable for small field relative dosimetry. Further investigation is required to study the spatial resolution of the diamond detector in different measurement geometry and the suitability in determining percentage depth dose in the buildup region.
published_or_final_version
Diagnostic Radiology
Master
Master of Medical Sciences

Contemporary radiotherapy focuses on achieving the best patient outcomes by delivering highly targeted treatments that often include small fields and high dose gradients. Plastic scintillators outperform traditional dosimeters in these fields as they are close to water-equivalent. However, the translation of scintillation dosimeters into the clinic has been limited by three roadblocks. The generation of Cerenkov radiation in an optic fibre irradiated by megavoltage radiation contaminates the scintillation signal. Two Cerenkov removal methods (spectral discrimination and air core) were found to be accurate in accounting for Cerenkov radiation and their clinical robustness was improved. The light readout system is often the limiting factor for the accuracy of scintillators. PMTs outperform camera-based systems, though their implementation for array dosimetry is complex. A novel system with a multianode PMT was constructed and enabled multiple light signals from an array to be simultaneously measured. Arrays of scintillation dosimeters are difficult to create due to the complex arrangement of detectors and their optical pathways. Two innovative approaches (square waveguides and 3D printing) were used to build prototype scintillation dosimeter arrays. These arrays showed that scintillation dosimeters can measure dose distributions with high spatial and temporal resolution. Addressing these roadblocks has enabled the clinical translation of scintillation dosimeters. In small field dosimetry, an air core dosimeter was used as a reference to calculate and predict correction factors for existing dosimeters. For brachytherapy, an array of scintillators provided real-time dose measurements that improved the safety of the treatment. For rotational treatments, a cylindrical array was used to verify the dose delivered during simulated stereotactic treatments. Traditional dosimeters cannot be used in these applications and this demonstrates the potential of scintillation dosimetry.

A new thermoluminescence dosimetry system for environmental applications was tested, which used high sensitivity lithium fluoride (TLD-100H). The energy response of the bare thermoluminescence dosimeters (TLDs) was measured for photon beams with mean energies from 24 keV to 1.1 MeV, and the results were compared with standard lithium fluoride (TLD-100). The energy response was also measured for TLD-100H card-mounted dosimeters encapsulated in Teflon RTM, used as part of the Harshaw Type 8855 environmental dosimeter. The EGSnrc Monte Carlo system was used to calculate the dose to the TLDs in both the bare chip holder and the 8855 dosimeter, in order to calculate the thermoluminescence per unit of absorbed dose to the TLDs. The results were broadly consistent with existing data, with the response of both TLD materials correlating with the ionization density of the photon beams.

The aim of this study is to develop an intraoperative dose assessment procedure that can be performed after an I-125 prostate seed implantation, while the patient is still under anaesthesia. To accomplish this, we reconstruct the 3D position of each seed and co-register it with the prostate contour acquired with a transrectal ultrasound (TRUS) probe. Our seed detection method involves a tomosynthesis-based filtered reconstruction of the volume of interest requiring 7 projections acquired over an angle of 60o with an isocentric imaging system. The co-registration between the tomosynthesis-based seed positions and the TRUS-based prostate contour is based on the planned position. A phantom and a clinical study (25 patients) were carried out to validate the technique. In the patient study, the automatic tomosynthesis-based reconstruction yields a seed detection rate of 96.7% and less than 2.6% false-positive. The seed localization error obtained with a phantom study is 0.4 ± 0.4 mm. The co-registration method based on planned seed position has proved to be not accurate enough for dosimetric purposes. We believe that this technique may be used to discover considerable underdosage and to improve the dosimetric coverage by potentially reimplanting additional seeds.
L'objectif de ce projet est de développer une procédure d'évaluation dosimétrique intra-opératoire en implantation prostatique de grains d'iode 125. Pour y arriver, la position 3D des grains doit être reconstruite et recalée avec les contours de la prostate imagée en échographie endorectale. La reconstruction des grains est basée sur une technique de tomosynthèse requérant 7 projections acquises entre -30o et 30o. Le recalage entre la position 3D des grains et les contours utilise comme cible la position planifiée des grains. Notre technique de reconstruction dosimétrique a été testée sur un mannequin et dans une étude clinique incluant 25 patients. Notre méthode permet de reconstruire la position 3D des grains avec une précision de 0.4 ± 0.4 mm. De plus, l'étude clinique a démontré un taux de détection de 96.7% des grains et incluant moins de 2.6% de faux-positifs. La méthode de recalage n'a pas permis d'atteindre une précision acceptable pour une application clinique. La technique développée permet de repérer la présence de sous-dosage considérable et ouvre la porte vers la réimplantation de grains additionnels afin d'améliorer la couverture dosimétrique de la prostate.

Use of composite non-uniform radiation fields, which consist of a multitude of small fields, is very common in modern radiotherapy techniques. The conventional reference dosimetry protocols, however, use a 10 × 10 cm2 field as the reference machine calibration condition. The purpose of this work is to develop new, direct absorbed dose calibration methods for modern radiotherapy techniques that use static and composite nonstandard fields. An IAEA-AAPM international working group [Med. Phys. 35:5179–5186 (2008)] proposed a new formalism and introduced two intermediate fields, machine specific reference (msr) field fmsr and plan-class specific reference (pcsr) field fpcsr, for reference dosimetry of static and composite nonstandard fields, respectively. In the new formalism, correction factors which account for the difference in chamber calibration conditions between the reference field and msr field k^fmsr,fref_Qmsr,Q , pcsr field k^fpcsr,fref_Qpcsr,Q or clinical field k^fclin,fref_Qclin,Q were defined. This thesis focuses on the characterization of these correction factors. The dosimetry techniques to accurately measure the absorbed dose to water in nonstandard fields were established using four different radiation detectors, for which collecting volumes are radiologically water-equivalent. The characteristics of each radiation detector response were thoroughly investigated. Dose measurementin a nonstandard field normalized to that in the reference 10 × 10 cm2 field can be performed with an uncertainty of 0.2–0.3% when the dose distribution in the reference measurement region is homogeneous. Correction factors k^fmsr,fref_Qmsr,Q and k^fpcsr,fref_Qpcsr,Q were measured for one static nonstandard field and two different composite nonstandard fields, respectively, using different types of air-filled ionization chambers. Using the established dosimetry techniques, the k^fpcsr,fref_Qpcsr,Q were measured for different composite nonstandard fields which deliver various dose distributions in the reference measurement region. This work proved that the values of k^fpcsr,fref_Qpcsr,Q depend on the dose heterogeneity over the chamber collecting volume. Based on the measurement results, guidelines were suggested to select a new intermediate field for reference dosimetry of composite nonstandard fields. Finally, the IAEA-AAPM new formalism with values of k^fclin,fref_Qclin,Q obtained by experiments and MC methods was applied to reference dose measurement of clinical composite nonstandard fields using a calibrated air-filled ionization chamber. The corrected measured dose for each clinical field was compared with dose calculated using clinical treatment planning software or Monte Carlo methods. It was found that the accurate positioning of the reference detector and air-filled ionization chamber becomes more important when the dose heterogeneity in the reference measurement region increases. In conclusion, this thesis provides a method for accurate dose measurements in static and composite nonstandard fields. This work will help pave the way to improve the dosimetric consistency in these dynamic modern radiotherapy techniques.
L'utilisation de champs de rayonnement composes non uniformes, qui consistent en une multitude de petits champs, est tres commune dans les techniques modernes de radiotherapie. Cependant, les protocoles de dosimetrie de reference conventionnels utilisent un champ standard de 10×10 cm2 pour calibrer les appareils. Le but de ce travail est de developper de nouvelles methodes de calibration de la dose absorbee pour des techniques modernes de radiotherapie, ce en utilisant autant des champs statiques que des champs composes non standards. Le groupe de travail AIEA-AAPM a propose un nouveau formalisme qui introduit deux champs intermediaires, soient le champ specifique a l'appareil (fmsr) et le champ specifique au plan de traitement (fpcsr), ce pour la dosimetrie de reference des champs statiques et des champs composes non standards, respectivement. Dans ce nouveau formalisme, des facteurs de corrections ontete definis afin de tenir compte des conditions de calibration de la chambre qui different entre le champ de reference et les champs fmsr, fpcsr ainsi que les champs cliniques (fclin). Ces facteurs sont respectivement d´efinis ainsi: k^fmsr,fref_Qmsr,Q , k^fpcsr,fref_Qpcsr,Q et k^fclin,fref_Qclin,Q . Cette these comporte sur la caracterisation exprimentale de ces facteurs de correction. Les techniques de dosimetrie visant a mesurer precisement la dose absorbe dans l'eau pour des champs non standards ont ete etablies en utilisant quatre differents detecteurs de radiation, chacun ayant un volume sensible radiologiquement equivalent a l'eau. Les caracteristiques de chaque detecteur ont ete approfondies. Les mesures de dose dans un champ non standard normalise a un champ de reference de 10×10 cm2 peuvent etre obtenues avec une incertitude de 0.2-0.3% lorsque la distribution de dose dans la region de mesure de reference est homogene. Les facteurs de correction k^fmsr,fref_Qmsr,Q et k^fpcsr,fref_Qpcsr,Q ont ete mesures pour un champ statique non standard et pour deux differents champs composes non standards, respectivement, en utilisant differents types de chambres d'ionisation a air. En utilisant les techniques de dosimetries etablies, les k^fpcsr,fref_Qpcsr,Q ont ete mesures pour plusieurs champs composes non standards qui produisent diff´erentes distributions de dose dans la region de mesure de reference. Ce travail demontre que les valeurs de k^fpcsr,fref_Qpcsr,Q d´ependent de l'heterogeneite de la dose dans le volume sensible de la chambre. Base sur les resultats des mesures, des lignes de conduite sont suggereespour determiner un champ intermediaire necessaire a la dosimetrie de reference des champs composes non standards. Finalement, le nouveau formalisme de l'AIEA-AAPM a ete applique a des mesures de dose de reference de champs composes non standards cliniques avec les valeurs k^fclin,fref_Qclin,Q obtenues experimentalement et avec des methodes Monte Carlo pour une chambre d'ionisation a air etalonnee. La dose mesuree et corrigee pourchacun des champs a ete comparee avec la dose calculee en utilisant un logiciel de planification de traitement ou des methodes Monte Carlo. Il a ete determine que la precision du positionnement du detecteur de reference ainsi que celui de la chambre d'ionisation a air devient plus important lorsque l'heterogeneite de dose dans la regionde mesure augmente. En conclusion, cette these fournit une methode precise de mesure de la dose absorbee pour des champs statiques et des champs compose non standards. Ce travail aidera a ameliorer la coherence des methodes dosimetrique appliquables aux techniques modernes de radiotherapie.

This thesis presents interdisciplinary, collaborative research in the field of synchrotron microbeam radiation therapy (MRT). Synchrotron MRT is an experimental radiotherapy technique under consideration for clinical use, following demonstration of efficacy in tumour-bearing rodent models with remarkable sparing of normal tissue. A high flux, X-ray beam from a synchrotron is segmented into micro-planar arrays of narrow beams, typically 25 μm wide and with peak-to-peak separations of 200 μm. The radiobiological effect of MRT and the underlying cellular mechanisms are poorly understood. The ratio between dose in the ‘peaks’of the microbeams to the dose in the ‘valleys’, between the microbeams, has strong biological significance. However, there are difficulties in accurately measuring the dose distribution for MRT. The aim of this thesis is to address elements of both the dosimetric and radiobiological gaps that exist in the field of synchrotron MRT. A method of film dosimetry and microdensitometry was adapted in order to measure the peak-to-valley dose ratios for synchrotron MRT. Two types of radiochromic film were irradiated in a phantom and also flush against a microbeam collimator on beamline BL28B2 at the SPring-8 synchrotron. The HD-810 and EBT varieties of radiochromic film were used to record peak dose and valley dose respectively. In other experiments, a dose build-up effect was investigated and the half value layer of the beam with and without the microbeam collimator was measured to investigate the effect of the collimator on the beam quality. The valley dose obtained for films placed flush against the collimator was approximately 0.25% of the peak dose. Within the water phantom, the valley dose had increased to between 0.7–1.8% of the peak dose, depending on the depth in the phantom. We also demonstrated, experimentally and by Monte Carlo simulation, that the dose is not maximal on the surface and that there is a dose build-up effect. The microbeam collimator did not make an appreciable difference to the beam quality. The measured values of peak-to-valley dose ratio were higher than those predicted by previously published Monte Carlo simulation papers. For the radiobiological studies, planar (560 Gy) or cross-planar (2 x 280 Gy or 2 x 560 Gy) irradiations were delivered to mice inoculated with mammary tumours in their leg, on beamline BL28B2 at the SPring-8 synchrotron. Immunohistochemical staining for DNA double strand breaks, proliferation and apoptosis was performed on irradiated tissue sections. The MRT response was compared to conventional radiotherapy at 11, 22 or 44 Gy. The results of the study provides the first evidence for a differential tissue response at a cellular level between normal and tumour tissues following synchrotron MRT. Within 24 hours of MRT to tumour, obvious cell migration had occurred into and out of irradiated zones. MRT-irradiated tumours showed significantly less proliferative capacity by 24 hours post-irradiation (P = 0.002). Median survival times for EMT-6.5 and 67NR tumour-bearing mice following MRT (2 x 560 Gy) and conventional radiotherapy (22 Gy) increased significantly compared to unirradiated controls (P < 0.0005). However, there was markedly less normal tissue damage from MRT than from conventional radiotherapy. MRT-treated normal skin mounts a more coordinated repair response than tumours. Cell-cell communication of death signals from directly irradiated, migrating cells, may explain why tumours are less resistant to high dose MRT than normal tissue.

Radiation therapy is an established modality in the treatment of tumours. With treatments ever evolving and increasing in terms of their complexities, the need arises to ensure the best quality treatment is delivered; the survival of the patient relies upon it. A modern treatment such as Intensity Modulated Radiation Therapy employs steep dose gradients varying dynamically to deliver complex dose profiles, whilst the experimental Microbeam Radiation Therapy (MRT) involves the delivery of an array of intense beams tens-of-microns wide separated by several hundred microns. In both cases, conventional dosimetry is inadequate in providing both spatial and temporal information about complex dose profiles.The silicon strip detector was created to fill this void in current dosimetry techniques. Designed to withstand the intense beam of a synchrotron wriggler x-rays whilst not significantly perturbing the beam, the detector provides linear sensitive volume elements two hundred microns in pitch. This enables the ability to perform high spatial resolution dosimetry in real time.This thesis investigates the use of the silicon strip detector as an on-line dosimetry system for MRT with applications to clinical radiotherapy. Of particular interest is the distribution and magnitude of energy deposition within the detector and the perturbative effect the strip detector has on a synchrotron wriggler x-ray beam.Monte Carlo simulations are performed to investigate the properties of radiation incident upon the detector. These seek to understand how a beam traversing the detector interacts with it, as well as the effects the detector has on the transmitted beam and its properties.The energy deposition spectrum within the detector was found to be predominant at low energies of below 100 keV. The deposition of dose through the detector was found to be largely constant with depth through the central axis of a beam, dropping to ~10-3 of the central value at 50 µm off the central beam axis for an infinitesimally thin pencil beam and ~10-4 at 100 µm off-axis. Energy deposition laterally through water was determined as dominated by secondary electrons from the beam-edge to 150 µm, and Compton photons thereafter.The depth dose of a MRT pencil beam was found to have an average decrease in dose of (1.44 ± 0.15) % (95% C.I.) when the strip detector was introduced into the beam. The probability of interaction of incident photons with the detector for the MRT spectrum was determined with GEANT4 and theoretically with a comparison made. The overall interaction probability of an MRT photon is (1.97 ± 4.43×10-4) % (95% C.I.).A simulation to determine the PVDR (peak-to-valley dose ratio) in a MRT field was created, however only the peak dose could be determined due to an inadequate primary photon count. The peak dose was found to decrease by 1.41 ± 0.03 % (95% C.I.). Qualitative film measurements (deliberate overexposure of peak regions) displayed an increase of valley dose to film at 10 mm in water with the strip detector in the beam, but no such phenomenon at a depth of 1 mm. A simplified GEANT4 simulation was created to replicate such results with only five beamlets. Peak-to-valley dose ratio calculations from the simulation show no discernible effect at 1 mm depth, but a discernible increase in the PVDR at 10 mm depth; replicating experimental results.Since charge collection across a semiconductor device is often complex and dynamically varies with the bias conditions. Ion beam induced charge collection (IBICC) studies seek to investigate the charge collection properties of the detector in various voltage-biasing conditions. It was found that the application of reverse bias to strips adjacent to that being read out reduced the effective sensitive volume of the read-out strip. This provides evidence for a proposal to incorporate biased guard-ring structures to prevent charge sharing, and improve the confinement of the sensitive volume.Finally, clinical irradiations are performed with a highly collimated orthovoltage x-ray beam down to beam sizes of hundreds of microns. The spatial resolution of the detector in this configuration was found to be 500 µm. The efficacy of the detector in contemporary radiotherapy is also investigated through the use of a 6 MV linear accelerator’s photon beam. Excellent agreement was found between strip detector read-outs and reference data for the linear accelerator. A quadratic relation was found between dose rate and charge per strip.