En radiothérapie, la tomodensitométrie (CT) fournit l’information anatomique du patient utile au calcul de dose durant la planification de traitement. Afin de considérer la composition hétérogène des tissus, des techniques de calcul telles que la méthode Monte Carlo sont nécessaires pour calculer la dose de manière exacte. L’importation des images CT dans un tel calcul exige que chaque voxel exprimé en unité Hounsfield (HU) soit converti en une valeur physique telle que la densité électronique (ED). Cette conversion est habituellement effectuée à l’aide d’une courbe d’étalonnage HU-ED. Une anomalie ou artefact qui apparaît dans une image CT avant l’étalonnage est susceptible d’assigner un mauvais tissu à un voxel. Ces erreurs peuvent causer une perte cruciale de fiabilité du calcul de dose. Ce travail vise à attribuer une valeur exacte aux voxels d’images CT afin d’assurer la fiabilité des calculs de dose durant la planification de traitement en radiothérapie. Pour y parvenir, une étude est réalisée sur les artefacts qui sont reproduits par simulation Monte Carlo. Pour réduire le temps de calcul, les simulations sont parallélisées et transposées sur un superordinateur. Une étude de sensibilité des nombres HU en présence d’artefacts est ensuite réalisée par une analyse statistique des histogrammes. À l’origine de nombreux artefacts, le durcissement de faisceau est étudié davantage. Une revue sur l’état de l’art en matière de correction du durcissement de faisceau est présentée suivi d’une démonstration explicite d’une correction empirique. / Computed tomography (CT) is widely used in radiotherapy to acquire patient-specific data for an accurate dose calculation in radiotherapy treatment planning. To consider the composition of heterogeneous tissues, calculation techniques such as Monte Carlo method are needed to compute an exact dose distribution. To use CT images with dose calculation algorithms, all voxel values, expressed in Hounsfield unit (HU), must be converted into relevant physical parameters such as the electron density (ED). This conversion is typically accomplished by means of a HU-ED calibration curve. Any discrepancy (or artifact) that appears in the reconstructed CT image prior to calibration is susceptible to yield wrongly-assigned tissues. Such tissue misassignment may crucially decrease the reliability of dose calculation. The aim of this work is to assign exact physical values to CT image voxels to insure the reliability of dose calculation in radiotherapy treatment planning. To achieve this, origins of CT artifacts are first studied using Monte Carlo simulations. Such simulations require a lot of computational time and were parallelized to run efficiently on a supercomputer. An sensitivity study on HU uncertainties due to CT artifacts is then performed using statistical analysis of the image histograms. Beam hardening effect appears to be the origin of several artifacts and is specifically addressed. Finally, a review on the state of the art in beam hardening correction is presented and an empirical correction is exposed in detail.

Pour analyser les images en tomodensitométrie, une méthode stœchiométrique est gé- néralement utilisée. Une courbe relie les unités Hounsfield d’une image à la densité électronique du milieu. La tomodensitométrie à double énergie permet d’obtenir des informations supplémentaires sur ces images. Une méthode stœchiométrique a été dé- veloppée pour permettre de déterminer les valeurs de densité électronique et de numéro atomique effectif à partir d’une paire d’images d’un tomodensitomètre à double énergie. Le but de cette recherche est de développer une nouvelle méthode d’identification de tissus en utilisant ces paramètres extraits en tomodensitométrie à double énergie. Cette nouvelle méthode est comparée avec la méthode standard de tomodensitométrie à simple énergie. Par ailleurs, l’impact dosimétrique de bien identifier un tissu est déterminé. Des simulations Monte Carlo permettent d’utiliser des fantômes numériques dont tous les paramètres sont connus. Les différents fantômes utilisés permettent d’étalonner les méthodes stœchiométriques, de comparer la polyvalence et la robustesse des méthodes d’identification de tissus double énergie et simple énergie, ainsi que de comparer les distributions de dose dans des fantômes uniformes de mêmes densités, mais de compo- sitions différentes. La méthode utilisant la tomodensitométrie à double énergie fournit des valeurs de densi- tés électroniques plus exactes, quelles que soient les conditions étudiées. Cette méthode s’avère également plus robuste aux variations de densité des tissus. L’impact dosimé- trique d’une bonne identification de tissus devient important pour des traitements aux énergies plus faibles, donc aux énergies d’imagerie et de curiethérapie. / A stoichiometric method is usually used to analyze computed tomography images. A curve links the Hounsfield units on the images to the electron density in a given me- dium. Dual-energy computed tomography gives additional information on a scan. A stoi- chiometric method was developed to acquire both electron density and effective atomic number from a pair of images. The aim of this research is to develop a new method to identify tissues using the parame- ters extracted from dual-energy computed tomography. This new method is compared to the standard single-energy computed tomography segmentation method. Furthermore, the effect of correctly assigning tissues on dose distribution is studied. Monte Carlo simulations allow the use of perfectly known numerical phantoms. Dif- ferent phantoms allowed the calibration of the stoichiometric methods, the comparison of the versatility and the robustness of the dual-energy and the single-energy methods, and the comparison of dose distribution in phantoms of same densities, but of different compositions. The dual-energy identification method gives more accurate values of electron density in any studied condition. This method is also more robust to tissues of variable density. The dosimetric impact of an accurate identification becomes more important for treatments using lower energy photons, such as imaging energies and brachytherapy.

Le cancer pulmonaire est la principale cause de décès parmi tous les cancers au Canada. Le pronostic est généralement faible, de l'ordre de 15% de taux de survie après 5 ans. Les déplacements internes des structures anatomiques apportent une incertitude sur la précision des traitements en radio-oncologie, ce qui diminue leur efficacité. Dans cette optique, certaines techniques comme la radio-chirurgie et la radiothérapie par modulation de l'intensité (IMRT) visent à améliorer les résultats cliniques en ciblant davantage la tumeur. Ceci permet d'augmenter la dose reçue par les tissus cancéreux et de réduire celle administrée aux tissus sains avoisinants. Ce projet vise à mieux évaluer la dose réelle reçue pendant un traitement considérant une anatomie en mouvement. Pour ce faire, des plans de CyberKnife et d'IMRT sont recalculés en utilisant un algorithme Monte Carlo 4D de transport de particules qui permet d'effectuer de l'accumulation de dose dans une géométrie déformable. Un environnement de simulation a été développé afin de modéliser ces deux modalités pour comparer les distributions de doses standard et 4D. Les déformations dans le patient sont obtenues en utilisant un algorithme de recalage déformable d'image (DIR) entre les différentes phases respiratoire générées par le scan CT 4D. Ceci permet de conserver une correspondance de voxels à voxels entre la géométrie de référence et celles déformées. La DIR est calculée en utilisant la suite ANTs («Advanced Normalization Tools») et est basée sur des difféomorphismes. Une version modifiée de DOSXYZnrc de la suite EGSnrc, defDOSXYZnrc, est utilisée pour le transport de particule en 4D. Les résultats sont comparés à une planification standard afin de valider le modèle actuel qui constitue une approximation par rapport à une vraie accumulation de dose en 4D. / Pulmonary cancer is the main cause of death amongst all cancers in Canada with a prognosis of about 15% survival rate in 5 years. The efficiency of radiotherapy treatments is lower when high displacements of the tumors are observed, mostly caused by intrafraction respiratory motion. Advanced techniques such as radiosurgery and intensity-modulated radiotherapy treatments (IMRT) are expected to provide better clinical results by delivering higher radiation doses to the tumor while sparing the surrounding healthy lung tissues. The goal of this project is to perform 4D Monte Carlo dose recalculations to assess the dosimetric impact of moving tumors in CyberKnife and IMRT treatments using dose accumulation in deforming anatomies. Scripts developed in-house were used to model both situations and to compare the Monte Carlo dose distributions with those obtained with standard clinical plans. Displacement vectors fields are obtained from a 4D CT data set and a deformable image registration (DIR) algorithm which allows a voxel-to-voxel correspondence between each respiratory phase. The DIR is computed by the Advanced Normalization Tools (ANTs) software and is mostly based on diffeormophisms. A modified version of DOSXYZnrc from EGSnrc software, defDOSXYZnrc, is used to transport radiation through non-linear geometries. These results are then compared to a typical 3D plan to determine whether or not the current planification is a good approximation of the true 4D dose calculation.

No description available.

<p>Traditional dosimetric devices are inherently point dose dosimeters (PDDs) and can only measure the magnitude of the radiation exposure; hence, they are one-dimensional (1D). To measure the magnitude and spatial location of dose within a volume either several PDDs must be used at one time, or one PDD must be translated from point-to-point. Using PDDs for spatially distributed, two-dimensional (2D), dosimetry is laborious, time consuming, limited in spatial resolution, susceptible to positioning errors, and the currently accepted approach to measuring dose distribution in 2D. This work seeks to expand the current limits of indirectly ionizing radiation dosimetry by using radiochromic film (RCF) for a high-resolution, accurate dosimetry system. Using RCF will extend the current field of radiation dosimetry to spatially quantitative 2D and three-dimensional (3D) measurements. </p> <p>This work was generalized into two aims. The first aim was the development of the RCF dosimetry system; it was accomplished by characterizing the film and the readout devices and developing a method to calibrate film response for absolute dose measurements. The second aim was to apply the RCF dosimetry system to three areas of dosimetry that were inherently volumetric and could benefit from multiple dimensional (2D or 3D) dose analysis. These areas were representative of a broad range of radiation energy levels and were: low-mammography, intermediate-computed tomography (CT), and high-radiobiologcal small animal irradiation and cancer patient treatment verification. The application of a single dosimeter over a broad range of energy levels is currently unavailable for most traditional dosimeters, and thus, was used to demonstrate the robustness and flexibility of the RCF dosimetry system.</p> <p>Two types of RCF were characterized for this work: EBT and XRQA film. Both films were investigated for: radiation interaction with film structure; light interaction with film structure for optimal film readout (densitometry) sensitivity; range of absorbed dose measurements; dependence of film dose measurement response as a function of changing radiation energy; fractionation and dose rate effects on film measurement response; film response sensitivity to ambient factors; and stability of measured film response with time. EBT film was shown to have the following properties: near water equivalent atomic weight (Z_eff); dynamic dose range of (10<super>-1</super>-10<super>2</super>) Gy; 3% change in optical density (OD) response for a single exposure level when exposed to radiation energies from (75-18,000) kV; and best digitized using transmission densitometry. XRQA film was shown to have: a Zeff of ~25; a 12 fold increase in sensitivity at lower photon energies for a dynamic dose range of 10-3-100 Gy, a difference of 25% in OD response when comparing 120 kV to 320 kV, and best digitized using reflective densitometry. Both XRQA and EBT films were shown to have: a temporal stability (&#916;OD) of ~1% for t > 24 hr post film exposure for up to ~20 days; a change in dose response of ~0.03 mGy hr-1 when exposed to fluorescent room lighting at standard room temperature and humidity levels; a negligible dose rate and fractionation effect when operated within the optimal dose ranges; and a light wavelength dependence with dose for film readout.</p> <p>The flat bed scanner was chosen as the primary film digitizer due to its availability, cost, OD range, functionality (transmission and reflection scanning), and digitization speed. As a cost verses functionality comparison, the intrinsic and operational limitations were determined for two flat bed scanners. The EPSON V700 and 10000XL exhibited equal spatial and OD accuracy. The combined precision of both the scanner light sources and CCD sensors measured < 2% and < 7% deviation in pixel light intensities for 50 consecutive scans, respectively. Both scanner light sources were shown to be uniform in transmission and reflection scan modes along the center axis of light source translation. Additionally, RCFs demonstrated a larger dynamic range in pixel light intensities, and to be less sensitive to off axis light inhomogeneity, when scanned in landscape mode (long axis of film parallel with axis of light source translation). The EPSON 10000XL demonstrated slightly better light source/CCD temporal stability and provided a capacity to scan larger film formats at the center of the scanner in landscape mode. However, the EPSON V700 only measured an overall difference in accuracy and precision by 2%, and though smaller in size, at the time of this work, was one sixth the cost of the 10000XL. A scan protocol was developed to maximize RCF digitization accuracy and precision, and a calibration fitting function was developed for RCF absolute dosimetry. The fitting function demonstrated a superior goodness of fit for both RCF types over a large range of absorbed dose levels as compared to the currently accepted function found in literature.</p> <p>The RCF dosimetry system was applied to three novel areas from which a benefit could be derived for 2D or 3D dosimetric information. The first area was for a 3D dosimetry of a pendant breast in 3D-CT mammography. The novel method of developing a volumetric image of the breast from a CT acquisition technique was empirically measured for its dosimetry and compared to standard dual field digital mammography. The second area was dose reduction in CT for pediatric and adult scan protocols. In this application, novel methodologies were developed to measure 3D organ dosimetry and characterize a dose reduction scan protocol for pediatric and adult body habitus. The third area was in the field of small animal irradiation for radiobiology purposes and cancer patient treatment verification. Two methods for small animal irradiation were analyzed for their dosimetry. The first technique was within a gamma irradiator environment using a <super>137</super>Cs source (663 keV), and the second, a novel approach to mouse irradiation, was developed for fast neutron (10 MeV) irradiated by a Tandem Van de Graff accelerator in a <super>2</super>H(d,n)<super>3</super>He reaction. For the patient cancer treatment, RCF was used to verify a 3D radiochromic plastic, PRESAGETM, using multi-leaf collimation (MLC) on a medical linear accelerator (LINAC) with 6 MV x-rays. The RCF and PRESAGE<super>TM</super> dosimeters were employed to verify a simple respiratory-gated lung treatment for a small nodule; the film was considered the gold standard. In every case, the RCF dosimetry system was verified for accuracy using a traditional PDD as the golden standard. When considering all areas of radiation energy applications, the RCF dosimetry system agreed to better than 7% of the golden standard, and in some cases within better than 1%. In many instances, this work provided vital dosimetric information that otherwise was not captured using the PDD in similar geometry. This work demonstrates the need for RCF to more accurately measure volumetric dose.</p> / Dissertation

En radiothérapie, la tomodensitométrie (CT) fournit l’information anatomique du patient utile au calcul de dose durant la planification de traitement. Afin de considérer la composition hétérogène des tissus, des techniques de calcul telles que la méthode Monte Carlo sont nécessaires pour calculer la dose de manière exacte. L’importation des images CT dans un tel calcul exige que chaque voxel exprimé en unité Hounsfield (HU) soit converti en une valeur physique telle que la densité électronique (ED). Cette conversion est habituellement effectuée à l’aide d’une courbe d’étalonnage HU-ED. Une anomalie ou artefact qui apparaît dans une image CT avant l’étalonnage est susceptible d’assigner un mauvais tissu à un voxel. Ces erreurs peuvent causer une perte cruciale de fiabilité du calcul de dose. Ce travail vise à attribuer une valeur exacte aux voxels d’images CT afin d’assurer la fiabilité des calculs de dose durant la planification de traitement en radiothérapie. Pour y parvenir, une étude est réalisée sur les artefacts qui sont reproduits par simulation Monte Carlo. Pour réduire le temps de calcul, les simulations sont parallélisées et transposées sur un superordinateur. Une étude de sensibilité des nombres HU en présence d’artefacts est ensuite réalisée par une analyse statistique des histogrammes. À l’origine de nombreux artefacts, le durcissement de faisceau est étudié davantage. Une revue sur l’état de l’art en matière de correction du durcissement de faisceau est présentée suivi d’une démonstration explicite d’une correction empirique. / Computed tomography (CT) is widely used in radiotherapy to acquire patient-specific data for an accurate dose calculation in radiotherapy treatment planning. To consider the composition of heterogeneous tissues, calculation techniques such as Monte Carlo method are needed to compute an exact dose distribution. To use CT images with dose calculation algorithms, all voxel values, expressed in Hounsfield unit (HU), must be converted into relevant physical parameters such as the electron density (ED). This conversion is typically accomplished by means of a HU-ED calibration curve. Any discrepancy (or artifact) that appears in the reconstructed CT image prior to calibration is susceptible to yield wrongly-assigned tissues. Such tissue misassignment may crucially decrease the reliability of dose calculation. The aim of this work is to assign exact physical values to CT image voxels to insure the reliability of dose calculation in radiotherapy treatment planning. To achieve this, origins of CT artifacts are first studied using Monte Carlo simulations. Such simulations require a lot of computational time and were parallelized to run efficiently on a supercomputer. An sensitivity study on HU uncertainties due to CT artifacts is then performed using statistical analysis of the image histograms. Beam hardening effect appears to be the origin of several artifacts and is specifically addressed. Finally, a review on the state of the art in beam hardening correction is presented and an empirical correction is exposed in detail.

Durant la dernière décennie, les développements technologiques en radiothérapie ont transformé considérablement les techniques de traitement. Les nouveaux faisceaux non standard améliorent la conformité de la dose aux volumes cibles, mais également complexifient les procédures dosimétriques. Puisque des études récentes ont démontré l’invalidité de ces protocoles actuels avec les faisceaux non standard, un nouveau protocole applicable à la dosimétrie de référence de ces faisceaux est en préparation par l’IAEA-AAPM. Le but premier de cette étude est de caractériser les facteurs responsables des corrections non unitaires en dosimétrie des faisceaux non standard, et ainsi fournir des solutions conceptuelles afin de minimiser l’ordre de grandeur des corrections proposées dans le nouveau formalisme de l’IAEA-AAPM. Le deuxième but de l’étude est de construire des méthodes servant à estimer les incertitudes d’une manière exacte en dosimétrie non standard, et d’évaluer les niveaux d’incertitudes réalistes pouvant être obtenus dans des situations cliniques. Les résultats de l’étude démontrent que de rapporter la dose au volume sensible de la chambre remplie d’eau réduit la correction d’environ la moitié sous de hauts gradients de dose. Une relation théorique entre le facteur de correction de champs non standard idéaux et le facteur de gradient du champ de référence est obtenue. En dosimétrie par film radiochromique, des niveaux d’incertitude de l’ordre de 0.3% sont obtenus par l’application d’une procédure stricte, ce qui démontre un intérêt potentiel pour les mesures de faisceaux non standard. Les résultats suggèrent également que les incertitudes expérimentales des faisceaux non standard doivent être considérées sérieusement, que ce soit durant les procédures quotidiennes de vérification ou durant les procédures de calibration. De plus, ces incertitudes pourraient être un facteur limitatif dans la nouvelle génération de protocoles. / During the past decade, technological developments in radiation therapy have considerably transformed treatment techniques. Novel nonstandard beams improve target dose conformity, but increase the complexity of dosimetry procedures. As recent studies demonstrated the invalidity of these protocols to nonstandard beams, a new protocol applicable to nonstandard beam reference dosimetry is in preparation by the IAEA-AAPM. The first goal of the study is to characterize the factors responsible for non-unity corrections in nonstandard beam dosimetry, and provide conceptual solutions to minimize the magnitude of the corrections. The second goal is to provide methods to estimate uncertainties accurately in nonstandard beam dosimetry, and estimate uncertainty levels achievable in typical clinical situations. Results of this study show that reporting dose to the sensitive volume of the chamber filled with water reduces the correction factor approximately by half under high gradients. A theoretical expression of correction factor is obtained for ideal nonstandard reference fields. In radiochromic film dosimetry, levels of uncertainty of the order of 0.3% are achieved with strict procedures and show great potential for nonstandard beam measurements. Results also suggest that experimental uncertainties in nonstandard beam are an important issue to consider both during daily QA routine and reference dosimetry, and could be a limiting factor in the new generation of protocols.

Raman spectroscopy is a form of vibrational spectroscopy that is capable of probing biological samples at a molecular level. In this work it was used in the analysis of ionizing radiation-induced damage in DNA. Spectra of both simple, short-stranded DNA oligomers (SS-DNA) and the more complicated calf-thymus DNA (CT-DNA) were acquired before and after irradiation to a variety of doses from 0 to ~2000 Gy. In a technique known as ultraviolet resonance Raman spectroscopy (UVRRS), three UV wavelengths of 248, 257 and 264 nm were utilized in order to selectively enhance contributions from different molecular groups within the samples. Assignment of the spectral peaks was aided by the literature, as well as through analysis of UVRR spectra of short strands of the individual DNA bases obtained at each of the three incident UV wavelengths. Difference spectra between the irradiated and unirradiated samples were calculated and the samples exposed to ~2000 Gy showed significant radiation-induced features. Intensity increases of spectral peaks, observed primarily in the CT-DNA, indicated unstacking of the DNA bases and disruption of Watson-Crick hydrogen bonds, while intensity decreases of spectral peaks, observed only in the SS-DNA, indicated both base damage and the loss of structural integrity of the DNA molecule. The high molecular specificity of UVRRS allowed for precise identification of the specific bonds affected by the radiation, and the use of the varying incident wavelengths allowed for the observation of damage to moieties that would otherwise have been excluded. The use of UVRRS shows promise in the study of radiation-induced damage to DNA and would be well suited for extension to the study of more complicated biological systems.

Image guided radiation therapy (IGRT) is a new type of radiotherapy used to deliver lethal doses of radiation to mobile tumors, while preventing surrounding healthy structures from receiving high doses of radiation. It relies on image guidance to track the tumor and ensure its prescribed position in the radiation beam. The main goal of this work was to determine if a new three-dimensional ultrasound (3D US) image guidance device, called the Restitu System, could safely replace (or be used interchangeably with) an existing method involving x-ray images of implanted fiducial markers (FMs) for prostate IGRT. Using comparison statistics called 95 % limits of agreement (LOA), it was found that the new 3D US system did not produce measurements that agreed sufficiently closely to those made using the FM technique, and therefore, could not safely replace FMs for prostate IGRT. Ultrasound image quality and user variability were determined to have a significant impact on the agreement between the two methods. It was further shown that using the Restitu System offered no significant clinical advantages over a conventional patient re-positioning technique.

The remarkable accuracy of Monte Carlo (MC) dose calculation algorithms has led to the widely accepted view that these methods should and will play a central role in the radiotherapy treatment verification and planning of the future. The advantages of using MC clinically are particularly evident for radiation fields passing through inhomogeneities, such as lung and air cavities, and for small fields, including those used in today's advanced intensity modulated radiotherapy techniques. Many investigators have reported significant dosimetric differences between MC and conventional dose calculations in such complex situations, and have demonstrated experimentally the unmatched ability of MC calculations in modeling charged particle disequilibrium. The advantages of using MC dose calculations do come at a cost. The nature of MC dose calculations require a highly detailed, in-depth representation of the physical system (accelerator head geometry/composition, anatomical patient geometry/composition and particle interaction physics) to allow accurate modeling of external beam radiation therapy treatments. To perform such simulations is computationally demanding and has only recently become feasible within mainstream radiotherapy practices. In addition, the output of the accelerator head simulation can be highly sensitive to inaccuracies within a model that may not be known with sufficient detail. The goal of this dissertation is to both improve and advance the implementation of MC dose calculations in modern external beam radiotherapy. To begin, a novel method is proposed to fine-tune the output of an accelerator model to better represent the measured output. In this method an intensity distribution of the electron beam incident on the model is inferred by employing a simulated annealing algorithm. The method allows an investigation of arbitrary electron beam intensity distributions and is not restricted to the commonly assumed Gaussian intensity. In a second component of this dissertation the design, implementation and evaluation of a technique for reducing a latent variance inherent from the recycling of phase space particle tracks in a simulation is presented. In the technique a random azimuthal rotation about the beam's central axis is applied to each recycled particle, achieving a significant reduction of the latent variance. In a third component, the dissertation presents the first MC modeling of Varian's new RapidArc delivery system and a comparison of dose calculations with the Eclipse treatment planning system. A total of four arc plans are compared including an oropharynx patient phantom containing tissue inhomogeneities. Finally, in a step toward introducing MC dose calculation into the planning of treatments such as RapidArc, a technique is presented to feasibly generate and store a large set of MC calculated dose distributions. A novel 3-D dyadic multi-resolution (MR) decomposition algorithm is presented and the compressibility of the dose data using this algorithm is investigated. The presented MC beamlet generation method, in conjunction with the presented 3-D data MR decomposition, represents a viable means to introduce MC dose calculation in the planning and optimization stages of advanced radiotherapy.