Proton therapy uses proton beams with energies of 70 – 230 MeV to treat cancerous tumours very effectively, while preserving surrounding healthy tissues as much as possible. During nuclear interactions of these protons with matter, secondary neutrons can be produced. These neutrons can have energies ranging up to the maximum energy of the protons and can thus be particularly difficult to attenuate. In fact, the rooms of a proton therapy facility are generally surrounded by concrete walls of at least ~2 m in thickness, in order to protect the members of the staff and the public from the stray radiation. Today, the design of the shielding walls is generally based on Monte Carlo simulations. Amongst the numerous parameters on which these simulations depend, some are difficult to control and are therefore selected in a conservative manner. Despite these conservative choices, it remains important to carry out accurate neutron dose measurements inside proton therapy facilities, in order to assess the effectiveness of the shielding and the conservativeness of the simulations. There are, however, very few studies in literature which focus on the comparison of such simulations with neutron measurements performed outside the shielding in proton therapy facilities. Moreover, the published measurements were not necessarily acquired with detectors that possess a good sensitivity to neutrons with energies above 20 MeV, while these neutrons actually give an important contribution to the total dose outside the shielding. A first part of this work was dedicated to the study of the energy response function of the WENDI-2, a rem meter that possesses a good sensitivity to neutrons of more than 20 MeV. The WENDI-2 response function was simulated using the Monte Carlo code MCNPX and validation measurements were carried out with 252Cf and AmBe sources as well as high-energy quasi-monoenergetic neutron beams. Then, WENDI-2 measurements were acquired inside and outside four rooms of the proton therapy facility of Essen (Germany). MCNPX simulations, based on the same conservative choices as the original shielding design simulations, were carried out to calculate the neutron spectra and WENDI-2 responses in the measurement positions. A relatively good agreement between the simulations and the measurements was obtained in front of the shielding, whereas overestimates by at least a factor of 2 were obtained for the simulated responses outside the shielding. This confirmed the conservativeness of the simulations with respect to the neutron fluxes transmitted through the walls. Two studies were then carried out to assess the sensitivity of the MCNPX simulations to the defined concrete composition and the selected physics models for proton and neutron interactions above 150 MeV. Both aspects were found to have a significant impact on the simulated neutron doses outside the shielding. Finally, the WENDI-2 responses measured outside the fixed-beam treatment room were also compared to measurements acquired with an extended-range Bonner Sphere Spectrometer and a tissue-equivalent proportional counter. A satisfactory agreement was obtained between the results of the three measurement techniques. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Radiotherapy delivered using scanned beams of protons enables greater conformity between the dose distribution and the tumour than conventional radiotherapy using X rays. However, the dose distributions are more sensitive to changes in patient anatomy, and tend to deteriorate in the presence of motion. Online dose calculation during treatment delivery offers a way of monitoring the delivered dose in real time, and could be used as a basis for mitigating the effects of motion. The aim of this work has therefore been to investigate how the computational power offered by graphics processing units can be harnessed to enable fast analytical dose calculation for online monitoring in proton therapy. The first part of the work consisted of a systematic investigation of various approaches to implementing the most computationally expensive step of the pencil beam algorithm to run on graphics processing units. As a result, it was demonstrated how the kernel superposition operation, or convolution with a spatially varying kernel, can be efficiently implemented using a novel scatter-based approach. For the intended application, this outperformed the conventional gather-based approach suggested in the literature, permitting faster pencil beam dose calculation and potential speedups of related algorithms in other fields. In the second part, a parallelised proton therapy dose calculation engine employing the scatter-based kernel superposition implementation was developed. Such a dose calculation engine, running all of the principal steps of the pencil beam algorithm on a graphics processing unit, had not previously been presented in the literature. The accuracy of the calculation in the high- and medium-dose regions matched that of a clinical treatment planning system whilst the calculation was an order of magnitude faster than previously reported. Importantly, the calculation times were short, both compared to the dead time available during treatment delivery and to the typical motion period, making the implementation suitable for online calculation. In the final part, the beam model of the dose calculation engine was extended to account for the low-dose halo caused by particles travelling at large angles with the beam, making the algorithm comparable to those in current clinical use. By reusing the workflow of the initial calculation but employing a lower resolution for the halo calculation, it was demonstrated how the improved beam model could be included without prohibitively prolonging the calculation time. Since the implementation was based on a widely used algorithm, it was further predicted that by careful tuning, the dose calculation engine would be able to reproduce the dose from a general beamline with sufficient accuracy. Based on the presented results, it was concluded that, by using a single graphics processing unit, dose calculation using the pencil beam algorithm could be made sufficiently fast for online dose monitoring, whilst maintaining the accuracy of current clinical systems.

The prompt gamma-ray timing (PGT) method offers a relatively simple approach for range verification in proton therapy. Starting from the findings of previous experiments, several steps toward a clinical application of PGT have been performed in this work. First of all, several scintillation materials have been investigated in the context of PGT. The time resolution was determined at high photon energies in the MeV-region. In conclusion, the fast and bright scintillator CeBr3 is the material of choice in combination with a timing photomultiplier tube as light detector. A second study was conducted at Universitäts Protonen Therapie Dresden (UPTD) to characterize the proton bunch structure of a clinical beam concerning its time width and relative arrival time. The data is mandatory as input for simulation studies and to correct for phase drifts. The obtained data could furthermore be used for the first 2D imaging of a heterogeneous phantom based on prompt gamma-rays. In a last step, a PGT prototype system was designed using the findings from the first two studies. The prototype system is based on a newly developed digital spectrometer and a CeBr3 detector. The device is characterized at the ELBE bremsstrahlung beam. It was verified that the prototype operates within the specifications concerning time and resolution as well as throughput rate. Finally, for the first time the PGT system was used under clinical conditions in the treatment room of UPTD. Here, PGT data was obtained from the delivery of a three-dimensional treatment plan onto PMMA phantoms. The spot-by-spot analysis helped to investigate the performance of the prototype device under clinical conditions. As a result, range variations of 5 mm could be detected for the first time with an uncollimated system at clinically relevant doses. To summarize, the obtained results help to bring PGT closer to a clinical application.

Proton therapy (PT) is expected to greatly benefit from the integration with magnetic resonance imaging (MRI). This holds true especially for moving tumors, as the combination allows tumor motion tracking and subsequently a gated treatment or real-time treatment adaptation. At the time of starting the research work as described in this thesis, only one research-grade prototype 0.22 T MRiPT (MR integrated proton therapy) system existed at a static horizontal proton research beamline. The technical feasibility of imaging at that beamline has been presented previously (Schellhammer, 2019). However, a detailed magnetometric study of magnetic field interactions between the MRI scanner and all components of the proton therapy facility was missing so far. Furthermore, to bring the concept of MRiPT towards clinical application, active proton beam delivery seems essential (Oborn et al., 2017). Therefore, the aim of this thesis is to exploratively investigate the feasibility of integrating an MRI scanner with an actively scanned proton beam, focussing on the magnetic field interactions between the MRI and PT systems and their effects on MR image quality. In the first part of this thesis, a study is described which shows the effects of (1) different positions and rotation of the gantry in the nearby treatment room, (2) the operation of the static proton beamline in the research room, and (3) the operation of the treatment room beamline on the B0 field of the in-beam MRI scanner. While the operation of the gantry was found to have negligible effect on the resonance frequency and magnetic field homogeneity of the in-beam MRI scanner, the operation of the two beamlines was found to result in a beam energy-dependent change in resonance frequency on the order of 0.5 μT (20 Hz). This measured change in resonance frequency results in an apparent shift of the MR images. This effect was observed in a previous image quality study during simultaneous imaging and static irradiation performed with the same setup (Gantz et al., 2021; Schellhammer, 2019). It is therefore mandatory to monitor all beamline activities and synchronize the MR image acquisition with the operation of both beamlines in order to guarantee artefact-free MR images and the correct spatial representation of objects in the MR images. Furthermore, a daily drift of the static magnetic field of the MRI scanner was observed and could be correlated to ambient temperature changes, indicating limitations in the heating and the thermal insulation of the permanent magnet material of the MRI scanner. However, this drift can be accounted for by an optimization of the MR frequency calibration prior to each image acquisition. The second part of this thesis presents the combination of the in-beam MRI scanner with an actively scanned proton beam at a Pencil Beam Scanning (PBS) beamline. The investigation focusses on the influences of the magnetic fringe fields of the PT system onto the MR image quality. First, the suitability of the beam-stopper is shown. Moreover, the maximum radiation field of the beamline for operation with the MRI scanner at the beamline is theoretically presented and confirmed by radiochromic film measurements. In order to prevent a direct irradiation of the MRI scanner, it is shown that a reduction of the field size in vertical direction to 20 cm is required, while the full 40 cm field size is applicable in horizontal direction. Furthermore, a beam energy-dependent trapezoidal distortion of the rectangular radiation field induced by the B0 field of the MRI scanner is, for the first time, experimentally quantified at the isocenter of the MRI scanner and confirms previously published computer simulation studies (Oborn et al., 2015). Additionally, a previously unknown proton beam spot rotation is observed for spot positions in the outer corners of the radiation field, with rotations relative to the main axis of up to 22°, which requires future studies to understand the observed effect. Second, the feasibility of simultaneous imaging and dynamic PBS irradiation is investigated, by (1) a magnetometry study and (2) MR image quality experiments during simultaneous PBS irradiation. These measurements reveal that the operation of the horizontal scanning magnet results in a severe loss of image quality in the form of ghosting artefacts along the phase-encoding direction, whereas vertical beam scanning and proton beam energy variation is found to cause no visual degradation of image quality. The origin of the observed ghosting artefacts is unravelled by phase-offsets in the k-space information of the acquired images. A theoretical description of these artefacts is presented, which is capable to explain the experimentally observed image artefacts due to the B0 field perturbations found in the magnetometry study. In order to eliminate the observed artefacts, two concepts for artefact-free imaging during PBS dose delivery are suggested, which include magnetic decoupling of the MRI scanner and PT system, and an online image correction strategy that accounts for the changes in the B0 field caused by the operation of the horizontal scanning magnet. Future studies are crucial to evaluate the feasibility and effectiveness of these approaches. The third part of the thesis tests the hypothesis that a proton beam-induced signal change in MR images, which is indicative of effective proton dose delivery in fluid-filled phantom material, is caused by heat-induced convection (Schellhammer, 2019). It is clearly shown that the inhibition of water flow could fully suppress the beam-induced MRI signal loss that was observed in previous experiments. Furthermore, the introduction of an external flow condition using similar flow velocities as expected during proton irradiation produces similar MRI signal losses. The combination of both results suggests that the observed MRI signal loss is most likely caused by convection and is hence most likely not transferable to solid materials and tissues. However, the method holds potential for the coordinate system co-localization of the MRI scanner and PT system, as well as for verification of the proton beam range during machine quality control. In conclusion, this thesis greatly improves the understanding of the origin and magnitude of perturbations of the static magnetic field of the MRI scanner due to the presence of static and dynamic fringe fields of the beamline and scanning magnets of the PT system. The work shows that these interactions result in a severe loss of image quality during simultaneous MR imaging and active proton beam delivery. Combining the knowledge obtained from magnetometry, imaging and theoretical considerations, solid evidence is provided to understand why this loss of image quality is observed for one scanning direction only. Furthermore, this work shows that the current method used for online MRI-based proton beam visualization is caused by buoyancy-driven convection. These results stimulate further research targeting both non-clinical research solutions and the development of a first prototype MRiPT system for clinical use.:List of Figures vii List of Tables ix List of Abbreviations xi 1 Introduction 1 2 Theoretical background 5 2.1 Proton therapy 5 2.1.1 Physical principle 5 2.1.2 Beam delivery 8 2.2 Magnetic resonance imaging 10 2.2.1 Physical principle of MRI 10 2.2.2 Spatial encoding 12 2.2.3 Basic pulse sequences 13 2.3 Magnetometry for MRI systems 14 3 Magnetometry of the in-beam MRI scanner at the static research beamline 17 3.1 Material and methods 18 3.1.1 Measurement setup 18 3.1.2 Magnetic field camera 19 3.1.3 Magnetic field drift 20 3.1.4 Influence of gantry position and rotation 21 3.1.5 Effect of FBL and GTR beamline magnets 21 3.2 Results 22 3.2.1 Frequency drift and reference measurements 22 3.2.2 Influence of gantry position and rotation 24 3.2.3 Influence of FBL and GTR beamline operation 25 3.3 Discussion 25 4 Combination of the MRI scanner with a horizontal dedicated PBS Beamline 29 4.1 Installation of the MRI scanner at the PBS beamline 29 4.2 Position verification of the beam-stopper 31 4.3 Determination of maximum radiation field size inside the MRI scanner 36 4.4 Discussion 40 5 Magnetic interference and image artefacts during simultaneous imaging and irradiation 41 5.1 Material and methods 41 5.1.1 Magnetometry of external influences on the magnetic field of the MRI scanner 42 5.1.2 Image quality experiments 44 5.1.3 Theory and computer simulation 45 5.2 Results 47 5.2.1 Magnetometry results 47 5.2.2 Image quality experiments 50 5.2.3 Computer simulation 51 5.3 Discussion 52 6 Proton beam visualization by online MR imaging: Unravelling the convection hypothesis 59 6.1 Material and methods 60 6.1.1 Experimental setup 60 6.1.2 MRI sequence design 62 6.1.3 Baseline experiments: Validation of beam energy and current dependency 63 6.1.4 Flow restriction and inhibition 65 6.1.5 External flow measurements 66 6.2 Results 68 6.2.1 Baseline experiments 68 6.2.2 Vertical flow restriction and flow inhibition 71 6.2.3 MRI signal loss by external flow 73 6.3 Discussion 74 7 General discussion and future perspectives 77 7.1 General discussion 77 7.1.1 Magnetometry of the in-beam MRI system 77 7.1.2 Simultaneous MR imaging and active PBS beam delivery 79 7.1.3 MRI-based proton beam visualization 80 7.2 Future perspectives for MRiPT 82 7.2.1 Short-term perspectives 82 7.2.2 Long-term perspectives 83 7.3 Conclusion 87 8 Summary 89 9 Zusammenfassung 93 Bibliography 97 Appendix 109 A Results of film measurements at MR isocenter 109 B Angio TOF MRI pulse sequence parameters 110

Proton therapy, a relatively young modality in radiation therapy, has proven useful in cases where a sharp dose gradient or low secondary irradiation is required. In Canada proton therapy it was performed at the TRIUMF Proton Therapy Facility in the treatment of large or difficultly positioned ocular melanomas. This rare primary malignant cancer of the eye has a poor prognosis if untreated. Patient vision sparing is critical for quality of life and is strongly affected by the accuracy of the chosen treatment. Reduction in irradiation of critical structures is a proven strength of proton therapy due to the high dose-gradient and finite range in tissue. But, with the advantage of steep dose gradients, comes the requirement of precision target positioning and planning. Monte Carlo particle transport software is a valuable tool for understanding treat- ment doses in cases where measurement is time consuming or difficult. Accurate simulation of primary proton dose to water aids in the evaluation of beam charac- teristics and allows for study into improving dose application for patient treatment. In this work, a full Monte Carlo model of the TRIUMF proton therapy facility was developed. Measurements were taken in water to validate simulated results within 2% over the treatment depth for a wide range of beam modulations. The second advantage of proton therapy lies in its reduced dose bath to healthy tissue. This is especially important in pediatric cases where extraneous dose comes with a high risk of secondary carcinogenesis. Whereas multi-angle photon treatments necessarily irradiate large volumes of healthy tissue to produce a flat target dose, proton treatments may irradiate a target with a single beam. With this advantage comes a trade-off - protons produce a large number of neutrons as they are prepared for patient treatment. These neutrons are the largest contributor to secondary dose in proton therapy and must be well modeled and shielded to ensure patient safety. The second part of this work involves the measurement of secondary neutron doses in the TRIUMF treatment room. Measurements were validated within 20% of simulated values with uncertainties dominated by calibration of the detector. Neutron doses to an anatomic human model showed that calibrated secondary doses were in line with similar treatment facilities reporting globally. Simulations indicated that the source of neutrons was primarily in the unshieldable region of the beamline opening. Thus the total treatment time was the determining factor in secondary dose to the patient. With primary proton dose well modeled, it became possible to study the pre- cision of treatment and possible avenues for improvement. The beam modulation wheels and optimization scheme was developed in the late 90‘s when computational and manufacturing technologies were less developed. Updated optimization methods indicated that moving to a smooth scheme of energy modulation, as opposed to a stepped modulation wheel, could improve distal dose sharpness. This was contrary to the long-held belief that there was an optimal number of steps for modulation. The third portion of this work explored the use of 3D printers to enable the fabri- cation of smoothly transitioning modulator wheels. Materials and printer methods were studied, indicating a strong candidate in the PolyJet TM method for beam mod- ulation. Both stepped and newly-optimized smooth modulator wheels were printed and validated. Total turnaround time for modulator production was under 24 hours - proving the feasibility of patient-specific beam modulation. The last portion of this work explored the use of positron emitting isotopes for dose validation. Protons traversing tissue or plastic generate β + emitting isotopes via nuclear interactions. The resulting back-to-back annihilation photons can be re- constructed into the isotope distribution produced by the beam. This can potentially provide information about beam position in the target and hence position of a phan- tom or patient. An anatomic 3D printed eye phantom was designed and irradiated to test the feasibility of this method. While a strong isotope signal was reconstructed, the test did not yield a viable technique due to the low resolution of the phantom scan. The phantom position was poorly reconstructed using the transmission scan. Despite this, it could be possible to improve this method by using other methods for phantom position registration. / Graduate

In radiotherapy, a quantity asked for by clinics when calculating a treatment plan, along withdose, is linear energy transfer. Linear energy transfer is defined as the absorbed energy intissue per particle track length and has been shown to increase with relative biologicaleffectiveness untill the overkilling effect. In this master thesis the dose averaged linear energytransfer from proton and carbon ion beams was simulated using the FLUKA multi purposeMonte Carlo code. The simulated distributions have been compared to algorithms fromRaySearch Laboratories AB in order to investigate the agreement between the computationmethods. For the proton computation algorithm improvements to the current scoring algorithmwere also implemented. A first version of the linear energy transfer validation code was alsoconstructed. Scoring of linear energy transfer in the RaySearch algorithm was done with theproton Monte Carlo dose engine and the carbon pencil beam dose engine. The results indicatedthat the dose averaged linear energy transfer from RaySearch Laboratories agreed well for lowenergies for both proton and carbon beams. For higher energies shape differences were notedwhen using both a small and large field size. The protons, the RaySearch algorithm initiallyoverestimates the linear energy transfer which could result from fluence differences in FLUKAcompared to the RaySearch algorithm. For carbon ions, the difference could stem from someloss of information in the tables used to calculate the linear energy transfer in the RaySearchalgorithm. From validation γ-tests the proton linear energy transfer passed for (3%/3mm) and(1%/1mm) with no voxels out of tolerance. γ-tests for the carbon linear energy transfer passedwith no voxels out of tolerance for (5%/5mm) and a fail rate of 2.92% for (3%/3mm).

No description available.

L'objectif principal de cette thèse est de développer et optimiser les algorithmes caractérisant les propriétés physiques et biologiques des mini-faisceaux de protons pour la réalisation des traitements avec modulation d'intensité. Un modèle basé sur la superposition et décomposition des mini-faisceaux en faisceaux élémentaires a été utilisé. Un nouveau modèle de description des mini-faisceaux primaires a été développé à partir de la sommation de trois fonctions gaussiennes. Les algorithmes ont été intégrés dans un logiciel de planification de traitement, puis validés expérimentalement et par comparaison avec des simulations Monte Carlo. Des approximations ont été réalisées et validées afin de réduire les temps de calcul en vue d'une utilisation clinique. Dans un deuxième temps, un travail en collaboration avec les équipes de radiobiologie de l'institut Curie a été réalisé afin d'introduire des résultats radiobiologiques dans l'optimisation biologique des plans de traitement. En effet, les faisceaux balayés sont délivrés avec des débits de dose très élevés (de 10 à 100 Gy/s) et de façon discontinue, et l'efficacité biologique des protons est encore relativement méconnue vue la diversité d'utilisation de ces faisceaux : les différents modèles disponibles et notamment leur dépendance avec le transfert d'énergie linéique ont été étudiés. De bons accords (écarts inférieurs à 3 % et 2 mm) ont été obtenus entre calculs et mesures de dose. Un protocole d'expérimentation pour caractériser les effets des hauts débits pulsés a été mis en place et les premiers résultats obtenus sur une lignée cellulaire suggèrent des variations d'efficacité biologique inférieures à 10 %, avec toutefois de larges incertitudes. / The main objective of this thesis is to develop and optimize algorithms for intensity modulated proton therapy, taking into account the physical and biological pencil beam properties. A model based on the summation and fluence weighted division of the pencil beams has been used. A new parameterization of the lateral dose distribution has been developed using a combination of three Gaussian functions. The algorithms have been implemented into a treatment planning system, then experimentally validated and compared with Monte Carlo simulations. Some approximations have been made and validated in order to achieve reasonable calculation times for clinical purposes. In a second phase, a collaboration with Institut Curie radiobiological teams has been started in order to implement radiobiological parameters and results into the optimization loop of the treatment planning process. Indeed, scanned pencil beams are pulsed and delivered at high dose rates (from 10 to 100 Gy/s), and the relative biological efficiency of protons is still relatively unknown given the wide diversity of use of these beams: the different models available and their dependence with linear energy transfers have been studied. A good agreement between dose calculations and measurements (deviations lower than 3 % and 2 mm) has been obtained. An experimental protocol has been set in order to qualify pulsed high dose rate effects and preliminary results obtained on one cell line suggested variations of the biological efficiency up to 10 %, though with large uncertainties.

Proton radiation therapy is an alternative to conventional photon radiation therapy, which accounts for the majority of radiation treatments today. The rationale for using protons in radiation therapy lies in their dose deposition properties; photons deposit a radiation dose inversely proportional to the energy, and therefore tissue depth, while protons exhibit a sharp Bragg peak when traversing matter. This property could increase the precision of dose delivery to the target region, and spare healthy tissue in distal and proximal regions. As part of the proton therapy treatment planning, a computed tomography (CT) scan of the patient is performed and the stopping power ratios (SPR) relative to water of the tissues are derived from the CT numbers. Estimates of SPR values are known to be a significant source of uncertainty, leading to increased margins and radiation to healthy tissue. Photon-counting detectors within CT have demonstrated many advantages over their energy-integrating counterparts, such as improved spectral imaging, higher resolution and filtering of electronic noise. In this study, the potential of photon-counting computed tomography for improving proton therapy planning was assessed by training a deep neural network on a domain transform from photon-counting CT images to SPR maps. Since one of the main types of cancer treated with proton therapy are tumours in the brain and head area, head phantoms were constructed and used to simulate photon-counting CT images, as well as to calculate the ground truth SPR value in each image point. The CT images and SPR maps were then used as input and labels to a neural network. Prediction of SPR with this method yielded relative errors of 0.52 - 0.96 %, and RMSE of 0.54 - 1.25 %, which is comparable to methods based on dual energy CT (DECT) using energy-integrating detectors. / Protonterapi är ett alternativ till konventionell strålbehandling med fotoner, som idag utgör majoriteten av strålbehandlingar. Partiklarnas respektive dosegenskaper utgör det främsta skälet till att strålbehandla med protoner istället för fotoner. Fotoners deponerade dosnivå avtar med energi, och därmed vävnadsdjup. Protoner deponerar förhållandevis låg dos fram till en dostopp ('Bragg peak'), efter vilken stråldosen snabbt avtar. Detta ökar dosprecisionen och kan göra behandlingen mer skonsam för den friska vävnad som omger tumören. Inför strålterapibehandling med protoner utförs en datortomografi av patienten, där vävnadernas bromsförmåga (stopping power ratio, SPR) relativt vatten beräknas från CT-talen. De skattade SPR-värdena utgör en källa till osäkerhet, vilket leder till tilltagna marginaler under behandlingen och ökad stråldos till frisk vävnad. Fotonräknande detektorer inom datortomografi har uppvisat många fördelar gentemot konventionella energiintegrerande detektorer, som exempelvis förbättrade spektrala mätningar, högre bildupplösning samt filtrering av elektroniskt brus. Studien syftar till att undersöka huruvida fotonräknande detektorteknik kan förbättra protonterapiplanering, genom att träna ett neuralt nätverk på en domäntransform från fotonräknande datortomografbilder till SPR-kartor. Då en av de främsta typerna av cancer som behandlas med protonterapi är tumörer i huvudet och hjärnan, konstruerades huvudfantom som dels användes för att simulera bilder från den fotonräknande datortomografen, och dels för att beräkna det sanna SPR-värdet i varje punkt. Dessa utgjorde in- och utdata till ett neuralt nätverk. Beräkning av SPR med denna metod gav relativa fel mellan 0.52 - 0.96 % och RMSE mellan 0.54 - 1.25 %, vilket är jämförbart med metoder baserade på datortomografi med dubbelenergi (dual energy CT, DECT) för energiintegrerande detektorer.

With the growing use and complexity of proton therapy, the safety and accuracy of the machines becomes increasing important. This, to be able to deliver the prescribed dose to the target while minimizing the dose to healthy tissue. In this project, machine quality assurance data are analyzed to quantify the existing positional machine uncertainties in the form of deviations from expected value and their effect on the dose accuracy in order to improve precision. The method consisted of two main parts. In the first part, two systems to monitor the measured deviations variations from the machine quality assurance tests were implemented. In the second part, two ways to measure the impact of the positional machine uncertainties were developed. The monitoring systems showed that the uncertainties had shrunken over time or were stable, and that the tolerance limits currently used for the machine quality assurance can be lowered. The measured impact of the positional machine uncertainties showed that a margin of 0.61 mm for treatment room 1 and a margin of 1.02 mm for treatment room 2 was required to compensated for the machine uncertainties. When the uncertainties we reincorporated into a clinical approved robust optimized plan, the result showed no significant change in dose to the different treatment volumes. The result gives the Scandion clinic insight and tools to minimize the impact of machine uncertainties and to be able to improve the precision of future treatments.