Cervix cancer affects women of all ages and causes significant morbidity and mortality. Locally advanced disease is curable with radiotherapy (RT) in about 50% of patients, although often at the expense of serious side effects. In order to improve the therapeutic ratio of tumour control versus normal tissue toxicity, conformal intensity-modulated radiotherapy (IMRT) is being investigated. However, inter- and intra-fractional motion of cervix cancer can contribute to both geographical miss of the target and overdosing of surrounding normal tissues, particularly in the setting of conformal IMRT with steep dose gradients. Defining the target volume accurately and understanding the dose consequence of these complex intra-pelvic organ dynamics during external beam radiotherapy forms the essential foundations for future treatment optimization and adaptation. This in turn will lead to improvements in tumour control and disease-free survival while minimising treatment toxicity.

Dose management in CT is an increasingly important issue as the number of CT scans per capita continues to rise. One proposed approach for enhanced dose management is to allow the spatial pattern of x-ray fluence delivered to the patient to change dynamically as the x-ray tube rotates about the patient. The changes in incident fluence could be guided using a patient model and optimization method in order to deliver user-defined image quality criteria while minimizing dose. This approach is referred to as fluence field modulated CT (FFMCT). In this work, a framework and optimization method was developed for evaluating the dose and image quality benefits of FFMCT, both in simulated and experimental data. Modulated fluence profiles were optimized for different objects and image quality criteria using a simulated annealing algorithm. Analysis involved comparing predicted image quality maps and dose outcomes to those using conventional methods. Results indicated that image quality distributions using FFMCT agreed better with prescribed image qualities than conventional techniques allow. Dose reductions ranged depending on the task and object of interest. Simulation studies using a simulated anthropomorphic phantom of the chest suggest an average dose reduction of at least 20% compared to conventional techniques is possible, where local dose reductions may be greater than 60%. Across different imaging tasks and objects, integral dose reductions ranged from 20-50% when compared to a conventional bowtie filter. The results of this study suggest that given a suitable collimator approach, FFMCT could reap significant benefits in terms of reducing dose and optimizing image quality. Though the tradeoff between image quality and imaging dose may not be eliminated, it may be better managed using an FFMCT approach.

Intensity modulated arc therapy is a novel treatment technique that has shown great potential to be superior to conventional intensity modulated radiotherapy, both in terms of treatment plan quality as well as treatment delivery. Based on previous literature, a simplified technique called two-step intensity modulated arc therapy (2-step IMAT) was implemented into a treatment planning system. In order to automatically generate treatment plans for this technique, a beam portal shaping method was developed to generate beam segments. A sensitivity analysis was carried out on a geometric phantom to determine optimal parameters for the 2-step IMAT implementation for that particular phantom. The segment weights were optimized using the dose-based and dose-volume-based objective functions. The optimal solution search was based on the gradient-descend algorithm. The dose-based objective function was implemented using a so-called lambda-value-dose-based objective function developed in this work in order to increase both speed and flexibility of the optimization. The successful implementation demonstrated the feasibility of automatic 2-step IMAT treatment planning. A comparison of conventional arc therapy and 2-step IMAT showed improvements in the target dose uniformity by about 50% for both geometric phantom and clinical paraspinal tumor case, whilst also improving the organ sparing. The comparisons between the lambda-value-dose-based and dose-volume-based optimizations showed a speed advantage of the former by a factor of over five in the phantom study. The current beam portal shaping approach can be improved by optimizing the segment width and including multiple organs-at-risk in the segment generation algorithm. Future work will also include the implementation of a stochastic optimization to minimize the chance of getting trapped in local minima during the segment weight optimization. In summary, the work of this research showed that the automatic 2-step IMAT planning is a viable technique that can result in highly conformal plans while keeping the treatment planning and delivery simple and straightforward.

Dose management in CT is an increasingly important issue as the number of CT scans per capita continues to rise. One proposed approach for enhanced dose management is to allow the spatial pattern of x-ray fluence delivered to the patient to change dynamically as the x-ray tube rotates about the patient. The changes in incident fluence could be guided using a patient model and optimization method in order to deliver user-defined image quality criteria while minimizing dose. This approach is referred to as fluence field modulated CT (FFMCT). In this work, a framework and optimization method was developed for evaluating the dose and image quality benefits of FFMCT, both in simulated and experimental data. Modulated fluence profiles were optimized for different objects and image quality criteria using a simulated annealing algorithm. Analysis involved comparing predicted image quality maps and dose outcomes to those using conventional methods. Results indicated that image quality distributions using FFMCT agreed better with prescribed image qualities than conventional techniques allow. Dose reductions ranged depending on the task and object of interest. Simulation studies using a simulated anthropomorphic phantom of the chest suggest an average dose reduction of at least 20% compared to conventional techniques is possible, where local dose reductions may be greater than 60%. Across different imaging tasks and objects, integral dose reductions ranged from 20-50% when compared to a conventional bowtie filter. The results of this study suggest that given a suitable collimator approach, FFMCT could reap significant benefits in terms of reducing dose and optimizing image quality. Though the tradeoff between image quality and imaging dose may not be eliminated, it may be better managed using an FFMCT approach.

L'imagerie à travers les milieux turbides comme le brouillard, les tissus, les colloïdes, etc. répond à plusieurs besoins de la vie courante. L'imagerie à travers de tels milieux diffusants est un défi auquel peuvent répondre les nouveaux systèmes d'imagerie, la théorie de l'information et l'étude des lois de transport de la lumière dans les milieux aléatoires. La thèse est divisée en deux parties adressant deux modalités d'imagerie différentes, à savoir : l'imagerie de contraste polarimétrique et l'imagerie modulée en intensité. Dans les deux cas, des systèmes d'imagerie en temps réel sont proposés et mis au point. Leurs performances sont évaluées à la fois théoriquement et expérimentalement. Dans la première partie de la thèse, une caméra polarimétrique à deux canaux instantanés conçue autour d'un prisme de Wollaston est utilisée pour imager de manière optimale une source de lumière polarisée noyée dans un brouillard. Une expérience en situation réelle a été mise en place à proximité du campus de Beaulieu à Rennes. La source est placée sur une tour de télécommunication située à plus d'un kilomètre du système imageant. Les données acquises dans diverses conditions météorologiques montrent que l'efficacité de cette caméra polarimétrique dépend de la corrélation du bruit de fond dans les deux images initiales. Ceci a été confirmé grâce à une analyse fondée sur la théorie de l'information qui montre que le contraste polarimétriques maximal est obtenu par une combinaison linéaire des deux canaux polarimétriques dont la pondération dépendant de la corrélation du bruit de fond dans les deux canaux. Un système de détection, intégrant cette représentation polarimétrique optimale, a été développé pour explorer de bout en bout les capacités offertes par l'imagerie polarimétrique à deux canaux à travers le brouillard. Ces études trouvent des applications directes dans le transport par temps dégradé, y compris pour l'aide à l'atterrissage d'aéronefs. Dans la même logique, la deuxième partie de la thèse porte sur l'apport de la modulation d'intensité plein champ pour imager les photons balistiques dans les milieux diffusants. En utilisant de concert la théorie de la diffusion et la théorie de l'information, nous avons pu montrer que, pour un budget de photons donné, il existait une fréquence de modulation minimale pour laquelle le filtrage de photons balistique devient efficace. Cette fréquence dépend des propriétés de diffusion du milieu intermédiaire et se trouve être dans la gamme du MHz en situation réelle. L'imagerie en temps réel à de telles fréquences étant un vrai défi, nous avons proposé un système de démodulation plein champ inédit basé sur l'utilisation d'un cristal électro-optique. Ce système d'imagerie, dont nous avons breveté le principe, est en mesure de démoduler avec une caméra standard une scène en temps réel et en plein champ à des fréquences de plusieurs MHz (voire GHz) sans synchronisation de phase. Un prototype de ce système a été développé permettant de confirmer qu'il était robuste, portable et rentable. Le travail présenté dans cette thèse ouvre la voie à la mise en œuvre de systèmes d'imagerie de pointe fonctionnant dans des situations réelles, allant de l'imagerie biomédicale, à la sécurité. / Imaging through turbid media like fog, tissues, colloids etc. has various applications in real-life situations. The problem of imaging through such scattering media presents a challenge that can be addressed by using novel imaging schemes, information theory and laws of light transport through random scattering media. The thesis is divided into two parts corresponding to two different imaging modalities, namely, polarimetric contrast imaging and intensity modulated light imaging. In both the cases, advanced imaging systems, capable of imaging in real-time are used and their performances are evaluated both theoretically and experimentally. In the first part of the thesis, a two-channel, snapshot polarimetric camera, based on a Wollaston prism is used to attain optimal imaging of polarized light source through fog. An original outdoor experiment is setup in the vicinity of the campus Beaulieu in Rennes, France, where a source is placed on a telecommunication tower more than a kilometer away from the imaging system. Data acquired in various weather conditions show that the efficiency of the two-channel polarimetric camera depends on the background noise correlation in the two images. Further, this was confirmed using an information theoretical analysis, which showed that a polarimetric contrast maximizing image representation is a linear combination of the two polarimetric images whose weights depend on the background noise correlation. Based on the derived optimal polarimetric representation, a detection scheme was presented, leading to an end-to-end study of two-channel polarimetric imaging through fog that may be useful in transport applications like aircraft landing/taxiing in degraded weather. The second part of the thesis deals with intensity modulated light and its potential for ballistic photon imaging through scattering media. First, using the diffusion theory of photon transport and information theory, it was shown that for a given photon budget, ballistic imaging can be achieved for a minimum modulation frequency that depends on the scattering properties of the intervening medium. In real-life situation, the minimum frequency can be in the range of MHz. Real-time imaging at these frequencies is a challenge. Hence, a novel demodulation camera system based on electro-optics was proposed and patented. The imaging system is capable of real-time, full-field demodulation at frequencies of several MHz (potentially, in GHz as well), without requiring a phase synchronized source. A prototype of the imaging system was developed and shown that a demodulation camera based on the proposed design is robust, portable and cost-effective. Finally, the work presented in this thesis pave way for implementation of advanced imaging systems in real-life situations, varying from biomedical imaging to transport safety.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22146号 / 医博第4537号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 富樫 かおり, 教授 武田 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18170号 / 医博第3890号 / 新制||医||1003(附属図書館) / 31028 / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 小川 修, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13032号 / 論医博第2114号 / 新制||医||1016(附属図書館) / 32990 / 横浜市立大学大学院医科学専攻 / (主査)教授 増永 慎一郎, 教授 坂井 義治, 教授 小川 修 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Treatment planning for radiation therapy inherently involves tradeoffs, such as between tumor control and normal tissue sparing, between time-efficiency and dose quality, and between nominal plan quality and robustness. The purpose of this thesis is to develop methods that can facilitate decision making related to such tradeoffs. The main focus of the thesis is on multicriteria optimization methods where a representative set of treatment plans are first calculated and the most appropriate plan contained in this representation then selected by the treatment planner through continuous interpolation between the precalculated alternatives. These alternatives constitute a subset of the set of Pareto optimal plans, meaning plans such that no criterion can be improved without a sacrifice in another. Approximation of Pareto optimal sets is first studied with respect to fluence map optimization for intensity-modulated radiation therapy. The approximation error of a discrete representation is minimized by calculation of points one at the time at the location where the distance between an inner and outer approximation of the Pareto set currently attains its maximum. A technique for calculating this distance that is orders of magnitude more efficient than the best previous method is presented. A generalization to distributed computational environments is also proposed. Approximation of Pareto optimal sets is also considered with respect to direct machine parameter optimization. Optimization of this form is used to calculate representations where any interpolated treatment plan is directly deliverable. The fact that finite representations of Pareto optimal sets have approximation errors with respect to Pareto optimality is addressed by a technique that removes these errors by a projection onto the exact Pareto set. Projections are also studied subject to constraints that prevent the dose-volume histogram from deteriorating. Multicriteria optimization is extended to treatment planning for volumetric-modulated arc therapy and intensity-modulated proton therapy. Proton therapy plans that are robust against geometric errors are calculated by optimization of the worst case outcome. The theory for multicriteria optimization is extended to accommodate this formulation. Worst case optimization is shown to be preferable to a previous more conservative method that also protects against uncertainties which cannot be realized in practice. / En viktig aspekt av planering av strålterapibehandlingar är avvägningar mellan behandlingsmål vilka står i konflikt med varandra. Exempel på sådana avvägningar är mellan tumörkontroll och dos till omkringliggande frisk vävnad, mellan behandlingstid och doskvalitet, och mellan nominell plankvalitet och robusthet med avseende på geometriska fel. Denna avhandling syftar till att utveckla metoder som kan underlätta beslutsfattande kring motstridiga behandlingsmål. Primärt studeras en metod för flermålsoptimering där behandlingsplanen väljs genom kontinuerlig interpolation över ett representativt urval av förberäknade alternativ. De förberäknade behandlingsplanerna utgör en delmängd av de Paretooptimala planerna, det vill säga de planer sådana att en förbättring enligt ett kriterium inte kan ske annat än genom en försämring enligt ett annat. Beräkning av en approximativ representation av mängden av Paretooptimala planer studeras först med avseende på fluensoptimering för intensitetsmodulerad strålterapi. Felet för den approximativa representationen minimeras genom att innesluta mängden av Paretooptimala planer mellan inre och yttre approximationer. Dessa approximationer förfinas iterativt genom att varje ny plan genereras där avståndet mellan approximationerna för tillfället är som störst. En teknik för att beräkna det maximala avståndet mellan approximationerna föreslås vilken är flera storleksordningar snabbare än den bästa tidigare kända metoden. En generalisering till distribuerade beräkningsmiljöer föreslås även. Approximation av mängden av Paretooptimala planer studeras även för direkt maskinparameteroptimering, som används för att beräkna representationer där varje interpolerad behandlingsplan är direkt levererbar. Det faktum att en ändlig representation av mängden av Paretooptimala lösningar har ett approximationsfel till Paretooptimalitet hanteras via en metod där en interpolerad behandlingsplan projiceras på Paretomängden. Projektioner studeras även under bivillkor som förhindrar att den interpolerade planens dos-volym histogram kan försämras. Flermålsoptimering utökas till planering av rotationsterapi och intensitetsmodulerad protonterapi. Protonplaner som är robusta mot geometriska fel beräknas genom optimering med avseende på det värsta möjliga utfallet av de föreliggande osäkerheterna. Flermålsoptimering utökas även teoretiskt till att innefatta denna formulering. Nyttan av värsta fallet-optimering jämfört med tidigare mer konservativa metoder som även skyddar mot osäkerheter som inte kan realiseras i praktiken demonstreras experimentellt. / <p>QC 20130527</p>

The thesis aims to improve treatment dose accuracy in brachytherapy using a high dose rate (HDR) Ir-192 stepping source and in external beam therapy using intensity modulated radiation therapy (IMRT). For HDR brachytherapy, this has been achieved by investigating dose errors in the near field and the transit dose of the HDR brachytherapy stepping source. For IMRT, this study investigates the volume effect of detectors in the dosimetry of small fields, and the clinical implementation and dosimetric verification of a 6MV photon beam for IMRT. For the study of dose errors in the near field of an HDR brachytherapy stepping source, the dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter was calculated with Monte Carlo code MCNP 4.A. The Monte Carlo (MC) results were used to compare with the results calculated with the Nucletron Brachytherapy Planning System (BPS) formalism. Using the MC calculated radial dose function and anisotropy function with the BPS formalism, 1% dose calculation accuracy can be achieved even in the near field with negligible extra demand on computation time. A video method was used to analyse the entrance, exit and the inter-dwell transit speed of the HDR stepping source for different path lengths and step sizes ranging from 2.5 mm to 995 mm. The transit speeds were found to be ranging from 54 to 467 mm/s. The results also show that the manufacturer has attempted to compensate for the effects of inter-dwell transit dose by reducing the actual dwell time of the source. A well-type chamber was used to determine the transit doses. Most of the measured dose differences between stationary and stationary plus inter-dwell source movement were within 2%. The small-field dosimetry study investigates the effect of detector size in the dosimetry of small fields and steep dose gradients with a particular emphasis on IMRT measurements. Due to the finite size of the detector, local discrepancies of more than 10 % are found between calculated cross profiles of intensity modulated beams and intensity modulated profiles measured with film. A method to correct for the spatial response of finite sized detectors and to obtain the