In recent years, the impressive progress performed in imaging, computational and technological fields have made possible the emergence of image-guided radiation therapy (IGRT) and adaptive radiation therapy (ART). The accuracy in radiation dose delivery reached by IMRT offers the possibility to increase locoregional dose-intensity, potentially overcoming the poor tumor control achieved by standard approaches. However, before implementing such a technique in clinical routine, a particular attention has to be paid at the target volumes definition and delineation procedures to avoid inadequate dosage to TVs/OARs. In head and neck squamous cell carcinoma (HNSCC), the GTV is typically defined on CT acquired prior to treatment. However, providing functional information about the tumor, FDG-PET might advantageously complete the classical CT-Scan to better define the TVs. Similarly, re-imaging the tumor with optimal imaging modality might account for the constantly changing anatomy and tumor shape occurring during the course of fractionated radiotherapy. Integrating this information into the treatment planning might ultimately lead to a much tighter dose distribution. From a methodological point of view, the delineation of TVs on anatomical or functional images is not a trivial task. Firstly, the poor soft tissue contrast provided by CT comes out of large interobserver variability in GTV delineation. In this regard, we showed that the use of consistent delineation guidelines significantly improved consistency between observers, either with CT and with MRI. Secondly, the intrinsic characteristics of PET images, including the blur effect and the high level of noise, make the detection of the tumor edges arduous. In this context, we developed specific image restoration tools, i.e. edge-preserving filters for denoising, and deconvolution algorithms for deblurring. This procedure restores the image quality, allowing the use of gradient-based segmentation techniques. This method was validated on phantom and patient images, and proved to be more accurate and reliable than threshold-based methods. Using these segmentation methods, we proved that GTVs significantly shrunk during radiotherapy in patients with HNSCC, whatever the imaging modality used (MRI, CT, FDG-PET). No clinically significant difference was found between CT and MRI, while FDG-PET provided significantly smaller volumes than those based on anatomical imaging. Refining the target volume delineation by means of functional and sequential imaging ultimately led to more optimal dose distribution to TVs with subsequent soft tissue sparing. In conclusion, we demonstrated that a multi-modality-based adaptive planning is feasible in HN tumors and potentially opens new avenues for dose escalation strategies. As a high level of accuracy is required by such approach, the delineation of TVs however requires a special care.

Positron emission tomography (PET) is a molecular imaging technique that provides a direct and accurate evaluation of tissue function in vivo. PET of the glucose analogue 18F-fluoro-deoxy-glucose, is increasingly in use to aid in gross target volume delineation in radiotherapy treatment planning (RTP) where it shows reduced inter-observer variability. The aim of this thesis was to develop and investigate a new technique for delineating PET-GTV with sufficient accuracy for RTP. A new technique, volume and contrast adjusted thresholding (VCAT), has been developed to automatically determine the optimum threshold value that measures the true volume on PET images. The accuracy was investigated in spherical and irregular lesions in phantoms using both iterative and filtered back-projection reconstructions and different image noise levels. The accuracy of delineation for the irregular lesions was assessed by comparison with CT using the Dice Similarity Coefficient and Euclidean Distance Transformation. A preliminarily investigation of implementing the newly developed technique in patients was carried out. VCAT proved to determine volumes and delineate tumour boundaries on PET/CT well within the acceptable errors for radiotherapy treatment planning irrespective of lesion contrast, image noise level and reconstruction technique.

Este trabalho visa estudar as margens necessárias para definir o volume de planejamento do alvo (PTV) requeridas para tratar adequadamente tumores móveis como os localizados na próstata ou tumores localizados em áreas com pouca mobilidade como os da região da cabeça e pescoço, na ausência de localização do alvo por imagem. Também tem como objetivo avaliar o impacto causado pelo PTV, em termos de dose, nas estruturas críticas ao seu redor e sua influência quando planejamento inverso é utilizado na radioterapia com modulação de feixe (IMRT). Dados de 387 pacientes de próstata foram analizados retrospectivamente. Todos os pacientes receberam localização pré-tratamento com ultra-som 2D resultando em 10.327 localizações, cada uma com deslocamento de isocentro em três direções: antero-posterior (AP), lateral direitaesquerda (DE), e superior-inferior (SI). O deslocamento médio e desvio padrão (SD) para cada direção foi estimado a partir dos dados de tratamento gravados diariamente. As incertezas (SD) na posição do alvo foram 4,4 mm (AP), 3,6 mm (DE), e 4,5 mm (SI). O estudo das incertezas no posicionamento diário de 78 pacientes com tumores de cabeça e pescoço que utilizaram máscaras termoplásticas como imobilizadores, avaliados com equipamento de portal com imagem eletrônica (EPID), mostrou variações (SD) na posição do isocentro de tratamento de 3,1 mm (AP), 1,5 mm (DE), 4,5 mm (SI). Aplicando estes desvios num simulador antropomórfico estudou-se os histogramas de dose-volume resultantes do deslocamento do isocentro no tratamento diário. Os resultados mostraram a importância de se colocar margens no volume clínico do alvo para garantir um tratamento adequado e também mostraram que a variação diária do isocentro de tratamento pode causar um aumento de dose maior que o nível de tolerância dos órgãos críticos. / This work intends to study the margins required to define a planning target volume (PTV) for adequate treatment of the mobile tumors such as prostate or those located in areas with less mobility as the ones in head and neck region, in the absence of daily localization imaging based. It is also intends to evaluate the impact caused by the PTV, in terms of dose, to the critical structures surrounding the PTV and its influence when inverse planning is used in the intensity-modulated radiation therapy (IMRT). Data from 387 prostate patients were analyzed retrospectively. Every patient in the study received daily pre-treatment localization with 2D ultrasound resulting in a total of 10,327 localizations, each comprising of an isocenter displacement in 3 directions: anterior-posterior (AP), right-left lateral (RL), and superior-inferior (SI). The mean displacement and standard deviation (SD) for each direction for each patient was computed from daily treatment records. The uncertainties (SD) in the target position were 4.4 mm (AP), 3.6 mm (RL), and 4.5 mm (SI). A study of the uncertainties in the daily positioning of 78 head and neck patients who used thermoplastic mask to immobilize them, evaluated with electronic portal imaging device (EPID), showed variations (SD) in the isocenter treatment position of 3.1 mm (AP), 1.5 mm (RL), and 4.5 mm (SI). By applying these shifts in an anthropomorphic phantom it was studied the dose-volume histograms resultant of the isocenter displacement in the daily treatment. The result showed the importance of putting margins in the clinical target volume to assure an adequate treatment and also showed that isocenter daily variation can cause an increase to the dose greater than the tolerance level to the critical organs.

Este trabalho visa estudar as margens necessárias para definir o volume de planejamento do alvo (PTV) requeridas para tratar adequadamente tumores móveis como os localizados na próstata ou tumores localizados em áreas com pouca mobilidade como os da região da cabeça e pescoço, na ausência de localização do alvo por imagem. Também tem como objetivo avaliar o impacto causado pelo PTV, em termos de dose, nas estruturas críticas ao seu redor e sua influência quando planejamento inverso é utilizado na radioterapia com modulação de feixe (IMRT). Dados de 387 pacientes de próstata foram analizados retrospectivamente. Todos os pacientes receberam localização pré-tratamento com ultra-som 2D resultando em 10.327 localizações, cada uma com deslocamento de isocentro em três direções: antero-posterior (AP), lateral direitaesquerda (DE), e superior-inferior (SI). O deslocamento médio e desvio padrão (SD) para cada direção foi estimado a partir dos dados de tratamento gravados diariamente. As incertezas (SD) na posição do alvo foram 4,4 mm (AP), 3,6 mm (DE), e 4,5 mm (SI). O estudo das incertezas no posicionamento diário de 78 pacientes com tumores de cabeça e pescoço que utilizaram máscaras termoplásticas como imobilizadores, avaliados com equipamento de portal com imagem eletrônica (EPID), mostrou variações (SD) na posição do isocentro de tratamento de 3,1 mm (AP), 1,5 mm (DE), 4,5 mm (SI). Aplicando estes desvios num simulador antropomórfico estudou-se os histogramas de dose-volume resultantes do deslocamento do isocentro no tratamento diário. Os resultados mostraram a importância de se colocar margens no volume clínico do alvo para garantir um tratamento adequado e também mostraram que a variação diária do isocentro de tratamento pode causar um aumento de dose maior que o nível de tolerância dos órgãos críticos. / This work intends to study the margins required to define a planning target volume (PTV) for adequate treatment of the mobile tumors such as prostate or those located in areas with less mobility as the ones in head and neck region, in the absence of daily localization imaging based. It is also intends to evaluate the impact caused by the PTV, in terms of dose, to the critical structures surrounding the PTV and its influence when inverse planning is used in the intensity-modulated radiation therapy (IMRT). Data from 387 prostate patients were analyzed retrospectively. Every patient in the study received daily pre-treatment localization with 2D ultrasound resulting in a total of 10,327 localizations, each comprising of an isocenter displacement in 3 directions: anterior-posterior (AP), right-left lateral (RL), and superior-inferior (SI). The mean displacement and standard deviation (SD) for each direction for each patient was computed from daily treatment records. The uncertainties (SD) in the target position were 4.4 mm (AP), 3.6 mm (RL), and 4.5 mm (SI). A study of the uncertainties in the daily positioning of 78 head and neck patients who used thermoplastic mask to immobilize them, evaluated with electronic portal imaging device (EPID), showed variations (SD) in the isocenter treatment position of 3.1 mm (AP), 1.5 mm (RL), and 4.5 mm (SI). By applying these shifts in an anthropomorphic phantom it was studied the dose-volume histograms resultant of the isocenter displacement in the daily treatment. The result showed the importance of putting margins in the clinical target volume to assure an adequate treatment and also showed that isocenter daily variation can cause an increase to the dose greater than the tolerance level to the critical organs.

No description available.

The purpose of this study was to investigate whether it is possible to create the ITV using a reduced set of 4DCT phases. Methods: Ten lung cancer patients were identified who had received 4DCT imaging as part of their treatment simulation, and who had a noticeable tumor motion. For each patient, a GTV was drawn on the exhale phase, based on the original physician-drawn ITV (our clinical practice is for the physician to directly draw the ITV based using the 4DCT images). This GTV was then propagated to the other phases of the 4DCT using a commercial image registration package (MIMVista, Cleveland OH). 4 different ITVs were created using N phases closest to exhale (N=1-10). For each ITV contour a RapidArc plan was created on the exhale phase CT, normalized so that the 95% isodose line covered at least 95% of the ITV. Each plan was applied to each CT phase (1-10), and the doses deformably mapped to the exhale phase. The effect of the motion was quantified in terms of the dose to the 95% of the target on the exhale phase (D95). The change in these parameters as N was reduced from 10 was calculated. Also, the difference in the 3D calculations of the original plans and the 4D calculations was noted as a function of N. Results: Differences in 3D and 4D dose calculations varied from 3% to 14% with an average of 7% for ITV_10/10. For 9 out 10 of ten patients we can have less than 5% reduction in the D95 by using ITV_8/10. For 3 out of ten patients we can have less than 5% reduction in the D95 by using ITV_7/10 and for 1 out of 10 patients we can patients we can have less than 5% reduction in the D95 by using ITV_6/10. Conclusions: No rule for reducing ITV works for all patients. Some reduction (8/10 phases) is possible for most of the patients but not all and also the volume reduction is small. Therefore what we are currently doing is reasonable. 4D dose calculations give different DVHs to 3D also shown by other groups. Reduction in ITV volume is possible for some patients (e.g. patient 2 17% reduction), but 4D dose calculation is necessary. / Ο σκοπός αυτής της εργασίας είναι να ερευνήσουμε εάν είναι εφικτή η δημιουργία ενός ITV το οποίο θα αποτελείται από μειωμένες φάσεις του 4DCT. Μέθοδοι: Για την εργασία χρησιμοποιήθηκαν δέκα ασθενείς με διαγνωσμένο καρκίνο του πνεύμονα οι οποίοι είχαν λάβει 4DCT σαν μέρος της εξομοίωσης τής θεραπείας τους. Για κάθε ασθενή ένα GTV σχεδιάστηκε στην φάση της εκπνοής του 4DCT. To συγκεκριμένο GTV τοποθετήθηκε ανάλογα και στις υπόλοιπες φάσεις του 4DCT χρησιμοποιώντας ειδικό λογισμικό με δυνατότητες ‘deformable registration’ (MIMVista, Cleveland OH). 4 διαφορετικά ITVs δημιουργήθηκαν χρησιμοποιώντας Ν φάσεις πλησιέστερα στην εκπνοή (Ν=1-10). Για κάθε ITV ενα πλάνο VMAT δημιουργήθηκε στην φάση της εκπνοής, και κανονικοποιήθηκε ώστε το 95% του στόχου να παίρνει τουλάχιστον 95% της δόσης. Κάθε πλάνο εφαρμόστηκε σε όλες τις υπόλοιπες φάσεις του 4DCT και η αθροιστική δόση που παίρνει το GTV από όλο τον αναπνευστικό κύκλο υπολογίστηκε στη φάση της εκπνοής. Το πόσο επηρεάζει η κίνηση υπολογίστηκε με όρους δόσης στο 95% του στόχου πάνω στην φάση της εκπνοής (D95). Επίσης η διαφορά μεταξύ των 3D και των 4D υπολογισμών δόσης υπολογίστηκε σαν συνάρτηση του Ν (Ν=1-10). Αποτελέσματα: Παρατηρήθηκαν διαφορές στους 3D και 4D υπολογισμούς δόσης από 3% έως 14% με μέσο όρο 7% για το ITV_10/10. Σε 9 από τους 10 μπορούμε να πετύχουμε μείωση μικρότερη του 5% στο D95 χρησιμοποιώντας το ITV_8/10. Σε 3 από τους 10 ασθενείς μπορούμε να πετύχουμε μείωση μικρότερη του 5% στο D95 χρησιμοποιώντας το ITV_7/10 και για 1 από τους 10 ασθενείς μπορούμε να πετύχουμε μείωση μικρότερη το 5% στο D95 χρησιμοποιώντας το ITV_6/10. Συμπεράσματα: Δεν υπάρχει γενικός κανόνας για την μείωση του ITV για όλους τους ασθενείς. Συνιστάται εξατομίκευση θεραπείας. Η μείωση των φάσεων σε 8 από 10 φαίνεται αποτελεσματική για τους περισσότερους αλλά όχι όλους τους ασθενείς. Η μείωση του όγκου που προκύπτει είναι σχετικά μικρή. Η τρέχουσα πρακτική στην κλινική εφαρμογή φαίνεται και λογική και αποτελεσματική.

No description available.

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

L'objectif de notre thèse est de contribuer à une meilleure délimitation de la forme et de l'extension de tumeurs intracrâniennes afin de pouvoir mieux les traiter par radiothérapie conformationnelle. Plusieurs approches ont été utilisées. Par une étude anatomo-pathologique autopsique, nous avons pu démontrer que les métastases cérébrales de plusieurs types de tumeurs s'étendent au moins 1 mm au-delà de leur bord macroscopiquement visible. Les métastases de tumeurs pulmonaires à petites cellules sont celles pour lesquelles nous observons la plus grande extension. En utilisant des techniques de spectroscopie et de l'imagerie par RMN, nous avons observé que des discordances existent dans 47% des voxels examinés. Le plus souvent, l'image apparaît pathologique en RMN et normale en spectroscopie, peut-être en raison d'un oedème périlésionnel important. Une troisième approche a été l'analyse comparative de l'extension de méningiomes intracrâniens par la RMN et par une nouvelle méthode d'imagerie métabolique (PET scan à un acide aminé marqué au fluor 18). Tous les méningiomes sont bien visualisés par le PET scan. Une concordance complète entre image de RMN et de PET scan est observée dans 54% des cas, l'image est plus étendue en PET scan dans 38 % des cas et la situation inverse est observée dans 8% des cas. Enfin, nous avons validé toute la chaîne de traitement en radiochirurgie sur des neurinomes de l'acoustique. Nous obtenons des résultats cliniques comparables à ceux de grandes séries publiées. En conclusion, nos travaux montrent que l'image anatomique seule (la RMN) est insuffisante pour délimiter la plupart des tumeurs intracrâniennes et que des méthodes complémentaires (spectroscopie, imagerie dite métabolique) sont nécessaires pour la préparation au traitement par radiothérapie de précision.

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