Accumulation de dose à partir de champs de déformation 4D appliqués aux traitements au CyberKnife et à l'IMRT

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.

Ottimizzazione di un sistema di calcolo Voxel dosimetry e implementazione di grandezze radiobiologiche per MRT

Il presente lavoro di tesi nasce in seguito all’esperienza di tirocinio svolta presso l’Arcispedale Santa Maria Nuova di Reggio Emilia. Fulcro di questo lavoro è lo sviluppo di un sistema di pianificazione della dose per il trattamento dei pazienti sottoposti a Molecular Radionuclide Therapy (MRT). Presso tale struttura ospedaliera è già stato sviluppato uno strumento che si appoggia all’ambiente di lavoro Matlab per il calcolo dosimetrico. Tale programma è chiamato VoxelMed. Si tratta di uno strumento di calcolo che lavora al così detto voxel-level, tecnica di sviluppo recente che permette il calcolo della dose assorbita all’interno di un paziente in modo più dettagliato rispetto ai metodi di calcolo basati unicamente sulla stima media per organo, tipicamente impiegati in dosimetria tradizionale. Parte del lavoro di tesi consiste nell’implementare nuove modalità di calcolo ed aggiungere ulteriori accorgimenti all’attuale versione di VoxelMed. In VoxelMed è stata poi integrata ex-novo una componente di calcolo di misure radiobiologiche, in particolare della BED. La dose assorbita non è infatti un parametro sufficiente per valutare gli effetti della radiazione sui tessuti, a parità di tipo ed energia della radiazione gli effetti possono essere molto variabili. La BED è il parametro che tiene conto della risposta del tessuto sano o cancerogeno alla radiazione. Parte del lavoro è stato svolto sperimentalmente, tramite misure con fantocci acquisiti o preparati ad hoc. In particolare si sono utilizzati diverse tipologie di fantocci, per effettuare protocolli di calibrazione dei sistemi di acquisizione, misure di curve di effetto di volume parziale e test finali di verifica. Per un ulteriore verifica delle prestazioni di calcolo si sono effettuate misurazioni su un gruppo di pazienti e si sono confrontati i risultati con quelli ottenuti dal software maggiormente utilizzato nella pratica clinica, OLINDA/EXM.

Applications of metrological techniques for clinical implementation of dosimetry and radiobiology in molecular radiotherapy

Molecular radiotherapy (MRT) is a fast developing and promising treatment for metastasised neuroendocrine tumours. Efficacy of MRT is based on the capability to selectively "deliver" radiation to tumour cells, minimizing administered dose to normal tissues. Outcome of MRT depends on the individual patient characteristics. For that reason, personalized treatment planning is important to improve outcomes of therapy. Dosimetry plays a key role in this setting, as it is the main physical quantity related to radiation effects on cells. Dosimetry in MRT consists in a complex series of procedures ranging from imaging quantification to dose calculation. This doctoral thesis focused on several aspects concerning the clinical implementation of absorbed dose calculations in MRT. Accuracy of SPECT/CT quantification was assessed in order to determine the optimal reconstruction parameters. A model of PVE correction was developed in order to improve the activity quantification in small volume, such us lesions in clinical patterns. Advanced dosimetric methods were compared with the aim of defining the most accurate modality, applicable in clinical routine. Also, for the first time on a large number of clinical cases, the overall uncertainty of tumour dose calculation was assessed. As part of the MRTDosimetry project, protocols for calibration of SPECT/CT systems and implementation of dosimetry were drawn up in order to provide standard guidelines to the clinics offering MRT. To estimate the risk of experiencing radio-toxicity side effects and the chance of inducing damage on neoplastic cells is crucial for patient selection and treatment planning. In this thesis, the NTCP and TCP models were derived based on clinical data as help to clinicians to decide the pharmaceutical dosage in relation to the therapy control and the limitation of damage to healthy tissues. Moreover, a model for tumour response prediction based on Machine Learning analysis was developed.

Relações entre marcadores digito-palamres e aptidão fisica em atletas de judo de elite

Universidade Estadual de Campinas . Faculdade de Educação Física

Dosimetria esporular: Bacillus subtilis TKJ6312 como biossensor de radiação solar biologicamente ativa

Since 2000, spore dosimetry and spectral photometry have been performed in parallel at the Southern Space Observatory, São Martinho da Serra (Southern Brazil). A comparative study involving data from Punta Arenas - Chile (53.2º S), São Martinho da Serra (29.5º S), Padang - Indonesia (0.9ºS), Brussels - Belgium (50.9º N) and Kiyotake - Japan (31.9º N) from 2000 to 2006 is presented. The Spore Inactivation Doses presented the higher values in summer (973 ± 73 for Punta Arenas and 4,369 ± 202 for São Martinho da Serra, as well 1,402 ± 170 and 3,400 ± 1,674 for Brussels and Kiyotake, respectively). The simplicity, robustness and high resistance of bacterial spores makes the biosensor an potential biological tool for UV-B monitoring.

Diffusive Synchronization of Hyperchaotic Lorenz Systems

The synchronizing properties of two diffusively coupled hyperchaotic Lorenz 4D systems are investigated by calculating the transverse Lyapunov exponents and by observing the phase space trajectories near the synchronization hyperplane. The effect of parameter mismatch is also observed. A simple electrical circuit described by the Lorenz 4D equations is proposed. Some results from laboratory experiments with two coupled circuits are presented. Copyright (C) 2009 Ruy Barboza.

Gene Expression Profiles in Radiation Workers Occupationally Exposed to Ionizing Radiation

Ionizing radiation OR) imposes risks to human health and the environment. IR at low doses and low (lose rates has the potency to initiate carcinogenesis. Genotoxic environmental agents such as IR trigger a cascade of signal transduction pathways for cellular protection. In this study, using cDNA microarray technique, we monitored the gene expression profiles in lymphocytes derived from radiation-ex posed individuals (radiation workers). Physical dosimetry records on these patients indicated that the absorbed dose ranged from 0.696 to 39.088 mSv. Gene expression analysis revealed statistically significant transcriptional changes in a total of 78 genes (21 up-regulated and 57 clown-regulated) involved in several biological processes such as ubiquitin cycle (UHRF2 and PIAS1), DNA repair (LIG3, XPA, ERCC5, RAD52, DCLRE1C), cell cycle regulation/proliferation (RHOA, CABLES2, TGFB2, IL16), and stress response (GSTP1, PPP2R5A, DUSP22). Some of the genes that showed altered expression profiles in this study call be used as biomarkers for monitoring the chronic low level exposure in humans. Additionally, alterations in gene expression patterns observed in chronically exposed radiation workers reinforces the need for defining the effective radiation dose that causes immediate genetic damage as well as the long-term effects on genomic instability, including cancer.