A Terapia com Laser de Baixa Intensidade (TLBI) pode ser utilizada para tratar dores agudas e crônicas. Entender as vias da dor e as interações de fótons com tecidos neurais possibilitará compreender melhor essas terapias. A nocicepção pode ser autocontrolada por analgésicos endógenos, opióides naturais que bloqueiam a liberação de neurotransmissores excitatórios e, portanto, fazem uma inibição sensorial total e inespecífica. Sabe-se que a TLBI pode estimular a liberação desses analgésicos endógenos e inibir temporariamente o transporte axonal em fibras de pequeno diâmetro. Conhecer a fluência luminosa no interior do tecido neural é essencial para avaliar as hipóteses descritas, no entanto, devido à complexidade dos tecidos biológicos, calcular (ou simular) as interações da luz com os tecidos é impraticável. Para superar esse problema, desenvolvemos experimentos para estimar a fluência de luz em aplicação transcraniana de laser e mapeamos as propriedades ópticas do encéfalo de rato. Foi possível diferenciar tecidos encefálicos por suas características de atenuação da intensidade luminosa e estimar a profundidade da penetração da luz que pode ser de mais de 20 mm. Encontramos redução da dor evocada por pressão, calor, frio ou inflamação após TLBI transcraniana em camundongos. Para esse estudo comportamental, desenvolvemos um equipamento para avaliar o limiar de dor por aplicação de pressão nos animais, que opera com melhor precisão que os instrumentos comerciais. Os mecanismos de fotoneuromodulação foram investigados por quantificação de Trifosfato de Adenosina (ATP), imunofluorescência e marcação com hematoxilina-eosina de tecidos encefálicos que foram visualizados por microscópio confocal. A iluminação transcraniana aumentou a produção de ATP e de Fosfatase ácida prostática (um analgésico endógeno) e reduziu a quantidade do neurotransmissor glutamato, responsável pela condução da informação nociceptiva. Por outro lado, não observamos alteração na concentração de tubulina, um dos constituintes do citoesqueleto, e a marcação com hematoxilina-eosina revelou que não houve dano ao tecido decorrente da iluminação. Os achados apresentados nesse estudo atestam a relevância e eficácia da fotoneuromodulação proveniente de iluminação transcraniana com laser de 808 nm para suprimir a nocicepção em camundongos. Esse estudo é pioneiro na elucidação dos mecanismos de ação da fotoneuromodulação da dor in vivo. / Low-level Light therapy (LLLT) can treat acute and chronic pain. Getting knowledge about the pain pathways and the photon-neuron interactions may contribute to a better understanding of this therapy. The nociception may be self-controlled by endogenous analgesics, natural opioids that block the release of excitatory neurotransmitters, and thus make a total and nonspecific sensory inhibition. It is known that LLLT can stimulate the release of these endogenous analgesics, so it temporarily inhibits axonal transport in small diameter fibers. The knowledge of light fluence through neural tissue is essential to test the discussed assumptions. However, due to the complexity of biological tissues, the calculation (or simulation) of light-tissue interactions is impractical. In order to overcome this problem, we developed an experimental setup to estimate the light fluence in a transcranial LLLT and to map the optical properties of rat brains. It was possible to differentiate cerebral tissues and to estimate the depth of light penetration, which is more than 20 mm. We found a decrease in pain evoked either by pressure, heat, cold or inflammation after transcranial LLLT in mice. For this animal behavioral study, we developed an equipment to assess the pain threshold with pressure stimulus, which operates with better precision than commercial instruments. The LLLT mechanisms were investigated by Adenosine triphosphate ATP quantification, immunofluorescence and haematoxylin and eosin staining of brain tissues which were imaged by confocal microscopy. The transcranial irradiation increased ATP and prostatic acid phosphatase (an endogenous analgesic) production and reduced the amount of glutamate, the neurotransmitter responsible for conducting nociceptive information. There was no change in the concentration of tubulin, a constituent of the cytoskeleton, and the haematoxylin and eosin staining revealed no tissue damage due to the irradiation. This study is pioneer in elucidating the mechanisms of in vivo photoneuromodulation of pain.

A modelagem de processos em física e engenharia frequentemente resulta em problemas inversos. Em geral, esses problemas apresentam difícil resolução, pois são classificados como mal-postos. Resolvê-los, tratando-os como problemas de otimização, requer a minimização de uma função objetivo, que mede a discrepância entre os dados experimentais e os obtidos pelo modelo teórico, somada a uma função de regularização. Na maioria dos problemas práticos, essa função objetivo é não-convexa e requer o uso de métodos de otimização estocásticos. Dentre eles, tem-se o algoritmo de recozimento simulado (Simulated Annealing), que é baseado em três pilares: i) distribuição de visitação no espaço de soluções; ii) critério de aceitação; e iii) controle da estocasticidade do processo. Aqui, propomos uma nova generalização do algoritmo de recozimento simulado e da função de regularização. No algoritmo de otimização, generalizamos o cronograma de resfriamento, que usualmente são considerados algébricos ou logarítmicos, e o critério de Metropolis. Com relação à função de regularização, unificamos as versões mais utilizadas, em uma única fórmula. O parâmetro de controle dessa generalização permite transitar continuamente entre as regularizações de Tikhonov e entrópica. Por meio de experimentos numéricos, aplicamos nosso algoritmo na resolução de dois importantes problemas inversos na área de Física Médica: a determinação do espectro de um feixe de raios X, a partir de sua curva de atenuação, e a reconstrução da imagem na tomografia de impedância elétrica. Os resultados mostram que o algoritmo de otimização proposto é eficiente e apresenta um regime ótimo de parâmetros, relacionados à divergência do segundo momento da distribuição de visitação. / Modeling of processes in Physics and Engineering frequently yields inverse problems. These problems are normally difficult to be solved since they are classified as ill-posed. Solving them as optimization problems require the minimization of an objective function which measures the difference between experimental and theoretical data, added to a regularization function. For most of practical inverse problems, this objective function is non-convex and needs a stochastic optimization method. Among them, we have Simulated Annealing algorithm, which is based on three fundamentals: i) visitation distribution in the search space; ii) acceptance criterium; and iii) control of process stochasticity. Here, we propose a new generalization of simulated annealing algorithm and of the regularization function. On the optimization algorithm, we have generalized both the cooling schedule, which usually is algebric or logarithmic, and the Metropolis acceptance criterium. Regarding to regularization function, we have unified the most used versions in an unique equation. The generalization control parameter allows exchange continuously between the Tikhonov and entropic regularization. Through numerical experiments, we applied our algorithm to solve two important inverse problems in Medical Physics: determination of a beam X-rays spectrum from its attenuation curve and the image reconstruction of electrical impedance tomography. Results show that the proposed algorithm is efficient and presents an optimal arrangement of parameters, associated to the divergence of the visitation distribution.

O estudo do espectro de raios X é importante para predizer a qualidade da imagem em sistemas radiográficos. Nesse trabalho usamos um detector semicondutor CdTe para medir os espectros de raios X na faixa de 25 a 120 kVp. Esse detector é pequeno e fácil de ser transportado. As medidas feitas diretamente do tubo de raios X não são aconselháveis devido à alta taxa de fluência que estão acima dos limites de detecção dos detectores usuais e podem causar armadilhamento de carga no detector CdTe. A alternativa é medir os fótons espalhados a 900 a partir de um pequeno objeto espalhador, no nosso caso um cilindro de lucite (PMMA). A partir do espectro espalhado, corrigido para tempo morto e eficiência, e calibrado em energia, efetuamos correções para o ângulo de espalhamento e espalhamento coerente (somente para baixas energias). Só então formalismo de Klein-Nishina para as seções de choque do efeito Compton é aplicado aos espectros, resultando nos espectros primários. Para energia de 120 kVp foi medido um espectro do feixe direto e comparado com o obtido através do espectro espalhado para mesma energia. Para o mesmo feixe, a camada semi-redutora foi avaliada experimentalmente e com o espectro obtido por espalhamento Compton, obtendo-se boa concordância. Observamos na curva de eficiência uma descontinuidade, prevista teoricamente e também observada por outros autores, que deforma o espectro corrigido. Foi aplicado um ajuste polinomial a essa curva, suavizando os espectros obtidos e não alterando sua forma. Os resultados foram satisfatórios e validaram o formalismo apresentado por outros autores, utilizando detectores distintos. / The analysis of x-ray spectra is important to predict image quality in radiographic systems. In this work we used a semiconductor CdTe detector to measure x-ray spectra with a CdTe detector, in the range from 25 to 120 kVp. The CdTe detector is small and portable. The measurements done directly in the primary X rays beam can be difficult because of the high photon fluence rates that cause significant detector photon pile up, and can cause charge trapping in the CdTe. The alternative is to measure the photons scattered at 900 by a small scattering object, in our case a Lucite cylinder (PMMA). Starting from the scattered spectrum, corrected to dead time and efficiency and calibrated in energy, we made corrections for the scattering angle and coherent scattering (only at low energies). After that, the Klein Nishina cross section for Compton scattering are applied to the spectra, resulting in the primary spectra. For the 120 kVp beam a spectrum of the direct beam was measured and compared to the one obtained it through the scattered spectrum for the same energy. The half value layer of the same spectrum was determined experimentally and through the calculated spectrum, and the agreement was very good. The efficiency curve presents a discontinuity, also observed by other authors and predicted theoretically, that deforms the corrected spectrum. A polynomial fitting was adjusted to the efficiency curve, smoothing the corrected spectra without and not altering its form. The results were satisfactory and they validated the methodology presented by other authors, using different detectors.

A common co-pathology of large lung tumors located near the central airways is collapse of portions of lung due to blockage of airflow by the tumor. Not only does the lung volume decrease as collapse occurs, but fluid from capillaries also fills the space no longer occupied by air, greatly altering tissue appearance. During radiotherapy, typically administered to the patient over multiple weeks, the tumor can dramatically shrink in response to the treatment, restoring airflow to the lung sections which were collapsed when therapy began. While return of normal lung function is a positive development, the change in anatomy presents problems for future radiation sessions since the treatment was planned on lung geometry which is no longer accurate. The treatment must be adapted to the new lung state so that the radiation continues to accurately target the tumor while safely avoiding healthy tissue. However, to account for the dose delivered previously, correspondences of anatomy between the former image when the lung was collapsed and the re-expanded lung in a current image must be obtained. This process, known as deformable image registration, is performed by registration software. Most registration algorithms assume that identical anatomy is contained in the images and that intensities of corresponding image elements are similar; both assumptions are untrue when collapsed lung re-expands. This work was to develop an algorithm which accurately registers images in the presence of lung expansion. The lung registration method matched CT images of patients aided by vessel enhancement and information of individual lobe boundaries. The algorithm was tested on eighteen patients with lung collapse using physician-specified correspondences to measure registration error. The image registration algorithm developed in this work which was designed for challenging lung patients resulted in accuracy comparable to that of other methods when large lung changes are absent.

The design and construction of a tri-cable, planar robotic device for use in neurophysical rehabilitation is presented. The criteria for this system are based primarily on marketability factors, rather than ideal models or mathematical outcomes. The device is designed to be low cost and sufficiently safe for a somewhat disabled individual to use unsupervised at home, as well as in a therapist's office. The key features are the use of a barrier that inhibits the user from coming into contact with the cables as well as a "break-away" joystick that the user utilizes to perform the rehabilitation tasks. In addition, this device is portable, aesthetically acceptable and easy to operate. Other uses of this system include sports therapy, virtual reality and teleoperation of remote devices. / by Melissa M. Morris. / Includes a thesis demonstration video (QuickTImeMovie ; time [2:25] ; size [16.6MB] ; frame width [640] ; frame height [480]. / Thesis (M.S.C.S.)--Florida Atlantic University, 2007. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Les faisceaux de photons produits par les accélérateurs d'électrons linéaires médicaux sont plats, grâce à un cône égalisateur. Les technologies ont évolué et la présence d'un cône n'est plus indispensable. On parle alors de faisceaux FFF (flattening filter free). Les faisceaux FFF présentent des débits de dose plus élevés, des profils de dose hétérogènes, des spectres énergétiques différents et une diminution de la dose hors-champ. Cette thèse a eu pour but d'étudier les caractéristiques des faisceaux FFF, ainsi que l'impact de leur utilisation thérapeutique. Plusieurs thématiques ont été. Des expériences d'irradiation in vitro ont tout d'abord permis de s'assurer que les débits de dose FFF n'ont pas d'impact radiobiologique sur la réponse des cellules irradiées. Une large revue de la littérature a permis de corroborer ces résultats. Afin de maitriser les caractéristiques physiques des faisceaux FFF, des mesures ont été faites avec différents détecteurs. Les effets du spectre et du débit de dose sur la calibration en dose ont aussi été étudiés. Les faisceaux FFF ont été modélisés dans deux TPS. Les modèles ont été comparés entre les deux types de faisceaux et entre les deux TPS. La mise en place des traitements stéréotaxiques a aussi été l'occasion d'appréhender la dosimétrie des petits faisceaux. Nous avons étudié des cas VMAT de cancer de la prostate et des cas de stéréotaxies 3D de tumeurs pulmonaires. La comparaison donne un avantage aux faisceaux FFF. La maitrise de la physique et de la biologie des haut débits a permis de débuter les traitements FFF à l'IPC. Des études comparatives nous permettent aujourd'hui d'adapter leur utilisation au cas par cas. / In medical linear electron accelerators, photon beams profiles are homogenised using flattening filters. Technologies have evolved and the presence of this filter is no longer necessary. Flattening filter free (FFF) beams exhibit higher dose rates, heterogeneous dose profiles, modified energy spectra and lower out-of-field dose. This PhD aimed at studying the characteristics of unflattened beams, as well as their impact in clinical utilization. Several subjects were thoroughly investigated: radiobiology, dosimetry, quality controls, modelling and treatment planning. In vitro experiments ensured that the high dose-rate of FFF beams had not a radiobiological impact. A wide review of the literature was conducted to corroborate these results. In order to understand thoroughly the characteristics of FFF beams, measurements were conducted using several detectors. The effect of the spectra and dose rates of unflattened beams on dose calibration were also studied. FFF beams were modeled in two TPSs. The methods, results and model parameters have been compared between the available beam qualities as well as between both TPSs. Furthermore, the implementation of stereotactic treatments technique was the occasion to investigate small beam dosimetry. Prostate cancer cases treated with VMAT and pulmonary tumors treated with stereotactic 3D beams were also studied. The comparison of dose distributions and treatment metrics give advantage to FFF beams. Mastering physical and biological aspects of flattening filter free beams allowed the IPC to start FFF treatments. Comparative studies have since resulted in a deeper understanding on the pertinent use of these beams.

Magnesium is an essential element. An adult body contains approximately 21-28 grams of magnesium, with 50-60% present in the bones. Too high or too low levels of magnesium intake can have harmful effects on human body. To study how magnesium intake and storage in the body affect human health, it is important to identify a credible biomarker for the intake and storage. Usually, the amount of magnesium in the body is determined by a blood draw, but blood contains less than 1 percent of the total amount of magnesium in the body. In addition, the concentration of magnesium in blood is not stable. Bone holds the majority of magnesium in the body; therefore, bone is expected to be an ideal biomarker for measuring any surplus or deficiencies in the body. This thesis investigates the feasibility of quantifying magnesium in hand bone <i>in vivo</i> using MCNP simulation models and experiments with magnesium doped phantoms. The fast neutrons, generated by a deuterium-deuterium neutron generator with a flux of 1e9 neutrons/second, were moderated and guided to produce maximum number of thermal neutrons in an irradiation cave with acceptable radiation dose to the hand. The dimensions of the neutron generator along with the current shielding techniques were simulated in MCNP. The data show that the differences between the experimental and simulated calibration lines resulted in a percent difference of 9.40%. The experimental detection limit for bone magnesium was found to be 334 µg magnesium/g dry bone with a total body dose of 11 µSv.

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

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