Radiation therapy with light ions improves treatment outcome for a number of tumor types. The advantageous dose distributions of light ion beams en-able exceptional target conformity, which assures high dose delivery to the tumor while minimizing the dose to surrounding normal tissues. The demand of high target conformity necessitates development of accurate methods to calculate absorbed dose distributions. This is especially important for heavy charged particle irradiation, where the patient is exposed to a complex radia-tion field of primary and secondary ions. The presented approach combines accurate Monte Carlo calculations using the SHIELD-HIT07 code with a fast analytical pencil beam model, to pro-vide dose distributions of light ions. The developed model allows for ana-lytical descriptions of multiple scattering and energy loss straggling proc-esses of both primary ions and fragments, transported in tissue equivalent media. By applied parameterization of the radial spread of fragments, im-proved description of radial dose distributions at every depth is obtained. The model provides a fast and accurate tool of practical value in clinical work. Compared to conventional radiation modalities, an enhanced tissue response is seen after light ion irradiation and biological optimization calls for accu-rate model description and prediction of the biological effects of ion expo-sure. In a joint study, the performance of some radiobiological models is compared for facilitating the development towards more robust and precise models. Specifically, cell survival after exposure to various ion species is modeled by a fast analytical cellular track structure approach in conjunction with a simple track-segment model of ion beam transport. Although the stud-ies show that descriptions of complex biological effects of ion beams, as given by simple radiobiological models, are approximate, the models may yet be useful in analyzing clinical results and designing new strategies for ion therapy.

Acquired data from dynamic contrast enhanced MRI measurements can be used to non-invasively assess tumour vascular characteristics through pharmacokinetic modelling. The modelling requires an arterial input function which is the concentration of contrast agent in the blood reaching the volume of interest as a function of time. The aim of this work is testing and optimizing a turboFLASH sequence to appraise its suitability for measuring the arterial input function by measuring phase. Contrast concentration measurements in a phantom were done with both phase and relaxivity techniques. The results were compared to simulations of the experiment conditions to compare the conformance. The results using the phase technique were promising, and the method was carried on to in-vivo testing. The in-vivo data displayed a large signal loss which motivated a new phantom experiment to examine the cause of this signal reduction. Dynamic measurements were made in a phantom with pulsatile flow to mimic a blood vessel with a somewhat modified turboFLASH sequence. The conclusions drawn from analyzing the data were used to further improve the sequence and this modified turboFLASH sequence was tested in an in-vivo experiment. The obtained concentration curve showed significant improvement and was deemed to be a good representation of the true blood concentration. The conclusion is that phase measurements can be recommended over relaxivity based measurements. This recommendation holds for using a slice selective saturation recovery turboFLASH sequence and measuring the arterial input function in the neck. Other areas of application need more thorough testing.

<p>Developing radiation delivery systems for optimisation of absorbed dose to the target without normal tissue toxicity requires advanced calculations for transport of radiation. In this thesis absorbed dose and fluence in different radiotherapy applications were calculated by using Monte Carlo (MC) simulations.</p><p>In paper I-III external neutron activation of gadolinium (Gd) for intravascular brachytherapy (GdNCB) and tumour therapy (GdNCT) was investigated. MC codes MCNP and GEANT4 were compared. MCNP was chosen for neutron capture reaction calculations. Gd neutron capture reaction includes both very short range (Auger electrons) and long range (IC electrons and gamma) products. In GdNCB the high-energetic gamma gives an almost flat absorbed dose delivery pattern, up to 4 mm around the stent. Dose distribution at the edges and inside the stent may prevent stent edge and in-stent restenosis. For GdNCT the absorbed dose from prompt gamma will dominate over the dose from IC and Auger electrons in an in vivo situation. The absorbed dose from IC electrons will enhance the total absorbed dose in the tumours and contribute to the cell killing.</p><p>In paper IV a model for calculation of inter-cluster cross-fire radiation dose from β-emitting radionuclides in a breast cancer model was developed. GEANT4 was used for obtaining absorbed dose. The dose internally in cells binding the isotope (self-dose) increased with decreasing β-energy except for the radionuclides with substantial amounts of conversion electrons and Auger electrons. An effective therapy approach may be a combination of radionuclides where the high self-dose from nuclides with low β-energy should be combined with the inter-cell cluster cross-fire dose from high energy β-particles.</p><p>In paper V MC simulations using correlated sampling together with importance sampling were used to calculate spectra perturbations in detector volumes caused by the detector silicon chip and its encapsulation. Penelope and EGSnrc were used and yielded similar results. The low energy part of the electron spectrum increased but to a less extent if the silicon detector was encapsulated in low z-materials.</p>

A quantitative evaluation of single photon emission computed tomography (SPECT) and planar scintigraphic imaging may be valuable for both diagnostic and therapeutic purposes. For an accurate quantification it is usually necessary to correct for attenuation and scatter and in some cases also for septal penetration. For planar imaging a background correction for the contribution from over- and underlying tissues is needed. In this work a few correction methods have been evaluated and further developed. Much of the work relies on the Monte Carlo method as a tool for evaluation and optimisation. A method for quantifying the activity of I-125 labelled antibodies in a tumour inoculated in the flank of a mouse, based on planar scintigraphic imaging with a pin-hole collimator, has been developed and two different methods for background subtraction have been compared. The activity estimates of the tumours were compared with measurements in vitro. The major part of this work is attributed to SPECT. A method for attenuation and scatter correction of brain SPECT based on computed tomography (CT) images of the same patient has been developed, using an attenuation map calculated from the CT image volume. The attenuation map is utilised not only for attenuation correction, but also for scatter correction with transmission dependent convolution subtraction (TDCS). A registration method based on fiducial markers, placed on three chosen points during the SPECT examination, was evaluated. The scatter correction method, TDCS, was then optimised for regional cerebral blood flow (rCBF) SPECT with Tc-99m, and was also compared with a related method, convolution scatter subtraction (CSS). TDCS has been claimed to be an iterative technique. This requires however some modifications of the method, which have been demonstrated and evaluated for a simulation with a point source. When the Monte Carlo method is used for evaluation of corrections for septal penetration, it is important that interactions in the collimator are taken into account. A new version of the Monte Carlo program SIMIND with this capability has been evaluated by comparing measured and simulated images and energy spectra. This code was later used for the evaluation of a few different methods for correction of scatter and septal penetration of I-123 brain SPECT. The methods were CSS, TDCS and a method where correction for scatter and septal penetration are included in the iterative reconstruction. This study shows that quantitative accuracy in I-123 brain SPECT benefits from separate modelling of scatter and septal penetration.

Developing radiation delivery systems for optimisation of absorbed dose to the target without normal tissue toxicity requires advanced calculations for transport of radiation. In this thesis absorbed dose and fluence in different radiotherapy applications were calculated by using Monte Carlo (MC) simulations. In paper I-III external neutron activation of gadolinium (Gd) for intravascular brachytherapy (GdNCB) and tumour therapy (GdNCT) was investigated. MC codes MCNP and GEANT4 were compared. MCNP was chosen for neutron capture reaction calculations. Gd neutron capture reaction includes both very short range (Auger electrons) and long range (IC electrons and gamma) products. In GdNCB the high-energetic gamma gives an almost flat absorbed dose delivery pattern, up to 4 mm around the stent. Dose distribution at the edges and inside the stent may prevent stent edge and in-stent restenosis. For GdNCT the absorbed dose from prompt gamma will dominate over the dose from IC and Auger electrons in an in vivo situation. The absorbed dose from IC electrons will enhance the total absorbed dose in the tumours and contribute to the cell killing. In paper IV a model for calculation of inter-cluster cross-fire radiation dose from β-emitting radionuclides in a breast cancer model was developed. GEANT4 was used for obtaining absorbed dose. The dose internally in cells binding the isotope (self-dose) increased with decreasing β-energy except for the radionuclides with substantial amounts of conversion electrons and Auger electrons. An effective therapy approach may be a combination of radionuclides where the high self-dose from nuclides with low β-energy should be combined with the inter-cell cluster cross-fire dose from high energy β-particles. In paper V MC simulations using correlated sampling together with importance sampling were used to calculate spectra perturbations in detector volumes caused by the detector silicon chip and its encapsulation. Penelope and EGSnrc were used and yielded similar results. The low energy part of the electron spectrum increased but to a less extent if the silicon detector was encapsulated in low z-materials.

Made available in DSpace on 2014-12-17T15:47:46Z (GMT). No. of bitstreams: 1 FrederikoSLNA.pdf: 5281687 bytes, checksum: 9fe12b6bcc355f7c67cf2f2c3ad9812b (MD5) Previous issue date: 2006-02-16 / This work performs an algorithmic study of optimization of a conformal radiotherapy plan treatment. Initially we show: an overview about cancer, radiotherapy and the physics of interaction of ionizing radiation with matery. A proposal for optimization of a plan of treatment in radiotherapy is developed in a systematic way. We show the paradigm of multicriteria problem, the concept of Pareto optimum and Pareto dominance. A generic optimization model for radioterapic treatment is proposed. We construct the input of the model, estimate the dose given by the radiation using the dose matrix, and show the objective function for the model. The complexity of optimization models in radiotherapy treatment is typically NP which justifyis the use of heuristic methods. We propose three distinct methods: MOGA, MOSA e MOTS. The project of these three metaheuristic procedures is shown. For each procedures follows: a brief motivation, the algorithm itself and the method for tuning its parameters. The three method are applied to a concrete case and we confront their performances. Finally it is analyzed for each method: the quality of the Pareto sets, some solutions and the respective Pareto curves / O presente trabalho realiza um Estudo Algor?tmico para Otimiza??o do Plano de Tratamento da Radioterapia Conformal. Inicialmente s?o apresentadas: uma vis?o geral sobre o c?ncer, o tratamento com radioterapia e no??es sobre a intera??o do feixe de radia??es ionizantes com a mat?ria. Uma proposta para Otimiza??o do Plano de Tratamento Radioter?pico ? desenvolvida de modo sistem?tico. ? apresentado o paradigma de problemas multicrit?rio, os conceitos de Pareto otimalidade e Pareto Domin?ncia. Um modelo Gen?rico de Otimiza??o para o Plano de Tratamento Radioter?pico ? proposto. S?o constru?das suas entradas, ? calculada a dose depositada no corpo do paciente atrav?s do conceito de matriz de dose, e ? apresentada a fun??o objetivo deste modelo. A complexidade dos problemas de otimiza??o do tratamento radioter?pico s?o classificados como de complexidade NP, este resultado justifica o desenvolvimento de m?todos heur?sticos para a sua resolu??o. S?o propostas tr?s metaheur?sticas para a Otimiza??o do Plano de Tratamento Radioter?pico: MOGA, MOSA e MOTS de acordo como o modelo gen?rico de otimiza??o proposto. Os projetos desses procedimentos metaheur?sticos s?o devidamente apresentados. Para cada m?todo se faz uma introdu??o liter?ria, dos seus algoritmos e a da metodologia usada para a afina??o dos par?metros. Os m?todos s?o aplicados a um caso concreto e confrontados atrav?s de medidas de performance. Finalmente ? analisado a qualidade dos conjuntos de Pareto produzidos por cada m?todo, s?o exibidas algumas solu??es geradas e as respectivas curvas de Pareto associadas