Made available in DSpace on 2014-10-09T12:48:40Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:59:57Z (GMT). No. of bitstreams: 1 09020.pdf: 3988111 bytes, checksum: 2604028ac5be423a7b85b745a959fb86 (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-10-09T12:48:40Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:59:57Z (GMT). No. of bitstreams: 1 09020.pdf: 3988111 bytes, checksum: 2604028ac5be423a7b85b745a959fb86 (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

<p dir="ltr">Introduction: Radiotherapy is a treatment modality that is prescribed for more than 50% of cancer patients around the globe. Through decades of clinical application, RT has witnessed considerable advancements achieving significant tumor control with minimal damage to healthy tissues. Recently, a paradigm shift has recognized RT's potential to induce anti-tumor immune responses, where patients receiving radiation to the primary tumor also resolved lesions outside the treatment field. This out-of-field response also referred to as an abscopal effect, is believed to promote immunogenic cell death (ICD) initiated by the radiation-induced DNA damage and subsequent activation of the cGAS-STING-IFNβ pathways. However, clinical realization of an abscopal effect remains rare. We <i><u>hypothesize</u></i> by selectively irradiating cancer cells with high metastatic potential within a solid tumor (intra-tumor radiotherapy treatment planning) with high metastatic potential, a more efficient anti-tumor response can be achieved while minimizing inflammatory responses from surrounding tumor and normal tissues, obfuscating a potential adaptive immune response, thus help in overcoming the rarity observed in the clinical practice. To achieve this <i><u>objective</u></i>, radiotherapy treatment plans targeting hypoxic regions (known to harbor a metastatic phenotype) within a solid tumor and optimally activating IFNβ will be investigated.</p><p dir="ltr">Methods: Hypoxic conditions within tumor microenvironments significantly reduce DNA damage, conferring a radioresistant phenotype that leads to RT failure. To address the inherent radioresistance and immunosuppression of hypoxic tumors, high linear energy transfer (LET) modalities are used. Our research aims to enhance the specificity and efficiency of ICD, particularly in highly metastatic (hypoxic) regions within the tumor, by employing heavy charged particle (HCP) beams to optimize DSB induction. Empirical mathematical models have been developed to predict the dose-response of IFNb based on in vitro data and Monte Carlo methods of DSB-induction. These methods are used in maximizing type I interferon (IFNβ) production and subsequent immune response while minimizing the inflammatory response and damage to surrounding tissue. Immunogenic treatment plans, iTPS, have been developed to integrate charged particle beam models for proton, helium, and carbon ions and the above-empirical models into FLUKA Monte Carlo simulations and subsequently evaluated in clinical case studies of brain and lung cancer. Next, new biophysical models accounting for tumor hypoxia were developed and integrated into the iTPS, and clinical case studies were reevaluated.</p><p dir="ltr">Results: SA(1): Developed and integrated charged particle beam models into FLUKA MC for both homogeneous and heterogeneous treatment planning. Empirical equations for RBE_{DSB, pO2}, LET, and IFNβ dose-response were incorporated into FLUKA for voxel-based simulations across oxygen levels. SA(2): RBE_DSB-weighted optimization yielded uniform IFNβ production. High LET enabled carbon ion beams to require the lowest doses, achieving superior peak-to-entrance ratios of 15.85 compared to 10.78 and 7.60 for helium and proton beams, respectively. Patient simulations demonstrated carbon ions' superiority, with D_95% values of 7.68 Gy for the brain and 7.60 Gy for lung tumors, excelling in IFNβ production. SA(3): An optimized treatment plan for uniform IFNβ in hypoxia utilizing empirical equations for RBE_DSB across hypoxia levels was created for different charged particles. MCC13 adjustments based on OER_DSB from MCDS were confirmed by measured data in U251 cell lines, showing an OER of 1.5 between normoxia and 1% hypoxia, closely matching MCDS predictions within a 7% discrepancy. Carbon ions achieved optimal IFNβ at 11.02 Gy for brain tumors under 0.1% hypoxia in FLUKA simulations.</p><p dir="ltr">Conclusions: Our results from both homogeneous target and patient cases demonstrate that charged particles have the potential to elicit higher levels of IFNβ at lower doses compared to photon irradiations in different pO₂ levels. High LET irradiation not only ensures a highly localized IFNβ response in the target but also effectively spares surrounding normal tissues, thereby minimizing treatment-related toxicity. This finding underscores the superiority of high LET irradiation in achieving targeted immunogenic effects while enhancing the therapeutic window by reducing damage to normal cells.</p>

Radiotherapy is used in clinics to treat cancer with highly energetic ionizing particles. The radiation dose can be measured indirectly by means of radiation detectors or dosimeters. The dose deposited in a detector can be related to dose deposited in a point within the patient. In theory, however, this is only possible under charged particle equilibrium (CPE). The motivation behind the dissertation was driven by the difficult, yet crucial, dosimetry in non-CPE regions. Inaccurate dose assessment performed with standard dosimetry using ionization chambers may significantly impact the outcomes of radiotherapy treatments. Therefore, advanced dosimetry methods tailored specifically to suit non-CPE conditions must be used. This work aims to improve dosimetry in two types of non-CPE conditions that pose dosimetric challenges: regions near interfaces of tissues with low- and high- density media and in small photon fields. To achieve the main dissertation objectives, an enhanced film dosimetry protocol with a novel film calibration approach was implemented. This calibration method is based on the percent depth dose (PDD) tables and was shown to be efficient and accurate. As a result, the PDD calibration method was used for the film dosimetry process throughout the dissertation work. Monte Carlo (MC) calculations for the small field dosimetry were performed using phase-space files (PSFs) provided by Varian for TrueBeam linac. The MC statistical uncertainty in these types of calculations is limited by the number of particles (due to latent variance) in the used PSFs. This study investigated the behaviour of the latent variances (LV) with beam energy, depth in phantom, and calculation resolution (voxel size). LV was evaluated for standard 10x10 cm2 fields as well as small fields (down to 1.3 mm diameter). The results showed that in order to achieve sub-percent LV in open 10x10 cm2 field MC simulations a single PSF can be used, whereas for small SRS fields (1.3—10 mm) more PSFs (66—8 PSFs) would have to be summed. The first study in this dissertation compared the performance of several dosimetric methods in three multi-layer heterogeneous phantoms with water/air, water/lung, and water/steel interfaces irradiated with 6 and 18 MV photon beams. MC calculations were used, along with Acuros XB, anisotropic analytical algorithm (AAA), GafChromic EBT2 film, and MOSkin dosimeters. PDDs were calculated and measured in these heterogeneous phantoms. The result of this study showed that Acuros XB, AAA, and MC calculations were within 1% in the regions with CPE. At media interfaces and buildup regions, differences between Acuros XB and MC were in the range of +4.4% to -12.8%. MOSkin and EBT2 measurements agreed to MC calculations within ~ 2.5%-4.5%. AAA did not predict the backscatter dose from the high-density heterogeneity. For the third, multilayer lung phantom, 6 MV beam PDDs calculated by all treatment planning system (TPS) algorithms were within 2% of MC. 18 MV PDDs calculated by Acuros XB and AAA differed from MC by up to 3.2 and 6.8%, respectively. MOSkin and EBT2 each differed from MC by up to 3%. All dosimetric techniques, except AAA, agreed within 3% in the regions with particle equilibrium. Differences between the dosimetric techniques were larger for the 18 MV than the 6 MV beam. This study provided a comparative performance evaluation of several advanced dosimeters in heterogeneous phantoms. This combination of experimental and calculation dosimetry techniques was used for the first time to evaluate the dose near these interfaces. The second study in the dissertation aims to improve dose measurement accuracy in small radiotherapy fields. Field output factors of 6 MV beams from TrueBeam linear accelerator (linac) collimated with 1.27-40 mm diameter cones were calculated and measured using MC and EBT3 films. A set of detector specific correction factors for two widely used dosimeters (EFD-3G diode and PTW-60019 microDiamond detectors) were determined based on GafChromic EBT3 film measurements and calculated using MC methods. MC calculations were performed for microDiamond detector in parallel and perpendicular orientations relative to the beam axis. The result of this study showed that the measured OFs agreed within 2.4% for fields ≥10 mm. For the cones of 1.27, 2.46, and 3.77 mm diameter maximum differences were 17.9%, 1.8% and 9.0%, respectively. MC calculated OF in water agreed with those obtained using EBT3 film within 2.2% for all fields. MC calculated output correction factors for microDiamond detector in fields ≥10 mm ranged within 0.975-1.020 for perpendicular and parallel orientations. MicroDiamond detector correction factors calculated for the 1.27, 2.46 and 3.77 mm fields were 1.974, 1.139 and 0.982 with detector in parallel orientation, and these factors were 1.150, 0.925 and 0.914 in perpendicular orientation. EBT3 and MC obtained correction factors agreed within 3.7% for fields of ≥3.77 mm and within 5.9% for smaller cones. This work provided output correction factors for microDiamond and EFD-3G detectors in very small fields of 1.27 – 3.77 mm diameter and demonstrated over and under-response of these detectors in such fields. These correction factors allow improve the accuracy of dose measurements in small photon fields using these detectors. / Graduate / 2019-08-30

This thesis contains a study of the robustness of the artificial neural network used in the ATLAS track reconstruction algorithm as a tool to recover tracks in dense environments. Different variations, motivated by potential discrepancies between data and simulation, are performed to the neural network’s input while monitoring the corresponding change in the output. Within reasonable variation magnitudes, the neural networks prove to be robust to most variations. In addition, a measurement of charged particle distributions is summarised. This is one of the first such measurements carried out for proton-proton colli- sions at √s = 13 TeV, limited to a phase space defined by transverse momentum pT &gt; 100 MeV and absolute pseudorapidity |η| &lt; 2.5. Tracks are corrected for de- tector inefficiencies and unfolded to particle-level. The result is compared to the prediction of different models. Overall, the EPOS and Pythia 8 A2 models show the best agreement with the data. / Spår från elektriskt laddade partiklar rekonstrueras i ATLAS genom att kombinera mätningar från de innersta subdetektorerna. I de extrema miljöer som skapas i proton-proton-kollisionerna i Large Hadron Collider vid CERN är det av yttersta vikt att algoritmen för att rekonstruera spår är högpresterande. Uppgiften är särskilt svår i partikelrika miljöer där flera partiklar färdas nära varandra, åtskilda av avstånd jämförbara med storleken på detektorns utläsningselement. Ett artificiellt neuralt nätverk används i algoritmen för att klassificera mätdata från pixeldetektorn, belägen närmast interaktionspunkten, för att lyckas identifiera spår i partikelrika miljöer som annars hade gått förlorade. I denna avhandling utreds det neurala nätverkets stabilitet. Dess känslighet studeras genom att manuellt manipulera dess indata och därefter utvärdera dess resultat. Nätverket tränas med simulerad data. Variationerna i indata är utformade för att undersöka skillnader mellan data och simulering, orsakade av osäkerheter i simuleringsmodellen eller osäkerheter i pixeldetektorns kalibrering. Av de undersökta variationerna har en osäkerhet i skalan eller utläsningströskeln för pixeldetektorns kalibrering den största effekten på nätverkets resultat. Andra variationer har en betydligt mindre påverkan. Avhandlingen presenterar också en studie av distributioner av elektriskt laddade partiklar producerade i proton-proton-kollisioner. Det är en av de första studierna av partikeldistributioner för Large Hadron Colliders andra körning med mass-centrum-energi √s = 13 TeV. Mätningen är begränsad till fasrymden definierad av en transversell rörelsemängd pT &gt; 100 MeV, och absolut rapiditet |η| &lt; 2.5. Spår av partiklar rekonstrueras och korrigeras för detektorns ineffektiviteter för att presenteras på partikelnivå. Dessa jämförs sedan med förutsägelser från olika modeller. Modellerna EPOS och Pythia 8 A2 är generellt de som bäst överensstämmer med data. Författaren har undersökt partiklar som migrerar in och ut ur fasrymden. Andelen spår associerade till partiklar som migrerat utifrån uppskattas med simulerad data, till som mest 10% nära fasrymdens gränser. Osäkerheten på denna andel uppskattas till att vara som mest 4.5%, huvudsakligen orsakad av osäkerheten på mängden material i de innersta subdetektorerna. / <p>QC 20160817</p>

Thesis (MSc)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: See full text for abstract / AFRIKAANSE OPSOMMING: Sien volteks vir opsomming

No description available.

No description available.

<p>Mass spectrometry is widely considered to be the gold standard of elemental analysis techniques due to its ability to resolve atomic and molecular and biological species. Expanding the application space of mass spectrometry often requires the need for portable or hand-held systems for use in field work or harsh environments. While only requiring “sufficient” mass resolution to meet the needs of their application space, these miniaturized systems suffer from poor signal to background ratio which limits their sensitivity as well as their usefulness in field applications. </p><p>Spatial aperture coding techniques have been used in optical spectroscopy to achieve large increases in signal intensity without compromising system resolution. In this work similar computational methods are used in the application of these techniques to the field of magnetic sector mass spectrometry. Gains in signal intensity of 10x and 4x were achieved for 1D and 2D coding techniques (respectively) using a simple 90 degree magnetic sector test setup. Initial compatibility with a higher mass resolution double focusing Mattauch-Herzog mass spectrograph is demonstrated experimentally and with high fidelity particle tracing simulations. A novel electric sector lens system was designed to stigmate high order coded aperture patterned beam which shows simulated gains in signal intensity of 50x are achievable using these techniques.</p> / Dissertation

The objective of this research is to design, fabricate, and demonstrate a microfabricated monolithic ion trap for applications in quantum computation and quantum simulation. Most current microfabricated ion trap designs are based on planar-segmented surface electrodes. Although promising scalability to trap arrays containing ten to one hundred ions, these planar designs suffer from the challenges of shallow trap depths, radial asymmetry of the confining potential, and electrode charging resulting from laser interactions with dielectric surfaces. In this research, the design, fabrication, and testing of a monolithic and symmetric two-level ion trap is presented. This ion trap overcomes the challenges of surface-electrode ion traps. Numerical electrostatic simulations show that this symmetric trap produces a deep (1 eV for 171Yb+ ion), radially symmetric RF confinement potential. The trap has an angled through-chip slot that allows back-side ion loading and generous through laser access, while avoiding surface-light scattering and dielectric charging that can corrupt the design control electrode compensating potentials. The geometry of the trap and its dimensions are optimized for trapping long and linear ion chains with equal spacing for use with quantum simulation problems and quantum computation architectures.