This thesis introduces an innovative approach for enhancing the characterization of radiation field quality through microdosimetry. Over the past 30 years, clinical results have shown that ion therapy may be a superior treatment option for several types of cancer, including recurrent cancers, compared to conventional radiation. Despite these promising results, there are still several treatment uncertainties related to biological and physical processes that prevent the full exploitation of particle therapy. Among the physical characterizations, it is paramount to measure the quality of the irradiating field in order to link the biological effect to its physical description. In this way, uncertainties in treatment can be reduced and outcomes optimized. One tool for studying the radiation field that has become increasingly important in the last decade is microdosimetry . Over the last years, microdosimetry has proved to be a superior tool for describing radiation quality, especially when compared to standard reference quantities used nowadays in the clinic. In microdosimetry, the fundamental quantity is the lineal energy y, defined as the energy deposition in the detector divided by the Mean Chord Length (MCL): an approximation used to estimate the track length traveled by radiation in the detector, valid in an isotropic, uniform radiation field. As a consequence, microdosimeters has evolved in obtaining the best possible energy release estimation, without improving the accuracy of the MCL approximation. Measuring the Real Track Length (RTL) traveled by the particle inside the detector could provide a better description of the radiation quality. In fact, from a biological perspective, it is critical if a large amount of energy is released over a long particle track, or if it is extremely dense over a small particle track. If the energy released is more dense, the biological damage induced is likely to be more complex and therefore more significant. For these reasons, a novel approach to microdosimetry is presented that considers the RTL in the radiation quality description. The first chapter of the thesis presents standard microdosimetry and its main quantities. A special emphasis is given to the microdosimeter used in this work, i.e. the TEPC or Tissue Equivalent Proportional Counter, a gas microdosimeter that is equivalent in terms of energy deposition to 2 um of tissue. A comprehensive characterization of the TEPC response to different ions and energies can be found in the literature. A topic missing in the literature is the investigation of the TEPC response to clinical protons of different particles rates. A section is dedicated to the TEPC detector response to pileup. Pileup occurs where two or more energy deposition events are processed together, disrupting the normal signal processing. By exposing the TEPC to particles rates ranging from few particles per seconds to 106 particles per second, it was possible to estimate the distortion of the acquired spectra due to pileup. On the other hand, by using Monte Carlo simulations, it was possible to reproduce the effect of pileup on microdosimetric spectra. Using a quantitative approach, the experimental spectra measured at different particles rate and the spectra simulated at a different pileup probability are matched based on a similarity criteria. In this way, it was possible to build a particle rate-pileup curve for the TEPC, used to quantify the pileup probability contribution. More in general, this approach could be extended and used to other microdosimeters. The acquisition of the data in pileup condition is sometimes inevitable, and some microdosimeters are more likely to suffer from high particle rates. With this part of the thesis, I aim to provide a tool to acquire microdosimetric spectra even in pileup condition. A description of the TEPC acquisition chain is provided in the next section. This is an important topic as any further integration or improvement will require the modification of at least one element of the acquisition. Then, the typical data analysis carried out on the microdosimetric spectra is presented, together with the calibration procedure of the TEPC detector based on Monte Carlo simulation using Geant4. Finally, I provide an overview of the software Mandarina, which is the implemented Graphical User Interface (GUI), written in C# language, and developed specifically to analyze the experimental microdosimetric data. By using this software, users can build a microdosimetric spectra starting from raw acquired data. In addition, the software provides the ability to modify key acquisition parameters and provides real-time feedback on how the microdosimetric spectra change under these modifications. Then, I introduce the concept of Hybrid Detector of Microdosimetry (HDM). HDM is composed of a commercial TEPC, and 4 layers of Low Gain Avalanche Detectors (LGADs). LGADs are silicon detectors featuring an internal gain by exploring the avalanche effect. This makes them suitable to detect particles with a broad range of energy release in the silicon. A detailed description of how the LGADs detect ionizing radiation is provided in this work. LGADs are used in the HDM as a tracking component, capable of reconstructing the particle trajectories inside the TEPC. In this way, instead of relying on the MCL approximation to calculate the value of y, it is possible to define a new quantity: yr. yr differs from the standard y because it uses the real track length instead of the mean chord length approximation. Next, a preliminary Geant4-based study for optimizing the detector geometry is discussed. Tracking capability and simulated microdosimetric spectra with the estimated track length were assessed and are presented in this thesis. To experimentally realize HDM, the acquisition chain of the TEPC must be upgraded since the original acquisition system cannot directly integrate the tracking information from the LGADs strips. A chapter of this work is dedicated to the implementation of the new acquisition system, which allows for the digitalization of the time series signal produced by the detector. The system is based on an Eclypse-Z7 FPGA development board which can host up to 4 Analog to Digital Converters (ADC). Following a bottom-up approach, this chapter describes first the main characteristics of the signal to be digitized. An overview of the Eclypse-Z7 development board with its main capabilities is provided. Finally, the controller in charge of driving the ADC is described. Being a Zynq FPGA, both Programming Logic (PL) and Processing System (PS) need to be programmed. The PL is responsible for driving the ADC at a low level, controlling the triggering and the data flow to the PS. The PS hosts a custom Linux distribution with the task of supervising the acquisition by setting the main parameters, like the number of samples to acquire, the trigger condition and position with respect to the acquisition window. The PS is also responsible for storing the data safely into an SD card connected to the Eclypse-Z7. With a fully customizable system, it is then possible to integrate other systems by properly synchronizing the acquisition with other devices. In the specific case of HDM, a correspondence between the energy release and the LGAD-based tracking component needs to be implemented. Once the time series is properly acquired, the data analysis needs to be developed. A specific section of the thesis is dedicated to this important task, as the correct processing of the signals is a requirement to obtain robust microdosimetric spectra. The time series processing features a classification algorithm that allows to identify artifacts of the acquired signals, such as saturation, double hits and noisy signals. Once the time series are correctly processed and the relevant information is extracted, it is possible to calculate the microdosimetric spectra. In this acquisition chain the detector signal is processed with 3 different levels of gain, obtaining the same version of the signal but with different amplification. In this way it is possible to span a large dynamic range while maintaining the required resolution typical of microdosimetry. However, the three signals must be then joined together to span the required dynamic range. This process goes under the name of intercalibration and has a dedicated section in the chapter. Once the signals are intercalibrated, it is necessary to apply a calibration. The new calibration process developed within this work differs from the previously adopted calibration method based on Monte Carlo simulation, and is described in detail. Finally, the spectra obtained with the new acquisition are compared to those obtained with the original acquisition chain. The next chapter is dedicated to the LGAD readout. Again, following a bottom up approach, an introduction to the LGAD signal is provided. This readout acquisition chain is already partially available since it has been developed by the INFN-TO (Istituto Nazionale di Fisica Nucleare) of Turin. For the first stage of signal processing, two main components developed by the aforementioned INFN-TO are available: the ABACUS chip and the ESA_ABACUS printed circuit board (PCB) board. The ABACUS chip is an ASIC (application-specific integrated circuit) designed to process directly the small signal coming from the LGADs strips. At each activation of one LGAD strip, a digital signal is generated. Each ABACUS is capable of handling up to 24 LGADs strips and can adjust the threshold of each channel within a limited range. Threshold adjustment is required to separate the signal from the noise, as it is expected that all the channels do not share a common threshold due to their specific noise. The ABACUS PCB has been developed to physically host up to 6 ABACUS chips plus the LGAD sensor. It is equipped with an internal DAC (Digital to Analog Converted) used to set a common threshold for all 24 channels managed by one ABACUS chip. In this way, a common threshold can be selected using the ABACUS DAC, and then, to satisfy the specific needs of each channel, the ABACUS chip is used. In order to program the thresholds, the manufacturer required specific serial communication protocols. It is necessary to integrate this communication protocol into the acquisition system. To meet these requirements, I developed an FPGA-based readout system capable of processing the signal from the ABACUS chip and setting the threshold for each channel. I describe in detail the implementation of such a system in a dedicated chapter, again following a bottom-up approach starting from the PL, and moving to the PS. In a specific section, I show how the communication protocol has been implemented and tested and how the fast digital pulses, coming from the ABACUS chip, are processed in the PL. I also describe how the PS system was built. As in the case of the new TEPC acquisition, a Linux system was run on the PS. This made it easier for the end user to work with the acquired data and threshold controls. The movement of data from the PL to the PS is accomplished using DMA or Direct Memory Access. This is a critical component because it allows fast (within one clock cycle) data transfer from the PL to the user in the PS. The implementation of such architecture is quite complex and demands both knowledge in advanced electronics and Linux systems. In fact, the DMA requires the implementation of a Linux kernel driver to correctly move the data. This process is described in a dedicated section of this thesis. With this implementation design in the FPGA it was possible to acquire the signal from 24 LGADs strips and control the thresholds. An experimental campaign was conducted at the proton therapy center in Trento where the whole acquisition system was tested extensively. The results are reported in a dedicated section of this thesis. All the signals coming from the protons with energies ranging from 70 to 228 MeV were correctly discriminated, proving that the readout system can work with protons of clinical energies. Finally, thermal tests were conducted on the acquisition setups since during the experimental campaign some thermal drifts of the baseline were observed. The test results are shown in a dedicated section of this thesis. Finally, I included a chapter on discussion on the results achieved and on future perspective.

Uncertainties persist regarding the assessment of the carcinogenic risk associated with galactic cosmic ray (GCR) exposure. The GCR spectrum peaks in the range of 300 MeV/n to 700 MeV/n and is comprised of elemental ions from H to Ni. While Fe ions represent only 0.03% of the GCR spectrum in terms of particle abundance, they are responsible for nearly 30% of the dose equivalent in free space. Because of this, radiation biology studies focusing on understanding the biological effects of GCR exposure generally use Fe ions. Acting as a thin shield, the Martian atmosphere alters the GCR spectrum in a manner that significantly reduces the importance of Fe ions. Additionally, albedo particles emanating from the regolith complicate the radiation environment. The present study uses the Monte Carlo code FLUKA to simulate the response of a tissue-equivalent proportional counter on the surface of Mars to produce dosimetry quantities and microdosimetry distributions. The dose equivalent rate on the surface of Mars was found to be 0.18 Sv/y with an average quality factor of 2.9 and a dose mean lineal energy of 18.4 keV/µm. Albedo neutrons accounted for 25% of the dose equivalent. Additionally, differential energy spectra were generated in order to determine the fractional contribution to frequency, dose, and dose equivalent for each elemental ion from H to Ni on the surface of Mars. Fe ions were found to account for just 1.3% of the dose equivalent while H and He ions were found to account for 32% and 17%, respectively. It is anticipated that these data will provide relevant benchmarks for use in future risk assessment and mission planning studies.

Thesis (M.S. in computer science)--Washington State University. / Includes bibliographical references.

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When astronauts travel in space, they are exposed to high energy cosmic radiations. The cosmic ray spectrum contains very high energy particles, generally up to several GeV per nucleon. Currently NASA is funding research on the effects, such as acute radiation sickness, of cosmic radiation. Animal models are used to conduct the studies of radiation effects of particles in the range of several MeV/nucleon to about 1000 MeV/nucleon. In order to compare different radiations, the biological effectiveness relative to a specific radiation is usually used. For low energy heavy ions and neutrons 250 keV photons are usually used for the reference radiation but their depth dose distribution is very different from that for cosmic rays. In this research, the advantages of using high energy electrons as the reference radiation for research on cosmic radiation were demonstrated. The conclusion is based on the evaluation of the dose distributions and microdosimetric spectra of the electrons and high energy protons as a function of depth in a tissue equivalent absorber as determined by Geant4 simulation.

Thesis (Ph. D.)--University of Florida, 1988. / Description based on print version record. Typescript. Vita. Includes bibliographical references.

External radiotherapy with proton and ion beams needs accurate tools for the dosimetric characterization of treatment fields. Monte Carlo (MC) particle transport codes, such as FLUKA and GEANT4, can be a valuable method to increase accuracy of dose calculations and to support various aspects of ion beam therapy (IBT), such as treatment planning and monitoring. One of the prerequisites for such applications is however that the MC codes are able to model reliably and accurately the relevant physics processes. As a first focus of this thesis work, physics models of MC codes with importance for IBT are developed and validated with experimental data. As a result suitable models and code configurations for applications in IBT are established. The accuracy of FLUKA and GEANT4 in describing nuclear fragmentation processes and the production of secondary charged nuclear fragments is investigated for carbon ion therapy. As a complementary approach to evaluate the capability of FLUKA to describe the characteristics of mixed radiation fields created by ion beams, simulated microdosimetric quantities are compared with experimental data. The correct description of microdosimetric quantities is also important when they are used to predict values of relative biological effectiveness (RBE). Furthermore, two models describing Compton scattering and the acollinearity of two-quanta positron annihilation at rest in media were developed, validated and integrated in FLUKA. The detailed description of these processes is important for an accurate simulation of positron emission tomography (PET) and prompt-γ imaging. Both techniques are candidates to be used in clinical routine to monitor dose administration during cancer treatments with IBT. The second objective of this thesis is to contribute to the development of a MC-based treatment planning tool for protons and ions with atomic number Z ≤ 8 using FLUKA. In contrast to previous clinical FLUKA-based MC implementations for IBT which only re-calculate a given treatment plan, the developed prototype features inverse optimization of absorbed dose and RBE-weighted dose for single fields and simultaneous multiple-field optimization for realistic treatment conditions. In a study using this newly-developed tool, the robustness of IBT treatment fields to uncertainties in the prediction of RBE values is investigated, while comparing different optimization strategies. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Submitted. Paper 6: Manuscript.</p>

Absorbed dose distributions in lineal energy for neutrons and gamma rays were measured by using both a tissue-equivalent walled counter (TEPC) and a graphite-walled low pressure proportional counter (GPC) in the Am-Be neutron source facility at UOIT. A series of measurements were performed with the counters filled with propane-based TE gas (55.1% C3H8, 39.5% CO2 and 5.4% N2) at operating gas pressures corresponding to tissue spheres 2.0 , 4.0 and 8.0 μm in diameter. The results of these measurements indicated satisfactory performance of counters to measure microdosimetric spectra extending down to event-sizes that cover the gamma component of a mixed field. The spectra and the related mean values ̅y F and ̅y D are compared with other similar work but with monoenergetic neutrons of different energy range, the agreement between them is good. An assessment of the performance of different size TEPC has been done. An excellent agreement between their event size spectra was found and the proton edge appears at the same position on the lineal energy scale and differences in microdosimetric parameters ̅ and ̅ is not exceeding 3%, which is in the region of counting statistics. In Am-Be neutron field, the efficiency of the TEPCs was measured to have an average value of 250 counts per μSv or equivalently about 4.17 counts per minutes per μSv/hr. This efficiency is reasonable for dose equivalent measurements but needs a long integration period. The measurements showed that the dose equivalent which depends on the measurement of energy deposition by the secondary charged particles was originated mainly from elastic collisions of the incident neutrons with hydrogen atoms. Moreover the number of events in the sensitive gas is dominated by proton recoils. A non- negligible fraction of the dose equivalent resulted from gamma interactions, alpha and recoil nuclei. The energy deposition patterns in these micro-scale targets are strongly dependent on radiation quality, so differences of linear energy transfer (LET) of the components in a mixed radiation field are significant. Accordingly, in a radiation field with an unknown gamma ray energy spectrum, absorbed dose for neutrons can be obtained by the separation of neutron induced events from gamma events using their distribution in lineal energy. To separate neutron dose from gamma dose a simple lineal energy threshold technique has been used in addition to a more sophisticated methods using γ-fitting and the graphite-walled counter measurements. The results of this study will establish the degree of error introduced by using a lineal energy threshold, which is likely to be used in any hand-held neutron monitor based on TEPCs. / UOIT

The purpose of this study was to determine how well the Monte Carlo transport code FLUKA can simulate a tissue-equivalent proportional counter (TEPC) and produce the expected delta ray events when exposed to high energy heavy ions (HZE) like in the galactic cosmic ray (GCR) environment. Accurate transport codes are desirable because of the high cost of beam time, the inability to measure the mixed field GCR on the ground and the flexibility they offer in the engineering and design process. A spherical TEPC simulating a 1 um site size was constructed in FLUKA and its response was compared to experimental data for an 56Fe beam at 360 MeV/nucleon. The response of several narrow beams at different impact parameters were used to explain the features of the response of the same detector exposed to a uniform field of radiation. Additionally, an investigation was made into the effect of the wall thickness on the response of the TEPC and the range of delta rays in the tissue-equivalent (TE) wall material. A full impact parameter test (from IP = 0 to IP = detector radius) was performed to show that FLUKA produces the expected wall effect. That is, energy deposition in the gas volume can occur even when the primary beam does not pass through the gas volume. A final comparison to experimental data was made for the simulated TEPC exposed to various broad beams in the energy range of 200 - 1000 MeV/nucleon. FLUKA overestimated energy deposition in the gas volume in all cases. The FLUKA results differed from the experimental data by an average of 25.2 % for yF and 12.4 % for yD. It is suggested that this difference can be reduced by adjusting the FLUKA default ionization potential and density correction factors.