Silicon microdosimetry in hadron therapy using Geant4

Hadron therapy, referring to treating cancer with protons and heavier ions, provides many advantages over conventional X-ray radiotherapy, including better dose conformity and dose sparing to healthy tissue. One open problem associated with hadron therapy is that the radiobiological effectiveness (RBE), which is an important input parameter in the clinical treatment planning, changes significantly along the Bragg peak/spread out Bragg peak. It is paramount to be able to estimate the RBE to improve the treatment in terms of clinical outcome. The solution proposed by the Centre For Medical Radiation Physics (CMRP), University of Wollongong, is given by silicon-based microdosimetry technology, which offers a powerful solution to estimate the RBE with sub-mm spatial resolution. Such high spatial resolution is particularly important at the distal edge of the Bragg peak/spread out Bragg peak where organs at risk may be positioned. Microdosimetry is conventionally performed using tissue equivalent proportional counters which feature complex and bulky operation and do not achieve a sub-mm spatial resolution. Silicon microdosimetry offers a more simple compact design, which is more well suited to the sharp dose gradients of hadron therapy beams and for routine quality assurance measurements. However, silicon microdosimetry is not without its difficulties, namely the measurement is not tissue equivalent and the design is not angularly independent. This thesis describes the in-silico characterisation and design optimisation of novel silicon microdosimeters developed at the CMRP. The study has been performed by means of the Geant4 Monte Carlo Toolkit, which has been validated against experimental measurements in this project to quantify its accuracy for hadron therapy and for microdosimetric studies. The tissue equivalence and angular dependence have been investigated. A method to convert the response of the detector from silicon to tissue was developed, which is now routinely used at the CMRP to convert experimental microdosimetric measurements to tissue, in proton and carbon ion therapy. Due to the strong directionality of hadron therapy beams and the angular dependence of the silicon microdosimeter designs, it was found that the traditional method of converting the energy deposition to lineal energy using the mean chord length of the silicon sensitive volumes (SVs) of the device was inappropriate. Instead, the mean path length was found to be more appropriate to generate the lineal energy deposition. Based on the results of this project, the SV design was optimised to reduce the variance of the path length to reduce the angular dependence

Validation of Geant4 fragmentation for Heavy Ion Therapy

12C ion therapy has had growing interest in recent years for its excellent dose conformity. However at therapeutic energies, which can be as high as 400 MeV/u, carbon ions produce secondary fragments. For an incident 400 MeV/u 12C ion beam, ∼70% of the beam will undergo fragmentation before the Bragg Peak. The dosimetric and radiobiological impact of these fragments must be accurately characterised, as it can result in increasing the risk of secondary cancer for the patient as well as altering the relative biological effectiveness. This work investigates the accuracy of three different nuclear fragmentation models available in the Monte Carlo Toolkit Geant4, the Binary Intranuclear Cascade (BIC), the Quantum Molecular Dynamics (QMD) and the Liege Intranuclear Cascade (INCL++). The models were benchmarked against experimental data for a pristine 400 MeV/u 12C beam incident upon a water phantom, including fragment yield, angular and energy distribution. For fragment yields the three alternative models agreed between ∼5 and ∼35% with experimental measurements, the QMD using the "Frag" option gave the best agreement for lighter fragments but had reduced agreement for larger fragments. For angular distributions INCL++ was seen to provide the best agreement among the models for all elements with the exception of Hydrogen, while BIC and QMD was seen to produce broader distributions compared to experiment. BIC and QMD performed similar to one another for kinetic energy distributions while INCL++ suffered from producing lower energy distributions compared to the other models and experiment

Correction factors to convert microdosimetry measurements in silicon to tissue in \u3csup\u3e12\u3c/sup\u3eC ion therapy

Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length (lPath) to calculate the lineal energy was introduced as an alternative to the mean chord length (l) because it was found that adopting Cauchy\u27s formula for the (l) was not appropriate for the radiation field typical of HIT as it is very directional (lPath) can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12C ion beam can be adopted as (lPath). The tissue equivalence conversion method and (lPath) were adopted to determine the RBE10, calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of the determination of (lPath)

3D silicon microdosimetry and RBE study using C-12 ion of different energies

This paper presents a new version of the 3D mesa "bridge" microdosimeter comprised of an array of 4248 silicon cells fabricated on 10 µm thick silicon-on-insulator substrate. This microdosimeter has been designed to overcome limitations existing in previous generation silicon microdosimeters and it provides well-defined sensitive volumes and high spatial resolution. The charge collection characteristics of the new 3D mesa microdosimeter were investigated using the ANSTO heavy ion microprobe, utilizing 5.5 MeV He2+ ions. Measurement of microdosimetric quantities allowed for the determination of the Relative Biological Effectiveness of 290 MeV/u and 350 MeV/u 12C heavy ion therapy beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. The microdosimetric RBE obtained showed good agreement with the tissue-equivalent proportional counter. Utilizing the high spatial resolution of the SOI microdosimeter, the LET spectra for 70 MeV 12C+6 ions, like those present at the distal edge of 290 and 350 MeV/u beams, were obtained as the ions passed through thin layers of polyethylene film. This microdosimeter can provide useful information about the lineal energy transfer (LET) spectra downstream of the protective layers used for shielding of electronic devices for single event upset prediction

Thin Silicon Microdosimeter utilizing 3D MEMS Fabrication Technology: Charge Collection Study and its application in mixed radiation fields

New 10-μm-thick silicon microdosimeters utilizing 3-D technology have been developed and investigated in this paper. The TCAD simulations were carried out to understand the electrical properties of the microdosimeters\u27 design. A charge collection study of the devices was performed using 5.5-MeV He2+ ions which were raster scanned over the surface of the detectors and the charge collection median energy maps were obtained and the detection yield was also evaluated. The devices were tested in a 290 MeV/u carbon ion beam at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Japan. Based on the microdosimetric measurements, the quality factor and dose equivalent out of field were obtained in a mixed radiation field mimicking the radiation environment for spacecraft in deep space

Report on G4‐Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group

Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro‐ and nano‐ dosimetry, imaging, radiation protection and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. To respond to these needs, we developed G4‐Med, a benchmarking and regression testing system of Geant4 for medical physics, that currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the pre‐built, Geant4 physics lists are tested. The tests included in G4‐Med are executed on the CERN computing infrastructure via the use of the geant‐val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. This paper describes the tests included in G4‐Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.D. Bolst acknowledges the support of the Australian Government Research Training Program Scholarship. M. A. Cort ́es-Giraldo, A. Perales, and J. M. Quesada acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness under grant FPA2016-77689-C2-1-R. B. Faddegon and J. Ramos-M ́endez acknowledge partial financial support from the NIH grant U24CA215123. D. Bolst, S. Guatelli, D. Sakata, S.Incerti, and I. Kyriakou acknowledge financial support from the Australian Research Council, ARC DP170100967. S. Incerti acknowledges the financial support of CNRS through the IN2P3/MOVI Master Project and through the France-Greece PICS 8235 funding scheme. I. Kyriakou acknowledges additional financial support from the European Space Agency (Contract No. 4000126645/19/NL/BW). E. C. Simpson acknowledges financial support from the Australian Research Council under grant DP170102423. I. Sechopoulos and C. Fedon acknowledge financial support from the Susan G Komen Foundation for the Cure grant IIR13262248. S. Guatelli and D. Bolst acknowlege the use of computing resources of the Aus-tralian National Computing Infrastructure (NCI), through the NCMAS 2020 grant scheme

Characterization of the mixed radiation field produced by carbon and oxygen ion beams of therapeutic energy: A Monte Carlo simulation study

2019 Wolters Kluwer Medknow Publications. All rights reserved. Purpose: The main advantages of charged particle radiotherapy compared to conventional X-ray external beam radiotherapy are a better tumor conformality coupled with the capability of treating deep-seated radio-resistant tumors. This work investigates the possibility to use oxygen beams for hadron therapy, as an alternative to carbon ions. Materials and Methods: Oxygen ions have the advantage of a higher relative biological effectiveness (RBE) and better conformality to the tumor target. This work describes the mixed radiation field produced by an oxygen beam in water and compares it to the one produced by a therapeutic carbon ion beam. The study has been performed using Geant4 simulations. The dose is calculated for incident carbon ions with energies of 162 MeV/u and 290 MeV/u, and oxygen ions with energies of 192 MeV/u and 245 MeV/u, and hence that the range of the primary oxygen ions projectiles in water was located at the same depth as the carbon ions. Results: The results show that the benefits of oxygen ions are more pronounced when using lower energies because of a slightly higher peak-to-entrance ratio, which allows either providing higher dose in tumor target or reducing it in the surrounding healthy tissues. It is observed that, per incident particle, oxygen ions deliver higher doses than carbon ions.Conclusions: This result coupled with the higher RBE shows that it may be possible to use a lower fluence of oxygen ions to achieve the same therapeutic dose in the patient as that obtained with carbon ion therapy

Optimisation of the design of SOI microdosimeters for hadron therapy quality assurance

Silicon-on-insulator (SOI) microdosimeters offer a promising method for routine quality assurance (QA) for hadron therapy due to their ease of operation and high spatial resolution. However, one complication which has been shown previously is that the traditional use of the mean chord length, (lCauchy), calculated using Cauchy\u27s formula, for SOI devices in clinical carbon ion fields is not appropriate due to the strong directionality of the radiation field. In a previous study, we demonstrated that the mean path length, (lPath), which is the mean path of charged particles in the sensitive volume (SV), is a more appropriate method to obtain microdosimetric quantities and biological relevant values, namely the relative biological effectiveness (RBE) by means of the microdosimetric kinetic model. The previous work, which was limited to mono-energetic 12C ion beams typical of heavy ion therapy (HIT), is extended here to investigate the (lPath) in a pristine proton beam as well as for spread out Bragg peaks (SOBP) for both proton and carbon ion clinical beams. In addition, the angular dependence of the SOI device for a number of different SV designs is also investigated to quantify the effects which the alignment has on the (lPath). It is demonstrated that the (lPath) can be accurately estimated along the depth of a pristine or SOBP using the energy deposition spectra for both proton and 12C ion beams. This observation allows a quick and accurate estimation of the (lPath) for experimental use

Modelling the Biological Beamline at HIMAC using Geant4

A Geant4 simulation modelling the passive Biological beamline at the Heavy Ion Medical Accelerator Chiba (HIMAC) is described and validated against experimental measurements for a mono-energetic and spread out Bragg peak (SOBP) 12 C beam. Comparisons to experimental data showed good agreement for both lateral and depth dose profiles. It was found that simplifying the simulation model by generating a cone beam instead of using the wobbler magnets provided a good approximation for both lateral and depth dose measurements

Characterization of angular detection dependence of prompt gamma-rays with respect to the Bragg peak in a water phantom using proton beam irradiations

The rationale for utilizing the prompt gamma (PG) signal for in vivo proton beam range verification is such that the PG fall-off distribution along the beam path is associated with the dose profile in the Bragg peak (BP) distal fall-off region. Quantitative characterization of this association, particularly with respect to the BP, is of great importance to assess its limitation and aid in the development of a clinically reliable PG imaging system to maximize PG detection. In this work we investigate the angular dependence of PG detection with respect to the BP for in vivo beam range verification in proton radiation therapy. Geant4 Monte Carlo simulations have been used to study the energy spectral and spatial characteristics of the PG signal from high-energy proton beam irradiations. A cylindrical water phantom (φ30 cm × 50 cm) with an ideal detecting cylinder (φ100 cm × 50 cm) coaxially surrounding the phantom has been used in the simulation. The angular dependence of PG detection as a function of beam energy and PG energy has been characterized with respect to the BP. Our results show that there exists an angular preference for PG detection, which has a strong dependence on the beam energy. As the beam energy increases, the longitudinal angular preference for PG detection becomes increasingly backward with respect to the BP position. This implies that the detector with sufficient longitudinal angular coverage is desired for the BP tracking, especially for the Spread-Out Bragg Peak tracking