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Objective. Ion radiotherapy with protons or carbon ions is one of the most advanced clinical methods for cancer treatment. To further improve the local tumor control, ion radiotherapy using multiple ion species has been investigated. Due to complexity of dose distributions delivered by multi-ion therapy in a tumor, a validation strategy for the planned treatment efficacy must be established that can be potentially used in the quality assurance (QA) protocol for the multi-ion treatment plans. In previous work, we demonstrated that the microdosimetric approach using the silicon on insulator (SOI) microdosimeter is practical for validating cell surviving fraction (SF) of MIA PaCa-2 cells in the independent fields of helium, carbon, oxygen, and neon ion beams. Approach. This paper extends the previous study, and we demonstrate a microdosimetry based approach as a pilot study to build the QA protocol in the multi-ion therapy predicting the cell SF along the spread-out Bragg peak obtained by combined irradiations of He+O and C+Ne ions. Across the study, the SOI microdosimeter system MicroPlus was used for measurement of the lineal energy in individual ion fields followed by deriving the lineal energy of combined ion fields delivered by a pencil beam scanning system at HIMAC. Main results. The predicted cell SF based on derived lineal energy and dose in the combined fields was in good agreement with the planned cell SF by our in-house treatment planning system. Significance. The presented results indicated the potential benefit of the SOI microdosimeter system MicroPlus as the QA system in the multi-ion radiotherapy., (© 2022 Institute of Physics and Engineering in Medicine.)

In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10 × 10 × 6 cm 3 , treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases.

Microdosimetry is a particularly powerful method to estimate the relative biological effectiveness (RBE) of any mixed radiation field. This is particularly convenient for therapeutic heavy ion therapy (HIT) beams, referring to ions larger than protons, where the RBE of the beam can vary significantly along the Bragg curve. Additionally, due to the sharp dose gradients at the end of the Bragg peak (BP), or spread out BP, to make accurate measurements and estimations of the biological properties of a beam a high spatial resolution is required, less than a millimetre. This requirement makes silicon microdosimetry particularly attractive due to the thicknesses of the sensitive volumes commonly being  ∼10 [Formula: see text]m or less. Monte Carlo (MC) codes are widely used to study the complex mixed HIT radiation field as well as to model the response of novel microdosimeter detectors when irradiated with HIT beams. Therefore it is essential to validate MC codes against experimental measurements. This work compares measurements performed with a silicon microdosimeter in mono-energetic [Formula: see text], [Formula: see text] and [Formula: see text] ion beams of therapeutic energies, against simulation results calculated with the Geant4 toolkit. Experimental and simulation results were compared in terms of microdosimetric spectra (dose lineal energy, [Formula: see text]), the dose mean lineal energy, y  D and the RBE 10 , as estimated by the microdosimetric kinetic model (MKM). Overall Geant4 showed reasonable agreement with experimental measurements. Before the distal edge of the BP, simulation and experiment agreed within  ∼10% for y  D and  ∼2% for RBE 10 . Downstream of the BP less agreement was observed between simulation and experiment, particularly for the [Formula: see text] and [Formula: see text] beams. Simulation results downstream of the BP had lower values of y  D and RBE 10 compared to the experiment due to a higher contribution from lighter fragments compared to heavier fragments.

Compact silicon on insulator (SOI) microdosimeters have been used to characterise the radiation field of many different hadron therapy beams. SOI devices are particularly attractive in hadron therapy fields due to their spatial resolution being well suited to the sharp dose gradients at the end of the primary beam's range. Due to the small size of SOI's sensitive volumes (SVs), which are usually  ∼1-10 [Formula: see text]m thick, the fabrication of these devices can present challenges which are not as common for more conventional thickness silicon devices such as silicon spectroscopy detectors. Microdosimetry is the study of the energy deposition in micrometre sized volumes representing biological sites and is a powerful approach to estimate the biological effect of radiation on the micron-scale level, in a cell. However, cell sizes vary extensively translating in different energy deposition spectra. This work studies SV thicknesses between 1 and 100 [Formula: see text]m using Geant4 and examines the impact of SV dimensions on microdosimetric quantities. The quantities studied were the frequency mean lineal energy, [Formula: see text], and the dose mean lineal energy, [Formula: see text]. Additionally the relative biological effectiveness (RBE), estimated by the microdosimetric kinetic model (MKM), is also investigated. To study the impact of the SV thickness, SOI microdosimeters were irradiated with proton, [Formula: see text] and [Formula: see text] ion beams with ranges of  ∼160 mm, with the microdosimeter being set at various positions along the Bragg curve. It was found that [Formula: see text] was influenced the least in proton beams and increased for heavier ion beams. Conversely, [Formula: see text] was impacted by the SV thickness the most in proton beams and [Formula: see text] was the least. Similar to [Formula: see text], protons were impacted the most by the SV thickness when estimating the RBE using the MKM. The cause of these differences was largely due to the different densities of the delta electron track structure for the case of [Formula: see text] and the energy transferred to the medium from the primary beam for [Formula: see text].

The shift from reactor to accelerator based neutron production has created a renewed interested in Boron Neutron Capture Therapy (BNCT). BNCT is reliant upon the favourable uptake of 10 B by tumour cells along with the interaction with neutrons to produce high LET fragments (He and Li nuclei) that deposit energy locally within the tumour cells. As with any radiation based treatment, Quality Assurance (QA) is crucial. In particular, Geant4 was used to model and optimise the geometry and packaging of Silicon on Insulator (SOI) microdosimeters for BNCT Quality Assurance purposes in view of experimental measurements at the KUR research reactor, in Japan. In this context, design optimisation pertains to the sensitive volume size and probability of neutron activation. This study has shown conclusively that whilst the materials currently used in the fabrication of silicon based microdosimeters are appropriate, there are changes with respect to the sensitive volume thickness that should be addressed to reduce the number of 'stoppers' in the microdosimeter., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Microdosimetric energy depositions have been suggested as a key variable for the modeling of the relative biological effectiveness (RBE) in proton and ion radiation therapy. However, microdosimetry has been underutilized in radiation therapy. Recent advances in detector technology allow the design of new mico- and nano-dosimeters. At the same time Monte Carlo (MC) simulations have become more widely used in radiation therapy. In order to address the growing interest in the field, a microdosimetric extension was developed in TOPAS. The extension provides users with the functionality to simulate microdosimetric spectra as well as the contribution of secondary particles to the spectra, calculate microdosimetric parameters, and determine RBE with a biological weighting function approach or with the microdosimetric kinetic (MK) model. Simulations were conducted with the extension and the results were compared with published experimental data and other simulation results for three types of microdosimeters, a spherical tissue equivalent proportional counter (TEPC), a cylindrical TEPC and a solid state microdosimeter. The corresponding microdosimetric spectra obtained with TOPAS from the plateau region to the distal tail of the Bragg curve generally show good agreement with the published data.

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, [Formula: see text], calculated using Cauchy's 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, [Formula: see text], 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 [Formula: see text] ion beams typical of heavy ion therapy (HIT), is extended here to investigate the [Formula: see text] 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 [Formula: see text]. It is demonstrated that the [Formula: see text] can be accurately estimated along the depth of a pristine or SOBP using the energy deposition spectra for both proton and [Formula: see text] ion beams. This observation allows a quick and accurate estimation of the [Formula: see text] for experimental use.

This paper presents the feasibility study of a novel 3D mesa bridge microdosimeter and its use for BNCT dosimetry. The performance of the microdosimeter was studied using Monte Carlo simulation. The clinical BNCT field at Kyoto University Reactor (KUR) using both thermal and epithermal irradiation modes were used in this study. Results show that this microdosimeter can be utilised as an effective tool to measure microdosimetric spectrum in the BNCT field and experimental validation will follow once KUR is operational., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Using the CMRP 'bridge' μ+ probe, microdosimetric measurements were undertaken out-of-field using a therapeutic scanning proton pencil beam and in-field using a 12C ion therapy field. These measurements were undertaken at Mayo Clinic, Rochester, USA and at HIMAC, Chiba, Japan, respectively. For a typical proton field used in the treatment of deep-seated tumors, we observed dose-equivalent values ranging from 0.62 to 0.99 mSv/Gy at locations downstream of the distal edge. Lateral measurements at depths close to the entrance and along the SOBP plateau were found to reach maximum values of 3.1 mSv/Gy and 5.3 mSv/Gy at 10 mm from the field edge, respectively, and decreased to ~0.04 mSv/Gy 120 mm from the field edge. The ability to measure the dose-equivalent with high spatial resolution is particularly relevant to healthy tissue dose calculations in hadron therapy treatments. We have also shown qualitatively and quantitively the effects critical organ motion would have in treatment using microdosimetric spectra. Large differences in spectra and RBE10 were observed for treatments where miscalculations of 12C ion range would result in critical structures being irradiated, showing the importance of motion management.

Background: The aim of this study was to measure the microdosimetric distributions of a carbon pencil beam scanning (PBS) and passive scattering system as well as to evaluate the relative biological effectiveness (RBE) of different ions, namely 12 C, 14 N, and 16 O, using a silicon-on-insulator (SOI) microdosimeter with well-defined 3D-sensitive volumes (SV). Geant4 simulations were performed with the same experimental setup and results were compared to the experimental results for benchmarking., Method: Two different silicon microdosimeters with rectangular parallelepiped and cylindrical shaped SVs, both 10 μm in thickness were used in this study. The microdosimeters were connected to low noise electronics which allowed for the detection of lineal energies as low as 0.15 keV/μm in tissue. The silicon microdosimeters provide extremely high spatial resolution and can be used for in-field and out-of-field measurements in both passive scattering and PBS deliveries. The response of the microdosimeters was studied in 290 MeV/u 12 C, 180 MeV/u 14 N, 400 MeV/u 16 O passive ion beams, and 290 MeV/u 12 C scanning carbon therapy beam at heavy ion medical accelerator in Chiba (HIMAC) and Gunma University Heavy Ion Medical Center (GHMC), Japan, respectively. The microdosimeters were placed at various depths in a water phantom along the central axis of the ion beam, and at the distal part of the Spread Out Bragg Peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the microdosimetric lineal energy spectra and the modified microdosimetric kinetic model (MKM), using MKM input parameters corresponding to human salivary gland (HSG) tumor cells. Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results., Results: For a 180 MeV/u 14 N pristine BP, the dose-mean lineal energy yD¯ obtained with two types of silicon microdosimeters started from approximately 29 keV/μm at the entrance to 92 keV/μm at the BP, with a maximum value in the range of 412 to 438 keV/μm at the distal edge. For 400 MeV/u 16 O ions, the dose-mean lineal energy yD¯ started from about 24 keV/μm at the entrance to 106 keV/μm at the BP, with a maximum value of approximately 381 keV/μm at the distal edge. The maximum derived RBE 10 values for 14 N and 16 O ions were found to be 3.10 ± 0.47 and 2.93 ± 0.45, respectively. Silicon microdosimetry measurements using pencilbeam scanning 12 C ions were also compared to the passive scattering beam., Conclusions: These SOI microdosimeters with well-defined three-dimensional (3D) SVs have applicability in characterizing heavy ion radiation fields and measuring lineal energy deposition with sub-millimeter spatial resolution. It has been shown that the dose-mean lineal energy increased significantly at the distal part of the BP and SOBP due to very high LET particles. Good agreement was observed for the experimental and simulation results obtained with silicon microdosimeters in 14 N and 16 O ion beams, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in charged particle therapy., (© 2018 American Association of Physicists in Medicine.)

Purpose: This work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well-defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam., Methods: A novel silicon microdosimeter with well-defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/μm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread-out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results., Results: For a 131 MeV PBS spot (124.6 mm R 90 range in water), the measured dose-mean lineal energy yD¯ increased from 2 keV/μm at the entrance to 8 keV/μm in the BP, with a maximum value of 10 keV/μm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP., Conclusions: The SOI microdosimeter with its well-defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy., (© 2017 American Association of Physicists in Medicine.)

Purpose: Microdosimetry is a vital tool for assessing the microscopic patterns of energy deposition by radiation, which ultimately govern biological effect. Solid-state, silicon-on-insulator microdosimeters offer an approach for making microdosimetric measurements with high spatial resolution (on the order of tens of micrometers). These high-resolution, solid-state microdosimeters may therefore play a useful role in characterizing proton radiotherapy fields, particularly for making highly resolved measurements within the Bragg peak region. In this work, we obtain microdosimetric measurements with a solid-state microdosimeter (MicroPlus probe) in a clinical, spot-scanning proton beam of small spot size., Methods: The MicroPlus probe had a 3D single sensitive volume on top of silicon oxide. The sensitive volume had an active cross-sectional area of 250 μm × 10 μm and thickness of 10 μm. The proton facility was a synchrotron-based, spot-scanning system with small spot size (σ ≈ 2 mm). We performed measurements with the clinical beam current (≈1 nA) and had no detected pulse pile-up. Measurements were made in a water-equivalent phantom in water-equivalent depth (WED) increments of 0.25 mm or 1.0 mm along pristine Bragg peaks of energies 71.3 MeV and 159.9 MeV, respectively. For each depth, we measured lineal energy distributions and then calculated the dose-weighted mean lineal energy, y¯D. The measurements were repeated for two field sizes: 4 × 4 cm 2 and 20 × 20 cm 2 ., Results: For both 71.3 MeV and 159.9 MeV and for both field sizes, y¯D increased with depth toward the distal edge of the Bragg peak, a result consistent with Monte Carlo calculations and measurements performed elsewhere. For the 71.3 MeV, 4 × 4 cm 2 beam (range at 80% distal falloff, R 80  = 3.99 cm), we measured y¯D=1.96±0.08 keV/μm at WED = 2 cm, and y¯D=10.6±0.32 keV/μm at WED = 3.95 cm. For the 71.3 MeV, 20 × 20 cm 2 beam, we measured y¯D=2.46±0.12 keV/μm at WED = 2.6 cm, and y¯D=11.0±0.24 keV/μm at WED = 3 cm. For the 159.9 MeV, 4 × 4 cm 2 beam (R 80  = 17.7 cm), y¯D=2.24±0.15 keV/μm at WED = 5 cm, and y¯D=8.99±0.71 keV/μm at WED = 17.6 cm. For the 159.9 MeV, 20 × 20 cm 2 beam, y¯D=2.56±0.10 keV/μm at WED = 5 cm, and y¯D=9.24±0.73 keV/μm at WED = 17.6 cm., Conclusions: We performed microdosimetric measurements with a novel solid-state, silicon-on-insulator microdosimeter in a clinical spot-scanning proton beam of small spot size and unmodified beam current. For all of the proton field sizes and energies considered, the measurements of y¯D were in agreement with expected trends. Furthermore, we obtained measurements with a spatial resolution of 10 μm in the beam direction. This spatial resolution greatly exceeded that possible with a conventional gaseous tissue-equivalent proportional counter and allowed us to perform a high-resolution investigation within the Bragg peak region. The MicroPlus probe is therefore suitable for applications in proton radiotherapy., (© 2017 American Association of Physicists in Medicine.)

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 12 C 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 [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] 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 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 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 [Formula: see text].