Microdosimetric Measurements Research Articles

Microdosimetric measurements for LET monitoring in proton therapy. The development of engineered mini-TEPCs for clinical applications: First results

Innovative Treatment Planning Systems (TPS) in proton therapy based on a variable radiation quality with depth with respect to the conventional one with a fixed Relative Biological Effectiveness (RBE) of 1.1 are under study. Experimental methods are needed to verify the consistency between what is planned and what is delivered in terms of radiation quality. Microdosimetry studies the stochastics of the energy deposition process at micrometric and sub-micrometric level which is known to be related to the biological effectiveness of ionising radiation fields. For this reason, it is recognised by the scientific community that it is a useful tool to monitor the radiation quality of hadron therapy beams where the effectiveness varies with the penetration depth in patients. Detectors are needed to perform a microdosimetric characterization of a clinical beam and they need to satisfy specific requirements to enter the clinical practice as instruments for the Quality Assurance (QA). With this aim, at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (LNL-INFN) a technological transfer project was carried out with the final goal of developing engineered miniaturized Tissue Equivalent Proportional Counters (mini-TEPCs) for clinical applications. This work presents the characterization performed on the new detectors and the results obtained in neutron and proton fields.

Overview of DISCOVER22 experiment in the framework of INFN-LNGS Cosmic Silence activity: challenges and improvements in underground radiobiology

One of the most intriguing and still pending questions in radiobiology is to understand whether and how natural environmental background radiation has shaped Life over millions of years of evolution on Earth. Deep Underground Laboratories (DULs) represent the ideal below-background exposure facilities where to address such a question. Among the few worldwide DULs, INFN-Laboratorio Nazionale del Gran Sasso (LNGS) is one of the largest in terms of size and infrastructure. Designed and built to host neutrino and dark matter experiments, since the 1990 s the LNGS has been one of the first DULs to systematically host radiobiology experiments. Here we present the DISCOVER22 (DNA Damage and Immune System Cooperation in VEry low Radiation environment 2022) experiment recently started at LNGS. DISCOVER22 aims at investigating how the low radiation background modulates the Immune System (IS) response in in vitro and in vivo models. Underground radiobiology experiments are particularly complex and tricky to design and perform. In these studies, the accurate characterization of exposure scenarios is mandatory, but a challenging aspect is to understand how the very few ionizing tracks in the ultra-Low Radiation Environment (LRE) interact with the living matter in space and time in order to trigger different biological responses. In this Perspective, we describe these challenges and how we address them through a microdosimetric and a radiobiological approaches. We aim at linking physical microdosimetric measurements and the corresponding biological radiation responses by using radiation biophysical models that could shed light on many as yet unresolved questions.

First microdosimetric measurements with a tissue-equivalent proportional counter at the MedAustron ion-beam therapy facility.

The aim of this work is to present the first microdosimetric spectra measured with a miniaturised tissue-equivalent proportional counter in the clinical environment of the MedAustron ion-beam therapy facility. These spectra were gathered with a 62.4-MeV proton beam and have been compared with microdosimetric spectra measured in the 62-MeV clinical proton beam of the CATANA beam line. Monte Carlo simulations were performed using the Geant4 toolkit GATE and a fully commissioned clinical beam line model. Finally, similarities and discrepancies of the measured data to simulations based on a simple and complex detector geometry are discussed.

Microdosimetric analysis of the radiation quality of two different proton beams in the distal edge of the depth-dose profile.

Proton-therapy exploits the advantageous depth-dose profile of protons to induce the highest damage to tumoral cells in the last millimetres of their range in sharp Bragg Peak. To cover the whole tumoral volume, beams of different energies are combined to create the Spread Out Bragg Peak (SOBP). In passive modulated beams, the energy spread is created with modulators in which the highest energy beam is degraded through different thicknesses of calibrated plastic materials. The highest energy is chosen depending on the deepest point that needs to be treated. This study aims to investigate differences in the radiation quality in the distal edge of SOBP beams with different initial energy and modulation techniques based on microdosimetric measurements with mini Tissue-Equivalent Proportional Counters. The beams investigated are the 62MeV proton SOBP of the clinical facility of CATANA and the 148MeV proton SOBP of the research beam line of the proton-therapy centre of Trento.

The complexity of DNA damage by radiation follows a Gamma distribution: insights from the Microdosimetric Gamma Model.

DNA damage is the main predictor of response to radiation therapy for cancer. Its Q8 quantification and characterization are paramount for treatment optimization, particularly in advanced modalities such as proton and alpha-targeted therapy. We present a novel approach called the Microdosimetric Gamma Model (MGM) to address this important issue. The MGM uses the theory of microdosimetry, specifically the mean energy imparted to small sites, as a predictor of DNA damage properties. MGM provides the number of DNA damage sites and their complexity, which were determined using Monte Carlo simulations with the TOPAS-nBio toolkit for monoenergetic protons and alpha particles. Complexity was used together with a illustrative and simplistic repair model to depict the differences between high and low LET radiations. DNA damage complexity distributions were were found to follow a Gamma distribution for all monoenergetic particles studied. The MGM functions allowed to predict number of DNA damage sites and their complexity for particles not simulated with microdosimetric measurements (yF) in the range of those studied. Compared to current methods, MGM allows for the characterization of DNA damage induced by beams composed of multi-energy components distributed over any time configuration and spatial distribution. The output can be plugged into ad hoc repair models that can predict cell killing, protein recruitment at repair sites, chromosome aberrations, and other biological effects, as opposed to current models solely focusing on cell survival. These features are particularly important in targeted alpha-therapy, for which biological effects remain largely uncertain. The MGM provides a flexible framework to study the energy, time, and spatial aspects of ionizing radiation and offers an excellent tool for studying and optimizing the biological effects of these radiotherapy modalities.

A vacuum chamber for operation of a GEM-based detector in sealed-mode and at low pressure for LET measurements

The GEMTEQ is a gaseous detector with Gas Electron Multipliers for signal amplification and Timepix ASICS as highly pixelated readout. It is based on the GEMPix detector and designed for microdosimetry. This paper describes the vacuum chamber developed to house the three versions of the GEMTEQ and to operate the detector in sealed-mode and at low pressure. A sealed version avoiding the need of a gas system offers clear advantages for its transport and use, e.g., for measurements at a clinical particle therapy centre. Operating the detector at a pressure lower than atmospheric increases the spatial resolution, one of the key parameters in microdosimetry. A gas-tight detector housing, a pumping system, and a pressure and temperature monitoring system were developed and tested in operational conditions. These extensive tests have proven the vacuum chamber to be gas tight and well suited for the foreseen microdosimetric measurements: the GEMTEQ can be operated for several weeks at 1000 mbar without noticeable degradation of the detector signal. First measurements have been carried out successfully at pressure values as low as 200 mbar. Further tests are planned to reach the design goal of 10 mbar. Overall, the vacuum chamber fulfils the requirements for a sealed-mode and low-pressure operation of the GEMTEQ. Measurement campaigns using this setup for example for LET measurements in hadron beams have already been carried out and will be discussed in forthcoming papers.

Introduction and implementation of the CMRP radiodosimeter — a novel wireless microdosimetry system

Microdosimetry is a useful method to evaluate the relative biological effectiveness (RBE) as well as dose equivalent of any mixed radiation field without prior knowledge of type of charged particles and their spectra. The need of portable, user friendly devices for microdosimetric Quality Assurance measurements in particle therapy are greatly preferable to avoid sophisticated setup and time-consuming data analysis.Currently, the ability to perform microdosimetric measurements is restricted to those with extensive prior knowledge of the electronics involved and their experimental setup.The Centre for Medical Radiation Physics (CMRP) has developed a compact microdosimetric system named Radiodosimeter - a novel acquisition system that combines both wireless communication and plug-and-play design to provide a device that can be used with minimal setup. The system is compatible with current CMRP MicroPlus probe technology. The Radiodosimeter communicates with the client computer via Wi-Fi, allowing remote management and monitoring of acquisitions.The system was bench-marked against the standard microdosimetric setup at Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan and was found to have the same response. Several redundancy methods were demonstrated such as continuing an acquisition following disconnection from the client software and the ability to connect through different Wi-Fi modes (WPA2 Personal/Enterprise).These features prove that the Radiodosimeter can operate independently of a client computer, indicating its potential to be used as a portable device for personal monitoring in mixed radiation fields, including for microdosimetric quantity verification predicted by Treatment Planning Software in particle therapy.

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector

Objective. Treatment planning based on computer simulations was proposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison. Approach. Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10 μm) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose-mean values, and the RBE calculated with a biological weighting function were compared with PHITS simulations (microdosimetric target = 1 μm water sphere), and published clonogenic survival in vitro RBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR). Main results. Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose-mean lineal energy and the RBE10 up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR. Significance. This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies.

Repeatability and Reproducibility of Microdosimetry With a Mini-TEPC

Experimental microdosimetry measures the energy deposited in a microscopic sensitive volume (SV) by single ionizing particles traversing the SV or passing by. The fundamental advantage of experimental microdosimetry over the computational approach is that the first allows to determine distributions of energy deposition when information on the energy and nature of the charged particles at the point of interest is incomplete or fragmentary. This is almost always the case in radiation protection applications, but discrepancies between the modelled and the actual scenarios should be considered also in radiation therapy. Models for physical reality are always imperfect and rely both on basic input data and on assumptions and simplifications that are necessarily implemented. Furthermore, unintended events due to human errors or machine/system failures can be minimized but cannot be completely avoided.Though in proton radiation therapy (PRT) a constant relative biological effectiveness (RBE) of 1.1 is assumed, there is evidence of an increasing RBE towards the end of the proton penetration depth. Treatment Planning Systems (TPS) that take into account a variable linear energy transfer (LET) or RBE are already available and could be implemented in PRT in the near future. However, while the calculated dose distributions produced by the TPS are routinely verified with ionization chambers as part of the quality assurance program of every radiotherapy center, there is no commercial detector currently available to perform routine verification of the radiation quality, calculated by the TPS through LET or RBE distributions. Verification of calculated LET is required to make sure that a complex robustly optimized plan will be delivered as planned. The scientific community is coming to conclusion that a new domain of Quality Assurance additionally to the physical dose verification is required, and microdosimetry can be the right approach to address that. A first important prerequisite is the repeatability and reproducibility of microdosimetric measurements. This work aims at studying experimentally the repeatability and reproducibility of microdosimetric measurements performed with a miniaturized Tissue Equivalent Proportional Counter (mini-TEPC) in a 62 MeV proton beam. Experiments were carried out within 1 year and without propane gas recharging and by different operators. RBE was also calculated by applying the Loncol’s weighting function r(y) to microdosimetric distributions. Demonstration of reproducibility of measured microdosimetric quantities y¯F, y¯D and RBE10 in 62 MeV proton beam makes this TEPC a possible metrological tool for LET verification in proton therapy. Future characterization will be performed in higher energy proton beams.

Uncertainty in tissue equivalent proportional counter assessments of microdosimetry and RBE estimates in carbon radiotherapy

Microdosimetry is an important tool for assessing energy deposition distributions from ionizing radiation at cellular and cellular nucleus scales. It has served as an input parameter for multiple common mathematical models, including evaluation of relative biological effectiveness (RBE) of carbon ion therapy. The most common detector used for microdosimetry is the tissue-equivalent proportional counter (TEPC). Although it is widely applied, TEPC has various inherent uncertainties. Therefore, this work quantified the magnitude of TEPC measurement uncertainties and their impact on RBE estimates for therapeutic carbon beams. Microdosimetric spectra and frequency-, dose-, and saturation-corrected dose-mean lineal energy (****) were calculated using the Monte Carlo toolkit Geant4 for five monoenergetic and three spread-out Bragg peak carbon beams in water at every millimeter along the central beam axis. We simulated the following influences on these spectra from eight sources of uncertainty: wall effects, pulse pile-up, electronics, gas pressure, W-value, gain instability, low energy cut-off, and counting statistics. Statistic uncertainty was quantified as the standard deviation of perturbed values for each source. Bias was quantified as the difference between default lineal energy values and the mean of perturbed values for each systematic source. Uncertainties were propagated to RBE using the modified microdosimetric kinetic model (MKM). Variance introduced by statistic sources in and averaged 3.8% and 3.4%, respectively, and 1.5% in across beam depths and energies. Bias averaged 6.2% and 7.3% in and and 4.8% in These uncertainties corresponded to 1.2 ± 0.9% on average in RBEMKM. The largest contributors to variance and bias were pulse pile-up and wall effects. This study established an error budget for microdosimetric carbon measurements by quantifying uncertainty inherent to TEPC measurements. It is necessary to understand how robust the measurement of RBE model input parameters are against this uncertainty in order to verify clinical model implementation.

A Novel Hybrid Microdosimeter for Radiation Field Characterization Based on the Tissue Equivalent Proportional Counter Detector and Low Gain Avalanche Detectors Tracker: A Feasibility Study

In microdosimetry, lineal energies y are calculated from energy depositions ϵ inside the microdosimeter divided by the mean chord length, whose value is based on geometrical assumptions on both the detector and the radiation field. This work presents an innovative two-stages hybrid detector (HDM: hybrid detector for microdosimetry) composed by a tissue equivalent proportional counter and a silicon tracker made of 4 low gain avalanche diode. This design provides a direct measurement of energy deposition in tissue as well as particles tracking with a submillimeter lateral spatial resolution. The data collected by the detector allow to obtain the real track length traversed by each particle in the tissue equivalent proportional counter and thus estimates microdosimetry spectra without the mean chord length approximation. Using Geant4 toolkit, we investigated HDM performances in terms of detection and tracking efficiencies when placed in water and exposed to protons and carbon ions in the therapeutic energy range. The results indicate that the mean chord length approximation underestimate particles with short track, which often are characterized by a high energy deposition and thus can be biologically relevant. Tracking efficiency depends on the low gain avalanche diode configurations: 34 strips sensors have a higher detection efficiency but lower spatial resolution than 71 strips sensors. Further studies will be performed both with Geant4 and experimentally to optimize the detector design on the bases of the radiation field of interest.The main purpose of HDM is to improve the assessment of the radiation biological effectiveness via microdosimetric measurements, exploiting a new definition of the lineal energy (yT), defined as the energy deposition ϵ inside the microdosimeter divided by the real track length of the particle.

Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models

Different qualities of radiation are known to cause different biological effects at the same absorbed dose. Enhancements of the biological effectiveness are a direct consequence of the energy deposition clustering at the scales of DNA molecule and cell nucleus whilst absorbed dose is a macroscopic averaged quantity which does not take into account heterogeneities at the nanometer and micrometer scales. Microdosimetry aims to measure radiation quality at cellular or sub-cellular levels trying to increase the understanding of radiation damage mechanisms and effects. Existing microdosimeters rely on the well-established gas-based detectors or the more recent solid-state devices. They provide specific energy z spectra and other derived quantities as lineal energy (y) spectra assessed at the micrometer level. The interpretation of the radio-biological experimental data in the framework of different models has raised interest and various investigations have been performed to link in vitro and in vivo radiobiological outcomes with the observed microdosimetric data. A review of the major models based on experimental microdosimetry, with a particular focus on ion beam therapy applications and an emphasis on the microdosimetric kinetic model (MKM), will be presented in this work, enlightening the advantages of each one in terms of accuracy, initial assumptions, and agreement with experimental data. The MKM has been used to predict different kinds of radiobiological quantities such as the relative biological effects for cell inactivation or the oxygen enhancement ratio. Recent developments of the MKM will be also presented, including new non-Poissonian correction approaches for high linear energy transfer radiation, the inclusion of partial repair effects for fractionation studies, and the extension of the model to account for non-targeted effects. We will also explore developments for improving the models by including track structure and the spatial damage correlation information, by using the full fluence spectrum and by better accounting for the energy-deposition fluctuations at the intra- and inter-cellular level.

Medical Applications of the GEMPix

The GEMPix is a small gaseous detector with a highly pixelated readout, consisting of a drift region, three Gas Electron Multipliers (GEMs) for signal amplification, and four Timepix ASICs with 55 µm pixel pitch and a total of 262,144 pixels. A continuous flow of a gas mixture such as Ar:CO2:CF4, Ar:CO2 or propane-based tissue equivalent gas is supplied externally at a rate of 5 L/h. This article reviews the medical applications of the GEMPix. These include relative dose measurements in conventional photon radiation therapy and in carbon ion beams, by which on-line 2D dose images provided a similar or better performance compared to gafchromic films. Depth scans in a water phantom with 12C ions allowed measuring the 3D energy deposition and reconstructing the Bragg curve of a pencil beam. Microdosimetric measurements performed in neutron and photon fields allowed comparing dose spectra with those from Tissue Equivalent Proportional Counters and, additionally, to obtain particle track images. Some preliminary measurements performed to check the capabilities as the detector in proton tomography are also illustrated. The most important on-going developments are: (1) a new, larger area readout to cover the typical maximum field size in radiation therapy of 20 × 20 cm2; (2) a sealed and low-pressure version to facilitate measurements and to increase the equivalent spatial resolution for microdosimetry; (3) 3D particle track reconstruction when operating the GEMPix as a Time Projection Chamber.

Microdosimetric measurements as a tool to assess potential in-field and out-of-field toxicity regions in proton therapy

Relative biological effectiveness (RBE) variations are thought to be one of the primary causes of unexpected normal-tissue toxicities during tumor treatments with charged particles. Unlike carbon therapy, where treatment planning is optimized on the basis of the RBE-weighted dose, a constant RBE value of 1.1 is currently used in proton therapy. Assuming a uniform value can lead to under- or over-dosage, not just to the tumor but also to surrounding normal tissue. RBE changes have been linked with dose/fraction, the biological endpoint and beam properties. Understanding radiation quality and the associated RBE can improve the prediction of normal-tissue toxicities.In this study, we exploited microdosimetry for characterizing radiation quality in proton therapy in-field, and off-beam at 20 (beam edge), 50 (close out-of-field) and 100 (far out-of-field) mm from the beam center. We measured the lineal energy y spectra in a water phantom irradiated with 152 MeV protons, from which beam quality as well as the physical dose could be obtained. Taking advantage of the linear quadratic model and a modified version of the microdosimetric kinetic model, the microdosimetric data were combined with radiobiological parameters (α and β) of human salivary gland tumor cells for assessing cell survival RBE and RBE-weighted dose.The results indicate that if a dose of 60 Gy is delivered to the peak, the beam edge receives up to 6 Gy while the close and far out-of-field regions receive doses on the order of 10−3 Gy and 10−4 Gy, respectively. The RBE estimate in-beam shows large variations, ranging from 1.0 ± 0.2 at the entrance channel to 2.51 ± 0.15 at the tail. The beam edge follows a similar trend but the RBE calculated at the Bragg peak depth is 2.27 ± 0.17, i.e. twice the RBE in-beam (1.05 ± 0.15). Out-of-field, the estimated RBE is always significantly higher than 1.1 and increases with increasing lateral distance, reaching the overall highest value of 3.4 ± 0.3 at a depth of 206 mm and a lateral distance of 10 mm. The combination of RBE and dose into the biological dose points to the beam edge and the end-of-range in-beam as the areas with the highest risk of potential toxicities.

Characterizing Radiation Effectiveness in Ion-Beam Therapy Part II: Microdosimetric Detectors

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modelling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical beams of protons and carbon ions, the lineal-energy parameters are correlated to the clinical concept of Linear Energy Transfer (LET) and RBE. The possibilities of applying experimental microdosimetry in ion-beam therapy are discussed considering the consolidated irradiation characteristics as well as the most recent developments.

Radiation Shielding Evaluation of Spacecraft Walls Against Heavy Ions Using Microdosimetry

Despite the low contribution of heavy ions to the total fluence in the space radiation environment, their radiobiological effect on the human body is extremely high. In this article, we investigated the radiation field which resulted from the interaction of galactic cosmic rays (GCRs), specifically some heavy ions and energies, typically encountered in space with a realistic multilayer sample of the International Space Station (ISS) Columbus module's shielding wall. The quality factor, Q, and the normalized dose equivalent, H, derived from microdosimetric measurements for C, Ne, and Si ions behind different spacecraft wall configurations and materials are presented in this article. Particularly, carbon fiber, polyoxymethylene, and perspex with same areal density compared to currently used aluminum were investigated.

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter.

The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62MeV ocular therapy proton beams. A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100µm×100µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy ( ), dose mean lineal energy ( ) as well as microdosimetric relative biological effectiveness (RBEµ ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1keV/μm. The and values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

Characterizing Radiation Effectiveness in Ion Beam Therapy Part I: Introduction and Biophysical Modeling of RBE Using the LEMIV

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the inverted dose profile with a Bragg peak and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of the relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modelling of RBE and the microdosimetric measurements in complex radiation fields. This first paper gives a brief introduction into these fields and then focuses on aspects of biophysical modelling of RBE, specifically on semi-empirical approaches that are currently used in treatment planning for ion beam therapy. It summarizes the status and recent developments of the Local Effect Model (LEM) and its conceptual framework and shows examples of model validation using recent experimental data. The model is compared to other approaches, e.g. to the Microdosimetric-Kinetic Model (MKM), that builds the bridge to the experimental microdosimetric work.

Microdosimetry with a 3D silicon on insulator (SOI) detector in a low energy proton beamline

IntroductionAn accurate description of the radiation quality of proton beams is a precondition to increase our understanding of radiobiological mechanisms and to develop accurate biological response models for radiotherapy. However, there are few detectors capable of measuring microdosimetric quantities with high spatial resolution along the entire Bragg curve due to the rapid increase in stopping power at the Bragg peak (BP) and distal dose fall-off (DDF). The aim of this work was to measure the microdosimetric spectra along the Bragg curve in a low energy proton beamline used for radiobiological experiments with a novel 3D silicon-on-insulator (SOI) “mushroom” microdosimeter. MethodA silicon microdosimeter with an array of 3D structured diodes, creating well-defined sensitive volumes (SV) with excellent spatial resolution was used for microdosimetry. The microdosimeter was used to measure microdosimetric spectra and the relative dose throughout the Bragg curve of a 15 MeV proton beam by sequential insertion of 16 μm thick polyamide absorption films in front of the microdosimeter. The results were tissue corrected with a novel correction function and compared to Monte Carlo (MC) simulations performed in GATE. ResultsThe measured dose-mean lineal energy (yD‾) increased from 8 keV/μm at the entrance to 24 keV/μm at the BP, rising to a maximum of 35 keV/μm at the DDF. The measured yD‾ showed an overall good agreement with the MC simulated values, with deviation of less than 2% at the BP and DDF, while the largest deviation (12%) was found at the entrance. Clear changes in microdosimetric spectra were seen for each 16 μm step at the BP and DDF. ConclusionThe SOI microdosimeter with its well-defined 3D sensitive volumes is an excellent tool for characterizing low energy beamlines that demands very high spatial resolution. The good overall agreement between experimental and simulated results indicated that the detector is capable of accurate microdosimetric measurements.

Therapeutic proton beams: LET, RBE and microdosimetric spectra with gas and silicon detectors

A sealed mini-TEPC able to work in gas-steady modality, a monolithic silicon device composed by a matrix of micrometric cylindrical diodes and a residual energy measurement stage and the silicon MicroPlus Bridge detector were used to perform microdosimetric measurements at the 62 MeV proton clinical SOBP of CATANA at the Southern National Laboratories of INFN (LNS – INFN, Catania, Italy). Measurements were taken at the same different positions in a PMMA phantom, in order to analyse the detector response differences.Finally, a weighting function was applied to the spectra to see if the microdosimetric detectors are able to monitor RBE data for glioma cells (U87) irradiated at six positions along the same modulated 62-MeV proton beam. The results obtained with the three microdosimeters are compared and discussed.