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Background: Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high‐spatial‐resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. Purpose: The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. Methods: The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron‐doped CVD diamond. The cross‐section of the sensitive volume of the dosimetric element is 4 mm2 and 1 μm‐thick, while the microdosimetric one has an active cross‐sectional area of 100 × 100 μm2 and a thickness of about 6.2 μm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7 MeV/u and proton beam of 148.7 MeV. The particle flux in the region of the microdosimeter was 6·107 cm2/s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE‐Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. Results: Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2 keV/μm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. Conclusions: The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to compare the response of two different types of solid‐state microdosimeters, that is, silicon and diamond, and their uncertainties. A study of the conversion of silicon microdosimetric spectra to the diamond equivalent for microdosimeters with different geometry of the sensitive volumes is performed, including the use of different stopping power databases. Method: Diamond and silicon microdosimeters were irradiated under the same conditions, aligned at the same depth in a carbon‐ion beam at the MedAustron ion therapy center. In order to estimate the microdosimetric quantities, the readout electronic linearity was investigated with three different methods, that is, the first being a single linear regression, the second consisting of a double linear regression with a channel transition and last a multiple linear regression by splitting the data into odd and even groups. The uncertainty related to each of these methods was estimated as well. The edge calibration was performed using the intercept with the horizontal axis of the tangent through the inflection point of the Fermi function approximation multi‐channel analyzer spectrum. It was assumed that this point corresponds to the maximum energy difference of particle traversing the sensitive volume (SV) for which the residual range difference in the continuous slowing down approximation is equal to the thickness of the SV of the microdosimeter. Four material conversion methods were explored, the edge method, the density method, the maximum‐deposition energy method and the bin‐by‐bin transformation method. The uncertainties of the microdosimetric quantities resulting from the linearization, the edge calibration and the detectors thickness were also estimated. Results: It was found that the double linear regression had the lowest uncertainty for both microdosimeters. The propagated standard (k = 1) uncertainties on the frequency‐mean lineal energy y¯F${\bar{y}}_{\rm{F}}$ and the dose‐mean lineal energy y¯D${\bar{y}}_{\rm{D}}$ values from the marker point, in the spectra, in the plateau were 0.1% and 0.2%, respectively, for the diamond microdosimeter, whilst for the silicon microdosimeter data converted to diamond, the uncertainty was estimated to be 0.1%. In the range corresponding to the 90% of the amplitude of the Bragg Peak at the distal part of the Bragg curve (R90) the uncertainty was found to be 0.1%. The uncertainty propagation from the stopping power tables was estimated to be between 5% and 7% depending on the method. The uncertainty on the y¯F${\bar{y}}_{\rm{F}}$ and y¯D${\bar{y}}_{\rm{D}}$ coming from the thickness of the detectors varied between 0.3% and 0.5%. Conclusion: This article demonstrate that the linearity of the readout electronics affects the microdosimetric spectra with a difference in y¯F${\bar{y}}_{\rm{F}}$ values between the different linearization methods of up to 17.5%. The combined uncertainty was dominated by the uncertainty of stopping power on the edge. [ABSTRACT FROM AUTHOR]

Microdosimetry is increasingly adopted in the characterization of proton and carbon ion beams used in cancer therapy. Spectra and mean values of lineal energy calculated in frequency and dose are seen by many as the tools which, by complementing dosimetric measurements, allow for the most complete characterization of the therapeutic radiation fields. The urgency is now to consolidate the experience and converge to commonly accepted methodologies. In this context, the purpose of this work is to study the effects of the energy-loss straggling and the delta-ray escape, considering slab-sensitive volumes; these are, in fact, the typical shapes of solid-state microdosimeters, which are widely used in investigating light ion therapy beams. The method considers the energy distribution of delta rays resulting from the collision of the impinging ion and, taking into account the escape, convolutes it with itself as many times as the expected number of collisions in the sensitive volume thickness. The resulting distribution is compared to the experimental microdosimetric spectrum showing a substantially good agreement. The extension of the methodology to a wider range of ion energy and detector characteristics is instrumental for a detector-independent microdosimetric assessment of the radiation fields. [ABSTRACT FROM AUTHOR]

An improved biological weighting function (IBWF) is proposed to phenomenologically relate microdosimetric lineal energy probability density distributions with the relative biological effectiveness (RBE) for the in vitro clonogenic cell survival (surviving fraction = 10%) of the most commonly used mammalian cell line, i.e. the Chinese hamster lung fibroblasts (V79). The IBWF, intended as a simple and robust tool for a fast RBE assessment to compare different exposure conditions in particle therapy beams, was determined through an iterative global-fitting process aimed to minimize the average relative deviation between RBE calculations and literature in vitro data in case of exposure to various types of ions from 1H to 238U. By using a single particle- and energy- independent function, it was possible to establish an univocal correlation between lineal energy and clonogenic cell survival for particles spanning over an unrestricted linear energy transfer range of almost five orders of magnitude (0.2 keV µm−1 to 15 000 keV µm−1 in liquid water). The average deviation between IBWF-derived RBE values and the published in vitro data was ∼14%. The IBWF results were also compared with corresponding calculations (in vitro RBE10 for the V79 cell line) performed using the modified microdosimetric kinetic model (modified MKM). Furthermore, RBE values computed with the reference biological weighting function (BWF) for the in vivo early intestine tolerance in mice were included for comparison and to further explore potential correlations between the BWF results and the in vitro RBE as reported in previous studies. The results suggest that the modified MKM possess limitations in reproducing the experimental in vitro RBE10 for the V79 cell line in case of ions heavier than 20Ne. Furthermore, due to the different modelled endpoint, marked deviations were found between the RBE values assessed using the reference BWF and the IBWF for ions heavier than 2H. Finally, the IBWF was unchangingly applied to calculate RBE values by processing lineal energy density distributions experimentally measured with eight different microdosimeters in 19 1H and 12C beams at ten different facilities (eight clinical and two research ones). Despite the differences between the detectors, irradiation facilities, beam profiles (pristine or spread out Bragg peak), maximum beam energy, beam delivery (passive or active scanning), energy degradation system (water, PMMA, polyamide or low-density polyethylene), the obtained IBWF-based RBE trends were found to be in good agreement with the corresponding ones in case of computer-simulated microdosimetric spectra (average relative deviation equal to 0.8% and 5.7% for 1H and 12C ions respectively). [ABSTRACT FROM AUTHOR]

Purpose: To investigate for the first time the potentialities of obtaining microdosimetric measurements in scanned clinical carbon‐ion beams using synthetic single crystal diamond detector and to verify the spectral conversion methods. Methods: Microdosimetric measurements were performed at different depths in a water phantom at the therapeutic scanned carbon‐ion beam of the National Center of Oncological Hadrontherapy (CNAO) in Pavia, using waterproof encapsulated diamond microdosimeter developed at "Tor Vergata" University. A monoenergetic carbon‐ion beam of 195 MeV/μ scanned over a square field of 2 × 2 cm2 was used. Experimental microdosimetric spectra were compared with those obtained with a propane‐filled Tissue Equivalent Proportional Counters (TEPCs) microdosimeter in the same facility at the same conditions. To this purpose, the spectra in diamond were converted to the spectra that would have been collected with a propane‐filled cylindrical sensitive volume by means of a novel analytic methodology, recently developed at MedAustron. Results: The microdosimetric spectra acquired by the diamond microdosimeter show different shapes in the 10 keV µm−1 ÷ 103 keV µm−1 lineal‐energy range at different water depths. In spite of the high counting rate, no spectral distortion, due to pile‐up events and polarization effects, were observed. The experimental spectra have a low detection threshold of about 6 keV µm−1 due to the electronic noise in the irradiation room. The comparison between the spectra converted to propane from diamond detector and the spectra collected directly with propane‐filled TEPC shows a good agreement in the whole lineal‐energy range. Furthermore this comparison confirms that diamond detector response is LET independent. The frequency‐ and dose‐mean lineal energy values were also assessed for all spectra. The frequency‐mean values obtained with diamond microdosimeter at different depths scales rather well with the absorbed dose values. Conclusions: Microdosimetric characterization of a synthetic single crystal diamond detector in high‐energy scanned carbon‐ion beams was performed. The results of the present study showed that this detector is suitable for microdosimetry of clinical carbon ion beams. In addition, the good agreement between the converted diamond spectra and those obtained with TEPC provides the first experimental validation of the spectra conversion methodologies as valuable tools for the comparison of spectra collected with different detectors. [ABSTRACT FROM AUTHOR]

Microdosemeters are frequently used today to specify the radiation quality in the framework of ion-beam therapy. The heterogeneity of the detector shapes and the materials limits the possibility of comparing directly spectra and mean lineal energies. A method was recently studied to convert the spectra obtained with unidirectional ion beams in slab detectors to those obtained with detectors of different in shape and material. The method is based on the observation that the lineal-energy spectra of slab detector, in a restricted energy interval, approximate the Linear Energy Transfer distributions at corresponding material and particle type and energies. In this study, the experimental spectra collected with a slab diamond detector are converted to the spectra that would be obtained using water detectors of spherical and cylindrical shapes. [ABSTRACT FROM AUTHOR]

The information of the dose is not sufficiently describing the biological effects of ions on tissue since it does not express the radiation quality, i.e. the heterogeneity of the processes due to the slowing-down and the fragmentation of the particles when crossing a target. Depending on different circumstances, the radiation quality can be determined using measurements, calculations, or simulations. Microdosimeters are the primary tools used to provide the experimental information of the radiation quality and their role is becoming crucial for the recent clinical developments in particular with carbon ion therapy. Microdosimetry is strongly linked to the biological effectiveness of the radiation since it provides the physical parameters which explicitly distinguish the radiation for its capability of damaging cells. In the framework of ion-beam therapy microdosimetry can be used in the preparation of the treatment to complement radiobiological experiments and to analyze the modification of the radiation quality in phantoms. A more ambitious goal is to perform the measurements during the irradiation procedure to determine the non-targeted radiation and, more importantly, to monitor the modification of the radiation quality inside the patient. These procedures provide the feedback of the treatment directly beneficial for the single patient but also for the characterization of the biological effectiveness in general with advantages for all future treatment. Traditional and innovative tools are currently under study and an outlook of present experience and future development is presented here. [ABSTRACT FROM AUTHOR]

This paper represents the first attempt to discuss the use of an artificial single-crystal diamond as a new microdosimeter. The Diamond MicroDosimeter (DMD) detecting region is a thin layer of highly controlled thickness (< 5~\mu m) and high purity intrinsic monocrystalline diamond grown over a backing boron doped monocrystalline diamond. This viable, small, compact and user-friendly device is able to obtain spectra of the energy deposition in sensitive volumes of the order of micrometer. The paper reports the first experimental tests performed to measure the dose distribution in terms of lineal energy and the simulation performed by the Monte Carlo code FLUKA to optimize the design of the new DMD. Advantages and shortcomings of the DMD are discussed. [ABSTRACT FROM PUBLISHER]

Objective. Microdosimetry is gaining increasing interest in particle therapy. Thanks to the advancements in microdosimeter technologies and the increasing number of experimental studies carried out in hadron therapy frameworks, it is proving to be a reliable experimental technique for radiation quality characterisation, quality assurance, and radiobiology studies. However, considering the variety of detectors used for microdosimetry, it is important to ensure the consistency of microdosimetric results measured with different types of microdosimeters. Approach. This work presents a novel multi-thickness microdosimeter and a methodology to characterise the radiation quality of a clinical carbon-ion beam. The novel device is a diamond detector made of three sensitive volumes (SVs) of different thicknesses: 2, 6 and 12 µ m. The SVs, which operate simultaneously, were accurately aligned and laterally positioned within 3 mm. This alignment allowed for a comparison of the results with a negligible impact of the SVs alignment and their lateral positioning, ensuring the homogeneity of the measured radiation quality. An experimental campaign was carried out at MedAustron using a carbon-ion beam of typical clinical energy (284.7 MeV u -1 ). Main results. The measurement results allowed for a meticulous interpretation of its radiation quality, highlighting the effect of the SV thickness. The consistency of the microdosimetric spectra measured by detectors of different thicknesses is discussed by critically analysing the spectra and the differences observed. Significance. The methodology presented will be highly valuable for future experiments investigating the effects of the target volume size in radiobiology and could be easily adapted to the other particles employed in hadron therapy for clinical (i.e. protons) and for research purposes (e.g. helium, lithium and oxygen ions)., (Creative Commons Attribution license.)

An improved biological weighting function (IBWF) is proposed to phenomenologically relate microdosimetric lineal energy probability density distributions with the relative biological effectiveness (RBE) for the in vitro clonogenic cell survival (surviving fraction = 10%) of the most commonly used mammalian cell line, i.e. the Chinese hamster lung fibroblasts (V79). The IBWF, intended as a simple and robust tool for a fast RBE assessment to compare different exposure conditions in particle therapy beams, was determined through an iterative global-fitting process aimed to minimize the average relative deviation between RBE calculations and literature in vitro data in case of exposure to various types of ions from 1 H to 238 U. By using a single particle- and energy- independent function, it was possible to establish an univocal correlation between lineal energy and clonogenic cell survival for particles spanning over an unrestricted linear energy transfer range of almost five orders of magnitude (0.2 keV µm -1 to 15 000 keV µm -1 in liquid water). The average deviation between IBWF-derived RBE values and the published in vitro data was ∼14%. The IBWF results were also compared with corresponding calculations (in vitro RBE 10 for the V79 cell line) performed using the modified microdosimetric kinetic model (modified MKM). Furthermore, RBE values computed with the reference biological weighting function (BWF) for the in vivo early intestine tolerance in mice were included for comparison and to further explore potential correlations between the BWF results and the in vitro RBE as reported in previous studies. The results suggest that the modified MKM possess limitations in reproducing the experimental in vitro RBE 10 for the V79 cell line in case of ions heavier than 20 Ne. Furthermore, due to the different modelled endpoint, marked deviations were found between the RBE values assessed using the reference BWF and the IBWF for ions heavier than 2 H. Finally, the IBWF was unchangingly applied to calculate RBE values by processing lineal energy density distributions experimentally measured with eight different microdosimeters in 19 1 H and 12 C beams at ten different facilities (eight clinical and two research ones). Despite the differences between the detectors, irradiation facilities, beam profiles (pristine or spread out Bragg peak), maximum beam energy, beam delivery (passive or active scanning), energy degradation system (water, PMMA, polyamide or low-density polyethylene), the obtained IBWF-based RBE trends were found to be in good agreement with the corresponding ones in case of computer-simulated microdosimetric spectra (average relative deviation equal to 0.8% and 5.7% for 1 H and 12 C ions respectively).

Experimental studies of microdosimetry in therapeutic ion beams have been performed using several detectors. The differences among the microdosimeters lie on the shapes, the site sizes, and the material. The present study proposes a method to extract from the heterogeneous information collected with the different microdosimeters a univocal specification of the radiation quality of the radiation field. Historically the specification of the radiation quality is provided either in terms of linear energy transfer (LET) or in terms of lineal energy, y. The first part of this study focuses on identifying the correlation between the distributions of LET and the lineal energy spectra as well as the correspondence between their mean values calculated from the frequency and dose distributions. The evaluation is inspired by the method of LET analysis described by Kellerer (1972 Phys. Med. Biol. 17 232-40) with adaptation to the peculiarities of ion-beam therapy where the pristine irradiation is unidirectional and made of a single species of essentially mono-energetic ions. The second objective of this study is to interpret the spectra collected by a slab and perform the necessary conversion to estimate what the spectrum would be if it was collected by a detector different in shape, material, or size. An example is provided using as starting point the simulated lineal energy spectrum of carbon ions impinging a slab detector of graphite and applying the method to convert it to the spectra that would be obtained in the same radiation field with spherical, cylindrical, and slab detectors made of water.

Ion-beam therapy provides a high dose conformity and increased radiobiological effectiveness with respect to conventional radiation-therapy. Strict constraints on the maximum uncertainty on the biological weighted dose and consequently on the biological weighting factor require the determination of the radiation quality, defined as the types and energy spectra of the radiation at a specific point. However the experimental determination of radiation quality, in particular for an internal target, is not simple and the features of ion interactions and treatment delivery require dedicated and optimized detectors. Recently chemical vapor deposition (CVD) diamond detectors have been suggested as ion-beam therapy microdosimeters. Diamond detectors can be manufactured with small cross sections and thin shapes, ideal to cope with the high fluence rate. However the sensitive volume of solid state detectors significantly deviates from conventional microdosimeters, with a diameter that can be up to 1000 times the height. This difference requires a redefinition of the concept of sensitive thickness and a deep study of the secondary to primary radiation, of the wall effects and of the impact of the orientation of the detector with respect to the radiation field. The present work intends to study through Monte Carlo simulations the impact of the detector geometry on the determination of radiation quality quantities, in particular on the relative contribution of primary and secondary radiation. The dependence of microdosimetric quantities such as the unrestricted linear energy L and the lineal energy y are investigated for different detector cross sections, by varying the particle type (carbon ions and protons) and its energy.

PARTNER (Particle Training Network for European Radiotherapy) is a project funded by the European Commission's Marie Curie-ITN funding scheme through the ENLIGHT Platform for 5.6 million Euro. PARTNER has brought together academic institutes, research centres and leading European companies, focusing in particular on a specialized radiotherapy (RT) called hadron therapy (HT), interchangeably referred to as particle therapy (PT). The ultimate goal of HT is to deliver more effective treatment to cancer patients leading to major improvement in the health of citizens. In Europe, several hundred million Euro have been invested, since the beginning of this century, in PT. In this decade, the use of HT is rapidly growing across Europe, and there is an urgent need for qualified researchers from a range of disciplines to work on its translational research. In response to this need, the European community of HT, and in particular 10 leading academic institutes, research centres, companies and small and medium-sized enterprises, joined together to form the PARTNER consortium. All partners have international reputations in the diverse but complementary fields associated with PT: clinical, radiobiological and technological. Thus the network incorporates a unique set of competencies, expertise, infrastructures and training possibilities. This paper describes the status and needs of PT research in Europe, the importance of and challenges associated with the creation of a training network, the objectives, the initial results, and the expected long-term benefits of the PARTNER initiative.