Diamond based integrated detection system for dosimetric and microdosimetric characterization of radiotherapy ion beams.

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.

A diamond detector based dosimetric system for instantaneous dose rate measurements in FLASH electron beams.

Objective.A reliable determination of the instantaneous dose rate (I-DR) delivered in FLASH radiotherapy treatments is believed to be crucial to assess the so-called FLASH effect in preclinical and biological studies. At present, no detectors nor real-time procedures are available to do that in ultra high dose rate (UH-DR) electron beams, typically consisting ofµs pulses characterized by I-DRs of the order of MGy/s. A dosimetric system is proposed possibly overcoming the above reported limitation, based on the recently developed flashDiamond (fD) detector (model 60025, PTW-Freiburg, Germany).Approach.A dosimetric system is proposed, based on a flashDiamond detector prototype, properly modified and adapted for very fast signal transmission. It was used in combination with a fast transimpedance amplifier and a digital oscilloscope to record the temporal traces of the pulses delivered by an ElectronFlash linac (SIT S.p.A., Italy). The proposed dosimetric systems was investigated in terms of the temporal characteristics of its response and the capability to measure the absolute delivered dose and instantaneous dose rate (I-DR). A 'standard' flashDiamond was also investigated and its response compared with the one of the specifically designed prototype.Main results. Temporal traces recorded in several UH-DR irradiation conditions showed very good signal to noise ratios and rise and decay times of the order of a few tens ns, faster than the ones obtained by the current transformer embedded in the linac head. By analyzing such signals, a calibration coefficient was derived for the fD prototype and found to be in agreement within 1% with the one obtained under reference60Co irradiation. I-DRs as high as about 2 MGy s-1were detected without any undesired saturation effect. Absolute dose per pulse values extracted by integrating the I-DR signals were found to be linear up to at least 7.13 Gy and in very good agreement with the ones obtained by connecting the fD to a UNIDOS electrometer (PTW-Freiburg, Germany). A good short term reproducibility of the linac output was observed, characterized by a pulse-to-pulse variation coefficient of 0.9%. Negligible differences were observed when replacing the fD prototype with a standard one, with the only exception of a somewhat slower response time for the latter detector type.Significance.The proposed fD-based system was demonstrated to be a suitable tool for a thorough characterization of UH-DR beams, providing accurate and reliable time resolved I-DR measurements from which absolute dose values can be straightforwardly derived.

On the measurement uncertainty of microdosimetric quantities using diamond and silicon microdosimeters in carbon-ion beams.

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.

Application of a novel diamond detector for commissioning of FLASH radiotherapy electron beams.

PURPOSE: A diamond detector prototype was recently proposed by Marinelli et al. (Medical Physics 2022, https://doi.org/10.1002/mp.15473) for applications in ultrahigh-dose-per-pulse (UH-DPP) and ultrahigh-dose-rate (UH-DR) beams, as used in FLASH radiotherapy (FLASH-RT). In the present study, such so-called flashDiamond (fD) was investigated from the dosimetric point of view, under pulsed electron beam irradiation. It was then used for the commissioning of an ElectronFlash linac (SIT S.p.A., Italy) both in conventional and UH-DPP modalities. METHODS: Detector calibration was performed in reference conditions, under 60 Co and electron beam irradiation. Its response linearity was investigated in UH-DPP conditions. For this purpose, the DPP was varied in the 1.2-11.9 Gy range, by changing either the beam applicator or the pulse duration from 1 to 4 µs. Dosimetric validation of the fD detector prototype was then performed in conventional modality, by measuring percentage depth dose (PDD) curves, beam profiles, and output factors (OFs). All such measurements were carried out in a motorized water phantom. The obtained results were compared with the ones from commercially available dosimeters, namely, a microDiamond, an Advanced Markus ionization chamber, a silicon diode detector, and EBT-XD GAFchromic films. Finally, the fD detector was used to fully characterize the 7 and 9 MeV UH-DPP electron beams delivered by the ElectronFlash linac. In particular, PDDs, beam profiles, and OFs were measured, for both energies and all the applicators, and compared with the ones from EBT-XD films irradiated in the same experimental conditions. RESULTS: The fD calibration coefficient resulted to be independent from the investigated beam qualities. The detector response was found to be linear in the whole investigated DPP range. A very good agreement was observed among PDDs, beam profiles, and OFs measured by the fD prototype and reference detectors, both in conventional and UH-DPP irradiation modalities. CONCLUSIONS: The fD detector prototype was validated from the dosimetric point of view against several commercial dosimeters in conventional beams. It was proved to be suitable in UH-DPP and UH-DR conditions, for which no other commercial real-time active detector is available to date. It was shown to be a very useful tool to perform fast and reproducible beam characterizations in standard clinical motorized water phantom setups. All of the previously mentioned demonstrate the suitability of the proposed detector for the commissioning of UH-DR linac beams for preclinical FLASH-RT applications.

Design, realization, and characterization of a novel diamond detector prototype for FLASH radiotherapy dosimetry.

PURPOSE: FLASH radiotherapy (RT) is an emerging technique in which beams with ultra-high dose rates (UH-DR) and dose per pulse (UH-DPP) are used. Commercially available active real-time dosimeters have been shown to be unsuitable in such conditions, due to severe response nonlinearities. In the present study, a novel diamond-based Schottky diode detector was specifically designed and realized to match the stringent requirements of FLASH-RT. METHODS: A systematic investigation of the main features affecting the diamond response in UH-DPP conditions was carried out. Several diamond Schottky diode detector prototypes with different layouts were produced at Rome Tor Vergata University in cooperation with PTW-Freiburg. Such devices were tested under electron UH-DPP beams. The linearity of the prototypes was investigated up to DPPs of about 26 Gy/pulse and dose rates of approximately 1 kGy/s. In addition, percentage depth dose (PDD) measurements were performed in different irradiation conditions. Radiochromic films were used for reference dosimetry. RESULTS: The response linearity of the diamond prototypes was shown to be strongly affected by the size of their active volume as well as by their series resistance. By properly tuning the design layout, the detector response was found to be linear up to at least 20 Gy/pulse, well into the UH-DPP range conditions. PDD measurements were performed by three different linac applicators, characterized by DPP values at the point of maximum dose of 3.5, 17.2, and 20.6 Gy/pulse, respectively. The very good superimposition of three curves confirmed the diamond response linearity. It is worth mentioning that UH-DPP irradiation conditions may lead to instantaneous detector currents as high as several mA, thus possibly exceeding the electrometer specifications. This issue was properly addressed in the case of the PTW UNIDOS electrometers. CONCLUSIONS: The results of the present study clearly demonstrate the feasibility of a diamond detector for FLASH-RT applications.

Microdosimetric characterization of clinical carbon-ion beams using synthetic diamond detectors and spectral conversion methods.

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.

Development of a new microdosimetric biological weighting function for the RBE10 assessment in case of the V79 cell line exposed to ions from 1H to 238U.

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).

S-band hybrid amplifiers based on hydrogenated diamond FETs.

The first realizations of S-band hybrid amplifiers based on hydrogenated-diamond (H-diamond) FETs are reported. As test vehicles of the adopted H-diamond technology at microwave frequencies, two designs are proposed: one, oriented to low-noise amplification, the other, oriented to high-power operation. The two amplifying stages are so devised as to be cascaded into a two-stage amplifier. The activities performed, from the technological steps to characterization, modelling, design and realization are illustrated. Measured performance demonstrates, for the low-noise stage, a noise figure between 7 and 8 dB in the 2-2.5 GHz bandwidth, associated with a transducer gain between 5 and 8 dB. The OIP3 at 2 GHz is 21 dBm. As to the power-oriented stage, its transducer gain is 5-6 dB in the 2-2.5 GHz bandwidth. The 1-dB output compression point at 2 GHz is 20 dBm whereas the OIP3 is 33 dBm. Cascading the measured S-parameters of the two stages yields a transducer gain of 15 ± 1.2 dB in the 2-3 GHz bandwidth.

Novel Hybrid Composites Based on PVA/SeTiO2 Nanoparticles and Natural Hydroxyapatite for Orthopedic Applications: Correlations between Structural, Morphological and Biocompatibility Properties.

The properties of poly(vinyl alcohol) (PVA)-based composites recommend this material as a good candidate for the replacement of damaged cartilage, subchondral bone, meniscus, humeral joint and other orthopedic applications. The manufacturing process can be manipulated to generate the desired biomechanical properties. However, the main shortcomings of PVA hydrogels are related to poor strength and bioactivity. To overcome this situation, reinforcing elements are added to the PVA matrix. The aim of our work was to develop and characterize a novel composition based on PVA reinforced with Se-doped TiO2 nanoparticles and natural hydroxyapatite (HA), for possible orthopedic applications. The PVA/Se-doped TiO2 composites with and without HA were structurally investigated by FTIR and XRD, in order to confirm the incorporation of the inorganic phase in the polymeric structure, and by SEM and XRF, to evidence the ultrastructural details and dispersion of nanoparticles in the PVA matrix. Both the mechanical and structural properties of the composites demonstrated a synergic reinforcing effect of HA and Se-doped TiO2 nanoparticles. Moreover, the tailorable properties of the composites were proved by the viability and differentiation potential of the bone marrow mesenchymal stem cells (BMMSC) to osteogenic, chondrogenic and adipogenic lineages. The novel hybrid PVA composites show suitable structural, mechanical and biological features to be considered as a promising biomaterial for articular cartilage and subchondral bone repair.

High-current stream of energetic α particles from laser-driven proton-boron fusion.

The nuclear reaction known as proton-boron fusion has been triggered by a subnanosecond laser system focused onto a thick boron nitride target at modest laser intensity (∼10^{16}W/cm^{2}), resulting in a record yield of generated α particles. The estimated value of α particles emitted per laser pulse is around 10^{11}, thus orders of magnitude higher than any other experimental result previously reported. The accelerated α-particle stream shows unique features in terms of kinetic energy (up to 10 MeV), pulse duration (∼10 ns), and peak current (∼2 A) at 1 m from the source, promising potential applications of such neutronless nuclear fusion reactions. We have used a beam-driven fusion scheme to explain the total number of α particles generated in the nuclear reaction. In this model, protons accelerated inside the plasma, moving forward into the bulk of the target, can interact with ^{11}B atoms, thus efficiently triggering fusion reactions. An overview of literature results obtained with different laser parameters, experimental setups, and target compositions is reported and discussed.

MICRODOSIMETRY OF CLINICAL ION BEAMS: CONVERTING SPECTRA FROM DIAMOND SLAB TO WATER OF DIFFERENT SHAPES.

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.

Is the PTW 60019 microDiamond a suitable candidate for small field reference dosimetry?

A systematic study of the PTW microDiamond (MD) output factors (OF) is reported, aimed at clarifying its response in small fields and investigating its suitability for small field reference dosimetry. Ten MDs were calibrated under 60Co irradiation. OF measurements were performed in 6 MV photon beams by a CyberKnife M6, a Varian DHX and an Elekta Synergy linacs. Two PTW silicon diodes E (Si-D) were used for comparison. The results obtained by the MDs were evaluated in terms of absorbed dose to water determination in reference conditions and OF measurements, and compared to the results reported in the recent literature. To this purpose, the Monte Carlo (MC) beam-quality correction factor, [Formula: see text], was calculated for the MD, and the small field output correction factors, [Formula: see text], were calculated for both the MD and the Si-D by two different research groups. An empirical function was also derived, providing output correction factors within 0.5% from the MC values calculated for all of the three linacs. A high reproducibility of the dosimetric properties was observed among the ten MDs. The experimental [Formula: see text] values are in agreement within 1% with the MC calculated ones. Output correction factors within +0.7% and -1.4% were obtained down to field sizes as narrow as 5 mm. The resulting MD and Si-D field factors are in agreement within 0.2% in the case of CyberKnife measurements and 1.6% in the other cases. This latter higher spread of the data was demonstrated to be due to a lower reproducibility of small beam sizes defined by jaws or multi leaf collimators. The results of the present study demonstrate the reproducibility of the MD response and provide a validation of the MC modelling of this device. In principle, accurate reference dosimetry is thus feasible by using the microDiamond dosimeter for field sizes down to 5 mm.