Metrology for advanced radiotherapy using particle beams with ultra-high dose rates.

Dosimetry of ultra-high dose rate beams is one of the critical components which is required for safe implementation of FLASH radiotherapy (RT) into clinical practice. In the past years several national and international programmes have emerged with the aim to address some of the needs that are required for translation of this modality to clinics. These involve the establishment of dosimetry standards as well as the validation of protocols and dosimetry procedures. This review provides an overview of recent developments in the field of dosimetry for FLASH RT, with particular focus on primary and secondary standard instruments, and provides a brief outlook on the future work which is required to enable clinical implementation of FLASH RT.

State-of-the-art silicon carbide diode dosimeters for ultra-high dose-per-pulse radiation at FLASH radiotherapy.

Objective.The successful implementation of FLASH radiotherapy in clinical settings, with typical dose rates >40 Gy s-1, requires accurate real-time dosimetry.Approach.Silicon carbide (SiC) p-n diode dosimeters designed for the stringent requirements of FLASH radiotherapy have been fabricated and characterized in an ultra-high pulse dose rate electron beam. The circular SiC PiN diodes were fabricated at IMB-CNM (CSIC) in 3µm epitaxial 4H-SiC. Their characterization was performed in PTB's ultra-high pulse dose rate reference electron beam. The SiC diode was operated without external bias voltage. The linearity of the diode response was investigated up to doses per pulse (DPP) of 11 Gy and pulse durations ranging from 3 to 0.5µs. Percentage depth dose measurements were performed in ultra-high dose per pulse conditions. The effect of the total accumulated dose of 20 MeV electrons in the SiC diode sensitivity was evaluated. The temperature dependence of the response of the SiC diode was measured in the range 19 °C-38 °C. The temporal response of the diode was compared to the time-resolved beam current during each electron beam pulse. A diamond prototype detector (flashDiamond) and Alanine measurements were used for reference dosimetry.Main results.The SiC diode response was independent both of DPP and of pulse dose rate up to at least 11 Gy per pulse and 4 MGy s-1, respectively, with tolerable deviation for relative dosimetry (<3%). When measuring the percentage depth dose under ultra-high dose rate conditions, the SiC diode performed comparably well to the reference flashDiamond. The sensitivity reduction after 100 kGy accumulated dose was <2%. The SiC diode was able to follow the temporal structure of the 20 MeV electron beam even for irregular pulse estructures. The measured temperature coefficient was (-0.079 ± 0.005)%/°C.Significance.The results of this study demonstrate for the first time the suitability of silicon carbide diodes for relative dosimetry in ultra-high dose rate pulsed electron beams up to a DPP of 11 Gy per pulse.

First use of silicon carbide detectors with graphene-enhanced contacts for medical dosimetry.

Silicon Carbide (SiC) is a radiation hard wide bandgap semiconductor, which makes it an interesting alternative for radiation detector fabrication, with potential applications such as High Energy Physics, synchrotron and radiotherapy instrumentation. In addition, by reducing the amount of metal over the active area of said detectors (typically used for electrical connectivity with the implant of the pn-junction) unwanted effects from secondary interactions which can affect the accuracy of the measurement can be diminished, essential to meet the medical standards of precision. In this article, the use of epitaxially-grown graphene is explored as an alternative to metallic contacts with these prototypes. To this end, the first prototypes of SiC diodes with epitaxial graphene contacts were produced at IMB-CNM for radiation detection,along with reference devices. In order to characterise the feasibility of the technology in the medical application, the dose rate linearity of the SiC device with graphene was measured in a radiotherapy Linac in the dose rate range of 1-6 Gy/min. The response of the device was compared to that observed on devices with similar geometries reported elsewhere. To fully characterise the devices, the same exercise was repeated in a laboratory X-ray tube. Under the later set-up, the prototype is compared against a device with a fully metallised active region.

First experimental measurements of 2D microdosimetry maps in proton therapy.

BACKGROUND: Empirical data in proton therapy indicate that relative biological effectiveness (RBE) is not constant, and it is directly related to the linear energy transfer (LET). The experimental assessment of LET with high resolution would be a powerful tool for minimizing the LET hot spots in intensity-modulated proton therapy, RBE- or LET-guided evaluation and optimization to achieve biologically optimized proton plans, verifying the theoretical predictions of variable proton RBE models, and so on. This could impact clinical outcomes by reducing toxicities in organs at risk. PURPOSE: The present work shows the first 2D LET maps obtained at a proton therapy facility using the double scattering delivery mode in clinical conditions by means of new silicon 3D-cylindrical microdetectors. METHODS: The device consists of a matrix of 121 independent silicon-based detectors that have 3D-cylindrical electrodes of 25-µm diameter and 20-µm depth, resulting each one of them in a well-defined micrometric radiation sensitive volume etched inside the silicon. They have been specifically designed for a hadron therapy, improving the performance of current silicon-based microdosimeters. Microdosimetry spectra were obtained at different positions of the Bragg curve by using a water-equivalent phantom along an 89-MeV pristine proton beam generated in the Y1 proton passive scattering beamline of the Orsay Proton Therapy Centre (Institut Curie, France). RESULTS: Microdosimetry 2D-maps showing the variation of the lineal energy with depth in the three dimensions were obtained in situ during irradiation at clinical fluence rates (∼108  s-1  cm-2 ) for the first time with a spatial resolution of 200 µm, the highest achieved in the transverse plane so far. The experimental results were cross-checked with Monte Carlo simulations and a good agreement between the spectra shapes was found. The experimental frequency-mean lineal energy values in silicon were 1.858 ± 0.019 keV µm-1 at the entrance, 2.61 ± 0.03 keV µm-1 at the proximal distance, 4.97 ± 0.05 keV µm-1 close to the Bragg peak, and 8.6 ± 0.1 keV µm-1 at the distal edge. They are in good agreement with the expected trends in the literature in clinical proton beams. CONCLUSIONS: We present the first 2D microdosimetry maps obtained in situ during irradiation at clinical fluence rates in proton therapy. Our results show that the arrays of 3D-cylindrical microdetectors are a reliable microdosimeter to evaluate LET maps not only in the longitudinal axis of the beam, but also in the transverse plane allowing for LET characterization in three dimensions. This work is a proof of principle showing the capacity of our system to deliver LET 2D maps. This kind of experimental data is needed to validate variable proton RBE models and to optimize LET-guided plans.

Microdosimetry performance of the first multi-arrays of 3D-cylindrical microdetectors.

The present work reports on the microdosimetry measurements performed with the two first multi-arrays of microdosimeters with the highest radiation sensitive surface covered so far. The sensors are based on new silicon-based radiation detectors with a novel 3D cylindrical architecture. Each system consists of arrays of independent microdetectors covering 2 mm[Formula: see text]2 mm and 0.4 mm[Formula: see text]12 cm radiation sensitive areas, the sensor distributions are arranged in layouts of 11[Formula: see text]11 microdetectors and 3[Formula: see text]3 multi-arrays, respectively. We have performed proton irradiations at several energies to compare the microdosimetry performance of the two systems, which have different spatial resolution and detection surface. The unitcell of both arrays is a 3D cylindrical diode with a 25 [Formula: see text]m diameter and a 20 [Formula: see text]m depth that results in a welldefined and isolated radiation sensitive micro-volume etched inside a silicon wafer. Measurements were carried out at the Accélérateur Linéaire et Tandem à Orsay (ALTO) facility by irradiating the two detection systems with monoenergetic proton beams from 6 to 20 MeV at clinical-equivalent fluence rates. The microdosimetry quantities were obtained with a spatial resolution of 200 [Formula: see text]m and 600 [Formula: see text]m for the 11[Formula: see text]11 system and for the 3[Formula: see text]3 multi-array system, respectively. Experimental results were compared with Monte Carlo simulations and an overall good agreement was found. The good performance of both microdetector arrays demonstrates that this architecture and both configurations can be used clinically as microdosimeters for measuring the lineal energy distributions and, thus, for RBE optimization of hadron therapy treatments. Likewise, the results have shown that the devices can be also employed as a multipurpose device for beam monitoring in particle accelerators.

Silicon 3D Microdetectors for Microdosimetry in Hadron Therapy.

The present overview describes the evolution of new microdosimeters developed in the National Microelectronics Center in Spain (IMB-CNM, CSIC), ranging from the first ultra-thin 3D diodes (U3DTHINs) to the advanced 3D cylindrical microdetectors, which have been developed over the last 10 years. In this work, we summarize the design, main manufacture processes, and electrical characterization of these devices. These sensors were specifically customized for use in particle therapy and overcame some of the technological challenges in this domain, namely the low noise capability, well-defined sensitive volume, high spatial resolution, and pile-up robustness. Likewise, both architectures reduce the loss of charge carriers due to trapping effects, the charge collection time, and the voltage required for full depletion compared to planar silicon detectors. In particular, a 3D‒cylindrical architecture with electrodes inserted into the silicon bulk and with a very well‒delimited sensitive volume (SV) mimicked a cell array with shapes and sizes similar to those of mammalian cells for the first time. Experimental tests of the carbon beamlines at the Grand Accélérateur National d'Lourds (GANIL, France) and Centro Nazionale Adroterapia Oncologica (CNAO, Italy) showed the feasibility of the U3DTHINs in hadron therapy beams and the good performance of the 3D‒cylindrical microdetectors for assessing linear energy distributions of clinical beams, with clinical fluence rates of 5 × 107 s-1cm-2 without saturation. The dose-averaged lineal energies showed a generally good agreement with Monte Carlo simulations. The results indicated that these devices can be used to characterize the microdosimetric properties in hadron therapy, even though the charge collection efficiency (CCE) and electronic noise may pose limitations on their performance, which is studied and discussed herein. In the last 3D‒cylindrical microdetector generation, we considerably improved the CCE due to the microfabrication enhancements, which have led to shallower and steeper dopant profiles. We also summarize the successive microdosimetric characterizations performed with both devices in proton and carbon beamlines.

The European Joint Research Project UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates.

UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates is a recently started European Joint Research Project with the aim to develop and improve dosimetry standards for FLASH radiotherapy, very high energy electron (VHEE) radiotherapy and laser-driven medical accelerators. This paper gives a short overview about the current state of developments of radiotherapy with FLASH electrons and protons, very high energy electrons as well as laser-driven particles and the related challenges in dosimetry due to the ultra-high dose rate during the short radiation pulses. We summarize the objectives and plans of the UHDpulse project and present the 16 participating partners.