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Publications (16)
Jacinta S.L. Yap, Navrit J.S. Bal, Mark D. Brooke, Cristina Oancea, Carlos Granja, Andrzej Kacperek, Simon Jolly, Frank Van den Heuvel, Jason L. Parsons, Carsten P. Welsch
Proton therapy can achieve a highly targeted treatment by utilising the advantageous dosimetric characteristics of the Bragg Peak. Protons traversing through a material will deposit their maximum energy at the Bragg Peak through ionisation and other interactions, transferring minimal excess dose to surrounding tissue and organs. This rate of energy loss is also quantified by the linear energy transfer (LET), which is indicative of radiation quality and radiobiological effects. However it is a challenging physical quantity to measure, as characterisation of radiation fields and the impact of LET on treatment requires advanced tools and technology. The MiniPIX-Timepix is a miniaturised, hybrid semiconductor pixel detector capable of high resolution spectrometric tracking, enabling wide-range detection of the deposited energy, position and direction of single particles. Experimental measurements were performed at a clinical facility, the Clatterbridge Cancer Centre which houses a 60 MeV ocular proton therapy beamline. A realistic end-to-end model of the facility was developed in the Monte Carlo code TOPAS (TOol for PArticle Simulation) and was used to simulate the experimental conditions. The detector was held at 45° and 60° perpendicular to the beam, and placed downstream of various thickness Polymethyl methacrylate (PMMA) blocks to acquire data along the dose deposition depth. Empirical cluster data providing track length and the energy deposition distributions were used to obtain the LET spectra. The determined values for the LET in silicon and dose averaged LET across the BP show general agreement with simulated results, supporting the applicability of the TOPAS CCC model. This work explores the capability of the MiniPIX detector to measure physical quantities to resolve the LET, and discusses experimental considerations and further possibilities.
Paulina Stasica-Dudek, Carlos Granja, Renata Kopeć, Dawid Krzempek, Cristina Oancea, Antoni Rucinski, Marzena Rydygier, Mateusz Winiarz, Jan Gajewski
Objective. This study addresses the need for experimental validation of linear energy transfer (LET) in proton therapy by presenting a methodology and results for LET spectra measurements using a miniaturized Timepix3 pixel detector. Approach. LET was measured in spread-out Bragg peak (SOBP) and IMPT fields using homogeneous and heterogeneous phantoms. A GPU-accelerated Monte Carlo (MC) simulation was used for validation. Main results. Experimental results showed good agreement with MC simulations, with a mean relative difference in dose-averaged LET of ~5.1%. Significance. This validates the feasibility of using the Timepix3 detector for LET-based patient-specific quality assurance (PSQA) in proton therapy, supporting future clinical implementation of LET optimization in treatment planning.
Linh Tran, Cristina Oancea, Satoshi Kodaira, David Bolst, James Vohradsky, Carlos Granja, Jan Jakubek, Jaroslav Šolc, Elisabeth Bodenstein, Sebastian Gantz, Jörg Pawelke, Lukas Marek, Anatoly Rosenfeld
Fragments and neutrons produced by inelastic reactions in particle therapy can make a significant contribution to the Relative Biological Effectiveness (RBE) and as a consequence the biologically weighted-dose in the distal part of the Spread-out Bragg Peak (SOBP); this also make changes to the radiation quality and dose equivalent in surrounding organs near the target tumour. These mixed radiation fields of secondary fragments and neutrons are difficult to characterise which is why this paper reviews some solid state radiation detectors that can measure the radiation field produced out of primary field in particle therapy, and also assess the radiation quality and dose equivalent to normal organs located near the target volume. These detectors include active types such as the silicon on insulator (SOI) microdosimeter, the monolithic ΔE-E telescope, the pixel detectors TimePix3, and passive detectors such as CR-39 plastic charged particle track detector, and the fluorescent nuclear track detector (FNTD). This paper also reports on the microdosimetric measurements obtained with silicon-based microdosimeters, both laterally and downstream of the target volume, for proton and carbon ion beams. It also details the measurements taken by the TimePix3 detector, including a customised, miniaturized version with enhanced resolving power, for characterizing secondary radiation in proton therapy through single-particle tracking. The CR-39 and FNTD passive linear energy transfer (LET) detectors are also reviewed and the advantages and disadvantages of each type of detector are discussed. The SOI microdosimeter and ΔE-E telescope are suitable for characterising the typical mixed radiation field for out-of-field in particle therapy. An SOI microdosimeter can provide dose equivalent values to evaluate risk to normal organs, while the ΔE-E telescope can operate as a microdosimeter and distinguish the type of particles in the secondary radiation field. The TimePix3 chip can provide mixed field decomposition, particle flux, dose rate, and LET spectra while the CR-39 plastic detector could measure the LET spectra, absorbed dose, and dose equivalent from secondary particles of Carbon ion beam via nuclear targeted fragmentation reactions.
Paulina Stasica-Dudek, Cristina Oancea, Carlos Granja, Konrad Guguła, Jan Jakubek, Renata Kopeć, Dawid Krzempek, Michal Matous, Antoni Rucinski, Marzena Rydygier, Jan Gajewski
Purpose: With the increasing use of proton therapy, there is a growing emphasis on including radiation quality, often quantified by linear energy transfer, as a treatment plan optimization factor. The Timepix detectors offer energy-sensitive particle tracking useful for the characterization of proton linear energy transfer. To improve the detector's performance in mixed radiation fields produced in proton therapy, we customized the detector settings and performed the per-pixel energy calibration. Methods: The detection threshold and per-pixel signal shaping time (I krum current) were customized, and energy calibration was performed for MiniPIX Timepix3. The detector calibration was verified using α source and clinical proton beams, as well as Monte Carlo simulations. The effects on the detector's performance, in terms of spectral saturation and pixel occupancy, were evaluated. Results: Measurements with proton beams showed a good agreement with simulations. With the customized settings, the measurable energy range in the detector data-driven mode was extended, and the signal duration time was reduced by 80%, while the yield of pixel time occupancy reduction depends on the number of occupied pixels. For performed measurements with proton beams, the number of occupied pixels was further reduced up to 40% due to the increased threshold. Conclusions: Customized detector configuration of the Timepix3 detector allowed for reduced pixel occupancy and mitigation of signal saturation in a data-driven mode without significantly interfering with the energy deposition measurement. The presented approach enables the extension of the operational range, including higher intensities and mixed-radiation fields in particle radiotherapy environments.
K. Sykorova, Z. Buk, M. Cepek, C. Granja, C. Oancea, L. Marek
Semiconductor hybrid pixel detectors with Timepix 3 ASIC chips developed by the Medipix collaboration at CERN enable high-resolution, single-particle detection, measuring deposited energy and time of arrival per pixel. This study introduces machine learning models—BiLSTM, fully connected neural networks, and CatBoost decision trees—for classifying individual particle events based on morphological and spectral features. These models were trained on an extensive, labeled experimental dataset and validated on a separate test set. Classification was performed across five particle categories: electrons & photons, alpha particles, heavy nuclei, low-energy protons, and high-energy protons. The models demonstrated high accuracy, with BiLSTM requiring no preprocessing but slower inference, while CatBoost achieved the fastest predictions. Additionally, an unsupervised Gaussian Mixture Model was used to explore the separation between electrons and photons. Feature importance analysis revealed LET, energy distribution, and cluster morphology as key discriminators. Future work will integrate these models into the TraX Engine platform developed by ADVACAM.
C. Bălan, C. Granja, G. Mytsin, S. Shvidky, A. Molokanov, V. Chiș, C. Oancea
A rapid increase in the use of proton therapy for cancer treatment has been seen in the last decade due to its clinical advantages. Therefore, more and more patients with implants and other metallic devices will be among those who will be treated. This study experimentally examines the effect and changes in the delivered fields, using water-equivalent phantoms with and without titanium (Ti) dental implants positioned along the primary beam path. We measured in detail the composition and spectral-tracking characterization of particles generated in the plateau region of the Bragg curve towards the Sub-peak region using high-spatial resolution, spectral and time-sensitive imaging detectors with a pixelated array provided by the ASIC chip Timepix3. A 170 MeV proton beam was collimated and modulated in a polymethyl methacrylate (PMMA) block. Placing two dental implants behind the PMMA block, the radiation was measured using two pixeled detectors with silicon (Si) sensors. The Timepix3 (TPX3) detectors measured in detail particle fluxes, dose rates (DR) and linear energy transfer (LET) spectra for resolved particle types. Artificial intelligence (AI)-based trained neural networks (NN) calibrated in well-defined radiation fields were used to analyze and identify particles based on morphology and characteristic spectral-tracking response. The beam was characterized and single-particle tracks were registered and decomposed into particle-type groups. The resulting particle fluxes in both setups are resolved into three main classes of particles: i) protons, ii) electrons and photons, and iii) ions. Protons are the main particle component responsible for dose deposition. High-energy transfer particles (HETP), namely ions, exhibited differences in both dosimetric aspects that were investigated: DR and particle fluxes, when the Ti implants were placed in the setup. The detailed multi-parametric information of the secondary radiation field provides a comprehensive understanding of the impact of Ti materials in proton therapy.
C. Granja, J. Solc, J. Gajewski, A. Rucinski, P. Stasica, M. Rydygier, L. Marek, C. Oancea
Mixed radiation fields in environments such as particle radiotherapy and outer space exhibit large complexity in terms of composition and spectral distribution which are difficult to measure in detail. For this purpose, we present a high-sensitivity technique using the pixel detector Timepix3 to measure the composition and spectral-tracking characterization of secondary fields produced in proton radiotherapy. Particle-event classes are resolved into broad groups of high-energy transfer particles (HETP), such as protons, ions and neutrons, as well as low-energy transfer particles (LETP), such as electrons, X rays and, partly, low-energy gamma rays. The quantum-imaging capability of Timepix3 is exploited to enhance the resolving power for particle-type classification. The particle tracks are analyzed by spectral-sensitive pattern recognition algorithms. The response matrix for Timepix3 is newly derived based on experimental calibrations in well‑defined radiation fields including in‑beam rotational scans of protons performed at various energies and directions. Clinical proton beams of radiotherapeutic intensities and energies in the range 12–225 MeV were used in experimental configurations with and without a tissue‑equivalent phantom. Detailed results of radiation components can be used to produce total and partial particle fluxes, dose rate, absorbed dose, deposited energy and linear‑energy‑transfer (LET) spectra. Dedicated Monte Carlo (MC) simulations are compared with experimental results of field composition, particle fluence, and deposited energy. The numerical information aids the interpretation of experimental data which includes also secondary neutrons. The technique and developed methodology can be applied for research and routine measurements in environments of varying complexity.
Cristina Bălan, Carlos Granja, Gennady Mytsin, Sergey Shvidky, Alexander Molokanov, Lukas Marek, Vasile Chiș, Cristina Oancea
This study evaluates the composition of scattered particles in proton therapy near titanium dental implants. Using a therapeutic conformal proton beam, the experiment was conducted on a head phantom implanted with Ti and plastic inserts. A MiniPIX Timepix3 hybrid pixel detector was used to detect scattered radiation behind the tumor during irradiation. Algorithms trained with artificial intelligence (AI) were used to recognize particles and decompose the radiation field. Measurements were collected at two beam angles (0° and 60°), and AI identified protons, electrons & photons, and fast neutrons. Scattered radiation with Ti implants was mainly electrons and photons (52.2%), while plastic implants showed higher proton contributions (65.4%). LET spectra ranged from 0.01 to 7.5 keV/μm. Low-LET was mostly from electrons and photons, and high-LET from protons and ions. The findings help quantify out-of-field radiation risks, supporting safer, more precise treatment validation.
Nathan Harrison, Serdar Charyyev, Cristina Oancea, Alexander Stanforth, Edgar Gelover, Shuang Zhou, William S Dynan, Tiezhi Zhang, Steven Biegalski, Liyong Lin
This study presents a methodology to validate dose, dose rate (DR), and linear energy transfer (LET) in ultra high dose rate (UHDR) proton therapy, also known as conformal FLASH. FLASH aims to reduce normal tissue damage while preserving tumor control, but its clinical use is limited by challenges in quality assurance (QA) measurements. Researchers used a 250-MeV proton beam and a 3D-printed ridge filter to deliver conformal FLASH to a spherical target. Dose and DR were measured using a 4D multi-layer strip ionization chamber (MLSIC), while LET was assessed using a high-resolution Timepix3 detector with an under-sample and recover (USRe) technique to avoid pile-up. Results from these measurements were compared with those from the MatriXX PT detector and Monte Carlo simulations. The data showed high agreement between experimental results and simulations, with >95% gamma passing rates for dose comparisons and <0.3% difference in DR at the lateral margins. LET measurements also showed strong alignment, with Bhattacharyya distances <1.3% across margins. The study concludes that this methodology is effective for experimental validation and QA of FLASH treatment plans.
Paulina Stasica, Hanh Nguyen, Carlos Granja, Renata Kopeć, Lukas Marek, Cristina Oancea, Łukasz Raczyński, Antoni Rucinski, Marzena Rydygier, Keith Schubert, Reinhard Schulte, Jan Gajewski
Protons have advantageous dose distributions and are increasingly used in cancer therapy. At the depth of the Bragg peak range, protons produce a mixed radiation field with low- and high-linear energy transfer (LET) components, where the high-LET is associated with increased biological effectiveness. LET prediction by Monte Carlo simulations is challenging to verify experimentally. This study presents measurements using the Timepix detector in a mixed radiation field produced by a therapeutic proton beam in water, validated by Monte Carlo simulations. The Timepix detector, with high-resolution particle tracking enhanced by artificial intelligence, identified particle types and measured deposited energy. Biologically relevant LET parameters, including single proton LET and dose-averaged LET, were computed. The neural network achieved over 95% accuracy in proton recognition. The LET spectra from measurements matched simulations with a mean dose-averaged LET difference of 17%. A wide LET range from sub-keV/μm to 10 keV/μm was observed. The proposed method offers accessible, experimental LET data for treatment planning validation and can be implemented in clinical proton therapy facilities.
A. Novak, C. Granja, A. Sagatova, J. Jakubek, B. Zatko, V. Vondracek, M. Andrlik, V. Zach, S. Polansky, A. Rathi, C. Oancea
The hybrid architecture of the Timepix (TPX) family of detectors enables the use of different semiconductor sensors, most commonly silicon (Si), as well as high-density materials such as Cadmium Telluride (CdTe) or Gallium Arsenide (GaAs). For this purpose, we explore the potential of a silicon carbide (SiC) sensor bump-bonded on a Timepix3 detector as a radiation imaging and particle tracking detector. SiC stands as a radiation-hard material also with the ability to operate at elevated temperatures up to several hundreds of degrees Celsius. As a result, this sensor material is more suitable for radiation harsh environments compared to conventional Si sensors. In this work, we evaluate the response for precise radiation spectrometry and high-resolution particle tracking of newly developed SiC Timepix3 detector which is built and operated as a compact radiation camera MiniPIX-Timepix3 with integrated readout electronics. Calibration measurements were conducted with mono-energetic proton beams with energies of 13, 22, and 31 MeV at the U-120M cyclotron at the Nuclear Physics Institute Czech Academy of Science (NPI CAS), Prague, as well as 100 and 226 MeV at the Proton Therapy Center Czech (PTC) in Prague. High-resolution pattern recognition analysis and single-particle spectral tracking are used for detailed inspection and understanding of the sensor response. Results include distributions of deposited energy and linear energy transfer (LET) spectra. The spatial uniformity of the pixelated detector response is examined in terms of homogeneously distributed deposited energy.
Cristina Oancea, Carlos Granja, Lukas Marek, Jan Jakubek, Jaroslav Šolc, Elisabeth Bodenstein, Sebastian Gantz, Jörg Pawelke, Jiri Pivec
Stray radiation produced by ultra-high dose-rates (UHDR) proton pencil beams is characterized using ASIC-chip semiconductor pixel detectors. A proton pencil beam with an energy of 220 MeV was utilized to deliver dose rates (DR) ranging from conventional radiotherapy DRs up to 270 Gy/s. A MiniPIX Timepix3 detector equipped with a silicon sensor and integrated readout electronics was used. The chip-sensor assembly and chipboard on water-equivalent back and backing were detached and immersed in the water phantom. The deposited energy, particle flux, DR, and the linear energy transfer (LET(Si)) spectra were measured in the silicon sensor at different positions both laterally across the pencil beam and behind the Bragg peak. At low-intensity beams, the detector is operated in the event-by-event data-driven mode for high-resolution spectral tracking of individual particles. This technique provides precise energy loss response and LET(Si) spectra with radiation field composition resolving power. At higher beam intensities a rescaling of LET(Si) can be performed as the distribution of the LET (Si) spectra exhibits the same characteristics regardless of the delivered DR. The integrated deposited energy and the absorbed dose can be thus measured in a wide range. A linear response of measured absorbed dose was obtained by gradually increasing the delivered DR to reach UHDR beams. Particle tracking of scattered radiation in data-driven mode could be performed at DRs up to 0.27 Gy/s. In integrated mode, the saturation limits were not reached at the measured out-of-field locations despite the delivered DR of over 270 Gy/s. A good agreement was found between measured and simulated absorbed doses.
A. Novak, C. Granja, A. Sagatova, V. Zach, J. Stursa, C. Oancea
This work evaluates the performance of the Timepix3 detector equipped with different semiconductor sensors (GaAs:Cr, CdTe, and Si) for spectral tracking of proton beams. Measurements were performed at the U120-M cyclotron using monoenergetic proton beams (8–31 MeV) and varying incident angles. Detectors were calibrated and operated in data-driven mode with the AdvaPIX interface. Results include deposited energy, track morphology, and LET spectra, with clear dependence on sensor material, thickness, and bias voltage. High-Z materials (CdTe, GaAs:Cr) showed superior energy deposition and stopping power compared to Si. Cluster analysis revealed performance differences in resolution and particle discrimination across sensors. The study supports optimizing sensor choice for high-LET particle detection in applications like ion therapy and space radiation. Future work includes Monte Carlo validation and testing novel materials like SiC and refined GaAs.
R. Nabha, O. Van Hoey, C. Granja, A. Parisi, M. De Saint-Hubert, L. Struelens, C. Oancea, E. Sterpin, V. Zach, J. Stursa, A. Rucinski, J. Gajewski, P. Stasica, F. Vanhavere
This study presents a method to evaluate the incident angle and linear energy transfer (LET) of protons using a compact single-layer hybrid pixel detector—Timepix. The study explores correlations between the track shape and the proton incidence angle for varying proton energies (89 MeV and 226.7 MeV) and angles (0° to 75°). Monte Carlo simulations using TOPAS were used to validate the experimental results. The detector, equipped with a 300 μm thick silicon sensor, was irradiated with a mono-energetic proton beam and the resulting cluster shapes analyzed to extract information about incident angles and LET values. A statistical model based on cluster elongation and deposited energy allowed for effective classification and angle estimation. The findings demonstrate the feasibility of using a single-layer Timepix device for angular and LET characterization in proton fields, which could support particle therapy quality assurance and beam monitoring applications.
Jacinta Yap, Navrit Bal, Mark Brooke, Carlos Granja, Andrzej Kacperek, Cristina Oancea, Carsten Welsch
Recent advancements in accelerator technology have led the rapid emergence of particle therapy facilities worldwide, affirming the need for enhanced characterisation methods of radiation fields and radiobiological effects. The Clatterbridge Cancer Centre, UK operates a 60 MeV proton beam to treat ocular cancers and facilitates studies into proton-induced radiobiological responses. Accordingly, an indicator of radiation quality is the linear energy transfer (LET), a challenging physical quantity to measure. The MiniPIX-Timepix is a miniaturised, hybrid semiconductor pixel detector with a Timepix ASIC, enabling wide-range measurements of the deposited energy, position and direction of individual charged particles. High resolution spectrometric tracking and simultaneous energy measurements of single particles enable the beam profile, time, spatial dose mapping and LET (0.1 to >100 keV/µm) to be resolved. Measurements were performed to determine the LET spectra in silicon, at different positions along the Bragg Peak (BP). We discuss the experimental setup, preliminary results and applicability of the MiniPIX for clinical environments.
C. Oancea, K. Shipulin, G. Mytsin, A. Molokanov, D. Niculae, I. Ambrožová, M. Davídková
A dosimetric experiment was performed at the Medico-Technical Complex in the Joint Institute for Nuclear Research, Dubna, to investigate the effects of metallic dental implants in the treatment of head and neck tumours with proton therapy. The study evaluated 2D dose distributions of clinical treatment plans measured in an anthropomorphic phantom and compared them to a treatment planning system. Two grade 4 Titanium implants were inserted in a maxillary area. GafChromic EBT2 films measured the 2D delivered dose. Two target scenarios were assessed—implants in the isocentre and in the entrance region of the Bragg curve. Results showed gamma index values of 84.3% and 86.4% respectively, indicating uncertainties in clinically planned dose distributions. LET spectra near implants were also studied using solid-state nuclear track detectors, detecting scattered particles outside the target.