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Konstantinos Chatzipapas

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Journal article (2026) - Nils Krah, Nicolas Arbor, Thomas Baudier, Julien Bert, Konstantinos Chatzipapas, Martina Favaretto, Hermann Fuchs, Loïc Grevillot, Hussein Harb, More authors...
Over the past years, we have developed GATE version 10, a major re-implementation of the long-standing Geant4-based Monte Carlo application for particle and radiation transport simulation in medical physics. This release introduces many new features and significant improvements, most notably a Python-based user interface replacing the legacy static input files. The new functionality of GATE version 10 is described in the part 1 companion paper (Sarrutet al2025 arXiv:2507.09842). The development brought significant challenges. In this paper, we present the solutions that we have developed to overcome these challenges. In particular, we present a modular design that robustly manages the core components of a simulation: particle sources, geometry, physics processes, and data acquisition. The architecture consists of integrated C++ and Python codes. This framework allows for the precise, time-aware generation of primary particles, a critical requirement for accurately modeling positron emission tomography, radionuclide therapies, or prompt-gamma timing systems. We present how GATE 10 handles complex Geant4 physics settings while exposing a simple interface to the user. Furthermore, we describe the methodological solutions that facilitate the seamless integration of advanced physics models and variance reduction techniques. The architecture supports sophisticated scoring of physical quantities (such as Linear Energy Transfer and Relative Biological Effectiveness) and is designed for multithreaded execution. The new user interface allows researchers to script complex simulation workflows and directly couple external tools, such as artificial intelligence models for source generation or detector response. By detailing these architectural innovations, we demonstrate how GATE 10 provides a more powerful and flexible tool for research and innovation in medical physics. This paper is not intended to be a developer guide. Its purpose is to share with the research community in-depth explanations of our development effort that made the new GATE 10 possible. ...
Journal article (2026) - David Sarrut, Nicolas Arbor, Thomas Baudier, Julien Bert, Konstantinos Chatzipapas, Martina Favaretto, Hermann Fuchs, Loïc Grevillot, N. Krah, More authors...
We present GATE version 10, a major evolution of the open-source Monte Carlo simulation application for medical physics, built on Geant4. This release marks a transformative evolution, featuring a modern Python-based user interface, enhanced multithreading and multiprocessing capabilities, the ability to be embedded as a library within other software, and a streamlined framework for collaborative development. In this Part 1 paper, we outline GATE's position among other Monte Carlo codes, the core principles driving this evolution, and the robust development cycle employed. We also detail the new features and improvements. Part 2 will focus on the architectural innovations and technical challenges. By combining an open, collaborative framework with cutting-edge features, such a Monte Carlo platform supports a wide range of academic and industrial research, solidifying its role as a critical tool for innovation in medical physics. ...
Journal article (2025) - R. Liénard, P. Barberet, K. Chatzipapas, G. Devès, T. Dhôte, T. Guérin, H. Seznec, F. Gobet
We report in situ single-molecule measurements of proton-induced double-strand breaks (DSBs) in DNA immersed in water, using real-time fluorescence tracking along the entire proton path, including the Bragg peak region. By chemically suppressing radical-mediated processes, we isolate direct DNA damage mechanisms and determine DSB cross sections as a function of depth. Near the Bragg peak, we observe a tenfold reduction in DSB cross sections in aqueous DNA compared to dry DNA, providing quantitative evidence for the protective role of water. These findings highlight the importance of intermolecular energy dissipation in mitigating radiationinduced damage in condensed biological matter, with implications for radiobiology and proton therapy modeling. ...
Journal article (2025) - Tim Heemskerk, Celebrity Groenendijk, Marta Rovituso, Ernst van der Wal, Wouter van Burik, Konstantinos Chatzipapas, Danny Lathouwers, Roland Kanaar, Jeremy M.C. Brown, Jeroen Essers
Background and purpose:
Understanding the cellular and molecular effect of proton radiation, particularly the increased DNA damage complexity at the distal end of the Bragg curve, is current topic of investigation. This work aims to study in vitro clonogenic survival and DNA damage foci kinetics of a head and neck squamous cell carcinoma cell line at various positions along a double passively scattered Bragg curve. Complementary in silico studies are conducted to gain insights into the link between cell survival variations, experimentally yielded foci and the number and complexity of double strand breaks (DSBs).

Materials and methods:
Proton irradiations are performed at the HollandPTC R&D proton beamline, using a double passively scattered setup. A custom water phantom setup is employed to accurately position the samples within the Bragg curve. FaDu cells are irradiated at the proximal 36 % point of the Bragg peak, (P36), proximal 80 % point of the Bragg peak (P80) and distal 20 % point of the Bragg peak (D20), with dose-averaged mean lineal energies (yD¯) of 1.10 keV/μm, 1.80 keV/μm and 7.25 keV/μm, respectively.

Results:
Clonogenic survival correlates strongly with yD¯, showing similar survival for P36 (D37%=3.0 Gy) and P80 (D37%=2.9 Gy), but decreased survival for D20 (D37% = 1.6 Gy). D20 irradiated samples exhibit increased 53BP1 foci shortly after irradiation, slower resolution of the foci, and larger residual 53BP1 foci after 24 h, indicating unrepaired complex breaks. These experimental observations are supported by the in silico study which demonstrates that irradiation at D20 leads to a 1.7-fold increase in complex DSBs with respect to the total number of strand breaks compared to P36 and P80.

Conclusions:
This combined approach provides valuable insights into the cellular and molecular effect of proton radiation, emphasizing the increased DNA damage complexity at the distal end of the Bragg curve, and has the potential to enhance the efficacy of proton therapy. ...
Journal article (2025) - Jay W. Archer, Matthew J. Large, David Bolst, Dousatsu Sakata, Hoang Ngoc Tran, Konstantinos P. Chatzipapas, Vladimir Ivantchenko, Anatoly B. Rosenfeld, Sébastien Incerti, More Authors...
The early DNA damage on the surface of the Moon due to GCR protons and alpha particles were assessed using a multiscale approach in Geant4. This consisted of three simulation stages. A periodic boundary conditions approach was used to obtain the radiation field on the surface and inside a proposed lunar habitat. The radiation field on the cellular scale was obtained in the organs of male and female astronauts using the ICRP145 tetrahedral mesh phantoms. This was subsequently simulated using a full human cell model in Geant4-DNA to obtain the early DNA damage. Geant4-DNA track structure ionisation models upper energy limits were extended to be able to model the interactions of the GCR at sub-cellular level, covering an energy range from a few eV up to 1 TeV. Hadronic interactions and the modelling of induced radiochemical species were also implemented. The early DNA damage was assessed using the Geant4-DNA molecularDNA example. A greater yield of DNA damage was observed on the lunar surface compared with the habitat, and indirect damage due to induced hydroxyl radicals constituted most of the damage. This study demonstrates a complete simulation pipeline for the assessment of early DNA damage in astronauts in the space radiation environment. ...

Glottal imaging dataset for advanced segmentation, analysis, and facilitative playbacks evaluation

Review (2025) - Gustavo Andrade-Miranda, Konstantinos Chatzipapas, Julián D. Arias-Londoño, Juan I. Godino-Llorente
The advances in the development of Facilitative Playbacks extracted from High-Speed videoendo- scopic sequences of the vocal folds are hindered by a notable lack of publicly available datasets annotated with the semantic segmentations corresponding to the area of the glottal gap. This fact also limits the reproducibility and further exploration of existing research in this field. To address this gap, GIRAFE (Glottal Imaging Repository for Advanced Segmentation, Analysis, and Facilitative Playbacks Evaluation) is a data repository designed to facilitate the devel- opment of advanced techniques for the semantic segmentation, analysis, and fast evaluation of High-Speed videoendoscopic sequences of the vocal folds. The repository includes 65 high-speed videoendoscopic recordings from a cohort of 50 patients (30 female, 20 male). The dataset com- prises 15 recordings from healthy controls, 26 from patients with diagnosed voice disorders, and 24 with an unknown health condition. All of them were manually annotated by an expert, including the masks corresponding to the semantic segmentation of the glottal gap. The repository is also complemented with the automatic segmentation of the glottal area using different state-of-the-art approaches. This data set has already supported several studies, which demonstrates its usefulness for the development of new glottal gap segmentation algorithms from High-Speed-Videoendoscopic sequences to improve or create new Facilitative Playbacks. Despite these advances and others in the field, the broader challenge of performing an accurate and completely automatic semantic segmentation method of the glottal area remains open. ...

Generative ANsatz for DNA damage evALuation and Forecast. A neural network-based regression for estimating early DNA damage across micro-nano scales

Journal article (2025) - Alberto Sciuto, Serena Fattori, Sebastien Incerti, Alma Kurmanova, Demetrio Oliva, Alfio D. Pappalardo, Giada Petringa, Dousatsu Sakata, Hoang N. Tran, G. A.Pablo Cirrone, Farmesk Abubaker, Sahar Arjmand, Roberto Catalano, Konstantinos Chatzipapas, Giacomo Cuttone, Fateme Farokhi, Mariacristina Guarrera, Ali Hassan
Purpose: This study aims to develop a comprehensive simulation framework to connect radiation effects from the microscopic to the nanoscopic scale. Method: The process begins with a Geant4-DNA simulation based on the example ”molecularDNA”, producing a dataset of twelve different types of early DNA damages within an Escherichia coli (E. coli) bacterium, generated by proton irradiation at different kinetic energies, giving a nano-scale view of the particle–matter interaction. Then we pass to the micro-scale with a Geant4 simulation, based on the example ”radiobiology”, providing a microscopic view of proton interactions with matter through the Linear Energy Transfer (LET). Then GANDALF (Generative ANsatz for DNA damage evALuation and Forecast) Machine Learning (ML) toolkit, a Neural Network (NN)-based regression system, is employed to correlate the micro-scale LET data with the nano-scale occurrences of DNA damages in the E. coli bacterium. Results: The trained ML algorithm provides a practical tool to convert LET curves versus depth in a water phantom into DNA damage curves for twelve distinct types of DNA damage. To assess the performance, we evaluated the choice and optimization of the regression system based on its interpolation and extrapolation capabilities, ensuring the model could reliably predict DNA damage under various conditions. Conclusions: Through the synergistic integration of Geant4, Geant4-DNA and ML, the study provides a tool to easily convert the results at the micro-scale of Geant4 to those at the nano-scale of Geant4-DNA without having to deal with the high CPU time requirements of the latter. ...
Journal article (2024) - Aleksandra M.Ristić Fira, Otilija D. Keta, Ngoc Hoang Tran, Konstantinos Chatzipapas, Sebastien Incerti, Ivan M. Petrović, Vladana D. Petković, Miloš Đorđević, Giada Petringa, Serena Fattori, Roberto Catalano, Giuseppe Pablo Cirrone, Giacomo Cuttone, Dousatsu Sakata
Purpose: Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET). Materials and methods: The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci. Results: With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines. Conclusion: Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions. ...
Journal article (2024) - Le Tuan Anh, Tran Ngoc Hoang, Yann Thibaut, Konstantinos Chatzipapas, Dousatsu Sakata, Sébastien Incerti, Carmen Villagrasa, Yann Perrot
Purpose: Interdisciplinary scientific communities have shown large interest to achieve a mechanistic description of radiation-induced biological damage, aiming to predict biological results produced by different radiation quality exposures. Monte Carlo track-structure simulations are suitable and reliable for the study of early DNA damage induction used as input for assessing DNA damage. This study presents the most recent improvements of a Geant4-DNA simulation tool named “dsbandrepair”. Methods: “dsbandrepair” is a Monte Carlo simulation tool based on a previous code (FullSim) that estimates the induction of early DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). It uses DNA geometries generated by the DNAFabric computational tool for simulating the induction of early single-strand breaks (SSBs) and double-strand breaks (DSBs). Moreover, the new tool includes some published radiobiological models for survival fraction and un-rejoined DSB. Its application for a human fibroblast cell and human umbilical vein endothelial cell containing both heterochromatin and euchromatin was conducted. In addition, this new version offers the possibility of using the new IRT-syn method for computing the chemical stage. Results: The direct and indirect strand breaks, SSBs, DSBs, and damage complexity obtained in this work are equivalent to those obtained with the previously published simulation tool when using the same configuration in the physical and chemical stages. Simulation results on survival fraction and un-rejoined DSB are in reasonable agreement with experimental data. Conclusions: “dsbandrepair” is a tool for simulating DNA damage and repair, benchmarked against experimental data. It has been released as an advanced example in Geant4.11.2. ...
Preprint (2024) - Youness Mellak, Konstantinos Chatzipapas, Alexandre Bousse, Catherine Chez-Le Rest, Dimitris Visvikis, Julien Bert
In recent years, the use of Monte Carlo (MC) simulations in the domain of Medical Physics has become a state-of-the-art technology that consumes lots of computational resources for the accurate prediction of particle interactions. The use of generative adversarial network (GAN) has been recently proposed as an alternative to improve the efficiency and extending the applications of computational tools in both medical imaging and therapeutic applications. This study introduces a new approach to simulate positron paths originating from Fluorine 18 (18 F) isotopes through the utilization of GANs. The proposed methodology developed a pure conditional transformer least squares (LS)-GAN model, designed to generate positron paths, and to track their interaction within the surrounding material. Conditioning factors include the pre-determined number of interactions, and the initial momentum of the emitted positrons, as derived from the emission spectrum of 18 F. By leveraging these conditions, the model aims to quickly and accurately simulate electromagnetic interactions of positron paths. Results were compared to the outcome produced with Geant4 Application for Tomography Emission (GATE) MC simulations toolkit. Less than 10 % of difference was observed in the calculation of the mean and maximum length of the path and the 1-D point spread function (PSF) for three different materials (Water, Bone, Lung). ...
Conference paper (2024) - Youness Mellak, Konstantinos Chatzipapas, Alexandre Bousse, Catherine Chez Le Rest, Dimitris Visvikis, Julien Bert
In recent years, the use of Monte Carlo (MC) simulations in the domain of Medical Physics has become a state-of-the-art technology that consumes lots of computational resources for the accurate prediction of particle interactions. The use of generative adversarial network (GAN) has been recently proposed as an alternative to improve the efficiency and extending the applications of computational tools in both medical imaging and therapeutic applications. This study introduces a new approach to simulate positron paths originating from Fluorine 18 (18F) isotopes through the utilization of GANs. The proposed methodology developed a pure conditional transformer least squares (LS)-GAN model, designed to generate positron paths, and to track their interaction within the surrounding material. Conditioning factors include the predetermined number of interactions, and the initial momentum of the emitted positrons, as derived from the emission spectrum of 18F. By leveraging these conditions, the model aims to quickly and accurately simulate electromagnetic interactions of positron paths. Results were compared to the outcome produced with Geant4 Application for Tomography Emission (GATE) MC simulations toolkit. Less than 10 % of difference was observed in the calculation of the mean and maximum length of the path and the 1-D point spread function (PSF) for three different materials (Water, Bone, Lung). ...
Journal article (2024) - Efstathia Petrou, Konstantinos Chatzipapas, Panagiotis Papadimitroulas, Gustavo Andrade-Miranda, Paraskevi F. Katsakiori, Nikolaos D. Papathanasiou, Dimitris Visvikis, George C. Kagadis
Background: This study investigated alternative, non-invasive methods for human papillomavirus (HPV) detection in head and neck cancers (HNCs). We compared two approaches: analyzing computed tomography (CT) scans with a Deep Learning (DL) model and using radiomic features extracted from CT images with machine learning (ML) models. Methods: Fifty patients with histologically confirmed HNC were included. We first trained a modified ResNet-18 DL model on CT data to predict HPV status. Next, radiomic features were extracted from manually segmented regions of interest near the oropharynx and used to train four ML models (K-Nearest Neighbors, logistic regression, decision tree, random forest) for the same purpose. Results: The CT-based model achieved the highest accuracy (90%) in classifying HPV status. Among the ML models, K-Nearest Neighbors performed best (80% accuracy). Weighted Ensemble methods combining the CT-based model with each ML model resulted in moderate accuracy improvements (70–90%). Conclusions: Our findings suggest that CT scans analyzed by DL models hold promise for non-invasive HPV detection in HNC. Radiomic features, while less accurate in this study, offer a complementary approach. Future research should explore larger datasets and investigate the potential of combining DL and radiomic techniques. ...
Journal article (2024) - Konstantinos P. Chatzipapas, Hoang Ngoc Tran, Milos Dordevic, Dousatsu Sakata, Sebastien Incerti, Dimitris Visvikis, Julien Bert
Background: This study aimed to develop a novel human cell geometry for the Geant4-DNA simulation toolkit that explicitly incorporates all 23 chromosome pairs of the human cell. This approach contrasts with the existing, default human cell, geometrical model, which utilizes a continuous Hilbert curve. Methods: A Python-based tool named “complexDNA” was developed to facilitate the design of both simple and complex DNA geometries. This tool was employed to construct a human cell geometry with individual pairs of chromosomes. Subsequently, the performance of this chromosomal model was compared to the standard human cell model provided in the “molecularDNA” Geant4-DNA example. Results: Simulations using the new chromosomal model revealed minimal discrepancies in DNA damage yield and fragment size distribution compared to the default human cell model. Notably, the chromosomal model demonstrated significant computational efficiency, requiring approximately three times less simulation time to achieve equivalent results. Conclusions: This work highlights the importance of incorporating chromosomal structure into human cell models for radiation biology research. The “complexDNA” tool offers a valuable resource for creating intricate DNA structures for future studies. Further refinements, such as implementing smaller voxels for euchromatin regions, are proposed to enhance the model's accuracy. ...
Journal article (2024) - Pierre Beaudier, Sara A. Zein, Konstantinos Chatzipapas, Hoang Ngoc Tran, Guillaume Devès, Laurent Plawinski, Rémy Liénard, Denis Dupuy, Hervé Seznec, More authors...
Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose–effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences. In addition, we propose a method for directly measuring the single-strand break (SSB) yield. Furthermore, through a comparative study with a collection of previous works on dry DNA irradiation, we show that the irradiation protocol leads to biases in the definition of ionizing sources. We support this scenario by discussing the size distributions of nanopore sequencing reads in the light of Geant4 and Geant4-DNA simulation toolkit predictions. We show that integrating long-read sequencing technologies with advanced Monte Carlo simulations paves a promising path toward advancing our comprehension and prediction of radiation-induced DNA fragmentation. ...
Journal article (2024) - Konstantinos Chatzipapas, Anastasia Nika, Agathoklis A. Krimpenis
The evolution of 3D printing has ushered in accessibility and cost-effectiveness, spanning various industries including biomedical engineering, education, and microfluidics. In biomedical engineering, it encompasses bioprinting tissues, producing prosthetics, porous metal orthopedic implants, and facilitating educational models. Hybrid Additive Manufacturing approaches and, more specifically, the integration of Fused Deposition Modeling (FDM) with bio-inkjet printing offers the advantages of improved accuracy, structural support, and controlled geometry, yet challenges persist in cell survival, interaction, and nutrient delivery within printed structures. The goal of this study was to develop and present a low-cost way to produce physical phantoms of human organs that could be used for research and training, bridging the gap between the use of highly detailed computational phantoms and real-life clinical applications. To this purpose, this study utilized anonymized clinical Computed Tomography (CT) data to create a liver physical model using the Creality Ender-3 printer. Polylactic Acid (PLA), Polyvinyl Alcohol (PVA), and light-bodied silicone (Polysiloxane) materials were employed for printing the liver including its veins and arteries. In brief, PLA was used to create a mold of a liver to be filled with biocompatible light-bodied silicone. Molds of the veins and arteries were printed using PVA and then inserted in the liver model to create empty channel. In addition, the PVA was then washed out by the final product using warm water. Despite minor imperfections due to the printer’s limitations, the final product imitates the computational model accurately enough. Precision adjustments in the design phase compensated for this variation. The proposed novel low-cost 3D printing methodology successfully produced an anatomically accurate liver physical model, presenting promising applications in medical education, research, and surgical planning. Notably, its implications extend to medical training, personalized medicine, and organ transplantation. The technology’s potential includes injection training for medical professionals, personalized anthropomorphic phantoms for radiation therapy, and the future prospect of creating functional living organs for organ transplantation, albeit requiring significant interdisciplinary collaboration and financial investment. This technique, while showcasing immense potential in biomedical applications, requires further advancements and interdisciplinary cooperation for its optimal utilization in revolutionizing medical science and benefiting patient healthcare. ...
Journal article (2023) - Konstantinos Chatzipapas, Milos Dordevic, Sara Zivkovic, Ngoc Hoang Tran, Nathanael Lampe, Dousatsu Sakata, Ivan Petrovic, Aleksandra Ristic-Fira, Wook Geun Shin, More Authors...
Purpose:
This study aimed to develop a computational environment for the accurate simulation of human cancer cell irradiation using Geant4-DNA. New cell geometrical models were developed and irradiated by alpha particle beams to induce DNA damage. The proposed approach may help further investigation of the benefits of external alpha irradiation therapy.

Methods:
The Geant4-DNA Monte Carlo (MC) toolkit allows the simulation of cancer cell geometries that can be combined with accurate modelling of physical, physicochemical and chemical stages of liquid water irradiation, including radiolytic processes. Geant4-DNA is used to calculate direct and non-direct DNA damage yields, such as single and double strand breaks, produced by the deposition of energy or by the interaction of DNA with free radicals.

Results:
In this study, the “molecularDNA” example application of Geant4-DNA was used to quantify early DNA damage in human cancer cells upon irradiation with alpha particle beams, as a function of linear energy transfer (LET). The MC simulation results are compared to experimental data, as well as previously published simulation data. The simulation results agree well with the experimental data on DSB yields in the lower LET range, while the experimental data on DSB yields are lower than the results obtained with the “molecularDNA” example in the higher LET range.

Conclusion:
This study explored and demonstrated the possibilities of the Geant4-DNA toolkit together with the “molecularDNA” example to simulate the helium beam irradiation of cancer cell lines, to quantify the early DNA damage, or even the following DNA damage response. ...
Journal article (2023) - Ioanna Stamouli, Thomas Nanos, Konstantinos Chatzipapas, Panagiotis Papadimitroulas, Lydia Aggeliki Zoglopitou, Theodoros Kalathas, Paraskevi F. Katsakiori, Anna Makridou, George C. Kagadis
This study aimed to compare the commercial dosimetric software Planet® Dose (version 3.1.1) from DOSIsoft and the open-source toolkit GATE. Dosimetry was performed for six patients receiving 200 mCi of Lutathera® every 8 weeks for four treatment cycles. For the dose calculation with Planet®, SPECT/CT images were acquired at 4, 24, 72 and 192 h post-injection. After the registration of all the time points to T0, the organs of interest (OOIs) were segmented. Time-activity curves were produced and the absorbed dose was calculated using the bi- and tri-exponential fitting methods. Regarding GATE simulations, the SPECT images of the 24 h time point were utilized for the radiopharmaceutical biodistribution in the OOIs and the attenuation maps were produced using the CT images. For liver and spleen, the average relative difference between GATE and Planet® was 9.6% and 11.1% for biexponential and 12.4% and 30.5% for triexponential fitting, respectively. The right and left kidneys showed differences up to 10.7% and 10.4% for the biexponential and up to 60.6% and 11.9% for the triexponential model, respectively. The absorbed dose calculated with GATE, Planet®(bi-exp) and Planet®(tri-exp) was in agreement with the literature. The results of the bi-exponential fitting were similar to the GATE-resulted calculations, while the tri-exponential fitting had a higher relative difference. ...
Journal article (2023) - Vasileios Eleftheriadis, Georgios Savvidis, Valentina Paneta, Konstantinos Chatzipapas, George C. Kagadis, Panagiotis Papadimitroulas
Objective: A methodology is introduced for the development of an internal dosimetry prediction toolkit for nuclear medical pediatric applications. The proposed study exploits Artificial Intelligence techniques using Monte Carlo simulations as ground truth for accurate prediction of absorbed doses per organ prior to the imaging acquisition considering only personalized anatomical characteristics of any new pediatric patient.

Approach: GATE Monte Carlo simulations were performed using a population of computational pediatric models to calculate the specific absorbed dose rates (SADRs) in several organs. A simulated dosimetry database was developed for 28 pediatric phantoms (age range 2–17 years old, both genders) and 5 different radiopharmaceuticals. Machine Learning regression models were trained on the produced simulated dataset, with leave one out cross validation for the prediction model evaluation. Hyperparameter optimization and ensemble learning techniques for a variation of input features were applied for achieving the best predictive power, leading to the development of a SADR prediction toolkit for any new pediatric patient for the studied organs and radiopharmaceuticals. Main results. SADR values for 30 organs of interest were calculated via Monte Carlo simulations for 28 pediatric phantoms for the cases of five radiopharmaceuticals. The relative percentage uncertainty in the extracted dose values per organ was lower than 2.7%. An internal dosimetry prediction toolkit which can accurately predict SADRs in 30 organs for five different radiopharmaceuticals, with mean absolute percentage error on the level of 8% was developed, with specific focus on pediatric patients, by using Machine Learning regression algorithms, Single or Multiple organ training and Artificial Intelligence ensemble techniques.

Significance: A large simulated dosimetry database was developed and utilized for the training of Machine Learning models. The developed predictive models provide very fast results (<2 s) with an accuracy >90% with respect to the ground truth of Monte Carlo, considering personalized anatomical characteristics and the biodistribution of each radiopharmaceutical. The proposed method is applicable to other medical dosimetry applications in different patients’ populations. ...

An overview of the “molecularDNA” example application

Journal article (2023) - Konstantinos P. Chatzipapas, Ngoc Hoang Tran, Milos Dordevic, Sara Zivkovic, Sara Zein, Wook Geun Shin, Dousatsu Sakata, Nathanael Lampe, Jeremy M.C. Brown, More authors...
Purpose
The scientific community shows great interest in the study of DNA damage induction, DNA damage repair, and the biological effects on cells and cellular systems after exposure to ionizing radiation. Several in silico methods have been proposed so far to study these mechanisms using Monte Carlo simulations. This study outlines a Geant4-DNA example application, named “molecularDNA”, publicly released in the 11.1 version of Geant4 (December 2022).

Methods
It was developed for novice Geant4 users and requires only a basic understanding of scripting languages to get started. The example includes two different DNA-scale geometries of biological targets, namely “cylinders” and “human cell”. This public version is based on a previous prototype and includes new features, such as: the adoption of a new approach for the modeling of the chemical stage, the use of the standard DNA damage format to describe radiation-induced DNA damage, and upgraded computational tools to estimate DNA damage response.

Results
Simulation data in terms of single-strand break and double-strand break yields were produced using each of the available geometries. The results were compared with the literature, to validate the example, producing less than 5% difference in all cases. Conclusion: “molecularDNA” is a prototype tool that can be applied in a wide variety of radiobiology studies, providing the scientific community with an open-access base for DNA damage quantification calculations. New DNA and cell geometries for the “molecularDNA” example will be included in future versions of Geant4-DNA. ...
Journal article (2021) - David Sarrut, Mateusz Bała, Manuel Bardiès, Julien Bert, Maxime Chauvin, Konstantinos Chatzipapas, Mathieu Dupont, Ane Etxebeste, Louise M. Fanchon, More authors...
Built on top of the Geant4 toolkit, GATE is collaboratively developed for more than 15 years to design Monte Carlo simulations of nuclear-based imaging systems. It is, in particular, used by researchers and industrials to design, optimize, understand and create innovative emission tomography systems. In this paper, we reviewed the recent developments that have been proposed to simulate modern detectors and provide a comprehensive report on imaging systems that have been simulated and evaluated in GATE. Additionally, some methodological developments that are not specific for imaging but that can improve detector modeling and provide computation time gains, such as Variance Reduction Techniques and Artificial Intelligence integration, are described and discussed. ...