B. Faddegon's research while affiliated with University of California, San Francisco and other places

Publications (193)

Article
Track structure Monte Carlo simulations are a useful tool to investigate the damage induced to DNA by ionizing radiation. These simulations usually rely on simplified geometrical representations of the DNA subcomponents. DNA damage is determined by the physical and physico-chemical processes occurring within these volumes. In particular, damage to...
Article
Current Monte Carlo simulations of DNA damage have been reported only at ambient temperature. The aim of this work is to use TOPAS-nBio to simulate the yields of DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) produced in plasmids under low-LET irradiation incorporating the effect of the temperature changes in the environment. A new...
Preprint
Full-text available
Our understanding of radiation induced cellular damage has greatly improved over the past decades. Despite this progress, there are still many obstacles to fully understanding how radiation interacts with biologically relevant cellular components to form observable endpoints. One hurdle is the difficulty faced by members of different research group...
Article
The chemical stage of the Monte Carlo track-structure code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by 60Co or 137Cs γ-rays. A comprehensive evaluati...
Article
The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation chan...
Preprint
Electron-positron pairs, produced in intense laser-solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility (NIF) Electron Positron Proton Spectrometers (EPPS). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measuremen...
Article
Full-text available
Electron–positron pairs, produced in intense laser–solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility Electron–Positron–Proton Spectrometers (EPPSs). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measurement qua...
Article
Full-text available
Purpose: Simulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time...
Article
This article presents a millimeter-scale CMOS 64 × 64 single charged particle radiation detector system for external beam cancer radiotherapy. A 1 × 1 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> diode measures energy deposition by a single charged particle in the depletion region, and th...
Article
Purpose: The simulation of individual particle tracks and the chemical stage following water radiolysis in biological tissue is an effective means of improving our knowledge of the physico-chemical contribution to the biological effect of ionizing radiation. However, the step-by-step simulation of the reaction kinetics of radiolytic species is the...
Article
FLASH radiotherapy delivers a high dose (≥10 Gy) at a high rate (≥40 Gy/s). In this way, particles are delivered in pulses as short as a few nanoseconds. At that rate, intertrack reactions between chemical species produced within the same pulse may affect the heterogeneous chemistry stage of water radiolysis. This stochastic process suits the capab...
Article
The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages ca...
Preprint
This paper presents a millimeter-scale CMOS 64$\times$64 single charged particle radiation detector system for external beam cancer radiotherapy. A 1$\times$1 $\mu m^2$ diode measures energy deposition by a single charged particle in the depletion region, and the array design provides a large detection area of 512$\times$512 $\mu m^2$. Instead of s...
Article
Background: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against referen...
Article
TOPAS-nBio was used to simulate, collision-to-collision, the complete trajectories of electrons in water generated during the explicit simulation of 64Cu decay. S-values and direct damage to the DNA were calculated representing the cell (C) and the cell nucleus (N) with concentric spheres of 5 μm and 4 μm in radius, respectively. The considered "ta...
Article
Full-text available
Purpose This paper covers recent developments and applications of the TOPAS TOol for PArticle Simulation and presents the approaches used to disseminate TOPAS. Materials and methods Fundamental understanding of radiotherapy and imaging is greatly facilitated through accurate and detailed simulation of the passage of ionizing radiation through appa...
Conference Paper
Full-text available
60% of all cancer treatment requires radiation therapy and the fundamental goal is to deposit sufficient energy in a tumor to irreparably damage its DNA. Unlike high energy photons which pass through the body, charged particles such as protons deposit the majority of their energy at a specific depth, the location of the Bragg peak. In theory, this...
Article
Monte Carlo (MC) track structure simulation tools are commonly used for predicting radiation induced DNA damage by modeling the physical and chemical reactions at the nanometer scale. However, the outcome of these MC simulations is particularly sensitive to the adopted parameters which vary significantly across studies. In this study, a previously...
Article
Dose calculation plays an important role in the accuracy of radiotherapy treatment planning and beam delivery. The Monte Carlo (MC) method is capable of achieving the highest accuracy in radiotherapy dose calculation and has been implemented in many commercial systems for radiotherapy treatment planning. The objective of this task group was to assi...
Article
This paper presents the influence of electron elastic scattering models, electron thermalization models, and chemical parameters on Geant4-DNA simulations of liquid water radiolysis under mega-electron-volt electron irradiation. The radiochemical yields are simulated using a new Geant4-DNA example. In particular, the influence of the new elastic sc...
Article
Microdosimetric energy depositions have been suggested as a key variable for the modeling of the relative biological effectiveness (RBE) in proton and ion radiation therapy. However, microdosimetry has been underutilized in radiation therapy. Recent advances in detector technology allow the design of new mico- and nano-dosimeters. At the same time...
Article
Full-text available
The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a...
Article
Inverse treatment planning in intensity modulated particle therapy (IMPT) with scanned carbon-ion beams is currently based on the optimization of RBE-weighted dose to satisfy requirements of target coverage and limited toxicity to organs-at-risk (OARs) and healthy tissues. There are many feasible IMPT plans that meet these requirements, which allow...
Article
Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a ma...
Article
Details of the pattern of ionization formed by particle tracks extends knowledge of dose effects on the nanometer scale. Ionization detail (ID), frequently characterized by ionization cluster size distributions (ICSD), is obtained through time-consuming Monte Carlo (MC) track-structure simulations. In this work, TOPAS-nBio was used to generate a hi...
Article
To describe the international landscape of clinical trials in carbon‐ion radiotherapy (CIRT), the authors reviewed the current status of 63 ongoing clinical trials (median, 47 participants) involving CIRT identified from the US clinicaltrials.gov trial registry and the World Health Organization International Clinical Trials Platform Registry. The o...
Article
Computational simulations, such as Monte Carlo track structure simulations, offer a powerful tool for quantitatively investigating radiation interactions within cells. The modelling of the spatial distribution of energy deposition events as well as diffusion of chemical free radical species, within realistic biological geometries, can help provide...
Article
Purpose: To evaluate the accuracy of relative stopping power and spatial resolution of images reconstructed with simulated helium CT (HeCT) in comparison to proton CT (pCT). Methods: A Monte Carlo (MC) study with the TOPAS tool was performed to compare the accuracy of relative stopping power (RSP) reconstruction and spatial resolution of low-flu...
Article
Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advan...
Article
Flagged uniform particle splitting was implemented with two methods to improve computational efficiency of Monte Carlo track structure simulations with TOPAS-nBio by enhancing the production of secondary electrons in ionization events. In Method 1 the Geant4 kernel was modified. In Method 2 Geant4 was not modified. In both methods a unique flag num...
Article
Purpose: To determine the dependence of the accuracy in reconstruction of relative stopping power (RSP) with proton computerized tomography (pCT) scans on the purity of the proton beam and the technological complexity of the pCT scanner using standard phantoms and a digital representation of a pediatric patient. Methods: The Monte Carlo method w...
Article
Full-text available
Computational simulations offer a powerful tool for quantitatively investigating radiation interactions with biological tissue and can help bridge the gap between physics, chemistry and biology. The TOPAS collaboration is tackling this challenge by extending the current Monte Carlo tool to allow for sub-cellular in silico simulations in a new exten...
Article
Purpose:New advances in radiation therapy are most likely to come from the complex interface of physics, chemistry and biology. Computational simulations offer a powerful tool for quantitatively investigating radiation interactions with biological tissue and can thus help bridge the gap between physics and biology. The aim of TOPAS-nBio is to provi...
Article
Purpose:Monte Carlo particle transport simulation (MC) codes have become important tools in proton therapy and biology, both for research and practice. TOPAS is an MC toolkit serving users worldwide (213 licensed users at 95 institutions in 21 countries). It provides unprecedented ease in 4D placement of geometry components, beam sources and scorin...
Article
Purpose:High dose rate flattening filter free (FFF) beams pose new challenges and considerations for accurate reference and relative dosimetry. The authors report errors associated with commonly used ion chambers and introduce simple methods to mitigate them. Methods:Dosimetric errors due to (1) ion recombination effects of high dose per pulse (DPP...
Article
Full-text available
The goal of this work was to determine the scattered photon dose and secondary neutron dose and resulting risk for the sensitive fetus from photon and proton radiotherapy when treating a brain tumor during pregnancy. Anthropomorphic pregnancy phantoms with three stages (3-, 6-, 9-month) based on ICRP reference parameters were implemented in Monte C...
Article
Full-text available
To measure depth dose curves for a 67.5 ± 0.1 MeV proton beam for benchmarking and validation of Monte Carlo simulation. Depth dose curves were measured in 2 beam lines. Protons in the raw beam line traversed a Ta scattering foil, 0.1016 or 0.381 mm thick, a secondary emission monitor comprised of thin Al foils, and a thin Kapton exit window. The b...
Article
The aim of this work was to improve the computational efficiency of Monte Carlo simulations when tracking protons through a proton therapy treatment head. Two proton therapy facilities were considered, the Francis H Burr Proton Therapy Center (FHBPTC) at the Massachusetts General Hospital and the Crocker Lab eye treatment facility used by Universit...
Article
The aim of this work was to develop a framework for modeling organ effects within TOPAS (TOol for PArticle Simulation), a wrapper of the Geant4 Monte Carlo toolkit that facilitates particle therapy simulation. The DICOM interface for TOPAS was extended to permit contour input, used to assign voxels to organs. The following dose response models were...
Article
The aim of this work is to extend a widely used proton Monte Carlo tool, TOPAS, towards the modeling of relative biological effect (RBE) distributions in experimental arrangements as well as patients.TOPAS provides a software core which users configure by writing parameter files to, for instance, define application specific geometries and scoring c...
Article
To develop and verify an extension to TOPAS for calculation of dose response models (TCP/NTCP). TOPAS wraps and extends Geant4. The TOPAS DICOM interface was extended to include structure contours, for subsequent calculation of DVH's and TCP/NTCP. The following dose response models were implemented: Lyman-Kutcher-Burman (LKB), critical element (CE)...
Article
We used TOPAS (TOPAS wraps and extends Geant4 for medical physicists) to compare Geant4 physics models with published data for neutron shielding calculations. Subsequently, we calculated the source terms and attenuation lengths (shielding data) of the total ambient dose equivalent (TADE) in concrete for neutrons produced by protons in brass. Stage1...
Article
To develop tools for performing 4D proton computed tomography (CT). A suitable patient with a tumor in the right lower lobe was selected from a set of 4D CT scans. The volumetric CT images formed the basis for calculating the parameters of a breathing model that allows reconstruction of a static reference CT and CT images in each breathing phase. T...
Article
Radiation therapy (RT) and chemotherapy (CTX) following surgery are mainstays of treatment for breast cancer (BC). While multiple studies have recently revealed the significance of immune cells as mediators of CTX response in BC, less is known regarding roles for leukocytes as mediating outcomes following RT. To address this, we utilized a syngenei...
Article
s: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; February 26 — March 1, 2014; San Diego, CA In patients with locally advanced breast cancer, radiation therapy (RT) and chemotherapy following surgery has been a mainstay of treatment for breast cancer with demonstrated survival advantage in numerous randomized tria...
Conference Paper
Full-text available
Purpose/Objective(s): To measure a pristine proton Bragg Peak for a 67.5 MeV proton beam with depth known to a few tenths of a millimeter and energy known with better accuracy than the depth. Materials/Methods: A time of flight (TOF) system was previously used to establish the energy of the proton beam exiting the cyclotron used for the benchmark m...
Poster
Full-text available
A Submillimeter Experimental Benchmark of a 67.5 MeV Proton Depth Dose Curve in Water B.A. Faddegon,1 I.K. Dafarti,1 J. Shin,2 and C.M. Castaneda3; 1University of California San Francisco, San Francisco, CA, 2St. Jude Children’s Research Hospital, Memphis, TN, 3Crocker Nuclear Laboratory, Davis, CA Purpose/Objective(s): To measure a pristine proton...
Article
Purpose: To expand Monte Carlo simulations of TOPAS to directly calculate radiobiological effects using various biological models. Methods: We use the TOPAS toolkit version beta9 and expand the provided scoring system to directly include scorers for relative biological effect (RBE) modeling. A scorer is a class to record a given physical property i...
Article
Purpose: To develop a method to compare dose distributions based on the least restrictive of dose and distance differences, and to evaluate the method for IMRT QA on a conventional linac. Methods: Lrad is defined as the least restrictive of the dose difference at each point in the distributions being compared (%D), with dose normalized by the same...
Article
Full-text available
Purpose: To evaluate the efficiency of multithreaded Geant4 (Geant4-MT, version 10.0) for proton Monte Carlo dose calculations using a high performance computing facility.
Article
Purpose: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with T...
Article
Purpose: As the number and diversity of 4D radiation therapy treatment modalities increases, with techniques from IMRT, VMAT, SBRT, IGRT and IMPT to proton and ion beam scanning, the value of a comprehensive 4D Monte Carlo dose calculation tool has become evident. In silico experiments provide a powerful platform to study sensitivity of dose calcu...
Article
Purpose: To determine the optimal parameters when using variance reduction techniques for the generation of treatment head phase space files for proton therapy dose calculations. To validate the doses generated from these phase spaces with respect to reference simulations. Methods: The treatment nozzles at the Francis H Burr Proton Therapy Cente...
Article
Purpose: To present the implementation and validation of a geometrical based variance reduction technique for the calculation of phase space data for proton therapy dose calculation. Methods: The treatment heads at the Francis H Burr Proton Therapy Center were modeled with a new Monte Carlo tool (TOPAS based on Geant4). For variance reduction pu...
Article
Purpose: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in pr...
Article
Full-text available
Second malignant neoplasms (SMNs) are therapy-induced malignancies and a growing problem in cancer survivors, particularly survivors of childhood cancers. The lack of experimental models of SMNs has limited understanding of their pathogenesis. It is currently not possible to predict or prevent this devastating late complication. Individuals with Ne...
Article
Purpose: The TOPAS Tool for Particle Simulation was developed to make Geant4 Monte Carlo simulation more readily available for research and clinical physicists. Before releasing this new tool to the proton therapy community, several test have been performed to ensure accurate simulations in a variety of proton therapy setups. Methods: TOPAS can mod...
Article
Monte Carlo(MC) dose calculation algorithms are currently available for routine clinical planning in several commercial treatment planning systems. As noted in the AAPM Task Group Report No. 105 on issues associated with clinical implementation of MC dose algorithms, there are several fundamental differences between MC and other algorithms that nee...
Article
Purpose: To investigate the necessity of the verification of dose distributions using Monte Carlo (MC) simulations for proton therapy of head and neck patients and other complex patient geometries. Methods: TOPAS, a TOol for PArticle Simulations that makes MC simulations easy-to-use for research and clinical use and is layered on top of Geant4, has...
Article
Monte Carlo simulation for dose calculation is available in several commercial treatment planning systems. A range of source models and beam commissioning methodology is available with the different systems. Source models are currently analytical or hybrid models, combining Monte Carlo simulation with analytical approaches. The models are character...
Article
Purpose: To implement a geometry based particle splitting technique in order to reduce the computation time when generating treatment head phase space files for proton therapy dose calculations using Monte Carlo (MC) calculations and to validate the doses generated from these phase spaces with respect to reference simulations. Methods: The treat...
Article
Full-text available
A key task within all Monte Carlo particle transport codes is 'navigation', the calculation to determine at each particle step what volume the particle may be leaving and what volume the particle may be entering. Navigation should be optimized to the specific geometry at hand. For patient dose calculation, this geometry generally involves voxelized...
Article
A general method for handling time-dependent quantities in Monte Carlo simulations was developed to make such simulations more accessible to the medical community for a wide range of applications in radiotherapy, including fluence and dose calculation. To describe time-dependent changes in the most general way, we developed a grammar of functions t...
Article
Full-text available
The assumption of cylindrical symmetry in radiotherapy accelerator models can pose a challenge for precise Monte Carlo modeling. This assumption makes it difficult to account for measured asymmetries in clinical dose distributions. We have performed a sensitivity study examining the effect of varying symmetric and asymmetric beam and geometric para...
Article
Full-text available
An extendable x-ray multi-leaf collimator (eMLC) is investigated for collimation of electron beams on a linear accelerator. The conventional method of collimation using an electron applicator is impractical for conformal, modulated and mixed beam therapy techniques. An eMLC would allow faster, more complex treatments with potential for reduction in...
Article
Intensity-modulated photon-electron radiation therapy (IMPERT) takes advantage of the high conformity of photon intensity-modulated radiation therapy (IMRT) and low distal dose of electrons to reduce the total energy delivered to healthy tissue, potentially reducing serious side effects including secondary malignancies. This theoretical study was u...
Article
Monte Carlo (MC) simulation can be used for accurate electron beam treatment planning and modeling. Measurement of large electron fields, with the applicator removed and secondary collimator wide open, has been shown to provide accurate simulation parameters, including asymmetry in the measured dose, for the full range of clinical field sizes and p...
Article
Purpose: Provide the proton therapy community a comprehensive free software tool to improve usability of Monte Carlo simulation for patient safety, research, QA and clinical applications. Methods: TOPAS incorporates the already‐proven Geant4 simulation toolkit into a comprehensive architecture for treatment delivery system simulations and patient c...
Article
In patients with locally advanced breast cancer, radiation therapy (RT) and chemotherapy following surgery has been a mainstay of treatment with demonstrated survival advantage in numerous randomized trials. However, despite recent advances in treatment, many women still ultimately succumb to disease highlighting the need to improve therapeutic str...
Article
Full-text available
Secondary malignant neoplasms (SMN) are increasingly common complications of cancer therapy that have proven difficult to model in mice. Clinical observations suggest that the development of SMN correlates with radiation dose; however, this relationship has not been investigated systematically. We developed a novel procedure for administering fract...