DOI: 10.5061/dryad.44j0zpcpf
title: Reactive oxygen species produced by ultra-short electron pulses

description: The development of laser driven accelerators-on-chip has provided an
 opportunity to miniaturise devices for electron radiotherapy delivery.
 Laser driven accelerators produce highly time-compressed electron pulses,
 on the hundred femtoseconds to one picosecond scale. This delivers
 electrons at high peak power yet low average beam current compared to
 conventional delivery devices which generate pulses of around 3
 microseconds. The biophysical effects of this time structure, however, are
 unclear. Here we use a Monte Carlo simulation approach to explore the
 effects of the electron beam time structure on the production of reactive
 oxygen species (ROS) in water. Our results show a power law increase in
 the generation of hydroxyl ions per deposited electron with decreasing
 pulse length over the pulse length range of 10 microseconds to 100
 femtoseconds. Similar trends were observed for hydrogen peroxide,
 superoxide, hydroperoxyl, hydronium, and solvated electrons. In practical
 terms, this indicates a four-fold increase in the efficiency of free
 radical production for sub-picosecond pulses, relative to that of
 conventional microsecond pulses, for the same number of deposited
 electrons.
description: Simulations were performed using the TOPAS-nBio Monte Carlo
 package to trace particle trajectories, tracking energy exchange and free
 radical production from the physical electron interactions with the
 constituent atoms of the medium.<sup> </sup>This
 implementation of the Independent Reaction Times (IRT) Monte Carlo
 technique allows for calculation of time-dependent radiolytic yields and
 tracking of ROS via independent pair approximation to simulate reaction
 times between ROS created at the end of the pre-chemical stage. Prior to
 the main simulation run, the setup was verified using matched molecules,
 reactions, reaction rate coefficients, and diffusion coefficients from
 previous work.<sup> </sup>The single pulse analysis within
 TOPAS-nBio was adapted to accumulate data from all particles within the
 pulse, allowing direct comparison. In response to the significant
 computational demands of this particular study, multithreading was
 integrated to effectively reduce processing time. Furthermore,
 modifications were made to the original FLASH scorer to facilitate
 inspection of the single pulse results. Global variables were implemented
 to preserve key outputs across the parallel threads. Following calculation
 of G values that represents the production of a specific ROS of interest
 by every 100-eV deposited into the target for each thread, a Mutex lock
 and counter were activated to ensure the sequential execution of
 concurrent processes or threads. This approach facilitated the aggregation
 of individual G values generated by each thread, that could be managed and
 fed back into the single-thread design of the main code. The original
 conditional statement governing the processing of energy deposition and G
 values was revised, removing the dose parameter with the current count of
 histories scored, incremented by 1 to account for the initial count at 0.
 This value was assigned to a variable referred to as the ‘final count’,
 representing the total number of events to be processed divided by the
 number of active worker threads. This adjustment enabled the seamless
 functioning of the code across both single-thread and multithread
 operations, ensuring the comprehensive scoring of all particles before
 initiating the final output calculations. The modified section of code is
 provided. All simulations used a 5 µm (FWHM) Gaussian electron beam
 aligned with the z-axis into a 200 x 200 x 400 µm (x,y,z) water phantom,
 via a 100 µm air layer. Simulations were performed for a range of pulse
 durations (10<sup>-13</sup> – 10<sup>-6</sup> s),
 electron energies (10<sup>4</sup> – 10<sup>6</sup>
 eV), and number of electrons per pulse (1-100). TOPAS output was analysed
 using in-house MATLAB code enabling a description of overall ROS
 production from each parameter set. A second simulation applied and
 compared characteristic parameters from DLA (300 fs, 100 keV, 28
 electrons, 100 kHz repetition rate), FLASH (2 µs, 500 keV, 0.2 Gy, 20 Hz
 repetition rate), and conventional (4 µs, 500 keV, 0.002 Gy, 100 Hz
 repetition rate), recording the same output parameters.
description: # Reactive oxygen species produced by ultra-short electron pulses
 Simulations were performed using the TOPAS-nBio Monte Carlo package to
 trace particle trajectories, tracking energy exchange and free radical
 production from the physical electron interactions with the constituent
 atoms of the medium. This implementation of the Independent Reaction Times
 (IRT) Monte Carlo technique allows for the calculation of time-dependent
 radiolytic yields and tracking of ROS via independent pair approximation
 to simulate reaction times between ROS created at the end of the
 pre-chemical stage. ROS values are represented by G values that are the
 production of a specific ROS of interest by every 100-eV deposited into
 the target. ## Description of the data and file structure Each text file
 is an extract of the ROS species generated via different time pulse
 durations with all other values remaining the same specifications of 100
 KeV, 10 electron single pulses. Each text file name is the time pulse
 duration value in picoseconds, its important to keep this format as the
 matlab code Time_analysis organises the data based on the text file
 name picoseconds value. Each text file data has 3 columns, the first being
 the G value, the second being time in picoseconds, and the third being the
 chemical species name. Inside contains a MATLAB file able to obtain the
 specific ROS species and graph their result concerning all different time
 pulses. ## Code/Software Software that is needed to replicate the results,
 is TOPAS, TOPAS-nBio and MATLAB. **Modifying of Scorer for
 TsIRTInterPulse.txt** The change allows for the TOPAS-nBio to accumulate
 data from all particles within the pulse. Also due to significant
 computational demands. Multithreading was integrated to effectively reduce
 processing time.  To install the modification, once TOPAS and TOPAS-nBio
 is installed, locate and edit the following
 file `TOPAS-nBio/scorers/TsScoreWithIRTCummulative.cc`, once opened the
 text "// Scorer for TsIRTInterPulse" will be displayed. Then
 open the given text file called Modifying of Scorer for TsIRTInterPulse.
 Copy and paste the global variables from the text file into the
 TsScoreWithIRTCummulative.cc, then
 locate TsScoreWithIRTCummulative::UserHookForEndOfEvent(). copy and paste
 the contents of Modifying of Scorer for TsIRTInterPulse
 TsScoreWithIRTCummulative::UserHookForEndOfEvent()
 into TsScoreWithIRTCummulative.cc
 TsScoreWithIRTCummulative::UserHookForEndOfEvent().  **Time_analysis** Is
 a MATLAB script that needs to be located in the same files as all text
 file data with the picosecond time duration used for that title. To begin
 simple press run in MATLAB. In the script line 18 is the input name of
 which species you wish to see affected by the change of the time pulse
 duration.