The microdosimetric extension in TOPAS: development and comparison with published data

Zhu, Hongyu; Chen, Yizheng; Sung, Wonmo; McNamara, Aimee L.; Tran, Linh T.; Burigo, Lucas; Rosenfeld, Anatoly B.; Li, Junli; Faddegon, Bruce A.; Schuemann, Jan; Paganetti, Harald

doi:10.1088/1361-6560/ab23a3

Cited by 32 publications

(51 citation statements)

References 50 publications

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“…( 74), where k is an index of the deposition events and the sum is performed from 1 to N ij , the observed number of the deposition events in cell i delivered by the j-th beam. To obtain the energy imparted e k and the number N ij , Monte Carlo (MC) simulations are used, taking advantage of available codes such as, for example, those derived from the Geant4 libraries [97][98][99] and Fluka [100].…”

Section: Track Structure Model Incorporationmentioning

confidence: 99%

Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models

et al. 2021

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Different qualities of radiation are known to cause different biological effects at the same absorbed dose. Enhancements of the biological effectiveness are a direct consequence of the energy deposition clustering at the scales of DNA molecule and cell nucleus whilst absorbed dose is a macroscopic averaged quantity which does not take into account heterogeneities at the nanometer and micrometer scales. Microdosimetry aims to measure radiation quality at cellular or sub-cellular levels trying to increase the understanding of radiation damage mechanisms and effects. Existing microdosimeters rely on the well-established gas-based detectors or the more recent solid-state devices. They provide specific energy z spectra and other derived quantities as lineal energy (y) spectra assessed at the micrometer level. The interpretation of the radio-biological experimental data in the framework of different models has raised interest and various investigations have been performed to link in vitro and in vivo radiobiological outcomes with the observed microdosimetric data. A review of the major models based on experimental microdosimetry, with a particular focus on ion beam therapy applications and an emphasis on the microdosimetric kinetic model (MKM), will be presented in this work, enlightening the advantages of each one in terms of accuracy, initial assumptions, and agreement with experimental data. The MKM has been used to predict different kinds of radiobiological quantities such as the relative biological effects for cell inactivation or the oxygen enhancement ratio. Recent developments of the MKM will be also presented, including new non-Poissonian correction approaches for high linear energy transfer radiation, the inclusion of partial repair effects for fractionation studies, and the extension of the model to account for non-targeted effects. We will also explore developments for improving the models by including track structure and the spatial damage correlation information, by using the full fluence spectrum and by better accounting for the energy-deposition fluctuations at the intra- and inter-cellular level.

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Section: Track Structure Model Incorporationmentioning

confidence: 99%

Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models

et al. 2021

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“…The index j is referred to all n ions generated by the primary beam in hadronic interactions 17 . The new approach is statistically more stable than the previous one 42 and presents a negligible dependence with the cut variations. It hence allows for a precise and simultaneous evaluation of deposited dose and average LETs, for a voxel size of arbitrary dimensions.…”

Section: Methodsmentioning

confidence: 98%

“…[13] and [33], was used. The use of the general

r (y)

function, although reported in literature for different detector shapes and sizes, 15–17,41,42 is somehow arbitrary. The function

r (y)

used in this work was unfolded from radiobiological data considering the biological endpoint of in vivo early intestine tolerance in mice, and microdosimetric spectra obtained with spherical microdosimeters.…”

Section: Methodsmentioning

confidence: 99%

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter

et al. 2020

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Purpose The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62 MeV ocular therapy proton beams. Methods A novel diamond microdosimeter with a well‐defined sensitive volume was fabricated and tested with a monoenergetic and spread‐out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar‐sectional area of 100 µm × 100 µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy (y¯F), dose mean lineal energy (y¯D) as well as microdosimetric relative biological effectiveness (RBEµ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. Results The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile‐up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1 keV/μm. The y¯F and y¯D values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. Conclusions The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

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“…The full derivations for

y_{f}

and

y_{d}

have been described in detail elsewhere but, can be summarized using Eqs. (1) and (2) 35‐37 …”

Section: Methodsmentioning

confidence: 99%

Radiobiological impact of gadolinium neutron capture from proton therapy and alternative neutron sources using TOPAS‐nBio

2021

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Purpose: A multi-scale investigation of the biological properties of gadolinium neutron capture (GdNC) therapy with applications in particle therapy is conducted using the TOPAS Monte Carlo (MC) simulation code. The simulation results are used to quantify the amount of gadolinium dose enhancement produced as a result of the secondary neutron production from proton therapy scaled by measured data. Materials and methods: MC modeling was performed using the radiobiology extension TOol for PArticle Simulation TOPAS-nBio MC simulation code to study the radiobiological effects produced from GdNC on a segment of DNA, a spherical cellular model, and from the modeling of previous experimental measurements. The average RBE values were calculated from two methods, microdosimetric kinematic (MK) and biological weighting r(y) within a 2 nm DNA segment for GdNC. The single-strand breaks (SSBs) and double-strand breaks (DSBs) were calculated from within the nucleus of a 20 µm diameter, spherical cell model. From a previous experimental proton therapy measurement using a spread-out Bragg peak (SOBP) of 4.5-9.5 cm and a delivered absorbed dose of 10.4 Gy, the amount of Gd neutron captures was calculated and used to quantify the amount of GdNC absolute dose from particle therapy. Results: The average RBE from microdosimetric kinematic and biological weighting was 1.35, and 1.70 for a 10% cell survival on HSG cell-line and weighting function data from early intestinal tolerance of mice. From a central isotropic GdNC source, the energy deposition is found to decrease from roughly 2.7 eV per capture down to approximately 0.01 eV per capture, a drop of two orders of magnitude within 50 nm. This result suggests that Gd needs to be close to the DNA (within 10-20 nm) in order for neutron capture to induce a significant dose enhancement due to the short-range electrons emitted after Gd neutron capture. Within a spherical cell model, the SSBs, and DSBs were determined to be 39 and 1.5 per neutron capture, respectively. From the total neutron captures produced from an experimental proton therapy measurement on a 3000 PPM Gd solution, an insignificant absolute Gd dose enhancement was quantified to be 5.4 × 10 −6 Gy per Gy of administered proton dose. Conclusion: From this study and literature review, the production of secondary thermal neutrons from proton therapy is determined to be a limiting factor and unlikely to produce a clinically useful dose enhancement for secondary neutron capture therapy. Moreover, alternative neutron sources, such as, a compact deuterium-tritium (D-T) neutron generator, a "high yield" deuterium-deuterium (D-D) generator, or an industrial strength (100 mg) 252 Cf source were investigated, with the 252 Cf source the most likely to be capable of producing enough neutrons for 1 Gy of localized GdNC absolute dose within a reasonable treatment time.

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The microdosimetric extension in TOPAS: development and comparison with published data

Cited by 32 publications

References 50 publications

Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models

Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter

Radiobiological impact of gadolinium neutron capture from proton therapy and alternative neutron sources using TOPAS‐nBio

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