Microdosimetry: Principles and applications

Cruz, Gustavo A. Santa

doi:10.1016/j.rpor.2014.10.006

Cited by 23 publications

(8 citation statements)

References 20 publications

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“…Microdosimetry systematically studies the stochastic energy deposition in microscopic structures (Santa Cruz 2016, Bolst et al 2017a. Monte Carlo simulations have already been used to estimate lineal energy or specific energies in micron sized sensitive volumes for microdosimetry (Bolst et al 2017a, Chacon et al 2019b.…”

Section: Biological Dosementioning

confidence: 99%

Influence of momentum acceptance on range monitoring of ¹¹C and ¹⁵O ion beams using in-beam PET

et al. 2020

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In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u−1) and 15O (312 MeV u−1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume.

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Section: Biological Dosementioning

confidence: 99%

Influence of momentum acceptance on range monitoring of ¹¹C and ¹⁵O ion beams using in-beam PET

et al. 2020

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“…As shown in Figure 1C, exposure to low-LET radiation causes isolated DSBs to be distributed throughout the nucleus, while multiple DSBs formed by dense ionizing (high-LET) radiation are closely concentrated along the particle trajectory. However, for both radiation types, the severity and character of DNA lesions at individual damage sites, i.e., their multiplicity [40] and complexity (combination with other non-DSB damage types) [41], differ dramatically, because radiation releases its energy randomly along the photon or particle path [42,43].…”

Section: Global Versus Local Dsb Repair Pathway Selection and Regulationmentioning

confidence: 99%

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

Falk

Hausmann

2020

Cancers

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DNA double-strand breaks (DSBs) have been recognized as the most serious lesions in irradiated cells. While several biochemical pathways capable of repairing these lesions have been identified, the mechanisms by which cells select a specific pathway for activation at a given DSB site remain poorly understood. Our knowledge of DSB induction and repair has increased dramatically since the discovery of ionizing radiation-induced foci (IRIFs), initiating the possibility of spatiotemporally monitoring the assembly and disassembly of repair complexes in single cells. IRIF exploration revealed that all post-irradiation processes—DSB formation, repair and misrepair—are strongly dependent on the characteristics of DSB damage and the microarchitecture of the whole affected chromatin domain in addition to the cell status. The microscale features of IRIFs, such as their morphology, mobility, spatiotemporal distribution, and persistence kinetics, have been linked to repair mechanisms. However, the influence of various biochemical and structural factors and their specific combinations on IRIF architecture remains unknown, as does the hierarchy of these factors in the decision-making process for a particular repair mechanism at each individual DSB site. New insights into the relationship between the physical properties of the incident radiation, chromatin architecture, IRIF architecture, and DSB repair mechanisms and repair efficiency are expected from recent developments in optical superresolution microscopy (nanoscopy) techniques that have shifted our ability to analyze chromatin and IRIF architectures towards the nanoscale. In the present review, we discuss this relationship, attempt to correlate still rather isolated nanoscale studies with already better-understood aspects of DSB repair at the microscale, and consider whether newly emerging “correlated multiscale structuromics” can revolutionarily enhance our knowledge in this field.

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“…This is why biological effects should be linked to the energy actually deposited in each cell nucleus rather than the macroscopic dose. Analysis of the energy deposition at the corresponding spatial scale can be achieved using microdosimetry, which gives the formalism [65,66] to describe the distribution of energy depositions that occur stochastically. Indeed, energy depositions in cell nuclei result from the combination of the number of tracks traversing the volume of interest as well as the energy deposited per track, with both having a statistical dispersion.…”

Section: Microdosimetric Calculations In the Cell Populationmentioning

confidence: 99%

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

Tang

Bueno

Meylan³

et al. 2019

IJMS

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The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.

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Microdosimetry: Principles and applications

Abstract: a b s t r a c tAim: to present the most important aspects of Microdosimetry, a research field in radiation biophysics.Background: microdosimetry is the branch of radiation biophysics that systematically studies

Cited by 23 publications

References 20 publications

Influence of momentum acceptance on range monitoring of ¹¹C and ¹⁵O ion beams using in-beam PET

Influence of momentum acceptance on range monitoring of ¹¹C and ¹⁵O ion beams using in-beam PET

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

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Microdosimetry: Principles and applications

Abstract: a b s t r a c tAim: to present the most important aspects of Microdosimetry, a research field in radiation biophysics.Background: microdosimetry is the branch of radiation biophysics that systematically studies

Cited by 23 publications

References 20 publications

Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET

Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

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Influence of momentum acceptance on range monitoring of ¹¹C and ¹⁵O ion beams using in-beam PET

Influence of momentum acceptance on range monitoring of ¹¹C and ¹⁵O ion beams using in-beam PET