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

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 a...

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Main Authors: V. E. Bellinzona, F. Cordoni, M. Missiaggia, F. Tommasino, E. Scifoni, C. La Tessa, A. Attili
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Physics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphy.2020.578492/full
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author V. E. Bellinzona
V. E. Bellinzona
F. Cordoni
F. Cordoni
M. Missiaggia
M. Missiaggia
F. Tommasino
F. Tommasino
E. Scifoni
C. La Tessa
C. La Tessa
A. Attili
author_facet V. E. Bellinzona
V. E. Bellinzona
F. Cordoni
F. Cordoni
M. Missiaggia
M. Missiaggia
F. Tommasino
F. Tommasino
E. Scifoni
C. La Tessa
C. La Tessa
A. Attili
author_sort V. E. Bellinzona
collection DOAJ
description 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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spelling doaj.art-77df71eebe494cd4a3b540ea18604b732022-12-21T23:01:18ZengFrontiers Media S.A.Frontiers in Physics2296-424X2021-02-01810.3389/fphy.2020.578492578492Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other ModelsV. E. Bellinzona0V. E. Bellinzona1F. Cordoni2F. Cordoni3M. Missiaggia4M. Missiaggia5F. Tommasino6F. Tommasino7E. Scifoni8C. La Tessa9C. La Tessa10A. Attili11Department of Physics, University of Trento, Trento, ItalyDepartment of Physics, TIFPA-INFN, Trento, ItalyDepartment of Physics, TIFPA-INFN, Trento, ItalyDepartment of Computer Science, University of Verona, Verona, ItalyDepartment of Physics, University of Trento, Trento, ItalyDepartment of Physics, TIFPA-INFN, Trento, ItalyDepartment of Physics, University of Trento, Trento, ItalyDepartment of Physics, TIFPA-INFN, Trento, ItalyDepartment of Physics, TIFPA-INFN, Trento, ItalyDepartment of Physics, University of Trento, Trento, ItalyDepartment of Physics, TIFPA-INFN, Trento, ItalyINFN Sezione di Roma Tre, Roma, ItalyDifferent 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.https://www.frontiersin.org/articles/10.3389/fphy.2020.578492/fullmicrodosimetrymicrodosimetric kinetic modelrelative biological effectivenessoxygen enhancement ratiobiophysical modelingion beam therapy
spellingShingle V. E. Bellinzona
V. E. Bellinzona
F. Cordoni
F. Cordoni
M. Missiaggia
M. Missiaggia
F. Tommasino
F. Tommasino
E. Scifoni
C. La Tessa
C. La Tessa
A. Attili
Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
Frontiers in Physics
microdosimetry
microdosimetric kinetic model
relative biological effectiveness
oxygen enhancement ratio
biophysical modeling
ion beam therapy
title Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
title_full Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
title_fullStr Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
title_full_unstemmed Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
title_short Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
title_sort linking microdosimetric measurements to biological effectiveness in ion beam therapy a review of theoretical aspects of mkm and other models
topic microdosimetry
microdosimetric kinetic model
relative biological effectiveness
oxygen enhancement ratio
biophysical modeling
ion beam therapy
url https://www.frontiersin.org/articles/10.3389/fphy.2020.578492/full
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