Microdosimetry in ion-beam therapy

The information of the dose is not sufficiently describing the biological effects of ions on tissue since it does not express the radiation quality, i.e. the heterogeneity of the processes due to the slowing-down and the fragmentation of the particles when crossing a target. Depending on different circumstances, the radiation quality can be determined using measurements, calculations, or simulations. Microdosimeters are the primary tools used to provide the experimental information of the radiation quality and their role is becoming crucial for the recent clinical developments in particular with carbon ion therapy. Microdosimetry is strongly linked to the biological effectiveness of the radiation since it provides the physical parameters which explicitly distinguish the radiation for its capability of damaging cells. In the framework of ion-beam therapy microdosimetry can be used in the preparation of the treatment to complement radiobiological experiments and to analyze the modification of the radiation quality in phantoms. A more ambitious goal is to perform the measurements during the irradiation procedure to determine the non-targeted radiation and, more importantly, to monitor the modification of the radiation quality inside the patient. These procedures provide the feedback of the treatment directly beneficial for the single patient but also for the characterization of the biological effectiveness in general with advantages for all future treatment. Traditional and innovative tools are currently under study and an outlook of present experience and future development is presented here.

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

Frontiers in Physics ◽

10.3389/fphy.2020.578492 ◽

2021 ◽

Vol 8 ◽

Author(s):

V. E. Bellinzona ◽

F. Cordoni ◽

M. Missiaggia ◽

F. Tommasino ◽

E. Scifoni ◽

...

Keyword(s):

Experimental Data ◽

Energy Deposition ◽

Biological Effects ◽

Ion Beam ◽

Absorbed Dose ◽

Radiation Quality ◽

Ion Beam Therapy ◽

Biological Effectiveness

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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Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques

Cancers ◽

10.3390/cancers12123658 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3658

Author(s):

Lawrence Bronk ◽

Fada Guan ◽

Darshana Patel ◽

Duo Ma ◽

Benjamin Kroger ◽

...

Keyword(s):

High Throughput ◽

Relative Biological Effectiveness ◽

Biological Effects ◽

Ion Beam ◽

Particle Beam ◽

Clonogenic Survival ◽

Carbon Ions ◽

Charged Particle Beams ◽

Biological Effectiveness ◽

Therapy Center

Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.

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Radiation quality and ion-beam therapy: understanding the users' needs

Radiation Protection Dosimetry ◽

10.1093/rpd/ncv175 ◽

2015 ◽

Vol 166 (1-4) ◽

pp. 271-275 ◽

Cited By ~ 3

Author(s):

G. Magrin ◽

R. Mayer ◽

C. Verona ◽

Loïc Grevillot

Keyword(s):

Ion Beam ◽

Radiation Quality ◽

Ion Beam Therapy

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Biophysical modeling and experimental validation of relative biological effectiveness (RBE) for 4He ion beam therapy

Radiation Oncology ◽

10.1186/s13014-019-1295-z ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 5

Author(s):

Stewart Mein ◽

Ivana Dokic ◽

Carmen Klein ◽

Thomas Tessonnier ◽

Till Tobias Böhlen ◽

...

Keyword(s):

Experimental Validation ◽

Relative Biological Effectiveness ◽

Ion Beam ◽

Biophysical Modeling ◽

Ion Beam Therapy ◽

Biological Effectiveness

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Characterization of secondary radiation in ion beam therapy using synchronized timepix detectors with a mixed pixel operation mask

Physica Medica ◽

10.1016/j.ejmp.2014.07.217 ◽

2014 ◽

Vol 30 ◽

pp. e72-e73

Author(s):

I. Caicedo ◽

C. Granja ◽

B. Gómez ◽

B. Hartmann ◽

M. Martisikova ◽

...

Keyword(s):

Ion Beam ◽

Secondary Radiation ◽

Ion Beam Therapy ◽

Mixed Pixel

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Imaging and characterization of primary and secondary radiation in ion beam therapy

10.1063/1.4955377 ◽

2016 ◽

Author(s):

Carlos Granja ◽

Maria Martisikova ◽

Jan Jakubek ◽

Lukas Opalka ◽

Klaus Gwosch

Keyword(s):

Ion Beam ◽

Secondary Radiation ◽

Ion Beam Therapy

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Laser Acceleration of Ions for Radiation Therapy

Reviews of Accelerator Science and Technology ◽

10.1142/s1793626809000296 ◽

2009 ◽

Vol 02 (01) ◽

pp. 201-228 ◽

Cited By ~ 81

Author(s):

Toshiki Tajima ◽

Dietrich Habs ◽

Xueqing Yan

Keyword(s):

Scaling Laws ◽

Ion Beam ◽

Clinical Approach ◽

Carbon Ions ◽

Dense Particle ◽

Ion Beam Therapy ◽

Conventional Technology ◽

Ion Therapy ◽

Laser Acceleration ◽

Cost Efficient

Ion beam therapy for cancer has proven to be a successful clinical approach, affording as good a cure as surgery and a higher quality of life. However, the ion beam therapy installation is large and expensive, limiting its availability for public benefit. One of the hurdles is to make the accelerator more compact on the basis of conventional technology. Laser acceleration of ions represents a rapidly developing young field. The prevailing acceleration mechanism (known as target normal sheath acceleration, TNSA), however, shows severe limitations in some key elements. We now witness that a new regime of coherent acceleration of ions by laser (CAIL) has been studied to overcome many of these problems and accelerate protons and carbon ions to high energies with higher efficiencies. Emerging scaling laws indicate possible realization of an ion therapy facility with compact, cost-efficient lasers. Furthermore, dense particle bunches may allow the use of much higher collective fields, reducing the size of beam transport and dump systems. Though ultimate realization of a laser-driven medical facility may take many years, the field is developing fast with many conceptual innovations and technical progress.

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