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Register a new userNanodosimetry - on the tracks of biological radiation effectiveness
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Hans Rabus
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Biological effectiveness of a certain absorbed dose of ionizing radiation depends on the radiation quality, i. e. the spectrum of ionizing particles and their energy distribution. As has been shown in several studies, the biological effectiveness is related to the pattern of energy deposits on the microscopic scale, the so-called track structure. Clusters of lesions in the DNA molecule within site sizes of few nanometers play a particular role in this context. This work presents a brief overview of nanodosimetric approaches to relate biological effects with track structure derived quantities and experimental techniques to derive such quantities.
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This work aims at carving out more clearly the basic assumptions behind the track-event theory (TET) and its derivate radiation action model based on nanodosimetry (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency of single and clustered DNA lesions are dispensable for multi-event distributions, because they follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that making these assumptions for the single-event distributions of the number of lethal and sublethal lesions within a cell would lead to an essentially exponential dose dependence of survival for practically relevant values of the absorbed dose. Furthermore, it is elucidated that the model equation used in the literature for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently and that the model equation is presumably inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the methodology for deriving model parameters from nanodosimetric properties of particle track structure is critically assessed. Based on data from proton track simulations it is shown that the assumption of statistically independent targets leads to a prediction of negligible frequency of clustered DNA damage. An approach is outlined how track structure could be considered in determining the model parameters, and the implications for TET and RAMN are discussed.
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. A review of the major models based on experimental microdosimetry, with 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 (OER). Recent developments of the MKM will be also presented, including new non-Poissonian correction approaches for high linear energy transfer (LET) 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, briefly, nanodosimetric quantities to better account for the energy-deposition fluctuations at the intra- and inter-cellular level.
In modern surgery, a multitude of minimally intrusive operational techniques are used which are based on the punctual heating of target zones of human tissue via laser or radio-frequency currents. Traditionally, these processes are modeled by the bioheat equation introduced by Pennes, who considers Fouriers theory of heat conduction. We present an alternative and more realistic model established by the hyperbolic equation of heat transfer. To demonstrate some features and advantages of our proposed method, we apply the obtained results to different types of tissue heating with high energy fluxes, in particular radiofrequency heating and pulsed laser treatment of the cornea to correct refractive errors. Hopefully, the results of our approach help to refine surgical interventions in this novel field of medical treatment.
This manuscript provides a response to a recent report by Mazzone et al. available online on arXiv that, in turn, tentatively aims at demonstrating the inefficacy of proton boron capture in hadrotherapy. We clarify that Mazzone et al. do not add any scientific or technical insights to the points extensively discussed in the original manuscript by Cirrone et al., and/or in the series of iterations had with the Referee, which ultimately lead to the publication of our original and pioneering experimental work. Here we summarize some of the key points of the long scientific debate we had during the review process of paper by Cirrone et al., which are very similar to the considerations presented by Mazzone et al.. In conclusion, no quantitative explanation of our robust experimental achievements presented in Cirrone et al. is provided in Mazzone et al.
An intercomparison of microdosimetric and nanodosimetric quantities simulated Monte Carlo codes is in progress with the goal of assessing the uncertainty contribution to simulated results due to the uncertainties of the electron interaction cross-sections used in the codes. In the first stage of the intercomparison, significant discrepancies were found for nanodosimetric quantities as well as for microdosimetric simulations of a radiation source placed at the surface of a spherical water scoring volume. This paper reports insight gained from further analysis, including additional results for the microdosimetry case where the observed discrepancies in the simulated distributions could be traced back to the difference between track-structure and condensed-history approaches. Furthermore, detailed investigations into the sensitivity of nanodosimetric distributions to alterations in inelastic electron scattering cross-sections are presented which were conducted in the lead up to the definition of an approach to be used in the second stage of the intercomparison to come. The suitability of simulation results for assessing the sought uncertainty contributions from cross-sections is discussed and a proposed framework is described.
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