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Microdosimetry is an important tool for assessing energy deposition distributions from ionizing radiation at cellular and cellular nucleus scales. It has served as an input parameter for multiple common mathematical models, including evaluation of relative biological effectiveness (RBE) of carbon ion therapy. The most common detector used for microdosimetry is the tissue-equivalent proportional counter (TEPC). Although it is widely applied, TEPC has various inherent uncertainties. Therefore, this work quantified the magnitude of TEPC measurement uncertainties and their impact on RBE estimates for therapeutic carbon beams. Microdosimetric spectra and frequency-, dose-, and saturation-corrected dose-mean lineal energy (****) were calculated using the Monte Carlo toolkit Geant4 for five monoenergetic and three spread-out Bragg peak carbon beams in water at every millimeter along the central beam axis. We simulated the following influences on these spectra from eight sources of uncertainty: wall effects, pulse pile-up, electronics, gas pressure, W-value, gain instability, low energy cut-off, and counting statistics. Statistic uncertainty was quantified as the standard deviation of perturbed values for each source. Bias was quantified as the difference between default lineal energy values and the mean of perturbed values for each systematic source. Uncertainties were propagated to RBE using the modified microdosimetric kinetic model (MKM). Variance introduced by statistic sources iny¯Fandy¯Daveraged 3.8% and 3.4%, respectively, and 1.5% iny*across beam depths and energies. Bias averaged 6.2% and 7.3% iny¯Fandy¯D,and 4.8% iny*.These uncertainties corresponded to 1.2 ± 0.9% on average in RBE MKM . The largest contributors to variance and bias were pulse pile-up and wall effects. This study established an error budget for microdosimetric carbon measurements by quantifying uncertainty inherent to TEPC measurements. It is necessary to understand how robust the measurement of RBE model input parameters are against this uncertainty in order to verify clinical model implementation., (© 2021 Institute of Physics and Engineering in Medicine.)

A new mini-TEPC with cylindrical sensitive volume of 0.9 mm in diameter and height, and with external diameter of 2.7 mm, has been developed to work without gas flow. With such a mini counter we have measured the physical quality of the 62 MeV therapeutic proton beam of CATANA (Catania, Italy). Measurements were performed at six precise positions along the Spread-Out Bragg Peak (SOBP): 1.4, 19.4, 24.6, 29.0, 29.7 and 30.8 mm, corresponding to positions of clinical relevance (entrance, proximal, central, and distal-edge of the SOBP) or of high lineal energy transfer (LET) increment (distal-dose drop off). Without refilling the microdosimeter with new gas, the measurements were repeated at the same positions 4 months later, in order to study the stability of the response in sealed-mode operation. From the microdosimetric spectra the frequency-mean lineal energy y- F and the dose-mean lineal energy y- D were derived and compared with average LET values calculated by means of Geant4 simulations. The comparison points out, in particular, a good agreement between microdosimetric y- D and the total dose-average LET¯ d , which is the average LET of the mixed radiation field, including the contribution by nuclear reactions., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Radiation-induced bone diseases were frequently reported in radiotherapy patients. To study the diseases, microdosimeters were constructed with walls of A150-A150, A150-B100, B100-A150 and B100-B100 interfaces. Monte Carlo simulations of these microdosimeters were performed to determine the lineal energy spectra of an interface site at different depths in water for 230 MeV protons. Comparing these spectra with data of ICRU tissue and bone walls, better agreements were found at shallow depths for protons and delta-rays than deep depths for nuclear interactions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The authors attempt to establish the relative biological effectiveness (RBE) calculation for designing therapeutic proton beams on the basis of microdosimetry. The tissue-equivalent proportional counter (TEPC) was used to measure microdosimetric lineal energy spectra for proton beams at various depths in a water phantom. An RBE-weighted absorbed dose is defined as an absorbed dose multiplied by an RBE for cell death of human salivary gland (HSG) tumor cells in this study. The RBE values were calculated by a modified microdosimetric kinetic model using the biological parameters for HSG tumor cells. The calculated RBE distributions showed a gradual increase to about 1cm short of a beam range and a steep increase around the beam range for both the mono-energetic and spread-out Bragg peak (SOBP) proton beams. The calculated RBE values were partially compared with a biological experiment in which the HSG tumor cells were irradiated by the SOBP beam except around the distal end. The RBE-weighted absorbed dose distribution for the SOBP beam was derived from the measured spectra for the mono-energetic beam by a mixing calculation, and it was confirmed that it agreed well with that directly derived from the microdosimetric spectra measured in the SOBP beam. The absorbed dose distributions to planarize the RBE-weighted absorbed dose were calculated in consideration of the RBE dependence on the prescribed absorbed dose and cellular radio-sensitivity. The results show that the microdosimetric measurement for the mono-energetic proton beam is also useful for designing RBE-weighted absorbed dose distributions for range-modulated proton beams.