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Boron neutron capture therapy (BNCT) is an emerging radiation treatment modality, exhibiting the potential to selectively destroy cancer cells. Currently, BNCT is conducted using a nuclear reactor. However, the future trend is to move toward an accelerator-based system for use in hospital environments. A typical BNCT radiation field has several different types of radiation. The beam quality should be quantified to accurately determine the dose to be delivered to the target. This study utilized a tissue equivalent proportional counter (TEPC) to measure microdosimetric and macrodosimetric quantities of an accelerator-based neutron source. The micro- and macro-dosimetric quantities measured with the TEPC were compared with those obtained via the the particle and heavy ion transport code system (PHITS) Monte Carlo simulation. The absorbed dose from events >20 keV/μm measured free in air for a 1-h irradiation was calculated as 1.31 ± 0.02 Gy. The simulated result was 1.41 ± 0.07 Gy. The measured and calculated values exhibit good agreement. The relative biological effectiveness (RBE) that was evaluated from the measured microdosimetric spectrum was calculated as 3.7 ± 0.02, similar to the simulated value of 3.8 ± 0.1. These results showed the PHITS Monte Carlo simulation can simulate both micro- and macro-dosimetric quantities accurately. The RBE was calculated using a single-response function, and the results were compared with those of several other institutes that used a similar method. However, care must be taken when using such a single-response function for clinical application, as it is only valid for low doses. For clinical dose ranges (i.e., high doses), multievent distribution inside the target needs to be considered.

TEPC is the preferred device for measuring microdoses due to its excellent organizational equivalence and high energy response. The most important factor affecting its energy response is the electric field distribution in the avalanche region. This paper uses finite element analysis to examine the electric field distribution of a spherical structure with a sensitive area diameter of 2 cm and a cylindrical structure with a sensitive area of 2 cm × 2 cm. While the spherical structure exhibits better isotropy, it has significant distortions in the electric field at the anode wire end, making compensation optimization complex and hindering miniaturization. Cylindrical structures can compensate for the electric field by adding insulators at the anode wire end. When the insulator diameter is 3mm, the optimal protrusion length into the chamber is also 3mm. This lays the foundation for the miniaturization of TEPCs in subsequent research.

The frequency distributions of the lineal energy, y, of 160 MeV proton, 150 MeV/u helium, and 490 MeV/u silicon ion beams were measured using a wall-less tissue equivalent proportional counter (TEPC) with a site size of 0.72 μm. The measured frequency distributions of y as well as the dose-mean values, yD, agree with the corresponding data calculated using the microdosimetric function of the particle and heavy ion transport code system PHITS. The values of yD in the range of LET below ～10 keV μm-1 because of discrete energy deposition by delta rays, while the relation is reversed above ～10 keV μm-1 as the amount of energy escaping via delta rays increases. These results indicate that care should be taken with the difference between yD and LET when estimating the ionization density that usually relates to relative biological effectiveness (RBE) of energetic heavy ions.

Using a wall-less tissue-equivalent proportional counter for a 0.72-μm site in tissue, we measured the radial dependence of the lineal energy distribution, yf ( y ), of 290-MeV/u carbon ions and 500-MeV/u iron ion beams. The measured yf ( y ) distributions and the dose-mean of y , y¯D , were compared with calculations performed with the track structure simulation code TRACION and the microdosimetric function of the Particle and Heavy Ion Transport code System (PHITS). The values of the measured y¯D were consistent with calculated results within an error of 2%, but differences in the shape of yf ( y ) were observed for iron ion irradiation. This result indicates that further improvement of the calculation model for yf ( y ) distribution in PHITS is needed for the analytical function that describes energy deposition by delta rays, particularly for primary ions having linear energy transfer in excess of a few hundred keV μm −1 .

A microdosimetric characterization of the 62 MeV proton beam line of CATANA has been performed all along the Spread Out Bragg Peak with three different detectors. Two silicon detectors and a Tissue Equivalent Proportional Counter measured at approximately the same depths of the SOBP. The TEPC is a new miniaturized gas counter developed at the Legnaro National Laboratories of INFN, modified to work without gas flow. The first silicon detector has been developed at the Politecnico of Milano and it is a monolithic telescope composed by a matrix of 2 µm thick cylindrical diodes with a diameter 9 µm. that compose the ΔE layer. The E and ΔE layers are fabricated on a single substrate of silicon. The third detector is the MicroPlus probe developed at the CMRP - University of Wollongong, it is an array of 3D sensitive volumes each with dimension 30x30 µm and 10 µm thick fabricated on SOI. Measurements performed with the three detectors are presented and discussed.

It is recognized today that the observable radiobiological effects of ionizing radiations are strongly correlated to the clustering of damages in micrometer- and nanometer-sized subcellular structures, hence to the particle track structure. The characteristic properties of track structure are directly measurable nowadays with bulky experimental apparatuses, which cannot be easily operated in a clinical environment. It is therefore interesting to investigate the feasibility of new portable detectors able to characterize the real therapeutic beams. With this in mind, a novel avalanche-confinement Tissue Equivalent Proportional Counter (TEPC) was constructed for simulating nanometric sites down to 25 nm. Experimental cluster size distributions measured with this TEPC were compared with Monte Carlo simulations of the same experiment and with cluster size distributions measured with the Startrack nanodosimeter.

The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of common TEPCs is about 0.3 μm. On the other hand, the pattern of particle interactions is measured by track-nanodosimetry, which derives the single-event distribution of ionization cluster size at the nanometric scale. Anyway, only three nanodosimeters are available worldwide. A feasibility study for extending the performances of TEPC down to the nanometric region was performed and a novel avalanche-confinement TEPC was designed and constructed. This detector is constituted by a cylindrical chamber, based on a three-electrode structure, connected to a vacuum and gas flow system to ensure a continuous replacement of the tissue equivalent gas, thus allowing to simulate different biological site sizes in the range 300-25 nm. This TEPC can be calibrated by exploiting a built-in alpha source and a miniaturized solid-state detector as a trigger. Irradiations with photons, fast neutrons and two hadron beams demonstrated the good performances of the device. A satisfactory agreement with FLUKA simulations was obtained.

The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring microdosimetric properties of particle beams. Since microdosimetric quantities span over several decades, the electronic and acquisition chain should meet specific requirements. In order to cover the wide dynamic range of the signals generated by the TEPC, the output signal from the preamplifier is fed in parallel to three linear amplifiers which shape and amplify the signal with different gains. Very low-energy deposition events are filtered in the high-gain stage, and high-energy deposition events are processed in the low-gain stage. A new system with high acquisition performance and compact hardware was developed for this purpose. The analog-to-digital conversion is performed by a commercial acquisition system that includes a FPGA. Thanks to the FPGA a parallel high-speed acquisition on three channels can be performed. The software merges signals together from the three electronic chains and computes a real time microdosimetric spectrum giving a prompt information about the irradiation field. This acquisition system, which performs analog-to-digital conversion and signal processing at a sampling rate up to 15 MS/s, was tested by irradiating a TEPC with an Am-Be fast neutron field, an intense quasi-monoenergetic neutron beam and a 62 MeV/u helium ion beam.

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.

Purpose This paper explores the application of microdosimetry in the context of Boron Neutron Capture Therapy (BNCT). In particular it aims to elucidate the crucial role of microdosimetry in measuring dose enhancement resulting from elevated boron-10 concentrations in tumor cells during BNCT. Methods A critical survey on microdosimetry is first given, to underline the relevance of the stochastic fluctuations of the radiation interactions at the microscopic level. Successively, the methodology of microdosimetric application to BNCT is reviewed. Significant examples are reported that help understanding the potentialities of microdosimetry on BNCT. The analysis involves examining the energy spectra in mixed radiation fields, taking into account both small and large energy events influenced by the stopping power and range of the particle. Results The findings of this study reveal valuable insights into the contribution of microdosimetry in BNCT. The analysis of energy spectra enables the differentiation of various components within the radiation field, both in terms of dose and of biological effectiveness. The results shed light on the dose enhancement attributed to higher concentrations of boron-10 in tumor cells, providing a comprehensive understanding of the biological effectiveness of boron neutron capture reaction products. Conclusions This paper underscores the pivotal role of microdosimetry in BNCT, emphasizing its capability to unravel the intricacies of energy deposition and dose distribution at the micrometric scale. The application of microdosimetry emerges as a valuable tool in optimizing BNCT protocols and advancing our comprehension of radiation effects in targeted cancer therapy.