Abstract
Background/Aim: There are only a few studies on dosimetry with ultrahigh-dose-rate (uHDR) scanned carbon-ion beams. This study investigated the characteristics of four types of ionization chambers for the uHDR beam. Materials and Methods: We employed a newly developed large-plane parallel chamber to monitor a 208.3-MeV/u uHDR scanned carbon-ion beam with a 110-Gy/s average dose rate. The ionization chambers used were the Advanced Markus chamber (AMC), PinPoint 3D chamber (PPC), Farmer chamber (FC), and large-plane parallel chamber (StingRay). The AMC and StingRay surfaces and the PPC and FC geometric centers were aligned to the radiation isocenter using treatment room lasers. Using the voltage range stated in the instruction manuals, we obtained the saturation curves of the chambers. From these curves, we obtained the ion recombination correction factors using the two-voltage and three-voltage linear methods. The dose linearity was evaluated using five measurement points, and the chamber repeatability was verified by conducting repeated measurements for different dose values. Results: Although all chambers, except for AMC, reached saturation when specified voltages were applied, they exhibited excellent linearity for different dose values. The ion recombination correction factors of the AMC obtained using the aforementioned linear methods were nearly 1. Additionally, all chambers exhibited excellent repeatability. Although the standard deviation of the PPC for the lowest dose was ~1.5%, those of all the other chambers were <1.0%. Conclusion: All ionization chambers can be used for measuring the relative dose, and absolute dose can be conveniently measured using the AMC with an uHDR carbon-ion scanned beam.
Ultrahigh-dose-rate (uHDR; FLASH) irradiation has received attention because of a particular effect, called the FLASH effect. By exploiting this effect, tumor growth can be suppressed to the same level as that achieved by employing commonly used normal-dose rate (typically approximately some cGy/s) methods, and the damage caused to normal tissues can be reduced. Recent studies have demonstrated the FLASH-effect with electron (1) and proton beams (2). The advantage of the FLASH effect can be extended to tumor therapy for achieving a balance between tumor control and normal-tissue damage. The application of uHDR beams to humans and the possibility of FLASH radiotherapy have been demonstrated in literature (3, 4). Studies on uHDR carbon-ion beams have been reported in literature. Using a ~40 Gy/s uHDR carbon-ion beam at 7.4 Gy, the normal tissue-sparing effect in brain organoids has been previously reported (5). The FLASH effect was observed during the treatment of hypoxic Chinese hamster ovary cells (CHO-K1) using a 70-Gy/s carbon-ion beam at 7.4 Gy (6). However, this effect was not observed under aerobic conditions for HFL1 and HSGc-C5 cells using a 96-195 Gy/s carbon-ion beam at 1-3 Gy (7). Although some FLASH-effect mechanisms when using carbon-ion beams have been proposed (8), additional research is required in this regard. Therefore, investigating the FLASH-effect mechanism when using a carbon-ion beam is valuable.
Currently, only a few facilities worldwide offer uHDR scanned carbon-ion beams. Thus, it is important to investigate the beam-related requirements to advance the research on uHDR carbon-ion beams. We have previously developed a mono-chromatic beam mode (9, 10) for uHDR scanned carbon-ion beams at the Osaka Heavy-Ion Therapy Center (Osaka-HIMAK) using the HyBeat Heavy-ion Therapy System (Hitachi, Ltd., Tokyo, Japan). This system employs raster scanning, and the minimum and maximum values of the irradiation spots are 0.0006 and 0.15 MU, respectively, when using a common treatment mode (11). Using the monochromatic beam mode, the nozzle, which is usually used for treatment of patients undergoing carbon-ion radiotherapy, can be removed from the beam path (10, 12), but a different beam monitoring system is required to control the scanned beam. Accordingly, we developed a large plane-parallel ionization chamber, which was used as a beam-monitoring system to accurately control the uHDR scanned beam operating in a specific irradiation mode (9). Furthermore, utilizing this ionization chamber as a dose monitoring system, we observed that accurate uHDR scanned carbon-ion beams could be produced.
Furthermore, the investigation of dosimetry in the context of uHDR scanned carbon-ion beams by employing ionization chambers is important for advancing the research on carbon-ion FLASH radiotherapy. Although the dosimetry in FLASH radiotherapy using proton and electron beams has been widely investigated (13-16), there are only few reports regarding uHDR scanned carbon-ion beams. To the best of our knowledge, no study has been conducted on the characteristics of commercially available ionization chambers for dosimetry of uHDR scanned carbon-ion beams. In this study, basic chamber characteristics, such as dose linearity and repeatability, are investigated for four types of ionization chambers.
Materials and Methods
Ionization chamber for beam monitoring. As reported in a previous study (9), we redeveloped the large-plane parallel ionization chamber. The new chamber had an active area of 120 mm × 120 mm and exclusive electrical circuits (Hayashi-Repic, Tokyo, Japan); it was used to monitor uHDR scanned carbon-ion beams. In the aforementioned study, we investigated the basic characteristics of the new ionization chamber such as position dependency and saturation curve of the ion collection efficiency. Additionally, we demonstrated that the new ionization chamber provides uHDR scanned carbon-ion beams with useful dose levels (9). Therefore, we employed this chamber for monitoring and controlling uHDR beams in this study.
Ionization chamber types whose characteristics were investigated. We investigated the characteristics of the following ionization chambers: Advanced Markus chamber (AMC; type 34045, PTW-Freiburg GmbH, Freiburg, Germany), PinPoint 3D chamber (PPC; type 31022), Farmer chamber (FC; type 30013), and large plane-parallel chamber (StingRay; IBA Dosimetry GmbH, Schwarzenbruck, Germany). Each chamber was connected to an electrometer (UNIDOSwebline, PTW-Freiburg GmbH, Freiburg, Germany).
Saturation curves and calculation of the ion recombination correction factors. We conducted measurements to obtain the saturation curves of all types of ionization chambers. A 10-150 V voltage was applied to the StingRay, and a 400-V voltage was applied to the other chambers; the maximum applied voltage values stated in the instruction manuals for the StingRay and the other chambers were 150 and 400 V, respectively. We set 9 voltage measurements points for StingRay and 12 points for the other chambers. Based on a previous study (17), the ion recombination correction factors ks were obtained using the two-voltage method (2V-method) (18) and three-voltage linear method (3VL-method) (19), which have been used in the particle therapy dosimetry.
Linearity and repeatability tests. To confirm the dose linearity of each chamber, we used the following six dose values: 1.64 Gy (0.05 MU), 3.09 Gy (0.0931 MU), 5.65 Gy (0.1715 MU), 6.62 Gy (0.2009 MU), 7.5 Gy (0.2303 MU), and 10.0 Gy (0.3087 MU). Each dose measurement was performed thrice. To verify the repeatability of the chambers, the dose measurement was performed 10 times using low (0.05 MU), medium (0.1715 MU), and high (0.2303 MU) dose values.
Experimental setup. The ionization chambers were placed in dedicated acrylic holders, and the surfaces of the AMC and StingRay as well as the geometric centers of the other chambers were aligned to the radiation isocenter using treatment room lasers. To fix the length extending from the acrylic holder to the AMC surface, a 10-mm acrylic plate was placed on the top of the AMC (Figure 1).
Setup of each ionization chamber using dedicated acrylic holders. (A) Advanced Markus electron chamber; (B) PinPoint 3D chamber; (C) Farmer chamber; (D) Large plane-parallel chamber (StingRay). The surface and geometrical center of each chamber were aligned to the radiation isocenter using treatment room lasers.
We produced uHDR scanned carbon-ion beams operating in a monochromatic beam mode (Figure 2); the beams did not pass through a nozzle (10, 12). The accelerator system (20) at Osaka-HIMAK (10, 12) produced a 208.3 MeV/u carbon-ion beam. The developed large-plane parallel ionization chamber used for beam monitoring (9) was set to the upstream direction of each ionization chamber shown in Figure 2. The irradiation field was set to 18 mm × 18 mm with a 3.0-mm spot spacing (total spots: 49) using a mean average dose rate of ~110 Gy/s (12, 21) at 5.65 Gy in the plateau region wherein the corresponding linear energy transfer was 19 keV/μm.
Schematic diagram of monochromatic beam mode and scanning pattern of irradiation. (A) Schematic of the experimental setup in the monochromatic beam mode in a treatment room. The carbon-ion beam exiting the beamline did not pass through the nozzle. The chambers were connected to an electrometer. The large plane-parallel ionization chamber (used for ultrahigh dose rates) was set in the upstream direction of the beam and used as a dose monitoring system. (B) Irradiation pattern. The green cross-point indicates the initial position of the scanning pattern.
Measurement uncertainties. The measurement uncertainties were estimated based on recommendations of the Joint Committee for Guides in Metrology (22). The Type A uncertainty in each measurement item was determined by the calculation of standard deviation of the means of repeated measurements. The Type B uncertainties were estimated from published factors. The combined standard uncertainties were calculated using a coverage factor (k) of 1.
Results
Saturation curves and ion recombination correction factors. We obtained the saturation curve of each ionization chamber using a 208.3 MeV/u uHDR scanned carbon-ion beam. The results for each chamber are shown in Figure 3; the combined standard uncertainties are shown with error bars. The horizontal axis represents the applied voltage, while the vertical axis represents the output obtained from the chambers. The uncertainty results are presented in Table I. The range of the combined standard uncertainties corresponds to each measurement point.
Saturation curves obtained from measurements with a 208.3 MeV/u uHDR scanned carbon-ion beam in the (A) Advanced Markus chamber, (B) PinPoint 3D chamber, (C) Farmer chamber, and (D) large plane-parallel chamber (StingRay). Error bars indicate the combined standard uncertainties.
Uncertainty of each item and the combined standard uncertainties with a coverage factor (k) of 1.
In the AMC, the saturation region was observed at a voltage of approximately 300 V. The saturation regions of the PPC and StingRay were observed almost at the maximum applied voltage. No saturation region was observed in the FC in the applied voltage range.
The ion recombination correction factors were obtained for each ionization chamber using the 2V- and 3VL-methods. The results are presented in Table II. In case of the AMC, the ion-recombination correction factor obtained using both methods was almost equal to 1.0. The corresponding factors for PPC obtained using the 2V- and 3VL-methods were approximately 6.2% and 3.6%, respectively.
Ion recombination correction factors obtained using the two-voltage method (2V-method) and the three-voltage linear method (3VL-method) for each ionization chamber. “R2” is the fitting coefficient calculated using a linear function.
Linearity and repeatability. We calculated the dose linearity and repeatability of the four types of ionization chambers used in the experiments. The linearity results are presented in Figure 4 and Table III, while the repeatability results are shown in Table IV. In Figure 4, the combined standard uncertainties are indicated as error bars. All ionization chambers exhibited excellent linearity, as shown in Figure 4. Based on linear fitting of the results, the calculated fitting coefficients R2 were ~1. Additionally, all ionization chambers exhibited good repeatability of <1.0%, except for the PPC with the lowest dose. The maximum standard deviation of the PPC repeatability was approximately 1.5% for the lowest dose.
Linearity measurement results in the (A) Advanced Markus and PinPoint 3D chambers and (B) Farmer and large plane-parallel (StingRay) chambers. Error bars indicate the combined standard uncertainties (k=1), and “R2” is the calculated fitting coefficient. All chambers exhibit excellent linearity within the dose range.
Uncertainties in the linearity measurement of each ionization chamber. The coverage factor (k) was set to 1.
Ionization chamber repeatability results calculated using a coverage factor (k) of 1.
Discussion
In this study, we investigated the response of four types of ionization chambers for a 208.3 MeV/u uHDR scanned carbon-ion beam. As shown in Figure 4, excellent dose linearity was observed for all types of chambers. As shown in Table II, although the repeatability uncertainty of the PPC was >1% for the lowest dose, excellent repeatability was observed for the other types of ionization chambers. Although the AMC, which is a plane-parallel chamber, has a 5.0-mm diameter and the PPC has a 2.9-mm diameter and a 2.9-mm length cylinder, the detector area of the PPC visible from the upstream side was approximately half that of the AMC. Furthermore, the beam size in the monochromatic beam mode was smaller than that in the normal treatment mode because the beam does not pass through the nozzle, resulting in less beam scatter. The measurements of the PPC are more sensitive than those of the other ionization chambers owing to the beam size and detector sensitive volume size. Overall, the results obtained for all types of ionization chambers investigated in this study can be used for measuring the relative dose.
As shown in Figure 5, the output of the ionization chambers, except the AMC, did not reach saturation when the usable voltage ranges were applied. These results are in agreement with the standard ion-recombination theory posited by Boag et al. (23) and the recommendation suggested by Esplen et al. (13), according to which a small-volume ionization chamber with small electrode gaps (plane parallel chambers) or effective spacing (cylindrical chambers) may be more suitable to high-dose rate dosimetry than other chambers. The ion-recombination correction factors obtained using both methods (2V- and 3VL-methods) were <0.5% for the AMC, whereas those obtained using the 2V-method for the other chambers were >3.0%, indicating that the 2V-method is unsuitable for calculating the correction factors (17). Furthermore, the AMC is better suited for absolute dose measurements than the other chambers.
Comparison of the saturation curves of the Advanced Markus chamber and large plane-parallel chamber (StingRay). The output values are normalized to 150 V. The red dashed line indicates the electric field corresponding to 400 V in the PinPoint 3D chamber.
Although the maximum usable voltage of StingRay is lower than that of the AMC, the electrode gap of StingRay is equal to that of the AMC. Therefore, the electric field strengths of these chambers are considered almost equal. By plotting their corresponding saturation curves on the same graph and normalizing the output values to 150 V, we observed that the curves almost match, as shown in Figure 5. Although we could not conduct measurements using voltages above 150 V owing to the maximum operating voltage indicated in the instruction manuals, it seems that StingRay can also reach saturation (similar to the AMC) by applying an ~300 V voltage.
As the PPC is a type of cylindrical ionization chamber, the electric field strength in it can be calculated as follows:
(1)
where E represents the electric field strength, V represents the operating voltage, r represents the distance from the cylinder center, and a and b represent the distances from the cylinder center to the outside and inside electrodes, respectively. The mean electric field of the PPC calculated using the aforementioned formula (a=1.495 mm, b=0.3 mm, and V=400 V) was ~290 V/mm, which is indicated by the red dashed line shown in Figure 5. This estimation of electric field strength approximately matched the saturation curve, which did not quite reach saturation at 400 V. Based on the electric field strength, we can estimate whether an ionization chamber can be used for uHDR scanned carbon-ion beams.
Conclusion
We investigated the response of ionization chambers to uHDR scanned carbon-ion beams. Although good repeatability and dose linearity was observed for all types of chambers, their output did not reach saturation at specified applied voltages, except for the AMC. In the of the uHDR scanned carbon-ion beams, the characteristics of the ionization chamber should be carefully considered when measuring absolute doses.
Acknowledgements
The Authors acknowledge and thank the staff of Osaka-HIMAK for their help in conducting uHDR beam measurements, and the staff of Osaka Heavy-Ion Administration Company, and Hitachi, Ltd., for their help in operating the accelerator.
Footnotes
Authors’ Contributions
Conceptualization: Noriaki Hamatani, Masashi Yagi. Methodology: Noriaki Hamatani, Masashi Yagi, Naoki Ishino, Toshiro Tsubouchi, Masaaki Takashina, Tatsuaki Kanai. Validation: Noriaki Hamatani. Formal analysis: Noriaki Hamatani. Investigation: Noriaki Hamatani, Masashi Yagi, Naoki Ishino, Toshiro Tsubouchi, Masaki Shimizu, Yoshiaki Kuwana. Resources: Masaki Shimizu, Yoshiaki Kuwana, Takuto Miyoshi, Takuya Nomura, Takashi Toyoda, Masumi Umezawa. Writing – original draft preparation: Noriaki Hamatani. Writing – review and editing: Masashi Yagi, Tatsuaki Kanai. Visualization: Noriaki Hamatani, Masashi Yagi. Supervision: Masashi Yagi, Tatsuaki Kanai. Project administration: Shinichi Shimizu, Teiji Nishio, Masahiko Koizumi, Kazuhiko Ogawa, Tatsuaki Kanai. Funding acquisition: Masashi Yagi, Masaaki Takashina.
Conflicts of Interest
The Authors, Takuto Miyoshi, Takuya Nomura, Takashi Toyoda, Masaki Shimizu, Yoshiaki Kuwana, and Masumi Umezawa are employees of Hitachi Ltd.
Funding
This work is part of the collaborative research project 2021_2195 at Osaka University and was supported by a grant from the JSPS KAKENHI (Grant Number 22K07695), with partial support from JSPS KAKENHI (Grant Numbers 22K07770 and 22H03025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Received June 6, 2024.
- Revision received July 3, 2024.
- Accepted July 4, 2024.
- Copyright © 2024 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
