Development of a silicone-based radio-fluorogenic dosimeter using dihydrorhodamine 6G.

A silicon-based three-dimensional dosimeter can be formed in a free shape without a container and deformed because of its flexibility. Several studies have focused on enhancing its radiological characteristics and assessing its applicability as a quality assurance tool for image-guided and adaptive radiation therapy, considering motion and deformation. Here, we applied a fluorescence probe (dihydrorhodamine 6G, DHR6G) to a silicon elastomer as a new radiosensitive compound that converts nonfluorescent into fluorescent dyes using irradiation, and its fluorescence intensity increases linearly with the absorbed dose. In this study, we demonstrated a cost-effective synthesis method and optimized the composition conditions. The results showed that the DHR6G-SE prepared from 2.2 × 10-3 wt% DHR6G, 0.024 wt% pyridine, and a silicone elastomer (SE) (SILPOT TM 184, base/curing agent = 10/1) exhibited a linear increase in fluorescence with radiation exposure within a dose range of 0-8 Gy and a highly stable sensitivity for as long as 64 h. To demonstrate its container-less characteristics, the possibility of dosimetry for low-energy X-rays using DHR6G-SE was investigated.

Radio-fluorogenic nanoclay gel dosimeters with reduced linear energy transfer dependence for carbon-ion beam radiotherapy.

PURPOSE: The precise assessment of the dose distribution of high linear energy transfer (LET) radiation remains a challenge, because the signal of most dosimeters will be saturated due to the high ionization density. Such measurements are particularly important for heavy-ion beam cancer therapy. On this basis, the present work examined the high LET effect associated with three-dimensional gel dosimetry based on radiation-induced chemical reactions. The purpose of this study was to create an ion beam radio-fluorogenic gel dosimeter with a reduced effect of LET. METHODS: Nanoclay radio-fluorogenic gel (NC-RFG) dosimeters were prepared, typically containing 100 µM dihydrorhodamine 123 (DHR123) and 2.0 wt% nanoclay together with catalytic additives promoting Fenton or Fenton-like reactions. The radiological properties of NC-RFG dosimeters having different compositions in response to a carbon-ion beam were investigated using a fluorescence gel scanner. RESULTS: An NC-RFG dosimeter capable of generating a fluorescence intensity distribution reflecting the carbon-ion beam dose profile was obtained. It was clarified that the reduction of the unfavorable LET dependence results from an acceleration of the reactions between DHR123 and H2 O2 , which is a molecular radiolysis product. The effects of varying the preparation conditions on the radiological properties of these gels were also examined. The optimum H2 O2 catalyst was determined to include 1 mM Fe3+ ions, and the addition of 100 mM pyridine was also found to increase the sensitivity. CONCLUSIONS: This technique allows the first-ever evaluation of the depth-dose profile of a carbon-ion beam at typical therapeutic levels of several Gy without LET effect.

Verification of dose distribution in high dose-rate brachytherapy for cervical cancer using a normoxic N-vinylpyrrolidone polymer gel dosimeter.

The polymer gel dosimeter has been proposed for use as a 3D dosimeter for complex dose distribution measurement of high dose-rate (HDR) brachytherapy. However, various shapes of catheter/applicator for sealed radioactive source transport used in clinical cases must be placed in the gel sample. The absorbed dose readout for the magnetic resonance (MR)-based polymer gel dosimeters requires calibration data for the dose-transverse relaxation rate (R2) response. In this study, we evaluated in detail the dose uncertainty and dose resolution of three calibration methods, the multi-sample and distance methods using the Ir-192 source and the linear accelerator (linac) method using 6MV X-rays. The use of Ir-192 sources increases dose uncertainty with steep dose gradients. We clarified that the uniformly irradiated gel sample improved the signal-to-noise ratio (SNR) due to the large slice thickness of MR images and could acquire an accurate calibration curve using the linac method. The curved tandem and ovoid applicator used for intracavitary irradiation of HDR brachytherapy for cervical cancer were reproduced with a glass tube to verify the dose distribution. The results of comparison with the treatment planning system (TPS) calculation by gamma analysis on the 3%/2 mm criterion were in good agreement with a gamma pass rate of 90%. In addition, the prescription dose could be evaluated accurately. We conclude that it is easy to place catheter/applicator in the polymer gel dosimeters, making them a useful tool for verifying the 3D dose distribution of HDR brachytherapy with accurate calibration methods.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Whole Three-Dimensional Dosimetry of Carbon Ion Beams with an MRI-Based Nanocomposite Fricke Gel Dosimeter Using Rapid T1 Mapping Method.

MRI-based gel dosimeters are attractive systems for the evaluation of complex dose distributions in radiotherapy. In particular, the nanocomposite Fricke gel dosimeter is one among a few dosimeters capable of accurately evaluating the dose distribution of heavy ion beams. In contrast, reduction of the scanning time is a challenging issue for the acquisition of three-dimensional volume data. In this study, we investigated a three-dimensional dose distribution measurement method for heavy ion beams using variable flip angle (VFA), which is expected to significantly reduce the MRI scanning time. Our findings clarified that the whole three-dimensional dose distribution could be evaluated within the conventional imaging time (20 min) and quality of one cross-section.

Verification of dose distribution in high-dose-rate brachytherapy using a nanoclay-based radio-fluorogenic gel dosimeter.

Dose distributions have become more complex with the introduction of image-guided brachytherapy in high-dose-rate (HDR) brachytherapy treatments. Therefore, to correctly execute HDR, conducting a quality assurance programme for the remote after-loading system and verifying the dose distribution in the patient treatment plan are necessary. The characteristics of the dose distribution of HDR brachytherapy are that the dose is high near the source and rapidly drops when the distance from the source increases. Therefore, a measurement tool corresponding to the characteristic is required. In this study, using an Iridium-192 (Ir-192) source, we evaluated the basic characteristics of a nanoclay-based radio-fluorogenic gel (NC-RFG) dosimeter that is a fluorescent gel dosimeter using dihydrorhodamine 123 hydrochloride as a fluorescent probe. The two-dimensional dose distribution measurements were performed at multiple source positions to simulate a clinical plan. Fluorescence images of the irradiated NC-RFG were obtained at a high resolution (0.04 mm pixel-1) using a gel scanner with excitation at 465 nm. Good linearity was confirmed up to a dose range of 100 Gy without dose rate dependence. The dose distribution measurement at the five-point source position showed good agreement with the treatment planning system calculation. The pass ratio by gamma analysis was 92.1% with a 2%/1 mm criterion. The NC-RFG dosimeter demonstrates to have the potential of being a useful tool for quality assurance of the dose distribution delivered by HDR brachytherapy. Moreover, compared with conventional gel dosimeters such as polymer gel and Fricke gel dosimeters it solves the problems of diffusion, dose rate dependence and inhibition of oxygen-induced reactions. Furthermore, it facilitates dose data to be read in a short time after irradiation, which is useful for clinical use.

Potential Mechanisms for Protective Effect of D-Methionine on Plasmid DNA Damage Induced by Therapeutic Carbon Ions.

D-methionine (D-met), a dextrorotatory isoform of the amino acid L-methionine (L-met), can prevent oral mucositis and salivary hypofunction in mice exposed to radiation. However, the mechanism of its radioprotection is unclear, especially with regard to the stereospecific functions of D-met. Radiation is known to cause injury to normal tissue by triggering DNA damage in cells. Thus, in this study we sought to determine whether the chirality of D-/L-met affects radiation-induced events at the DNA level. We selected plasmid DNA assays to examine this effect in vitro, since these assays are highly sensitive and allow easy detection of DNA damage. Samples of supercoiled pBR322 plasmid DNA mixed with D-met, L-met or dimethylsulfoxide (DMSO) were prepared and irradiated with a Bragg peak beam of carbon ions (∼290 MeV/u) with a 6-cm spread. DNA strand breaks were indicated by the change in the form of the plasmid and were subsequently quantified using agarose gel electrophoresis. We found that D-met yielded approximately equivalent protection from carbon-ion-induced DNA damage as DMSO. Thus, we propose that the protective functions of methionine against plasmid DNA damage could be explained by the same mechanism as that for DMSO, namely, hydroxyl radical scavenging. This stereospecific radioprotective mechanism occurred at a level other than the DNA level. There was no significant difference between the radioprotective effect of D-met and L-met on DNA.

End-to-end delivery quality assurance of computed tomography-based high-dose-rate brachytherapy using a gel dosimeter.

PURPOSE: The purpose of this study was to develop a novel quality assurance (QA) program to check the entire treatment chain of image-guided brachytherapy with dose distribution evaluation in a single setup and irradiation using a gel dosimeter. METHODS AND MATERIALS: A polymer gel was used, and the readout was performed by magnetic resonance scanning. A CT-based treatment plan was generated using the Oncentra planning system (Elekta, Sweden), and irradiation was performed three times using an afterloading device with an Ir-192 source. The dose-response curve of the gel was created using 6-MV X-ray, which is independent of the source beams. Planar gamma images on a coronal plane along the source transport axis were calculated using the measured dose as a reference, and the calculated doses were used in several error simulations (no error; 2.0 or 2.5 mm systematic and random source dwell mispositioning; and dose error of 2%, 5%, 10%, and 20%). RESULTS: The dose-R2 (spin-spin relaxation rate) conversion table revealed that the uncertainty and dose resolution of 6-MV X-ray were better than those of Ir-192 and also constant between the three measurements. With the 3%/1 mm criteria, there were statistically significant differences between each pair of settings except dose error of 2% and 5%. CONCLUSION: This work depicts a simple and efficient end-to-end test that can provide a clinically useful tool for QA of image-guided brachytherapy. In this QA program, air kerma strength and dwell position setting could also be verified. This test can also distinguish between different types of error.

Sensitivity enhancement of DHR123 radio-fluorogenic nanoclay gel dosimeter by incorporating surfactants and halogenides.

Dosimetry of spatial dose distribution of ionizing radiation in tissue equivalent materials is particularly important for cancer radiotherapy. Here, we describe a radio-fluorogenic gel-based dosimeter that has achieved 16 times higher sensitivity by incorporating surfactants and halogenides. The gel dosimeters were prepared from dihydrorhodamine 123 (DHR123) and small amounts of nano-sized clay and a radiosensitizer. By comprehensively changing the type of additives for the sensitizer (three surfactants: Triton X-100, sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide, and three halogenides: trichloroacetic acid, tribromoacetic acid and 2,2,2-trichloroethanol), the increase in sensitivity can be explained by an increase in relative fluorescence quantum yield and an increase in radiation chemical yield. These highly sensitive gel dosimeters also show dose rate independent sensitivity under irradiation at 0.64 and 0.77 Gy min-1 using a 6 MV X-ray therapeutic beam from the medical linac.

Dose distribution verification in high-dose-rate brachytherapy using a highly sensitive normoxic N-vinylpyrrolidone polymer gel dosimeter.

Rapid technological advances in high-dose-rate brachytherapy have led to a requirement for greater accuracy in treatment planning system calculations and in the verification of dose distributions. In high-dose-rate brachytherapy, it is important to measure the dose distribution in the low-dose region at a position away from the source in addition to the high-dose range in the proximity of the source. The aim of this study was to investigate the accuracy of a treatment plan designed for prostate cancer in the low-dose range using a normoxic N-vinylpyrrolidone-based polymer gel (VIPET gel) dosimeter containing inorganic salt as a sensitizer (iVIPET). The dose response was evaluated on the basis of the transverse relaxation rate (R2) measured by magnetic resonance scanning. In the verification of the treatment plan, gamma analysis showed that the dose distributions obtained from the polymer gel dosimeter were in good agreement with those calculated by the treatment planning system. The gamma passing rate according to the 2%/2 mm criterion was 97.9%. The iVIPET gel dosimeter provided better accuracy for low doses than the normal VIPET gel dosimeter, demonstrating the potential to be a useful tool for quality assurance of the dose distribution delivered by high-dose-rate brachytherapy.

[Fricke Gel Dosimeters].

Fricke gel dosimeters are based on the aqueous ferrous sulfate solution that has been used as a reliable chemical dosimeter for more than 90 years. The amount of radiation-induced oxidation of ferrous ions to ferric ions could be evaluated three-dimensionally via optical computed tomography (OCT) or magnetic resonance imaging (MRI). Three-dimensional dosimetry is expected to be a useful tool, in particular, for the verification of complex radiation dose planning in advanced radiation cancer therapy. Compared with other 3D gel dosimeters, there are several problems such as retention of dose distribution or dose sensitivity; however, they can easily be prepared in a chemistry laboratory. In addition, a unique gel dosimeter was also reported for heavy-ion beam irradiation. In this review, recent papers concerning the Fricke gel dosimeter and its application in 3D dosimetry are summarized.

Organic-Gelatin-Free Nanocomposite Fricke Gel Dosimeter.

We report a nanocomposite Fricke gel (NC-FG) dosimeter prepared using only Fe2+ and nanoclay in water, without any organic gelling agents. This dosimeter gels due to its thixotropic properties and exhibits linear energy transfer (LET)-independent radiological properties under carbon ion beam irradiation. The radiation sensitivity of this dosimeter was 1.8 [s-1 kGy-1], which is three times higher than that reported previously (0.6 [s-1 kGy-1]) for a similar dosimeter containing gelatin. The Fe3+ yield was determined to be 0.19 µmol/J by evaluating the difference in spin-lattice relaxivity between Fe3+ and Fe2+. A further increase in the radiation sensitivity was observed upon addition of the hydrated electron scavenger N2O, suggesting the reduction of Fe3+ by a hydrated electron. LET-dependent variations of the contributions of OH radicals and hydrated electrons compensate each other in the oxidation yield of NC-FG. This is the main mechanism of the suppression of LET effects in the Bragg peak compared to conventional Fricke dosimeters. The radiation-induced oxidation yield G(Fe3+) can be described by the stoichiometric equation {G(Fe3+) = G(OH) - G(eaq-) + 2G(H2O2) + G(H)} with the reported LET dependence of the primary yield of water decomposition radicals. The calculated results are in approximate agreement with the absolute value of the experimental oxidation yield of NC-FG. The effects of the addition of small amounts of radical scavengers (nitrate, selenate, or cadmium) are also evaluated. The sensitivity was divided into two types, and influences of intermediate radicals after scavenging reaction are indicated.

[Polymer Gel Dosimetry for the High-Dose-Rate Brachytherapy Using Ir-192 Source].

High-dose-rate (HDR) brachytherapy is performed with the remote after-loading system (RALS) to transport an Ir-192 source directly to inside or near the tumor. Quality assurance (QA) of equipment should be performed at sufficient frequency to ensuring safety and quality of HDR brachytherapy treatment. Polymer gel dosimeters have been attracting attention in recent years as a QA tools of HDR brachytherapy, because they can measure the three-dimensional steep dose gradients around HDR sources. In this paper, we introduce our preliminary results using VIPET polymer gel dosimeters for Ir-192 HDR brachytherapy dosimetry.

Radiological properties of nanocomposite Fricke gel dosimeters for heavy ion beams.

The radiological properties of nanocomposite Fricke gel (NC-FG) dosimeters prepared with different concentrations of nano-clay, perchloric acid and ferrous ions in deaerated conditions were investigated under carbon and argon ion beam irradiation covering a linear-energy-transfer (LET) range of 10 to 3000 eV/nm. We found that NC-FG exhibits radiological properties distinct from those of conventional Fricke gel. The radiation sensitivity of NC-FG is independent of the LET and is nearly constant even at very high LET (3000 eV/nm) values in the Bragg peak region of the argon ion beam. In addition, whereas conventional Fricke gel dosimeters only operate under acidic conditions, NC-FG dosimeters function under both acidic and neutral conditions. The radiation sensitivity decreases with decreasing nano-clay concentration in NC-FG, which indicates that the nano-clay plays a vital role in the radiation-induced oxidation of Fe(2.)

Mechanism of radiation-induced reactions in aqueous solution of coumarin-3-carboxylic acid: effects of concentration, gas and additive on fluorescent product yield.

The radiation-induced reactions of a water-soluble coumarin derivative, coumarin-3-carboxyl acid (C3CA), have been investigated in aqueous solutions by pulse radiolysis with a 35 MeV electron beam, final product analysis following (60)Co γ-irradiations and deterministic model simulations. Pulse radiolysis revealed that C3CA reacted with both hydroxyl radicals ((•)OH) and hydrated electrons (e(-) (aq)) with near diffusion-controlled rate constants of 6.8 × 10(9) and 2.1 × 10(10) M(-1) s(-1), respectively. The reactivity of C3CA towards O(2)(• -) was not confirmed by pulse radiolysis. Production of the fluorescent molecule, 7-hydroxy-coumarin-3-carboxylic acid (7OH-C3CA), was confirmed by final product analysis with a fluorescence spectrometer coupled to a high performance liquid chromatography (HPLC) system. Production yields of 7OH-C3CA following (60)Co γ-irradiations depended on the irradiation conditions and ranged from 0.025 to 0.18 (100 eV) (-1). Yield varied with saturating gas, additive and C3CA concentration, implying the presence of at least two pathways capable of providing 7OH-C3CA as a stable product following the scavenging reaction of C3CA with (•)OH, including a peroxidation/elimination sequence and a disproportionation pathway. A reaction mechanism for the two pathways was proposed and incorporated into a deterministic simulation, showing that the mechanism can explain experimentally measured 7OH-C3CA yields with a constant conversion factor of 4.7% from (•)OH scavenging to 7OH-C3CA production, unless t-BuOH was added.