Optimization of the Dose Rate Effect in Tetrazolium Gellan Gel Dosimeters.

Tetrazolium salts provide an appealing candidate for 3D gel dosimeters as they exhibit a low intrinsic color, no signal diffusion and excellent chemical stability. However, a previously developed commercial product (the ClearView 3D Dosimeter) based on a tetrazolium salt dispersed within a gellan gum matrix presented a noticeable dose rate effect. The goal of this study was to find out whether ClearView could be reformulated in order to minimize the dose rate effect by optimizing of the tetrazolium salt and gellan gum concentrations and by the addition a thickening agent, ionic crosslinkers, and radical scavengers. To that goal, a multifactorial design of experiments (DOE) was conducted in small-volume samples (4-mL cuvettes). It showed that the dose rate could be effectively minimized without sacrificing the integrity, chemical stability, or dose sensitivity of the dosimeter. The results from the DOE were used to prepare candidate formulations for larger-scale testing in 1-L samples to allow for fine-tuning the dosimeter formulation and conducting more detailed studies. Finally, an optimized formulation was scaled-up to a clinically relevant volume of 2.7 L and tested against a simulated arc treatment delivery with three spherical targets (diameter 3.0 cm), requiring different doses and dose rates. The results showed excellent geometric and dosimetric registration, with a gamma passing rate (at 10% minimum dose threshold) of 99.3% for dose difference and distance to agreement criteria of 3%/2 mm, compared to 95.7% in the previous formulation. This difference may be of clinical importance, as the new formulation may allow the quality assurance of complex treatment plans, relying on a variety of doses and dose rates; thus, expanding the potential practical application of the dosimeter.

Gellan gum gel tissue phantoms and gel dosimeters with tunable electrical, mechanical and dosimetric properties.

Gellan gum gels have been proposed as tissue- and water-mimicking materials (phantoms) applied in medical imaging and radiotherapy dosimetry. Phantoms often require ionic additives to induce desirable electrical conductivity, resistance to biological spoilage, and radical scavenging properties. However, gellan gum is strongly crosslinked by the typically used sodium salts, forming difficult-to-work with gels with reduced optical clarity. Herein we investigated lithium and tetramethylammonium chloride to induce the required electrical conductivity while maintaining optical clarity; lithium formate and methylparaben were used as a radical scavenger and antimicrobial additive, respectively. Using a multifactorial design of experiments, we studied and modeled the electrical and mechanical properties and liquid expulsion (syneresis) properties of the gels. Finally, by the addition of a radiation-sensitive tetrazolium salt, dosimeters with favorable properties were produced. The results described herein may be used to prepare tissue phantoms and dosimeters with tuned electrical, mechanical, and dosimetric properties.

Gellan gum-based gels with tunable relaxation properties for MRI phantoms.

OBJECT: The research follows the analysis of gellan gum-based gels as novel MRI phantom material with the implementation of a design of experiments model to obtain tunable relaxation properties. MATERIALS AND METHODS: Gellan gum gels doped with newly synthesized superparamagnetic iron oxide nanoparticles (SPIONs) and either MnCl2 or GdCl3 were prepared and scanned from 230 µT to 3 T. Nineteen gel samples were formulated with varying concentrations of contrast agents to determine the linear, quadratic, and interactive effects of the contrast agents by a central composite design of experiment. To inhibit microbial growth in the gels and to enable long-term use, methyl 4­hydroxybenzoate (methylparaben) was utilized. RESULTS: The model containing SPIONs and metal salts relaxivity was analyzed with ANOVA, and the resulting significant coefficients were tabulated. The mathematical model was able to accurately predict the intended relaxation property from the concentration of the contrast agent with adjusted R2 values > 0.97 for longitudinal (R1) relaxation rates and 0.87 for transverse (R2) relaxation rates. CONCLUSION: The gel material maintained physical, chemical, and biological stability for at least four months and contained controllable relaxation properties while maintaining optical clarity.

Multifactorial study and kinetics of signal development in ferrous-methylthymol blue-gelatin gel dosimeters.

PURPOSE: To develop and characterize a ferrous-methylthymol blue-gelatin gel dosimeter with low optical background and appropriate additives for reduced rate of auto-oxidation and diffusion. METHODS: A mixed-level multifactorial design of experiments was used to test the effects of the concentrations of sulfuric acid, 5-nitro-1,10-phenanthroline (Nn), and glyoxal (Gx) on the background absorbance, dose sensitivity, and auto-oxidation of the tested gel dosimeter. The dosimetric properties of the proposed ferrous-methylthymol blue-gelatin dosimeter, doped with Nn and Gx, were compared with the undoped formulation and with ferrous-xylenol orange-gelatin gel dosimeters. Irradiations were performed in both small-scale cuvette samples and large 400-mL bulk samples. In addition to that, a new kinetic model for the signal development postirradiation was derived based on chemical principles and used for comparison of the different formulations. RESULTS: The new formulation showed a reduced auto-oxidation rate, while maintaining low background absorbance relative to the common ferrous-xylenol orange-gelatin gel dosimeter. Compared with undoped ferrous-xylenol orange or ferrous-methylthymol blue gels, the dose sensitivity of the new formulation is approximately 2 to 3 times lower, but remains clinically adequate. A previously unreported dose rate dependence of the dose sensitivity was observed, and a new kinetic model for the signal development postirradiation was used to investigate this effect. Similar dose rate dependences in gels containing either methylthymol blue or xylenol orange, with or without doping with Nn and Gx, were observed, suggesting that the low ferrous ammonium sulfate concentrations used in studied formulations were responsible for this effect. CONCLUSIONS: A multifactorial design of experiments and a new kinetic model for the signal development postirradiation were successfully employed to optimize the composition and characterize the properties of a new ferrous-methylthymol blue-gelatin gel dosimeter doped with 5-nitro-1,10-phenanthroline and glyoxal. Concrete recommendations were provided for precise dosimetry using the new formulation.

Controlling sensitivity and stability of ferrous-xylenol orange-gelatin 3D gel dosimeters by doping with phenanthroline-type ligands and glyoxal.

The ferrous-xylenol orange-gelatin (FXG) dosimeter is widely used for three-dimensional ionizing radiation field mapping through optical scanning. Upon irradiation, the ferrous iron (Fe(2+)) is oxidized to ferric iron (Fe(3+)), which forms an intensely coloured complex with xylenol orange (XO). XO also acts as a diffusion-limiting additive; however, its presence may cause rapid auto-oxidation of Fe(2+) during storage and low stability of the dose response. In this work, phenanthroline-type ligands were added to FXG system in a bid to bind the ferrous iron in a stable complex and minimize the rate of the auto-oxidation, whereas glyoxal was used as a chemical cross-linker, aiming to minimize the ferric iron diffusion. It was found that addition of either 1,10-phenanthroline or 5-nitro-1,10-phenanthroline can improve the auto-oxidation behaviour of the gels. However, the initial background absorbance was slightly increased, and the sensitivity of the dosimeters was decreased. Doping with glyoxal led to a moderate decrease of the diffusion only in those gels that also contained a phenanthroline-type ligand, and did not affect the initial dose response. Glyoxal also afforded an extended period of stable background absorbance level after an initial period of bleaching of the gel. Following re-irradiation, most glyoxal-containing dosimeters showed an excellent linearity of the dose response, albeit at a decreased sensitivity. We recommend further testing of FXG dosimeters, doped with phenanthroline-type ligands and glyoxal as a means for controlling the dose response and improving the long-term storage properties of the gels and the potential for dose fractionation.