Characterization of long-term dose stability of N-isopropylacrylamide polymer gel dosimetry

In this study, the detailed characteristics, including spatial uniformity, dose distributions, inter-batch variability, reproducibility, and long-term temporal stability, of N-isopropylacrylamide (NIPAM) polymer gel dosimeter were investigated. A commercial 10x fast optical computed tomography scanner (OCTOPUS^TM-10×, MGS Research, Inc., Madison, CT, USA) was used to measure NIPAM polymer gel dosimeter. A cylindrical NIPAM gel phantom that measured 10 cm × 10 cm was irradiated via a single-field treatment plan with a field size of 4 cm × 4 cm. The maximum standard deviation of spatial uniformity for NIPAM gel was less than 0.29 %. The average standard deviation among the three batches of gel dosimeters was less than 1 %. The gamma pass rate could reach as high as 96.76 % when a 3 % dose difference and a 3 mm dose-to-agreement criteria were used. The long-term measurement of irradiated NIPAM gel dosimeter indicated that the dose maps attained a gradually stable value 15 h post-irradiation and remained stable until 72 h post-irradiation. The gamma pass rate could achieve a maximum value between 24 and 72 h post-irradiation. The edge enhancement effect that occurred around the irradiated region was observed 72 h post-irradiation. Thus, the results from this study suggest that NIPAM gel dosimeter should be measured approximately 24 h post-irradiation to reduce the occurrence of the edge enhancement effect.     

An approach in exploring the fundamental dosimetric characteristics for a long shelf life irradiated acrylamide-based gel

In this study, a long shelf life irradiated gel made from a low-toxicity N-isopropylacrylamide (NIPAM) monomer was used to study the dosimetric characteristics associated with magnetic resonance imaging (MRI). Specifically, the Taguchi method was utilized to investigate the influence of MRI scanning parameters on the performance objectives of NIPAM gels, and the priorities of the parameters that influence the process were determined using Delta statistics. The influence of different echo spacing on the relaxation rate–dose response of the gel and the relationship among the dose resolution (D _Δ ^P ), dose accuracy, and reproducibility were also examined. The results indicated that the repetition time (TR) and echo time (TE), having Delta values of 3.81042 and 4.52752, respectively, were the most influential factors. Analysis of variance further confirmed that TE was the major factor, with a percentage contribution of 58.36 %, and TR was the second factor with a percentage contribution of 41.34 %. The maximum sensitivity was 0.1506 s^?1 Gy^?1 from 0 to 15 Gy, and the best D _Δ ^P of the NIPAM gel was 0.017 Gy. Two months after the irradiation, no obvious changes in linearity and sensitivity were observed, indicating that the NIPAM gels are highly stable. The gel dosimeters were also applied in comparing the planar dose distributions of the gel dosimeters and treatment planning system. The comparison showed good agreement of isodose lines on selected planes in the transverse plane. This result indicates the great potential of the NIPAM dosimeter has a clinical dose verification tool.     

On the Development of the VIPAR Polymer Gel Dosimeter for Three-Dimensional Dose Measurements

Summary: The new polymer gel dosimeter, based on the modification of the VIPAR gel composition, is described for the purpose of radiation dose distribution measurement in radiotherapy. It features increased concentration of the two VIPAR substrates: N-vinylpyrrolidone (8%) and gelatine (7.5%) (N,N′-methylenebisacrylamide was maintained at 4%), and the addition of copper sulphate (0.0008%) and ascorbic acid (0.007%) in order to facilitate the preparation through elimination of the need for deoxygenation of the gel. Following the exposure to ionizing radiation, polymerisation and cross-linking of the new gel monomers occurs retaining the spatial distribution of absorbed dose and causing opacity of the gel. Quantitative parameters of the new gel dose response were studied using magnetic resonance imaging to relate polymerisation induced physicochemical changes of the gel to dose. The dose threshold is found significantly lower than that of the original VIPAR gel. The linear part of measured spin-spin relaxation rate R₂(D) ( = 1/T₂(D)) reaches up to 35 Gy. Its slope and an intercept are slightly higher relative to the original VIPAR. The efficiency of the new polymer gel-magnetic resonance imaging dosimeter was also tested for dose verification of a 3D dose distribution planned by a commercially available treatment planning software (Eclipse External Beam v.6.5) and delivered by a 6 MV medical linear accelerator. The new polymer gel is proposed to be called, VIPAR^nd (after VIPAR-normoxic-double).     

Preliminary investigation of a new type of propylene based gel dosimeter (DEMBIG)

Radiotherapy widely uses the polymer gel dosimeter. The advantage of polymer gel dosimetry is the mapped 3D absorbed dose distribution that other dosimeters cannot achieve. The Acrylamide (AAm) is a frequently used monomer; however, the extreme toxicity of Acrylamide (ORL-RAT LD50: 124 mg/kg) raises a concern. Therefore, this study developed a new type of Propylene acid based gel dosimeter, named DEMBIG gel. The following outlines the aim of this study: (1) using two-point formulation to find the optimal scan parameter of MRI according to the best sensitivity and linearity (correlation coefficient) of DEMBIG gel, (2) using the optimal scan parameter of MRI to observe the properties of DEMBIG gel, and (3) verifying the three-dimensional (3D) dose distributions of radiotherapy. This study obtained three major results: 1. The scan protocol of MRI was established. 2. The preliminary results of DEMBIG gel were: (1) The range of absorbed dose of DEMBIG gel: 0–20 Gy. (2) The sensitivity and correlation coefficient of DEMBIG gel at verification as slope: 0.181 sGy^?1, R ²:0.997. (3) There is no energy dependency of the DEMBIG gel. 3. The dose difference was 3% in the three-dimensional (3D) isocenter dose in clinical radiotherapy. These data show that DEMBIG gel is a potential candidate for the 3D dosimeter.     

Dose distribution verification in intraoperative radiation therapy using an N-isopropyl acrylamide-based polymer gel dosimeter

The purpose of the current study was to verify the dose distribution of an Intrabeam-50 kV IORT system using polymer gel dosimetry technique. Results of dose distribution evaluation using NIPAM polymer gel dosimetry were compared with those measured using an ionization chamber and simulated using MCNPX code. Results showed the calculated gamma index was less than 1 with 2% dose-difference/2 mm distance-to-agreement for comparison between NIPAM and ionization chamber as well as between NIPAM and MCNPX simulation. It was concluded that the NIPAM polymer gel dosimetry is useful for verifying the dose distribution of low energy X-ray IORT technique.

     

How do monomeric components of a polymer gel dosimeter respond to ionising radiation: A steady-state radiolysis towards preparation of a 3D polymer gel dosimeter

Ionising radiation-induced reactions of aqueous single monomer solutions and mixtures of poly(ethylene glycol) diacrylate (PEGDA) and N,N′-methylenebisacrylamide (Bis) in a steady-state condition are presented below and above gelation doses in order to highlight reactions in irradiated 3D polymer gel dosimeters, which are assigned for radiotherapy dosimetry. Both monomers are shown to undergo radical polymerisation and cross-linking, which result in the measured increase in molecular weight and radius of gyration of the formed polydisperse polymer coils. The formation of nanogels was also observed for Bis solutions at a low concentration. In the case of PEGDA-Bis mixtures, co-polymerisation is suggested as well. At a sufficiently high radiation dose, the formation of a polymer network was observed for both monomers and their mixture. For this reason a sol–gel analysis for PEGDA and Bis was performed gravimetrically and a proposition of an alternative to this method employing a nuclear magnetic resonance technique is made. The two monomers were used for preparation of 3D polymer gel dosimeters having the acronyms PABIG and PABIG^nx. The latter is presented for the first time in this work and is a type of the formerly established PABIG polymer gel dosimeter. The elementary characteristics of the new composition are presented, underlining the ease of its preparation, low dose threshold, and slightly increased sensitivity but lower quasi-linear range of dose response in comparison to PABIG.     

A study on dose response of NIPAM-based dosimeter used in radiotherapy

The newly manufactured N-isopropylacrylamide (NIPAM) polymer gel is composed of four components, i.e., gelatin, monomer (NIPAM), crosslinker (N,N’-methylenebisacrylamide, Bis), and antioxidant (tetrakis hydroxymethyl phosphonium chloride, THPC). In this study, we investigated the effects of gel composition on the dose response of NIPAM polymer gel. A statistical experiment to analyze the contribution of each composition to the linearity and sensitivity of NIPAM gel was performed. Results indicate that the amount of gelatin, NIPAM (15.17%), Bis, and THPC have dominant effects on the sensitivity of the gel, with contributions of 59.73, 15.17, 10.64, and 14.45%, respectively. The amount of gelatin and Bis mainly affected the linearity of the gel, with contributions of 44.70 and 50.99%, respectively. The linearity of most compositions of the gel was greater than 0.99 when (%C)/(%T) was lower than 8.0. Optimal (%C)/(%T) for higher sensitivity should be in the range of 4−9. The temporal stability experiment showed that the dose response curve attained stability at about 5 h after irradiation and persisted up to 3 months.     

Optimal composition of a new polymer gel dosimeter-DEMBIG

Polymeric gel dosimeters are used to verify three-dimensional (3D) dose distributions of various types of radiotherapy treatments, particularly radiosurgery. The present paper investigates the low toxicity and high dose response of a new acrylate gel. The optimal recipe with the best linearity (R ² = 0.998) is 7% gelatin, 5% 2-(dimethylamino) ethyl acrylate monomer, and 4% N′N′-methylene-bisacrylamide crosslinker. The dose range is 0–30 Gy, and the temporal stability time is 12 h after irradiation. No significant energy dependency has been observed. The results show that the 2-(dimethylamino) ethyl acrylate N′N′-methylene-bisacrylamide gelatin gel is a potential 3D dosimeter.     

Modeling of Free‐radical Crosslinking Copolymerization of Acrylamide and N,N′‐Methylenebis(acrylamide) for Radiation Dosimetry

Over the past decade there has been much interest in the development of three‐dimensional gel dosimeters to aid in the determination of the distribution and magnitude of absorbed dose in clinical radiation therapy. A widely used dosimeter for verification of spatial dose distribution is the polyacrylamide system, sometimes termed polyacrylamide gel (PAG). In this paper, we develop a model to describe the kinetic mechanisms in this gel dosimeter, based on the radiation‐induced copolymerization of acrylamide and bisacrylamide monomers in water and gelatin. Using the proposed model, the conversion of both monomers and total vinyl groups, the concentrations of pendant double bonds (PDB), cyclized groups and crosslinks along the polymer chains as well as temperature changes were simulated. The model predictions and experimental findings in PAG dosimeters agree for a variety of recipes and spatially uniform radiation conditions. Further experiments are required to obtain accurate kinetic parameter estimates and to verify model predictions.

Comparison between the temperatures changes predicted by the model (dotted lines) and experimental data (solid lines) for PAGs irradiated to different doses.     

Mathematical Modeling of PAG‐ and NIPAM‐Based Polymer Gel Dosimeters Contaminated by Oxygen and Inhibitor

A mathematical model for crosslinking copolymerization of acrylamide (or NIPAM) and N,N'‐methylenebisacrylamide is extended to account for contamination by oxygen and the inhibitor MEHQ. This model improves basic understanding of interactions among oxygen, MEHQ and polymerization reactions in gel dosimeters that are used to verify radiation doses delivered by cancer treatment equipment. Improved parameter estimates result in a good match between model predictions and data. The model predicts that a larger absorbed dose will be required to overcome the oxygen inhibition with increasing oxygen contamination, in agreement with experimental data. The model also predicts that MEHQ, in the absence of oxygen, has almost no influence on dosimeter response.

     

Effects of pigments on the volume‐phase‐transition properties of N‐isopropylacrylamide gels as light‐modulation materials

The effects of pigments contained in N‐isopropylacrylamide (NIPAM) gels on their volume‐change properties were investigated. All the NIPAM gel particles, containing various kinds and concentrations of pigments, showed a volume phase transition at 34 °C. No pigment affected the volume‐phase‐transition temperature of the NIPAM gels. As the concentration of the pigment in the NIPAM gels was increased, the amount of the volume change of the NIPAM gels was reduced. The water absorptivity of the NIPAM gels in the swollen state decreased as the pigment concentration increased, whereas the water absorptivity in the shrunken state was almost constant. Reducing the initial monomer concentration of the polymerization of the NIPAM gel increased the water absorptivity in the swollen state. With an increase in the water absorptivity, the volume changes of the NIPAM gels containing pigments were increased. Prototype light modulators in which the NIPAM gel particles containing pigment were dispersed between glass plates were fabricated. The light modulator using the gel particles with improved diameter change (d/d₀ = 2.3, where d and d₀ are the equilibrium diameter and the diameter of the fully shrunken state at 50 °C, respectively) exhibited a larger transmittance change from 8 to 79% than that using the gel particles before the improvement (d/d₀ = 1.7; from 38 to 79%) according to temperature changes. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4644–4655, 2006     

Effect of DMSO on the sensitivity and diffusion of FPGX gel dosimeter

A stable hydrogel 3D dosimeter was prepared by using Fricke solution, poly (vinyl alcohol) (PVA) and glutaraldehyde (GA). A linear relationship between the dose and the UV absorbency was obtained by determining the color change of the dosimeter in the range of 0–2.5 Gy. Dimethyl sulfoxide (DMSO) was used as a free radical scavenger to analyze the thermo-stability and diffusion of FPGX gel dosimeter systems. The results showed that increasing the DMSO concentration could slow down the color change and the Fe³⁺ diffusion rate in a certain range. With the addition of DMSO, the FPGX gel dosimeter was stable in the storage time before exposure to radiation.     

琼脂糖基类丁二炔凝胶剂量计的辐照响应行为

将类丁二炔(10, 12-二十五碳二炔酸)囊泡固载于琼脂糖凝胶制备出了新型辐射变色凝胶复合凝胶材料。利用γ射线辐照研究了所制备凝胶的辐照响应行为,结果显示:当γ辐射剂量在500-2000 Gy内,随着剂量增加,凝胶由无色逐渐变为蓝色,颜色不断加深,采用紫外-可见光分光光度计测试其吸收光谱,发现其主要吸收峰值在660 nm附近,且辐照前后凝胶的吸光度差值与剂量有良好线性关系(相关系数R² =0.9942)。进一步研究表明:所制备的凝胶材料对γ射线和电子束辐照有相同的剂量响应,且无明显的能量和剂量率依赖性;凝胶的辐射后效应较弱,辐照后24 h,吸光度基本恒定;分次辐照对凝胶剂量计准确性的影响极小;凝胶在0-30℃范围内的响应性基本保持稳定;在辐照后48 h内,并未观察到囊泡有明显扩散效应,显示出良好的稳定性。此外,琼脂糖具有价廉、无毒且易制备为任意形状凝胶的优点,因此该凝胶剂量计有望应用于真实场景的三维剂量分布测定。     

Facile synthesis of triple‐stimuli (photo/pH/thermo) responsive copolymers of 2‐diazo‐1,2‐naphthoquinone‐mediated poly(N‐isopropylacrylamide‐co‐N‐hydroxymethylacrylamide)

A series of poly(N‐isopropylacrylamide‐co‐N‐hydroxymethylacrylamide) P(NIPAM‐co‐NHMA) copolymers were firstly synthesized via free radical polymerization. Then, the hydrophobic, photosensitive 2‐diazo‐1,2‐naphthoquinone (DNQ) molecules were partially and randomly grafted onto P(NIPAM‐co‐NHMA) backbone through esterification to obtain a triple‐stimuli (photo/pH/thermo) responsive copolymers of P(NIPAM‐co‐NHMA‐co‐DNQMA). UV‐vis spectra showed that the lower critical solution temperature (LCST) of P(NIPAM‐co‐NHMA) ascended with increasing hydrophilic comonomer NHMA molar fraction and can be tailored by pH variation as well. The LCST of the P(NIPAM‐co‐NHMA) went down firstly after DNQ modification and subsequently shifted to higher value after UV irradiation. Meanwhile, the phase transition profile of P(NIPAM‐co‐NHMA‐co‐DNQMA) could be triggered by pH and UV light as expected. Thus, a triple‐stimuli responsive copolymer whose solution properties could be, respectively, modulated by temperature, light, and pH, has been achieved. These stimuli‐responsive properties should be very important for controlled release delivery system. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2763–2773, 2009     

Spore Film Dosimeters Are Feasible for UV Dose Monitoring During Heliotherapy

The objective of the study was to compare Bacillus subtilis spore film dosimeters with a Robertson Berger UV meter (RB meter) and diary records for assessing personal UV-B doses during a 13-day heliotherapy (HT) for atopic dermatitis (AD). In addition, the relationship between the personal UV-B dose and change in serum 25-hydroxyvitamin D (25(OH)D) was studied. Altogether 21 adult patients with AD completed the study arranged in the Canary Islands, either in January or March 2005. The spore film dosimeters were used throughout the day during the HT. Serum 25(OH)D was analyzed using radioimmunoassay. The mean personal UV-B dose measured with the dosimeters was 75 SED in January and 131 SED in March. The respective results gained from the RB meter combined with diary records were 63 SED and 119 SED showing a close correlation with the dosimeter results. Serum 25(OH)D concentration increased by 9.7 nmol L⁻¹ in January and by 26.0 7 nmol L⁻¹ in March. The increase in serum 25(OH)D correlated with the UV-B dose received. The patients complied well to use the dosimeters. We conclude spore films to be a feasible and reliable personal UV dosimeter in vivo in field conditions.     

Polymer Gel Dosimeters with Increased Solubility: A Preliminary Investigation of the NMR and Optical Dose-Response Using Different Crosslinkers and Co-Solvents

Summary: The potential of ten different crosslinkers was investigated, with the aim of improving the performance of polymer gel dosimeters used for detecting radiation dose distributions generated by cancer radiation therapy equipment. Unfortunately, none of the candidate crosslinkers was shown to be more effective than N,N′-methylene-bisacrylamide, the standard crosslinker used in polymer gel dosimetry applications. Two co-solvents, glycerol and isopropanol, were used to increase the solubility of N,N′-methylene-bisacrylamide crosslinker in polymer gel dosimeter recipes. Using isopropanol, the crosslinker solubility increased from approximately from 3 to 10% by weight, enabling the manufacture of polymer gel dosimeters with much higher levels of crosslinking than was previously possible. The new dosimeter recipes can be imaged effectively using nuclear magnetic resonance and optical techniques, and may be suitable for read-out using x-ray CT (Computed Tomography).     

Synthesis and characterization of well‐defined diblock and triblock copolymers of poly(N‐isopropylacrylamide) and poly(ethylene oxide)

Well‐defined diblock and triblock copolymers composed of poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene oxide) (PEO) were successfully synthesized through the reversible addition–fragmentation chain transfer polymerization of N‐isopropylacrylamide (NIPAM) with PEO capped with one or two dithiobenzoyl groups as a macrotransfer agent. ¹H NMR, Fourier transform infrared, and gel permeation chromatography instruments were used to characterize the block copolymers obtained. The results showed that the diblock and triblock copolymers had well‐defined structures and narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight < 1.2), and the molecular weight of the PNIPAM block in the diblock and triblock copolymers could be controlled by the initial molar ratio of NIPAM to dithiobenzoate‐terminated PEO and the NIPAM conversion. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4873–4881, 2004     

Radiation-sensitive nanogel-incorporated Fricke hydrogel dosimeters with reduced diffusion rates

Fricke gel dosimeters have great potential for three-dimensional (3D) dose verification in radiation therapy; however, they suffer from time-dependent ion diffusion after irradiation, severely affecting their stability and reliability. In this work, a pullulan-based amphiphilic molecule was synthesized, characterized, and self-assembled into nanogels. Nanogel structures were embedded into gel dosimeters to reduce the diffusion rates, and radiation-sensitive nanogel-incorporated Fricke hydrogel nanocomposites were prepared successfully. The results demonstrated that the diffusion coefficient of improved dosimeters was reduced to 0.125 ± 0.001 mm² h⁻¹, while maintaining the high optical dose sensitivity (0.0410 ± 0.0004 Gy⁻¹ cm⁻¹). It provides a powerful tool toward the practical application of 3D dosimeters.     

Nitroxide‐mediated controlled statistical copolymerizations of N‐isopropylacrylamide with N‐tert‐butylacrylamide

The copolymerization of N‐isopropylacrylamide (NIPAM) and N‐tert‐butylacrylamide (TBAM) via conventional radical polymerization and nitroxide‐mediated polymerization (NMP) with N‐tert‐butyl‐N‐[1‐diethylphosphono‐(2,2‐dimethylpropyl)]nitroxide (SG1) was investigated. The monomer reactivity ratios were determined to be 0.58 and 1.00 for NIPAM and TBAM, respectively. The reactivities were approximately the same at 120 and 60 °C in N,N‐dimethylformamide (DMF) and toluene, respectively, for the conventional copolymerizations and in DMF at 120 °C for NMP. Controlled/living characteristics for NMP were achieved with a 2,2′‐azobisisobutyronitrile/SG1 bimolecular system and a unimolecular polystyrene [poly(STY)]–SG1 macroinitiator in the presence of excess free SG1. Block copolymers of poly(N‐isopropylacrylamide‐stat‐N‐tert‐butylacrylamide) [poly(NIPAM‐stat‐TBAM)] with styrene {poly(N‐isopropylacrylamide‐stat‐N‐tert‐butylacrylamide)‐block‐polystyrene [poly(NIPAM‐stat‐TBAM)‐block‐poly(STY)]} were obtained by chain extension of either poly(NIPAM‐stat‐TBAM)–SG1 with styrene or poly(STY)–SG1 with NIPAM/TBAM. A comparison of the number‐average molecular weight calculated from the end‐group content with the number‐average molecular weight measured by gel permeation chromatography for poly(NIPAM‐stat‐TBAM)‐block‐poly(STY)–SG1 indicated that nearly all poly(NIPAM‐stat‐TBAM) chains were capped by SG1 and were thus living. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6410–6418, 2006     

New chemical Fricke gel radiation dosimeter

Dosimetric gel is used in several measurements due to its linearity, low cost, and possibility for 3D measurements. This work brings a new possibility to apply the Fricke Xylenol Gel recipe in the diagnostic measurements region. The Fricke Xilenol Gel (FXG) dosimeter is associated with the Fe(II) to Fe(III) oxidation, when irradiated, being the final ion concentration proportional to the absorbed dose. To achieve the scope, the former dosimeter was modified through the benzoic acid addition in the original recipe forming a new dosimeter, the Benzoic Xylenol Gel (BFXG). The results obtained with this new dosimeter demonstrated a higher sensibility for low absorbed dose values, bringing down the absorbed dose inferior limit from 0.1 to 0.006 Gy, that is more adequate for radiodiagnostic absorbed dose measurements. This result shows the possibly of BFXG dosimeter to be used for measurements in the radiodiagnostic region, as for tomography and mammography techniques.