Optical and NMR dose response of N-isopropylacrylamide normoxic polymer gel for radiation therapy dosimetry

Background

Application of less toxic normoxic polymer gel of N-isopropyl acrylamide (NIPAM) for radiation therapy has been studied in recent years.

Aim

In the current study the optical and NMR properties of NIPAM were studied for radiation therapy dosimetry application.

Materials and methods

NIPAM normoxic polymer gel was prepared and irradiated by 9 MV photon beam of a medical linac. The optical absorbance was measured using a conventional laboratory spectrophotometer in different wavelengths ranging from 390 to 860 nm. R₂ measurements of NIPAM gels were performed using a 1.5 T scanner and R₂–dose curve was obtained.

Results

Our results showed R₂ dose sensitivity of 0.193 ± 0.01 s⁻¹ Gy⁻¹ for NIPAM gel. Both R₂ and optical absorbance showed a linear relationship with dose from 1.5 to 11 Gy for NIPAM gel dosimeter. Moreover, absorbance–dose response varied considerably with light wavelength and highest sensitivity was seen for the blue part of the spectrum.

Conclusion

Our results showed that both optical and NMR approaches have acceptable sensitivity and accuracy for dose determination with NIPAM gel. However, for optical reading of the gel, utilization of an optimum optical wavelength is recommended.     

Small-Field Measurements of 3D Polymer Gel Dosimeters through Optical Computed Tomography

With advances in therapeutic instruments and techniques, three-dimensional dose delivery has been widely used in radiotherapy. The verification of dose distribution in a small field becomes critical because of the obvious dose gradient within the field. The study investigates the dose distributions of various field sizes by using NIPAM polymer gel dosimeter. The dosimeter consists of 5% gelatin, 5% monomers, 3% cross linkers, and 5 mM THPC. After irradiation, a 24 to 96 hour delay was applied, and the gel dosimeters were read by a cone beam optical computed tomography (optical CT) scanner. The dose distributions measured by the NIPAM gel dosimeter were compared to the outputs of the treatment planning system using gamma evaluation. For the criteria of 3%/3 mm, the pass rates for 5 × 5, 3 × 3, 2 × 2, 1 × 1, and 0.5 × 0.5 cm² were as high as 91.7%, 90.7%, 88.2%, 74.8%, and 37.3%, respectively. For the criteria of 5%/5 mm, the gamma pass rates of the 5 × 5, 3 × 3, and 2 × 2 cm² fields were over 99%. The NIPAM gel dosimeter provides high chemical stability. With cone-beam optical CT readouts, the NIPAM polymer gel dosimeter has potential for clinical dose verification of small-field irradiation.     

A new less toxic polymer gel dosimeter: Radiological characteristics and dosimetry properties

PurposeA new polymer gel dosimeter recipe was investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomer 2-Acrylamido 2-Methyl Propane Sulfonic acid (AMPS).MethodsThe new formulation was named PAMPSGAT. The MRI response (R2) of the dosimeters was analyzed for conditions of varying dose, dose rate, and temperature during scanning. Radiological properties of the PAMPSGAT polymer gel dosimeter were investigated.ResultsThe dose-response (R2) of AMPS/Bis appears to be linear over a dose range 10–40 Gy. The percentage of difference between the R2 values for imaging at 15 °C and MRI room temperature is about 4.6% for vial with 40 Gy absorbed dose which decreased to less than 1% for imaging at 20 °C. The percentage difference of Zeff of PAMPSGAT gel and soft tissue was less than 1% in the practical energy range (100 KeV–100 MeV). The electron density of the PAMPSGAT polymer gel was 2.9% higher than that of muscle. Results showed that the sensitivity of PAMPSGAT polymer gel dosimeter irradiated by ⁶⁰Co (energy = 1.25 MeV) is about 27.7% higher than that of irradiated using a 6 MeV Linac system.ConclusionsTemperature during MRI scanning has a small effect on the R2 response of the PAMPSGAT polymer gel dosimeter. Results confirmed tissue equivalency of the PAMPSGAT polymer gel dosimeter in most practical energy range. The PAMPSGAT polymer gel dosimeter response depends on energy and dose rate.     

Normoxic polymer gel dosimetry using less toxic monomer of N-isopropyl acrylamide and X-ray computed tomography for radiation therapy applications

Background

Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry.

Aim

The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application.

Material and methods

A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with ⁶⁰Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters.

Results

The results showed the dose sensitivity of ΔN_CT (H) = 0.282 ± 0.018 (H Gy⁻¹) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kV_p and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data.

Conclusion

According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.     

γ-irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: II. Effect of Oxygen and EPR Investigation

The purpose of this research was to evaluate how the presence of oxygen can affect irradiation-induced degradation reactions of PEGd,lPLA and PEG-PLGA multiblock copolymers submitted to gamma irradiation and to investigate the radiolytic behavior of the polymers. PEGd,lPLA, PEG-PLGA, PLA, and PLGA were irradiated by using a ⁶⁰Co irradiation source in air and under vacuum at 25 kGy total dose. Mw and Mn were evaluated by gel permeation chromatography. The stability study was carried out on three samples sets: (a) polymer samples irradiated and stored in air, (b) polymer samples irradiated and stored under vacuum, and (c) polymer samples irradiated under vacuum and stored in air. The thermal and radiolytic behavior was investigated by differential scanning calorimetry and electron paramagnetic resonance (EPR), respectively. Samples irradiated in air showed remarkable Mw and Mn reduction and Tg value reduction due to radiation-induced chain scission reactions. Higher stability was observed for samples irradiated and stored under vacuum. EPR spectra showed that the presence of PEG units in multiblock copolymer chains leads to: (a) decrease of the radiolytic yield of radicals and (b) decrease of the radical trapping efficiency and faster radical decay rates. It can be concluded that the presence of oxygen during the irradiation process and the storage phase significantly increases the entity of irradiation-induced damage.     

Structural and mechanical properties of UV-photo-cross-linked poly(N-vinyl-2-pyrrolidone) hydrogels

Biocompatible poly( N-vinyl-2-pyrrolidone) (PVP) hydrogels have been produced by UV irradiation of aqueous polymer mixtures, using a high-pressure mercury lamp. The resulting materials have been characterized by a combination of experimental techniques, including rheology, small-angle neutron scattering (SANS), electron paramagnetic resonance (EPR), and pulsed gradient spin-echo nuclear magnetic resonance (PGSE-NMR), to put in evidence the relationship between the microstructural properties and the macrofunctional behavior of the gels. Viscoelastic measurements showed that UV photo-cross-linked PVP hydrogels present a strong gel mechanical behavior and viscoelastic moduli values similar to those of biological gels. The average distance between the cross-linking points of the polymer network was estimated from the hydrogels elastic modulus. However, SANS measurements showed that the network microstructure is highly inhomogeneous, presenting polymer-rich regions more densely cross-linked, surrounded by a water-rich environment. EPR and PGSE-NMR data further support the existence of these water-rich domains. Inclusion of a third component, such as glycerol, in the PVP aqueous mixture to be irradiated has been also investigated. A small amount of glycerol (<3% w/w) can be added keeping satisfactory properties of the hydrogel, while higher amounts significantly affect the cross-linking process.     

Image reconstruction of optical computed tomography by using the algebraic reconstruction technique for dose readouts of polymer gel dosimeters

Optical computed tomography (optical CT) has been proven to be a useful tool for dose readouts of polymer gel dosimeters. In this study, the algebraic reconstruction technique (ART) for image reconstruction of gel dosimeters was used to improve the image quality of optical CT. Cylindrical phantoms filled with N-isopropyl-acrylamide polymer gels were irradiated using a medical linear accelerator. A circular dose distribution and a hexagonal dose distribution were produced by applying the VMAT technique and the six-field dose delivery, respectively. The phantoms were scanned using optical CT, and the images were reconstructed using the filtered back-projection (FBP) algorithm and the ART. For the circular dose distribution, the ART successfully reduced the ring artifacts and noise in the reconstructed image. For the hexagonal dose distribution, the ART reduced the hot spots at the entrances of the beams and increased the dose uniformity in the central region. Within 50% isodose line, the gamma pass rates for the 2 mm/3% criteria for the ART and FBP were 99.2% and 88.1%, respectively. The ART could be used for the reconstruction of optical CT images to improve image quality and provide accurate dose conversion for polymer gel dosimeters.     

Effect of Composition Interactions on the Dose Response of an N-Isopropylacrylamide Gel Dosimeter

In this study, a two-level full factorial design was used to identify the effects of the interactions between compositions in an N-isopropylacrylamide (NIPAM) gel dosimeter involving the following variables: (A) gelatin, (B) NIPAM, (C) the crosslinker N, N′-methylene-bis-acrylamide (Bis), and (D) the antioxidant tetrakis (hydroxymethyl) phosphonium chloride (THPC). The dose range was from 0 Gy to 5 Gy. Optical computed tomography was used to scan the polymer gel dosimeter. Each component was set to two levels for all four variables, including (A) 4% and 6%, (B) 4% and 6%, (C) 2% and 4%, as well as (D) 5 and 15 mM. Response surface methodology and a central composite design were adopted for the quantitative investigation of the respective interaction effects on the dose response curve of the gel. The results showed that the contributions of the interaction effects, i.e., AB (6.22%), AC (8.38%), AD (7.74%), BC (9.44%), ABC (18.24%), BCD (12.66%), and ABCD (13.4%), were greater than those of the four main effects, accounting for over 76.08% of the total variability. These results also indicated that the NIPAM gel recipe with the highest sensitivity was at 40%C (mass fraction of Bis).     

Some quantitative aspects of the disc electrophoresis of ovalbumin using amido black 10B stain

The quantitative aspects of the disc electrophoretic technique were investigated using a purified protein, egg ovalbumin. Depending on the filter used, a linear relationship between peak area and protein concentration was found up to about 40 μg of protein by densitometry. Both diffusion and gel slicing studies indicated that linearity could be extended to almost 160 μg of protein. By elution of the amido black dye from the protein-dye complex in the gel, a nearly constant dye to protein ratio was indicated. These results suggested that quantitation of the stained bands on polyacrylamide gels was limited by the nonlinear response of the densitometer, perhaps due to the nonlinearity of dye absorbance at large optical densities and not by variable amounts of dye binding to the protein bands.     

Pouring and Running a Protein Gel by reusing Commercial Cassettes

The evaluation of proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is a common technique used by biochemistry and molecular biology researchers^1-4. For laboratories that perform daily analyses of proteins, the cost of commercially available polyacrylamide gels (˜$10/gel) can be considerable over time. To mitigate this cost, some researchers prepare their own polyacrylamide gels. Traditional methods of pouring these gels typically utilize specialized equipment and glass gel plates that can be expensive and preclude pouring many gels and storing them for future use. Furthermore, handling of glass plates during cleaning or gel pouring can result in accidental breakage creating a safety hazard, which may preclude their use in undergraduate laboratory classes. Our protocol demonstrates how to pour multiple protein gels simultaneously by recycling Invitrogen Nupage Novex minigel cassettes, and inexpensive materials purchased at a home improvement store. This economical and streamlined method includes a way to store the gels at 4°C for a few weeks. By re-using the plastic gel cassettes from commercially available gels, labs that run frequent protein gels can save significant costs and help the environment. In addition, plastic gel cassettes are extremely resistant to breakage, which makes them ideal for undergraduate laboratory classrooms.     

γ-Irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: I. Effect of Irradiation Doses

To evaluate the effects of different gamma irradiation doses on PEGd,lPLA and PEG-PLGA multiblock copolymers. The behaviour of the multiblock copolymers to irradiation was compared to that of PLA, PLGA polymers. PEGd,lPLA, PEG-PLGA, PLA and PLGA polymers were irradiated by using a ⁶⁰Co irradiation source at 5, 15, 25 and 50 kGy total dose. Characterization was performed on all samples before and after irradiation, by nuclear magnetic resonance (NMR), infrared absorption spectrophotometry (FTIR) and gel permeation chromatography (GPC). The effect of gamma irradiation on polymer stability was also evaluated. Results of NMR and FTIR suggest an increase in -OH and -COOH groups, attributed to scission reactions induced by irradiation treatment. Data of GPC analysis showed that the weight average molecular weight (Mw) of polymer samples decreased with increasing irradiation dose. The extent of Mw degradation expressed as percentage of Mw reduction was more prominent for polymers with high molecular weight as PEGd,lPLA and PLA. The dominant effect of gamma-irradiation on both polymer samples was chain scission. The multiblock copolymer PEGd,lPLA presented higher sensitivity to irradiation treatment with respect to PLA, likely due to the presence of PEG in the matrix. The effect of gamma irradiation continues over a much longer period of time after gamma irradiation has been performed. It is suggested that the material reacts with oxygen to form peroxyl free radicals, which may further undergo degradation reactions during storage after irradiation.     

Dosimetric characteristics of a new polymer gel and their dependence on post-preparation and post-irradiation time: Effect on X-ray beam profile measurements

The aim of this study is to dosimetrically characterize a new MRI based polymer gel system and to evaluate its usefulness in clinical practice just in terms of beam profile measurements.Normoxic N-vinylpyrrolidone based polymer gel (VIPET) phantoms were produced and used in order to perform three main sets of experiments: a) dose–response evaluation and reproducibility experiments, b) experiments for the evaluation of sensitivity of dose characteristics on ‘gel manufacture – irradiation’ time interval and c) experiments for the evaluation of sensitivity of dose characteristics on ‘irradiation – MRscanning’ time interval. It has been shown that this gel system can be used in a wide dose-range of 0–60 Gy. It exhibits a linear dose–response in the dose-range of 2–35 Gy. Following the proposed manufacturing method the dose–response characteristics are reproducible. Moreover, it seems that the optimum ‘gel manufacturing – irradiation’ time interval is 1 day. However, a ‘gel manufacturing – irradiation’ time interval up to ～1 week can be safely used. The optimum ‘irradiation – MRscanning’ time interval in terms of dose–response sensitivity and dose resolution can be reliably ranged from 1 day to 3 weeks. Finally, X-ray beam profile gel-measurements were performed and found to be in satisfying agreement with corresponding small sensitive volume ion chamber measurements. VIPET gel dosimeters preserved the spatial integrity of the dose distribution during a time period of 50 days post-irradiation. The studied gel system can be safely used in clinical practice within the practical limitations found and described in this work.     

Optical anisotropy of calcium-induced alginate gels

Alginate gels formed by diffusion of calcium ions into solutions of sodium alginate were found to exhibit optical anisotropy depending on preparation conditions. When observed under crossed nicols, the anisotropic alginate gels showed a birefringence pattern which is characteristic of radial orientation of polymer chains. Calcium alginate gels were prepared from different concentrations of sodium alginate and calcium ion, and the conditions for formation of the anisotropic gels were determined. The gel-formation process was measured by monitoring the development of the birefringent layer and was compared with the model in which the diffusion of calcium ions dominates gel formation.     

A correlation between mechanical and electrical properties of the synthetic hydrogel chosen as an experimental model of cytoskeleton

The correlation between the electrochemical (Donnan) potential and volume swelling was studied for synthetic polyelectrolyte hydrogels considered as models of cytoskeleton gel-forming biopolymers. Hydrogels involving polyacrylic and polymethacrylic acids with varying network density were synthesized by a radical polymerization in aqueous solution. Electrical charge was introduced into the gel network by partial neutralization of monomer acids with several alkali and alkali earth (hydr)oxides. The electrochemical (Donnan) potential of synthetic gels was determined using conventional microelectrode tools for cell potential determination. It was demonstrated that the negative electrical potential of many anionic gels with various charges and network densities decreased with the decrease of equilibrium swelling, i.e., with the decrease in water content in the gel. It was shown that a drastic phase transition in the gel structure from a swollen to a compressed state induced by K⁺/Ca²⁺ exchange is accompanied by an analogous decrease in the absolute Donnan potential of the gels. A kinetic study demonstrated that the gel volume changed ahead of its electrical potential. This suggests that the volume phase transition in gel is the main cause of the electrical response. A similarity between the swelling/compression transition in synthetic gels and the volume changes in the cytoskeleton in the vicinity of the cell membrane was demonstrated. Based on the universal analogy between the properties of synthetic and natural polymer gels, a possible involvement of swelling of the gel-like cytoskeleton structures in electrical regulation in the cell was postulated.     

Dewatering of biological slurry by using water-absorbent polymer gel

A new concentrating/dewatering process utilizing water-absorbent polymer gels as dewatering media for biological slurries is proposed. The polymer gel applied to the process should be of porous structure for rapid water-absorption and of larger size for easier separation of gel from slurry. Poly(vinylmethylether) gel (PVMEG) prepared by gamma-ray irradiation was found to be suitable for the purpose. PVMEG swelled or shrunk reversibly in response to temperature and its transition temperature was 310K. Slurries of different properties were dewatered quite well by applying PVMEG. The water-absorbability of the gel was unaffected by the properties of organic substances contained in the slurries. An engineering calculation of the proposed dewatering process, which was called "gel dewatering process," revealed that the process was promising for concentrating/dewatering microbe-rich slurries in the respect that it would be composed of compact and simple apparatuses and be an energy saving system.     

Synthesis of antibacterial PVA/CM-chitosan blend hydrogels with electron beam irradiation

A series of excellent hydrogels were prepared from poly(vinyl alcohol) (PVA) and carboxymethylated chitosan (CM-chitosan) with electron beam irradiation (EB) at room temperature. Electron spectroscopy analysis of the blend hydrogels revealed that good miscibility was sustained between CM-chitosan and PVA. The properties of the prepared hydrogels, such as the mechanical properties, gel fraction and swelling behavior were investigated. The mechanical properties and equilibrium degree of swelling improved obviously after adding CM-chitosan into PVA hydrogels. The gel fraction determined gravimetrically showed that a part of CM-chitosan was immobilized onto PVA hydrogel. The further analyses of FTIR and DSC spectra of the prepared gels after extracting sol manifested that there was a grafting interaction between PVA and CM-chitosan molecules under irradiation. The antibacterial activity of the hydrogels against Escherichia coli was also measured via optical density method. The blend hydrogels exhibited satisfying antibacterial activity against E. coli, even when the CM-chitosan concentration was only 3 wt%.     

Dose-response of Fricke- and PAGAT-dosimetry gels in kilovoltage and megavoltage photon beams: Impact of LET on sensitivity

Purpose: Dosimetry of ionizing radiation quantifies the energy deposited by an incident beam to the medium. This study presents the relative response of two types of gel dosimeters describing their differences by estimating radiation chemical yields produced in water radiolysis.Methods: Two types of gel dosimeter were used, namely an acid ferrous ion solution infused with xylenol orange known as Fricke gel and a polymer gel based on acrylamide and N,N’-methylenebis(acrylamide) known as PAGAT. Samples were irradiated using two photon beam energies, one from a conventional X-ray tube operated at 44 kV and the other one from a LINAC operated at 6 MV. The dosimeters were analyzed by optical absorbance and magnetic resonance imaging. Additionally, the linear energy transfer of each beam was calculated using Monte Carlo simulations for further estimation of the radiation chemical yields produced during water radiolysis.Results: Obtained results for both gel dosimeters indicate that their response at 44 kV and 6 MV are different, regardless of the read-out technique. On average, the sensitivity at 44 kV was found to be 65 % of the response at 6 MV. The calculated radiation chemical yields are in agreement with the observed experimental results.Conclusions: The main reason for the difference in the response of the dosimeters may be related to the linear energy transfer of each photon beam, which varies the production of primary chemical species during water radiolysis.     

Polymer gel dosimeters for pretreatment radiotherapy verification using the three-dimensional gamma evaluation and pass rate maps

Polymer gel dosimeters (PGDs) have been widely studied for use in the pretreatment verification of clinical radiation therapy. However, the readability of PGDs in three-dimensional (3D) dosimetry remain unclear. In this study, the pretreatment verifications of clinical radiation therapy were performed using an N-isopropyl-acrylamide (NIPAM) PGD, and the results were used to evaluate the performance of the NIPAM PGD on 3D dose measurement. A gel phantom was used to measure the dose distribution of a clinical case of intensity-modulated radiation therapy. Magnetic resonance imaging scans were performed for dose readouts. The measured dose volumes were compared with the planned dose volume. The relative volume histograms showed that relative volumes with a negative percent dose difference decreased as time elapsed. Furthermore, the histograms revealed few changes after 24 h postirradiation. For the 3%/3 mm and 2%/2 mm criteria, the pass rates of the 12- and 24-h dose volumes were higher than 95%, respectively. This study thus concludes that the pass rate map can be used to evaluate the dose-temporal readability of PGDs and that the NIPAM PGD can be used for clinical pretreatment verifications.     

A Novel Method of Estimating Dose Responses for Polymer Gels Using Texture Analysis of Scanning Electron Microscopy Images

Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM) images. The modified N-isopropyl-acrylamide (NIPAM) gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM). The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R ² value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were −7.60%, 5.80%, 2.53%, and −0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.