Direct response to proton beam linear energy transfer (LET) in a novel polymer gel dosimeter formulation.

Linear energy transfer (LET) of clinical proton beams is an important parameter influencing the biological effects of radiation. This work demonstrates LET-induced response enhancement in novel formulations of polymer gel dosimeters, potentially useful for LET mapping of clinical proton beams. A series of four polymer gel dosimeters (labeled A through D), prepared based on the BANG3-Pro2 formulation, but with varying concentrations of polymerization modifiers, were irradiated by a clinical proton beam with a spread out Bragg peak modulation (SOBP) and read out using the OCTOPUS-IQ optical CT scanner. The evaluation of optical density profiles in the SOBP (constant physical dose) revealed response deviations at the distal end consistent with variations in gel composition. Maximum response deviations were as follows: -3% (under-response) for gel A, and over-response of 2%, 12%, and 17% for gels B, C, and D, respectively, relative to the mean dose in the center of the SOBP. This enhancement in optical response was correlated to LET by analytical calculations. Gels A and B showed no measurable dependence on LET. Gel C responded linearly in the limited range from 1.5 to 3.5 keV/µm. LET response of gel D was linear up to at least 5.5 keV/µm, with the threshold at about 1.3 keV/µm. These results suggest that it may be possible to develop a polymer gel system with direct optical response to LET for mapping of LET distributions for particle therapy beams.

Dosimetric evaluation of a novel polymer gel dosimeter for proton therapy.

PURPOSE: The aim of this study is to evaluate the dosimetric performance of a newly developed proton-sensitive polymer gel formulation for proton therapy dosimetry. METHODS: Using passive scattered modulated and nonmodulated proton beams, the dose response of the gel was assessed. A next-generation optical CT scanner is used as the readout mechanism of the radiation-induced absorbance in the gel medium. Comparison of relative dose profiles in the gel to ion chamber profiles in water is performed. A simple and easily reproducible calibration protocol is established for routine gel batch calibrations. Relative stopping power ratio measurement of the gel medium was performed to ensure accurate water-equivalent depth dose scaling. Measured dose distributions in the gel were compared to treatment planning system for benchmark irradiations and quality of agreement is assessed using clinically relevant gamma index criteria. RESULTS: The dosimetric response of the gel was mapped up to 600 cGy using an electron-based calibration technique. Excellent dosimetric agreement is observed between ion chamber data and gel. The most notable result of this work is the fact that this gel has no observed dose quenching in the Bragg peak region. Quantitative dose distribution comparisons to treatment planning system calculations show that most (> 97%) of the gel dose maps pass the 3%/3 mm gamma criterion. CONCLUSIONS: This study shows that the new proton-sensitive gel dosimeter is capable of reproducing ion chamber dose data for modulated and nonmodulated Bragg peak beams with different clinical beam energies. The findings suggest that the gel dosimeter can be used as QA tool for millimeter range verification of proton beam deliveries in the dosimeter medium.

Characteristics of a new polymer gel for high-dose gradient dosimetry using a micro optical CT scanner.

The properties of a new polymer gel with two sensitivities, made specifically for high-dose-gradient dosimetry, were investigated. The measurements were performed at NIST using a 1cmx1cm calibrated (60)Co field, and a 1cm active diameter (90)Sr/(90)Y beta particle source. A high-resolution laser CT scanner was used to quantify the response. The results show that the high-sensitivity gel responds linearly to the absorbed dose for doses from 0.5 up to 15Gy, while the low-sensitivity one is linear up to 225Gy. For both radiation types, the gel response remains stable in time up to a month after the irradiation. The response of the gel was found to have no dose rate dependence for dose rates ranging from 3.7 to 15mGy/s. Within the measurement uncertainty, the gel response is more sensitive for beta particles than high energy photons.

The use of gel dosimetry to measure the 3D dose distribution of a 90Sr/90Y intravascular brachytherapy seed.

Absorbed dose distributions in 3D imparted by a single (90)Sr/(90)Y beta particle seed source of the type used for intravascular brachytherapy were investigated. A polymer gel dosimetry medium was used as a dosemeter and phantom, while a special high-resolution laser CT scanner with a spatial resolution of 100 microm in all dimensions was used to quantify the data. We have measured the radial dose function, g(L)(r), observing that g(L)(r) increases to a maximum value and then decreases as the distance from the seed increases. This is in good agreement with previous data obtained with radiochromic film and thermoluminescent dosemeters (TLDs), even if the TLDs underestimate the dose at distances very close to the seed. Contrary to the measurements, g(L)(r) calculated through Monte Carlo simulations and reported previously steadily decreases without a local maximum as a function of the distance from the seed. At distances less than 1.5 mm, differences of more than 20% are observed between the measurements and the Monte Carlo calculations. This difference could be due to a possible underestimation of the energy absorbed into the seed core and encapsulation in the Monte Carlo simulation, as a consequence of the unknown precise chemical composition of the core and its respective density for this seed. The results suggest that g(L)(r) can be measured very close to the seed with a relative uncertainty of about 1% to 2%. The dose distribution is isotropic only at distances greater than or equal to 2 mm from the seed and is almost symmetric, independent of the depth. This study indicates that polymer gel coupled with the special small format laser CT scanner are valid and accurate methods for measuring the dose distribution at distances close to an intravascular brachytherapy seed.

Performance evaluation of an improved optical computed tomography polymer gel dosimeter system for 3D dose verification of static and dynamic phantom deliveries.

The performance of a next-generation optical computed tomography scanner (OCTOPUS-5X) is characterized in the context of three-dimensional gel dosimetry. Large-volume (2.2 L), muscle-equivalent, radiation-sensitive polymer gel dosimeters (BANG-3) were used. Improvements in scanner design leading to shorter acquisition times are discussed. The spatial resolution, detectable absorbance range, and reproducibility are assessed. An efficient method for calibrating gel dosimeters using the depth-dose relationship is applied, with photon- and electron-based deliveries yielding equivalent results. A procedure involving a preirradiation scan was used to reduce the edge artifacts in reconstructed images, thereby increasing the useful cross-sectional area of the dosimeter by nearly a factor of 2. Dose distributions derived from optical density measurements using the calibration coefficient show good agreement with the treatment planning system simulations and radiographic film measurements. The feasibility of use for motion (four-dimensional) dosimetry is demonstrated on an example comparing dose distributions from static and dynamic delivery of a single-field photon plan. The capability to visualize three-dimensional dose distributions is also illustrated.

Characterisation of PRESAGE: A new 3-D radiochromic solid polymer dosemeter for ionising radiation.

For the past 50 years there has been interest in developing 3-D dosemeters for ionising radiation. Particular emphasis has been put on those dosemeters that change their optical properties in proportion to the absorbed dose. Many of the dosemeters that have been evaluated have had limitations such as lack of transparency, diffusion of the image of the dose distribution or poor stability of baseline optical density. Many of these performance limitations have been overcome by the development of PRESAGE, an optically clear polyurethane-based radiochromic 3-D dosemeter. The solid PRESAGE dosemeter is formulated with a free radical initiator and a leuco dye and it does not require a container to maintain its shape. The polyurethane matrix is tissue equivalent and prevents the diffusion of the dose distribution image. There is a linear dose-response, which is independent of both photon energy and dose rate. Simple precautions such as preventing long-term exposure to additional ionising radiation including ultraviolet and controlling storage temperatures prevent the bleaching of the radiochromic response field within the irradiated dosemeter.

Image registration of BANG gel dose maps for quantitative dosimetry verification.

BACKGROUND: The BANG (product symbol SGEL, MGS Research Inc., Guilford, CT) polymer gel has been shown to be a valuable dosimeter for determining three-dimensional (3D) dose distributions. Because the proton relaxation rate (R2) of the gel changes as a function of absorbed dose, MR scans of the irradiated gel can be used to generate 3D dose maps. Previous work with the gel, however, has not relied on precise localization of the measured dose distribution. This has limited its quantitative use, as no precise correlation exists with the planned distribution. This paper reports on a technique for providing this correlation, thus providing a quality assurance tool that includes all of the steps of imaging, treatment planning, dose calculation, and treatment localization. METHODS AND MATERIALS: The BANG gel formulation was prepared and poured into spherical flasks (15.3-cm inner diameter). A stereotactic head ring was attached to each flask. Three magnetic resonance imaging (MRI) and computed tomography (CT) compatible fiducial markers were placed on the flask, thus defining the central axial plane. A high-resolution CT scan was obtained of each flask. These images were transferred to a radiosurgery treatment-planning program, where treatment plans were developed. The gels were irradiated using our systems for stereotactic radiosurgery or fractionated stereotactic radiotherapy. The gels were MR imaged, and a relative 3D dose map was created from an R2 map of these images. The dose maps were transferred to an image-correlation program, and then fused to the treatment-planning CT scan through a rigid body match of the MRI/CT-compatible fiducial markers. The fused dose maps were imported into the treatment-planning system for quantitative comparison with the calculated treatment plans. RESULTS: Calculated and measured isodose surfaces agreed to within 2 mm at the worst points within the in-plane dose distributions. This agreement is excellent, considering that the pixel resolution of the MRI dose maps is 1.56 x 1.56 mm, and the treatment-planning dose distributions were calculated on a 1-mm dose grid. All points within the dose distribution were well within the tolerances set forth for commissioning and quality assurance of stereotactic treatment-planning systems. Moreover, the quantitative evaluation presented here tests the accuracy of the entire treatment-planning and delivery process, including stereotactic frame rigidity, CT localization, CT/MR correlation, dose calculation, and radiation delivery. CONCLUSION: BANG polymer gel dosimetry coupled with image correlation provides quantitative verification of the accuracy of 3D dose distributions. Such quantitative evaluation is imperative to ensure the high quality of the 3D dose distributions generated and delivered by stereotactic and other conformal irradiation systems.

The role of specific side groups and pH in magnetization transfer in polymers.

The nature of water-macromolecule interactions in aqueous model polymers has been investigated using quantitative measurements of magnetization transfer. Cross-linked polymer gels composed of 94% water, 3% N,N'-methylene-bis-acrylamide, and 3% functional monomer (acrylamide, methacrylamide, acrylic acid, methacrylic acid, 2-hydroxyethyl-acrylate, or 2-hydroxyethyl-methacrylate) were studied. Water-macromolecule interactions were modified by varying the pH and specific functional group on the monomer. The magnitudes of the interactions were quantified by measuring the rate of proton nuclear spin magnetization exchange between the polymer matrix and the water. This rate was highly sensitive to the presence of carboxyl side groups on the macromolecule. However, the dependence of the rate on pH was not consistent with simple acid/base-catalyzed chemical exchange, and instead, the data suggest that multiequilibria proton exchange, a wide distribution in surface group pK values, and/or a macromolecular structural dependence on pH may play a significant role in magnetization transfer in polymer systems. These model polymer gels afford useful insights into the relevance of chemical composition and chemical dynamics on relaxation in tissues.

Test objects for MRI quality assurance based on polymer gels.

Radiation-sensitive polymer gels have been adapted for making test objects that can be used to assess the imaging characteristics of magnetic resonance imaging (MRI) systems. The polymer gels contain acrylic monomers within a gel matrix, and when irradiated with x rays the constituents polymerize to produce highly cross-linked microparticles that dramatically affect water NMR relaxation rates where they form. The size of these effects depends on the radiation dose and composition of the mixture irradiated, while the spatial pattern of relaxation time changes can be precisely controlled by spatial modulation of the x-ray exposure. This permits the manufacture of complex test patterns free of susceptibility or edge effects, and overall image performance can be assessed by constructing contrast-detail diagrams using a singly irradiated gel containing areas of different sizes and contrasts. Polymer gels are stable and a variety of different tests objects can be constructed inexpensively. Such materials and test phantoms may find widespread application in diagnostic MRI quality assurance and testing programs.

Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of BANG polymer gel dosimeters.

PURPOSE/OBJECTIVE: The measurement of complex dose distributions (those created by irradiation through multiple beams, multiple sources, or multiple source dwell positions) requires a dosimeter that can integrate the dose during a complete treatment. Integrating dosimeter devices generally are capable of measuring only dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing use of conformal dose distributions requiring shaped, noncoplanar beams, there will be an increased requirement for a dosimeter that can record and display a 3D dose distribution. The use of a 3D dosimeter will be required to confirm the accuracy of treatment plans produced by the current generation of 3D treatment-planning computers. METHODS AND MATERIALS: The use of a Fricke-infused gel and magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic beams has been demonstrated (11). The recently developed BANG polymer gel dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel, surpasses the Fricke-gel method by providing accurate, quantitative dose distribution data that do not deteriorate with time (6, 9). The improved BANG2 formulation contains 3% N,N'-methylene-bisacrylamide, 3% acrylic acid, 1% sodium hydroxide, 5% gelatin, and 88% water, where all percentages are by weight. The gel was poured into volumetric flasks, of dimensions comparable to a human head. The gels were irradiated with complex beam arrangements, similar to those used for conformal radiation therapy. Images of the gels were acquired using a Siemens 1.5T imager and a Hahn spin-echo pulse sequence (90 degrees-tau-180 degrees-tau-acquire, for different values of tau). The images were transferred via network to a Macintosh computer for which a data analysis and display program was written. The program calculates R2 maps on the basis of multiple TE images, using a monoexponential nonlinear least-squares fit based on the Levenberg-Marquardt algorithm. The program also creates a dose-to-R2 calibration function by fitting a polynomial to a set of dose and R2 data points, obtained from gels irradiated in test tubes to known doses. This function can then be applied to any other R2 map, so that a dose map can be computed and displayed. RESULTS: Through exposure to known doses of radiation, the gel has been shown to respond linearly with dose in the range of 0 to 10 Gy, and its response is independent of the beam energy or modality. Dose distributions have been imaged in orthogonal planes, and can be displayed in a convenient form for comparison with isodose plans. The response of the gel is stable; the gel can be irradiated at any time after its manufacture, and imaging can be conducted any time following a brief interval after irradiation. CONCLUSION: The polymer gel dosimeter has been shown to be a valuable device for displaying three-dimensional dose distributions. The imaged dose distribution can be compared easily with calculated dose distributions, to validate a treatment planning system. In the future, gels may be prepared in anthropomorphic phantoms, to confirm unique patient dose distributions.

Effects of crosslinking and temperature on the dose response of a BANG polymer gel dosimeter.

The effects of varying the weight fraction (%C) of the crosslinker N, N'-methylene-bisacrylamide (bis) per total amount of monomer (6% w/w), and the NMR measurement temperature, on the dose response of the transverse relaxation rate (R2) of bis-acrylamide-nitrogen-gelatin (BANG) aqueous polymer gel dosimeters have been investigated. The gel samples were irradiated in test tubes with 250 kV x-rays, and the water proton NMR transverse relaxation rates were measured at 0.47 T using a Carr-Purcell-Meiboom-Gill multiecho pulse sequence. Both the dose sensitivity (slope of the linear portion of an R2-dose response) and the maximum rate at which the R2-dose response saturated (R2max), were found to depend strongly on the crosslinker fraction and on the temperature of the R2 measurement. The dose sensitivity peaked at approximately 50% C, and, for this composition, varied from 0.14 s-1 Gy-1 at 40 degrees C to 0.48 s-1 Gy-1 at 10 degrees C. The maximum transverse relaxation rates ranged from 0.8 s-1 at 33% C and 40 degrees C to 11.8 s-1 at 83% C and 5 degrees C. These results suggest that water proton transverse relaxation in the gel is controlled by an exchange of magnetization between the aqueous phase and the semi-solid protons associated with the polymer, and that the latter experience spectral broadening from immobilization which increases with crosslinking or cooling. Theoretical and practical implications of the above findings are discussed in the paper.

Radiation dose distributions in three dimensions from tomographic optical density scanning of polymer gels: II. Optical properties of the BANG polymer gel.

A newly developed method of radiation dosimetry makes use of the optical properties of polymer gels. The dose-response mechanism relies on the production of light-scattering polymer micro-particles in the gel at each site of radiation absorption. The scattering produces an attenuation of transmitted light intensity that is directly related to the dose and independent of dose rate. For the BANG polymer gel (bis, acrylamide, nitrogen, and gelatin) the shape of the dose-response curve depends on the fraction of the cross-linking monomer in the initial mixture and on the wavelength of light. At 500 nm the attenuation coefficient (mu) increases by approximately 0.7 mm-1 when the dose increases from 0 to 5 Gy. The refractive index of an irradiated gel shows no significant dispersion in the visible region and depends only slightly on the dose. Turbidity difference spectra are compared with theoretical spectra of efficiency factors for total scattering, derived using Mie-Debye theory, and the average sizes of the cross-linked particles produced by radiation, as a function of dose, are established. The particle sizes increase with dose and reach approximately the wavelength of red light. The dependence of the particle sizes on cross-linker fraction parallels a similar dependence of the water proton NMR transverse relaxation rate dose response.

Radiation dose distributions in three dimensions from tomographic optical density scanning of polymer gels: I. Development of an optical scanner.

A new method of dosimetry of ionizing radiations has been developed that makes use of tissue-equivalent polymer gels which are capable of recording three-dimensional dose distributions. The dosimetric data stored within the gels are measured using optical tomographic densitometry. The dose-response mechanism relies on the production of light scattering microparticles which result from the polymerization of acrylic comonomers dispersed in the gel. The attenuation of a collimated light beam caused by scattering in the irradiated optically turbid medium is directly related to the radiation dose over the range 0-10 Gy. An optical scanner has been developed which incorporates an He-Ne laser, photodiode detectors, and a rotating gel platform. Using mirrors mounted on a translating stage, the laser beam scans across the gel between each incremental rotation of the platform. Using the set of optical density projections obtained, a cross sectional image of the radiation field is then reconstructed. Doses in the range 0-10 Gy can be measured to better than 5% accuracy with a spatial resolution approximately 2 mm using the current prototype scanner. This method can be used for the determination of three-dimensional dose distributions in irradiated gels, including measurements of the complex distributions produced by multi-leaf collimators, dynamic wedge and stereotactic treatments, and for quality assurance procedures.

Radiation therapy dosimetry using magnetic resonance imaging of polymer gels.

Further progress in the development of polymer gel dosimetry using MRI is reported, together with examples of its application to verify treatment plans for stereotactic radiosurgery and high dose rate brachytherapy. The dose distribution image produced in the tissue-equivalent gel by radiation-induced polymerization, and encoded in the spatial distribution of the NMR transverse relaxation rates (R2) of the water protons in the gel, is permanent. Maps of R2 are constructed from magnetic resonance imaging data and serve as a template for dose maps, which can be used to verify complex dose distributions from external sources or brachytherapy applicators. The integrating, three-dimensional, tissue-equivalent characteristics of polymer gels make it possible to obtain dose distributions not readily measured by conventional methods. An improved gel formulation (BANG-2) has a linear dose response that is independent of energy and dose rate for the situations studied to date. There is excellent agreement between the dose distributions predicted using treatment planning calculations and those measured using the gel method, and the clinical practical utility of MRI-based polymer gel dosimetry is thereby demonstrated.

The effects of cross-link density and chemical exchange on magnetization transfer in polyacrylamide gels.

The effects of polymer structure and water-macromolecule interactions on proton relaxation in an aqueous model polymer have been investigated using quantitative measurements of magnetization transfer. Polyacrylamide gels composed of 95% water, 5% comonomers acrylamide and N,N'-methylene-bis-acrylamide were studied. The structure and rigidity were varied by changing the cross-linking density of the polymer. The polymer showed a biphasic change in transverse relaxation with increasing cross-linking density which was accompanied by a sudden increase in magnetization transfer above 40% cross linking. This change may be attributed to the formation of rigid domains in the polymer which exhibit solid-like behavior with a short T2 (11 microseconds) and a Gaussian lineshape. Water-macromolecule interactions were controlled by varying the pH of the gel. At high pH (> 8), there was an increase in magnetization transfer and transverse relaxivity consistent with a chemical-exchange-mediated interaction between water protons and the polymer. By analyzing the system as two proton reservoirs coupled by magnetization exchange, the proton populations, intrinsic relaxation rates, and exchange rates were estimated, for different degrees of cross linking and pH. This model affords useful insights into the relevance of both supramolecular structure and chemical exchange on relaxation in tissues.

Magnetic resonance imaging of radiation dose distributions using a polymer-gel dosimeter.

A new formulation of a tissue-equivalent polymer-gel dosimeter for the measurement of three-dimensional dose distributions of ionizing radiation has been developed. It is composed of aqueous gelatin infused with acrylamide and N, N'-methylene-bisacrylamide monomers, and made hypoxic by nitrogen saturation. Irradiation of the gel, referred to as BANG, causes localized polymerization of the monomers, which, in turn, reduces the transverse NMR relaxation times of water protons. The dose dependence of the NMR transverse relaxation rate, R2, is reproducible (less than 2% variation) and is linear up to about 8 Gy, with a slope of 0.25 s(-1)Gy(-1) at 1.5 T. Magnetic resonance imaging may be used to obtain accurate three-dimensional dose distributions with high spatial resolution. Since the radiation-induced polymers do not diffuse through the gelatin matrix, the dose distributions recorded by BANG gels are stable for long periods of time, and may be used to measure low-activity radioactive sources. Since the light-scattering properties of the polymerized regions are different from those of the clear, non-irradiated regions, the dose distributions are visible, and their optical densities are dependent on dose.

Assessment of the accuracy of stereotactic radiosurgery using Fricke-infused gels and MRI.

The treatment plans for stereotactic radiosurgery employ small, circular, noncoplanar fields applied in a series of arcs, or with synchronous rotation of the accelerator gantry and patient support assembly. Primary or metastatic brain tumors and arterial-venous malformations are localized in relation to a stereotactic head frame using CT, MRI, and angiography. As x-ray doses in the range of 20-40 Gy are delivered in a single treatment, it is critical that the dose distribution produced by the accelerator accurately reflect the one developed by the treatment planning computer. Until the advent of Fricke-infused gels, whose NMR characteristics are changed by irradiation, there was no practical method for assessing the accuracy of x-ray beam positioning on a target that was localized by both CT and MRI. A stereotactic head frame was attached to a hollow glass head filled with a Fricke-infused gel. A 2-mm target point at approximately the center of this manikin was localized by CT and MRI. The head frame was then mounted to the patient support assembly of a linear accelerator, and given a dose of 40 Gy to the isocenter from 6-MV x rays using a modified version of the dynamic stereotactic radiosurgery plan developed in Montreal. Subsequent MRI showed the target point at the center of the dose distribution, thus confirming the accuracy of the stereotactic radiosurgery procedure. This demonstrated the unique characteristics of the Fricke-infused gel for the simultaneous localization of x-ray beams in three dimensions.

NMR relaxation enhancement in gels polymerized and cross-linked by ionizing radiation: a new approach to 3D dosimetry by MRI.

A new type of tissue-equivalent medium for magnetic resonance imaging of the dose distributions produced by ionizing radiation has been developed. Agarose gel is infused with acrylamide and N,N'-methylene-bis-acrylamide (Bis) comonomers, which are readily polymerized by free radical initiators in de-aerated aqueous solutions. Polymerization and cross-linking induced locally by free radical products of water radiolysis increase the rate of water proton spin relaxation gradually up to doses of about 15 Gy. The slopes of the dose-response curves at 64 MHz are 0.015 and 0.28 s-1 Gy-1 for R1 and R2, respectively. The agarose matrix as well as the high (50% by weight) relative concentration of the cross-linker (Bis) per total comonomer limit the spread of polymerization so that the spatial distribution of the radiation dose is faithfully represented in the resultant spatial distribution of relaxation rates. The gel can be imaged with conventional magnetic resonance imaging devices with high spatial resolution and accuracy. In addition, due to the well established effect of the precipitation of insoluble agglomerates of highly cross-linked acrylamide, the optical turbidity of the gel increases gradually with the absorbed dose. This may provide an additional means of visualizing the dose distribution in three dimensions. The major advantage of the acrylamide-Bis-agarose gels over those that depend on ionic chemical dosimeters, for example, Fricke-infused gels, lies in the lack of diffusion of radiation-induced chemical changes subsequent to or concurrent with irradiation.