Commissioning of a solid tank design for fan-beam optical CT based 3D radiation dosimetry.

Objective.Optical computed tomography (CT) is one of the leading modalities for imaging gel dosimeters used in the verification of complex radiotherapy treatments. In previous work, a novel fan-beam optical CT scanner design was proposed that could significantly reduce the volume of the refractive index baths that are commonly found in optical CT systems. Here, the proposed scanner has been manufactured and commissioned.Approach.Image reconstruction is performed through algebraic reconstruction technique and iterated using the fast iterative shrinkage-thresholding algorithm (FISTA) algorithm. Ray tracing for algebraic reconstruction was performed using an in-house developed ray tracing simulator. A set of Sylgard® 184 phantoms were created to commission spatial resolution, geometric deformity, contrast-to-noise ratio (CNR), and scan settings.Main Results.The scanner is capable of a 0.929 mm-1spatial resolution, observed at 200 iterations, although the spatial resolution is highly dependent on the number of iterations. The geometric distortion, measured by scanning a needle phantom with the prototype scanner as well as a conventional x-ray CT was found to be within <0.25 mm. The CNR was found to peak between 65 and 190 occurring between 50 and 100 iterations and was highly dependent on the region chosen for background noise calculation. The proposed scanner is capable of scanning and reading out slices in less than 1 min per slice.Significance.This work displays the viability of a fan-beam optical CT scanner with minimal index matching using ray-traced algebraic reconstruction.

Linac-integrated kV-cone beam CT polymer gel dosimetry.

X-ray CT polymer gel dosimetry (PGD) remains a promising tool for three dimensional verification of high-dose treatment deliveries such as non-coplanar stereotactic irradiations. Recent demonstrations have shown a proof-of-principle application of linac-integrated cone beam CT-imaged (LI-CBCT) PGDs for 3D dose verification. LI-CBCT offers advantages over previous CT based PGD, including close to real-time imaging of the irradiated dosimeter, as well as the ability to maintain the dosimeter in the same physical location for irradiation and imaging, thereby eliminating spatial errors due to dosimeter re-positioning for read-out that may occur for other systems. However the dosimetric characteristics of a LI-CBCT PGD system remain to be established. The work herein determines the dosimetric properties and critical parameters needed to perform cone beam PGD. In particular, we show that imaging the dosimeter 20-30 min post irradiation offers excellent recovery of maximum polymerization yield ([Formula: see text]90%), averaging with as few as 10 image averages can provide ∼90% gamma pass rates (3%, 3 mm) as compared to treatment planning, and that eliminating outlier averaging points can improve the precision and signal to noise ratio of resultant images. In summary, with appropriate methodology LI-CBCT PGD can provide dosimetric data capable of verification of complex high dose radiation deliveries in three dimensions and may find use in commissioning and validation of novel complex treatments.

Optimization of solid tank design for fan-beam optical CT based 3D radiation dosimetry.

Optical computed tomography (CT) is one of the leading modalities for imaging gel dosimeters for 3D radiation dosimetry. There exist multiple scanner designs that have showcased excellent 3D dose verification capabilities of optical CT gel dosimetry. However, due to multiple experimental and reconstruction based factors there is currently no single scanner that has become a preferred standard. A significant challenge with setup and maintenance can be attributed to maintaining a large refractive index bath (1-15 l). In this work, a prototype solid 'tank' optical CT scanner is proposed that minimizes the volume of refractive index bath to between 10 and 35 ml. A ray-path simulator was created to optimize the design such that the solid tank geometry maximizes light collection across the detector array, maximizes the volume of the dosimeter scanned, and maximizes the collected signal dynamic range. An objective function was created to score possible geometries, and was optimized to find a local maximum geometry score from a set of possible design parameters. The design parameters optimized include the block length x bl , bore position x bc , fan-laser position x lp , lens block face semi-major axis length x ma , and the lens block face eccentricity x be . For the proposed design it was found that each of these parameters can have a significant effect on the signal collection efficacy within the scanner. Simulations scores are specific to the attenuation characteristics and refractive index of a simulated dosimeter. It was found that for a FlexyDos3D dosimeter, the ideal values for each of the five variables were: x bl = 314 mm, x bc = 6.5 mm, x lp = 50 mm, x ma = 66 mm, and x be = 0. In addition, a ClearView™ dosimeter was found to have ideal values at: x bl = 204 mm, x bc = 13 mm, x lp = 58 mm, x ma = 69 mm, and x be = 0. The ray simulator can also be used for further design and testing of new, unique and purpose-built optical CT geometries.

Evaluation of an x-ray CT polymer gel dosimetry system in the measurement of deformed dose.

This study is an evaluation of the use of a N-isopropylacrylamide (NIPAM)-based x-ray CT polymer gel dosimetry (PGD) system in the measurement of deformed dose. This work also compares dose that is measured by the gel dosimetry system to dose calculated by a novel deformable dose accumulation algorithm, defDOSXYZnrc, that uses direct voxel tracking. Deformable gels were first irradiated using a single 3.5 × 5 cm2 open field and the static dose was compared to defDOSXYZnrc as a control measurement. Gel measurement was found to be in excellent agreement with defDOSXYZnrc in the static case with gamma passing rates of 94.5% using a 3%/3 mm criterion and 93.3% using a 3%/2 mm criterion. Following the static measurements, a deformable gel was irradiated with the same single field under an external compression of 25 mm and then released from this compression for dosimetric read out. The measured deformed dose was then compared to deformed dose calculated by defDOSXYZnrc based on deformation vectors produced by the Velocity AI deformable image registration (DIR) algorithm. In the deformed dose distribution there were differences in the measured and calculated field position of up to 0.8 mm and differences in the measured in calculated field size of up to 11.9 mm. Gamma pass rates were 60.0% using a 3%/3 mm criterion and 56.8% using a 3%/2 mm criterion for the deforming measurements representing a decrease in agreement compared to the control measurements. Further analysis showed that passing rates increased to 86.5% using a 3%/3 mm criterion and 70.5% using a 3%/2 mm criterion in voxels within 5 mm of fiducial markers used to guide the deformable image registration. This work represents the first measurement of deformed dose using x-ray CT polymer gel dosimetry. Overall these results highlight some of the challenges in the calculation and measurement of deforming dose and provide insight into possible strategies for improvement.

Introduction of a deformable x-ray CT polymer gel dosimetry system.

This study introduces the first 3D deformable dosimetry system based on x-ray computed tomography (CT) polymer gel dosimetry and establishes the setup reproducibility, deformation characteristics and dose response of the system. A N-isopropylacrylamide (NIPAM)-based gel formulation optimized for x-ray CT gel dosimetry was used, with a latex balloon serving as the deformable container and low-density polyethylene and polyvinyl alcohol providing additional oxygen barrier. Deformable gels were irradiated with a 6 MV calibration pattern to determine dosimetric response and a dosimetrically uniform plan to determine the spatial uniformity of the response. Wax beads were added to each gel as fiducial markers to track the deformation and setup of the gel dosimeters. From positions of the beads on CT images the setup reproducibility and the limits and reproducibility of gel deformation were determined. Comparison of gel measurements with Monte Carlo dose calculations found excellent dosimetric accuracy, comparable to that of an established non-deformable dosimetry system, with a mean dose discrepancy of 1.5% in the low-dose gradient region and a gamma pass rate of 97.9% using a 3%/3 mm criterion. The deformable dosimeter also showed good overall spatial dose uniformity throughout the dosimeter with some discrepancies within 20 mm of the edge of the container. Tracking of the beads within the dosimeter found that sub-millimetre setup accuracy is achievable with this system. The dosimeter was able to deform and relax when externally compressed by up to 30 mm without sustaining any permanent damage. Internal deformations in 3D produced average marker movements of up to 12 mm along the direction of compression. These deformations were also shown to be reproducible over 100 consecutive deformations. This work has established several important characteristics of a new deformable dosimetry system which shows promise for future clinical applications, including the validation of deformable dose accumulation algorithms.

Plasmonic labeling of subcellular compartments in cancer cells: multiplexing with fine-tuned gold and silver nanoshells.

Fine-tuned gold and silver nanoshells were produced via an entirely reformulated synthesis. The new method yielded ultramonodisperse samples, with polydispersity indexes (PI) as low as 0.02 and narrow extinction bands suited for multiplex analysis. A library of nanoshell samples with localized surface plasmon resonances (LSPR) spanning across the visible range was synthesized. Hyperspectral analysis revealed that the average scattering spectrum of 100 nanoshells matched closely to the spectrum of a single nanoshell, indicating an unprecedented low level of nanoparticle-to-nanoparticle variation for this type of system. A cell labeling experiment, targeting different subcellular compartments in MCF-7 human breast cancer cells, demonstrated that these monodisperse nanoparticles can be used as a multiplex platform for single cell analysis at the intracellular and extracellular level. Antibody-coated gold nanoshells targeted the plasma membrane, while silver nanoshells coated with a nuclear localization signal (NLS) targeted the nuclear membrane. A fluorescence counterstaining experiment, as well as single cell hyperspectral microscopy showed the excellent selectivity and specificity of each type of nanoparticle for its designed subcellular compartment. A time-lapse photodegradation experiment confirmed the enhanced stability of the nanoshells over fluorescent labeling and their capabilities for long-term live cell imaging.

Improving the quality of reconstructed X-ray CT images of polymer gel dosimeters: zero-scan coupled with adaptive mean filtering.

This study evaluated the feasibility of combining the 'zero-scan' (ZS) X-ray computed tomography (CT) based polymer gel dosimeter (PGD) readout with adaptive mean (AM) filtering for improving the signal to noise ratio (SNR), and to compare these results with available average scan (AS) X-ray CT readout techniques. NIPAM PGD were manufactured, irradiated with 6 MV photons, CT imaged and processed in Matlab. AM filter for two iterations, with 3 × 3 and 5 × 5 pixels (kernel size), was used in two scenarios (a) the CT images were subjected to AM filtering (pre-processing) and these were further employed to generate AS and ZS gel images, and (b) the AS and ZS images were first reconstructed from the CT images and then AM filtering was carried out (post-processing). SNR was computed in an ROI of 30 × 30 for different pre and post processing cases. Results showed that the ZS technique combined with AM filtering resulted in improved SNR. Using the previously-recommended 25 images for reconstruction the ZS pre-processed protocol can give an increase of 44% and 80% in SNR for 3 × 3 and 5 × 5 kernel sizes respectively. However, post processing using both techniques and filter sizes introduced blur and a reduction in the spatial resolution. Based on this work, it is possible to recommend that the ZS method may be combined with pre-processed AM filtering using appropriate kernel size, to produce a large increase in the SNR of the reconstructed PGD images.

Design and application of 3D-printed stepless beam modulators in proton therapy.

A new method for the design of stepless beam modulators for proton therapy is described and verified. Simulations of the classic designs are compared against the stepless method for various modulation widths which are clinically applicable in proton eye therapy. Three modulator wheels were printed using a Stratasys Objet30 3D printer. The resulting depth dose distributions showed improved uniformity over the classic stepped designs. Simulated results imply a possible improvement in distal penumbra width; however, more accurate measurements are needed to fully verify this effect. Lastly, simulations were done to model bio-equivalence to Co-60 cell kill. A wheel was successfully designed to flatten this metric.

3D printed plastics for beam modulation in proton therapy.

Two 3D printing methods, fused filament fabrication (FFF) and PolyJet™ (PJ) were investigated for suitability in clinical proton therapy (PT) energy modulation. Measurements of printing precision, printed density and mean stopping power are presented. FFF is found to be accurate to 0.1 mm, to contain a void fraction of 13% due to air pockets and to have a mean stopping power dependent on geometry. PJ was found to print accurate to 0.05 mm, with a material density and mean stopping power consistent with solid poly(methyl methacrylate) (PMMA). Both FFF and PJ were found to print significant, sporadic defects associated with sharp edges on the order of 0.2 mm. Site standard PT modulator wheels were printed using both methods. Measured depth-dose profiles with a 74 MeV beam show poor agreement between PMMA and printed FFF wheels. PJ printed wheel depth-dose agreed with PMMA within 1% of treatment dose except for a distal falloff discrepancy of 0.5 mm.

Dose rate properties of NIPAM-based x-ray CT polymer gel dosimeters.

In this work we investigate radiation dose rate dependencies of N-isopropylacrylamide (NIPAM) based polymer gel dosimeters (PGDs) used in conjunction with x-ray computed tomography imaging for radiotherapy dose verification. We define four primary forms of dose rate variation: constant mean dose rate where beam on and beam off times both vary, variable mean dose rate where beam on time varies, variable mean dose rate where beam off time varies and machine dose rate (MU min(-1)). We utilize both small (20 mL) vials and large volume (1L) gel containers to identify and characterize dose rate dependence in NIPAM PGDs. Results indicate that all investigated constant and variable mean dose rates had negligible affect on PGD dose response with the exception of machine dose rates (100-600 MU min(-1)) which produced variations in dose response significantly lower than previously reported. Explanations of the reduced variability in dose response are given. It is also shown that NIPAM PGD dose response is not affected by variations in dose rate that may occur in modulated treatment deliveries. Finally, compositional changes in NIPAM PGDs are investigated as potential mitigating strategies for dose rate-dependent response variability.

Incorporating multislice imaging into x-ray CT polymer gel dosimetry.

PURPOSE: To evaluate multislice computed tomography (CT) scanning for fast and reliable readout of radiation therapy (RT) dose distributions using CT polymer gel dosimetry (PGD) and to establish a baseline assessment of image noise and uniformity in an unirradiated gel dosimeter. METHODS: A 16-slice CT scanner was used to acquire images through a 1 L cylinder filled with water. Additional images were collected using a single slice machine. The variability in CT number (NCT) associated with the anode heel effect was evaluated and used to define a new slice-by-slice background subtraction artifact removal technique for CT PGD. Image quality was assessed for the multislice system by evaluating image noise and uniformity. The agreement in NCT for slices acquired simultaneously using the multislice detector array was also examined. Further study was performed to assess the effects of increasing x-ray tube load on the constancy of measured NCT and overall scan time. In all cases, results were compared to the single slice machine. Finally, images were collected throughout the volume of an unirradiated gel dosimeter to quantify image noise and uniformity before radiation is delivered. RESULTS: Slice-by-slice background subtraction effectively removes the variability in NCT observed across images acquired simultaneously using the multislice scanner and is the recommended background subtraction method when using a multislice CT system. Image noise was higher for the multislice system compared to the single slice scanner, but overall image quality was comparable between the two systems. Further study showed NCT was consistent across image slices acquired simultaneously using the multislice detector array for each detector configuration of the slice thicknesses examined. In addition, the multislice system was found to eliminate variations in NCT due to increasing x-ray tube load and reduce scanning time by a factor of 4 when compared to imaging a large volume using a single slice scanner. Images acquired through an unirradiated, active gel revealed NCT varies between the top and bottom of the 1 L cylinder as well as across the diameter of the cylinder by up to 7 HU. CONCLUSIONS: Multislice CT imaging has been evaluated for CT PGD and found to be the superior technique compared to single slice imaging in terms of the time required to complete a scan and the tube load characteristics associated with each scanning method. The implementation of multislice scanning is straightforward and expected to facilitate routine gel dosimetry measurements for complex dose distributions in modern RT centers.

Dose calibration optimization and error propagation in polymer gel dosimetry.

This study reports on the relative precision, relative error, and dose differences observed when using a new full-image calibration technique in NIPAM-based x-ray CT polymer gel dosimetry. The effects of calibration parameters (e.g. gradient thresholding, dose bin size, calibration fit function, and spatial remeshing) on subsequent errors in calibrated gel images are reported. It is found that gradient thresholding, dose bin size, and fit function all play a primary role in affecting errors in calibrated images. Spatial remeshing induces minimal reductions or increases in errors in calibrated images. This study also reports on a full error propagation throughout the CT gel image pre-processing and calibration procedure thus giving, for the first time, a realistic view of the errors incurred in calibrated CT polymer gel dosimetry. While the work is based on CT polymer gel dosimetry, the formalism is valid for and easily extended to MRI or optical CT dosimetry protocols. Hence, the procedures developed within the work are generally applicable to calibration of polymer gel dosimeters.

An x-ray CT polymer gel dosimetry prototype: I. Remnant artefact removal.

In this study a new x-ray CT polymer gel dosimetry (PGD) filtering technique is presented for the removal of (i) remnant ring and streak artefacts, and (ii) 'structured' noise in the form of minute, intrinsic gel density fluctuations. It is shown that the noise present within x-ray CT PGD images is not purely stochastic (pixel by pixel) in nature, but rather is 'structured', and hence purely stochastic-based noise-removal filters fail in removing this significant, unwanted noise component. The remnant artefact removal (RAR) technique is based on a class of signal stripping (i.e. baseline-estimation) algorithms typically used in the estimation of unwanted non-uniform baselines underlying spectral data. Here the traditional signal removal algorithm is recast, whereby the 'signal' that is removed is the structured noise and remnant artefacts, leaving the desired polymer gel dose distribution. The algorithm is extended to 2D and input parameters are optimized for PGD images. RAR filter results are tested on (i) synthetic images with measured gel background images added, in order to accurately represent actual noise present in PGD images, and (ii) PGD images of a three-field gel irradiation. RAR results are compared to a top-performing noise filter (adaptive mean, AM), used in previous x-ray CT PGD studies. It is shown that, in all cases, the RAR filter outperforms the AM filter, particularly in cases where either (i) a low-dose gel image has been acquired or (ii) the signal-to-noise ratio of the PG image is low, as in the case when a low number of image averages are acquired within a given experiment. Guidelines for the implementation of the RAR filter are given.

An x-ray CT polymer gel dosimetry prototype: II. Gel characterization and clinical application.

This article reports on the dosimetric properties of a new N-isopropylacrylamide, high %T, polymer gel formulation (19.5%T, 23%C), optimized for x-ray computed tomography (CT) polymer gel dosimetry (PGD). In addition, a new gel calibration technique is introduced together with an intensity-modulated radiation therapy (IMRT) treatment validation as an example of a clinical application of the new gel dosimeter. The dosimetric properties investigated include the temporal stability, spatial stability, batch reproducibility and dose rate dependence. The polymerization reaction is found to stabilize after 15 h post-irradiation. Spatial stability investigations reveal a small overshoot in response for gels imaged later than 36 h post-irradiation. Based on these findings, it is recommended that the new gel formulation be imaged between 15-36 h after irradiation. Intra- and inter-batch reproducibility are found to be excellent over the entire range of doses studied (0-28 Gy). A significant dose rate dependence is found for gels irradiated between 100-600 MU min⁻¹. Overall, the new gel is shown to have promising characteristics for CT PGD, however the implication of the observed dose rate dependence for some clinical applications remains to be determined. The new gel calibration method, based on pixel-by-pixel matching of dose and measured CT numbers, is found to be robust and to agree with the previously used region of interest technique. Pixel-by-pixel calibration is the new recommended standard for CT PGD. The dose resolution for the system was excellent, ranging from 0.2-0.5 Gy for doses between 0-20 Gy and 0.3-0.6 Gy for doses beyond 20 Gy. Comparison of the IMRT irradiation with planned doses yields excellent results: gamma pass rate (3%, 3 mm) of 99.3% at the isocentre slice and 93.4% over the entire treated volume.

Poster - Thur Eve - 15: Production and assessment of astatine-211 for targeted alpha therapy.

Biologically-targeted alpha-particle radiation is the basis of new and promising treatments for eliminating disseminated micrometastases and the residual microscopic malignancies that remain after surgery or radiation therapy. The short-range alpha-particles are highly cytotoxic and capable of inactivating single, isolated cancer cells which may otherwise cause recurrence. Astatine-211 is a promising alpha emitter for therapy; the 7.2 hour half-life of 211 At provides sufficient time for biological-targeting to take place. However, this radionuclide is in short supply and future treatment strategies still require extensive preclinical evaluation. The present work aims to develop technologies that (1) increase the world-wide availability of 211 At for clinical use, and (2) assess the risks of 211 At-based therapies by quantifying the activity distributions in animal models. At TRIUMF (Vancouver, BC), the feasibility of a novel generator system for 211 At is under investigation which would allow distribution of 211 At across Canada and internationally. Briefly, a longer-lived parent radionuclide of 211 At, radon-211, would be produced and allowed to decay in containment to yield 211 At in solution. Additionally, a supplementary study is underway in collaboration with the University of Washington to evaluate the sub-organ biodistributions of astatinated targeting biomolecules, with cell-level resolution. These measurements involve high resolution quantitative alpha-particle imaging in thin tissue samples and can be done for a selection of applications (eg. lymphoma, metastatic prostate cancer, etc) using animal models. The planned alpha-camera measurements are primarily designed to predict and assess the risk of toxicity associated with 211 At-based therapies and aid in developing the future clinical applications.

Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy.

This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF(2) > 0.6) and the R3 cell lines are radiosensitive (SF(2) < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1) the regulated synthesis and degradation of structured proteins and (2) the expression of anti-apoptosis factors or other survival signals. This study demonstrates the utility of RS for noninvasive radiobiological analysis of tumour cell radiation response, and indicates the potential for future RS studies designed to investigate, monitor or predict radiation response.

Cosolvent-free polymer gel dosimeters with improved dose sensitivity and resolution for x-ray CT dose response.

This study reports new N-isopropylacrylamide (NIPAM) polymer gel recipes with increased dose sensitivity and improved dose resolution for x-ray CT readout. NIPAM can be used to increase the solubility of N, N'-methylenebisacrylamide (Bis) in aqueous solutions from approximately 3% to 5.5% by weight, enabling the manufacture of dosimeters containing up to 19.5%T, which is the total concentration of NIPAM and Bis by weight. Gelatin is shown to have a mild influence on dose sensitivity when gels are imaged using x-ray CT, and a stronger influence when gels are imaged optically. Phantoms that contain only 3% gelatin and 5 mM tetrakis hydroxymethyl phosphonium chloride are sufficiently stiff for dosimetry applications. The best cosolvent-free gel formulation has a dose sensitivity in the linear range (~0.88 H Gy(-1)) that is a small improvement compared to the best NIPAM-based gels that incorporate isopropanol as a cosolvent (~0.80 H Gy(-1)). This new gel formulation results in enhanced dose resolution (~0.052 Gy) for x-ray CT readout, making clinical applications of this imaging modality more feasible.

Raman spectroscopy of single human tumour cells exposed to ionizing radiation in vitro.

This work investigates the capability of Raman spectroscopy (RS) to study the effects of ionizing radiation on single human tumour cells. Prostate tumour cells (cell line DU145) are cultured in vitro and irradiated to doses between 15 and 50 Gy with single fractions of 6 MV photons. Single-cell Raman spectra are acquired from irradiated and unirradiated cultures up to 5 days post-irradiation. Principal component analysis is used to distinguish the uniquely radiation-induced spectral changes from inherent sources of spectral variability arising from cell cycle differences and other known factors. We observe uniquely radiation-induced spectral changes which are correlated with both the irradiated dose and the incubation time post-irradiation. The spectral changes induced by radiation arise from biochemical differences in lipids, nucleic acids, amino acids and conformational protein structures between irradiated and unirradiated cells. To our knowledge, this study is the first use of RS to observe radiation-induced biochemical differences in single cells, and is the first use of vibrational spectroscopy to observe uniquely radiation-induced biochemical differences in single cells independent of concurrent cell-cycle- or cell-death-related processes.

Polymer gel dosimeters with enhanced sensitivity for use in x-ray CT polymer gel dosimetry.

A primary limitation of current x-ray CT polymer gel dosimetry is the low contrast, and hence poor dose resolution, of dose images produced by the system. The low contrast is largely due to the low-dose sensitivity of current formulations of polymer gel for x-ray CT imaging. This study reports on the investigation of new dosimeter formulations with improved dose sensitivity for x-ray CT polymer gel dosimetry. We incorporate an isopropanol co-solvent into an N-isopropylacrylamide-based gel formulation in order to increase the total monomer/crosslinker concentration (%T) within the formulation. It is shown that gels of high %T exhibit enhanced dose sensitivity and dose resolutions over traditional formulations. The gels are shown to be temporally stable and reproducible. A single formulation (16%T) is used to demonstrate the capabilities of the x-ray CT polymer gel dosimetry system in measuring known dose distributions. A 1 L gel volume is exposed to three separate irradiations: a single-field percent depth dose, a two-field 'cross' and a three-field 'test case'. The first two irradiations are used to generate a dose calibration curve by which images are calibrated. The calibrated images are compared with treatment planning predictions and it is shown that the x-ray CT polymer gel dosimetry system is capable of capturing spatial and dose information accurately. The proposed new gel formulation is shown to be sensitive, stable and to improve the dose resolution over current formulations so as to provide a feasible gel for clinical applications of x-ray CT polymer gel dosimetry.

Polymer gel dosimetry.

Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented.