M Alqathami

Enhancement of radiation effects by bismuth oxide nanoparticles for kilovoltage x-ray beams: A dosimetric study using a novel multi-compartment 3D radiochromic dosimeter

The aim of this study is to present the first experimental validation and quantification of the dose enhancement capability of bismuth oxide nanoparticles (Bi2O3-Nps). A recently introduced multi-compartment 3D radiochromic dosimeter for measuring radiation dose enhancement produced from the interaction of X-rays with metal nanoparticles was employed to investigate the 3D spatial distribution of ionizing radiation dose deposition. Dose-enhancement factor for the dosimeters doped with Bi2O3-NPs was ~1.9 for both spectrophotometry and optical CT analyses. Our results suggest that bismuth-based nanomaterials are efficient dose enhancing agents and have great potential for application in clinical radiotherapy.

Novel Multicompartment 3-Dimensional Radiochromic Radiation Dosimeters for Nanoparticle-Enhanced Radiation Therapy Dosimetry

PURPOSE Gold nanoparticles (AuNps), because of their high atomic number (Z), have been demonstrated to absorb low-energy X-rays preferentially, compared with tissue, and may be used to achieve localized radiation dose enhancement in tumors. The purpose of this study is to introduce the first example of a novel multicompartment radiochromic radiation dosimeter and to demonstrate its applicability for 3-dimensional (3D) dosimetry of nanoparticle-enhanced radiation therapy. METHODS AND MATERIALS A novel multicompartment phantom radiochromic dosimeter was developed. It was designed and formulated to mimic a tumor loaded with AuNps (50 nm in diameter) at a concentration of 0.5 mM, surrounded by normal tissues. The novel dosimeter is referred to as the Sensitivity Modulated Advanced Radiation Therapy (SMART) dosimeter. The dosimeters were irradiated with 100-kV and 6-MV X-ray energies. Dose enhancement produced from the interaction of X-rays with AuNps was calculated using spectrophotometric and cone-beam optical computed tomography scanning by quantitatively comparing the change in optical density and 3D datasets of the dosimetric measurements between the tissue-equivalent (TE) and TE/AuNps compartments. The interbatch and intrabatch variability and the postresponse stability of the dosimeters with AuNps were also assessed. RESULTS Radiation dose enhancement factors of 1.77 and 1.11 were obtained using 100-kV and 6-MV X-ray energies, respectively. The results of this study are in good agreement with previous observations; however, for the first time we provide direct experimental confirmation and 3D visualization of the radiosensitization effect of AuNps. The dosimeters with AuNps showed small (<3.5%) interbatch variability and negligible (<0.5%) intrabatch variability. CONCLUSIONS The SMART dosimeter yields experimental insights concerning the spatial distributions and elevated dose in nanoparticle-enhanced radiation therapy, which cannot be performed using any of the current methods. The authors concluded that it can be used as a novel independent method for nanoparticle-enhanced radiation therapy dosimetry.

Experimental determination of the influence of oxygen on the PRESAGE® dosimeter.

It is generally accepted that the PRESAGE(®) radiochromic dosimeter is not sensitive to oxygen, however, this claim has not been supported or verified experimentally. Therefore, the aim of this study was to experimentally determine the potential influence of oxygen on dose sensitivity of the PRESAGE(®) dosimeter and its reporting system. Batches of PRESAGE(®) and its radical initiator-leuco dye reporting system were prepared in aerobic and anaerobic conditions. The anaerobic batches were deoxygenated by bubbling nitrogen through the dosimeter precursors or reporting system for 10 min. The dosimeters and reporting systems were prepared in spectrophotometric cuvettes and glass vials, respectively, and were irradiated with 6 MV photons to various radiation doses. Changes in optical density of the dosimeters and reporting system before and after irradiation were measured using a spectrophotometer. The overall results show that oxygen has some influence on the dosimetric characteristics of PRESAGE(®), although the radical initiator does appear to oxidize the leucomalachite green even in the presence of oxygen. Deoxygenation of the reporting system leads to an increase in sensitivity to radiation dose by ~30% when compared to the non-deoxygenated system. A minor increase in sensitivity (~5%) was also achieved by deoxygenating the PRESAGE(®) precursor prior to casting. In addition, dissolved oxygen measurements revealed low levels of dissolved oxygen (0.40 ± 0.04 mg l(-1)) in the polyurethane precursor used to fabricate the PRESAGE(®) dosimeters, as compared to water (8.60 ± 0.03 mg l(-1)) and the reporting system alone (1.30 ± 0.10 mg l(-1)). The results suggest that the presence of oxygen does not inhibit the radiochromic properties of the PRESAGE(®) system. However, deoxygenation of the dosimeter precursors prior to casting improves the dosimeters dose sensitivity by ~5%, which might be particularly useful for measuring low radiation doses. Nevertheless, we believe this is not sufficient enough to recommend the deoxygenation of commercial PRESAGE(®) precursor prior to casting. In addition, there were no observed changes in the dose linearity, absorption spectrum and post-response photofading characteristics of the PRESAGE(®) under the conditions investigated.

TH‐CD‐BRA‐08: Novel Iron‐Based Radiation Reporting Systems as 4D Dosimeters for MR‐Guided Radiation Therapy

PURPOSE To compare novel radiation reporting systems utilizing ferric ion (Fe3+ ) reduction versus ferrous ion (Fe2+ ) oxidation in gelatin matrixes for 3D and 4D (3D+time) MR-guided radiation therapy dosimetry. METHODS Dosimeters were irradiated using an integrated 1.5T MRI and 7MV linear accelerator (MR-Linac). Dosimeters were read-out with both a spectrophotometer and the MRI component of the MR-Linac immediately after irradiation. Changes in optical density (OD) were measured using a spectrophotometer; changes in MR signal intensity due to the paramagnetic differences in the iron ions were measured using the MR-Linac in real-time during irradiation (balanced-FFE sequences) and immediately after irradiation (T1 -weighted and inversion recovery sequences). RESULTS Irradiation of Fe3+ reduction dosimeters resulted in a stable red color with an absorbance peak at 512 nm. The change in OD relative to dose exhibited a linear response up to 100 Gy (R2 =1.00). T1 -weighted-MR signal intensity (SI) changed minimally after irradiation with increases of 8.0% for 17 Gy and 9.7% after escalation to 35 Gy compared to the un-irradiated region. Irradiation of Fe2+ oxidation dosimeters resulted in a stable purple color with absorbance peaks at 440 and 585 nm. The changes in OD, T1 -weighted-MR SI, and R1 relative to dose exhibited a linear response up to at least 8 Gy (R2 =1.00, 0.98, and 0.99) with OD saturation above 40 Gy. The T1 -weighted-MR SI increased 50.3% for 17 Gy compared to the un-irradiated region. The change in SI was observed in both 2D+time and 4D (3D+time) acquisitions post-irradiation and in real-time during irradiation with a linear increase with respect to dose (R2 >0.93). CONCLUSION The Fe2+ oxidation-based system was superior as 4D dosimeters for MR-guided radiation therapy due to its higher sensitivity in both optical and MR signal readout and feasibility for real-time 4D dose readout. The Fe3+ reduction system is recommended for high dose applications. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. LH-102SPS.

An investigation into the potential influence of oxygen on the efficiency of the PRESAGE® dosimeter

The influence of atmospheric oxygen on the efficiency of the PRESAGE® dosimeter was investigated. Batches of PRESAGE® and reporting system solution were deoxygenated using nitrogen and compared to similar batches that were exposed to atmospheric oxygen during fabrication. The overall results show little influence of oxygen on the characteristics of PRESAGE® with the radical initiator oxidizing the leucomalachite green in the presence of oxygen. However, when deoxygenating the reporting system the sensitivity to radiation dose increased by 30% compared to the non-deoxygenated system. A slight improvement in sensitivity (5%) was achieved by deoxygenating the PRESAGE® precursors prior to casting. The results suggest that the solid polyurethane matrix is not permeable to atmospheric oxygen. In addition, there were no observed changes in the dose linearity, absorption spectrum and post-response photofading characteristics of PRESAGE® under the conditions investigated.

Dose variations caused by setup errors in intracranial stereotactic radiotherapy: A PRESAGE study

Stereotactic radiotherapy (SRT) requires tight margins around the tumor, thus producing a steep dose gradient between the tumor and the surrounding healthy tissue. Any setup errors might become clinically significant. To date, no study has been performed to evaluate the dosimetric variations caused by setup errors with a 3-dimensional dosimeter, the PRESAGE. This research aimed to evaluate the potential effect that setup errors have on the dose distribution of intracranial SRT. Computed tomography (CT) simulation of a CIRS radiosurgery head phantom was performed with 1.25-mm slice thickness. An ideal treatment plan was generated using Brainlab iPlan. A PRESAGE was made for every treatment with and without errors. A prescan using the optical CT scanner was carried out. Before treatment, the phantom was imaged using Brainlab ExacTrac. Actual radiotherapy treatments with and without errors were carried out with the Novalis treatment machine. Postscan was performed with an optical CT scanner to analyze the dose irradiation. The dose variation between treatments with and without errors was determined using a 3-dimensional gamma analysis. Errors are clinically insignificant when the passing ratio of the gamma analysis is 95% and above. Errors were clinically significant when the setup errors exceeded a 0.7-mm translation and a 0.5° rotation. The results showed that a 3-mm translation shift in the superior-inferior (SI), right-left (RL), and anterior-posterior (AP) directions and 2° couch rotation produced a passing ratio of 53.1%. Translational and rotational errors of 1.5mm and 1°, respectively, generated a passing ratio of 62.2%. Translation shift of 0.7mm in the directions of SI, RL, and AP and a 0.5° couch rotation produced a passing ratio of 96.2%. Preventing the occurrences of setup errors in intracranial SRT treatment is extremely important as errors greater than 0.7mm and 0.5° alter the dose distribution. The geometrical displacements affect dose delivery to the tumor and the surrounding normal tissues.

Using 3D dosimetry to quantify the Electron Return Effect (ERE) for MR-image-guided radiation therapy (MR-IGRT) applications

Image-guided radiation therapy (IGRT) using computed tomography (CT), cone-beam CT, MV on-board imager (OBI), and kV OBI systems have allowed for more accurate patient positioning prior to each treatment fraction. While these imaging modalities provide excellent bony anatomy image quality, MRI surpasses them in soft tissue image contrast for better visualization and tracking of soft tissue tumors with no additional radiation dose to the patient. A pre-clinical integrated 1.5 T magnetic resonance imaging and 7 MV linear accelerator system (MR-linac) allows for real-time tracking of soft tissues and adaptive treatment planning prior to each treatment fraction. However, due to the presence of a strong magnetic field from the MR component, there is a three dimensional (3D) change in dose deposited by the secondary electrons. Especially at nonhomogeneous anatomical sites with tissues of very different densities, dose enhancements and reductions can occur due to the Lorentz force influencing the trajectories of secondary electrons. These dose changes at tissue interfaces are called the electron return effect or ERE. This study investigated the ERE using 3D dosimeters.

TU-H-CAMPUS-TeP3-04: Probing the Dose Enhancement Due to a Clinically-Relevant Concentration of Gold Nanoparticles and Yb-169 Gamma Rays Using PRESAGE Dosimeters

PURPOSE To probe physical evidences of the dose enhancement due to a low/clinically-relevant concentration of gold nanoparticles (GNPs) and Yb-169 gamma rays using PRESAGE dosimeters. METHODS A PRESAGE cuvette was placed at approximately 2 mm above the plane containing three novel Yb-169 brachytherapy seeds (3.2, 3.2, and 5.3 mCi each). Two types of PRESAGE dosimeters were used - plain PRESAGEs (controls) and PRESAGEs loaded with 0.02 wt. % of GNPs (GNP-PRESAGEs). Each PRESAGE dosimeter was irradiated with different time durations (0 to 24 hours) to deliver 0, 4, 8, 16 and 24 Gy of dose. For a reference/comparison, both types of PRESAGEs were also irradiated using 250 kVp x-rays with/without Er-filter to deliver 0, 3, 10, and 30 Gy of dose. Er-filter was used to emulate Yb-169 spectrum using 250 kVp x-rays. The absorption spectra of PRESAGEs were measured using a UV spectrophotometer and used to determine the corresponding optical densities (ODs). RESULTS GNP-PRESAGEs exposed to Yb-169 sources showed ∼65% increase in ODs compared with controls. When exposed to Er-filtered and unfiltered 250 kVp x-rays, they produced smaller increases in ODs, ∼41% and ∼37%, respectively. There was a linear relationship between ODs and delivered doses with a goodness-of-fit (R2) greater than 0.99. CONCLUSION A notable increase in the ODs (∼65%) was observed for GNP-PRESAGEs irradiated by Yb-169 gamma rays. Considering the observed OD increases, it was highly likely that Yb-169 gamma rays were more effective than both Er-filtered and unfiltered 250 kVp x-rays, in terms of producing the dose enhancement. Due to several unknown factors (e.g., possible difference in the dose response of GNP-PRESAGEs vs. PRESAGEs), however, a further investigations is necessary to establish the feasibility of quantifying the exact amount of macroscopic or microscopic/local GNP-mediated dose enhancement using PRESAGE or similar volumetric dosimeters. Supported by DOD/PCRP grant W81XWH-12-1-0198 This investigation was supported by DOD/PCRP grant W81XWH-12-1-0198.

TH-AB-BRA-11: Using 3D Dosimeters for the Investigation of the Electron Return Effect (ERE) in MR-Guided Radiation Therapy: A Feasibility Study

PURPOSE To demonstrate the capability of 3D radiochromic PRESAGE and Fricke-type dosimeters to measure the influence of magnetic fields on dose distribution, including the electron return effect (ERE), for MR-guided radiation therapy applications. METHODS Short cylindrical 3D dosimeters with PRESAGE and Fricke-type formulations were created in-house prior to irradiations in a 1.5T/7MV MR-linac. Each dosimeter was prepared with a concentric cylindrical air cavity with diameters of 1.5 cm and 2.5 cm, and the diameters of the dosimeters were 7.2 cm and 8.8 cm for PRESAGE and Fricke-type respectively. The dosimeters were irradiated within the bore of the MR-linac with the flat face of the dosimeters perpendicular to the magnetic field. Dosimeters were irradiated to approximately 9 Gy and 29 Gy to the center of dosimeters with a 15×15 cm2 field. The PRESAGE dosimeter was scanned using an optical-CT 2 hours post-irradiation; the Fricke-type dosimeter was immediately imaged with the MR component of the MR-linac post-irradiation. RESULTS Axial slices of the dose distributions show a clear demonstration of the dose enhancement due to the ERE above the cavity and the region of reduced dose below the cavity. The regions of increased and reduced dose are rotated with respect to the radiation beam axis due to the average directional change of the electrons. Measurements from line profiles show the dose enhanced up to ∼0.5 cm around the cavity by up to a factor of 1.3 and 1.4 for PRESAGE and Fricke-type dosimeters respectively. CONCLUSION PRESAGE and Fricke-type dosimeters are able to qualitatively measure the ERE with good agreement with previously published simulation and 2D dosimetry demonstrations of the ERE. Further investigation of these 3D dosimeters as promising candidates for quality assurance of MR-guided radiation therapy systems is encouraged to assess changes in response and measurement accuracy due to the magnetic field.

SU-G-JeP2-04: Comparison Between Fricke-Type 3D Radiochromic Dosimeters for Real-Time Dose Distribution Measurements in MR-Guided Radiation Therapy.

PURPOSE To assess MR signal contrast for different ferrous ion compounds used in Fricke-type gel dosimeters for real-time dose measurements for MR-guided radiation therapy applications. METHODS Fricke-type gel dosimeters were prepared in 4% w/w gelatin prior to irradiation in an integrated 1.5 T MRI and 7 MV linear accelerator system (MR-Linac). 4 different ferrous ion (Fe2?) compounds (referred to as A, B, C, and D) were investigated for this study. Dosimeter D consisted of ferrous ammonium sulfate (FAS), which is conventionally used for Fricke dosimeters. Approximately half of each cylindrical dosimeter (45 mm diameter, 80 mm length) was irradiated to ∼17 Gy. MR imaging during irradiation was performed with the MR-Linac using a balanced-FFE sequence of TR/TE = 5/2.4 ms. An approximate uncertainty of 5% in our dose delivery was anticipated since the MR-Linac had not yet been fully commissioned. RESULTS The signal intensities (SI) increased between the un-irradiated and irradiated regions by approximately 8.6%, 4.4%, 3.2%, and 4.3% after delivery of ∼2.8 Gy for dosimeters A, B, C, and D, respectively. After delivery of ∼17 Gy, the SI had increased by 24.4%, 21.0%, 3.1%, and 22.2% compared to the un-irradiated regions. The increase in SI with respect to dose was linear for dosimeters A, B, and D with slopes of 0.0164, 0.0251, and 0.0236 Gy-1 (R2 = 0.92, 0.97, and 0.96), respectively. Visually, dosimeter A had the greatest optical contrast from yellow to purple in the irradiated region. CONCLUSION This study demonstrated the feasibility of using Fricke-type dosimeters for real-time dose measurements with the greatest optical and MR contrast for dosimeter A. We also demonstrated the need to investigate Fe2+ compounds beyond the conventionally utilized FAS compound in order to improve the MR signal contrast in 3D dosimeters used for MR-guided radiation therapy. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. LH- 102SPS.