The Impact of Radiation Energy on Dose Homogeneity and Organ Dose in the Göttingen Minipig Total-Body Irradiation Model.

Animal models of total-body irradiation (TBI) are used to elucidate normal tissue damage and evaluate the efficacy of medical countermeasures (MCM). The accuracy of these TBI models depends on the reproducibility of the radiation dose-response relationship for lethality, which in turn is highly dependent on robust radiation physics and dosimetry. However, the precise levels of radiation each organ absorbs can change dramatically when different photon beam qualities are used, due to the interplay between their penetration and the natural variation of animal sizes and geometries. In this study, we evaluate the effect of varying the radiation energy, namely cobalt-60 (Co-60); of similar penetration to a 4-MV polyenergetic beam), 6 MV and 15 MV, in the absorbed dose delivered by TBI to individual organs of eight Göttingen minipigs of varying weights (10.3-24.1 kg) and dimensions (17.5-25 cm width). The main organs, i.e. heart, lungs, esophagus, stomach, bowels, liver, kidneys and bladder, were contoured by an experienced radiation oncologist, and the volumetric radiation dose distribution was calculated using a commercial treatment planning system commissioned and validated for Co-60, 6-MV and 15-MV teletherapy units. The dose is normalized to the intended prescription at midline in the abdomen. For each animal and each energy, the body and organ dose volume histograms (DVHs) were computed. The results show that more penetrating photon energies produce dose distributions that are systematically and consistently more homogeneous and more uniform, both within individual organs and between different organs, across all animals. Thoracic organs (lungs, heart) received higher dose than prescribed while pelvic organs (bowel, bladder) received less dose than prescribed, due to smaller and wider separations, respectively. While these trends were slightly more pronounced in the smallest animals (10.3 kg, 19 cm abdominal width) and largest animals (>20 kg, ∼25 cm abdominal width), they were observed in all animals, including those in the 9-15 kg range typically used in MCM models. Some organs received an average absorbed dose representing <80% of prescribed dose when Co-60 was used, whereas all organs received average doses of >87% and >93% when 6 and 15 MV were used, respectively. Similarly, average dose to the thoracic organs reached as high as 125% of the intended dose with Co-60, compared to 115% for 15 MV. These results indicate that Co-60 consistently produces less uniform dose distributions in the Göttingen minipig compared to 6 and 15 MV. Moreover, heterogeneity of dose distributions for Co-60 is accentuated by anatomical and geometrical variations across various animals, leading to different absorbed dose delivered to organs for different animals. This difference in absorbed radiation organ doses, likely caused by the lower penetration of Co-60 and 6 MV compared to 15 MV, could potentially lead to different biological outcomes. While the link between the dose distribution and variation of biological outcome in the Göttingen minipig has never been explicitly studied, more pronounced dose heterogeneity within and between organs treated with Co-60 teletherapy units represents an additional confounding factor which can be easily mitigated by using a more penetrating energy.

A 3D printed modular phantom for quality assurance of image-guided small animal irradiators: Design, imaging experiments, and Monte Carlo simulations.

PURPOSE: The goal of this work was to develop and test a cylindrical tissue-equivalent quality assurance (QA) phantom for micro computed tomography (microCT) image-guided small animal irradiators that overcomes deficiencies of existing phantoms due to its mouse-like dimensions and composition. METHODS: The 8.6-cm-long and 2.4-cm-diameter phantom was three-dimensionally (3D) printed out of Somos NeXt plastic on a stereolithography (SLA) printer. The modular phantom consisted of four sections: (a) CT number evaluation section, (b) spatial resolution with slanted edge (for the assessment of longitudinal resolution) and targeting section, (c) spatial resolution with hole pattern (for the assessment of radial direction) section, and (d) uniformity and geometry section. A Python-based graphical user interface (GUI) was developed for automated analysis of microCT images and evaluated CT number consistency, longitudinal and radial modulation transfer function (MTF), image uniformity, noise, and geometric accuracy. The phantom was placed at the imaging isocenter and scanned with the small animal radiation research platform (SARRP) in the pancake geometry (long axis of the phantom perpendicular to the axis of rotation) with a variety of imaging protocols. Tube voltage was set to 60 and 70 kV, tube current was set to 0.5 and 1.2 mA, voxel size was set to 200 and 275 µm, imaging times of 1, 2, and 4 min were used, and frame rates of 6 and 12 frames per second (fps) were used. The phantom was also scanned in the standard (long axis of the phantom parallel to the axis of rotation) orientation. The quality of microCT images was analyzed and compared to recommendations presented in our previous work that was derived from a multi-institutional study. Additionally, a targeting accuracy test with a film placed in the phantom was performed. MicroCT imaging of the phantom was also simulated in a modified version of the EGSnrc/DOSXYZnrc code. Images of the resolution section with the hole pattern were acquired experimentally as well as simulated in both the pancake and the standard imaging geometries. The radial spatial resolution of the experimental and simulated images was evaluated and compared to experimental data. RESULTS: For the centered phantom images acquired in the pancake geometry, all imaging protocols passed the spatial resolution criterion in the radial direction (>1.5 lp/mm @ 0.2 MTF), the geometric accuracy criterion (<200 µm), and the noise criterion (<55 HU). Only the imaging protocol with 200-µm voxel size passed the criterion for spatial resolution in the longitudinal direction (>1.5 lp/mm @ 0.2 MTF). The 70-kV tube voltage dataset failed the bone CT number consistency test (<55 HU). Due to cupping artifacts, none of the imaging protocols passed the uniformity test of <55 HU. When the phantom was scanned in the standard imaging geometry, image uniformity and longitudinal MTF were satisfactory; however, the CT number consistency failed the recommended limit. A targeting accuracy of 282 and 251 µm along the x- and z-direction was observed. Monte Carlo simulations confirmed that the radial spatial resolution for images acquired in the pancake geometry was higher than the one acquired in the standard geometry. CONCLUSIONS: The new 3D-printed phantom presents a useful tool for microCT image analysis as it closely mimics a mouse. In order to image mouse-sized animals with acceptable image quality, the standard protocol with a 200-µm voxel size should be chosen and cupping artifacts need to be resolved.

Modeling a superficial radiotherapy X-ray source for relative dose calculations.

The purpose of this study was to empirically characterize and validate a kilovoltage (kV) X-ray beam source model of a superficial X-ray unit for relative dose calculations in water and assess the accuracy of the British Journal of Radiology Supplement 25 (BJR 25) percentage depth dose (PDD) data. We measured central axis PDDs and dose profiles using an Xstrahl 150 X-ray system. We also compared the measured and calculated PDDs to those in the BJR 25. The Xstrahl source was modeled as an effective point source with varying spatial fluence and spectra. In-air ionization chamber measurements were made along the x- and y-axes of the X-ray beam to derive the spatial fluence and half-value layer (HVL) measurements were made to derive the spatially varying spectra. This beam characterization and resulting source model was used as input for our in-house dose calculation software (kVDoseCalc) to compute radiation dose at points of interest (POIs). The PDDs and dose profiles were measured using 2, 5, and 15 cm cone sizes at 80, 120, 140, and 150 kVp energies in a scanning water phantom using IBA Farmer-type ionization chambers of volumes 0.65 and 0.13 cc, respectively. The percent difference in the computed PDDs compared with our measurements range from -4.8% to 4.8%, with an overall mean percent difference and standard deviation of 1.5% and 0.7%, respectively. The percent difference between our PDD measurements and those from BJR 25 range from -14.0% to 15.7%, with an overall mean percent difference and standard deviation of 4.9% and 2.1%, respectively - showing that the measurements are in much better agreement with kVDoseCalc than BJR 25. The range in percent difference between kVDoseCalc and measurement for profiles was -5.9% to 5.9%, with an overall mean percent difference and standard deviation of 1.4% and 1.4%, respectively. The results demonstrate that our empirically based X-ray source modeling approach for superficial X-ray therapy can be used to accurately compute relative dose in a homogeneous water-equivalent medium. They also show limitations in the accuracy of theBJR 25 PDD data.