A Rubinstein

Evaluation of hyperpolarized [1-13C]-pyruvate by magnetic resonance to detect ionizing radiation effects in real time

Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-13C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.

Technical Note: A Monte Carlo study of magnetic‐field‐induced radiation dose effects in mice

PURPOSE Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment using an MRI-linear accelerator (MRI-Linac), preclinical studies are needed to understand the biological consequences of magnetic-field-induced dose effects. In the present study, the authors sought to identify a beam energy and magnetic field strength combination suitable for preclinical murine experiments. METHODS Magnetic field dose effects were simulated in a mouse lung phantom using various beam energies (225 kVp, 350 kVp, 662 keV [Cs-137], 2 MV, and 1.25 MeV [Co-60]) and magnetic field strengths (0.75, 1.5, and 3 T). The resulting dose distributions were compared with those in a simulated human lung phantom irradiated with a 6 or 8 MV beam and orthogonal 1.5 T magnetic field. RESULTS In the human lung phantom, the authors observed a dose increase of 45% and 54% at the soft-tissue-to-lung interface and a dose decrease of 41% and 48% at the lung-to-soft-tissue interface for the 6 and 8 MV beams, respectively. In the mouse simulations, the magnetic fields had no measurable effect on the 225 or 350 kVp dose distribution. The dose increases with the Cs-137 beam for the 0.75, 1.5, and 3 T magnetic fields were 9%, 29%, and 42%, respectively. The dose decreases were 9%, 21%, and 37%. For the 2 MV beam, the dose increases were 16%, 33%, and 31% and the dose decreases were 9%, 19%, and 30%. For the Co-60 beam, the dose increases were 19%, 54%, and 44%, and the dose decreases were 19%, 42%, and 40%. CONCLUSIONS The magnetic field dose effects in the mouse phantom using a Cs-137, 3 T combination or a Co-60, 1.5 or 3 T combination most closely resemble those in simulated human treatments with a 6 MV, 1.5 T MRI-Linac. The effects with a Co-60, 1.5 T combination most closely resemble those in simulated human treatments with an 8 MV, 1.5 T MRI-Linac.

SU‐D‐144‐03: Respiratory Motion Management for High‐Precision Small Animal Irradiation

PURPOSE The ability to produce precisely targeted beams as small as 1 mm necessitates the understanding and management of intra-fraction motion. This study evaluated lung motion in free-breathing mice and compared free-breathing imaging (3D and 4D reconstruction) to breath-hold imaging for use in treatment planning. METHODS Five mice were imaged weekly for six weeks using the X-RAD 225Cx system. Each week, CBCT projections were acquired during free-breathing imaging under anesthesia and reconstructed into 3D and 4D images (6 phases). Superior-inferior, anterior-posterior, and right-left motion were evaluated using deformable registration of the 4D images, and confirmed by manual measurements on fluoroscopic images. Next, the mice were intubated and their breath was held at full-inhale for 20 seconds during image acquisition. Breath-hold scans from the same session were compared to assess reproducibility. RESULTS The average voxel motion in the lungs of free-breathing mice was 1.3 mm (stdev = 0.2mm) while the average maximum motion was 3.4 mm (stdev = 0.3mm). To ensure tumor coverage in free-breathing mice we can apply the ITV concept to 3D-CBCTs, using added margins defined by the 4D-CBCT image sets. However, in an area of maximum motion, the expanded target volume could cover 30% the length of the lung. Adding this margin could Result in substantial normal tissue toxicity. Breath-hold imaging was reproducible to within 0.6 mm except in areas close to the heart due to cardiac motion. A visual comparison of image quality found that the breath-hold images were substantially sharper than both the 3D and 4D free-breathing images due to blurring and reconstruction artifacts. CONCLUSION Given the large respiratory motion relative to lung size in mice, breath-hold imaging offers clear advantages in motion management and image quality. Breath-hold treatments using IGRT are feasible and are recommended in cases of large tumor motion.

TU-H-CAMPUS-TeP2-01: A Comparison of Noninvasive Techniques to Assess Radiation-Induced Lung Damage in Mice

PURPOSE To evaluate the use of post-irradiation changes in respiratory rate and CBCT-based morphology as predictors of survival in mice. METHODS C57L/J mice underwent whole-thorax irradiation with a Co-60 beam to four different doses [0Gy (n=3), 9Gy (n=5), 11Gy (n=7), and 13Gy (n=5)] in order to induce varying levels of pneumonitis. Respiratory rate measurements, breath-hold CBCTs, and free-breathing CBCTs were acquired pre-irradiation and at six time points between two and seven months post-irradiation. For respiratory rate measurements, we developed a novel computer-vision-based technique. We recorded mice sleeping in standard laboratory cages with a 30 fps, 1080p webcam (Logitech C920). We calculated respiratory rate using corner detection and optical flow to track cyclical motion in the fur in the recorded video. Breath-hold and free-breathing CBCTs were acquired on the X-RAD225Cx system. For breathhold imaging, the mice were intubated and their breath was held at full-inhale for 20 seconds. Healthy lung tissue was delineated in the scans using auto-threshold contouring (0-0.7 g/cm3 ). The volume of healthy lung was measured in each of the scans. Next, lung density was measured in a 6-mm2 ROI in a fixed anatomic location in each of the scans. RESULTS Day-to-day variability in respiratory rate with our technique was 13%. All metrics except for breath-hold lung volume were correlated with survival: lung density on free-breathing (r=-0.7482,p<0.01) and breath-hold images (r=-0.5864,p<0.01), free-breathing lung volume (r=0.7179,p<0.01), and respiratory rate (r= 0.6953,p<0.01). Lung density on free-breathing scans was correlated with respiratory rate (r=0.7142,p<0.01) and lung density on breath-hold scans (r=0.5543,p<0.01). One significant practical hurdle in the CBCT measurements was that at least one lobe of the lung was collapsed in 36% of free-breathing scans and 45% of breath-hold scans. CONCLUSION Lung density and lung volume on free-breathing CBCTs and respiratory rate outperform breath-hold CBCT measurements as indicators for survival from radiation-induced pneumonitis. This work was partially funded by Elekta.

SU‐D‐144‐02: Four‐Dimensional Cone Beam CT for a Small Animal Image Guided Radiation Therapy System Without Use of An External Respiratory Monitoring System

PURPOSE To develop four-dimensional cone beam CT for an image guided radiation system for small animals without the use of external respiration monitoring systems. METHODS Nine mice were scanned using the cone beam CT capabilities of an X-Rad 225Cx system. The mice were anesthetized with 1.5 to 3% isoflurane and scanned (60 kVp and 4 mA) at a sampling rate of 15 fps and gantry rotation rate of 0.5 rpm to yield a total of approximately 1800 975×975 projection images. The projections were used to obtain a respiratory signal using a modified Amsterdam Shroud method. Inspirations appeared approximately as vertical lines in the Amsterdam Shroud image due to the small ratio of inspiration to expiration times in mice anesthetized with isoflurane. The locations of these lines were extracted using vertical edge detection, dilation and projection onto one dimension. Four-dimensional cone beam CT images (voxel size 0.1 × 0.1 × 0.3 mm) were then obtained using these peak inspirations to sort the projections into 6 phases. The peak inspirations of two mice were manually extracted from the projections to test the peak extraction method. RESULTS 4D CBCT images were successfully created for each mouse with minimal streak artifacts. Some blurring in the initial phase was seen due to the sharpness of the inspiration peak. The peak finding algorithm determined the peaks correctly to within an average of 0.7 and 0.4 projections for the first and second mouse, respectively. 82% and 89% of the projections were sorted into the correct phase bin for the two mice. CONCLUSION The four-dimensional CBCT method developed here can be used to analyze lung motion in mice and assist in preclinical targeted radiation therapy studies.

TH‐CD‐BRA‐04: Effect of a Strong Magnetic Field On TLDs, OSLDs, and Gafchromic Films Using An Electromagnet

PURPOSE To study the effect of strong magnetic field on three types of dosimeters using an electromagnet inside a Linac vault. MATERIALS AND METHODS Three types of dosimeters, thermoluminescent Dosimeters (TLDs), optically stimulated luminescent Dosimeters (OSLDs), and EBT3 Film were used to measure radiation dose response inside an electromagnet that could produce a strong magnetic field (B>1.5 T). The dosimeters were placed inside a plastic phantom between the two poles of the magnet, at approximately 3 meters from the iso-center of an Elekta Versa HD Linac. The B field was calibrated with a Gauss meter (Model: GM-2, AlphaLab Inc). The dosimeters received ∼2 Gy with and without the presence of the 1.5 T magnetic field. The EBT3 films were scanned 24 hours before and 24 hours after irradiation. The TLD dosimeters were read 1 week after irradiation. The OSLDs were read two weeks after irradiation. The ratios of signals of dosimeters irradiated with the B field to the signals without the B field were calculated. Two experiments have been conducted so far. RESULTS The ratios (averaged over two experiments) of dosimeter signals with vs without B field were 0.994 for films, 0.994 for OSLDs, and 1.002 for TLDs. The statistical uncertainty was ∼3%. CONCLUSIONS The three types of dosimeters (film, TLD, OSLD) seem not affected by the presence of a magnetic field (B=1.5 T) with the uncertainty of ∼3%. They may be suitable for QA purposes in a strong B field up to 1.5 T. More measurements will be conducted for reproducibility testing. We acknowledge research support from Elekta AB.

Multi-institutional MicroCT image comparison of image-guided small animal irradiators

To recommend imaging protocols and establish tolerance levels for microCT image quality assurance (QA) performed on conformal image-guided small animal irradiators. A fully automated QA software SAPA (small animal phantom analyzer) for image analysis of the commercial Shelley micro-CT MCTP 610 phantom was developed, in which quantitative analyses of CT number linearity, signal-to-noise ratio (SNR), uniformity and noise, geometric accuracy, spatial resolution by means of modulation transfer function (MTF), and CT contrast were performed. Phantom microCT scans from eleven institutions acquired with four image-guided small animal irradiator units (including the commercial PXi X-RAD SmART and Xstrahl SARRP systems) with varying parameters used for routine small animal imaging were analyzed. Multi-institutional data sets were compared using SAPA, based on which tolerance levels for each QA test were established and imaging protocols for QA were recommended. By analyzing microCT data from 11 institutions, we established image QA tolerance levels for all image quality tests. CT number linearity set to R 2  >  0.990 was acceptable in microCT data acquired at all but three institutions. Acceptable SNR  >  36 and noise levels  <55 HU were obtained at five of the eleven institutions, where failing scans were acquired with current-exposure time of less than 120 mAs. Acceptable spatial resolution (>1.5 lp mm-1 for MTF  =  0.2) was obtained at all but four institutions due to their large image voxel size used (>0.275 mm). Ten of the eleven institutions passed the set QA tolerance for geometric accuracy (<1.5%) and nine of the eleven institutions passed the QA tolerance for contrast (>2000 HU for 30 mgI ml-1). We recommend performing imaging QA with 70 kVp, 1.5 mA, 120 s imaging time, 0.20 mm voxel size, and a frame rate of 5 fps for the PXi X-RAD SmART. For the Xstrahl SARRP, we recommend using 60 kVp, 1.0 mA, 240 s imaging time, 0.20 mm voxel size, and 6 fps. These imaging protocols should result in high quality images that pass the set tolerance levels on all systems. Average SAPA computation time for complete QA analysis for a 0.20 mm voxel, 400 slice Shelley phantom microCT data set was less than 20 s. We present image quality assurance recommendations for image-guided small animal radiotherapy systems that can aid researchers in maintaining high image quality, allowing for spatially precise conformal dose delivery to small animals.

Cost‐effective immobilization for whole brain radiation therapy

Abstract To investigate the inter‐ and intra‐fraction motion associated with the use of a low‐cost tape immobilization technique as an alternative to thermoplastic immobilization masks for whole‐brain treatments. The results of this study may be of interest to clinical staff with severely limited resources (e.g., in low‐income countries) and also when treating patients who cannot tolerate standard immobilization masks. Setup reproducibility of eight healthy volunteers was assessed for two different immobilization techniques. (a) One strip of tape was placed across the volunteers forehead and attached to the sides of the treatment table. (b) A second strip was added to the first, under the chin, and secured to the table above the volunteers head. After initial positioning, anterior and lateral photographs were acquired. Volunteers were positioned five times with each technique to allow calculation of inter‐fraction reproducibility measurements. To estimate intra‐fraction reproducibility, 5‐minute anterior and lateral videos were taken for each technique per volunteer. An in‐house software was used to analyze the photos and videos to assess setup reproducibility. The maximum intra‐fraction displacement for all volunteers was 2.8 mm. Intra‐fraction motion increased with time on table. The maximum inter‐fraction range of positions for all volunteers was 5.4 mm. The magnitude of inter‐fraction and intra‐fraction motion found using the “1‐strip” and “2‐strip” tape immobilization techniques was comparable to motion restrictions provided by a thermoplastic mask for whole‐brain radiotherapy. The results suggest that tape‐based immobilization techniques represent an economical and useful alternative to the thermoplastic mask.

TH‐CD‐BRA‐01: BEST IN PHYSICS (THERAPY): ‐Field‐Induced Dose Effects in a Mouse Lung Phantom: Monte Carlo and Experimental Assessments

PURPOSE To simulate and measure magnetic-field-induced radiation dose effects in a mouse lung phantom. This data will be used to support pre-clinical experiments related to MRI-guided radiation therapy systems. METHODS A mouse lung phantom was constructed out of 1.5×1.5×2.0-cm3 lung-equivalent material (0.3 g/cm3 ) surrounded by a 0.6-cm solid water shell. EBT3 film was inserted into the phantom and the phantom was placed between the poles of an H-frame electromagnet. The phantom was irradiated with a cobalt-60 beam (1.25 MeV) with the electromagnet set to various magnetic field strengths (0T, 0.35T, 0.9T, and 1.5T). These magnetic field strengths correspond to the range of field strengths seen in MRI-guided radiation therapy systems. Dose increases at the solid-water-to-lung-interface and dose decreases at the lung-to-solid-water interface were compared with results of Monte Carlo simulations performed with MCNP6. RESULTS The measured dose to lung at the solid-water-to-lung interface increased by 0%, 16%, and 29% with application of the 0.35T, 0.9T, and 1.5T magnetic fields, respectively. The dose to lung at the lung-to-solid-water interface decreased by 4%, 18%, and 24% with application of the 0.35T, 0.9T, and 1.5T magnetic fields, respectively. Monte Carlo simulations showed dose increases of 0%, 16%, and 31% and dose decreases of 4%, 16%, and 25%. CONCLUSION Only small dose perturbations were observed at the lung-solid-water interfaces for the 0.35T case, while more substantial dose perturbations were observed for the 0.9T and 1.5T cases. There is good agreement between the Monte Carlo calculations and the experimental measurements (within 2%). These measurements will aid in designing pre-clinical studies which investigate the potential biological effects of radiation therapy in the presence of a strong magnetic field. This work was partially funded by Elekta.

SU-E-J-203: Investigation of 1.5T Magnetic Field Dose Effects On Organs of Different Density

Purpose: For the combined 1.5T/6MV MRI-linac system, the perpendicular magnetic field to the radiation beam results in altered radiation dose distributions. This Monte Carlo study investigates the change in dose at interfaces for common organs neighboring soft tissue. Methods: MCNP6 was used to simulate the effects of a 1.5T magnetic field when irradiating tissues with a 6 MV beam. The geometries used in this study were not necessarily anatomically representative in size in order to directly compare quantitative dose effects for each tissue at the same depths. For this purpose, a 512 cm3 cubic material was positioned at the center of a 2744 cm3 cubic soft tissue material phantom. The following tissue materials and their densities were used in this study: lung (0.296 g/cm3), fat (0.95), spinal cord (1.038), soft tissue (1.04), muscle (1.05), eye (1.076), trabecular bone (1.40), and cortical bone (1.85). Results: The addition of a 1.5T magnetic field caused dose changes of +46.5%, +2.4%, −0.9%, −0.8%, −1.5%, −6.5%, and −8.8% at the entrance interface between soft tissue and lung, fat, spinal cord, muscle, eye, trabecular bone, and cortical bone tissues respectively. Dose changes of −39.4%, −4.1%, −0.8%, −0.8%, +0.5%, +6.7%, and +10.9% were observed at the second interface between the same tissues respectively and soft tissue. On average, the build-up distance was reduced by 0.6 cm, and a dose increase of 62.7% was observed at the exit interface between soft tissue and air of the entire phantom. Conclusion: The greatest changes in dose were observed at interfaces containing lung and bone tissues. Due to the prevalence and proximity of bony anatomy to soft tissues throughout the human body, these results encourage further examination of these tissues with anatomically representative geometries using multiple beam configurations for safe treatment using the MRI-linac system. NSF GRFP Grant Award #LH-102SPS