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.

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 R2 > 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.

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 , 2 MV, and 1.25 MeV ) 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. C 2015 American Association of Physicists in Medicine. [http://dx

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 volunteer's 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 volunteer's 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.

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