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Background and Objective: Optimization based image reconstruction algorithm is an advanced algorithm in medical imaging. However, the corresponding solving algorithm is challenging because the optimization model is usually large-scale and non-smooth. This work aims to devise a simple but universal solver for optimization models. Methods: The alternating direction method of multipliers (ADMM) algorithm is a simple and effective solver of the optimization models. However, there always exists a sub-problem that has not closed-form solution. One may use gradient descent algorithm to solve this sub-problem, but the step-size selection via line search is time-consuming. Or, one may use fast Fourier transform (FFT) to get a closed-form solution if the system matrix and the sparse transform matrix are both of special structure. In this work, we propose a simple but universal fully linearized ADMM (FL-ADMM) algorithm that avoids line search to determine step-size and applies to system matrix and sparse transform of any structures. Results: We derive the FL-ADMM algorithm instances for three total variation (TV) models in 2D computed tomography (CT). Further, we validate and evaluate one FL-ADMM algorithm and explore how the two important factors impact convergence rate. Also, we compare this algorithm with the Chambolle-Pock algorithm via real CT phantom reconstructions. These studies show that the FL-ADMM algorithm may accurately solve optimization models in image reconstruction. Conclusion: The FL-ADMM algorithm is a simple, effective, convergent and universal solver of optimization models in image reconstruction. Compared to the existing ADMM algorithms, the new algorithm does not need time-consuming step-size line-search or special demand to system matrix and sparse transform. It is a rapid prototyping tool for optimization based image reconstruction.

PURPOSE: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. METHODS AND MATERIALS: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (~1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx(1)) with boost (Rx(2)) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. RESULTS: Resolution test-patterns demonstrate practical printer resolution of ~0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V(95%) = 95%) with organ sparing (organs at risk D(max) < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V(95%,Rx2) = 91.6%, normoxic tumor V(95%,Rx1) = 95.7%, normal tissue V(100%,Rx1) = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V(95%,Rx2) = 90.9%, hypoxic tumor V(95%,Rx1) = 62.7%, and normal tissue V(100%,Rx2) = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. CONCLUSIONS: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.

Purpose Immune checkpoint inhibitors improve survival in metastatic diseases for some cancers. Multisite SBRT with pembrolizumab (SBRT + Pembro) was shown to be safe with promising local control using biologically effective doses (BEDs) = 95-120 Gy. Increased BED may improve response rate; however, SBRT doses are limited by surrounding organs at risk (OARs). The purpose of this work was to develop and validate methods for safe delivery of ultra-high doses of radiation (BED10 > 300) to be used in future clinical trials. Methods and materials The radiation plans from 15 patients enrolled on a phase I trial of SBRT + pembro were reanalyzed. Metastatic disease sites included liver (8/15), inguinal region (1/15), pelvis (2/15), lung (1/15), abdomen (1/15), spleen (1/15), and groin (1/15). Gross tumor volumes (GTVs) ranged from 80 to 708 cc. Following the same methodology used in the Phase I trial on which these patients were treated, GTVs > 65 cc were contracted to a 65 cc subvolume (SubGTV) resulting in only a portion of the GTV receiving prescription dose. Volumetric modulated arc therapy (VMAT) was used to plan treatments BED10 = 360 Gy. Plans utilizing both 6FFF and 10FFF beams were compared to clinical plans delivering BED10 = 112.50 Gy. The target primary goal was V100% > 95% with a secondary goal of V70% > 99% and OAR objectives per the trial. To demonstrate feasibility, plans were delivered to a diode array phantom and evaluated for fidelity using gamma analysis. Results All 30 plans met the secondary coverage goal and satisfied all OAR constraints. The primary goal was achieved in 12/15 of the 6FFF plans and 13/15 of the 10FFF plans. Average gamma analysis passing rate using criteria of 3% dose difference and 3, 2, and 1 mm were 99.1 ± 1.0%, 98.5 ± 1.6%, and 95.1 ± 3.8%, respectively. Conclusion Novel VMAT planning approaches with clinical treatment planning software and linear accelerators prove capable of delivering radiation doses in excess of 360 Gy BED10 to tumor subvolumes, while maintaining safe OAR doses.

The Halcyon™ platform is self‐contained, combining a treatment planning (Eclipse) system TPS) with information management and radiation delivery components. The standard TPS beam model is configured and locked down by the vendor. A portal dosimetry‐based system for patient‐specific QA (PSQA) is also included. While ensuring consistency across the user base, this closed model may not be optimal for every department. We set out to commission independent TPS (RayStation 9B, RaySearch Laboratories) and PSQA (PerFraction, Sun Nuclear Corp.) systems for use with the Halcyon linac. The output factors and PDDs for very small fields (0.5 × 0.5 cm2) were collected to augment the standard Varian dataset. The MLC leaf‐end parameters were estimated based on the various static and dynamic tests with simple model fields and honed by minimizing the mean and standard deviation of dose difference between the ion chamber measurements and RayStation Monte Carlo calculations for 15 VMAT and IMRT test plans. Two chamber measurements were taken per plan, in the high (isocenter) and lower dose regions. The ratio of low to high doses ranged from 0.4 to 0.8. All percent dose differences were expressed relative to the local dose. The mean error was 0.0 ± 1.1% (TG119‐style confidence limit ± 2%). Gamma analysis with the helical diode array using the standard 3%Global/2mm criteria resulted in the average passing rate of 99.3 ± 0.5% (confidence limit 98.3%–100%). The average local dose error for all detectors across all plans was 0.2% ± 5.3%. The ion chamber results compared favorably with our recalculation with Eclipse and PerFraction, as well as with several published Eclipse reports. Dose distribution gamma analysis comparisons between RayStation and PerFraction with 2%Local/2mm criteria yielded an average passing rate of 98.5% ± 0.8% (confidence limit 96.9%–100%). It is feasible to use the Halcyon accelerator with independent planning and verification systems without sacrificing dosimetric accuracy.

Highlights • Radiation is not typical in the standard of care for cardiac metastases. • MR-guided radiation uses real-time imaging and offers better soft tissue contrast. • Real-time MR-guidance allows for safe high dose radiation to cardiac metastases. • MR-guided stereotactic radiation can improve symptoms without acute toxicity., Aims To assess the safety and efficacy of MR-guided stereotactic body radiation therapy (MRgSBRT) for cardiac metastases. Materials/methods This single institution retrospective analysis evaluated our experience with MRgSBRT for cardiac metastases. Response rate was compared between pre-RT and post-RT imaging. Symptomatic changes were also tracked and documented. Results Between 4/2019 and 3/2020, five patients with cardiac metastases (4 intracardiac and 1 pericardial) were treated with MRgSBRT. Median age at treatment was 73 years (range 64–80) and two patients had pre-existing cardiac disease. Histologies included melanoma and breast adenocarcinoma. Median lesion diameter was 2 cm (range 1.96–5.8 cm). Three patients were symptomatic, one of whom had pulmonary hypertension and RV enlargement. Another patient had an asymptomatic arrythmia. Median PTV prescribed dose was 40 Gy (range 40–50 Gy) and delivered in five fractions on nonconsecutive days. Median PTV volume was 53.4 cc (range 8.7–116.6 cc) and median coverage was 95% (range 84.1–100%). A uniform 3 mm margin was used for real-time gating, allowing a median 7% (range 5–10%) pixel excursion tolerance. Median follow-up was 4.7 months (range 0.9–12.3). Two patients exhibited stable disease, two had a partial response and one exhibited a complete response. All symptomatic patients experienced some relief. There were no acute adverse events, however, one patient without prior cardiac disease developed atrial fibrillation 6 months after treatment. Two patients died of causes unrelated to cardiac MRgSBRT. Conclusion In this largest known series of cardiac metastasis MRgSBRT, real-time image guidance enables safe treatment resulting in good response with improving presenting symptoms without acute adverse events.

Whole brain radiotherapy with hippocampal avoidance (HA-WBRT) is a technique utilized to treat metastatic brain disease while preserving memory and neurocognitive function. We hypothesized that the treatment planning and delivery of HA-WBRT plans is feasible with an MRI-guided linear accelerator (linac) and compared plan results with clinical non-MRI-guided C-Arm linac plans.Twelve HA-WBRT patients treated on a non-MRI-guided C-Arm linac were selected for retrospective analysis. Treatment plans were developed using a 0.35T MRI-guided linac system for comparison to clinical plans. Treatment planning goals were defined as provided in the Phase II Trial NRG CC001. MRI-guided radiotherapy (MRgRT) treatment plans were developed by a dosimetrist and compared with clinical plans. quality assurance (QA) plans were generated and delivered on the MRI-guided linac to a cylindrical diode detector array. Planning target volume (PTV) coverage was normalized to ∼95% to provide a control point for comparison of dose to the organs at risk.MRgRT plans were deliverable and met all clinical goals. Mean values demonstrated that the clinical plans were less heterogeneous than MRgRT plans with mean PTV V37.5 Gy of 0.00% and 0.03% (p = 0.013), respectively. Average hippocampi maximum doses were 14.19 ± 1.29 Gy and 15.00 ± 1.51 Gy, respectively. The gamma analysis comparing planned and measured doses resulted in a mean of 99.9% ± 0.12% of passing points (3%/2mm criteria). MRgRT plans had an average of 38.33 beams with average total delivery time and beam-on time of 13.7 (11.2-17.5) min and 4.1 (3.2-5.4) min, respectively. Clinical plan delivery times ranged from 3 to 7 min depending on the number of noncoplanar arcs. Planning time between the clinical and MRgRT plans was comparable.This study demonstrates that HA-WBRT can be treated using an MRI-guided linear accelerator with comparable treatment plan quality and delivery accuracy.

Background Fiducial markers are frequently used before treatment for image‐guided patient setup in radiation therapy (RT), but can also be used during treatment for image‐guided intrafraction motion detection. This report describes our implementation of automatic marker detection with periodic kV imaging (TrueBeam v2.5) to monitor and correct intrafraction motion during prostate RT. Methods We evaluated the reproducibility and accuracy of software fiducial detection using a phantom with 3 implanted fiducial markers. Clinical implementation for patients with intraprostatic fiducials receiving volumetric modulated arc therapy (VMAT) utilized periodic on‐board kV imaging with 10 s intervals during treatment delivery. For each image, the software automatically identified fiducial locations and determined whether their distance relative to planned locations were within a 3 mm tolerance. Motion was corrected if either ≥2 fiducials in a single image or ≥1 fiducial in sequential images were out of tolerance. Results Phantom studies demonstrated poorer performance of linear fiducials compared to collapsible fiducials, and wide variability to accurately detect fiducials across eight software settings. For any given setting, results were relatively reproducible and precise to ~0.5 mm. Across 17 patients treated with a median of 20 fractions, the software recommended a shift in 44% of fractions, and a shift was actually implemented after visual confirmation of movement greater than the 3 mm threshold in 20% of fractions. Adjustment of our approach led to improved accuracy for the latter (n = 7) patient subset. On average, table repositioning added 3.0 ± 0.3 min to patient time on table. Periodic kV imaging increased skin dose by an estimated 1 cGy per treatment arc. Conclusions Periodic kV imaging with automatic detection of motion during VMAT prostate treatments is commercially available, and can be successfully implemented to mitigate effects of intrafraction motion with careful attention to software settings.

Purpose. The total variation (TV) minimization algorithm is an effective image reconstruction algorithm capable of accurately reconstructing images from sparse and/or noisy data. The TV model consists of two terms: a data fidelity term and a TV regularization term. Two constrained TV models, data divergence-constrained TV minimization (DDcTV) and TV-constrained data divergence minimization (TVcDM), have been successfully applied to computed tomography (CT) and electron paramagnetic resonance imaging (EPRI). In this work, we propose a new constrained TV model, a doubly constrained TV (dcTV) model, which has the potential to further improve the reconstruction accuracy for the two terms which are both of constraint forms. Methods. We perform an inverse crime study to validate the model and its Chambolle-Pock (CP) solver and characterize the performance of the dcTV-CP algorithm in the context of CT. To demonstrate the superiority of the dcTV model, we compare the convergence rate and the reconstruction accuracy with the DDcTV and TVcDM models via simulated data. Results and Conclusions. The performance-characterizing study shows that the dcTV-CP algorithm is an accurate and convergent algorithm, with the model parameters impacting the reconstruction accuracy and the algorithm parameters impacting the convergence path and rate. The comparison studies show that the dcTV-CP algorithm has a relatively fast convergence rate and can achieve higher reconstruction accuracy from sparse projections or noisy projections relative to the other two single-constrained TV models. The knowledge and insights gained in the work may be utilized in the application of the new model in other imaging modalities including divergence-beam CT, magnetic resonance imaging (MRI), positron emission tomography (PET), and EPRI.

The total variation (TV) minimization algorithms is a classical representative of the optimization algorithms and have been widely used for their simpleness, robustness, expandability and their pot...

Purpose/Objective(s) To monitor intrafraction motion during spine stereotactic radiosurgery (SRS) treatment delivery with readily available device, we implemented triggered kV imaging using the on-board imager of the medical linear accelerator advanced imaging package. Materials/Methods Triggered kV imaging technique was clinically implemented and applied to 32 spine SBS patients (75 fx, 20 T-spine tumors, 12 L-spine tumors) during VMAT delivery. Currently available trigger options in the medical linear accelerator software package are MU, gantry angle, time, and respiratory gating. Time trigger was selected to acquire kV images every 15 seconds, in an effort to balance temporal resolution with reasonable time for image evaluation. Upon each image acquisition, a 2D projection of the 3D image-guided radiotherapy (IGRT) structures was automatically calculated and updated at arbitrary angles as a qualitative visual guide for patient alignment during treatment delivery. For IGRT structures, patient anatomy (vertebra and spinous process) and orthopedic hardware if present were contoured, with a 1 mm expansion. As the technique depends on visual inspection, decisions could vary depending on interobserver variability. Therefore, a survey of 10 trained physicists (4) and physicians (6) was conducted to evaluate efficiency and accuracy of clinical decision with kV images collected using an anthropomorphic phantom with different CT slice thicknesses and shifts introduced. The survey consisted of 192 sample images. The participants were asked to determine if a shift requiring intervention was observed. Average time per decision was recorded. Results The robustness of our current patient immobilization system was validated in our clinical implementation. Based on visual inspection of projected IGRT contours on planar kV images, appreciable movement was detected in only one fraction (1.3%). However, in this instance, motion was well beyond PTV/PRV margins (2.4 mm) and treatment was stopped to take a CBCT and correct the displacement, which otherwise would have not been detected. From the survey, the average time spent per decision was 7.5 seconds. In all shift directions, detectability was proportional to the shift size and superior detectability was observed with contours drawn using CT images with 1 mm slice thickness. Shifts smaller than 1 mm are less noticeable (12.6%) compared to 2 mm shifts (42.6%). Participant detection capability was dependent on the level of training. Conclusion This approach provides an effective, non-invasive intrafraction motion monitoring solution, using the built in triggered-imaging technique of the medical linear accelerator. One of the benefits this technique offers is that it can serve as a quality assurance approach to verify adequacy of a patient immobilization system. An important limitation is that the monitoring result is qualitative and depends on observer visual detection capability. Enhanced precision and utility could be achieved if an automated quantitative evaluation feature is implemented. Author Disclosure J. Koo: None. L.Nardella: None. M.Degnan: None. J.Andreozzi: None. H.M. Yu: Honoraria; UpToDate. Speaker's Bureau; BrainLab. Advisory Board; Novocure, AbbVie. J.A.Penagaricano: None. P.A. Johnstone: None. D.E. Oliver: None. K.A. Ahmed: Research Grant; Bristol-Myers Squibb, Genentech. S.Rosenburg: Consulting; Novocure. E.J.Wuthrick: Research Grant; BMS. Honoraria; Regeneron/Sanofi, Varian. Consultant; Regeneron/Sanofi, Varian. R. Diaz: Honoraria; Zeiss; Global Health Outreach. V.Feygelman: None. E.G. Moros: Research Grant; Varian Medical Systems. Promote research in the AAPM; American Association of Physicists in Medicine. Promoting research in the AAPM; American Association of Physicists in Medicine. G.Redler: None.

Purpose/Objective(s) Whole brain radiotherapy with hippocampal avoidance (HA-WBRT) is a technique utilized to treat extensive metastatic brain disease while preserving memory and neurocognitive function. We hypothesized that the treatment planning and delivery of HA-WBRT plans is feasible with an MRI-guided linear accelerator (Linac) and compared plan results with clinical non-MRI-guided C-Arm Linac plans. Materials/Methods Twelve patients treated with HA-WBRT plans on a non-MRI-guided C-Arm Linac were selected for retrospective analysis. Treatment plans were developed for comparison using a 0.35T MRI-guided Linac. Hippocampi were contoured by the physician on a T1 MRI image fused to a planning CT image with a 5mm expansion to the hippocampi for the avoidance structure. The PTV was expanded from the CTV excluding the hippocampal avoidance structure. Treatment planning goals were defined as provided in the Phase II Trial NRG CC001. MRI-guided treatment (MRgRT) plans were developed by a dosimetrist and compared with clinical plans. QA plans were developed and a subset were delivered on the MRI-guided Linac and measured with a cylindrical diode detector array. PTV coverage was normalized to ∼95% to provide a control point for comparison of dose to the organs at risk. Results MRgRT plans were deliverable and met all clinical goals. Mean values demonstrated that the clinical plans were cooler than MRgRT plans with mean V37.5 of 0.00% and 0.66%, respectively. Average hippocampi maximum doses were 14.20 ± 2.04 Gy and 14.33 ± 1.19 Gy for clinical vs MRgRT plans, respectively. Average hippocampi D100% were 8.63 ± 0.52 Gy and 7.87 ± 0.23 Gy, respectively. Average maximum doses to 0.03 cc of optic structures were 30.93 ± 1.10 Gy and 31.78 ± 0.66 Gy, respectively. The gamma analysis comparing planned and measured doses resulted in a mean of 99.9% ± 0.14% of passing points (3%/2mm criteria). MRgRT plans had an average of 38.33 beams with total delivery time ranging from 10.7-15.7 minutes and 4.03 minutes for total beam on time. Clinical plans had average delivery times of 3-7 minutes depending on the number of coplanar arcs. Conclusion This study demonstrates that HA-WBRT can be treated using an MRI-guided linear accelerator with comparable treatment plan quality and delivery accuracy. Given the equitable dosimetric outcomes to traditional CT based plans, the use of MRgRT for hippocampal sparing whole brain radiotherapy opens the possibility of radiomic analysis and potential adaptive treatments (i.e., boost) to lesions based on disease response.

Purpose: There is growing interest in the use of modern 3D printing technology to implement intensity-modulated radiation therapy (IMRT) on the preclinical scale which is analogous to clinical IMRT. However, current 3D-printed IMRT methods suffer from complex modulation patterns leading to long delivery times, excess filament usage, and inaccurate compensator fabrication. In this work, we have developed a total variation regularization (TVR) approach to address these issues. Methods: TVR-IMRT, a technique designed to minimize the intensity difference between neighboring beamlets, was used to optimize the beamlet intensity map, which was then converted to corresponding compensator thicknesses in copper-doped PLA filament. IMRT and TVR-IMRT plans using five beams were generated to treat a mouse heart while sparing lung tissue. The individual field doses and composite dose were delivered to film and compared to the corresponding planned doses using gamma analysis. Results: TVR-IMRT reduced the total variation of both the beamlet intensities and compensator thicknesses by around 50% when compared to standard 3D printed compensator IMRT. The total mass of compensator material consumed and radiation beam-on time were reduced by 20-30%, while DVHs remained comparable. Gamma analysis passing rate with 3%/0.3mm criterion was 89.07% for IMRT and 95.37% for TVR-IMRT. Conclusion: TVR can be applied to small animal IMRT beamlet intensities in order to produce fluence maps and subsequent 3D-printed compensator patterns with less total variation, simplifying 3D printing and reducing the amount of filament required. The TVR-IMRT plan required less beam-on time while maintaining the dose conformity when compared to a traditional IMRT plan.

Emergence of the COVID-19 crisis has catalyzed rapid paradigm shifts throughout medicine. Even after the initial wave of the virus subsides, a wholesale return to the prior status quo is not prudent. As a specialty that values the proper application of new technology, radiation oncology should strive to be at the forefront of harnessing telehealth as an important tool to further optimize patient care. We remain cognizant that telehealth cannot and should not be a comprehensive replacement for in-person patient visits because it is not a one for one replacement, dependent on the intention of the visit and patient preference. However, we envision the opportunity for the virtual patient “room” where multidisciplinary care may take place from every specialty. How we adapt is not an inevitability, but instead, an opportunity to shape the ideal image of our new normal through the choices that we make. We have made great strides toward genuine multidisciplinary patient-centered care, but the continued use of telehealth and virtual visits can bring us closer to optimally arranging the spokes of the provider team members around the central hub of the patient as we progress down the road through treatment.

Introduction: Spine stereotactic body radiation therapy (SBRT) achieves favorable outcomes compared to conventional radiotherapy doses/fractionation. The spinal cord is the principal dose-limiting organ-at-risk (OAR), and safe treatment requires precise immobilization/localization. Therefore, image guidance is paramount to successful spine SBRT. Conventional X-ray imaging and alignment to surrogate bony anatomy may be inadequate, whereas magnetic resonance imaging (MRI) directly visualizes the dose-limiting cord. This work assessed the dosimetric capability of the ViewRay (ViewRay Inc. Oakwood Village, OH) magnetic resonance (MR) guided linac (MR-Linac) for spine SBRT. Methods: Eight spine SBRT patients without orthopedic hardware who were previously treated on a TrueBeam using volumetric modulated arc therapy (VMAT) were re-planned using MR-Linac fixed-field intensity-modulated radiation therapy (IMRT). Phantom measurements using film, ionization chamber, and a commercial diode-array assessed feasibility. Plans included a variety of prescriptions (30-50 Gy in 3-10 fractions). Results: MR-Linac plans satisfied all clinical goals. Compared to VMAT plans, both entrance dose and heterogeneity increased (Dmax: 134±3% vs. 120±2%, p=0.0270), while conformality decreased (conformity index: 1.28±0.06 vs. 1.06±0.06, p=0.0005), and heterogeneity increased. However, while not statistically significant, MR-linac cord sparing improved (cord Dmax: 16.1±2.7Gy vs. 19.5±1.6Gy, p=0.2066; cord planning organ at risk volume (cord PRV) Dmax: 20.0±2.6Gy vs. 24.5±2.0Gy, p=0.0996). Delivery time increased but was acceptable (14.39±1.26min vs. 9.57±1.19min). Ionization chamber measurements agreed with planned dose to within 2.5%. Film and diode measurements demonstrated accurate/precise delivery of dose gradients between the target and the cord. Conclusion: Spine SBRT with the MR-Linac is feasible as verified via re-planning eight clinical cases followed by delivery verification in phantoms using film, diodes, and an ionization chamber. Real-time visualization of the dose-limiting cord during spine SBRT may enable cord-based gating, reduced margins, alternate dose schemas, and/or adaptive therapy.

The optimization-based image reconstruction methods have been thoroughly investigated in the field of medical imaging. The Chambolle-Pock (CP) algorithm may be employed to solve these convex optimization image reconstruction programs. The preconditioned CP (PCP) algorithm has been shown to have much higher convergence rate than the ordinary CP (OCP) algorithm. This algorithm utilizes a preconditioner-parameter to tune the implementation of the algorithm to the specific application, which ranges from 0 and 2, but is often set to 1. In this work, we investigated the impact of the preconditioner-parameter on the convergence rate of the PCP algorithm when it is applied to the TV constrained, data-divergence minimization (TVDM) optimization based image reconstruction. We performed the investigations in the context of 2D computed tomography (CT) and 3D electron paramagnetic resonance imaging (EPRI). For 2D CT, we used the Shepp-Logan and two FORBILD phantoms. For 3D EPRI, we used a simulated 6-spheres phantom and a physical phantom. Study results showed that the optimal preconditioner-parameter depends on the specific imaging conditions. Simply setting the parameter equal to 1 cannot guarantee a fast convergence rate. Thus, this study suggests that one should adaptively tune the preconditioner-parameter to obtain the optimal convergence rate of the PCP algorithm.

Background and Objective: The constrained, total variation (TV) minimization algorithm has been applied in computed tomography (CT) for more than 10 years to reconstruct images accurately from sparse-view projections. Chambolle-Pock (CP) algorithm framework has been used to derive the algorithm instance for the constrained TV minimization programme. However, the ordinary CP (OCP) algorithm has slower convergence rate and each iteration is also time-consuming. Thus, we investigate the acceleration approaches for achieving fast convergence and high-speed reconstruction. Methods: To achieve fast convergence rate, we propose a new algorithm parameters setting approach for OCP. To achieve high-speed reconstruction in each iteration, we use graphics processing unit (GPU) to speed-up the two time-consuming operations, projection and backprojection. Results: We evaluate and validate our acceleration approaches via two-dimensional (2D) reconstructions of a low-resolution Shepp–Logan phantom from noise-free...

Objectives This work aims to explore more accurate pixel-driven projection methods for iterative image reconstructions in order to reduce high-frequency artifacts in the generated projection image. Methods Three new pixel-driven projection methods namely, small-pixel-large-detector (SPLD), linear interpolation based (LIB) and distance anterpolation based (DAB), were proposed and applied to reconstruct images. The performance of these methods was evaluated in both two-dimensional (2D) computed tomography (CT) images via the modified FORBILD phantom and three-dimensional (3D) electron paramagnetic resonance (EPR) images via the 6-spheres phantom. Specifically, two evaluations based on projection generation and image reconstruction were performed. For projection generation, evaluation was using a 2D disc phantom, the modified FORBILD phantom and the 6-spheres phantom. For image reconstruction, evaluations were performed using the FORBILD and 6-spheres phantom. During evaluation, 2 quantitative indices of root-mean-square-error (RMSE) and contrast-to-noise-ratio (CNR) were used. Results Comparing to the use of ordinary pixel-driven projection method, RMSE of the SPLD based least-square algorithm was reduced from 0.0701 to 0.0384 and CNR was increased from 5.6 to 19.47 for 2D FORBILD phantom reconstruction. For 3D EPRI, RMSE of SPLD was also reduced from 0.0594 to 0.0498 and CNR was increased from 3.88 to 11.58. In addition, visual evaluation showed that images reconstructed in both 2D and 3D images suffered from high-frequency line-shape artifacts when using the ordinary pixel-driven projection method. However, using 3 new methods all suppressed the artifacts significantly and yielded more accurate reconstructions. Conclusions Three proposed pixel-driven projection methods achieved more accurate iterative image reconstruction results. These new and more accurate methods can also be easily extended to other imaging modalities. Among them, SPLD method should be recommended to 3D and four dimensional (4D) EPR imaging.

Purpose/Objective(s) An innovative ring gantry CBCT-guided adaptive radiotherapy system enables efficient planning and online adaptation to account for interfraction changes. Initial planning strategies and plan quality for head and neck (HN 2) prioritize PTV coverage by excluding organ at risk (OAR) goals when OAR intersects PTVs; 3) generate and assign goals to OAR subvolumes cropped from PTVs. Utility of generalized helper structures for controlling hot spot location and low dose spillage is investigated. The best of each patient's 5 candidate AI plans (AcurosXB) is compared to clinical (collapsed cone) plan using NRG guidelines. Results Strategies 1 and 2 consistently result in PTV under-coverage, high PTV hot spots, and failed OAR goals when intersecting PTVs. Strategy 3 provides acceptable PTV coverage and OAR dosimetry comparable to clinical plans. Helper structures (posterior block, distal OAR subvolumes, and PTVmed/low cropped from PTVhigh) were found to be necessary for shaping dose distributions similarly to clinical plans. Optimal plan type varied: 12 (n = 5), 9 (n = 2), 7 (n = 1) field IMRT and 3 arc VMAT (n = 1). Comparison of AI and clinical plans is based on using strategy (3) with helper structures. Compared to clinical plans, for all PTVs, average D99%, D95%, and Dmax are higher by 3.1% (103.6% vs. 100.5%), 1.3% (102.2 vs. 100.9%), and 3.3% (108.8% vs. 105.5%), respectively, but still within NRG guidelines. However, global hot spots may fall outside of PTVs and are higher by 5%. Hot spot differences may be from differences in dose calculation algorithms. The spinal cord, brainstem, parotid, oral cavity, mandible and thyroid doses are below NRG guidelines for both plans, with AI plan doses slightly lower. Larynx, Pharynx and submandibular doses on average are higher than the NRG guidelines due to PTV proximity for both plans, with AI plan doses slightly higher. Conclusion The AI plan optimizer for this adaptive platform utilizes a novel planning paradigm based on clinical goals rather than direct optimization parameters and can efficiently generate H&N treatment plans. AI plans are comparable to clinical plans with slightly better PTV coverage and lower OAR doses. However, issues with higher and spatially undesirable calculated hot spots remain. All plans meet NRG guidelines.

The sparing of the parotid glands in the treatment of head and neck cancers is of clinical relevance as high doses to the salivary glands may result in xerostomia. Xerostomia is a major cause of decreased quality of life for head and neck patients. This paper explores the relationship between the overlap of the target volumes and their expansions with the parotid glands for helical delivery plans and their ability to be spared. Various overlapping volumes were examined, and an overlap with a high statistical relevance was found. A model that predicts exceeding tolerance parotid mean dose based on its fractional overlapping volume with PTVs was developed. A fractional overlapping volume of 0.083 between the parotid gland and the high dose PTV plus 5 mm expansion – was determined to be the threshold value to predict parotid Dmean > 26 Gy for parotids that overlap with the high dose PTV plus 5 mm expansion. If the parotid gland only overlaps with the intermediate dose target (and/or low dose target) and the overlapping volume of the parotid gland and the intermediate dose target is less than 25%, the parotid mean dose is likely less than 26 Gy. If the parotid overlaps with the low dose target only then the mean dose to the parotid is likely to be less than 26 Gy. This finding will prove as a very useful guide for the physicians and planners involved in the planning process to know prior whether the parotid glands will be able to be spared with the current set of target volumes or if revisions are necessary. This work will serve as a helpful guide in the planning process of head and neck target cases.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

By collecting photons scattered out of the therapy beam, scatter imaging creates images of the treated volume. Two phantoms were used to assess the possible application of scatter imaging for markerless tracking of lung tumors during stereotactic body radiation therapy (SBRT) treatment. A scatter-imaging camera was assembled with a CsI flat-panel detector and a 5 mm diameter pinhole collimator. Scatter images were collected during the irradiation of phantoms with megavoltage photons. To assess scatter image quality, spherical phantom lung tumors of 2.1–2.8 cm diameters were placed inside a static, anthropomorphic phantom. To show the efficacy of the technique with a moving target (3 cm diameter), the position of a simulated tumor was tracked in scatter images during sinusoidal motion (15 mm amplitude, 0.25 Hz frequency) in a dynamic lung phantom in open-field, dynamic conformal arc (DCA), and volumetric modulated arc therapy (VMAT) deliveries. Anatomical features are identifiable on static phantom scatter images collected with 10 MU of delivered dose (2.1 cm diameter lung tumor contrast-to-noise ratio of 4.4). The contrast-to-noise ratio increases with tumor size and delivered dose. During dynamic motion, the position of the 3.0 cm diameter lung tumor was identified with a root-mean-square error of 0.8, 1.2, and 2.9 mm for open field (0.3 s frame integration), DCA (0.5 s), and VMAT (0.5 s), respectively. Based on phantom studies, scatter imaging is a potential technique for markerless lung tumor tracking during SBRT without additional imaging dose. Quality scatter images may be collected at low, clinically relevant doses (10 MU). Scatter images are capable of sub-millimeter tracking precision, but modulation decreases accuracy.

Electron paramagnetic resonance imaging (EPRI) can yield information about the 3-dimensional (3D) spatial distribution of the unpaired-electron-spin density from which the spatial distribution of oxygen concentration within tumor tissue, referred to as the oxygen image or electron paramagnetic resonance (EPR) image in this work, can be derived. Existing algorithms for reconstruction of EPR images often require data collected at a large number of densely sampled projection views, resulting in a prolonged data-acquisition time and consequently numerous practical challenges especially to in vivo animal EPRI. Therefore, a strong interest exists in shortening data-acquisition time through reducing the number of data samples collected in EPRI, and one approach is to acquire data at a reduced number of sparsely distributed projection views from which existing algorithms may reconstruct images with prominent artifacts. In this work, we investigate and develop an optimization-based technique for image reconstruction from data collected at sparsely sampled projection views for reducing scanning time in EPRI. Specifically, we design a convex optimization program in which the EPR image of interest is formulated as a solution and then tailor the Chambolle-Pock (CP) primal-dual algorithm to reconstruct the image by solving the convex optimization program. Using computer-simulated EPRI data from numerical phantoms and real EPRI data collected from physical phantoms, we perform studies on the verification and characterization of the optimization-based technique for EPR image reconstruction. Results of the studies suggest that the technique may yield accurate EPR images from data collected at sparsely distributed projection views, thus potentially enabling fast EPRI with reduced acquisition time.

The importance of tissue oxygenation has led to a great interest in methods for imaging pO2 in vivo. Electron paramagnetic resonance imaging (EPRI) provides noninvasive, near absolute 1 mm-resolved 3D images of pO2 in the tissues and tumors of living animals. Current EPRI image reconstruction methods tend to be time consuming and preclude real-time visualization of information. Methods are presented to significantly accelerate the reconstruction process in order to enable real-time reconstruction of EPRI pO2 images. These methods are image reconstruction using graphics processing unit (GPU)-based 3D filtered back-projection and lookup table parameter fitting. The combination of these methods leads to acceleration factors of over 650 compared to current methods and allows for real-time reconstruction of EPRI images of pO2 in vivo.

Electron paramagnetic resonance imaging (EPRI) provides 3D images of absolute oxygen concentration (pO2) in vivo with excellent spatial and pO2 resolution. When investigating such physiologic parameters in living animals, the situation is inherently dynamic. Improvements in temporal resolution and experimental versatility are necessary to properly study such a system. Uniformly distributed projections result in efficient use of data for image reconstruction. This has dictated current methods such as equal-solid-angle (ESA) spacing of projections. However, acquisition sequencing must still be optimized to achieve uniformity throughout imaging. An object-independent method for uniform acquisition of projections, using the ESA uniform distribution for the final set of projections, is presented. Each successive projection maximizes the distance in the gradient space between itself and prior projections. This maximally spaced projection sequencing (MSPS) method improves image quality for intermediate images reconstructed from incomplete projection sets, enabling useful real-time reconstruction. This method also provides improved experimental versatility, reduced artifacts, and the ability to adjust temporal resolution post factum to best fit the data and its application. The MSPS method in EPRI provides the improvements necessary to more appropriately study a dynamic system.

Pulse electron paramagnetic resonance imaging (Pulse EPRI) is a robust method for noninvasively measuring local oxygen concentrations in vivo. For 3D tomographic EPRI, the most commonly used reconstruction algorithm is filtered back projection (FBP), in which the parabolic filtration process strongly influences image quality. In this work, we designed and compared 7 parabolic filtration methods to reconstruct both simulated and real phantoms. To evaluate these methods, we designed 3 error criteria and 1 spatial resolution criterion. It was determined that the 2 point derivative filtration method and the two-ramp-filter method have unavoidable negative effects resulting in diminished spatial resolution and increased artifacts respectively. For the noiseless phantom the rectangular-window parabolic filtration method and sinc-window parabolic filtration method were found to be optimal, providing high spatial resolution and small errors. In the presence of noise, the 3 point derivative method and Hamming-window parabolic filtration method resulted in the best compromise between low image noise and high spatial resolution. The 3 point derivative method is faster than Hamming-window parabolic filtration method, so we conclude that the 3 point derivative method is optimal for 3D FBP.

Purpose The Xoft Axxent Electronic Brachytherapy System (Xoft, Inc., San Jose, CA) is a viable option for intraoperative radiation therapy (IORT) treatment of early-stage breast cancer. The low-energy (50-kVp) X-ray source simplifies shielding and increases relative biological effectiveness but increases dose distribution sensitivity to medium composition. Treatment planning systems typically assume homogenous water for brachytherapy dose calculations, including precalculated atlas plans for Xoft IORT. However, Xoft recommends saline for balloon applicator filling. This study investigates dosimetric differences due to increased effective atomic number (Z eff ) for saline (Z eff = 7.56) versus water (Z eff = 7.42). Methods Balloon applicator diameters range from 3 to 6 cm. Monte Carlo N-Particle software is used to calculate dose at the surface ( D s ) of and 1 cm away ( D 1cm ) from the water-/saline-filled balloon applicator using a single dwell at the applicator center as a simple estimation of the dosimetry and multiple dwells simulating the clinical dose distributions for the atlas plans. Results Single-dwell plans show a 4.4–6.1% decrease in D s for the 3- to 6-cm diameter applicators due to the saline. Multidwell plans show similar results: 4.9% and 6.4% D s decrease, for 4-cm and 6-cm diameter applicators, respectively. For the single-dwell plans, D 1cm decreases 3.6–5.2% for the 3- to 6-cm diameter applicators. For the multidwell plans, D 1cm decreases 3.3% and 5.3% for the 4-cm and 6-cm applicators, respectively. Conclusions The dosimetric effect introduced by saline versus water filling for Xoft balloon applicator–based IORT treatments is ∼5%. Users should be aware of this in the context of both treatment planning and patient outcome studies.

PURPOSE Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. METHODS To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. RESULTS Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. CONCLUSIONS Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance.

Purpose EPR spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as pO2, pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl 3 relative to the corresponding di-acid 4.

Purpose Low oxygen concentration (hypoxia) in tumors strongly affects their malignant state and resistance to therapy. These effects may be more deleterious in regions undergoing cycling hypoxia. Electron paramagnetic resonance imaging (EPRI) has provided a noninvasive, quantitative imaging modality to investigate static pO2 in vivo. However, to image changing hypoxia, EPRI images with better temporal resolution may be required. The tradeoff between temporal resolution and signal-to-noise ratio (SNR) results in lower SNR for EPRI images with imaging time short enough to resolve cycling hypoxia. Methods Principal component analysis allows for accelerated image acquisition with acceptable SNR by filtering noise in projection data, from which pO2 images are reconstructed. Principal component analysis is used as a denoising technique by including only low-order components to approximate the EPRI projection data. Results Simulated and experimental studies show that principal component analysis filtering increases SNR, particularly for small numbers of sub-volumes with changing pO2, enabling an order of magnitude increase in temporal resolution with minimal deterioration in spatial resolution or image quality. Conclusion The SNR necessary for dynamic EPRI studies with temporal resolution required to investigate cycling hypoxia and its physiological implications is enabled by principal component analysis filtering. Magn Reson Med 71:440–450, 2014. © 2013 Wiley Periodicals, Inc.

Hypoxic tumors are resistant to radiotherapy, motivating the development of tools to image local oxygen concentrations. It is generally believed that stable or chronic hypoxia is the source of resistance, but more recent work suggests a role for transient hypoxia. Conventional EPR imaging (EPRI) is capable of imaging tissue pO2 in vivo, with high pO2 resolution and 1 mm spatial resolution but low imaging speed (10 min temporal resolution for T1-based pO2 mapping), which makes it difficult to investigate the oxygen changes, e.g. transient hypoxia. Here we describe a new imaging method which accelerates dynamic EPR oxygen imaging, allowing 3D imaging at 2 frames per minute, fast enough to image transient hypoxia at the “speed limit” of observed pO2 change. The method centers on a low-rank tensor model that decouples the tradeoff between imaging speed, spatial coverage/resolution, and number of inversion times (pO2 accuracy). We present a specialized sparse sampling strategy and image reconstruction algorithm for use with this model. The quality and utility of the method is demonstrated in simulations and in vivo experiments in tumor bearing mice.

The outcome of cancer radiation treatment is strongly correlated with tumor oxygenation. The aim of this study is to use oxygen tension distributions in tumors obtained using Electron Paramagnetic Resonance (EPR) imaging to devise better tumor radiation treatment. The proposed radiation plan is delivered in two steps. In the first step, a uniform 50 % tumor control dose (TCD50) is delivered to the whole tumor. For the second step an additional dose boost is delivered to radioresistant, hypoxic tumor regions. FSa fibrosarcomas grown in the gastrocnemius of the legs of C3H mice were used. Oxygen tension images were obtained using a 250 MHz pulse imager and injectable partially deuterated trityl OX63 (OX71) spin probe. Radiation was delivered with a novel animal intensity modulated radiation therapy (IMRT) XRAD225Cx microCT/radiation therapy delivery system. In a simplified scheme for boost dose delivery, the boost area is approximated by a sphere, whose radius and position are determined using an EPR O2 image. The sphere that irradiates the largest fraction of hypoxic voxels in the tumor was chosen using an algorithm based on Receiver Operator Characteristic (ROC) analysis. We used the fraction of irradiated hypoxic volume as the true positive determinant and the fraction of irradiated normoxic volume as the false positive determinant in the terms of that analysis. The most efficient treatment is the one that demonstrates the shortest distance from the ROC curve to the upper left corner of the ROC plot. The boost dose corresponds to the difference between TCD90 and TCD50 values. For the control experiment an identical radiation dose to the normoxic tumor area is delivered.

Electron paramagnetic resonance imaging (EPRI) has been used to noninvasively provide 3D images of absolute oxygen concentration (pO2) in small animals. These oxygen images are well resolved both spatially (~1 mm) and in pO2 (1-3 mmHg). EPRI preclinical images of pO2 have demonstrated extremely promising results for various applications investigating oxygen related physiologic and biologic processes as well as the dependence of various disease states on pO2, such as the role of hypoxia in cancer. Recent developments have been made that help to progress EPRI towards the eventual goal of human application. For example, a bimodal crossed-wire surface coil has been developed. Very preliminary tests demonstrated a 20 dB isolation between transmit and receive for this coil, with an anticipated additional 20 dB achievable. This could potentially be used to image local pO2 in human subjects with superficial tumors with EPRI. Local excitation and detection will reduce the specific absorption rate limitations on images and eliminate any possible power deposition concerns. Additionally, a large 9 mT EPRI magnet has been constructed which can fit and provide static main and gradient fields for imaging local anatomy in an entire human. One potential obstacle that must be overcome in order to use EPRI to image humans is the approved use of the requisite EPRI spin probe imaging agent (trityl). While nontoxic, EPRI trityl spin probes have been injected intravenously when imaging small animals, and require relatively high total body injection doses that would not be suitable for human imaging applications. Work has been done demonstrating the alternative use of intratumoral (IT) injections, which can reduce the amount of trityl required for imaging by a factor of 2000- relative to a whole body intravenous injection. The development of a large magnet that can accommodate human subjects, the design of a surface coil for imaging of superficial pO2, and the reduction of required spin probe using IT injections all are crucial steps towards the eventual use of EPRI to image pO2 in human subjects. In the future this can help investigate the oxygenation status of superficial tumors (e.g., breast tumors). The ability to image pO2 in humans has many other potential applications to diseases such as peripheral vascular disease, heart disease, and stroke.

Living tissue hypoxic resistance to radiation, has been known for over a century. Our research has validated the hypothesis that radiation dose boosts focused specifically on hypoxic regions of tumors would improve tumor curability in a fibrosarcoma mouse model. We used Electron Paramagnetic Resonance (EPR) imaging of absolute pO2 in volume elements of murine tumors with 1 torr pO2 resolution and 0.7 mm spatial resolution in FSa fibrosarcomas in the legs of C3H mice. Hypoxia was defined as subvolumes or voxels with pO2 less than 10 torr. This showed EPR pO2 images as a reliable identifier and locator of relevant radiobiologically hypoxia. For the first time in mammalian tumors pO2 based dose painting was shown to improves tumor cure. This required gantry based x-ray treatment with an XRAD225Cx system to deliver dose to mouse tumors accurately registered with EPR pO2 images. Tumors were pretreated with a dose of radiation sufficient to cure 15% of tumors, a TCD15. For hypoxic boosts or hypoxia avoidance of the same volume, 3D printing Tungsten loaded, highly conformal plastic blocks were used. This allowed comparison of treating 100% of hypoxic tumor voxels with hypoxia avoidance boosts. This showed significant (p=0.02) tumor control differences between hypoxic boosts and hypoxia avoiding boosts. This is the first validation of the curative effectiveness of focusing hypoxia based dose painting in mammalian tumors. This was motivated by a conclusive failure to demonstrate a difference between treating ~ 85% of hypoxic voxels with a hypoxic boost compared with radiation avoiding hypoxia which proved tenets of radiation biology: a few surviving hypoxic clonogens cause radiation treatment failure. To further validate this approach, we have applied the same techniques to a second mouse mammary carcinoma, the MCa4. We have determined the dose response of 325 μl IM tumors in C3H mouse legs with a 50% control at 180 days with 52 Gy radiation (the TCD50). We have begun the study of tumor control using a whole tumor TCD15 of 49 Gy and boosts of 11 Gy to hypoxic and well oxygenated tumor of the same volume. With a median follow up of35 days of 10 animals, none of the hypoxic boost cohort have failed. All failure has been in the well oxygenated tumor boost cohort. Log-Rank significance is ~0.2. Our past experience has been that these early results portend future significance. Support: R01 CA098575, P41 EB002035, R50 CA211408 Citation Format: Howard J. Halpern, Boris Epel, Matthew C. Maggio, Martyna Krzykawska-Serda, Gage H. Redler, Richard C. Miller, Eugene D. Barth, Ralph R. Weichselbaum, Victor M. Tormyshev. Second tumor type showing hypoxia targeting with radiation improves tumor control in a mammal tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4157.

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140–220 keV, and 40–50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min−1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.