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Quantification of cerivastatin toxicity supports organismal performance assays as an effective tool during pharmaceutical safety assessment

A major problem in pharmaceutical development is that adverse effects remain undetected during preclinical and clinical trials, but are later revealed after market release when prescribed to many patients. We have developed a fitness assay known as the organismal performance assay (OPA), which evaluates individual performance by utilizing outbred wild mice ( Mus musculus ) that are assigned to an exposed or control group, which compete against each other for resources within semi-natural enclosures. Performance measurements included reproductive success, survival, and male competitive ability. Our aim was to utilize cerivastatin (Baycol ® , Bayer), a pharmaceutical with known adverse effects, as a positive control to assess OPAs as a potential tool for evaluating the safety of compounds during preclinical trials. Mice were exposed to cerivastatin (~4.5 mg/kg/day) into early adulthood. Exposure ceased and animals were released into semi-natural enclosures. Within enclosures, cerivastatin-exposed females had 25% fewer offspring and cerivastatin-exposed males had 10% less body mass, occupied 63% fewer territories, sired 41% fewer offspring, and experienced a threefold increase in mortality when compared to controls. OPAs detected several cerivastatin-nduced adverse effects indicating that fitness assays, commonly used in ecology and evolutionary biology, could be useful as an additional tool in safety testing during pharmaceutical development.

59 BASIC BIOLOGICAL SCIENCES↗

A Rapid Decision Support Tool for Estimating Impacts of a Vadose Zone Volatile Organic Compound Source on Groundwater and Soil Gas

Diminishing rates of subsurface volatile contaminant removal by soil vapor extraction (SVE) oftentimes warrants an in‐depth performance assessment to guide remedy decision‐making processes. Such a performance assessment must include quantitative approaches to better understand the impact of remaining vadose zone contamination on soil gas and groundwater concentrations. The spreadsheet‐based Soil Vapor Extraction Endstate Tool (SVEET) software functionality has recently been expanded to facilitate quantitative performance assessments. The updated version, referred to as SVEET2, includes expansion of the input parameter ranges for describing a site (site geometry, source characteristics, etc.), an expanded list of contaminants, and incorporation of elements of the Vapor Intrusion Estimation Tool for Unsaturated‐zone Sources software to provide soil gas concentration estimates for use in vapor intrusion evaluation. As part of the update, SVEET2 was used to estimate the impact of a tetrachloroethene (PCE) vadose zone source on groundwater concentrations, comparing SVEET2 results to field‐observed values at an undisclosed site where SVE was recently terminated. PCE concentrations from three separate monitoring wells were estimated by SVEET2 to be within the range of 6.0–6.7 μg/L, as compared to actual field concentrations that ranged from 3 to 11 μg/L PCE. These data demonstrate that SVEET2 can rapidly provide representative quantitative estimates of impacts from a vadose zone contaminant source at field sites. Finally, in the context of the SVE performance assessment, such quantitative estimates provide a basis to support remedial and/or regulatory decisions regarding the continued need for vadose zone volatile organic compound remediation or technical justification for SVE termination, which can significantly reduce the cost to complete for a site.

54 ENVIRONMENTAL SCIENCES↗

High‐Resolution Direct Push NMR Tools for Groundwater Investigations

Abstract A small‐diameter nuclear magnetic resonance (NMR) technology optimized for use with direct push (DP) and cone penetrometer test (CPT) drilling has been developed. The DP NMR tool can be deployed through 2.25‐in. diameter DP and CPT drilling rods allowing high‐resolution NMR logging measurements to be acquired during retraction of drill rods. DP NMR technology runs from a person‐portable battery‐powered control unit and provides significantly higher resolution in both the spatial (vertical) dimension and in the time domain of the NMR measurement than previously available NMR technology. In this study, we summarize the development of two different DP NMR tools and demonstrate their application at different sites within the United States. We believe that this technology can provide a leap forward in adoption of NMR technology for high‐resolution hydrological and geophysical investigations in groundwater resources and environmental remediation applications.

54 ENVIRONMENTAL SCIENCES↗

A High-Fidelity Modeling Tool to Support the Design of Oxy-Combustors for Direct-Fired Supercritical CO2 Cycles

The challenge in the design of oxy-combustors for direct-fired supercritical CO 2 (sCO 2 ) cycles is in addressing disparate performance metrics and objectives. Key design parameters to consider include, among others, injector design for mixing and flame stability, split of recycled CO 2 diluent between injectors and cooling films, target flame temperatures to control noncondensable products, and strategies to inject the diluent CO 2 for film cooling and thermal control. In order to support novel oxy-combustor designs, a high-fidelity yet numerically efficient modeling framework based on the CRUNCH CFD® flow solver is presented, featuring key physics-based submodels relevant in this regime. For computational efficiency in modeling large kinetic sets, a flamelet/progress variable (FPV) based tabulated-chemistry approach is utilized featuring a three-stream extension to allow for the simulation of the CO 2 film cooling stream in addition to the fuel and oxidizer streams. Finite rate chemistry effects are modeled in terms of multiple progress variables for the primary flame as well as for slower-evolving chemical species such as NO x and SO x contaminants. Real fluid effects are modeled using advanced equations of states. The predictive capabilities of this computationally tractable design support tool are demonstrated on a conceptual injector design for an oxy-combustor operating near 30 MPa. Simulations results provide quantitative feedback on the effectiveness of the film cooling as well as the level of contaminants (CO, NO, and N) in the exhaust due to impurities entering from the injectors. These results indicate that this framework would be a useful tool for refining and optimizing the oxy-combustor designs as well as risk mitigation analyses.

Engineering↗

DASAO: software tool for the management of safeguards, waste and decommissioning

Decommissioning of nuclear facilities is a complex process involving operations such as detailed surveys, decontamination and dismantling of equipment's, demolition of buildings and management of resulting waste and nuclear materials if any. This process takes place in a well-developed legal framework and is controlled and followed-up by stakeholders like the Safety Authority, the Radwaste management Agency and the Safeguards Organism. In the framework of its nuclear waste and decommissioning program and more specifically the decommissioning of the BR3 reactor, SCK-CEN has developed different software tools to secure the waste and material traceability, to support the sound management of the decommissioning project and to facilitate the control and the follow-up by the stakeholders. In the case of Belgium, it concerns the Federal Agency for Nuclear Control, the National Agency for radioactive waste management and fissile material and EURATOM and IAEA. In 2005, Belgonucleaire decided to shutdown her Dessel MOX fuel fabrication plant and the production stopped in 2006. According to the final decommissioning plan ('PDF') approved by NIRAS, the decommissioning works should start in 2008 at the earliest. In 2006, the management of Belgonucleaire identified the need for an integrated database and decided to entrust SCK-CEN with its development, because SCK-CEN relies on previous experience in comparable applications namely already approved by authorities such as NIRAS, FANC and EURATOM. The main objectives of this integrated software tool are: - simplified and updated safeguards; - waste and material traceability; - computerized documentation; - support to project management; - periodic and final reporting to waste and safety authorities. The software called DASAO (Database for Safeguards, Waste and Decommissioning) was successfully commissioned in 2008 and extensively used from 2009 to the satisfaction of Belgonucleaire and the stakeholders. SCK-CEN is now implementing a simplified release of the software for the management of the decommissioning of the Thetis reactor. Its decommissioning will start in March 2013 and will be completed by the end of 2014. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Assessing the Importance of Nonlinearities in the Development of a Substructure Model for the Wind Turbine CAE Tool FAST: Preprint

Design and analysis of wind turbines are performed using aero-servo-elastic tools that account for the nonlinear coupling between aerodynamics, controls, and structural response. The NREL-developed computer-aided engineering (CAE) tool FAST also resolves the hydrodynamics of fixed-bottom structures and floating platforms for offshore wind applications. This paper outlines the implementation of a structural-dynamics module (SubDyn) for offshore wind turbines with space-frame substructures into the current FAST framework, and focuses on the initial assessment of the importance of structural nonlinearities. Nonlinear effects include: large displacements, axial shortening due to bending, cross-sectional transverse shear effects, etc.

17 WIND ENERGY↗

Implementing Nonlinear Buoyancy and Excitation Forces in the WEC-Sim Wave Energy Converter Modeling Tool: Preprint

Wave energy converters (WECs) are commonly designed and analyzed using numerical models that combine multi-body dynamics with hydrodynamic models based on the Cummins Equation and linearized hydrodynamic coefficients. These modeling methods are attractive design tools because they are computationally inexpensive and do not require the use of high performance computing resources necessitated by high-fidelity methods, such as Navier Stokes computational fluid dynamics. Modeling hydrodynamics using linear coefficients assumes that the device undergoes small motions and that the wetted surface area of the devices is approximately constant. WEC devices, however, are typically designed to undergo large motions in order to maximize power extraction, calling into question the validity of assuming that linear hydrodynamic models accurately capture the relevant fluid-structure interactions. In this paper, we study how calculating buoyancy and Froude-Krylov forces from the instantaneous position of a WEC device (referred to as instantaneous buoyancy and Froude-Krylov forces from herein) changes WEC simulation results compared to simulations that use linear hydrodynamic coefficients. First, we describe the WEC-Sim tool used to perform simulations and how the ability to model instantaneous forces was incorporated into WEC-Sim. We then use a simplified one-body WEC device to validate the model and to demonstrate how accounting for these instantaneously calculated forces affects the accuracy of simulation results, such as device motions, hydrodynamic forces, and power generation.

13 HYDRO ENERGY↗

Development of spectroscopic tools for nuclear forensics signatures development

The Savannah River National Laboratory (SRNL) has been developing advanced spectroscopic tools for the characterization of plutonium-bearing compounds with the intent to develop material and process signatures for nuclear forensics. Plutonium in a production, refining, or finishing facility will exist in many forms including oxide precursors (PuF4, PuF3, Pu oxalate, etc.), oxide, and metal. The ability to identify plutonium in each of these chemical forms and determine their processing history is crucial for the development of spectroscopic signatures. This presentation will focus on our work to develop and apply spectroscopic tools at SRNL using doubled-walled cells (DWC) to characterize the thermal decomposition of oxalates, calcination chemistry, alpha-decay-induced chemistry, age dating since last calcination, and other signatures related to plutonium processing.

Villa-Aleman, Eliel↗

A low dose simulation tool for CT systems with energy integrating detectors

Purpose: This paper introduces a new strategy for simulating low-dose computed tomography (CT) scans using real scans of a higher dose as an input. The tool is verified against simulations and real scans and compared to other approaches found in the literature. Methods: The conditional variance identity is used to properly account for the variance of the input high-dose data, and a formula is derived for generating a new Poisson noise realization which has the same mean and variance as the true low-dose data. The authors also derive a formula for the inclusion of real samples of detector noise, properly scaled according to the level of the simulated x-ray signals. Results: The proposed method is shown to match real scans in number of experiments. Noise standard deviation measurements in simulated low-dose reconstructions of a 35 cm water phantom match real scans in a range from 500 to 10 mA with less than 5% error. Mean and variance of individual detector channels are shown to match closely across the detector array. Finally, the visual appearance of noise and streak artifacts is shown to match in real scans even under conditions of photon-starvation (with tube currents as low as 10 and 80 mA). Additionally, the proposed method is shown to be more accurate than previous approaches (1) in achieving the correct mean and variance in reconstructed images from pure-Poisson noise simulations (with no detector noise) under photon-starvation conditions, and (2) in simulating the correct noise level and detector noise artifacts in real low-dose scans. Conclusions: The proposed method can accurately simulate low-dose CT data starting from high-dose data, including effects from photon starvation and detector noise. This is potentially a very useful tool in helping to determine minimum dose requirements for a wide range of clinical protocols and advanced reconstruction algorithms.

60 APPLIED LIFE SCIENCES↗

SU-E-J-17: A Study of Accelerator-Induced Cerenkov Radiation as a Beam Diagnostic and Dosimetry Tool

Purpose: To investigate accelerator-induced Cerenkov radiation imaging as a possible beam diagnostic and medical dosimetry tool. Methods: Cerenkov emission produced by clinical accelerator beams in a water phantom was imaged using a camera system comprised of a high-sensitivity thermoelectrically-cooled CCD camera coupled to a large aperture (f/0.75) objective lens with 16:1 magnification. This large format lens allows a significant amount of the available Cerenkov light to be collected and focused onto the CCD camera to form the image. Preliminary images, obtained with 6 MV photon beams, used an unshielded camera mounted horizontally with the beam normal to the water surface, and confirmed the detection of Cerenkov radiation. Several improvements were subsequently made including the addition of radiation shielding around the camera, and altering of the beam and camera angles to give a more favorable geometry for Cerenkov light collection. A detailed study was then undertaken over a range of electron and photon beam energies and dose rates to investigate the possibility of using this technique for beam diagnostics and dosimetry. Results: A series of images were obtained at a fixed dose rate over a range of electron energies from 6 to 20 MeV. The location of maximum intensity was found to vary linearly with the energy of the beam. A linear relationship was also found between the light observed from a fixed point on the central axis and the dose rate for both photon and electron beams. Conclusion: We have found that the analysis of images of beam-induced Cerenkov light in a water phantom has potential for use as a beam diagnostic and medical dosimetry tool. Our future goals include the calibration of the light output in terms of radiation dose and development of a tomographic system for 3D Cerenkov imaging in water phantoms and other media.

07 ISOTOPE AND RADIATION SOURCES↗

SU-E-T-278: Realization of Dose Verification Tool for IMRT Plan Based On DPM

Purpose: To build a Monte Carlo dose verification tool for IMRT Plan by implementing a irradiation source model into DPM code. Extend the ability of DPM to calculate any incident angles and irregular-inhomogeneous fields. Methods: With the virtual source and the energy spectrum which unfolded from the accelerator measurement data,combined with optimized intensity maps to calculate the dose distribution of the irradiation irregular-inhomogeneous field. The irradiation source model of accelerator was substituted by a grid-based surface source. The contour and the intensity distribution of the surface source were optimized by ARTS (Accurate/Advanced Radiotherapy System) optimization module based on the tumor configuration. The weight of the emitter was decided by the grid intensity. The direction of the emitter was decided by the combination of the virtual source and the emitter emitting position. The photon energy spectrum unfolded from the accelerator measurement data was adjusted by compensating the contaminated electron source. For verification, measured data and realistic clinical IMRT plan were compared with DPM dose calculation. Results: The regular field was verified by comparing with the measured data. It was illustrated that the differences were acceptable (<2% inside the field, 2–3mm in the penumbra). The dose calculation of irregular field by DPM simulation was also compared with that of FSPB (Finite Size Pencil Beam) and the passing rate of gamma analysis was 95.1% for peripheral lung cancer. The regular field and the irregular rotational field were all within the range of permitting error. The computing time of regular fields were less than 2h, and the test of peripheral lung cancer was 160min. Through parallel processing, the adapted DPM could complete the calculation of IMRT plan within half an hour. Conclusion: The adapted parallelized DPM code with irradiation source model is faster than classic Monte Carlo codes. Its computational accuracy and speed satisfy the clinical requirement, and it is expectable to be a Monte Carlo dose verification tool for IMRT Plan. Strategic Priority Research Program of the China Academy of Science(XDA03040000); National Natural Science Foundation of China (81101132)

60 APPLIED LIFE SCIENCES↗

SU-E-T-327: The Update of a XML Composing Tool for TrueBeam Developer Mode

Purpose: To introduce a major upgrade of a novel XML beam composing tool to scientists and engineers who strive to translate certain capabilities of TrueBeam Developer Mode to future clinical benefits of radiation therapy. Methods: TrueBeam Developer Mode provides the users with a test bed for unconventional plans utilizing certain unique features not accessible at the clinical mode. To access the full set of capabilities, a XML beam definition file accommodating all parameters including kV/MV imaging triggers in the plan can be locally loaded at this mode, however it is difficult and laborious to compose one in a text editor. In this study, a stand-along interactive XML beam composing application, TrueBeam TeachMod, was developed on Windows platforms to assist users in making their unique plans in a WYSWYG manner. A conventional plan can be imported in a DICOM RT object as the start of the beam editing process in which trajectories of all axes of a TrueBeam machine can be modified to the intended values at any control point. TeachMod also includes libraries of predefined imaging and treatment procedures to further expedite the process. Results: The TeachMod application is a major of the TeachMod module within DICOManTX. It fully supports TrueBeam 2.0. Trajectories of all axes including all MLC leaves can be graphically rendered and edited as needed. The time for XML beam composing has been reduced to a negligible amount regardless the complexity of the plan. A good understanding of XML language and TrueBeam schema is not required though preferred. Conclusion: Creating XML beams manually in a text editor will be a lengthy error-prone process for sophisticated plans. A XML beam composing tool is highly desirable for R and D activities. It will bridge the gap between scopes of TrueBeam capabilities and their clinical application potentials.

07 ISOTOPE AND RADIATION SOURCES↗

MO-E-18C-04: Advanced Computer Simulation and Visualization Tools for Enhanced Understanding of Core Medical Physics Concepts

Purpose: Most medical physics programs emphasize proficiency in routine clinical calculations and QA. The formulaic aspect of these calculations and prescriptive nature of measurement protocols obviate the need to frequently apply basic physical principles, which, therefore, gradually decay away from memory. E.g. few students appreciate the role of electron transport in photon dose, making it difficult to understand key concepts such as dose buildup, electronic disequilibrium effects and Bragg-Gray theory. These conceptual deficiencies manifest when the physicist encounters a new system, requiring knowledge beyond routine activities. Methods: Two interactive computer simulation tools are developed to facilitate deeper learning of physical principles. One is a Monte Carlo code written with a strong educational aspect. The code can “label” regions and interactions to highlight specific aspects of the physics, e.g., certain regions can be designated as “starters” or “crossers,” and any interaction type can be turned on and off. Full 3D tracks with specific portions highlighted further enhance the visualization of radiation transport problems. The second code calculates and displays trajectories of a collection electrons under arbitrary space/time dependent Lorentz force using relativistic kinematics. Results: Using the Monte Carlo code, the student can interactively study photon and electron transport through visualization of dose components, particle tracks, and interaction types. The code can, for instance, be used to study kerma-dose relationship, explore electronic disequilibrium near interfaces, or visualize kernels by using interaction forcing. The electromagnetic simulator enables the student to explore accelerating mechanisms and particle optics in devices such as cyclotrons and linacs. Conclusion: The proposed tools are designed to enhance understanding of abstract concepts by highlighting various aspects of the physics. The simulations serve as virtual experiments that give deeper and long lasting understanding of core principles. The student can then make sound judgements in novel situations encountered beyond routine clinical activities.

60 APPLIED LIFE SCIENCES↗

Novel tools for stepping source brachytherapy treatment planning: Enhanced geometrical optimization and interactive inverse planning

Purpose: Dose optimization for stepping source brachytherapy can nowadays be performed using automated inverse algorithms. Although much quicker than graphical optimization, an experienced treatment planner is required for both methods. With automated inverse algorithms, the procedure to achieve the desired dose distribution is often based on trial-and-error. Methods: A new approach for stepping source prostate brachytherapy treatment planning was developed as a quick and user-friendly alternative. This approach consists of the combined use of two novel tools: Enhanced geometrical optimization (EGO) and interactive inverse planning (IIP). EGO is an extended version of the common geometrical optimization method and is applied to create a dose distribution as homogeneous as possible. With the second tool, IIP, this dose distribution is tailored to a specific patient anatomy by interactively changing the highest and lowest dose on the contours. Results: The combined use of EGO–IIP was evaluated on 24 prostate cancer patients, by having an inexperienced user create treatment plans, compliant to clinical dose objectives. This user was able to create dose plans of 24 patients in an average time of 4.4 min/patient. An experienced treatment planner without extensive training in EGO–IIP also created 24 plans. The resulting dose-volume histogram parameters were comparable to the clinical plans and showed high conformance to clinical standards. Conclusions: Even for an inexperienced user, treatment planning with EGO–IIP for stepping source prostate brachytherapy is feasible as an alternative to current optimization algorithms, offering speed, simplicity for the user, and local control of the dose levels.

60 APPLIED LIFE SCIENCES↗

Development of an accurate EPID-based output measurement and dosimetric verification tool for electron beam therapy

Purpose: To develop an efficient and robust tool for output measurement and absolute dose verification of electron beam therapy by using a high spatial-resolution and high frame-rate amorphous silicon flat panel electronic portal imaging device (EPID). Methods: The dosimetric characteristics of the EPID, including saturation, linearity, and ghosting effect, were first investigated on a Varian Clinac 21EX accelerator. The response kernels of the individual pixels of the EPID to all available electron energies (6, 9, 12, 16, and 20 MeV) were calculated by using Monte Carlo (MC) simulations, which formed the basis to deconvolve an EPID raw images to the incident electron fluence map. The two-dimensional (2D) dose distribution at reference depths in water was obtained by using the constructed fluence map with a MC simulated pencil beam kernel with consideration of the geometric and structural information of the EPID. Output factor measurements were carried out with the EPID at a nominal source–surface distance of 100 cm for 2 × 2, 3 × 3, 6 × 6, 10 × 10, and 15 × 15 cm{sup 2} fields for all available electron energies, and the results were compared with that measured in a solid water phantom using film and a Farmer-type ion chamber. The dose distributions at a reference depth specific to each energy and the flatness and symmetry of the 10 × 10 cm{sup 2} electron beam were also measured using EPID, and the results were compared with ion chamber array and water scan measurements. Finally, three patient cases with various field sizes and irregular cutout shapes were also investigated. Results: EPID-measured dose changed linearly with the monitor units and showed little ghosting effect for dose rate up to 600 MU/min. The flatness and symmetry measured with the EPID were found to be consistent with ion chamber array and water scan measurements. The EPID-measured output factors for standard square fields of 2 × 2, 3 × 3, 6 × 6, 10 × 10, 15 × 15 cm{sup 2} agreed with film and ion chamber measurements. The average discrepancy between EPID and ion chamber/film measurements was 0.81% ± 0.60% (SD) and 1.34% ± 0.75%, respectively. For the three clinical cases, the difference in output between the EPID- and ion chamber array measured values was found to be 1.13% ± 0.11%, 0.54% ± 0.10%, and 0.74% ± 0.11%, respectively. Furthermore, the γ-index analysis showed an excellent agreement between the EPID- and ion chamber array measured dose distributions: 100% of the pixels passed the criteria of 3%/3 mm. When the γ-index was set to be 2%/2 mm, the pass rate was found to be 99.0% ± 0.07%, 98.2% ± 0.14%, and 100% for the three cases. Conclusions: The EPID dosimetry system developed in this work provides an accurate and reliable tool for routine output measurement and dosimetric verification of electron beam therapy. Coupled with its portability and ease of use, the proposed system promises to replace the current film-based approach for fast and reliable assessment of small and irregular electron field dosimetry.

60 APPLIED LIFE SCIENCES↗

SU-E-P-12: Pinnacle-Based Tool to Evaluate the Effect of Prostate Rotation as Determined by Calypso

Purpose: When the Calypso reports a large prostate rotation and one does not have the means to make corrections, it is helpful to quantify its dosimetric effects. We have devised a simple scheme to achieve this in Pinnacle TPS. If it is determined that the PTV margin is inadequate, an alternate larger-margin plan may be adapted for the day. Methods: A three-step process using the Pinnacle Image fusion module was formulated to analyze the clinical effect of prostate rotation. The process includes (1) translating the image set such that the rotational axis is about the isocenter, (2) performing 3D rotations of the structures of interest, and (3) restoring the coordinates associated with the plan. The rotated structures are imported and overlayed on the original plan for evaluation. The tool was applied to three prostate cancer patients with relatively large rotations (95 fractions total). Prostate rotations are primarily due to variations in bladder and rectal filling, which may also affect the seminal vesicles. It is difficult to estimate the perturbation of seminal vesicles for a given prostate rotation. Therefore, the Calypso-derived rotation matrix was applied only to CTV and PTV (CTV+5mm). Results: The rotations were predominantly in the pitch direction with an absolute value ranging from 0–29 degrees (Median = 10°, Average = 14.5°). For various magnitudes of rotation, the CTV V100 decreased from the original 100% to 99.6%/99%/95% for 10°/15°/29° rotations, respectively. Likewise, the PTV V100 diminished from 95% to 92%/89%/82%. Conclusion: A tool, consisting only of features within a TPS, was used to evaluate the dosimetric effect of prostate rotation. Our study shows that under large uncorrected rotations, the tumor coverage is degraded and may require intervention in the form of plan adaptation. To this end, alternate plans with variable margins can be generated in advance for daily adaption.

60 APPLIED LIFE SCIENCES↗

SU-E-J-137: Image Registration Tool for Patient Setup in Korea Heavy Ion Medical Accelerator Center

Purpose: A potential validation tool for compensating patient positioning error was developed using 2D/3D and 3D/3D image registration. Methods: For 2D/3D registration, digitally reconstructed radiography (DRR) and three-dimensional computed tomography (3D-CT) images were applied. The ray-casting algorithm is the most straightforward method for generating DRR. We adopted the traditional ray-casting method, which finds the intersections of a ray with all objects, voxels of the 3D-CT volume in the scene. The similarity between the extracted DRR and orthogonal image was measured by using a normalized mutual information method. Two orthogonal images were acquired from a Cyber-Knife system from the anterior-posterior (AP) and right lateral (RL) views. The 3D-CT and two orthogonal images of an anthropomorphic phantom and head and neck cancer patient were used in this study. For 3D/3D registration, planning CT and in-room CT image were applied. After registration, the translation and rotation factors were calculated to position a couch to be movable in six dimensions. Results: Registration accuracies and average errors of 2.12 mm ± 0.50 mm for transformations and 1.23° ± 0.40° for rotations were acquired by 2D/3D registration using an anthropomorphic Alderson-Rando phantom. In addition, registration accuracies and average errors of 0.90 mm ± 0.30 mm for transformations and 1.00° ± 0.2° for rotations were acquired using CT image sets. Conclusion: We demonstrated that this validation tool could compensate for patient positioning error. In addition, this research could be the fundamental step for compensating patient positioning error at the first Korea heavy-ion medical accelerator treatment center.

60 APPLIED LIFE SCIENCES↗

SU-E-J-148: Tools for Development of 4D Proton CT

Purpose: To develop tools for performing 4D proton computed tomography (CT). Methods: A suitable patient with a tumor in the right lower lobe was selected from a set of 4D CT scans. The volumetric CT images formed the basis for calculating the parameters of a breathing model that allows reconstruction of a static reference CT and CT images in each breathing phase. The images were imported into the TOPAS Monte Carlo simulation platform for simulating an experimental proton CT scan with 45 projections spaced by 4 degree intervals. Each projection acquired data for 2 seconds followed by a gantry rotation for 2 seconds without acquisition. The scan covered 180 degrees with individual protons passing through a 9-cm slab of the patient’s lung covering the moving tumor. An initial proton energy sufficient for penetrating the patient from all directions was determined. Performing the proton CT simulation, TOPAS provided output of the proton energy and coordinates registered in two planes before and after the patient, respectively. The set of projection data was then used with an iterative reconstruction algorithm to generate a volumetric proton CT image set of the static reference image and the image obtained under breathing motion, respectively. Results: An initial proton energy of 230 MeV was found to be sufficient, while for an initial energy of 200 MeV a substantial number of protons did not penetrate the patient. The reconstruction of the static reference image set provided sufficient detail for treatment planning. Conclusion: We have developed tools to perform studies of proton CT in the presence of lung motion based on the TOPAS simulation toolkit. This will allow to optimize 4D reconstruction algorithms by synchronizing the acquired proton CT data with a breathing signal and utilizing a breathing model obtained prior to the proton CT scan. This research has been supported by the National Institute Of Biomedical Imaging And Bioengineering of the National Institutes of Health under Award Number R01EB013118.

60 APPLIED LIFE SCIENCES↗