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VitroJet: new features and case studies

Single-particle cryo-electron microscopy has become a widely adopted method in structural biology due to many recent technological advances in microscopes, detectors and image processing. Before being able to inspect a biological sample in an electron microscope, it needs to be deposited in a thin layer on a grid and rapidly frozen. The VitroJet was designed with this aim, as well as avoiding the delicate manual handling and transfer steps that occur during the conventional grid-preparation process. Since its creation, numerous technical developments have resulted in a device that is now widely utilized in multiple laboratories worldwide. It features plasma treatment, low-volume sample deposition through pin printing, optical ice-thickness measurement and cryofixation of pre-clipped Autogrids through jet vitrification. This paper presents recent technical improvements to the VitroJet and the benefits that it brings to the cryo-EM workflow. A wide variety of applications are shown: membrane proteins, nucleosomes, fatty-acid synthase, Tobacco mosaic virus, lipid nanoparticles, tick-borne encephalitis viruses and bacteriophages. These case studies illustrate the advancement of the VitroJet into an instrument that enables accurate control and reproducibility, demonstrating its suitability for time-efficient cryo-EM structure determination.

59 BASIC BIOLOGICAL SCIENCES↗

TU-F-BRF-09: Feasibility Study of Spatial and Temporal Fractionation Using a Table-Top Image-Guided MRT System

Purpose: Microbeam radiation therapy is a promising experimental radiotherapy method for cancer treatment. Synchrotron studies have shown that MRT can preferentially ablate tumors while mostly preserving the surrounding normal tissues. Our purpose is to develop a compact microbeam irradiator that can be accessible for laboratory research on MRT's therapeutic mechanism, with the ultimate goal of translating this technique for clinical applications. Utilizing a carbon nanotube field emission X-ray source array, our lab has developed a first of its kind table-top microbeam irradiator. The purpose of this study is to investigate the possibility of increasing the total dose to the tumor region using spatial and temporal fractionation. Methods: MRI and CT scans were acquired and registered to locate both the target region and the landmark in the treatment coordinate space. A crossbeam treatment configuration was planned to achieve the desired dosage and tumor coverage. One array of 300 μm-thick microbeams was delivered to the target on the first day. Another array, perpendicular to the first one, was delivered the next day targeting the same region. The feasibility of this image-guided MRT procedure was evaluated using a phantom. Gafchromic EBT2 film was employed to characterize the targeting accuracy and the delivered tumor dose. Results: The preliminary phantom study showed that a cross-pattern of microbeam arrays was successfully delivered with sub-millimeter targeting accuracy. The delivered dose in the target region was doubled. The fraction of tumor volume that received the peak dose was increased. Conclusion: Temporal fractionation of crosspatterned microbeams can be delivered to the same target region. The feasibility of this procedure was investigated with a phantom study. Once implemented, this procedure has the potential of increasing the tumor control effect of MRT and of achieving better normal tissue recovery.

60 APPLIED LIFE SCIENCES↗

SU-F-T-266: Dynalogs Based Evaluation of Different Dose Rate IMRT Using DVH and Gamma Index

Purpose: This work investigates the impact of low and high dose rate on IMRT through Dynalogs by evaluating Gamma Index and Dose Volume Histogram. Methods: The Eclipse™ treatment planning software was used to generate plans on prostate and head and neck sites. A range of dose rates 300 MU/min and 600 MU/min were applied to each plan in order to investigate their effect on the beam ON time, efficiency and accuracy. Each plan had distinct monitor units per fraction, delivery time, mean dose rate and leaf speed. The DVH data was used in the assessment of the conformity and plan quality.The treatments were delivered on Varian™ Clinac 2100C accelerator equipped with 120 leaf millennium MLC. Dynalogs of each plan were analyzed by MATLAB™ program. Fluence measurements were performed using the Sun Nuclear™ 2D diode array and results were assessed, based on Gamma analysis of dose fluence maps, beam delivery statistics and Dynalogs data. Results: Minor differences found by adjusted R-squared analysis of DVH’s for all the plans with different dose rates. It has been also found that more and larger fields have greater time reduction at high dose rate and there was a sharp decrease in number of control points observed in dynalog files by switching dose rate from 300 MU/min to 600 MU/min. Gamma Analysis of all plans passes the confidence limit of ≥95% with greater number of passing points in 300 MU/min dose rate plans. Conclusion: The dynalog files are compatible tool for software based IMRT QA. It can work perfectly parallel to measurement based QA setup and stand-by procedure for pre and post delivery of treatment plan.

60 APPLIED LIFE SCIENCES↗

Human Factors and Habitability Challenges for Mars Missions

As NASA is planning to send humans deeper into space than ever before, adequate crew health and performance will be critical for mission success. Within the NASA Human Research Program (HRP), the Space Human Factors and Habitability (SHFH) team is responsible for characterizing the risks associated with human capabilities and limitations with respect to long-duration spaceflight, and for providing mitigations (e.g., guidelines, technologies, and tools) to promote safe, reliable and productive missions. SHFH research includes three domains: Advanced Environmental Health (AEH), Advanced Food Technology (AFT), and Space Human Factors Engineering (SHFE). The AEH portfolio focuses on understanding the risk of microbial contamination of the spacecraft and on the development of standards for exposure to potential toxins such as chemicals, bacteria, fungus, and lunar/Martian dust. The two risks that the environmental health project focuses on are adverse health effects due to changes in host-microbe interactions, and risks associated with exposure to dust in planetary surface habitats. This portfolio also proposes countermeasures to these risks by making recommendations that relate to requirements for environmental quality, foods, and crew health on spacecraft and space missions. The AFT portfolio focuses on reducing the mass, volume, and waste of the entire integrated food system to be used in exploration missions, and investigating processing methods to extend the shelf life of food items up to five years, while assuring that exploration crews will have nutritious and palatable foods. The portfolio also delivers improvements in both the food itself and the technologies for storing and preparing it. SHFE sponsors research to establish human factors and habitability standards and guidelines in five risk areas, and provides improved design concepts for advanced crew interfaces and habitability systems. These risk areas include: Incompatible vehicle/habitat design, inadequate human-computer interaction, inadequate critical task design, inadequate human-automation/robotic interaction, and performance errors due to training deficiencies. To address the identified research gaps within each risk, SHFH's research plan includes studies in the laboratory, in analogs, and on International Space Station (ISS). In addition to establishing and maintaining the risk-based research portfolio, SHFH is also implementing a qualitative approach to determine how we at NASA evaluate human performance. Via interviews with experts, such as trainers, flight controllers, and flight surgeons, we are collecting the metrics by which they assess human performance, evidence of performance issues, and potential or actual consequences. The Human Performance Data Project will determine what human performance data have been collected in the past at NASA, and what data should be collected in the future in order to complete our knowledgebase and reduce risks related to human factors and habitability.

Whitmore, Mihriban↗

TH-C-19A-08: PDD Discrepancies at Opposite Biases From Very Small Volume Ion Chambers When Using Water Scanners

Purpose: As more so-called micro ion chambers become commercially available, medical physicists may be inclined to use them during the linear accelerator commissioning process, in an attempt to better characterize the beam in steep dose gradient areas. The purpose of this work is to inform the medical physics community of a non-trivial, anomalous behavior observed when very small chambers are used in certain beam scanning configurations. Methods: A total of six ion chambers (0.007cc to 0.6cc) were used to scan PDDs from a 10×10cm2 field at both +300V and −300V biases. PDDs were scanned using three different water tank scanning systems to determine whether different scanners exhibit the same abnormality. Finally, PDDs were sampled using an external electrometer to bypass the internal electrometer of the scanner to determine the potential contributions of the scanner electronics to the abnormality observed. Results: We observed a reproducible, significant difference (over-response with depth) in PDDs acquired when using very small ion chambers with certain bias and watertank combinations, on the order of 3–5% at a depth of 25 cm in water. This difference was not observed when the PDDs were sampled using the ion chambers in conjunction with an external electrometer. This suggests a contribution of interference produced by the controller box and scanning system, which becomes significant for the very small signals collected by very small ion chambers, especially at depth, as the signal level is reduced even further. Conclusion: Based on the results observed here, if currently available very small ion chambers are used with specific bias and scanning water-tank combinations, erroneous PDD data may be collected. If this data is used as input to the Treatment Planning System, systematic errors on the order of 3%–5% may be introduced into the treatment planning process.

07 ISOTOPE AND RADIATION SOURCES↗

Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery

Purpose: The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. Methods: A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Results: Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as would be enabled by real-time imaging, gross tumor volume coverage was identical while notable reductions of bladder and rectal volumes exposed to large doses were possible. The quality of U.S. images obtained during beam operation was not appreciably degraded by radiofrequency interference and 2D tracking of a phantom object in U.S. images obtained with the beam on/off yielded no significant differences. Conclusions: Remotely controlled robotic U.S. imaging is feasible in the radiotherapy environment and for the first time may offer real-time volumetric soft-tissue guidance concurrent with radiotherapy delivery.

61 RADIATION PROTECTION AND DOSIMETRY↗

Tracking 3-D body motion for docking and robot control

An advanced method of tracking three-dimensional motion of bodies has been developed. This system has the potential to dynamically characterize machine and other structural motion, even in the presence of structural flexibility, thus facilitating closed loop structural motion control. The system's operation is based on the concept that the intersection of three planes defines a point. Three rotating planes of laser light, fixed and moving photovoltaic diode targets, and a pipe-lined architecture of analog and digital electronics are used to locate multiple targets whose number is only limited by available computer memory. Data collection rates are a function of the laser scan rotation speed and are currently selectable up to 480 Hz. The tested performance on a preliminary prototype designed for 0.1 in accuracy (for tracking human motion) at a 480 Hz data rate includes a worst case resolution of 0.8 mm (0.03 inches), a repeatability of plus or minus 0.635 mm (plus or minus 0.025 inches), and an absolute accuracy of plus or minus 2.0 mm (plus or minus 0.08 inches) within an eight cubic meter volume with all results applicable at the 95 percent level of confidence along each coordinate region. The full six degrees of freedom of a body can be computed by attaching three or more target detectors to the body of interest.

Donath, M.↗

Computational Investigation and Validation of Twin-Tail Buffet Response Including Dynamics and Control

Multidisciplinary tools for prediction of single rectangular-tail buffet are extended to single swept-back-tail buffet in transonic-speed flow, and multidisciplinary tools for prediction and control of twin-tail buffet are developed and presented. The configuration model consists of a sharp-edged delta wing with single or twin tails that are oriented normal to the wing surface. The tails are treated as cantilevered beams fixed at the root and allowed to oscillate in both bending and torsion. This complex multidisciplinary problem is solved sequentially using three sets of equations on a dynamic single or multi-block grid structure. The first set is the unsteady, compressible, Reynolds-averaged Navier-Stokes equations which are used for obtaining the flow field vector and the aerodynamic loads on the tails. The Navier-Stokes equations are solved accurately in time using the implicit, upwind, flux-difference splitting, finite volume scheme. The second set is the coupled bending and torsion aeroelastic equations of cantilevered beams which are used for obtaining the bending and torsion deflections of the tails. The aeroelastic equations'are solved accurately in time using, a fifth-order-accurate Runge-Kutta scheme. The third set is the grid-displacement equations and the rigid-body dynamics equations, which are used for updating the grid coordinates due to the tail deflections and rigid-body motions. The tail-buffet phenomenon is predicted for highly-swept, single vertical tail placed at the plane of geometric symmetry, and for highly-swept, vertical twin tails placed at three different spanwise separation distances. The investigation demonstrates the effects of structural inertial coupling and uncoupling of the bending and torsion modes of vibration, spanwise positions of the twin-tail, angle of attack, and pitching and rolling dynamic motions of the configuration model on the tail buffet loading and response. The fundamental issue of twin-tail buffet alleviation is addressed using two active flow-control methods. These methods are the tangential leading-edge blowing and the flow suction from the leading-edge vortex cores along their paths. Qualitative and quantitative comparisons with the available experimental data are presented. The comparisons indicate that the present multidisciplinary aeroelastic analysis tools are robust, accurate and efficient.

Kandil, Osama A.↗

Encouraging Early Clinical Outcomes With Helical Tomotherapy-Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Cislunar space infrastructure: Lunar technologies

Continuing its emphasis on the creation of a cisluar infrastructure as an appropriate and cost-effective method of space exploration and development, the University of Colorado explores the technologies necessary for the creation of such an infrastructure, namely (1) automation and robotics; (2) life support systems; (3) fluid management; (4) propulsion; and (5) rotating technologes. The technological focal point is on the development of automated and robotic systems for the implementation of a Lunar Oasis produced by automation and robotics (LOARS). Under direction from the NASA Office of Exploration, automation and robotics have been extensively utilized as an initiating stage in the return to the Moon. A pair of autonomous rovers, modular in design and built from interchangeable and specialized components, is proposed. Utilizing a 'buddy system', these rovers will be able to support each other and to enhance their individual capabilities. One rover primarily explores and maps while the second rover tests the feasibility of various materials-processing techniques. The automated missions emphasize availability and potential uses of lunar resources and the deployment and operations of the LOAR program. An experimental bio-volume is put into place as the precursor to a Lunar Environmentally Controlled Life Support System. The bio-volume will determine the reproduction, growth and production characteristics of various life forms housed on the lunar surface. Physiochemical regenerative technologies and stored resources will be used to buffer biological disturbances of the bio-volume environment. The in situ lunar resources will be both tested and used within this bio-volume. Second phase development on the lunar surface calls for manned operations. Repairs and reconfiguration of the initial framework will ensue. An autonomously initiated, manned Lunar Oasis can become an essential component of the United States space program. The Lunar Oasis will provide support to science, technology, and commerce. It will enable more cost-effective space exploration to the planets and beyond.

W. Faller↗

Automatic Mesh Generation of Hybrid Mesh on Valves in Multiple Positions in Feedline Systems

Fluid flow simulations through a valve often require evaluation of the valve in multiple opening positions. A mesh has to be generated for the valve for each position and compounding. The problem is the fact that the valve is typically part of a larger feedline system. In this paper, we propose to develop a system to create meshes for feedline systems with parametrically controlled valve openings. Herein we outline two approaches to generate the meshes for a valve in a feedline system at multiple positions. There are two issues that must be addressed. The first is the creation of the mesh on the valve for multiple positions. The second is the generation of the mesh for the total feedline system including the valve. For generation of the mesh on the valve, we will describe the use of topology matching and mesh generation parameter transfer. For generation of the total feedline system, we will describe two solutions that we have implemented. In both cases the valve is treated as a component in the feedline system. In the first method the geometry of the valve in the feedline system is replaced with a valve at a different opening position. Geometry is created to connect the valve to the feedline system. Then topology for the valve is created and the portion of the topology for the valve is topology matched to the standard valve in a different position. The mesh generation parameters are transferred and then the volume mesh for the whole feedline system is generated. The second method enables the user to generate the volume mesh on the valve in multiple open positions external to the feedline system, to insert it into the volume mesh of the feedline system, and to reduce the amount of computer time required for mesh generation because only two small volume meshes connecting the valve to the feedline mesh need to be updated.

Ross, Douglass H.↗

Fluid Shifts

Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.

Stenger, M. B.↗

Utilizing a Novel Acoustic Backscatter Array to Characterize Waste Consolidation and Settling in a Horizontal Flow Clarifier - 16051

As part of a collaboration between the University of Leeds, Sellafield Ltd and MMI Engineering Ltd, bespoke acoustic instrumentation and numerical simulation methods have been established to optimize nuclear legacy waste transfers. Specifically, a new ultrasonic measurement system has been developed, allowing suspended particle concentration and consolidation to be measured remotely. This technology has been combined with computational fluid dynamics (CFD) modelling of settling particulate systems, permitting full characterization, simulation and prediction of sludge separation processes. Presented here are experimental and numerical results on the transport and settling behavior of non-active nuclear-analogue suspensions in two flow geometries: gravitational settling of glass dispersions in a 250-liter column; and transport and sedimentation of flocculated calcite in a close-to-full-scale clarifier (9 m{sup 3} total volume and 4.8 m{sup 2} length). In addition, details of the design, construction and calibration of a custom-built Ultrasonic Array Research Platform (UARP) are described. Settling column results suggested that particle concentration changes could be simulated with good accuracy by a CFD model (developed using the open source OpenFOAM framework) when compared to measured samples. Large-scale clarifier trials were used to assess the effectiveness of the UARP controller with an attached in situ acoustic backscatter array (ABA). The ABA consisted of 8 transducers angled down at 20 deg. to the vertical, pulsing at 2-2.5 MHz in cycles (covering 1.8 m total depth). In comparison to a range of sampled concentrations across the length of the clarifier, results confirmed that the UARP-ABA system was highly successful at characterizing these complex flows over several hours of operation, allowing visualization of depth-wise bulk density changes and bed build-up over time. Collectively, this work highlights the capability of these tools to monitor and optimize a number of current waste transfer operations at Sellafield, with further potential applications for solid-liquid separations across waste, water treatment and minerals engineering industries. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Dynamic MLC leaf sequencing for integrated linear accelerator control systems

Purpose: Leaf positions for dynamic multileaf collimator (DMLC) intensity modulated radiation therapy must be closely synchronized with MU delivery. For the Varian C3 series MLC controller, if the planned trajectory (leaf position vs. MU) requires velocities exceeding the capability of the MLC, the leaves fall behind the planned positions, causing the controller to momentarily hold the beam and thereby introduce dosimetric errors. We investigated the merits of a new commercial linear accelerator, TrueBeam, that integrates MLC control with prospective dose rate modulation. If treatment is delivered at dose rates so high that leaves would fall behind, the controller reduces the dose rate such that harmony between MU and leaf position is preserved. Methods: For three sets of DMLC leaf trajectories, point doses and two-dimensional dose distributions were measured in phantom using an ionization chamber and film, respectively. The first set, delivered using both a TrueBeam and a conventional C3 controller, comprised a single leaf bank closing at planned velocities of 2.4, 7.1, and 14 cm/s. The maximum achievable leaf velocity for both systems was 3 cm/s. The remaining two sets were derived from clinical fluence maps using a commercial treatment planning system for a range of planned dose rates and were delivered using TrueBeam set to the maximum dose rate, 600 MU/min. Generating trajectories using a planned dose rate that is lower than the delivery dose rate effectively increased the leaf velocity constraint used by the planning system for trajectory calculation. The second set of leaf trajectories was derived from two fluence maps containing regions of zero fluence obtained from representative beams of two different patient treatment plans. The third set was obtained from all nine fields of a head and neck treatment plan. For the head and neck plan, dose-volume histograms of the spinal cord and target for each planned dose rate were obtained. Results: For the single closing leaf bank trajectories, the TrueBeam control system reduced the dose rate such that the leaf velocity was less than the maximum. Dose deviations relative to the 2.4 cm/s trajectory were less than 3%. For the conventional controller, the leaves repeatedly fell behind the planned positions until the beam hold threshold was reached, resulting in deviations of up to 19% relative to the 2.4 cm/s trajectory. For the two clinical fluence maps, reducing the planned dose rate reduced the dose in the zero fluence regions by 15% and 24% and increased the delivery time by 5 s and 14 s. No significant differences were noted in the high and intermediate dose regions measured using film. The DVHs for the head and neck plan showed a 10% reduction in cord dose for 20 MU/min relative to 600 MU/min sequencing dose rate, which was confirmed by measurement. No difference in target DVHs were observed. The reduction in cord dose increased total treatment time by 1.8 min. Conclusions: Leaf sequencing algorithms for integrated control systems should be modified to reflect the reduced importance of maximum leaf velocity for accurate dose delivery.

43 PARTICLE ACCELERATORS↗

Decentralized Control Synthesis for Air Traffic Management in Urban Air Mobility

Urban air mobility (UAM) refers to air transportation services within an urban area, often in an on-demand fashion. We study air traffic management (ATM) for vehicles in a UAM fleet, while guaranteeing system safety requirements such as traffic separation. Existing ATM methods for unmanned aerial systems, such as UAS traffic management, utilize alternative approaches which do not provide strict safety guarantees. No established infrastructure exists for providing ATM at scale for UAM. We provide a decentralized, hierarchical approach for UAM ATM that allows for scalability to high traffic densities as well as providing theoretical guarantees of correctness with respect to user-provided safety specifications. Our main contributions are two-fold. First, we propose a novel UAM ATM architecture that divides the control authority between vertihubs that are each in charge of all UAM vehicles in their local airspace. Each vertihub also contains a number of vertiports that are in charge of UAM vehicle takeoffs and landings. The resulting architecture is decentralized and hierarchical, which not only enables scalability, but also robustness in the event of any individual vertihub or vertiport no longer being operational. Second, we provide a contract-based correct-by-construction reactive synthesis approach that provably guarantees safety properties with respect to user-provided specifications in linear temporal logic. We demonstrate the approach on large-volume UAM air traffic data.

Urban Air Mobility↗

Tolerance of the Spinal Cord to Stereotactic Radiosurgery: Insights From Hemangioblastomas

Purpose: To evaluate spinal cord dose-volume effects, we present a retrospective review of stereotactic radiosurgery (SRS) treatments for spinal cord hemangioblastomas. Methods and Materials: From November 2001 to July 2008, 27 spinal hemangioblastomas were treated in 19 patients with SRS. Seventeen tumors received a single fraction with a median dose of 20 Gy (range, 18-30 Gy). Ten lesions were treated using 18-25 Gy in two to three sessions. Cord volumes receiving 8, 10, 12, 14, 16, 18, 20, 22, and 24 Gy and dose to 10, 100, 250, 500, 1000, and 2000 mm{sup 3} of cord were determined. Multisession treatments were converted to single-fraction biologically effective dose (SFBED). Results: Single-fraction median cord D{sub max} was 22.7 Gy (range, 17.8-30.9 Gy). Median V10 was 454 mm{sup 3} (range, 226-3543 mm{sup 3}). Median dose to 500 mm{sup 3} cord was 9.5 Gy (range, 5.3-22.5 Gy). Fractionated median SFBED{sub 3} cord D{sub max} was 14.1 Gy{sub 3} (range, 12.3-19.4 Gy{sub 3}). Potential toxicities included a Grade 2 unilateral foot drop 5 months after SRS and 2 cases of Grade 1 sensory deficits. The actuarial 3-year local tumor control estimate was 86%. Conclusions: Despite exceeding commonly cited spinal cord dose constraints, SRS for spinal hemangioblastomas is safe and effective. Consistent with animal experiments, these data support a partial-volume tolerance model for the human spinal cord. Because irradiated cord volumes were generally small, application of these data to other clinical scenarios should be made cautiously. Further prospective studies of spinal radiosurgery are needed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using {sup 11}C-choline Positron Emission Tomography Scans

Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for localized prostate cancer using {sup 11}C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

Purpose: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Methods and Materials: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). Results: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. Conclusions: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗