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At least 1,459 records · Page 81
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

WE-DE-BRA-11: A Study of Motion Tracking Accuracy of Robotic Radiosurgery Using a Novel CCD Camera Based End-To-End Test System

Purpose: A novel end-to-end test system using a CCD camera and a scintillator based phantom (XRV-124, Logos Systems Int’l) capable of measuring the beam-by-beam delivery accuracy of Robotic Radiosurgery (CyberKnife) was developed and reported in our previous work. This work investigates its application in assessing the motion tracking (Synchrony) accuracy for CyberKnife. Methods: A QA plan with Anterior and Lateral beams (with 4 different collimator sizes) was created (Multiplan v5.3) for the XRV-124 phantom. The phantom was placed on a motion platform (superior and inferior movement), and the plans were delivered on the CyberKnife M6 system using four motion patterns: static, Sine- wave, Sine with 15° phase shift, and a patient breathing pattern composed of 2cm maximum motion with 4 second breathing cycle. Under integral recording mode, the time-averaged beam vectors (X, Y, Z) were measured by the phantom and compared with static delivery. In dynamic recording mode, the beam spots were recorded at a rate of 10 frames/second. The beam vector deviation from average position was evaluated against the various breathing patterns. Results: The average beam position of the six deliveries with no motion and three deliveries with Synchrony tracking on ideal motion (sinewave without phase shift) all agree within −0.03±0.00 mm, 0.10±0.04, and 0.04±0.03 in the X, Y, and X directions. Radiation beam width (FWHM) variations are within ±0.03 mm. Dynamic video record showed submillimeter tracking stability for both regular and irregular breathing pattern; however the tracking error up to 3.5 mm was observed when a 15 degree phase shift was introduced. Conclusion: The XRV-124 system is able to provide 3D and 4D targeting accuracy for CyberKnife delivery with Synchrony. The experimental results showed sub-millimeter delivery in phantom with excellent correlation in target to breathing motion. The accuracy was degraded when irregular motion and phase shift was introduced.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Nanomaterials in Biomedicine

Nowadays, nanomaterials have become an emerging field that has shown great promise in the development of novel diagnostic, imaging and therapeutic agents for a variety of diseases, including cancer, due to their nanoscale size effects and increased surface area. In comparison to their larger counterparts, nanomaterials have unique physicochemical and biological properties including size, shape, chemical composition, surface structure and charge, aggregation and agglomeration, and solubility which can affect their interactions with biomolecules and cells. In addition, nanoparticles (NPs) with size-tunable light emission have demonstrated an impressive potential as high-efficiency delivery transporters for biomolecules into cells, being used to produce exceptional images of tumor sites. Moreover, NPs delivery system has been widely applied in pharmaceutical field to enhance absorption of bioactive compounds since they can interact with several phytochemicals by hydrogen bonds and hydrophobic interactions to encapsulate these phytochemicals in NPs and thus enhance aqueous solubility of the chemicals. Moreover, NPs also can prevent against oxidation/degradation of the phytochemicals encapsulated in the gastrointestinal tract and can be taken directly up by epithelial cells in the small intestine resulting in the increase of absorption and bioavailability of phytochemicals. In general, there are two specific fields of utilization of intrinsically active NPs as pharmacologic agents including oxidative-related pathologies and cancer. On the other hand, Redox active NPs have been shown to ameliorate many clinically relevant pathological disorders that implicate oxidative stress, reducing the oxidative burden and alleviating many important symptoms. In additionuch NPs act either in a catalytic way resembling the action of antioxidant enzymes such as catalase and superoxide dismutase, or as activating surfaces to facilitate reactions between the aqueous environment and the reactive oxygen species present at high level in the pathological tissues. In anticancer therapies, metal and metal oxide NPs are being used experimentally to directly kill tumor cells e.g., allowing extremely localized thermoablation by transforming applied magnetic fields into strong hyperthermia, or performing efficient photodynamic therapies able to reach even the internal tissues by transforming a penetrating infrared radiation into visible light inside the tumor. Moreover, NPs made of heavy atoms are able to react to irradiation producing cytocidal reactive oxygen species, consequently increasing the proapototic effects of radiotherapies once correctly localized at the site of the tumor. One of the most important applications of NPs in medicine is the controlled drug release. Sustained (or continuous) release drug delivery system involves NPs that release drugs at a controlled rate, by diffusion or degradation of the structure of the nanoparticle over time]. Other nano drug delivery approaches are focused on crossing certain physical barriers, such as the blood-brain barrier, or on finding alternative and acceptable routes for the delivery of a new generation of drugs based on proteins to be used through the gastrointestinal tract and prevent degradation. However, a successful system for the transfer of drugs needs to demonstrate optimal drug loading and good qualities of its release, a long duration in storage and low toxicity. On the other hand, carbon-based nanostructured materials, such as graphene, carbon nanotubes (CNTs) and nanodiamonds (NDs), have demonstrated to be highly promising materials for designing and fabricating nanoelectrodes and substrates for cell growth, by virtue of their peerless optical, electrical, thermal and mechanical properties. Nanoscience and nanotechnology are the basis of innovative and unprecedented techniques, offering unimaginable potential for the benefit of patients and new markets, companies that manufacture pharmaceuticals, and drug delivery systems.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2010

High-Volume Airborne Fluids Handling Technologies to Fight Wildfires

NASA recently partnered with the U.S. Forest Service (USFS) on a project to examine mission suitability and recommend policies and procedures for the use of very large aerial firefighting aircraft such as the Boeing 747 and DC-10 aerial retardant delivery aircraft. The aircraft under study included a 10Tanker DC-10 and an Evergreen B-747. NASA's Dryden Flight Research Center and Ames Research Center worked with the USFS to help determine the safe flight envelope for these Very Large Air Tanker (VLAT) aircraft for the USFS and the Department of the Interior (DOI). This new generation of supertankers includes aircraft like these that have as much as four times the delivery capacity of the previous generation of aerial firefighting aircraft. Dryden performed operational test and evaluation assessments and reported findings and recommendations on these aircraft in cooperation with Ames. The team developed, implemented, and directed an evaluation test plan for use in flight test and in simulation. Ames provided support using pilot-in-the-loop simulations and coordinated simulator models, flight profiles, and data analysis with Dryden. The test plan was designed to evaluate the suitability of VLAT aircraft as a function of mission environment. Based on this analysis, NASA generated interim flight envelope limitations to enhance safety and operational utility in the fire-retardant delivery mission. These recommended flight limitations were adopted by the USFS. The 10Tanker DC-10 has been in use for several years with the California Department of Forestry and Fire Protection(Cal-Fire), but until NASA took on the challenge of reviewing VLAT capabilities and limitations, the USFS was hesitant to add them to the federal wildfire arsenal. The DC-10 delivery system is based on an externally mounted set of tanks and a bomb-bay style set of clamshell doors that are opened in precisely calibrated ways to deliver the amounts and concentrations of retardant called for by the specific wildfire situation. The system was manufactured by Jordan Air of Central Point, OR, and was installed by Victorville Aerospace in Victorville, CA. It can deliver 12,000 gallons (45.4 kL) of retardant in as little as eight seconds. The aircraft can deliver a partial load of retardant and make multiple drops on the same flight, or the entire load can be rapidly delivered in one pass if required for maximum coverage. The Evergreen 747 uses internal tankage and a pressurized delivery system to enable volume and coverage levels that also meet USFS requirements, but enables computer control of flow for desired precision. This system was designed and built by Adaptive Aerospace of Tehachapi, CA and can deliver about 20,000 gallons (75.7 kL) of retardant in approximately ten seconds. The 747 can also make multiple independent drops, or deliver the entire load at once. NASA found that both of these VLAT aircraft are compatible with the wildfire suppression mission when used to supplement other aerial retardant delivery platforms. The major recommendations for deployment that resulted from this study relate to terrain clearance, the type of terrain in the drop area, availability of qualified lead planes to guide the VLAT approach to the drop area, and low-altitude maneuvering limitations. NASA s analysis suggests that with the appropriate flight procedures, these aircraft will provide a powerful set of tools to fight wildfires.

Dickerson, Mark↗
NASA NTRS2014

Determining the Source of Water Vapor in a Cerium Oxide Electrochemical Oxygen Separator to Achieve Aviator Grade Oxygen

More than a metric ton of water is transported to the International Space Station (ISS) each year to provide breathing oxygen for the astronauts. Water is a safe and compact form of stored oxygen. The water is electrolyzed on ISS and ambient pressure oxygen is delivered to the cabin. A much smaller amount of oxygen is used each year in spacesuits to conduct Extra Vehicular Activities (EVAs). Space suits need high pressure (>1000 psia) high purity oxygen (must meet Aviator Breathing Oxygen "ABO" specifications, >99.5% O2). The water / water electrolysis system cannot directly provide high pressure, high purity oxygen, so oxygen for EVAs is transported to ISS in high pressure gas tanks. The tanks are relatively large and heavy, and the majority of the system launch weight is for the tanks and not the oxygen. Extracting high purity oxygen from cabin air and mechanically compressing the oxygen might enable on-board production of EVA grade oxygen using the existing water / water electrolysis system. This capability might also benefit human spaceflight missions, where oxygen for EVAs could be stored in the form of water, and converted into high pressure oxygen on-demand. Cerium oxide solid electrolyte-based ion transport membranes have been shown to separate oxygen from air, and a supported monolithic wafer form of the CeO2 electrolyte membrane has been shown to deliver oxygen at pressures greater than 300 psia. These supported monolithic wafers can withstand high pressure differentials even though the membrane is very thin, because the ion transport membrane is supported on both sides (Fig 1). The monolithic supported wafers have six distinct layers, each with matched coefficients of thermal expansion. The wafers are assembled into a cell stack which allows easy air flow across the wafers, uniform current distribution, and uniform current density (Fig 2). The oxygen separation is reported to be "infinitely selective" to oxygen [1] with reported purity of 99.99% [2]. Combined with a mechanical compressor, a Solid Electrolyte Oxygen Separator (SEOS) should be capable of producing ABO grade oxygen at pressures >2400 psia, on the space station. Feasibility tests using a SEOS integrated with a mechanical compressor identified an unexpected contaminant in the oxygen: water vapour was found in the oxygen product, sometimes at concentrations higher than 40 ppm (the ABO limit for water vapour is 7 ppm). If solid electrolyte membranes are really "infinitely selective" to oxygen as they are reported to be, where did the water come from? If water is getting into the oxygen, what other contaminants might get into the oxygen? Microscopic analyses of wafers, welds, and oxygen delivery tubes were performed in an attempt to find the source of the water vapour contamination. Hot and cold pressure decay tests were performed. Measurements of water vapour as a function of O2 delivery rate, O2 delivery pressure, and process air humidity levels were the most instructive in finding the source of water contamination (Fig 3). Water contamination was directly affected by oxygen delivery rate (doubling the oxygen production rate cut the water level in half). Water was affected by process air humidity levels and delivery pressure in a way that indicates the water was diffusing into the oxygen delivery system.

Graf, John↗
NASA NTRSDate not supplied

Aerial Vehicle Routing and Scheduling for UAS Traffic Management: A Monte Carlo Tree Search Approach

Numerous unmanned aircraft systems operating at low altitudes to deliver goods and services may one day become ubiquitous in our cities. In the Unmanned Aircraft Systems (UAS) Traffic Management (UTM) framework, such a concept is envisioned, where aerial vehicles operate beyond visual line of sight (BVLOS) within specifically reserved and time stamped “corridors” in the airspace. For example, these corridors or operational intent volumes can connect an aerial vehicle’s origin site to its destination site for package delivery operations. There may also be more than one corridor available for an aerial vehicle to choose from and often different corridors may intersect with one another. Thus, it is imperative to ensure flight trajectories belonging to different aerial vehicles are not in conflict. Per the UTM CONOPs, we assume that a vehicle almost always stays inside its corridor or operational volume. This work provides a framework for strategic deconfliction of UTM or package delivery drones, where we schedule the departure time of all vehicles subject to various temporal constraints (including the corridor deconfliction at the intersections). We present the “multi-route weighted package delivery problem” which serves as an exemplifying model for strategic deconfliction in UTM. In the multi-route weighted package delivery problem, a graph network is given which consists of a set of depots (source) and drop-off (destination) nodes, with multiple routes (defined as a sequence of waypoints) connecting the depots to drop-off nodes. In addition, routes are weighted by the associated ground risk and total travel distance for package delivery. The goal is for a known set of aerial vehicles to depart from the depots, choose a route and take off time, while avoiding conflicts with other aerial vehicles, and minimizing both risk and distance traveled. We provide a mixed integer linear programming (MILP) formulation of the problem, as well as a heuristic solution based on Monte Carlo Tree Search (MCTS) – a method used in game theory and artificial intelligence – to overcome limitations inherent to optimal solvers. Computational results show the advantages of using MCTS over the MILP formulation; the former can provide a sub-optimal solution quickly, and may sometimes even reach an optimal solution, whereas the latter may not even produce a solution in reasonable time. Furthermore, results from both the MILP formulation and MCTS methods were validated using a preliminary agent-based simulator implementing the UTM concept of operations. Thus, the MCTS method can be seen as a scalable solution to the complex multi-route weighted package delivery problem and may possibly be extended to similar complex optimization problems.

Kenny Chour↗
DOE OSTI2014

Flex-fuel injector for gas turbines

A fuel injector (36) for alternate fuels (26A, 26B) with different energy densities. Vanes (47B) extend radially from a fuel delivery tube structure (20B) with first and second fuel supply channels (19A, 19B). Each vane has first and second radial passages (21A, 21B) communicating with the respective fuel supply channels, and first and second sets of apertures (23A, 23B). The first fuel supply channel, first radial passage, and first apertures form a first fuel delivery pathway providing a first fuel flow rate at a given fuel delivery pathway backpressure that is essentially common to both sets of fuel delivery pathway apertures. The second fuel supply channel, second radial passage, and second apertures form a second fuel delivery pathway providing a second fuel flow rate that may be at least 1 about twice the first fuel flow rate at the given fuel delivery pathway backpressure.

33 ADVANCED PROPULSION SYSTEMS↗
DOE OSTI2013

Chemical Renal Denervation in the Rat

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-273: Using a Diode Array to Explore the Weakness of TPS DoseCalculation Algorithm for VMAT and Sliding Window Techniques

Purpose: To identify the weakness of dose calculation algorithm in a treatment planning system for volumetric modulated arc therapy (VMAT) and sliding window (SW) techniques using a two-dimensional diode array. Methods: The VMAT quality assurance(QA) was implemented with a diode array using multiple partial arcs that divided from a VMAT plan; each partial arc has the same segments and the original monitor units. Arc angles were less than ± 30°. Multiple arcs delivered through consecutive and repetitive gantry operating clockwise and counterclockwise. The source-toaxis distance setup with the effective depths of 10 and 20 cm were used for a diode array. To figure out dose errors caused in delivery of VMAT fields, the numerous fields having the same segments with the VMAT field irradiated using different delivery techniques of static and step-and-shoot. The dose distributions of the SW technique were evaluated by creating split fields having fine moving steps of multi-leaf collimator leaves. Calculated doses using the adaptive convolution algorithm were analyzed with measured ones with distance-to-agreement and dose difference of 3 mm and 3%.. Results: While the beam delivery through static and step-and-shoot techniques showed the passing rate of 97 ± 2%, partial arc delivery of the VMAT fields brought out passing rate of 85%. However, when leaf motion was restricted less than 4.6 mm/°, passing rate was improved up to 95 ± 2%. Similar passing rate were obtained for both 10 and 20 cm effective depth setup. The calculated doses using the SW technique showed the dose difference over 7% at the final arrival point of moving leaves. Conclusion: Error components in dynamic delivery of modulated beams were distinguished by using the suggested QA method. This partial arc method can be used for routine VMAT QA. Improved SW calculation algorithm is required to provide accurate estimated doses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-305: Clinical Effects of Dosimetric Leaf Gap (DLG) Values Between Matched Varian Truebeam (TB) Linacs

Purpose: The dosimetric leaf gap (DLG) is an important parameter to be measured for dynamic beam delivery of modern linacs, like the Varian Truebeam (TB). The clinical effects of DLG-values on IMRT and/or VMAT commissioning of two “matched” TB linacs will be presented.Methods and Materials: The DLG values on two TB linacs were measured for all energy modalities (filtered and FFF-modes) as part of the dynamic delivery mode commissioning (IMRT and/or VMAT. After the standard beam data was modeled in eclipse treatment planning system (TPS) and validated, IMRT validation was performed based on TG1191 benchmark, IROC Head-Neck (H&N) phantom and sample of clinical cases, all measured on both linacs. Although there was a single-set of data entered in the TPS, a noticeable difference was observed for the DLG-values between the linacs. The TG119, IROC phantom and selected patient plans were furnished with DLG-values of TB1 for both linacs and the delivery was performed on both TB linacs for comparison. Results: The DLG values of TB1 was first used for both linacs to perform the testing comparisons. The QA comparison of TG119 plans revealed a great dependence of the results to the DLG-values used for the linac for all energy modalities studied, especially when moving from 3%/3mm to 2%/2mm γ-analysis. Conclusion: The DLG-values have a definite influence on the dynamic dose, delivery that increases with the plan complexity. We recommend that the measured DLG-values are assigned to each of the “matched” linacs, even if a single set of beam data describes multiple linacs. The user should perform a detail test of the dynamic delivery of each linac based on end-to-end benchmark suites like TG119 and IROC phantoms.1Ezzel G., et al., “IMRT commissioning: Multiple institution planning and dosimetry comparisons, a report from AAPM Task Group 119.” Med. Phys. 36:5359–5373 (2009). partly supported by CAMC Cancer Center and Alliance Oncology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-FG-CAMPUS-TeP2-05: Optimizing Stereotactic Radiosurgery Treatment of Multiple Brain Metastasis Lesions with Individualized Rotational Arc Trajectories

Purpose: Radiosurgery of multiple (n>4) brain metastasis lesions requires 3–4 noncoplanar VMAT arcs with excessively high monitor units and long delivery time. We investigated whether an improved optimization technique would decrease the needed arc numbers and increase the delivery efficiency, while improving or maintaining the plan quality. Methods: The proposed 4pi arc space optimization algorithm consists of two steps: automatic couch angle selection followed by aperture generation for each arc with optimized control points distribution. We use a greedy algorithm to select the couch angles. Starting from a single coplanar arc plan we search through the candidate noncoplanar arcs to pick a single noncoplanar arc that will bring the best plan quality when added into the existing treatment plan. Each time, only one additional noncoplanar arc is considered making the calculation time tractable. This process repeats itself until desired number of arc is reached. The technique is first evaluated in coplanar arc delivery scheme with testing cases and then applied to noncoplanar treatments of a case with 12 brain metastasis lesions. Results: Clinically acceptable plans are created within minutes. For the coplanar testing cases the algorithm yields singlearc plans with better dose distributions than that of two-arc VMAT, simultaneously with a 12–17% reduction in the delivery time and a 14–21% reduction in MUs. For the treatment of 12 brain mets while Paddick conformity indexes of the two plans were comparable the SCG-optimization with 2 arcs (1 noncoplanar and 1 coplanar) significantly improved the conventional VMAT with 3 arcs (2 noncoplanar and 1 coplanar). Specifically V16 V10 and V5 of the brain were reduced by 11%, 11% and 12% respectively. The beam delivery time was shortened by approximately 30%. Conclusion: The proposed 4pi arc space optimization technique promises to significantly reduce the brain toxicity while greatly improving the treatment efficiency.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Sequential and Simultaneous 4-Antenna Microwave Ablation in an Ex Vivo Bovine Liver Model

Aims: To determine the sizes and shapes of ablation zones in 4-antenna microwave ablation in ex vivo bovine liver model under different conditions of power delivery patterns, antenna spacings, and ablation durations, for further using of multi-antenna MWA strategies in the treatment of large hepatocellular carcinoma. Methods: We tested protocols of eight ablations each on ex vivo bovine livers, involving simultaneous or sequential activation of four microwave antennas, spaced either 3 cm, 4 cm, or 5 cm apart, for either 10 or 15 min, at 60-W power. We determined the diameters, shapes, and temperatures of the ablation zones. Results: Compared to sequential power delivery, simultaneous power delivery resulted in significantly larger ablation zone diameters (P < .001). The temperatures in ablation zones were significantly higher for simultaneous than for sequential power delivery. The largest ablation diameter (7.45 ± 0.06 cm) resulted from simultaneous delivery for 15 min using 4-cm antenna spacing. Conclusions: Simultaneous 4-antenna microwave ablation results in larger ablation zones than sequential ablation, and 4-cm antenna spacing with a 15-minute ablation duration creates the largest ablation zone. This information may provide multi-antenna MWA strategies for large HCC in the further clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Enhanced carbon-transfer and -utilization efficiencies achieved using membrane carbonation with gas sources having a range of CO 2 concentrations

The economic viability of microalgal biofuels relies on increasing productivity in a cost-effective manner. As microalgal biomass contains > 50% carbon, a high rate of CO 2 delivery is required for high productivity, and inefficient CO 2 delivery amplifies operating costs. Membrane carbonation using non-porous hollow fiber membranes can ideally deliver CO 2 without bubble formation and high carbon transfer efficiency. Because CO 2 streams from industrial resources are not 100% CO 2 , the buildup of inert gasses can significantly lower the CO 2 delivery rate when the distal end of the membrane is closed. To overcome the buildup of inert gases, we managed the distal end of the membranes with three different approaches: fully open end, restricted bleed valve, and restricted bleed valve with pH-actuated venting. For all approaches, CO 2 was delivered to membranes ondemand based on a pH set point. Evaluating a wide range of CO 2 concentrations (10% to 100%), we found that all approaches eliminated the buildup of inert gases, could maintain target pH values and gave the same biomass productivities and carbon distributions. However, carbon transfer efficiency depended on the operation of the distal end. Fully open-end operation gave a poor carbon transfer efficiency because of excessive loss of CO 2 from the distal end. However, restricting the exit flow rate to ≤4 cm 3 /min mitigated the problems of excessive CO 2 loss, but without incurring a large loss of CO 2 -delivery flux. For the continuous cultivation, combining a restricted bleed valve with pH-actuated venting improved the carbon-transfer efficiency and -utilization efficiencies up to 85% and 67%, respectively, with a sufficient CO 2 delivery flux.

42 ENGINEERING↗
DOE OSTI2013

Multicenter Collaborative Quality Assurance Program for the Province of Ontario, Canada: First-Year Results

Purpose: The objective of this work was to develop a collaborative quality assurance (CQA) program to assess the performance of intensity modulated radiation therapy (IMRT) planning and delivery across the province of Ontario, Canada. Methods and Materials: The CQA program was designed to be a comprehensive end-to-end test that can be completed on multiple planning and delivery platforms. The first year of the program included a head-and-neck (H and N) planning exercise and on-site visit to acquire dosimetric measurements to assess planning and delivery performance. A single dosimeter was used at each institution, and the planned to measured dose agreement was evaluated for both the H and N plan and a standard plan (linear-accelerator specific) that was created to enable a direct comparison between centers with similar infrastructure. Results: CQA program feasibility was demonstrated through participation of all 13 radiation therapy centers in the province. Planning and delivery was completed on a variety of infrastructure (treatment planning systems and linear accelerators). The planning exercise was completed using both static gantry and rotational IMRT, and planned-to-delivered dose agreement (pass rates) for 3%/3-mm gamma evaluation were greater than 90% (92.6%-99.6%). Conclusions: All centers had acceptable results, but variation in planned to delivered dose agreement for the same planning and delivery platform was noted. The upper end of the range will provide an achievable target for other centers through continued quality improvement, aided by feedback provided by the program through the use of standard plans and simple test fields.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

A study of the dosimetric characteristics between different fixed-field IMRT and VMAT in early-stage primary mediastinal B-cell lymphoma

This analysis was designed to compare dosimetric parameters among different fixed-field intensity-modulated radiation therapy (IMRT) solutions and volumetric-modulated arc therapy (VMAT) to identify which can achieve the lowest risk of organs at risk (OARs) and treatment delivery efficiently. A total of 16 patients (8 male and 8 female) with early-stage primary mediastinal large B-cell lymphoma (PMBCL) were enrolled with planned gross tumor volume (PGTV) 45 Gy and planning target volume (PTV) 40 Gy. Four different plans were generated: 5-, 7, 9-field IMRT, and VMAT. The dose distributions for PGTV and PTV OARs (lungs, left ventricle, heart, thyroid gland, and breasts) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. Mean conformity index (CI) and homogeneity index (HI) for PGTV in 5F-, 7F-, 9F-IMRT, and VMAT were 1.01 and 1.10, 1.01 and 1.10, 1.01 and 1.10, and 1.01 and 1.11 (p = 0.963 and 0.843), whereas these 2 indices for PTV were 1.04 and 1.22, 1.03 and 1.19, 1.03 and 1.17, and 1.08 and 1.14 (p = 0.964 and 0.969), respectively. D{sub mean} (Gy), V4 (%), D50 (Gy), and D80 (Gy) to the left and right breasts increased by 0.7 Gy and 0.1 Gy, 6.8% and 7.7%, 0.9 Gy and 1.7 Gy, and 1.0 Gy and 1.5 Gy in VMAT, respectively. The 9-beam IMRT plan had the highest MUs (25,762.4 MUs) and the longest treatment delivery time (10.7 minutes); whereas, the VMAT had the lowest MUs (13,345.0) and the shortest treatment delivery time (5.9 minutes). Seven- and 9-field IMRT and VMAT provide improved tumor coverage compared with 5F-IMRT, whereas VMAT shows higher treatment delivery efficiency than IMRT technique. Seven- and 9-field IMRT slightly reduce the low dose radiation exposure of breasts compared with VMAT technique. The 7- and 9-field IMRT and VMAT techniques both can be safely and efficiently delivered to patients with PMBCL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Rapid emission angle selection for rotating-shield brachytherapy

Purpose: The authors present a rapid emission angle selection (REAS) method that enables the efficient selection of the azimuthal shield angle for rotating shield brachytherapy (RSBT). The REAS method produces a Pareto curve from which a potential RSBT user can select a treatment plan that balances the tradeoff between delivery time and tumor dose conformity. Methods: Two cervical cancer patients were considered as test cases for the REAS method. The RSBT source considered was a Xoft Axxent{sup TM} electronic brachytherapy source, partially shielded with 0.5 mm of tungsten, which traveled inside a tandem intrauterine applicator. Three anchor RSBT plans were generated for each case using dose-volume optimization, with azimuthal shield emission angles of 90 Degree-Sign , 180 Degree-Sign , and 270 Degree-Sign . The REAS method converts the anchor plans to treatment plans for all possible emission angles by combining neighboring beamlets to form beamlets for larger emission angles. Treatment plans based on exhaustive dose-volume optimization (ERVO) and exhaustive surface optimization (ERSO) were also generated for both cases. Uniform dwell-time scaling was applied to all plans such that that high-risk clinical target volume D{sub 90} was maximized without violating the D{sub 2cc} tolerances of the rectum, bladder, and sigmoid colon. Results: By choosing three azimuthal emission angles out of 32 potential angles, the REAS method performs about 10 times faster than the ERVO method. By setting D{sub 90} to 85-100 Gy{sub 10}, the delivery times used by REAS generated plans are 21.0% and 19.5% less than exhaustive surface optimized plans used by the two clinical cases. By setting the delivery time budget to 5-25 and 10-30 min/fx, respectively, for two the cases, the D{sub 90} contributions for REAS are improved by 5.8% and 5.1% compared to the ERSO plans. The ranges used in this comparison were selected in order to keep both D{sub 90} and the delivery time within acceptable limits. Conclusions: The REAS method enables efficient RSBT treatment planning and delivery and provides treatment plans with comparable quality to those generated by exhaustive replanning with dose-volume optimization.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Fan-beam intensity modulated proton therapy

Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems.Conclusions: Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.

61 RADIATION PROTECTION AND DOSIMETRY↗