Results for “DELIVERY” — Page 7

DOE OSTI2020

Efficacy and Delivery of Novel FAST Agents for Coronaviruses

We proposed to test and develop advanced delivery for novel agents from our collaborators Facile Accelerated Specific Therapeutics (FAST) platform to reduce coronavirus replication. Sachi Bioworks Inc., Prof. Anushree Chatterjee, and Prof. Prashant Nagpal at the University of Colorado Boulder have developed a bioinformatics and synthesis pipeline to produce sequence specific theranostic agents (agents that can be therapies and/or diagnostics) that are inherently transported into the cytoplasm of mammalian host cells and sequence-specifically interfere in nucleic acid replication. The agent comprises a small nanoparticle (2-5 nm) chosen for ideal cellular transport and/or imaging conjugated to a short, synthetic DNA analog oligomer designed for binding to one or more target viral sequences. The sequence specific binding of the FAST agent to its target prevents nucleic acid replication due to its high affinity binding. While the small nanoparticle facilitates delivery in vitro, we plan to package the FAST agents into a larger nanoparticle (80-300 nm) for future in vivo delivery applications. Our team at Sandia has expertise encapsulating biomolecules including protein, DNA, and RNA into solid lipid nanoparticles (LNP) and lipid coated mesoporous silica nanoparticles (LC-MSN) and shown successful delivery in mouse models to multiple tissues. Our team focused on formulation parameters for FAST agents into lipid nanoparticles (LNP) and lipid coated mesoporous silica nanoparticles (LC-MSN) for enhanced delivery and/or efficacy and in vivo translation. We used lipid formulas that have been shown in literature to facility in vitro and more importantly, in vivo delivery. In our work discussed below, we successfully demonstrate loading and release of FAST agents on silica core and stable LC-MSN in a reasonable size range for in vivo testing.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2019

Review of Amendment Delivery and Distribution Methods, and Relevance to Potential In Situ Source Area Treatment at the Hanford Site

The U.S. Department of Energy’s Hanford Site in southeastern Washington State is a complex of multiple facilities where historical release events in the Central Plateau area have resulted in subsurface contamination of the vadose zone, a perched-water zone, and underlying aquifer. Although some contaminants have already migrated through the vadose zone into the groundwater, contaminants remaining in the unsaturated zone are a potential long-term risk as a source for further groundwater contamination. Moreover, a perched-water zone located in the 200-DV-1 Operable Unit at Hanford creates further remediation difficulties. Remediation options are limited for contaminants located in the vadose and perched-water zones within the Central Plateau due to considerable depth, co-located contaminants, and complexities associated with physical and biogeochemical heterogeneities. Existing comprehensive reviews discuss potential remedial technologies relevant to Hanford Site conditions (e.g., deep vadose zone and perched water) and provide treatment technology recommendations. Many of the recommended in situ remediation technologies rely on introduction of amendments into the subsurface to achieve remedial goals. However, there are currently few review or guidance documents that provide a comprehensive look at mechanisms and considerations related to amendment delivery and distribution. This document summarizes amendment types, delivery techniques, subsurface access methods, and the applicability of delivery methods and amendments for specific subsurface target zones, including in the context of Hanford Central Plateau applications. Guidance on the appropriateness of a remedial technology for a specific site and contaminant is not included within this document. Rather, this document is intended to be used when considering remediation technologies and the associated amendments. An overview of amendment types (i.e., liquid, gas, and solids) and access/distribution methods used in subsurface remediation is provided, along with discussion of the maturity level (low, medium, or high), advantages, and limitations that relate to the potential effectiveness of each approach in the context of site-specific factors (subsurface geology, geochemistry, contaminant properties, etc.). There are many Hanford Site-specific factors that influence the suitability and appropriateness of amendment delivery strategies. Excluding amendment delivery approaches that are unsuitable for the Hanford context, each approach was assessed for applicability to the following target zones: unsaturated high permeability, unsaturated low permeability, perched water, saturated high permeability, and saturated low permeability zones. This compilation and discussion related to amendment delivery mechanisms provides a useful resource for evaluating remedial alternatives for source area contamination in the Hanford Central Plateau.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

NASA NTRS2000

Deep Space Systems Technology Program Future Deliveries

NASA is in a period of frequent launches of low cost deep space missions with challenging performance needs. The modest budgets of these missions make it impossible for each to develop its own technology, therefore, efficient and effective development and insertion of technology for these missions must be approached at a higher level than has been done in the past. The Deep Space Systems Technology Program (DSST), often referred to as X2000, has been formed to address this need. The program is divided into a series of "Deliveries" that develop and demonstrate a set of spacecraft system capabilities with broad applicability for use by multiple missions. The First Delivery Project, to be completed in 2001, will provide a one MRAD-tolerant flight computer, power switching electronics, efficient radioisotope power source, and a transponder with services at 8.4 GHz and 32 GHz bands. Plans call for a Second Delivery in late 2003 to enable complete deep space systems in the 10 to 50 kg class, and a Third Delivery built around Systems on a Chip (extreme levels of electronic and microsystems integration) around 2006. Formulation of Future Deliveries (past the First Delivery) is ongoing and includes plans for such developments as highly miniaturized digital/analog/power electronics, optical communications, multifunctional structures, miniature lightweight propulsion, advanced thermal control techniques, highly efficient radioisotope power sources, and a unified flight ground software architecture to support the needs of future highly intelligent space systems. All developments are targeted at broad applicability and reuse, and will be commercialized within the US.

Salvo, Christopher G.↗

NASA NTRS2016

Assessment of Delivery Accuracy in an Operational-Like Environment

In order to enable arrival management concepts and solutions in a Next Generation Air Transportation System (NextGen) environment, ground-based sequencing and scheduling functions were developed to support metering operations in the National Airspace System. These sequencing and scheduling tools are designed to assist air traffic controllers in developing an overall arrival strategy, from enroute down to the terminal area boundary. NASA developed a ground system concept and protoype capability called Terminal Sequencing and Spacing (TSAS) to extend metering operations into the terminal area to the runway. To demonstrate the use of these scheduling and spacing tools in an operational-like environment, the FAA, NASA, and MITRE conducted an Operational Integration Assessment (OIA) of a prototype TSAS system at the FAA's William J. Hughes Technical Center (WJHTC). This paper presents an analysis of the arrival management strategies utilized and delivery accuracy achieved during the OIA. The analysis demonstrates how en route preconditioning, in various forms, and schedule disruptions impact delivery accuracy. As the simulation spanned both enroute and terminal airspace, the use of Ground Interval Management - Spacing (GIM-S) enroute speed advisories was investigated. Delivery accuracy was measured as the difference between the Scheduled Time of Arrival (STA) and the Actual Time of Arrival (ATA). The delivery accuracy was computed across all runs conducted during the OIA, which included deviations from nominal operations which are known to commonly occur in real operations, such as schedule changes and missed approaches. Overall, 83% of all flights were delivered into the terminal airspace within +/- 30 seconds of their STA and 94% of flights were delivered within +/- 60 seconds. The meter fix delivery accuracy standard deviation was found to be between 36 and 55 seconds across all arrival procedures. The data also showed when schedule disruptions were excluded, the percentage of aircraft delivered within +/- 30 seconds was between 85 and 90% across the various arrival procedures at the meter fix. This paper illustrates the ability to meet new delivery accuracy requirements in an operational-like environment using operational systems and NATCA controller participants, while also including common events that might cause disruptions to the schedule and overall system.

Air Traffic Scheduling↗

NASA NTRS2018

Angled Radial Fuel/Air Delivery System for Combustor

A combustor is provided. The combustor may comprise an axial fuel delivery system, and a radial fuel delivery system aft of the axial fuel delivery system. The radial fuel delivery system may be configured to direct fuel at least partially towards the axial fuel delivery system. A radial fuel delivery system is also provided. The system may comprise a combustor including a combustor liner, a mixer coupled to the combustor liner, and a nozzle disposed within the mixer, wherein the mixer and the nozzle are configured to direct fuel in a direction at least partially forward.

Kim, Wookyung↗

DOE OSTI2020

Designing a drone delivery network with automated battery swapping machines

Drones are projected to alter last-mile delivery, but their short travel range is a concern. In this study, we propose a drone delivery network design using automated battery swapping machines (ABSMs) to extend ranges. The design minimizes the long-term delivery costs, including ABSM investment, drone ownership, and cost of the delivery time, and locates ABSMs to serve a set of customers. We build a mixed-integer nonlinear program that captures the nonlinear waiting time of drones at ABSMs. To solve the problem, we create an exact solution algorithm that finds the globally optimal solution using a derivative-supported cutting-plane method. To validate the applicability of our program, we conduct a case study on the Chicago Metropolitan area using cost data from leading ABSM manufacturer and geographical data from the planning and operations language for agent-based regional integrated simulation (more commonly known as POLARIS). A sensitivity analysis identifies that ABSM service times and costs are the key parameters impacting the long-term adoption of drone delivery.

25 ENERGY STORAGE↗

DOE OSTI2015

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2015

Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using Orthogonal X-ray Fluoroscopic Imaging

Purpose: The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry–ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system. Methods and Materials: A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions. Results: In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases. Conclusions: An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA below 0.6°.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2022

Poly( N -vinylpyrrolidone)- block -Poly(dimethylsiloxane)- block -Poly( N -vinylpyrrolidone) Triblock Copolymer Polymersomes for Delivery of PARP1 siRNA to Breast Cancers

Nearly 20% of HER2-positive breast cancers develop resistance to HER2-targeted therapies requiring the use of advanced therapies. Silencing RNA therapy may be a powerful modality for treating resistant HER2 cancers due to its high specificity and low toxicity. However, the systemic administration of siRNAs requires a safe and efficient delivery platform because of siRNA’s low stability in physiological fluids, inefficient cellular uptake, immunoreactivity, and rapid clearance. We have developed theranostic polymeric vesicles to overcome these hurdles for encapsulation and delivery of small functional molecules and PARP1 siRNA for in vivo delivery to breast cancer tumors. The 100 nm polymer vesicles were assembled from biodegradable and non-ionic poly(N-vinylpyrrolidone) 14 -block-poly(dimethylsiloxane) 47 -block-poly(N-vinylpyrrolidone) 14 triblock copolymer PVPON 14 -PDMS 47 -PVPON 14 using nanoprecipitation and thin-film hydration. We demonstrated that the vesicles assembled from the copolymer covalently tagged with the Cy5.5 fluorescent dye for in vivo imaging could also encapsulate the model drug with high loading efficiency (40%). The dye-loaded vesicles were accumulated in tumors after 18 h circulation in 4TR breast tumor-bearing mice via passive targeting. We found that PARP1 siRNA encapsulated into the vesicles was released intact (13%) into solution by the therapeutic ultrasound treatment as quantified by gel electrophoresis. Additionally, the PARP1 siRNA-loaded polymersomes inhibited the proliferation of MDA-MB-361TR cells by 34% after 6 days of treatment by suppressing the NF-kB signaling pathway, unlike their scrambled siRNA-loaded counterparts. Finally, the treatment by PARP1 siRNA-loaded vesicles prolonged the survival of the mice bearing 4T1 breast cancer xenografts, with the 4-fold survival increase, unlike the untreated mice after 3 weeks following the treatment. These biodegradable, non-ionic PVPON 14 -PDMS 47 -PVPON 14 polymeric nanovesicles capable of the efficient encapsulation and delivery of PARP1 siRNA to successfully knock down PARP1 in vivo can provide an advanced platform for the development of precision-targeted therapeutic carriers, which could help develop highly effective drug delivery nanovehicles for breast cancer gene therapy.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-P-30: Clinical Assessment of Auto Beam-Hold Triggered by Fiducial Localization During Prostate RapidArc Delivery

Purpose: To assess the clinical efficacy of auto beam hold during prostate RapidArc delivery, triggered by fiducial localization on kV imaging with a Varian True Beam. Methods: Prostate patients with four gold fiducials were candidates in this study. Daily setup was accomplished by aligning to fiducials using orthogonal kV imaging. During RapidArc delivery, a kV image was automatically acquired with a momentary beam hold every 60 degrees of gantry rotation. The position of each fiducial was identified by a search algorithm and compared to a predetermined 1.4 cm diameter target area. Treatment continued if all the fiducials were within the target area. If any fiducial was outside the target area the beam hold was not released, and the operators determined if the patient needed re-alignment using the daily setup method. Results: Four patients were initially selected. For three patients, the auto beam hold performed seamlessly. In one instance, the system correctly identified misaligned fiducials, stopped treatment, and the patient was re-positioned. The fourth patient had a prosthetic hip which sometimes blocked the fiducials and caused the fiducial search algorithm to fail. The auto beam hold was disabled for this patient and the therapists manually monitored the fiducial positions during treatment. Average delivery time for a 2-arc fraction was increased by 59 seconds. Phantom studies indicated the dose discrepancy related to multiple beam holds is <0.1%. For a plan with 43 fractions, the additional imaging increased dose by an estimated 68 cGy. Conclusion: Automated intrafraction kV imaging can effectively perform auto beam holds due to patient movement, with the exception of prosthetic hip patients. The additional imaging dose and delivery time are clinically acceptable. It may be a cost-effective alternative to Calypso in RapidArc prostate patient delivery. Further study is warranted to explore its feasibility under various clinical conditions.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-C-BRC-00: Emerging Technologies in SRS/SBRT Delivery

The delivery techniques for SRS/SBRT have been under rapid developments in recent years, which pose new challenges to medical physicists ranging from planning and quality assurance to imaging and motion management. This educational course will provide a general overview of the latest delivery techniques in SRS/SBRT, and discuss the clinical processes to address the challenges of each technique with special emphasis on dedicated gamma-ray based device, robotic x-band linac-based system and conventional C-arm s-band linac-based SRS systems. (1). Gamma-ray based SRS/SRT: This is the gold standard of intracranial SRS. With the advent of precision imaging guidance and frameless patient positioning capabilities, novel stereoscopic CBCT and automatic dose adaption solution are introduced to the Gamma-ray based SRS for the first time. The first North American system has been approved by the US regulatory for patient treatments in the spring of 2016. (2). Robotic SRS/SBRT system: A number of technological milestones have been developed in the past few years, including variable aperture collimator, sequential optimization technique, and the time reduction technique. Recently, a new robotic model allows the option of a multi-leaf collimator. These technological advances have reduced the treatment time and improved dose conformity significantly and could potentially expand the application of radiosurgery for the treatment of targets not previously suitable for robotic SRS/SBRT or fractionated stereotactic radiotherapy. These technological advances have created new demanding mandates on hardware and patient quality assurance (QA) tasks, as well as the need for updating/educating the physicists in the community on these requirements. (3). Conventional Linac based treatments: Modulated arc therapy (MAT) has gained wide popularities in Linac-based treatments in recent years due to its high delivery efficiency and excellent dose conformities. Recently, MAT has been introduced to deliver highly conformal radiosurgery treatments to multiple targets simultaneously via a single isocenter to replace the conventional multi-iso multi-plan treatments. It becomes important to understand the advantages and limitations of this technique, and the pitfalls for implementing this technique in clinical practice. The planning process of single-iso multi-target MAT will be described, and its plan quality and delivery efficiency will be compared with multi-iso plans. The QA process for verifying such complex plans will be illustrated, and pitfalls in imaging and patient set up will be discussed. Overall, this session will focus on the following areas: 1) Update on the emerging technology in current SRS/SBRT delivery. 2) New developments in treatment planning and Quality Assurance program. 3) Imaging guidance and motion management. Learning Objectives: To understand the SRS/SBRT principles and its clinical applications, and gain knowledge on the emerging technologies in SRS/SBRT. To review planning concepts and useful tips in treatment planning. To learn about the imaging guidance procedures and the quality assurance program in SRS/SBRT. National Institutes of Health, Varian Medical System; L. Ren, The presenter is funded by National Institutes of Health and Varian Medical System.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-C-BRC-01: An Overview of Emerging Technologies in SRS/SBRT Delivery

The delivery techniques for SRS/SBRT have been under rapid developments in recent years, which pose new challenges to medical physicists ranging from planning and quality assurance to imaging and motion management. This educational course will provide a general overview of the latest delivery techniques in SRS/SBRT, and discuss the clinical processes to address the challenges of each technique with special emphasis on dedicated gamma-ray based device, robotic x-band linac-based system and conventional C-arm s-band linac-based SRS systems. (1). Gamma-ray based SRS/SRT: This is the gold standard of intracranial SRS. With the advent of precision imaging guidance and frameless patient positioning capabilities, novel stereoscopic CBCT and automatic dose adaption solution are introduced to the Gamma-ray based SRS for the first time. The first North American system has been approved by the US regulatory for patient treatments in the spring of 2016. (2). Robotic SRS/SBRT system: A number of technological milestones have been developed in the past few years, including variable aperture collimator, sequential optimization technique, and the time reduction technique. Recently, a new robotic model allows the option of a multi-leaf collimator. These technological advances have reduced the treatment time and improved dose conformity significantly and could potentially expand the application of radiosurgery for the treatment of targets not previously suitable for robotic SRS/SBRT or fractionated stereotactic radiotherapy. These technological advances have created new demanding mandates on hardware and patient quality assurance (QA) tasks, as well as the need for updating/educating the physicists in the community on these requirements. (3). Conventional Linac based treatments: Modulated arc therapy (MAT) has gained wide popularities in Linac-based treatments in recent years due to its high delivery efficiency and excellent dose conformities. Recently, MAT has been introduced to deliver highly conformal radiosurgery treatments to multiple targets simultaneously via a single isocenter to replace the conventional multi-iso multi-plan treatments. It becomes important to understand the advantages and limitations of this technique, and the pitfalls for implementing this technique in clinical practice. The planning process of single-iso multi-target MAT will be described, and its plan quality and delivery efficiency will be compared with multi-iso plans. The QA process for verifying such complex plans will be illustrated, and pitfalls in imaging and patient set up will be discussed. Overall, this session will focus on the following areas: 1) Update on the emerging technology in current SRS/SBRT delivery. 2) New developments in treatment planning and Quality Assurance program. 3) Imaging guidance and motion management. Learning Objectives: To understand the SRS/SBRT principles and its clinical applications, and gain knowledge on the emerging technologies in SRS/SBRT. To review planning concepts and useful tips in treatment planning. To learn about the imaging guidance procedures and the quality assurance program in SRS/SBRT. National Institutes of Health, Varian Medical System; L. Ren, The presenter is funded by National Institutes of Health and Varian Medical System.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-C-BRC-02: A Review of Emerging Technologies in Robotic SRS/SBRT Delivery

The delivery techniques for SRS/SBRT have been under rapid developments in recent years, which pose new challenges to medical physicists ranging from planning and quality assurance to imaging and motion management. This educational course will provide a general overview of the latest delivery techniques in SRS/SBRT, and discuss the clinical processes to address the challenges of each technique with special emphasis on dedicated gamma-ray based device, robotic x-band linac-based system and conventional C-arm s-band linac-based SRS systems. (1). Gamma-ray based SRS/SRT: This is the gold standard of intracranial SRS. With the advent of precision imaging guidance and frameless patient positioning capabilities, novel stereoscopic CBCT and automatic dose adaption solution are introduced to the Gamma-ray based SRS for the first time. The first North American system has been approved by the US regulatory for patient treatments in the spring of 2016. (2). Robotic SRS/SBRT system: A number of technological milestones have been developed in the past few years, including variable aperture collimator, sequential optimization technique, and the time reduction technique. Recently, a new robotic model allows the option of a multi-leaf collimator. These technological advances have reduced the treatment time and improved dose conformity significantly and could potentially expand the application of radiosurgery for the treatment of targets not previously suitable for robotic SRS/SBRT or fractionated stereotactic radiotherapy. These technological advances have created new demanding mandates on hardware and patient quality assurance (QA) tasks, as well as the need for updating/educating the physicists in the community on these requirements. (3). Conventional Linac based treatments: Modulated arc therapy (MAT) has gained wide popularities in Linac-based treatments in recent years due to its high delivery efficiency and excellent dose conformities. Recently, MAT has been introduced to deliver highly conformal radiosurgery treatments to multiple targets simultaneously via a single isocenter to replace the conventional multi-iso multi-plan treatments. It becomes important to understand the advantages and limitations of this technique, and the pitfalls for implementing this technique in clinical practice. The planning process of single-iso multi-target MAT will be described, and its plan quality and delivery efficiency will be compared with multi-iso plans. The QA process for verifying such complex plans will be illustrated, and pitfalls in imaging and patient set up will be discussed. Overall, this session will focus on the following areas: 1) Update on the emerging technology in current SRS/SBRT delivery. 2) New developments in treatment planning and Quality Assurance program. 3) Imaging guidance and motion management. Learning Objectives: To understand the SRS/SBRT principles and its clinical applications, and gain knowledge on the emerging technologies in SRS/SBRT. To review planning concepts and useful tips in treatment planning. To learn about the imaging guidance procedures and the quality assurance program in SRS/SBRT. National Institutes of Health, Varian Medical System; L. Ren, The presenter is funded by National Institutes of Health and Varian Medical System.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-C-BRC-03: Emerging Linac Based SRS/SBRT Technologies with Modulated Arc Delivery

The delivery techniques for SRS/SBRT have been under rapid developments in recent years, which pose new challenges to medical physicists ranging from planning and quality assurance to imaging and motion management. This educational course will provide a general overview of the latest delivery techniques in SRS/SBRT, and discuss the clinical processes to address the challenges of each technique with special emphasis on dedicated gamma-ray based device, robotic x-band linac-based system and conventional C-arm s-band linac-based SRS systems. (1). Gamma-ray based SRS/SRT: This is the gold standard of intracranial SRS. With the advent of precision imaging guidance and frameless patient positioning capabilities, novel stereoscopic CBCT and automatic dose adaption solution are introduced to the Gamma-ray based SRS for the first time. The first North American system has been approved by the US regulatory for patient treatments in the spring of 2016. (2). Robotic SRS/SBRT system: A number of technological milestones have been developed in the past few years, including variable aperture collimator, sequential optimization technique, and the time reduction technique. Recently, a new robotic model allows the option of a multi-leaf collimator. These technological advances have reduced the treatment time and improved dose conformity significantly and could potentially expand the application of radiosurgery for the treatment of targets not previously suitable for robotic SRS/SBRT or fractionated stereotactic radiotherapy. These technological advances have created new demanding mandates on hardware and patient quality assurance (QA) tasks, as well as the need for updating/educating the physicists in the community on these requirements. (3). Conventional Linac based treatments: Modulated arc therapy (MAT) has gained wide popularities in Linac-based treatments in recent years due to its high delivery efficiency and excellent dose conformities. Recently, MAT has been introduced to deliver highly conformal radiosurgery treatments to multiple targets simultaneously via a single isocenter to replace the conventional multi-iso multi-plan treatments. It becomes important to understand the advantages and limitations of this technique, and the pitfalls for implementing this technique in clinical practice. The planning process of single-iso multi-target MAT will be described, and its plan quality and delivery efficiency will be compared with multi-iso plans. The QA process for verifying such complex plans will be illustrated, and pitfalls in imaging and patient set up will be discussed. Overall, this session will focus on the following areas: 1) Update on the emerging technology in current SRS/SBRT delivery. 2) New developments in treatment planning and Quality Assurance program. 3) Imaging guidance and motion management. Learning Objectives: To understand the SRS/SBRT principles and its clinical applications, and gain knowledge on the emerging technologies in SRS/SBRT. To review planning concepts and useful tips in treatment planning. To learn about the imaging guidance procedures and the quality assurance program in SRS/SBRT. National Institutes of Health, Varian Medical System; L. Ren, The presenter is funded by National Institutes of Health and Varian Medical System.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-CD-209-10: Scanning Proton Arc Therapy (SPArc) - The First Robust and Delivery-Efficient Spot Scanning Proton Arc Therapy

Purpose: To develop a delivery-efficient proton spot-scanning arc therapy technique with robust plan quality. Methods: We developed a Scanning Proton Arc(SPArc) optimization algorithm integrated with (1)Control point re-sampling by splitting control point into adjacent sub-control points; (2)Energy layer re-distribution by assigning the original energy layers to the new sub-control points; (3)Energy layer filtration by deleting low MU weighting energy layers; (4)Energy layer re-sampling by sampling additional layers to ensure the optimal solution. A bilateral head and neck oropharynx case and a non-mobile lung target case were tested. Plan quality and total estimated delivery time were compared to original robust optimized multi-field step-and-shoot arc plan without SPArc optimization (Arcmulti-field) and standard robust optimized Intensity Modulated Proton Therapy(IMPT) plans. Dose-Volume-Histograms (DVH) of target and Organ-at-Risks (OARs) were analyzed along with all worst case scenarios. Total delivery time was calculated based on the assumption of a 360 degree gantry room with 1 RPM rotation speed, 2ms spot switching time, beam current 1nA, minimum spot weighting 0.01 MU, energy-layer-switching-time (ELST) from 0.5 to 4s. Results: Compared to IMPT, SPArc delivered less integral dose(−14% lung and −8% oropharynx). For lung case, SPArc reduced 60% of skin max dose, 35% of rib max dose and 15% of lung mean dose. Conformity Index is improved from 7.6(IMPT) to 4.0(SPArc). Compared to Arcmulti-field, SPArc reduced number of energy layers by 61%(276 layers in lung) and 80%(1008 layers in oropharynx) while kept the same robust plan quality. With ELST from 0.5s to 4s, it reduced 55%–60% of Arcmulti-field delivery time for the lung case and 56%–67% for the oropharynx case. Conclusion: SPArc is the first robust and delivery-efficient proton spot-scanning arc therapy technique which could be implemented in routine clinic. For modern proton machine with ELST close to 0.5s, SPArc would be a popular treatment option for both single and multi-room center.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double end-labeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF–nucleic acid ratios. In addition to high delivery efficiencies, the water-soluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits Introduced by Two Different Delivery Modalities

This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

36 MATERIALS SCIENCE↗

NASA NTRS2017

A Multi-Modality Mobility Concept for a Small Package Delivery UAV

This paper will discuss a different approach to the typical notional small package delivery drone concept. Most delivery drone concepts employ a point-to-point aerial delivery CONOPS (Concept of Operations) from a warehouse directly to the front or back yards of a customers residence or a commercial office space. Instead, the proposed approach is somewhat analogous to current postal deliveries: a small aerial vehicle flies from a warehouse to designated neighborhood VTOL (Vertical Take-Off and Landing) landing spots where the aerial vehicle then converts to a "roadable" (ground-mobility) vehicle that then transits on sidewalks and/or bicycle paths till it arrives to the residence/office drop-off points. This concept and associated platform or vehicle will be referred in this paper as MICHAEL (Multimodal Intra-City Hauling and Aerial-Effected Logistics) concept. It is suggested that the MICHAEL concept potentially results in a more community friendly "delivery drone" approach.

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