Results for “Delivery” — Page 85

DOE OSTI2016

SU-G-BRA-16: Target Dose Comparison for Dynamic MLC Tracking and Mid- Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

Purpose: Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid-ventilation planning approach, or by localizing the tumor in real-time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques. Methods: Lung stereotactic treatment plans (9-beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV-to-PTV margin: 2.6mm) or planned with a mid-ventilation approach and delivered without online motion compensation (GTV-to-PTV margin: 4.4-6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in-house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam-to-target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid-ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated. Results: When using the mid-ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4-1.2, 0.6-3.3 and 4.5-6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift. Conclusion: Intrafractional baseline drifts reduce the tumor dose in treatments based on mid-ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting clinical outcome in hypofractionated treatment protocols. Dynamic MLC tracking preserves tumor dose coverage even in the presence of extreme baseline drifts. We acknowledge financial and technical support of the MLC tracking research from Elekta AB. Research at ICR is supported by CRUK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR. MFF is supported by CRUK under Programme C33589/A19908.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-G-IeP4-06: Feasibility of External Beam Treatment Field Verification Using Cherenkov Imaging

Purpose: Cherenkov light emission has been shown to correlate with ionizing radiation (IR) dose delivery in solid tissue. In order to properly correlate Cherenkov light images with real time dose delivery in a patient, we must account for geometric and intensity distortions arising from observation angle, as well as the effect of monitor units (MU) and field size on Cherenkov light emission. To test the feasibility of treatment field verification, we first focused on Cherenkov light emission efficiency based on MU and known field size (FS). Methods: Cherenkov light emission was captured using a PI-MAX4 intensified charge coupled device(ICCD) system (Princeton Instruments), positioned at a fixed angle of 40° relative to the beam central axis. A Varian TrueBeam linear accelerator (linac) was operated at 6MV and 600MU/min to deliver an Anterior-Posterior beam to a 5cm thick block phantom positioned at 100cm Source-to-Surface-Distance(SSD). FS of 10×10, 5×5, and 2×2cm{sup 2} were used. Before beam delivery projected light field images were acquired, ensuring that geometric distortions were consistent when measuring Cherenkov field discrepancies. Cherenkov image acquisition was triggered by linac target current. 500 frames were acquired for each FS. Composite images were created through summation of frames and background subtraction. MU per image was calculated based on linac pulse delay of 2.8ms. Cherenkov and projected light FS were evaluated using ImageJ software. Results: Mean Cherenkov FS discrepancies compared to light field were <0.5cm for 5.6, 2.8, and 8.6 MU for 10×10, 5×5, and 2×2cm{sup 2} FS, respectably. Discrepancies were reduced with increasing field size and MU. We predict a minimum of 100 frames is needed for reliable confirmation of delivered FS. Conclusion: Current discrepancies in Cherenkov field sizes are within a usable range to confirm treatment delivery in standard and respiratory gated clinical scenarios at MU levels appropriate to standard MLC position segments.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-H-BRC-05: Catastrophic Error Metrics for Radiation Therapy

Purpose: Intuitive evaluation of complex radiotherapy treatments is impractical, while data transfer anomalies create the potential for catastrophic treatment delivery errors. Contrary to prevailing wisdom, logical scrutiny can be applied to patient-specific machine settings. Such tests can be automated, applied at the point of treatment delivery and can be dissociated from prior states of the treatment plan, potentially revealing errors introduced early in the process. Methods: Analytical metrics were formulated for conventional and intensity modulated RT (IMRT) treatments. These were designed to assess consistency between monitor unit settings, wedge values, prescription dose and leaf positioning (IMRT). Institutional metric averages for 218 clinical plans were stratified over multiple anatomical sites. Treatment delivery errors were simulated using a commercial treatment planning system and metric behavior assessed via receiver-operator-characteristic (ROC) analysis. A positive result was returned if the erred plan metric value exceeded a given number of standard deviations, e.g. 2. The finding was declared true positive if the dosimetric impact exceeded 25%. ROC curves were generated over a range of metric standard deviations. Results: Data for the conventional treatment metric indicated standard deviations of 3%, 12%, 11%, 8%, and 5 % for brain, pelvis, abdomen, lung and breast sites, respectively. Optimum error declaration thresholds yielded true positive rates (TPR) between 0.7 and 1, and false positive rates (FPR) between 0 and 0.2. Two proposed IMRT metrics possessed standard deviations of 23% and 37%. The superior metric returned TPR and FPR of 0.7 and 0.2, respectively, when both leaf position and MUs were modelled. Isolation to only leaf position errors yielded TPR and FPR values of 0.9 and 0.1. Conclusion: Logical tests can reveal treatment delivery errors and prevent large, catastrophic errors. Analytical metrics are able to identify errors in monitor units, wedging and leaf positions with favorable sensitivity and specificity. In part by Varian.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-AB-BRB-00: Research Opportunities with Digital Linear Accelerators

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapy involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-AB-BRB-01: Trajectory Modulated Arc Therapy: Application to Partial Breast Irradiation

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapy involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-AB-BRB-02: ET-Reloaded

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapy involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-AB-BRB-03: 4n Radiotherapy

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapy involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-AB-BRB-04: Quality Assurance for Advanced Digital Linac Implementations

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapy involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-AB-BRB-05: Using a Research Real-Time Control Interface to Go Beyond Dynamic MLC Tracking

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapy involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Commercial Vehicle Driver Behaviors and Decision Making: Lessons Learned from Urban Ridealongs

As e-commerce and urban deliveries spike, cities grapple with managing urban freight more actively. In order to effectively manage urban deliveries, city planners and policy makers need to better understand driver behaviors and the challenges they experience in performing deliveries. In this study, we collected data on commercial vehicle (CV) driver behaviors by performing ridealongs with various logistics carriers. Ridealongs were performed in Seattle, Washington, covering a range of vehicles (cars, vans, and trucks), goods (parcels, mail, beverages, and printed materials), and customer types (residential, office, large and small retail). Observers collected qualitative observations and quantitative data on trip and dwell times, while also tracking vehicles through GPS devices. The results showed that, on average, urban CVs spent 80 percent of their daily operating time parked. The study also found that, unlike the common belief, drivers (especially those operating heavier vehicles) parked in authorized parking locations, with only less than 5 percent of stops occurring in the travel lane. Dwell times associated with authorized parking locations were significantly longer than those of other parking locations, and mail and heavy goods deliveries generally had longer dwell times. We also identified three main criteria CV drivers used for choosing a parking location: avoiding unsafe maneuvers, minimizing conflicts with other users of the road, and coopetition with other commercial drivers. Here, the results provide estimates for trip times, dwell times, and parking choice types, as well as insights into why those decisions are made and the factors affecting driver choices.

33 ADVANCED PROPULSION SYSTEMS↗

DOE OSTI2018

Advanced Hydrogen Fueling Station Supply: Tube Trailers

Air Products and Chemicals, Inc. (Air Products) is reporting on the results of a DOE-funded program to develop and validate Advanced Hydrogen Fueling Station hydrogen tube trailers to support hydrogen and fuel cell market applications. The project involved the engineering design and development of a new composite over-wrapped pressure vessel to increase the pressure capability of tube trailers to deliver hydrogen to greater than 8500 psi (586 bar). The new composite over-wrapped pressure vessel tube trailer was expected to provide improved delivery technology and reduce the cost of transporting hydrogen from central hydrogen production sources. The project aimed to meet or exceed DOE’s 2020 delivery targets for tube trailer hydrogen distribution. A gated approach was taken for the project, with early project Go/No-Go decision points. Specific goals for this four-stage product development project included: Preliminary Study, Modeling, and Analysis: Complete a preliminary design analysis and cost viability of a >8500 psi (586 bar) hydrogen storage vessel with an appropriate frame and chassis configuration for a complete trailer to US DOT requirements; Develop New Tube Size for >8500 psi (586 bar) Vessel: Fabricate tubes for test units, perform testing, and submit test results for a DOT Special Permit; Design, fabricate, and test a delivery trailer unit; Deploy the delivery trailer to hydrogen stations and collect data. Work conducted under DE-EE0006524 established costs for US DOT Type III vessels at 8500 psi (586 bar), 12500 psi (862 bar), and 14000 psi (965 bar) with manufactured water volumes up to 375 liters. Trailer module designs were established for the maximum US DOT design limits and for Air Products’ design limit of a 40-foot trailer length that addresses California hydrogen fueling station ingress and egress operating constraints. Conceptual trailer designs were not capable of achieving the DOE 2020 capacity and cost targets, but they did exceed the DOE pressure target of 500 bar. Based on new trailer cost and simulated operating performance, the 8500 psi (586 bar) new trailer design is not feasible in comparison to Air Products’ DOT-approved 7500 psi (520 bar) trailer design in operation today. Also, the project was expected to incur significantly higher product development costs associated with new US DOT vessel development and approval. Alternative trailer design concepts were explored that included 700 bar compression-less mobile fueling that could be promising for early-market hydrogen infrastructure fueling station placement and development and niche military applications. Due to the economic and budget challenges identified in the feasibility phase of the program, Air Products, in agreement with the Department of Energy, decided to terminate this development program.

08 HYDROGEN↗

NASA NTRS2003

Alternating-pulse iontophoresis for targeted cutaneous anesthesia

In studies of sensory contributions to motor control, it may be advantageous to temporarily reduce the sensitivity of specific sensory systems. This article details a method for non-invasively inducing cutaneous anesthesia, leaving proprioceptive and motor functions intact. This method, called alternating-pulse iontophoresis, differs from conventional direct-current (DC) iontophoretic drug delivery in that adjacent drug delivery electrodes are stimulated out-of-phase. The total current delivered at any instant is then less than that produced during a comparable DC application, while the uniformity of drug delivery is expected to improve. Effective delivery of local anesthetics to the cutaneous foot soles by alternating-pulse iontophoresis was demonstrated using cutaneous pressure sensory threshold levels (STL's) assessed with Semmes-Weinstein monofilaments (arbitrary units of perceived force, or a.u.). Thirteen of 16 healthy subjects achieved a level of anesthesia greater than or equal to that normally associated with clinical peripheral sensory neuropathy. Average STL's measured prior to the anesthesia procedure were 4.00 a.u. ( approximately 10 mN). Immediately following the procedure, STL's were elevated to an average of 5.40 a.u. ( approximately 246 mN) and averaged 4.97 a.u. ( approximately 92 mN) after 50 min of standing. A number of research and clinical applications for this technique are suggested.

Non-NASA Center↗

DOE OSTI2015

An “Off-the-Shelf” System for Intraprocedural Electrical Current Evaluation and Monitoring of Irreversible Electroporation Therapy

IntroductionIrreversible electroporation (IRE) ablation uses a series of brief electric pulses to create nanoscale defects in cell membranes, killing the cells. It has shown promise in numerous soft-tissue tumor applications. Larger voltages between electrodes will increase ablation volume, but exceeding electrical limits may risk damage to the patient, cause ineffective therapy delivery, or require generator restart. Monitoring electrical current for these conditions in real-time enables managing these risks. This capacity is not presently available in clinical IRE generators.MethodsWe describe a system using a Tektronix TCP305 AC/DC Current Probe connected to a TCPA300 AC/DC Current Probe Amplifier, which is read on a computer using a Protek DSO-2090 USB computer-interfacing oscilloscope. Accuracy of the system was tested with a resistor circuit and by comparing measured currents with final outputs from the NanoKnife clinical electroporation pulse generator.ResultsAccuracy of measured currents was 1.64 ± 2.4 % relative to calculations for the resistor circuit and averaged 0.371 ± 0.977 % deviation from the NanoKnife. During clinical pulse delivery, the system offers real-time evaluation of IRE procedure progress and enables a number of methods for identifying approaching issues from electrical behavior of therapy delivery, facilitating protocol changes before encountering therapy delivery issues.ConclusionsThis system can monitor electrical currents in real-time without altering the electric pulses or modifying the pulse generator. This facilitates delivering electric pulse protocols that remain within the optimal range of electrical currents—sufficient strength for clinically relevant ablation volumes, without the risk of exceeding safe electric currents or causing inadequate ablation.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

Mathematical modeling in cancer nanomedicine: a review

Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine has made significant progress, but challenges remain that impede its clinical translation. Several biophysical barriers to the transport of nanocarriers to the tumor exist, and a much deeper understanding of nano-bio interactions is necessary to change the status quo. Mathematical modeling has been instrumental in improving our understanding of the physicochemical and physiological underpinnings of nanomaterial behavior in biological systems. Here, we present a comprehensive review of literature on mathematical modeling works that have been and are being employed towards a better understanding of nano-bio interactions for improved tumor delivery efficacy.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Aeration costs in stirred-tank and bubble column bioreactors

To overcome knowledge gaps in the economics of large-scale aeration for production of commodity products, Aspen Plus is used to simulate steady-state oxygen delivery in both stirred-tank and bubble column bioreactors, using published engineering correlations for oxygen mass transfer as a function of aeration rate and power input, coupled with new equipment cost estimates developed in Aspen Capital Cost Estimator and validated against vendor quotations. Here, these simulations describe the cost efficiency of oxygen delivery as a function of oxygen uptake rate and vessel size, and show that capital and operating costs for oxygen delivery drop considerably moving from standard-size (200 m 3 ) to world-class size (500 m 3 ) reactors, but only marginally in further scaling up to hypothetically large (1000 m 3 ) reactors. Finally, this analysis suggests bubble-column reactor systems can reduce overall costs for oxygen delivery by 10-20% relative to stirred tanks at low to moderate oxygen transfer rates up to 150 mmol/L-h.

09 BIOMASS FUELS↗

DOE OSTI2018

The effect of variable fuel staging transients on self-excited instabilities in a multiple-nozzle combustor

Combustion instability in gas turbine engines is often mitigated using fuel staging. Fuel staging, sometimes referred to as fuel splitting, is a strategy by which fuel is unevenly distributed between different nozzles of a multiple-nozzle combustor. These fuel splits are conducted in a transient manner in real engines, and the effects of these transients on instability are not well characterized. This work fills this gap by systematically studying the effects of transient fuel staging on self-excited combustion instability by varying the amount of staging fuel (staging amplitude), timescale in which the fuel is added (transient duration), and whether staging fuel is added or subtracted (transient direction). In this work, three staging amplitudes, five transient durations, and both transient directions are considered. The transient timescales are broadly divided into “short” duration transients, which have fuel delivery timescales shorter than the characteristic instability decay or onset timescales, and “long” duration transients, which have fuel delivery timescales longer than the characteristic instability decay or onset timescales. For short duration transients, we find the instability decay timescale depends on staging amplitude but does not depend on transient duration. For long duration transients, we find the instability decay timescale does not strongly depend on staging amplitude. The instability onset timescale is found to be longer and more variable between runs than the instability decay timescale for a given fuel delivery timescale. The onset timescale is also longer in duration and more variable than the decay timescale at a given fuel delivery timescale, implying that the instability rise process is overall more variable and slower than the instability decay process. Analysis of combustor damping rates show a strong dependence of damping rate on staging amplitude but no strong dependence on transient duration or direction. Instantaneous phase difference images between p' and are used to differentiate regions in the combustor that have constructive versus destructive interference between heat release rate oscillations and pressure fluctuations. Furthermore, the phase images show that p' and q . ' become in-phase early in the transient for the onset transients.

20 FOSSIL-FUELED POWER PLANTS↗

DOE OSTI2017

Empowering Intensity Modulated Proton Therapy Through Physics and Technology: An Overview

Considering the clinical potential of protons attributable to their physical characteristics, interest in proton therapy has increased greatly in this century, as has the number of proton therapy installations. Until recently, passively scattered proton therapy was used almost entirely. Notably, the overall clinical results to date have not shown a convincing benefit of protons over photons. A rapid transition is now occurring with the implementation of the most advanced form of proton therapy, intensity modulated proton therapy (IMPT). IMPT is superior to passively scattered proton therapy and intensity modulated radiation therapy (IMRT) dosimetrically. However, numerous limitations exist in the present IMPT methods. In particular, compared with IMRT, IMPT is highly vulnerable to various uncertainties. In this overview we identify three major areas of current limitations of IMPT: treatment planning, treatment delivery, and motion management, and discuss current and future efforts for improvement. For treatment planning, we need to reduce uncertainties in proton range and in computed dose distributions, improve robust planning and optimization, enhance adaptive treatment planning and delivery, and consider how to exploit the variability in the relative biological effectiveness of protons for clinical benefit. The quality of proton therapy also depends on the characteristics of the IMPT delivery systems and image guidance. Efforts are needed to optimize the beamlet spot size for both improved dose conformality and faster delivery. For the latter, faster energy switching time and increased dose rate are also needed. Real-time in-room volumetric imaging for guiding IMPT is in its early stages with cone beam computed tomography (CT) and CT-on-rails, and continued improvements are anticipated. In addition, imaging of the proton beams themselves, using, for instance, prompt γ emissions, is being developed to determine the proton range and to reduce range uncertainty. With the realization of the advances described above, we posit that IMPT, thus empowered, will lead to substantially improved clinical results.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Controlled release of ibuprofen by meso–macroporous silica

Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5}0% (black triangles), P84{sub 7}5% (white diamonds), P84{sub 7}5% functionalized by grafting (black squares) and P84{sub 7}5% functionalized by co-condensation method (white triangles). Display Omitted - Highlights: • Ordered meso–macroporous material is used as a controlled delivery system for ibuprofen. • Incorporation of macropores in mesoporous silica improves ibuprofen adsorption. • Meso–macroporous structures provide a lower delivery than mesoporous silica. • APTES functionalization in meso–macroporous materials improves ibuprofen adsorption and delivery behaviour.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗