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Accelerating polyketide synthase engineering for high TRY production of biofuels and bioproducts (Final Technical Report)

Polyketide synthase (PKS) enzymes have a modular, deterministic logic that holds the potential to act as a flexible chemical factory for the biological production of a huge diversity of valuable small molecule compounds. However, engineering a custom PKS to produce a specific desired product currently requires years of trial and error, for reasons that remain poorly understood. In this project, we have developed a rapid, high throughput, Design-Build-Test-Learn (DBTL) cycle for polyketide synthases (PKSs) and demonstrate its utility for production of materials precursors. The objectives are 1) to develop a rapid, high-throughput (HT) DBTL cycle for PKSs that will enable production of a large number of unnatural, organic molecules on demand at high titer, rate, and yield (TRY); 2) to demonstrate the utility of the PKS DBTL cycle to produce three molecules: one commodity chemical (caprolactam or valerolactam) and two novel materials precursors (caprolactam or valerolactam derivatives); and 3) to demonstrate the utility of the PKS DBTL cycle to increase the TRY of one molecule (caprolactam or valerolactam). In this project, we have successfully demonstrated our high throughput PKS DBTL pipeline, and have biologically produced valerolactam and several other novel nylon monomers.

60 APPLIED LIFE SCIENCES↗

TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program.

60 APPLIED LIFE SCIENCES↗

SU-F-T-527: A Novel Dynamic Multileaf Collimator Leaf-Sequencing Algorithm in Radiation Therapy

Purpose: A novel leaf-sequencing algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimator (MLC). The efficiency of this dynamic MLC leaf-sequencing method was evaluated using external beam treatment plans delivered by intensity modulated radiation therapy technique. Methods: To qualify and validate this algorithm, integral test for the beam segment of MLC generated by the CORVUS treatment planning system was performed with clinical intensity map experiments. The treatment plans were optimized and the fluence maps for all photon beams were determined. This algorithm started with the algebraic expression for the area under the beam profile. The coefficients in the expression can be transformed into the specifications for the leaf-setting sequence. The leaf optimization procedure was then applied and analyzed for clinical relevant intensity profiles in cancer treatment. Results: The macrophysical effect of this method can be described by volumetric plan evaluation tools such as dose-volume histograms (DVHs). The DVH results are in good agreement compared to those from the CORVUS treatment planning system. Conclusion: We developed a dynamic MLC method to examine the stability of leaf speed including effects of acceleration and deceleration of leaf motion in order to make sure the stability of leaf speed did not affect the intensity profile generated. It was found that the mechanical requirements were better satisfied using this method. The Project is sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.

60 APPLIED LIFE SCIENCES↗

TU-H-209-00: Planning and Delivering HDR APBI Treatments

Learnings Objectives: Although brachytherapy is the oldest form of radiation therapy, the rapid advancement of the methods of dose calculation, treatment planning and treatment delivery pushes us to keep updating our knowledge and experience to new procedures all the time. Our purpose is to present the newest applicators used in Accelerated Partial Breast Irradiation (APBI) and the techniques of using them for a maximum effective treatment. Our objective will be to get the user familiar with the Savi, Contura and ML Mammosite from the detailed description and measurements to cavity eval and choice or size, to acceptance tests and use of each. At the end of the session the attendants will be able to assist at the scanning of the patient for the first treatment, decide on the proper localization and immobilization devices, import the scans in the treatment planning system, perform the structure segmentation, reconstruct the catheters and develop a treatment plan using inverse planning (IPSA) or volume optimization. The attendant should be able to evaluate the quality of a treatment plan according to the ABS protocols and B39 after this session. Our goal is that all the attendants to gain knowledge of all the quality assurance procedures required to be performed prior to a treatment, at the beginning of a treatment day, weekly, monthly and annualy on the remote afterloader, the treatment planning system and the secondary check system. We will provide tips for a consistent treatment delivery of the 10 fractions in a BID (twice daily) regimen.

60 APPLIED LIFE SCIENCES↗

TH-C-12A-04: Dosimetric Evaluation of a Modulated Arc Technique for Total Body Irradiation

Purpose: A simplified Total Body Irradiation (TBI) was developed to work with minimal requirements in a compact linac room without custom motorized TBI couch. Results were compared to our existing fixed-gantry double 4 MV linac TBI system with prone patient and simultaneous AP/PA irradiation. Methods: Modulated arc irradiates patient positioned in prone/supine positions along the craniocaudal axis. A simplified inverse planning method developed to optimize dose rate as a function of gantry angle for various patient sizes without the need of graphical 3D treatment planning system. This method can be easily adapted and used with minimal resources. Fixed maximum field size (40×40 cm2) is used to decrease radiation delivery time. Dose rate as a function of gantry angle is optimized to result in uniform dose inside rectangular phantoms of various sizes and a custom VMAT DICOM plans were generated using a DICOM editor tool. Monte Carlo simulations, film and ionization chamber dosimetry for various setups were used to derive and test an extended SSD beam model based on PDD/OAR profiles for Varian 6EX/ TX. Measurements were obtained using solid water phantoms. Dose rate modulation function was determined for various size patients (100cm − 200cm). Depending on the size of the patient arc range varied from 100° to 120°. Results: A PDD/OAR based beam model for modulated arc TBI therapy was developed. Lateral dose profiles produced were similar to profiles of our existing TBI facility. Calculated delivery time and full arc depended on the size of the patient (∼8min/ 100° − 10min/ 120°, 100 cGy). Dose heterogeneity varied by about ±5% − ±10% depending on the patient size and distance to the surface (buildup region). Conclusion: TBI using simplified modulated arc along craniocaudal axis of different size patients positioned on the floor can be achieved without graphical / inverse 3D planning.

60 APPLIED LIFE SCIENCES↗

SU-C-BRE-06: Radiobiological Advantage of Very Rapid Irradiation

Purpose: To characterize the effect of very rapid dose delivery as compared to conventional therapeutic irradiation times on clonogenic cell survival. Methods: We used a Varian Trilogy linear accelerator to deliver doses up to 10 Gy using a 6 MV SRS photon beam. We irradiated four cancer cell lines in times ranging from 30 sec to 30 min. We also used a Varian TrueBeam linear accelerator to deliver 9 MeV electrons at 10 Gy in 10 s to 30 min to determine the effect of irradiation time on cell survival. We then evaluated the effect of using 60 and 120 MeV electrons on cell survival using the Next Linear Collider Test Accelerator (NLCTA) beam line at the SLAC National Accelerator Laboratory. During irradiation, adherent cells were maintained at 37oC with 20%O2/5%CO2. Clonogenic assays were completed following irradiation to determine changes in cell survival due to dose delivery time and beam quality, and the survival data were fitted with the linear-quadratic model. Results: Cell lines varied in radiosensitivity, ranging from two to four logs of cell kill at 10 Gy for both conventional and very rapid irradiation. Delivering radiation in shorter times decreased survival in all cell lines. Log differences in cell kill ranged from 0.2 to 0.7 at 10 Gy for the short compared to the long irradiation time. Cell kill differences between short and long irradiations were more pronounced as doses increased for all cell lines. Conclusion: Our findings suggest that shortening delivery of therapeutic radiation doses to less than 1 minute may improve tumor cell kill. This study demonstrates the potential advantage of technologies under development to deliver stereotactic ablative radiation doses very rapidly. Bill Loo and Peter Maxim have received Honoraria from Varian and Research Support from Varian and RaySearch.

60 APPLIED LIFE SCIENCES↗

Suppressing Irf2bp2 expressions accelerates metabolic syndrome-associated brain injury and hepatic dyslipidemia

Highlights: • Irf2bp2 deletion promotes HFD-induced metabolic syndrome and cognitive dysfunction in mice. • Irf2bp2 knockout aggravates brain injury in HFD-fed mice. • Irf2bp2 ablation alleviates oxidative stress and inflammation in brain of HFD-fed mice. • Suppressing Irf2bp2 expressions exacerbate inflammatory response in PAL- or LPS-treated BV2 cells. Increasing studies indicate that high fat diet (HFD) induces neuroinflammation in animal models with obesity, yet the pathology of it is unclear. Interferon Regulatory Factor 2 Binding Protein 2 (Irf2bp2) is a key regulator of macrophage polarization, playing an essential role in regulating inflammatory response. This study investigated the effects of Irf2bp2 on HFD-induced brain injury, and explored the possible molecular mechanisms using wild type (WT) and Irf2bp2 knockout (KO) mice. The results indicated that HFD-increased body weight of mice was further elevated by Irf2bp2-knockout. In addition, Irf2bp2-deletion accelerated HFD-induced metabolic syndrome, as evidenced by the promoted fasting glucose and insulin levels. In the results of behavioral measurements, Irf2bp2-knockout intensified cognitive deficit in HFD-fed mice by using Y-maze, passive avoidance, and morris water maze (MWM) tests. Further, Irf2bp2-deficiency accelerated the activation of astrocytes and microglia cells, as evidenced by the promoted expressions of glial fibrillary acidic protein (GFAP) and Iba-1 in hippocampus and hypothalamus of HFD-fed mice. HFD for 16 weeks induced oxidative stress in serum and brain of mice, as proved by the up-regulated malondialdehyde (MDA) levels and down-regulated superoxide dismutase (SOD) activity, which were significantly enhanced due to Irf2bp2 knockout. Moreover, HFD-triggered systematic and central nervous inflammation by increasing the release of interleukin 1β (IL-1β) and tumor necrosis factor (TNF)-α, accompanied with elevated p-nuclear factor-κB (NF-κB) expressions. Notably, HFD-induced inflammation was significantly exacerbated by Irf2bp2 deletion. Intriguingly, HFD-induced dyslipidemia in liver of mice was further aggravated by Irf2bp2 suppression. Our in vitro results verified the effects of Irf2bp2-inhibition on the promotion of inflammatory response in BV2 cells and lipid dysfunction in primary hepatocytes. Therefore, the findings above suggested that inhibiting Irf2bp2 expression provided a potential therapeutic approach for the prevention of metabolic syndrome-associated central nervous injury.

60 APPLIED LIFE SCIENCES↗

TH-C-17A-01: Imaging Sensor Comparison for Real-Time Cherenkov Signal Detection From Tissue for Treatment Verification

Purpose: To identify the optimum imaging sensor for a clinical system that would provide real-time imaging of the surface beam profile on patients as novel visual information to radiation therapy technologists, and more rapidly collect clinical data for large-scale studies of Cherenkov applications in radiotherapy. Methods: Four camera types, CMOS, CCD, ICCD and EMICCD, were tested to determine proficiency in the detection of Cherenkov signal in the clinical radiotherapy setting, and subsequent maximum supportable frame rate. Where possible, time-gating between the trigger signal from the LINAC and the intensifiers was implemented to detect signal with room lighting conditions comparable to patient treatment scenarios. A solid water phantom was imaged by the EM-ICCD and ICCD to evaluate the minimum number of accumulations-on-chip required for adequate Cherenkov detection, defined as >200% electron counts per pixel over background signal. Additionally, an ICCD and EM-ICCD were used clinically to image patients undergoing whole-breast radiation therapy, to understand the impact of the resolution limitation of the EM-ICCD. Results: The intensifier-coupled cameras performed best at imaging Cherenkov signal, even with room lights on, which is essential for patient comfort. The tested EM-ICCD was able to support single-shot imaging and frame rates of 30 fps, however, the current maximum resolution of 512 × 512 pixels was restricting. The ICCD used in current clinical trials was limited to 4.7 fps at a 1024 × 1024 resolution. An intensifier with higher quantum efficiency at the entrance photocathode in the red wavelengths (30% QE vs current 7%) promises 16 fps at the same resolution at lower cost than the EM-ICCD. Conclusion: The ICCD with the better red wavelength QE intensifier was determined to be the best suited commercial-off-the-shelf camera to detect real-time Cherenkov signal and provide the best potential for real-time display of radiation dose on the skin during treatment. Funding is from grants from the NIH numbers R01CA109558 and R21EB017559.

60 APPLIED LIFE SCIENCES↗

SU-G-JeP1-12: Head-To-Head Performance Characterization of Two Multileaf Collimator Tracking Algorithms for Radiotherapy

Purpose: Multi-leaf collimator (MLC) tracking is being clinically pioneered to continuously compensate for thoracic and abdominal motion during radiotherapy. The purpose of this work is to characterize the performance of two MLC tracking algorithms for cancer radiotherapy, based on a direct optimization and a piecewise leaf fitting approach respectively. Methods: To test the algorithms, both physical and in silico experiments were performed. Previously published high and low modulation VMAT plans for lung and prostate cancer cases were used along with eight patient-measured organ-specific trajectories. For both MLC tracking algorithm, the plans were run with their corresponding patient trajectories. The physical experiments were performed on a Trilogy Varian linac and a programmable phantom (HexaMotion platform). For each MLC tracking algorithm, plan and patient trajectory, the tracking accuracy was quantified as the difference in aperture area between ideal and fitted MLC. To compare algorithms, the average cumulative tracking error area for each experiment was calculated. The two-sample Kolmogorov-Smirnov (KS) test was used to evaluate the cumulative tracking errors between algorithms. Results: Comparison of tracking errors for the physical and in silico experiments showed minor differences between the two algorithms. The KS D-statistics for the physical experiments were below 0.05 denoting no significant differences between the two distributions pattern and the average error area (direct optimization/piecewise leaf-fitting) were comparable (66.64 cm2/65.65 cm2). For the in silico experiments, the KS D-statistics were below 0.05 and the average errors area were also equivalent (49.38 cm2/48.98 cm2). Conclusion: The comparison between the two leaf fittings algorithms demonstrated no significant differences in tracking errors, neither in a clinically realistic environment nor in silico. The similarities in the two independent algorithms give confidence in the use of either algorithm for clinical implementation.

60 APPLIED LIFE SCIENCES↗

TOPOS: A new topometric patient positioning and tracking system for radiation therapy based on structured white light

Purpose: A patient positioning system for radiation therapy based on structured white light and using off-the-shelf hardware components for flexibility and cost-effectiveness has been developed in house. Increased accuracy, patient comfort, abandonment of any skin marks, accelerated workflow, objective reading/recording, better usability and robust sensor design, compared to other positioning approaches, were the main goals of this work. Another aim was the application of a 6 degrees of freedom tracking system working without dose deposition. Methods: Two optical sensors are the main parts of the TOPOS Registered-Sign system (Topometrical Positioning, cyberTECHNOLOGIES, Germany). The components: cameras, projectors, and computers are commercial off-the-shelf products, allowing for low production costs. The black/white cameras of the prototype are capable of taking up to 240 frames per second (resolution: 640 Multiplication-Sign 488 pixels). The projector has a resolution of 1024 Multiplication-Sign 768 and a refresh rate of 120 Hz. The patient's body surface is measured continuously and registered to a reference surface, providing a transformation to superimpose the patient's surface to the reference (planning CT) surface as best as possible. The execution of the calculated transformation provides the correct patient position before the treatment starts. Due to the high-speed acquisition of the surfaces, a surveillance of the patient's (respiration) motion during treatment is also accomplished. The accuracy of the system was determined using a male mannequin. Two treatment sites were evaluated: one simulating a head and neck treatment and the other simulating a thoracic wall treatment. The mannequin was moved to predefined positions, and shift vectors given by the surface registration were evaluated. Additionally manual positioning using a color-coding system was evaluated. Results: Two prototypes have been developed, each allowing a continuous high density scan of a 500 Multiplication-Sign 500 Multiplication-Sign 400 mm{sup 3} (L Multiplication-Sign W Multiplication-Sign D) large volume with a refresh rate of 10 Hz (extendible to 20 Hz for a single sensor system). Surface and position correction display, as well as respiratory motion, is shown in real-time (delay < 200 ms) using present graphical hardware acceleration. For an intuitive view of the patient's misalignment, a fast surface registration algorithm has been developed and tested and a real-time color-coding technique is proposed and verified that allows the user to easily verify the position of the patient. Using first the surface registration and then the color coding the best results were obtained: for the head and neck case, the mean difference between the actual zero position and the final match was 0.1 {+-} 0.4, -0.2 {+-} 0.7, and -0.1 {+-} 0.3 mm in vertical, longitudinal, and lateral direction. For the thoracic case, the mean differences were 0.3 {+-} 0.5, -0.6 {+-} 1.9, 0.0 {+-} 0.4 mm. Conclusions: The presented system copes with the increasing demand for more accurate patient positioning due to more precise irradiation technologies and minimizes the preparation times for correct patient alignment, therefore optimizing the treatment workflow. Moreover, TOPOS is a versatile and cost effective image guided radiation therapy device. It allows an objective rating of the patient's position before and during the irradiation and could also be used for respiratory gating or tracking.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Poster — Thur Eve — 55: An automated XML technique for isocentre verification on the Varian TrueBeam

Isocentre verification tests, such as the Winston-Lutz (WL) test, have gained popularity in the recent years as techniques such as stereotactic radiosurgery/radiotherapy (SRS/SRT) treatments are more commonly performed on radiotherapy linacs. These highly conformal treatments require frequent monitoring of the geometrical accuracy of the isocentre to ensure proper radiation delivery. At our clinic, the WL test is performed by acquiring with the EPID a collection of 8 images of a WL phantom fixed on the couch for various couch/gantry angles. This set of images is later analyzed to determine the isocentre size. The current work addresses the acquisition process. A manual WL test acquisition performed by and experienced physicist takes in average 25 minutes and is prone to user manipulation errors. We have automated this acquisition on a Varian TrueBeam STx linac (Varian, Palo Alto, USA). The Varian developer mode allows the execution of custom-made XML script files to control all aspects of the linac operation. We have created an XML-WL script that cycles through each couch/gantry combinations taking an EPID image at each position. This automated acquisition is done in less than 4 minutes. The reproducibility of the method was verified by repeating the execution of the XML file 5 times. The analysis of the images showed variation of the isocenter size less than 0.1 mm along the X, Y and Z axes and compares favorably to a manual acquisition for which we typically observe variations up to 0.5 mm.

60 APPLIED LIFE SCIENCES↗

SU-G-BRB-03: Assessing the Sensitivity and False Positive Rate of the Integrated Quality Monitor (IQM) Large Area Ion Chamber to MLC Positioning Errors

Purpose: To examine both the IQM’s sensitivity and false positive rate to varying MLC errors. By balancing these two characteristics, an optimal tolerance value can be derived. Methods: An un-modified SBRT Liver IMRT plan containing 7 fields was randomly selected as a representative clinical case. The active MLC positions for all fields were perturbed randomly from a square distribution of varying width (±1mm to ±5mm). These unmodified and modified plans were measured multiple times each by the IQM (a large area ion chamber mounted to a TrueBeam linac head). Measurements were analyzed relative to the initial, unmodified measurement. IQM readings are analyzed as a function of control points. In order to examine sensitivity to errors along a field’s delivery, each measured field was divided into 5 groups of control points, and the maximum error in each group was recorded. Since the plans have known errors, we compared how well the IQM is able to differentiate between unmodified and error plans. ROC curves and logistic regression were used to analyze this, independent of thresholds. Results: A likelihood-ratio Chi-square test showed that the IQM could significantly predict whether a plan had MLC errors, with the exception of the beginning and ending control points. Upon further examination, we determined there was ramp-up occurring at the beginning of delivery. Once the linac AFC was tuned, the subsequent measurements (relative to a new baseline) showed significant (p <0.005) abilities to predict MLC errors. Using the area under the curve, we show the IQM’s ability to detect errors increases with increasing MLC error (Spearman’s Rho=0.8056, p<0.0001). The optimal IQM count thresholds from the ROC curves are ±3%, ±2%, and ±7% for the beginning, middle 3, and end segments, respectively. Conclusion: The IQM has proven to be able to detect not only MLC errors, but also differences in beam tuning (ramp-up). Partially supported by the Susan Scott Foundation.

60 APPLIED LIFE SCIENCES↗

Centralized Interactive Phenomics Resource: an integrated online phenomics knowledgebase for health data users

Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility. Here, we describe the development of the Centralized Interactive Phenomics Resource (CIPHER) knowledgebase, a comprehensive public-facing phenotype library, which aims to facilitate clinical and health services research. The platform was designed to collect and catalog EHR-based computable phenotype algorithms from any healthcare system, scale metadata management, facilitate phenotype discovery, and allow for integration of tools and user workflows. Phenomics experts were engaged in the development and testing of the site. The knowledgebase stores phenotype metadata using the CIPHER standard, and definitions are accessible through complex searching. Phenotypes are contributed to the knowledgebase via webform, allowing metadata validation. Data visualization tools linking to the knowledgebase enhance user interaction with content and accelerate phenotype development. The CIPHER knowledgebase was developed in the largest healthcare system in the United States and piloted with external partners. The design of the CIPHER website supports a variety of front-end tools and features to facilitate phenotype development and reuse. Health data users are encouraged to contribute their algorithms to the knowledgebase for wider dissemination to the research community, and to use the platform as a springboard for phenotyping. CIPHER is a public resource for all health data users available at https://phenomics.va.ornl.gov/ which facilitates phenotype reuse, development, and dissemination of phenotyping knowledge.

60 APPLIED LIFE SCIENCES↗

SU-G-TeP2-12: IROCHouston and MDAPL SRS Anthropomorphic Phantom Results

Purpose: To report the results of SRS phantom irradiations Methods: Anthropomorphic SRS head phantoms were sent to institutions participating in NCI sponsored SRS clinical trials and institutions interested in verifying SRS treatment delivery. The phantom shell was purchased from Phantom Laboratory and altered to house dosimetry and imaging inserts. The imaging insert has 1.9 cm diameter spherical target. The dosimetry insert holds two TLD capsules and radiochromic film in the coronal and sagittal planes through the center of the target. Institutions were asked to image, plan and treat the phantom as they would an SRS patient. GammaKnife, CyberKnife and c-arm accelerator institutions were asked to cover the target with 15 Gy, 20 Gy and 25 Gy, respectively. Following these guidelines and typical planning protocols for these three types of machines gives roughly 30 Gy to the center of the target for all units. Submission of the DICOM digital data set was required for analysis. Criteria of 5% for TLD results and 85% of pixels passing 5%/3mm gamma analysis were applied beginning in 2013. Results: The phantom was analyzed 269 times between the beginning of 2013 to present. The pass rate is 81%. Nineteen of the irradiation results failed only the TLD criteria, 19 failed only the film criteria and 12 failed both. Irradiations included 32 CyberKnife 23 GammaKnife, 3 TomoTherapy and 211 c-arm units. Planning systems included Eclipse, Ergo, GammaPlan, Hi-Art, iPlan, Monaco, MultiPlan, Pinnacle, RayStation, XiO and XKnife. Irradiations that were not accompanied with DICOM data were not included in this analysis. Conclusion: The phantom is a valuable end-to-end test used to independently verify the accuracy of SRS treatment delivery. This investigation was supported by IROC grant CA180803 awarded by the NCI.

60 APPLIED LIFE SCIENCES↗

Feature engineering for machine learning enabled early prediction of battery lifetime

Accurate battery lifetime estimates enable accelerated design of novel battery materials and determination of optimal use protocols for longevity in deployments. Unfortunately, traditional battery testing may take years to reach thousands of cycles. Recent studies have shown that machine learning (ML) tools can predict lithium-ion battery lifetimes from 100 or fewer preliminary cycles, representing only a few weeks of cycling. Until now, conclusions about the efficacy and broad applicability of these predictions across a variety of cathode chemistries have been limited by available experimental information. In this work, we leverage a battery cycling dataset representing six cathode chemistries (NMC111, NMC532, NMC622, NMC811, HE5050, and 5Vspinel), multiple electrolyte/anode compositions, and 300 total carefully prepared pouch batteries to explore feature selection and battery chemistry's role in ML battery lifetime predictions. Here, a mean absolute error (MAE) of 78 cycles in prediction was seen for a chemistry-spanning test set from 100 preliminary cycles. Furthermore, an MAE of 103 cycles was seen when using only the first cycle. This study represents an in-depth investigation of strategies for feature selection for battery lifetime prediction, ML models' generalization across multiple battery chemistries, and predictions beyond the training set in the chemical space.

25 ENERGY STORAGE↗

In-situ Detection of Glovebox Glove Degradation Prior to Glove Failure; Effects on Safety, Waste, and Operational Costs - 20402

Glovebox glove pressure decay leak testing and analysis of the data can greatly improve glovebox safety, minimize Transuranic (TRU) glove waste, and minimize operational cost. It is well known, the weakest point of containment on a glovebox is the glove. Mitigating unplanned openings in gloves is critical to minimizing operational and safety costs in glovebox operations. Mitigating unplanned glove openings due to glove failures will be discussed in this paper. The lack of an engineered solution to determine a gloves operational life in nuclear operations, has lead to use of theoretical and manual subjective methods to determine the life and safety of a glovebox glove. Whether the glove is inspected visually prior to use, or gloves are changed regularly to theoretically avoid failure, both the operators PPE and the room are being exposed to contamination, or un-necessary amounts of TRU glove waste are being generated. Millions of dollars yearly in operational costs are spent on glove failures due to loss of production, incident analysis, regulatory audits, clean up, and paperwork. In a nuclear application, a glove failure could contaminate an operator and laboratory, shut down the operation for weeks, potentially create a regulatory audit, and potentially create a media frenzy; the damages to the organization can be astronomical. Elimination of glove failures is possible by tracking glove material degradation and setting limits to allow glove change when it becomes necessary, prior to glove failure. Analytical pressure decay leak testing allows the detection of material degradation, and in turn the ability to limit operational glove failures. A German based company called MK Versuchsanlagen, e.K., has developed an advanced Glove Integrity Testing System. The system, with its use of proprietary RFID and special software technology, is unique in its capabilities. The system is capable to perform highly accurate regular glove testing on any size glovebox line in minimal time. The system records and can analyze a tremendous amount of system data that in turn can determine, for example, a safe glove change time prior to a glove material failure. This paper will show how an advanced Glove Integrity Testing System can detect glove material degradation and help determine a safe change point prior to glove failure. Pressure decay curves of new gloves and recorded effects of accelerated aging on the glove over time will be shown. The use of this technology in nuclear facilities can greatly improve glovebox operational safety, minimize glovebox glove TRU waste, and save organizations tremendous costs in downtime, clean up, documentation, and potential regulatory review. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

SU-G-JeP1-05: Clinical Impact of MLC Tracking for Lung SABR

Purpose: The objective of this study was to investigate the dosimetric benefits of multi-leaf collimator (MLC) tracking for lung SABR treatments in end-to-end clinically realistic planning and delivery scenarios. Methods: The clinical benefits of MLC tracking were assessed using previously delivered treatment plans and physical experiments. The 10 most recent single lesion lung SABR patients were re-planned following a 4D-GTV-based real-time adaptive protocol (PTV defined as the end-of-exhalation GTV plus 5.0 mm margins). The plans were delivered on a Trilogy Varian linac. Electromagnetic transponders (Calypso, Varian Medical Systems, USA) were embedded into a programmable moving phantom (HexaMotion platform) tracked with the Varian Calypso system. For each physical experiment, the MLC positions were collected and used as input for dose reconstruction. For both planned and physical experiments, the OAR dose metrics from the conventional and real-time adaptive SABR plans (Mean Lung Dose (MLD), V20 for lung, and near-maximum dose (D2%) for spine and heart) were statistically compared. The Wilcoxon test was used to compare plan and physical experiment dose metrics. Results: While maintaining target coverage, percentage reductions in dose metrics to the OARs were observed for both planned and physical experiments. Comparing the two plans showed MLD percentage reduction (MLDr) of 25.4% (absolute differences of 1.41 Gy) and 28.9% (1.29%) for the V20r. D2% percentage reduction for spine and heart were respectively 27.9% (0.3 Gy) and 20.2% (0.3 Gy). For the physical experiments, MLDr was 23.9% (1.3 Gy), and V20r 37.4% (1.6%). D2% reduction for spine and heart were respectively 27.3% (0.3 Gy) and 19.6% (0.3 Gy). For both plans and physical experiments, significant OAR dose differences (p<0.05) were found between the conventional SABR and real-time adaptive plans. Conclusion: Application of MLC tracking for lung SABR patients has the potential to reduce the dose to OARs during radiation therapy.

60 APPLIED LIFE SCIENCES↗

SU-E-T-775: Use of Electronic Portal Imaging Device (EPID) for Quality Assurance (QA) of Electron Beams On Varian Truebeam System

Purpose: In a previous study we have demonstrated the feasibility of using EPID to QA electron beam parameters on a single Varian TrueBeam LINAC. This study aims to provide further investigation on (1) reproducibility of using EPID to detect electron beam energy changes on multiple machines and (2) evaluation of appropriate calibration methods to compare results from different EPIDs. Methods: Ad-hoc mode electron beam images were acquired in developer mode with XML code. Electron beam data were collected on a total of six machines from four institutions. A custom-designed double-wedge phantom was placed on the EPID detector. Two calibration methods - Pixel Sensitivity Map (PSM) and Large Source-to-Imager Distance Flood Field (LSID-FF) - were used. To test the sensitivity of EPID in detecting energy drifts, Bending Magnet Current (BMC) was detuned to invoke energy changes corresponding to ∼±1.5 mm change in R50% of PDD on two machines from two institutions. Percent depth ionization (PDI) curves were then analyzed and compared with the respective baseline images using LSID-FF calibration. For reproducibility testing, open field EPID images and images with a standard testing phantom were collected on multiple machines. Images with and without PSM correction for same energies on different machines were overlaid and compared. Results: Two pixel shifts were observed in PDI curve when energy changes exceeded the TG142 tolerance. PSM showed the potential to correct the differences in pixel response of different imagers. With PSM correction, the histogram of images differences obtained from different machines showed narrower distributions than those images without PSM correction. Conclusion: EPID is sensitive for electron energy changes and the results are reproducible on different machines. When overlaying images from different machines, PSM showed the ability to partially eliminate the intrinsic variation of various imagers. Research Funding from Varian Medical Systems Inc.Dr. Sasa Mutic receives compensation for providing patient safety training services from Varian Medical Systems, the sponsor of this study.

60 APPLIED LIFE SCIENCES↗