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Continuous monitoring of prostate position using stereoscopic and monoscopic kV image guidance

Purpose: To demonstrate continuous kV x-ray monitoring of prostate motion using both stereoscopic and monoscopic localizations, assess the spatial accuracy of these techniques, and evaluate the dose delivered from the added image guidance. Methods: The authors implemented both stereoscopic and monoscopic fiducial localizations using a room-mounted dual oblique x-ray system. Recently developed monoscopic 3D position estimation techniques potentially overcome the issue of treatment head interference with stereoscopic imaging at certain gantry angles. To demonstrate continuous position monitoring, a gold fiducial marker was placed in an anthropomorphic phantom and placed on the Linac couch. The couch was used as a programmable translation stage. The couch was programmed with a series of patient prostate motion trajectories exemplifying five distinct categories: stable prostate, slow drift, persistent excursion, transient excursion, and high frequency excursions. The phantom and fiducial were imaged using 140 kVp, 0.63 mAs per image at 1 Hz for a 60 s monitoring period. Both stereoscopic and monoscopic 3D localization accuracies were assessed by comparison to the ground-truth obtained from the Linac log file. Imaging dose was also assessed, using optically stimulated luminescence dosimeter inserts in the phantom. Results: Stereoscopic localization accuracy varied between 0.13 ± 0.05 and 0.33 ± 0.30 mm, depending on the motion trajectory. Monoscopic localization accuracy varied from 0.2 ± 0.1 to 1.1 ± 0.7 mm. The largest localization errors were typically observed in the left–right direction. There were significant differences in accuracy between the two monoscopic views, but which view was better varied from trajectory to trajectory. The imaging dose was measured to be between 2 and 15 μGy/mAs, depending on location in the phantom. Conclusions: The authors have demonstrated the first use of monoscopic localization for a room-mounted dual x-ray system. Three-dimensional position estimation from monoscopic imaging permits continuous, uninterrupted intrafraction motion monitoring even in the presence of gantry rotation, which may block kV sources or imagers. This potentially allows for more accurate treatment delivery, by ensuring that the prostate does not deviate substantially from the initial setup position.

60 APPLIED LIFE SCIENCES↗

SU-C-207B-07: Deep Convolutional Neural Network Image Matching for Ultrasound Guidance in Radiotherapy

Purpose: Robust matching of ultrasound images is a challenging problem as images of the same anatomy often present non-trivial differences. This poses an obstacle for ultrasound guidance in radiotherapy. Thus our objective is to overcome this obstacle by designing and evaluating an image blocks matching framework based on a two channel deep convolutional neural network. Methods: We extend to 3D an algorithmic structure previously introduced for 2D image feature learning [1]. To obtain the similarity between two 3D image blocks A and B, the 3D image blocks are divided into 2D patches Ai and Bi. The similarity is then calculated as the average similarity score of Ai and Bi. The neural network was then trained with public non-medical image pairs, and subsequently evaluated on ultrasound image blocks for the following scenarios: (S1) same image blocks with/without shifts (A and A-shift-x); (S2) non-related random block pairs; (S3) ground truth registration matched pairs of different ultrasound images with/without shifts (A-i and A-reg-i-shift-x). Results: For S1 the similarity scores of A and A-shift-x were 32.63, 18.38, 12.95, 9.23, 2.15 and 0.43 for x=ranging from 0 mm to 10 mm in 2 mm increments. For S2 the average similarity score for non-related block pairs was −1.15. For S3 the average similarity score of ground truth registration matched blocks A-i and A-reg-i-shift-0 (1≤i≤5) was 12.37. After translating A-reg-i-shift-0 by 0 mm, 2 mm, 4 mm, 6 mm, 8 mm, and 10 mm, the average similarity scores of A-i and A-reg-i-shift-x were 11.04, 8.42, 4.56, 2.27, and 0.29 respectively. Conclusion: The proposed method correctly assigns highest similarity to corresponding 3D ultrasound image blocks despite differences in image content and thus can form the basis for ultrasound image registration and tracking.[1] Zagoruyko, Komodakis, “Learning to compare image patches via convolutional neural networks', IEEE CVPR 2015,pp.4353–4361.

60 APPLIED LIFE SCIENCES↗

SU-F-J-07: Evaluating the Adequacy of Biopsy Specimens for Genetic Signature Assessment by Measuring the Metabolic Activity in Specimens Obtained Under 18F-FDG PET/CT Guidance

Purpose: Genetic profiling of biopsied tissue is the basis for personalized cancer therapy. However biopsied materials may not contain sufficient amounts of DNA needed for analysis. We propose a method to determine the adequacy of specimens for performing genetic profiling by quantifying metabolic activity. Methods: We measured the response of two radiation detectors to the activity contained in the minimum amount of tumor cells needed for genetic profiling in biopsy specimens obtained under 2-deoxy-2-({sup 18}F)fluoro-D-glucose ({sup 18}F-FDG) PET/CT guidance. The expected tumor cell concentration in biopsy specimens was evaluated from the amount of DNA needed (∼100 µg) and the number of pathology sections typically used for the analysis. The average {sup 18}F-FDG uptake per cell was measured by incubating KPC-4662 pancreatic tumor cells and HT-29 colorectal adenocarcinoma tumor cells in {sup 18}F-FDG containing solution (activity concentrations between 0.0122 and 1.51 MBq/mL and glucose concentrations of 3.1 and 1 g/L) for 1 to 1.75 hours and then measuring the activity of a known number of cells. Measurements of surrogate specimens obtained using 18G needle biopsies of gels containing these cells in expected concentrations (∼10{sup 4} µL{sup −1}) were performed using an autoradiography CCD based device (up to 20 min exposure) and a scintillation well counter (∼1 min measurements) about 3 and 5 hours after the end of incubation respectively. Results: At start of autoradiography there were between 0.16 and 1.5 {sup 18}F-FDG molecules/cell and between 1.14 and 5.43×10{sup 7} {sup 18}F-FDG molecules/mL. For the scintillation well counter, sample to minimum-detectable-count rate ratios were greater than 7 and the counting error was less than 25% for ≤80 s measurement times. Images of the samples were identifiable on the autoradiograph for ∼10 min and longer exposure times. Conclusion: Scintillation well counter measurements and CCD based autoradiography have adequate sensitivity to detect the tumor burden needed for genetic profiling in 18G core needle biopsies. Supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 and by a sponsored research agreement with Biospace Lab S.A.

60 APPLIED LIFE SCIENCES↗

SU-F-J-71: Improving CT Quality for Radiation Therapy Planning and Delivery Guidance Using a Non-Linear Contrast Enhancement Technique

Purpose: Advanced image post-processing techniques which enhance soft-tissue contrast in CT have not been widely employed for RT planning or delivery guidance. The purpose of this work is to assess the soft-tissue contrast enhancement from non-linear contrast enhancing filters and its impact in RT. The contrast enhancement reduces patient alignment uncertainties. Methods: Non-linear contrast enhancing methods, such as Best Contrast (Siemens), amplify small differences in X-ray attenuation between two adjacent structure without significantly increasing noise. Best Contrast (BC) separates a CT into two frequency bands. The low frequency band is modified by a non-linear scaling function before recombination with the high frequency band. CT data collected using a CT-on-rails (Definition AS Open, Siemens) during daily CT-guided RT for 6 prostate cancer patients and an image quality phantom (The Phantom Laboratory) were analyzed. Images acquired with a standard protocol (120 kVp, 0.6 pitch, 18 mGy CTDIvol) were processed before comparison to the unaltered images. Contrast and noise were measured in the the phantom. Inter-observer variation was assessed by placing prostate contours on the 12 CT study sets, 6 enhanced and 6 unaltered, in a blinded study involving 8 observers. Results: The phantom data demonstrate that BC increased the contrast between the 1.0% supra-slice element and the background substrate by 46.5 HU while noise increased by only 2.3 HU. Thus the contrast to noise ratio increased from 1.28 to 6.71. Furthermore, the variation in centroid position of the prostate contours was decreased from 1.3±0.4 mm to 0.8±0.3 mm. Thus the CTV-to-PTV margin was reduced by 1.1 mm. The uncertainty in delineation of the prostate/rectum edge decreased by 0.5 mm. Conclusion: As demonstrated in phantom and patient scans the BC filter accentuates soft-tissue contrast. This enhancement leads to reduced inter-observer variation, which should improve RT planning and delivery. Supported by Siemens.

60 APPLIED LIFE SCIENCES↗

SU-G-BRA-01: A Real-Time Tumor Localization and Guidance Platform for Radiotherapy Using US and MRI

Purpose: To develop and validate a real-time motion management platform for radiotherapy that directly tracks tumor motion using ultrasound and MRI. This will be a cost-effective and non-invasive real-time platform combining the excellent temporal resolution of ultrasound with the excellent soft-tissue contrast of MRI. Methods: A 4D planar ultrasound acquisition during the treatment that is coupled to a pre-treatment calibration training image set consisting of a simultaneous 4D ultrasound and 4D MRI acquisition. The image sets will be rapidly matched using advanced image and signal processing algorithms, allowing the display of virtual MR images of the tumor/organ motion in real-time from an ultrasound acquisition. Results: The completion of this work will result in several innovations including: a (2D) patch-like, MR and LINAC compatible 4D planar ultrasound transducer that is electronically steerable for hands-free operation to provide real-time virtual MR and ultrasound imaging for motion management during radiation therapy; a multi- modal tumor localization strategy that uses ultrasound and MRI; and fast and accurate image processing algorithms that provide real-time information about the motion and location of tumor or related soft-tissue structures within the patient. Conclusion: If successful, the proposed approach will provide real-time guidance for radiation therapy without degrading image or treatment plan quality. The approach would be equally suitable for image-guided proton beam or heavy ion-beam therapy. This work is partially funded by NIH grant R01CA190298.

60 APPLIED LIFE SCIENCES↗

MO-DE-202-00: Image-Guided Interventions: Advances in Intraoperative Imaging, Guidance, and An Emerging Role for Medical Physics in Surgery

At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guided neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and R41CA192504 Disclosure and CoI: IGI Technologies, small-business partner on the grants.

61 RADIATION PROTECTION AND DOSIMETRY↗

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

60 APPLIED LIFE SCIENCES↗

WE-DE-209-05: Self-Held Breath Control with Respiratory Monitoring and Feedback Guidance

Breast radiation therapy is associated with some risk of lung toxicity as well as cardiac toxicity for left-sided cases. Radiation doses to the lung and heart can be reduced by using the deep inspiration breath hold (DIBH) technique, in which the patient is simulated and treated during the deep inspiration phase of the breathing cycle. During DIBH, the heart is usually displaced posteriorly, inferiorly, and to the right, effectively expanding the distance between the heart and the breast/chest wall. As a result, the distance between the medial treatment field border and heart/lung is increased. Also, in a majority of DIBH patients, the air drawn into the thoracic cavity increases the total lung volume. The DIBH was discussed by an AAPM Task Group 10 years ago in the AAPM TG 76 report. However, DIBH is still not the standard of care in many clinics, which may be partially due to challenges associated with its implementation. Therefore, this seccion will focus primarily on how to clinically implement four different DIBH techniques: (1) Active Breathing Control, (2) Spirometric Motion Management, (3) 3D Surface Image-Guided, and (4) Self-held Breath Control with Respiratory Monitoring and Feedback Guidance. Learning Objectives: Describe the physical displacement of the heart and the change in lung volume during DIBH and discuss dosimetric consequences of those changes. Provide an overview of the technical aspects. Describe work flow for patient simulation and treatment. Give an overview of commissioning and routine. Provide practical tips for clinical implementation.

60 APPLIED LIFE SCIENCES↗

TH-C-204-00: Medical Physics Workshop: An Update On the Journal’s Improvement Activities and Guidance On Writing and Reviewing Papers

In this presentation, the Editors will outline our vision for the future of Medical Physics and review recent work-in-progress initiatives to implement this vision. Finally, we will close with guidance to authors on how to write a good Medical Physics paper. A major focus will be the transition to a new publisher in 2017 following a more than 40-year association with American Institute of Physics Publishing (AIPP). Vision for Medical Physics and status of current initiatives: Jeff Williamson, Editor-in-Chief The broad vision of Medical Physics is “to continue the Journal’s tradition of publishing the very best science that propels our discipline forward and improves our contribution to patient care.” More concretely, the Journal should be the preeminent forum for exchange of cutting edge medical physics science. We seek to identify the best contributions in (a) high impact clinical physics innovations; (b) clinical translation and validation of basic science innovations; and (c) cutting edge basic science developments with potential for patient care improvements. Among the challenges and opportunities, we face are: electronic-only and open access publishing; competition from new radiological science journals; trends towards more interactive, social-media based scientific communities; and diversification of the medical physics research, authorship, and readership domains, including clinical applications quite foreign to core ABR clinical competencies. Recently implemented and ongoing initiatives include: Revised Table of Contents (TOC) and more contemporary topical submission categories Structured review template in HTML format Comprehensive hierarchical taxonomy for identifying reviewer expertise Formal process for soliciting high quality and impact Review and Vision 20/20 Articles We have recruited four Review Article Co-editors: John Rowlands and Ingrid Reiser (imaging physics) and Joao Seco and Tim Zhu (therapy physics). The Co-Editors will identify timely topics and solicit high profile authors to submit review manuscripts. To submit an article, authors will need to work with an assigned Co-Editor to develop a mutually acceptable outline and abstract. 5) A new and exciting class of articles: Medical Physics Dataset Articles (MPDAs) MPDAs describe scientifically or clinically valuable open-access datasets with high potential for contributing to the research of medical physicists working on related problems. In contrast to Research Articles, MPDAs should not include hypothesis testing; or data analyses supporting generalizable conclusions. The publically accessible dataset must be permanently archived before the MPDA can be published. This initiative is being led by Joe Deasy. Update on new publisher transition: The transition of AAPM scientific publishing operations to a major publishing house is a major opportunity to expand Medical Physics readership and its scholarly impact. The advantages include: (a) common manuscript management and web hosting platforms for Medical Physics and its sister journal, JACMP; (b) greater than 4-fold expansion of subscribing institutions; and (c) resources to mount data-driven, highly targeted marketing campaigns to enhance citation and download rates. A transition update of this epochal development, which has only begun as of this writing (3/31/16), will be given. Improving manuscript quality via structured reviews, enhanced scientific category taxonomy, and outreach: Shiva Das, Therapy Physics Editor Medical Physics is committed to continuous improvement with the ultimate goal of improving the potential impact of accepted manuscripts. In order to do so, Medical Physics must be able to tap into important/emerging areas and be able to select high quality contributions consistently via discerning reviews. Improving the quality of reviews is crucial to selecting high quality manuscripts and also to improving manuscript impact via feedback in the review process. With this in mind, Medical Physics is in the process of: (a) fostering outreach to important areas that are currently underrepresented in Medical Physics; (b) implementing a structured template review form; and (c) implementing a comprehensive scientific category taxonomy to identify reviewers who are best suited to an article. Outreach efforts have begun to various scientific areas. Strategies to increase submissions from these areas will be discussed. As a consequence of this effort, a special issue on particle therapy is under development. A review template was implemented in late 2014 on a limited test basis. Based on reviewer feedback, the template was restructured and shortened to capture essential review elements. The restructured template is due to be released shortly. The new scientific category taxonomy is in the process of being deployed to reviewers and associate editors. Salient aspects of the structured review template and scientific category taxonomy will be discussed in this talk. Writing good scientific papers and responding to critiques: Mitch Goodsitt, Imaging Physics Editor The essential components of the abstract, introduction, methods, discussion and conclusion sections of manuscripts, as well as the desired writing style and style of the figures and tables will be reviewed. Publishable Medical Physics manuscripts must include clear and concise statements of the novelty and clinical and/or scientific importance of the authors’ work. Examples of novelty include: new technical solution to an important clinical problem; new generalizable knowledge; and first demonstration that an existing engineering solution solves a clinical problem. Please note that we encourage authors of recently published conference proceedings (e.g., SPIE, IEEE) papers on novel medical physics related work to submit more substantial versions of that work to our journal. All submissions must include: sufficient background information and rationale; enough detail for others to reproduce the authors’ work; sufficient statistical analysis to refute or validate the authors’ hypotheses; a description of how the present work compares to, is distinct from, and improves upon others’ work; and sections devoted to the limitations of the study and future directions. Writing should be polished. Poor wording, grammar and composition frustrate the review process. Our journal does not have copyeditors for revising manuscripts. When authors receive critiques from the referees and associate editor, the authors should provide a detailed point-by-point response to each comment. The authors’ rebuttal should include the text of the original criticism, the authors’ response, and a pasted copy of the modified text along with the line numbers in the revised article. The new text should be highlighted in a different font color in the revised submission. Following these recommendations will improve submissions and facilitate the review process.

60 APPLIED LIFE SCIENCES↗

TH-CD-207A-06: Optimizing Four-Dimensional Digital Tomosynthesis Acquisition Based On Respiratory Guidance

Purpose: Patient breathing-related sorting method of projections in 4D digital tomosythesis (DTS) can be suffered from severe artifacts due to non-uniform angle distribution of projections and noncoplanar reconstructed images for each phase. In this study, we propose a method for optimally acquiring projection images in 4D DTS. Methods: In this method every pair of projections at x-ray tube’s gantry angles symmetrical with respect to the center of the range of gantry rotation is obtained at the same respiration amplitude. This process is challenging but becomes feasible with visual-biofeedback using a patient specific respiration guide wave which is in sinusoidal shape (i.e., smooth and symmetrical enough). Depending on scan parameters such as the number of acquisition points per cycle, total scan angle and projections per acquisition amplitude, acquisition sequence is pre-determined. A simulation study for feasibility test was performed. To mimic actual situation closely, a group of volunteers were recruited and breathing data were acquired both with/without biofeedback. Then, x-ray projections for a humanoid phantom were virtually performed following (1) the breathing data from volunteers without guide, (2) the breathing data with guide and (3) the planned breathing data (i.e., ideal situation). Images from all of 3 scenarios were compared. Results: Scenario #2 showed significant artifact reduction compared to #1 while did minimal increase from the ideal situation (i.e., scenario #3). We verified the performance of the method with regard to the degree of inaccuracy during respiratory guiding. Also, the scan angle dependence-related differences in the DTS images could reduce between using the proposed method and the established patient breathing-related sorting method. Conclusion: Through the proposed 4D DTS method, it is possible to improve the accuracy of image guidance between intra/inter fractions with relatively low imaging dose. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)

60 APPLIED LIFE SCIENCES↗

TH-CD-207A-08: Simulated Real-Time Image Guidance for Lung SBRT Patients Using Scatter Imaging

Purpose: To develop a comprehensive Monte Carlo-based model for the acquisition of scatter images of patient anatomy in real-time, during lung SBRT treatment. Methods: During SBRT treatment, images of patient anatomy can be acquired from scattered radiation. To rigorously examine the utility of scatter images for image guidance, a model is developed using MCNP code to simulate scatter images of phantoms and lung cancer patients. The model is validated by comparing experimental and simulated images of phantoms of different complexity. The differentiation between tissue types is investigated by imaging objects of known compositions (water, lung, and bone equivalent). A lung tumor phantom, simulating materials and geometry encountered during lung SBRT treatments, is used to investigate image noise properties for various quantities of delivered radiation (monitor units(MU)). Patient scatter images are simulated using the validated simulation model. 4DCT patient data is converted to an MCNP input geometry accounting for different tissue composition and densities. Lung tumor phantom images acquired with decreasing imaging time (decreasing MU) are used to model the expected noise amplitude in patient scatter images, producing realistic simulated patient scatter images with varying temporal resolution. Results: Image intensity in simulated and experimental scatter images of tissue equivalent objects (water, lung, bone) match within the uncertainty (∼3%). Lung tumor phantom images agree as well. Specifically, tumor-to-lung contrast matches within the uncertainty. The addition of random noise approximating quantum noise in experimental images to simulated patient images shows that scatter images of lung tumors can provide images in as fast as 0.5 seconds with CNR∼2.7. Conclusions: A scatter imaging simulation model is developed and validated using experimental phantom scatter images. Following validation, lung cancer patient scatter images are simulated. These simulated patient images demonstrate the clinical utility of scatter imaging for real-time tumor tracking during lung SBRT.

60 APPLIED LIFE SCIENCES↗

TH-EF-207A-07: An Integrated X-Ray/bioluminescence Tomography System for Radiation Guidance and Tumor Evaluation

Purpose: CT is not able to differentiate tumors from surrounding soft tissue. This study is to develop a bioluminescence tomography (BLT) system that is integrated onto our previously developed CT guided small animal arc radiation treatment system (iSMAART) to guide radiation, monitor tumor growth and evaluate therapeutic response. Methods: The BLT system employs a CCD camera coupled with a high speed lens, and is aligned orthogonally to the x-ray beam central axis. The two imaging modalities, CT and BLT, are physically registered through geometrical calibration. The CT anatomy provides an accurate contour of animal surface which is used to construct 3D mesh for BLT reconstruction. Bioluminescence projections are captured from multiple angles, once every 45 degree rotation. The diffusion equation based on analytical Kirchhoff approximation is adopted to model the photon propagation in tissues. A discrete cosine transform based reweighted L1-norm regularization (DCT-re-L1) algorithm is used for BLT reconstruction. Experiments are conducted on a mouse orthotopic prostate tumor model (n=12) to evaluate the BLT performance, in terms of its robustness and accuracy in locating and quantifying the bioluminescent tumor cells. Iodinated contrast agent was injected intravenously to delineate the tumor in CT. The tumor location and volume obtained from CT also serve as a benchmark against BLT. Results: With our cutting edge reconstruction algorithm, BLT is able to accurately reconstruct the orthotopic prostate tumors. The tumor center of mass in BLT is within 0.5 mm radial distance of that in CT. The tumor volume in BLT is significantly correlated with that in CT (R2 = 0.81). Conclusion: The BLT can differentiate, localize and quantify tumors. Together with CT, BLT will provide precision radiation guidance and reliable treatment assessment in preclinical cancer research.

60 APPLIED LIFE SCIENCES↗

Structural insights into the formation of repulsive netrin guidance complexes

Netrins dictate attractive and repulsive responses during axon growth and cell migration, where the presence of the receptor Uncoordinated-5 (UNC-5) on target cells results in repulsion. Here, we showed that UNC-5 is a heparin-binding protein, determined its structure bound to a heparin fragment, and could modulate UNC-5–heparin affinity using a directed evolution platform or structure-based rational design. We demonstrated that UNC-5 and UNC-6/netrin form a large, stable, and rigid complex in the presence of heparin, and heparin and UNC-5 exclude the attractive UNC-40/DCC receptor from binding to UNC-6/netrin to a large extent. Caenorhabditis elegans with a heparin-binding–deficient UNC-5 fail to establish proper gonad morphology due to abrogated cell migration, which relies on repulsive UNC-5 signaling in response to UNC-6. Combining UNC-5 mutations targeting heparin and UNC-6/netrin contacts results in complete cell migration and axon guidance defects. Our findings establish repulsive netrin responses to be mediated through a glycosaminoglycan-regulated macromolecular complex.

59 BASIC BIOLOGICAL SCIENCES↗

REGULATORY REQUIREMENTS, GUIDANCE, AND REVIEW OF EMBEDDED DIGITAL DEVICES IN SAFETY SYSTEMS

Interest in embedded digital devices (EDDs) for monitoring and providing control of components is increasing in the nuclear power market as more and more users both within and outside the nuclear sector are employing EDDs. EDDs in other industries or countries may be known by the related terms as smart devices, devices of limited functionality, or intelligent devices. EDDs can sometimes perform a safety role when embedded in components such as temperature transmitters, pressure transmitters, voltage regulators, gas analyzers, boiler controllers, relays, and radiation monitors. The introduction of EDDs can affect safety by creating new hazards, vulnerabilities, failure modes, triggering mechanisms, and other potential safety concerns at both the component and system levels. The U.S. Nuclear Regulatory Commission’s (NRC’s) existing regulations and guidance cover the use of EDDs in safety-related and important to safety systems in nuclear power plants (NPPs). In addition to potential future challenges, the nature of EDDs being implemented in similar or identical manners between different plants and industries opens up the potential of leveraging the reviews of other regulators or utilization of industry certifications.Key words: embedded digital device, firmware

Halverson, D. S.↗

Offshore Wind Guidance Document: Oceanography and Sediment Stability (Version 1) Development of a Conceptual Site Model.

This guidance document provide s the reader with an overview of the key environmental considerations for a typical offshore wind coastal location and the tools to help guide the reader through a thoro ugh planning process. It will enable readers to identify the key coastal processes relevant to their offshore wind site and perform pertinent analysis to guide siting and layout design, with the goal of minimizing costs associated with planning, permitting , and long - ter m maintenance. The document highlight s site characterization and assessment techniques for evaluating spatial patterns of sediment dynamics in the vicinity of a wind farm under typical, extreme, and storm conditions. Finally, the document des cribe s the assimilation of all of this information into the conceptual site model (CSM) to aid the decision - making processes.

Roberts, Jesse D.↗

Deep Energy Retrofit Guidance for the Building America Solutions Center

The U.S. DOE Building America program has established a research agenda targeting market-relevant strategies to achieve 40% reductions in existing home energy use by 2030. Deep Energy Retrofits (DERs) are part of the strategy to meet and exceed this goal. DERs are projects that create new, valuable assets from existing residences, by bringing homes into alignment with the expectations of the 21st century. Ideally, high energy using, dated homes that are failing to provide adequate modern services to their owners and occupants (e.g., comfortable temperatures, acceptable humidity, clean, healthy), are transformed through comprehensive upgrades to the building envelope, services and miscellaneous loads into next generation high performance homes. These guidance documents provide information to aid in the broader market adoption of DERs.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

PIV Logon Configuration Guidance

This document details the configurations and enhancements implemented to support the usage of federal Personal Identity Verification (PIV) Card for logon on unclassified networks. The guidance is a reference implementation of the configurations and enhancements deployed at the Los Alamos National Laboratory (LANL) by Network and Infrastructure Engineering – Core Services (NIE-CS).

97 MATHEMATICS AND COMPUTING↗

Measure Guideline: Ventilation Guidance for Residential High-Performance New Construction - Multifamily

The measure guideline provides ventilation guidance for residential high performance multifamily construction that incorporates the requirements of the ASHRAE 62.2 ventilation and indoor air quality standard. The measure guideline focus is on the decision criteria for weighing cost and performance of various ventilation systems. The measure guideline is intended for contractors, builders, developers, designers and building code officials. The guide may also be helpful to building owners wishing to learn more about ventilation strategies available for their buildings. The measure guideline includes specific design and installation instructions for the most cost effective and performance effective solutions for ventilation in multifamily units that satisfies the requirements of ASHRAE 62.2-2016.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗