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At least 1,315 records · Page 73

Opinion: Making the Most of Colour Rendition Research

After decades of debate, new methods for characterizing color rendition have been formalized, providing an improved system of tools to aid technology developers and lighting specifiers. Solid-state lighting, previously burdened by legacy measures based on outdated science, is positioned to take advantage of these new tools to provide tailored, efficient lighting that better meets the needs of specific architectural lighting applications. This transition requires new guidance, however, presenting an opportunity for researchers. There are several key methodological considerations specific to experiments investigating color rendition that will help build a base of guidance that can be widely applied. The importance of these ideas mostly stems from new knowledge gained in the last five years, but their origins date back much further. 1.The spectral power distribution must be adequately varied to stress the measure(s) of color rendition being evaluated. Often, this means varying the gamut shape—the pattern of shift across different hues—to probe weaknesses of hue-averaged characterizations, avoiding misleading conclusions resulting from limited variation in the stimuli. 2.Evaluating the role of chromaticity on color quality evaluations requires careful accommodation of chromatic adaptation to prevent a centering bias. Asking for delayed responses may be insufficient if chromaticity changes are apparent to participants, just as side-by-side viewing of different chromaticities may not produce results that can be reliably applied in the field. It is also critical that color rendition and chromaticity conditions are varied independently. 3.The stimulus being viewed is the interaction of light and objects’ spectral reflectances. This interaction should be quantified in order to assess how derived guidelines will apply measures using standardized color sample sets. Although light source characterizations are typically used to model responses, the objects and their presentation may strongly influence evaluations. 4.Context is important. Many factors—some investigated, others hypothesized—can influence subjective evaluations of color quality, including illuminance level, type of scene, object familiarity, color composition, viewing duration, and viewer traits. Although their influence on research results is unavoidable, the effects of these contextual factors must be carefully considered in developing guidance. Appropriate experimental design can often mitigate negative consequences arising from these considerations. At a minimum, it is crucial to understand how each of these considerations can influence experimental outcomes, as well as the interpretation and application of the results in practice. Consulting other experts prior to conducting an experiment can help ensure appropriate, up-to-date research methods will be used, so that the results will be novel and useful—and not rejected during peer review. There is an interesting feedback loop: technology development provides new research tools, which allow for refined research methods and new results that lead to more technology development. It is time to make a concerted, collective effort to improve color rendition research so that the full potential of solid-state lighting and new characterization methods can be realized, ensuring that high-efficiency, high-utility, high-appeal lighting systems become standard.

Royer, Michael P.↗

Raman − Ramsey pulsed excitation of coherent population trapping resonances in a {sup 87}Rb cell with a buffer gas

We report the results of experimental investigation of the Raman – Ramsey method of pulsed excitation of coherent population trapping (CPT) resonances in a rubidium vapour cell filled with a mixture of Ar and Ne buffer gases. For the development of compact quantum microwave frequency standards, this method is an alternative to the pulsed optical pumping method recently implemented using the same rubidium cell. Both methods have advantages over the traditional double radio-optical resonance technique, the main of which is the substantial suppression of the light shift of the clock transition frequency, since the evolution of the coherence of atomic states forming the clock transition occurs in the absence of laser radiation in the cell. The narrow (110 – 240 Hz) Raman – Ramsey resonances are obtained using the scheme of pulsed excitation of CPT resonances on the D{sub 1} lines of the {sup 87}Rb atom with the same linear (lin||lin) polarisations of the bichromatic laser radiation components. The process of optimising the central fringe linewidth, its contrast, and the linewidth-to-contrast ratio is described. The magnetic dependence of the Raman – Ramsey line central fringe linewidth is experimentally investigated. (paper)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Exploring Sensitivity of ICF Outputs to Design Parameters in Experiments Using Machine Learning

We report building a sustainable burn platform in inertial confinement fusion (ICF) requires an understanding of the complex coupling of physical processes and the effects that key experimental design changes have on implosion performance. While simulation codes are used to model ICF implosions, incomplete physics and the need for approximations deteriorate their predictive capability. Identification of relationships between controllable design inputs and measurable outcomes can help guide the future design of experiments and development of simulation codes, which can potentially improve the accuracy of the computational models used to simulate ICF implosions. In this article, we leverage developments in machine learning (ML) and methods for ML feature importance/sensitivity analysis to identify complex relationships in ways that are difficult to process using expert judgment alone. We present work using random forest (RF) regression for prediction of yield, velocity, and other experimental outcomes given a suite of design parameters, along with an assessment of important relationships and uncertainties in the prediction model. We show that RF models are capable of learning and predicting on ICF experimental data with high accuracy, and we extract feature importance metrics that provide insight into the physical significance of different controllable design inputs for various ICF design configurations. These results can be used to augment expert intuition and simulation results for optimal design of future ICF experiments.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Sorbent, Sublimation, and Icing Modeling Methods: Experimental Validation and Application to an Integrated MTSA Subassembly Thermal Model

This paper details the validation of modeling methods for the three core components of a Metabolic heat regenerated Temperature Swing Adsorption (MTSA) subassembly, developed for use in a Portable Life Support System (PLSS). The first core component in the subassembly is a sorbent bed, used to capture and reject metabolically produced carbon dioxide (CO2). The sorbent bed performance can be augmented with a temperature swing driven by a liquid CO2 (LCO2) sublimation heat exchanger (SHX) for cooling the sorbent bed, and a condensing, icing heat exchanger (CIHX) for warming the sorbent bed. As part of the overall MTSA effort, scaled design validation test articles for each of these three components have been independently tested in laboratory conditions. Previously described modeling methodologies developed for implementation in Thermal Desktop and SINDA/FLUINT are reviewed and updated, their application in test article models outlined, and the results of those model correlations relayed. Assessment of the applicability of each modeling methodology to the challenge of simulating the response of the test articles and their extensibility to a full scale integrated subassembly model is given. The independent verified and validated modeling methods are applied to the development of a MTSA subassembly prototype model and predictions of the subassembly performance are given. These models and modeling methodologies capture simulation of several challenging and novel physical phenomena in the Thermal Desktop and SINDA/FLUINT software suite. Novel methodologies include CO2 adsorption front tracking and associated thermal response in the sorbent bed, heat transfer associated with sublimation of entrained solid CO2 in the SHX, and water mass transfer in the form of ice as low as 210 K in the CIHX.

Bower, Chad↗

Validation of 3-D Ice Accretion Measurement Methodology for Experimental Aerodynamic Simulation

Determining the adverse aerodynamic effects due to ice accretion often relies on dry-air wind-tunnel testing of artificial, or simulated, ice shapes. Recent developments in ice accretion documentation methods have yielded a laser-scanning capability that can measure highly three-dimensional features of ice accreted in icing wind tunnels. The objective of this paper was to evaluate the aerodynamic accuracy of ice-accretion simulations generated from laser-scan data. Ice-accretion tests were conducted in the NASA Icing Research Tunnel using an 18-inch chord, 2-D straight wing with NACA 23012 airfoil section. For six ice accretion cases, a 3-D laser scan was performed to document the ice geometry prior to the molding process. Aerodynamic performance testing was conducted at the University of Illinois low-speed wind tunnel at a Reynolds number of 1.8 x 10(exp 6) and a Mach number of 0.18 with an 18-inch chord NACA 23012 airfoil model that was designed to accommodate the artificial ice shapes. The ice-accretion molds were used to fabricate one set of artificial ice shapes from polyurethane castings. The laser-scan data were used to fabricate another set of artificial ice shapes using rapid prototype manufacturing such as stereolithography. The iced-airfoil results with both sets of artificial ice shapes were compared to evaluate the aerodynamic simulation accuracy of the laser-scan data. For four of the six ice-accretion cases, there was excellent agreement in the iced-airfoil aerodynamic performance between the casting and laser-scan based simulations. For example, typical differences in iced-airfoil maximum lift coefficient were less than 3% with corresponding differences in stall angle of approximately one degree or less. The aerodynamic simulation accuracy reported in this paper has demonstrated the combined accuracy of the laser-scan and rapid-prototype manufacturing approach to simulating ice accretion for a NACA 23012 airfoil. For several of the ice-accretion cases tested, the aerodynamics is known to depend upon the small, three dimensional features of the ice. These data show that the laser-scan and rapid-prototype manufacturing approach is capable of replicating these ice features within the reported accuracies of the laser-scan measurement and rapid-prototyping method; thus providing a new capability for high-fidelity ice-accretion documentation and artificial ice-shape fabrication for icing research.

Scale Models↗

Experimental Validation of Numerical Simulations for an Acoustic Liner in Grazing Flow

A coordinated experimental and numerical simulation effort is carried out to improve our understanding of the physics of acoustic liners in a grazing flow as well our computational aeroacoustics (CAA) method prediction capability. A numerical simulation code based on advanced CAA methods is developed. In a parallel effort, experiments are performed using the Grazing Flow Impedance Tube at the NASA Langley Research Center. In the experiment, a liner is installed in the upper wall of a rectangular flow duct with a 2 inch by 2.5 inch cross section. Spatial distribution of sound pressure levels and relative phases are measured on the wall opposite the liner in the presence of a Mach 0.3 grazing flow. The computer code is validated by comparing computed results with experimental measurements. Good agreements are found. The numerical simulation code is then used to investigate the physical properties of the acoustic liner. It is shown that an acoustic liner can produce self-noise in the presence of a grazing flow and that a feedback acoustic resonance mechanism is responsible for the generation of this liner self-noise. In addition, the same mechanism also creates additional liner drag. An estimate, based on numerical simulation data, indicates that for a resonant liner with a 10% open area ratio, the drag increase would be about 4% of the turbulent boundary layer drag over a flat wall.

Tam, Christopher K. W.↗

Dynamic Nucleation of Supercooled Melts and Measurement of the Surface Tension and Viscosity

We investigate the phenomenon of acoustic pressure-induced nucleation by using a novel approach involving the large amplitude resonant radial oscillations and collapse of a single bubble intentionally injected into a supercooled liquid. Using a combination of previously developed and proven techniques, the bubble is suspended in a fluid host by an ultrasonic field which supplies both the levitation capability as well as the forcing of the radial oscillations. We observe the effects of an increase in pressure (due to bubble collapse) in a region no larger than 100 microns within the supercooled melt to rigorously probe the hypothesis of pressure-induced nucleation of the solid phase. The use of single bubbles operating in narrow temporal and spatial scales will allow the direct and unambiguous correlation between the origin and location of the generation of the disturbance and the location and timing of the nucleation event. In a companion research effort, we are developing novel techniques for the non-contact measurements of the surface tension and viscosity of highly viscous supercooled liquids. Currently used non-invasive methods of surface tension measurement for the case of undercooled liquids generally rely of the quantitative determination of the resonance frequencies of drop shape oscillations, of the dynamics of surface capillary waves, or of the velocity of streaming flows. These methods become quickly ineffective when the liquid viscosity rises to a significant value. An alternate and accurate method which would be applicable to liquids of significant viscosity is therefore needed. We plan to develop such a capability by measuring the equilibrium shape of levitated undercooled melt droplets as they undergo solid-body rotation. The experimental measurement of the characteristic point of transition (bifurcation point) between axisymmetric and two-lobed shapes will be used to calculate the surface tension of the liquid. Such an approach has already been validated through the experimental verification of numerical modeling results. The experimental approach involves levitation, melting, and solidification of undercooled droplets using a hybrid ultrasonic-electrostatic technique in both a gaseous as well as a vacuum environment. A shape relaxation method will be investigated in order to derive a reliable method to measure the viscosity of undercooled melts. The analysis of the monotonic relaxation to equilibrium shape of a drastically deformed and super-critically damped free drop has been used to derive interfacial tension of immiscible liquid combinations where one of the component has high viscosity. A standard approach uses the initial elongation of a droplet through shear flows, but an equivalent method could involve the initial deformation of a drop levitated in a gas by ultrasonic radiation pressure, electric stresses, or even solid body rotation. The dynamic behavior of the free drop relaxing back to equilibrium shape will be modeled, and its characteristic time dependence should provide a quantitative means to evaluate the liquid viscosity.

Trinh, E. H.↗

Advanced Methods for Aircraft Engine Thrust and Noise Benefits: Nozzle-Inlet Flow Analysis

In this project, we continue to develop the previous joint research between the Fluid Mechanics and Acoustics Laboratory (FM&AL) at Hampton University (HU) and the Jet Noise Team (JNT) at the NASA Langley Research Center (NASA LaRC). The FM&AL was established at Hampton University in June of 1996 and has conducted research under two NASA grants: NAG-1-1835 (1996-99), and NAG-1-1936 (1997-00). In addition, the FM&AL has jointly conducted research with the Central AeroHydrodynamics Institute (TsAGI, Moscow) in Russia under a Civilian Research and Development Foundation (CRDF) grant #RE2-136 (1996-99). The goals of the FM&AL programs are twofold: (1) to improve the working efficiency of the FM&AUs team in generating new innovative ideas and in conducting research in the field of fluid dynamics and acoustics, basically for improvement of supersonic and subsonic aircraft engines, and (2) to attract promising minority students to this research and training and, in cooperation with other HU departments, to teach them basic knowledge in Aerodynamics, Gas Dynamics, and Theoretical and Experimental Methods in Aeroacoustics and Computational Fluid Dynamics (CFD). The research at the HU FM&AL supports reduction schemes associated with the emission of engine pollutants for commercial aircraft and concepts for reduction of observables for military aircraft. These research endeavors relate to the goals of the NASA Strategic Enterprise in Aeronautics concerning the development of environmentally acceptable aircraft. It is in this precise area, where the US aircraft industry, academia, and Government are in great need of trained professionals and which is a high priority goal of the Minority University Research and Education (MUREP) Program, that the HU FM&AL can make its most important contribution. The main achievements for the reporting period in the development of concepts for noise reduction and improvement in efficiency for jet exhaust nozzles and inlets for aircraft engines are as follows: (1) Publications- The AIAA Paper #99-1924 has been presented at the 5th AIAA/CEAS Aeroacoustics Conference, May 10-12, 1999, Seattle, WA; the AIAA Paper #00-3315 has been accepted for the 36th AIAA/ASME/ SAE/ASEE Joint Propulsion Conference, 17-19 July, 2000, Huntsville, AL; and another paper has been accepted for the International Environmental Congress, 14-16 June, 2000, St.-Petersburg, Russia. (2) Two patents were granted on July 20, 1999, and January 12, 2000. (3) Three reports/presentations at the NASA LaRC and GRC (06/22199, 09/26/ 99, and 06/25/00). (4) Grants and Proposals: Four proposals were submitted to the NASA and CRDF; a NASA Faculty Award was granted on January, 2000. A CRDF Young Investigator Program Award was granted for a 3 months visit of the Russian scientist to the HU FM&AL (03/99-05/99). (5) Theory and Numerical Simulations- Analytical theory, numerical simulation, comparison of theoretical with experimental results, and modification of theoretical approaches, models, grids etc. have been conducted for several complicated 2D and 3D nozzle and inlet designs using NASA codes based on full Euler and Navier-Stokes solvers: CFL3D, CRAFT, GODUNOV, and others. New approach for environmental monitoring via infrasound. (6) Experimental Tests: Experimental acoustic tests at the TsAGI, Moscow, with nozzles having Screwdriver or Axisymmetric Plug and Permeable Shells. A small scale working model of the NASA Low Speed Wind Tunnel (LSWT) has been installed in the Experimental Hall of the HU FM&AL (June, 1999). Preliminary preparations for experimental tests were made. (7) Students Research Activity: Involvement of the two graduate students as research assistants in the current research project.

Gilinsky, Mikhail↗

Numerical solutions of forward-flight rotor flow using an upwind method

A finite-volume upwind algorithm for solving the 3-D Euler equations with a moving grid has been developed for computing helicopter forward-flight rotor flows. The computed pressure distributions and shock positions of high-speed rotor flow are compared with various experimental data as well as with other numerical results, and the agreement is encouraging. A comparison of quasi-steady solutions with unsteady solutions reveals that when a shock occurs in the flowfield, the assumption of quasi-steady flow may fail due to the time-lag of the shock motion. Similarly, three-dimensional effects cannot be neglected. Sufficient subiterations for each time step are required to avoid numerical lag effects in using the present method. The redistribution of the residual due to the coordinate transformation is discussed. For high-order MUSCL-type schemes, a coordinate-independent solution can be obtained by interpolating primitive variables.

Chen, C. L.↗

Real-Time Temperature Field State Observer and Digital Replica to Support Cyber-Physical Testing

Cyber-physical testing is a class of experimental methods in which a system is partitioned into physical and numerical components to study its overall behavior. Transfer systems are typically needed to capture relevant interactions by enforcing appropriate interface conditions between the physical and numerical portions. While cyber-physical testing is often performed using lumped-parameter systems, thermomechanical cyber-physical testing requires the use of thermal actuators as transfer systems to apply a thermal condition over a spatially distributed region or surface. Thus, the interactions between the numerical and physical components are of a distributed nature, i.e., a field rather than point values. In this paper, we develop and experimentally validate a state observer for temperature fields to enable thermomechanical cyber-physical testing. The state observer provides continuous estimates of temperature over a surface of the thermal actuator using only temperature measurements at discrete locations. The estimated temperature field is then leveraged to account for localized mechanical defects in the interface condition. The method consists of building a digital replica of one portion of the control plant. By imposing defects in the digital replica it is used to generate and output the response of a thermal load pattern that represents that of a physical system with mechanical defects.

Manuel Salmeron↗

Analysis and prediction of tilt rotor hover noise

This paper presents new and improved tilt rotor hover noise prediction methods. Calculations include both discrete frequency harmonic noise and broadband noise mechanisms due to the ground plane/fountain recirculating flow. The noise mechanisms studied are thickness, loading, and inflow turbulence noise. In each case aeroacoustic models are developed and compared to noise measurements obtained experimentally for the XV-15 experimental tilt rotor aircraft. Both the effects of the mean and the turbulent fountain flows are found to be important noise sources and have strongly directional radiation patterns toward the rear of the aircraft (the direction of the rotor motion through the fountain flow). Calculations also show that the noise generated by the inflow of ambient atmospheric turbulence can also be an important noise source in hover in some directions. Further development of the methods and models, and precise information about the fountain flow, are needed to improve the predictions and to initiate noise minimization studies.

Coffen, Charles D.↗

Jet Engine hot parts IR Analysis Procedure (J-EIRP)

A thermal radiation analysis method called Jet Engine IR Analysis Procedure (J-EIRP) was developed to evaluate jet engine cavity hot parts source radiation. The objectives behind J-EIRP were to achieve the greatest accuracy in model representation and solution, while minimizing computer resources and computational time. The computer programs that comprise J-EIRP were selected on the basis of their performance, accuracy, and flexibility to solve both simple and complex problems. These programs were intended for use on a personal computer, but include the ability to solve large problems on a mainframe or supercomputer. J-EIRP also provides the user with a tool for developing thermal design experience and engineering judgment through analysis experimentation, while using minimal computer resources. A sample jet engine cavity analysis demonstrates the procedure and capabilities within J-EIRP, and is compared to a simplified method for approximating cavity radiation. The goal is to introduce the terminology and solution process used in J-EIRP and to provide insight into the radiation heat transfer principles used in this procedure.

Baumeister, Joseph F.↗

Benchmarking characterization methods for noisy quantum circuits

Effective methods for characterizing the noise in quantum computing devices are essential for programming and debugging circuit performance. Existing approaches vary in the information obtained as well as the amount of quantum and classical resources required, with more information generally requiring more resources. Here we benchmark the characterization methods of gate set tomography, Pauli channel noise reconstruction, and empirical direct characterization for developing models that describe noisy quantum circuit performance on a 27-qubit superconducting transmon device. We evaluate these models by comparing the accuracy of noisy circuit simulations with the corresponding experimental observations. Here, we find that the agreement of noise model to experiment does not correlate with the information gained by characterization and that the underlying circuit strongly influences the best choice of characterization approach. Empirical direct characterization scales best of the methods we tested and produced the most accurate characterizations across our benchmarks.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

A Moving Embedded Boundary Approach for the Compressible Navier-Stokes Equations in a Block-Structured Adaptive Refinement Framework

A computational technique has been developed to perform compressible flow simulations involving moving boundaries using an embedded boundary approach within the block-structured adaptive mesh refinement (SAMR) framework of AMReX [1], [91], [92]. We leverage the SAMR capability to obtain quantitatively accurate results whilst using robust, second-order finite volume schemes. A conservative, unsplit, cut-cell approach is utilized and a ghost-cell approach is developed for computing the flux on the moving, embedded boundary faces. A third-order least-squares formulation has been developed to compute the wall velocity gradients, and was found to significantly improve the performance of the solver in terms of the quantitative comparison of surface quantities such as the skin friction coefficient. Various test cases are performed to validate the method, and compared with analytical, experimental, and other numerical results in literature. Inviscid and viscous test cases are performed that span a wide regime of flow speeds - acoustic (harmonically pulsating sphere), smooth flows (expansion fan created by a receding piston) and flows with shocks (shock-cylinder interaction, shock-wedge interaction, pitching NACA 0012 airfoil and shock-cone interaction). A closed system with moving boundaries - an oscillating piston in a cylinder, showed that the percentage error in mass within the system decreases with refinement, demonstrating that the numerical scheme is conservative with grid refinement, but is not discretely conservative. Viscous test cases involve that of a horizontally moving cylinder at Re = 40, an inline oscillating cylinder at Re = 100, and a transversely oscillating cylinder at Re = 185. The judicious use of adaptive mesh refinement with appropriate refinement criteria to capture the regions of interest leads to well-resolved flow features, and good quantitative comparison is observed with the results available in literature.

adaptive refinement↗

Numerical and Experimental Examination of Turbulent Mixing of a Heated Jet in Crossflow

The injection of fully-developed turbulent heated air from a tube into a cooler turbulent duct flow is examined, as an analogy to film cooled turbine blades. A LES numerical model is developed and applied in which tube and duct turbulence inflow effects are emulated using a divergence-free synthetic eddy method (SEM). For direct comparison, a hot-wire experiment is conducted within the ERB test cell SW-6 at NASA Glenn Research Center. Results related to velocity, temperature, and heat flux are obtained numerically and experimentally for a blowing ratio of 1.2, involving a 36 K temperature difference. The relative effect on the solutions of tube and duct inflow turbulence is systematically evaluated. The impact of inherent low-pass filtering of temperature measurements and probe wire offset on the experimental results are addressed.

Large Eddy Simulation↗

Surface Segregation Studies in Ternary Noble Metal Alloys: Comparing DFT and Machine Learning with Experimental Data

Abstract Surface segregation, whereby the surface composition of an alloy differs systematically from the bulk, has historically been hard to study, because it requires experimental and modeling methods that span alloy composition space. In this work, we study surface segregation in catalytically relevant noble and platinum‐group metal alloys with a focus on three ternary systems: AgAuCu, AuCuPd, and CuPdPt. We develop a data set of 2478 fcc slabs with those compositions including all three low‐index crystallographic orientations relaxed with Density Functional Theory using the PBEsol functional with D3 dispersion corrections. We fine‐tune a machine learning model on this data and use the model in a series of 1800 Monte Carlo simulations spanning ternary composition space for each surface orientation and ternary chemical system. The results of these simulations are validated against prior experimental surface segregation data collected using composition spread alloy films for AgAuCu and AuCuPd. Our findings reveal that simulations conducted using the (110) orientation most closely match experimentally observed surface segregation trends, and while predicted trends qualitatively match observation, biases in the PBEsol functional limit numeric accuracy. This study advances understanding of surface segregation and the utility of computational studies and highlights the need for further improvements in simulation accuracy.

Chemistry↗

Machine learning enabling high-throughput and remote operations at large-scale user facilities

Imaging, scattering, and spectroscopy are fundamental in understanding and discovering new functional materials. Contemporary innovations in automation and experimental techniques have led to these measurements being performed much faster and with higher resolution, thus producing vast amounts of data for analysis. These innovations are particularly pronounced at user facilities and synchrotron light sources. Machine learning (ML) methods are regularly developed to process and interpret large datasets in real-time with measurements. However, there remain conceptual barriers to entry for the facility general user community, whom often lack expertise in ML, and technical barriers for deploying ML models. Herein, we demonstrate a variety of archetypal ML models for on-the-fly analysis at multiple beamlines at the National Synchrotron Light Source II (NSLS-II). We describe these examples instructively, with a focus on integrating the models into existing experimental workflows, such that the reader can easily include their own ML techniques into experiments at NSLS-II or facilities with a common infrastructure. The framework presented here shows how with little effort, diverse ML models operate in conjunction with feedback loops via integration into the existing Bluesky Suite for experimental orchestration and data management.

36 MATERIALS SCIENCE↗

Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers

Background: Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed. Methods: Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others. Results: Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group. Conclusion: Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗