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WE-H-206-03: Promises and Challenges of Benchtop X-Ray Fluorescence CT (XFCT) for Quantitative in Vivo Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

Laser beam pointing stabilization using analog position-sensitive diodes

Laser wire scanners have been used for ion beam profile and emittance measurements at the Spallation Neutron Source linear accelerator. Due to propagation distances exceeding 100 m, reliable measurements require laser beam stabilization, previously accomplished with a feedback control loop using a digital camera as a position sensor [Hardin et al., Opt. Express 19, 2874 (2011)]. Here, this paper presents an upgraded pointing stabilization system utilizing analog position-sensitive diodes (PSDs) as the position detector, optimized with an optical diffuser. The new system significantly surpasses the previous system by offering an order-of-magnitude improvement in radiation tolerance and a bandwidth limited only by the burst repetition rate of the laser beam. Operating with a 60-Hz burst mode laser, the new system effectively suppresses laser beam drifts up to 30 Hz, compared to the previous system’s 4 Hz limit. In addition, the amplitude of spectral components below 0.1 Hz was reduced by a factor of more than 100, which is over seven times greater than was achieved by the previous system.

Data acquisition↗

Optical-property coefficient estimation of bulky medium in experiments with a succinctly analytical calculation

Diffuse optical imaging enables to reconstruct distribution of optical properties, absorption and scattering coefficients, in tissue for breast cancer detection based on diffusion equation with the help of the initial guess obtained from measured data. To estimate the initial guess of the optical-property coefficients, an analytical solution of diffusion equation can be used and compared with the measured data. The analytical solution for a homogeneous infinite medium can be obtained in the frequency domain, expressing that the photon intensity and the phase lag relative to the distance between source and detector in a linear relationship. In this study, a succinct calculation using the trigonometric relation is proposed to estimate the optical-property coefficients. A tank-type and a cylinder Lipovenoes phantoms with two concentrations of 1.25% and 2.5% are employed and measured for verification. It is found that the method proposed here shows better results and results in estimation errors of 0–14.81% for μ{sub a} and 20–42% for μ{sub s}′.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

A weak diffuse interstellar band in the far-ultraviolet spectrum of zeta Ophiuchi?

Goddard High Resolution Spectrograph (GHRS) observations at 3.5 km/s resolution reveal several new weak unidentified interstellar absorption lines in the ultraviolet spectrum of zeta Ophiuchi. The unidentified line at 1369.13 A has the appearance and characteristics of a weak diffuse interstellar band (DIB). The line has a smooth profile similar to many optical diffuse interstellar bands (i.e., a shallow asymmetric profile), it is clearly broader than identified interstellar lines near it in wavelength, and its full width at half maximum in ergs is comparable to the widths of the weak optical DIBs. The asymmetric profile cannot be attributed to blended absorption from diffuse clouds at different velocities; at this resolution the two principal cloud complexes on the sight line at heliocentric velocities of -27 and -15 km/s are clearly separated. We compare this unidentified absorption feature to identified interstellar atomic and molecular absorption lines and optical DIBs observed on the zeta Oph and xi Per sight lines, and we conclude that it is reasonable to suggest that this absorption feature might be a DIB. This is not a unique interpretation however; the unidentified line could alternatively be due to gas in the zeta Oph H II region or a blend of unknown neutral atomic or molecular absorption lines.

Tripp, Todd M.↗

Utilizing Highly Scattered Light for Intelligence through Aerosols

This communication is the final report for the project Utilizing Highly Scattered Light for Intelligence through Aerosols funded by the Laboratory Directed Research and Development (LDRD) program at Sandia National Laboratories and lasting six months in 2019. Aerosols like fog reduce visibility and cause down-time that for critical systems or operations are unacceptable. Information is lost due to the random scattering and absorption of light by tiny particles. Computational diffuse optical imaging methods show promise for interpreting the light transmitted through fog, enabling sensing and imaging to improve situational awareness at depths 10 times greater than current methods. Developing this capability first requires verification and validation of diffusion models of light propagation in fog. For this reason, analytical models were developed and compared to experimental data captured at the Sandia National Laboratory Fog Chamber facility. A methodology was developed to incorporate the propagation of scattered light through the imaging optics to a pixel array. The diffusion approximation to the radiative transfer equation was found to predict light propagation in fog under the appropriate conditions.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Remote sensing of the diffuse attenuation coefficient of ocean water

A technique was devised which uses remotely sensed spectral radiances from the sea to assess the optical diffuse attenuation coefficient, K (lambda) of near-surface ocean water. With spectral image data from a sensor such as the coastal zone color scanner (CZCS) carried on NIMBUS-7, it is possible to rapidly compute the K (lambda) fields for large ocean areas and obtain K "images" which show synoptic, spatial distribution of this attenuation coefficient. The technique utilizes a relationship that has been determined between the value of K and the ratio of the upwelling radiances leaving the sea surface at two wavelengths. The relationship was developed to provide an algorithm for inferring K from the radiance images obtained by the CZCS, thus the wavelengths were selected from those used by this sensor, viz., 443, 520, 550 and 670 nm. The majority of the radiance arriving at the spacecraft is the result of scattering in the atmospheric and is unrelated to the radiance signal generated by the water. A necessary step in the processing of the data received by the sensor is, therefore, the effective removal of these atmospheric path radiance signals before the K algorithm is applied. Examples of the efficacy of these removal techniques are given together with examples of the spatial distributions of K in several ocean areas.

Austin, R. W.↗

The faint galaxy contribution to the diffuse extragalactic background light

Models of the faint galaxy contribution to the diffuse extragalactic background light are presented, which are consistent with current data on faint galaxy number counts and redshifts. The autocorrelation function of surface brightness fluctuations in the extragalactic diffuse light is predicted, and the way in which these predictions depend on the cosmological model and assumptions of biasing is determined. It is confirmed that the recent deep infrared number counts are most compatible with a high density universe (Omega-0 is approximately equal to 1) and that the steep blue counts then require an extra population of rapidly evolving blue galaxies. The faintest presently detectable galaxies produce an interesting contribution to the extragalactic diffuse light, and still fainter galaxies may also produce a significant contribution. These faint galaxies still only produce a small fraction of the total optical diffuse background light, but on scales of a few arcminutes to a few degrees, they produce a substantial fraction of the fluctuations in the diffuse light.

Cole, Shaun↗

Influence of organic cation planarity on structural templating in hybrid metal-halides

Controlling the connectivity and topology of solids is a versatile way to target desired physical properties. This is especially relevant in the realm of hybrid halide semiconductors, where the long-range connectivity of the inorganic substructural unit can lead to significant changes in optoelectronic properties such as photoluminescence, charge transport, and absorption. We present a new series of hybrid metal-halide semiconductors, (phenH 2 )BiI 5 ·H 2 O, (2,2-bpyH 2 )BiI 5 , (BrbpyH)BiI 4 ·H 2 O, (phenH 2 ) 2 Pb 3 I 10 ·2H 2 O, and (2,2-bpyH 2 ) 2 Pb 3 I 10 where (phenH 2 ) 2+ = 1,10-phenanthroline-1,10-diium, (2,2-bpyH 2 ) 2+ = 2,2'-bipyridine-1,1'-diium and (BrbpyH) + = 6,6'-dibromo-2,2'-bipyridium. These compounds allow us to observe how the planarity of the cation, induced either through structural modification in the case of (phenH 2 ) 2+ or through non-covalent interactions in (BrbpyH) + , both relative to (2,2-bpyH 2 ) 2+ , modifies the inorganic substructural unit. While the Pb 2+ series of compounds show minimal changes in inorganic connectivity, we observe large differences in the Bi 3+ series, ranging from 0-D dimers to corner- and edge-sharing 1-D chains of octahedra. We find that compounds containing (phenH 2 ) 2+ and (BrbpyH) + pack more efficiently than those with (2,2-bpyH 2 ) 2+ due to their retention of planarity leading to greater inorganic connectivity. Electronic structure calculations and optical diffuse reflectance reveal that the band gaps of these compounds are influenced by the degree of inorganic connectivity and the inorganic substructural unit distances. These results show that the structure and planarity of organic cations can directly influence both the inorganic connectivity and the optical properties that could be tuned for certain optoelectronic applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A search for the 13175 A infrared diffuse band in dense environments

Models of ionized interstellar C60 predict a strong transition in the 1.2 micrometer region, and two candidate bands have recently been detected in reddened stars. We have searched for the stronger of these bands (at 13175 A) in the Taurus dark cloud complex, to determine its response to the dark-cloud environment. None of the three lines of sight studied (two near the cloud surface, one reaching A(sub V) greater than 20(sup m)) give rise to a detectable band; in one case the equivalent width is a factor of order three below that predicted. Since such behaviour is also shown by the optical Diffuse Interstellar Bands, we suggest that the 13175 A band is a genuine DIB, but we caution against an automatic interpretation in terms of an ionic carrier.

Adamson, A. J.↗

Thermal infrared imaging of subarcsecond structure in the trapezium nebula

We present 11.7 and 8.8 micron images of the central region of the Ney-Allen Nebula In Orion which reveal mid-infrared counterparts to the ionized globules previously discovered by optical and radio observations. The 0.5 arcsec full width at half maximum (FWHM) resolution images also reveal several arc-shaped structures which are associated with the compact sources. Each of the arcs points toward theta(sup 1) Ori C, providing further evidence for the strong-effects of the intense radiation and wind from this star on the central Orion Nebula. Low-resolution spectra of a few of these condensations and arcs are similar to spectra of the diffuse, optically thin silicate dust observed throughout the region. Photometry of one of the condensations, however, indicates that is cooler than the others. Simple momentum-balance arguments indicate that dust in the arcs could originate in the outflow from the compact sources and flow outward until stopped by the stellar wind and radiation pressure from theta(sup 1) Ori C.

Hayward, T. L.↗

Optoelectronic properties of candidate photovoltaic Cu 2 PbSiS 4 , Ag 2 PbGeS 4 and KAg 2 SbS 4 semiconductors

High temperature synthesis and optical band gaps are reported for three candidate photovoltaic earth-abundant Cu 2 PbSiS 4 , Ag 2 PbGeS 4 and KAg 2 SbS 4 semiconductors. The reported synthesis method is found to be more advantageous for KAg 2 SbS 4 compared to the literature reported synthesis utilizing supercritical ammonia as a reaction medium, which produces a mixture of chalcogenide products. Based on optical diffuse reflectance data, Cu 2 PbSiS 4 , Ag 2 PbGeS 4 and KAg 2 SbS 4 have band gaps in the 1.6–1.8 eV range, and are shown to be stable in ambient air for a period of 6 weeks, making them attractive candidates for solar cell applications. Density functional theory (DFT) calculations indicate indirect band gaps for Cu 2 PbSiS 4 and KAg 2 SbS 4 , and a nearly direct band gap for Ag 2 PbGeS 4 with the calculated difference between indirect and direct gaps of only 30 meV. The p-type semiconducting behavior of Cu 2 PbSiS 4 , Ag 2 PbGeS 4 is also verified by the transport measurments. The 3D connectivity of the polyanionic networks in these compounds results in dispersive valence and conduction bands, which is especially noticeable for KAg 2 SbS 4 . This fact is in part attributed to the presence of formally pentavalent SbV in this compound leading to empty Sb 5s orbitals in the conduction band. Finally, we discuss the potential of Cu 2 PbSiS 4 , Ag 2 PbGeS 4 and KAg 2 SbS 4 for photovoltaic applications based on synthesis, stability, band gap and electronic structure considerations.

14 SOLAR ENERGY↗

Phase identification and structure investigation of novel quaternary rare-earth substituted titanates

Novel quaternary lanthanide-substituted oxides of stoichiometry LnxY2-xTi2O7 (where Ln is lanthanum, neodymium, samarium, gadolinium, or ytterbium) were prepared by traditional high-temperature, solid-state techniques and characterized by X-ray powder diffraction. Samples with nominal values of x up to 1.0 were attempted. The well-studied ternary cubic pyrochlore compound yttrium titanium oxide (Y2Ti2O7, space group Fd-3m, Z = 8), served as a parent structural framework in which Ln3+ cations were substituted on the Y3+ site. Laboratory-grade X-ray powder diffraction data revealed pure quaternary pyrochlore phases for LnxY2-xTi2O7 with x ≤ 0.2. Pyrochlore phase purity was verified by Rietveld analysis using high-resolution synchrotron X-ray powder diffraction data when x ≤ 0.2, however, for La3+ substitution specifically, pure quaternary pyrochlore formed at x<0.1. Band gap energies on selected samples were determined using optical diffuse reflectance spectroscopy and showed that these materials can be classified as electrical insulators with indirect band gap energies around 3.7 eV.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Time-resolved single-photon detection module based on silicon photomultiplier: A novel building block for time-correlated measurement systems

We present the design and preliminary characterization of the first detection module based on Silicon Photomultiplier (SiPM) tailored for single-photon timing applications. The aim of this work is to demonstrate, thanks to the design of a suitable module, the possibility to easily exploit SiPM in many applications as an interesting detector featuring large active area, similarly to photomultipliers tubes, but keeping the advantages of solid state detectors (high quantum efficiency, low cost, compactness, robustness, low bias voltage, and insensitiveness to magnetic field). The module integrates a cooled SiPM with a total photosensitive area of 1 mm{sup 2} together with the suitable avalanche signal read-out circuit, the signal conditioning, the biasing electronics, and a Peltier cooler driver for thermal stabilization. It is able to extract the single-photon timing information with resolution better than 100 ps full-width at half maximum. We verified the effective stabilization in response to external thermal perturbations, thus proving the complete insensitivity of the module to environment temperature variations, which represents a fundamental parameter to profitably use the instrument for real-field applications. We also characterized the single-photon timing resolution, the background noise due to both primary dark count generation and afterpulsing, the single-photon detection efficiency, and the instrument response function shape. The proposed module can become a reliable and cost-effective building block for time-correlated single-photon counting instruments in applications requiring high collection capability of isotropic light and detection efficiency (e.g., fluorescence decay measurements or time-domain diffuse optics systems).

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Ex situ calibration of the scattered-light time-history diagnostic on the National Ignition Facility

The scattered-light time-history diagnostic (SLTD) suite measures time-resolved scattered light in three wavelength bands: stimulated Brillouin scattering (350–352 nm), stimulated Raman scattering (430–760 nm), and plasma emission at half the laser frequency (695–735 nm), at 15 locations around the National Ignition Facility (NIF) target chamber. The SLTD, along with the full-aperture backscatter station (FABS), collects scattered light from direct- and indirect-drive inertial confinement fusion experiments. The SLTD calibration was revisited after a discrepancy between FABS and SLTD measurements was observed on NIF polar direct-drive experiments. An integrated calibration of the SLTD was performed for the first time, and individual components were also calibrated for the wavelengths of 351, 527, and 532 nm. The optical transmission of the instrument was measured to be (1.12 ± 0.04) × 10 –7 and (1.96 ± 0.11) × 10 –7 for the wavelengths of 351 and 532 nm, respectively. The revised calibration at 351 nm brings the SLTD measured scattered energy in agreement with the FABS measured scattered energy after additionally accounting for the degradation of an optical element in FABS. Furthermore, this decreased the inferred absorption by 7% for a representative experiment. However, discrepancies remain between FABS and SLTD measurements in the SRS band (532 nm).

47 OTHER INSTRUMENTATION↗

WE-FG-BRA-03: Oxygen Interplay in Hypofractionated Radiotherapy: A Hidden Opportunity

Purpose: Local oxygen during a radiotherapy fraction has been shown to change over a full range of the oxygen enhancement ratio (OER) during the same time scale as the treatment fraction. Interplay with local oxygen is then likely a concern, especially for hypofractionation. Our experiments that show a strong role for metabolic dynamics suggesting one could manipulate this interplay for more efficacious treatments. Methods: Two published experiments are presented with the same human head and neck cancer cell line (UM-SCC-22B). One is a cell-specific in vitro prompt response to a 10 Gy dose of orthovotage radiation using fluorescence lifetime imaging (FLIM), benchmarked with a Seahorse assay. The other in vivo study uses autocorrelation analysis with blood oxygen level dependent magnetic resonance imaging (MRI-BOLD) on xenografts. In vivo results are verified with diffuse optics using spectra fitting and photoacoustic measurements. All these measurements are at high time resolution: sampling is one per minute. Results: Interplay happens when the radiosensitivity modulates at the same time scale as the radiation. These results show dynamics at these time scales. 1. The dominant time scale of the acute hypoxia in cell line xenografts is shown to be on the order of minutes to tens of minutes: similar to a metabolic oscillation known as the ‘glycolytic oscillator.’ 2. The radiation dose itself alters metabolism within minutes to tens of minutes also. Conclusion: These results vary with cell type. There is a possibility that special timing and dose levels could be used for radiation. Gating could be used for maximal oxygen during treatment. There is an analogy to the interplay discussions with tumor motion, except that an oxygen interplay could more likely be patient-specific at a more fundamental level.

60 APPLIED LIFE SCIENCES↗

Deep learning-based temporal deconvolution for photon time-of-flight distribution retrieval

The acquisition of the time of flight (ToF) of photons has found numerous applications in the biomedical field. Over the last decades, a few strategies have been proposed to deconvolve the temporal instrument response function (IRF) that distorts the experimental time-resolved data. However, these methods require burdensome computational strategies and regularization terms to mitigate noise contributions. Herein, we propose a deep learning model specifically to perform the deconvolution task in fluorescence lifetime imaging (FLI). The model is trained and validated with representative simulated FLI data with the goal of retrieving the true photon ToF distribution. Its performance and robustness are validated with well-controlled in vitro experiments using three time-resolved imaging modalities with markedly different temporal IRFs. The model aptitude is further established with in vivo preclinical investigation. Overall, these in vitro and in vivo validations demonstrate the flexibility and accuracy of deep learning model-based deconvolution in time-resolved FLI and diffuse optical imaging.

Pandey, Vikas (ORCID:0000000154771095)↗

Solar wind physics

A double-chambered gas proportional counter was constructed to detect and identify solar wind ions after acceleration by a high voltage power supply. It was determined that the best method of detecting deuterium in the solar wind is to use a tritium target as proposed for IMP H and J. The feasibility of detecting H(+) and He(+) ions of interstellar origin is considered. A program is described to carry out ground-based astronomical observations of faint, diffuse optical emission lines from interstellar gas. Hydrogen and oxygen emission lines from galactic sources were detected and the galactic and geocoronal H alpha and beta lines were clearly resolved.

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