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At least 1,315 records · Page 73

Evaluation of the FilmArray® system for detection of Bacillus anthracis, Francisella tularensis, and Yersinia pestis

To evaluate the sensitivity and specificity of the Idaho Technologies FilmArray® Biothreat Panel for the detection of Bacillus anthracis (Ba), Francisella tularensis (Ft), and Yersinia pestis (Yp) DNA, and demonstrate the detection of Ba spores. Methods and Results: DNA samples from Ba, Ft and Yp strains and near-neighbors, and live Ba spores were analyzed using the Biothreat Panel, a multiplexed PCR-based assay for 17 pathogens and toxins. Sensitivity studies with DNA suggest a limit of detection of 250 genome equivalents (GEs) per sample. Furthermore, the correct call of Ft, Yp or Bacillus species was made in 63 of 72 samples tested at 25 GE or less. With samples containing 25 Ba Sterne spores, at least one of the two possible Ba markers were identified in all samples tested. We observed no cross-reactivity with near-neighbor DNAs.

Biodetection, PCR, hand portable, pathogens, biote↗

Kinship, inbreeding and fine‐scale spatial structure influence gut microbiota in a hindgut‐fermenting tortoise

Abstract Herbivorous vertebrates rely on complex communities of mutualistic gut bacteria to facilitate the digestion of celluloses and hemicelluloses. Gut microbes are often convergent based on diet and gut morphology across a phylogenetically diverse group of mammals. However, little is known about microbial communities of herbivorous hindgut‐fermenting reptiles. Here, we investigate how factors at the individual level might constrain the composition of gut microbes in an obligate herbivorous reptile. Using multiplexed 16S rRNA gene sequencing, we characterized the faecal microbial community of a population of gopher tortoises ( Gopherus polyphemus ) and examined how age, genetic diversity, spatial structure and kinship influence differences among individuals. We recovered phylotypes associated with known cellulolytic function, including candidate phylum Termite Group 3, suggesting their importance for gopher tortoise digestion. Although host genetic structure did not explain variation in microbial composition and community structure, we found that fine‐scale spatial structure, inbreeding, degree of relatedness and possibly ontogeny shaped patterns of diversity in faecal microbiomes of gopher tortoises. Our findings corroborate widespread convergence of faecal‐associated microbes based on gut morphology and diet and demonstrate the role of spatial and demographic structure in driving differentiation of gut microbiota in natural populations.

Yuan, Michael L.↗

Engineering quantitative stomatal trait variation and local adaptation potential by cis‐regulatory editing

Summary Cis‐regulatory element editing can generate quantitative trait variation that mitigates extreme phenotypes and harmful pleiotropy associated with coding sequence mutations. Here, we applied a multiplexed CRISPR/Cas9 approach, informed by bioinformatic datasets, to generate genotypic variation in the promoter ofOsSTOMAGEN, a positive regulator of rice stomatal density. Engineered genotypic variation corresponded to broad and continuous variation in stomatal density, ranging from 70% to 120% of wild‐type stomatal density. This panel of stomatal variants was leveraged in physiological assays to establish discrete relationships between stomatal morphological variation and stomatal conductance, carbon assimilation and intrinsic water use efficiency in steady‐state and fluctuating light conditions. Additionally, promoter alleles were subjected to vegetative drought regimes to assay the effects of the edited alleles on developmental response to drought. Notably, the capacity for drought‐responsive stomatal density reprogramming instomagenand two cis‐regulatory edited alleles was reduced. Collectively our data demonstrate that cis‐regulatory element editing can generate near‐isogenic trait variation that can be leveraged for establishing relationships between anatomy and physiology, providing a basis for optimizing traits across diverse environments.

Biotechnology & Applied Microbiology↗

Use of an ocular wound chamber for the prevention of exposure keratopathy in a guinea pig model

Abstract Current therapies available to treat and heal ocular surface injuries and periocular burns are frequently inadequate, costly, and labor intensive. To address these limitations, we have employed a flexible, semitransparent ocular wound chamber (OWC) to provide protection as well as a watertight seal to allow for the constant delivery of therapeutics to the ocular surface and surrounding periocular tissue. This study demonstrates the safety and utilization of the OWC on uninjured eyes and in our exposure keratopathy model. For initial safety studies ( N = 3 per group), the eyelids remained intact and the eye uninjured. A blepharotomy ( N = 6 per group) was performed to remove the upper and lower eyelids surrounding the left (OS) eye to create our exposure keratopathy model. Right (OD) eyes served as uninjured controls in all studies. Following OWC placement, 0.5 mL HPMC gel or balanced saline solution (BSS) was injected into the chamber. Animals were monitored daily and fully assessed via white light, fluorescein, and OCT imaging at least through 72 hours post OWC placement. In studies that included a blepharotomy, skin samples were analyzed by multiplex cytokine analysis. Results of safety experiments revealed no significant differences between treatment groups in corneal thickness, fluorescein staining, OCT imaging, or histological eye or skin sections when compared to control eyes. In our exposure keratopathy model, OWC treated eyes showed significantly less fluorescein uptake and also were found to have significantly lower levels of cytokines IL‐13 and IL‐5 in skin samples. These results demonstrate for the first time that treatment using the OWC device is not only safe, but significantly protects against blepharotomy‐induced exposure keratopathy. As a whole, this study advances our overall efforts to develop a feasible solution to treat ocular surface injuries, infections, and periocular burns.

Holt, Andrew W.↗

In situ , in vivo , and in operando imaging and spectroscopy of liquids using microfluidics in vacuum

This review offers a succinct overview of the development of a vacuum-compatible microfluidic reactor system for analysis at the liquid vacuum interface (SALVI), and its diverse applications in in situ, in vivo, and in operando imaging of liquid surfaces as well as the air-liquid (a-l), liquid-liquid (l-l), and solid-liquid (s-l) interfaces in the past decade. SALVI is one of the first microfluidics-based reactors that has enabled direct analysis of volatile liquids in vacuum surface tools such as scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Its integration into ambient and vacuum spectroscopy and microscopy is illustrated. Several applications are highlighted including (1) imaging nanoparticles in liquid using in situ SEM; (2) mapping the evolving l-l interface using in situ x-ray absorption spectroscopy and ToF-SIMS; (3) following complex a-l interfacial oxidation reaction products using in situ ToF-SIMS; (4) capturing biological interfaces of cells and microbes via in vivo multimodal and correlative imaging; and (5) monitoring the dynamic solid electrode and liquid electrolyte interface using in operando molecular imaging. Finally, outlook and recommendations are presented. Besides showing the holistic information volume obtained by real-time multiplexed imaging, this review intends to convey the importance of tool development in revolutionizing surface and interface analysis using vacuum platforms previously limited to solid surfaces. Microfluidics is manifested to be not limited to ambient conditions in many examples in this review. Moreover, fundamental interfacial phenomena underpinning mass and charge transfer can now be pursued in real time via innovated chemical imaging and spectroscopy.

42 ENGINEERING↗

Line emission mapper microcalorimeter spectrometer

The line emission mapper (LEM) is a probe-class mission concept that is designed to detect x-ray emission lines from hot ionized gas (T > 10 6 K) that will enable us to test galaxy evolution theories. It will permit us to study the effects of stellar and black-hole feedback and flows of baryonic matter into and out of galaxies. The key to being able to study the hot gases that are otherwise invisible to current imaging x-ray spectrometers is that the energy resolution is sufficient to use cosmological redshift to separate extragalactic source lines from foreground Milky Way emission. LEM incorporates a large-format microcalorimeter array instrument called the LEM microcalorimeter spectrometer (LMS) with a light-weight x-ray optic with 10” half power diameter angular resolution. The LMS microcalorimeter array has pixels with 15" pixel pitch over a 33' field of view (FOV) optimized for the 0.3 to 2 keV energy band. The central 7' region of the array has an energy resolution of 1.3 eV at 1 keV and the rest of the FOV has 2.5 eV energy resolution at 1 keV. The array will be read out with state-of-the-art time-division multiplexing. We present an overview of the LMS instrument, including details of the entire detection chain, the focal plane assembly, as well as the cooling system and overall mechanical and thermal design. For each of the key technologies, we discuss the current technology readiness level and the plan to advance them to be ready for flight. We also describe the current system design and our estimate for the mass, power, and data rate of the instrument. The design details presented concentrate primarily on the unique aspects of the LMS design compared with prior missions and confirm that the type of microcalorimeter instrument needed for LEM is not only feasible but also technically mature.

47 OTHER INSTRUMENTATION↗

Large arrays of dual-polarized multichroic TES detectors for CMB measurements with the SPT-3G receiver

Now, detectors for cosmic microwave background (CMB) experiments are background limited, so a straightforward alternative to improve sensitivity is to increase the number of detectors. Large arrays of multichroic pixels constitute an economical approach to increasing the number of detectors within a given focal plane area. We present the fabrication of large arrays of dual-polarized multichroic transition-edge-sensor (TES) bolometers for the South Pole Telescope third-generation CMB receiver (SPT-3G). The complete SPT-3G receiver will have 2690 pixels, each with six detectors, allowing for individual measurement of three spectral bands (centered at 95 GHz, 150 GHz and 220 GHz) in two orthogonal polarizations. In total, the SPT-3G focal plane will have 16140 detectors. Each pixel is comprised of a broad-band sinuous antenna coupled to a niobium microstrip transmission line. In-line filters are used to define the different band-passes before the millimeter-wavelength signal is fed to the respective Ti/Au TES sensors. Detectors are read out using a 64x frequency domain multiplexing (fMux) scheme. The microfabrication of the SPT-3G detector arrays involves a total of 18 processes, including 13 lithography steps. Together with the fabrication process, the effect of processing on the Ti/Au TES's T-c is discussed. In addition, detectors fabricated with Ti/Au TES films with Tc between 400 mK 560 mK are presented and their thermal characteristics are evaluated. Optical characterization of the arrays is presented as well, indicating that the response of the detectors is in good agreement with the design values for all three spectral bands (95 GHz, 150 GHz, and 220 GHz). The measured optical efficiency of the detectors is between 0.3 and 0.8. Our results discussed here are extracted from a batch of research of development wafers used to develop the baseline process for the fabrication of the arrays of detectors to be deployed with the SPT-3G receiver. Results from these research and development wafers have been incorporated into the fabrication process to get the baseline fabrication process presented here. SPT-3G is scheduled to deploy to the South Pole Telescope in late 2016.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Optical design of PICO: a concept for a space mission to probe inflation and cosmic origins

The Probe of Inflation and Cosmic Origins (PICO) is a probe-class mission concept currently under study by NASA. PICO will probe the physics of the Big Bang and the energy scale of inflation, constrain the sum of neutrino masses, measure the growth of structures in the universe, and constrain its reionization history by making full sky maps of the cosmic microwave background with sensitivity 80 times higher than the Planck space mission. With bands at 21-799 GHz and arcmin resolution at the highest frequencies, PICO will make polarization maps of Galactic synchrotron and dust emission to observe the role of magnetic fields in Milky Way's evolution and star formation. We discuss PICO's optical system, focal plane, and give current best case noise estimates. The optical design is a two-reflector optimized open-Dragone design with a cold aperture stop. It gives a diffraction limited field of view (DLFOV) with throughput of 910 cm 2 sr at 21 GHz. The large 82 square degree DLFOV hosts 12,996 transition edge sensor bolometers distributed in 21 frequency bands and maintained at 0.1 K. We use focal plane technologies that are currently implemented on operating CMB instruments including three-color multi-chroic pixels and multiplexed readouts. To our knowledge, this is the first use of an open-Dragone design for mm-wave astrophysical observations, and the only monolithic CMB instrument to have such a broad frequency coverage. Finally, with current best case estimate polarization depth of 0.65 μKCMB-arcmin over the entire sky, PICO is the most sensitive CMB instrument designed to date.

79 ASTRONOMY AND ASTROPHYSICS↗

Design and characterization of the SPT-3G receiver (Conference Presentation)

(On behalf of the SPT-3G collaboration)The SPT-3G receiver was commissioned in early 2017 on the 10-meter South Pole Telescope (SPT) to map the Cosmic Microwave Background (CMB) with arcminute resolution. The new instrument significantly improves on previous SPT camera designs, offering unprecedented sensitivity to the CMB’s temperature and polarization anisotropies while maintaining a tight control on systematic effects.A restructured optics chain features new secondary and tertiary mirrors to increase the receiver’s field of view by a factor of four in area, coupling light through a set of four cryogenic 720 mm alumina elements, which re-image the Gregorian focus inside the receiver. The broad-band (70-270 GHz) anti-reflective coated lenses are paired with a Lyot stop and cooled to 4 K using a dedicated two-stage pulse-tube cooler (PTC) to minimize in-band attenuation, internal radiative loading, and stray light on the considerably larger focal plane, which is populated with ~2,700 diffraction-limited pixels.Each independent pixel incorporates a lenslet-coupled broadband sinuous antenna, which routes signals through superconducting transmission lines and in-line band-defining filters to six transition-edge sensors, each measuring one of three bands (90, 150, and 220 GHz) and two polarizations, yielding a total of ~16,000 bolometers distributed across ten 150 mm monolithic wafers on a 430 mm image plane. A robust mechanical and thermal architecture supports and cools all detectors across this sizable focal plane to ~250 mK using a closed-cycle Helium adsorption refrigerator backed by a PTC, allowing a duty cycle greater than 90%.This order of magnitude increase in detector count relies on an improved digital frequency-domain SQUID readout system which integrates superconducting inductor-capacitor resonators wired in series with each bolometer to achieve a 68x multiplexing factor while mitigating noise and crosstalk effects.Cumulatively, SPT-3G’s new optics, detector, and readout strategies boast a potential factor of ~20 improvement in mapping speed over its predecessor, SPT-Pol, offering the potential to improve our understanding of inflationary physics, astroparticle physics, and growth of structure. We summarize the new receiver’s core design principles, outline technology characterization results, and report on plans for future upgrades.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Polarization–frequency hyperentangled photons: generation, characterization, and manipulation

Frequency-bin encoding is massively parallelizable and robust for optical fiber transmission. When coupled with an additional degree of freedom (DoF), the expansion of the Hilbert space allows for deterministic controlled operations between two DoFs within a single photon. Such capabilities, when combined with photonic hyperentanglement, are of great value for quantum communication protocols, including dense coding and single-copy entanglement distillation. In this talk, we present an all-fiber-coupled, ultrabroadband polarization–frequency hyperentangled source and conduct comprehensive quantum state tomography across multiple dense wavelength division multiplexing channels spanning the optical C+L-band (1530–1625 nm). In addition, we design and implement a high-fidelity controlled-NOT (cnot) operation between polarization and frequency DoFs by exploiting electro-optic phase modulation within a fiber Sagnac loop. Collectively, our hyperentangled source and two-qubit gate should unlock new opportunities for harnessing polarization–frequency resources in established telecommunication fiber networks for future quantum applications.

Lu, Hsuan-Hao↗

A method to synchronize signals from multiple patient monitoring devices through a single input channel for inclusion in list-mode acquisitions

Purpose: This technical note documents a method that the authors developed for combining a signal to synchronize a patient-monitoring device with a second physiological signal for inclusion into list-mode acquisition. Our specific application requires synchronizing an external patient motion-tracking system with a medical imaging system by multiplexing the tracking input with the ECG input. The authors believe that their methodology can be adapted for use in a variety of medical imaging modalities including single photon emission computed tomography (SPECT) and positron emission tomography (PET). Methods: The authors insert a unique pulse sequence into a single physiological input channel. This sequence is then recorded in the list-mode acquisition along with the R-wave pulse used for ECG gating. The specific form of our pulse sequence allows for recognition of the time point being synchronized even when portions of the pulse sequence are lost due to collisions with R-wave pulses. This was achieved by altering our software used in binning the list-mode data to recognize even a portion of our pulse sequence. Limitations on heart rates at which our pulse sequence could be reliably detected were investigated by simulating the mixing of the two signals as a function of heart rate and time point during the cardiac cycle at which our pulse sequence is mixed with the cardiac signal. Results: The authors have successfully achieved accurate temporal synchronization of our motion-tracking system with acquisition of SPECT projections used in 17 recent clinical research cases. In our simulation analysis the authors determined that synchronization to enable compensation for body and respiratory motion could be achieved for heart rates up to 125 beats-per-minute (bpm). Conclusions: Synchronization of list-mode acquisition with external patient monitoring devices such as those employed in motion-tracking can reliably be achieved using a simple method that can be implemented using minimal external hardware and software modification through a single input channel, while still recording cardiac gating signals.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Evaluation of Matrix9 silicon photomultiplier array for small-animal PET

Purpose: The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 × 3 array of 4 × 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL’s front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 × 3.16 mm{sup 2} and the total size of the detector head is 47.8 × 46.3 mm{sup 2}. Using 8 × 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomography (PET). Methods: Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0–32.5 V in 0.5 V intervals) and at different temperatures (5 °C–25 °C in 5 °C degree steps) to find the optimal operating conditions. Results: The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5 °C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. Conclusions: In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Review of SPECT collimator selection, optimization, and fabrication for clinical and preclinical imaging

In single photon emission computed tomography, the choice of the collimator has a major impact on the sensitivity and resolution of the system. Traditional parallel-hole and fan-beam collimators used in clinical practice, for example, have a relatively poor sensitivity and subcentimeter spatial resolution, while in small-animal imaging, pinhole collimators are used to obtain submillimeter resolution and multiple pinholes are often combined to increase sensitivity. This paper reviews methods for production, sensitivity maximization, and task-based optimization of collimation for both clinical and preclinical imaging applications. New opportunities for improved collimation are now arising primarily because of (i) new collimator-production techniques and (ii) detectors with improved intrinsic spatial resolution that have recently become available. These new technologies are expected to impact the design of collimators in the future. The authors also discuss concepts like septal penetration, high-resolution applications, multiplexing, sampling completeness, and adaptive systems, and the authors conclude with an example of an optimization study for a parallel-hole, fan-beam, cone-beam, and multiple-pinhole collimator for different applications.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Multipinhole SPECT helical scan parameters and imaging volume

Purpose: The authors developed SPECT imaging capability on an animal PET scanner using a multiple-pinhole collimator and step-and-shoot helical data acquisition protocols. The objective of this work was to determine the preferred helical scan parameters, i.e., the angular and axial step sizes, and the imaging volume, that provide optimal imaging performance. Methods: The authors studied nine helical scan protocols formed by permuting three rotational and three axial step sizes. These step sizes were chosen around the reference values analytically calculated from the estimated spatial resolution of the SPECT system and the Nyquist sampling theorem. The nine helical protocols were evaluated by two figures-of-merit: the sampling completeness percentage (SCP) and the root-mean-square (RMS) resolution. SCP was an analytically calculated numerical index based on projection sampling. RMS resolution was derived from the reconstructed images of a sphere-grid phantom. Results: The RMS resolution results show that (1) the start and end pinhole planes of the helical scheme determine the axial extent of the effective field of view (EFOV), and (2) the diameter of the transverse EFOV is adequately calculated from the geometry of the pinhole opening, since the peripheral region beyond EFOV would introduce projection multiplexing and consequent effects. The RMS resolution results of the nine helical scan schemes show optimal resolution is achieved when the axial step size is the half, and the angular step size is about twice the corresponding values derived from the Nyquist theorem. The SCP results agree in general with that of RMS resolution but are less critical in assessing the effects of helical parameters and EFOV. Conclusions: The authors quantitatively validated the effective FOV of multiple pinhole helical scan protocols and proposed a simple method to calculate optimal helical scan parameters.

60 APPLIED LIFE SCIENCES↗

WE-H-206-00: Advances in Preclinical 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↗

WE-H-206-01: Photoacoustic Tomography: Multiscale Imaging From Organelles to Patients by Ultrasonically Beating the Optical Diffusion Limit

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↗

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

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↗

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↗