Results for “Biomedical Research” — Page 10

NASA NTRS1999

Extended Duration Orbiter Medical Project

Biomedical issues have presented a challenge to flight physicians, scientists, and engineers ever since the advent of high-speed, high-altitude airplane flight in the 1940s. In 1958, preparations began for the first manned space flights of Project Mercury. The medical data and flight experience gained through Mercury's six flights and the Gemini, Apollo, and Skylab projects, as well as subsequent space flights, comprised the knowledge base that was used to develop and implement the Extended Duration Orbiter Medical Project (EDOMP). The EDOMP yielded substantial amounts of data in six areas of space biomedical research. In addition, a significant amount of hardware was developed and tested under the EDOMP. This hardware was designed to improve data gathering capabilities and maintain crew physical fitness, while minimizing the overall impact to the microgravity environment. The biomedical findings as well as the hardware development results realized from the EDOMP have been important to the continuing success of extended Space Shuttle flights and have formed the basis for medical studies of crew members living for three to five months aboard the Russian space station, Mir. EDOMP data and hardware are also being used in preparation for the construction and habitation of International Space Station. All data sets were grouped to be non-attributable to individuals, and submitted to NASA s Life Sciences Data Archive.

Sawin, Charles F.↗

DOE OSTI2016

Semantic similarity between ontologies at different scales

In the past decade, existing and new knowledge and datasets has been encoded in different ontologies for semantic web and biomedical research. The size of ontologies is often very large in terms of number of concepts and relationships, which makes the analysis of ontologies and the represented knowledge graph computational and time consuming. As the ontologies of various semantic web and biomedical applications usually show explicit hierarchical structures, it is interesting to explore the trade-offs between ontological scales and preservation/precision of results when we analyze ontologies. This paper presents the first effort of examining the capability of this idea via studying the relationship between scaling biomedical ontologies at different levels and the semantic similarity values. We evaluate the semantic similarity between three Gene Ontology slims (Plant, Yeast, and Candida, among which the latter two belong to the same kingdom—Fungi) using four popular measures commonly applied to biomedical ontologies (Resnik, Lin, Jiang-Conrath, and SimRel). The results of this study demonstrate that with proper selection of scaling levels and similarity measures, we can significantly reduce the size of ontologies without losing substantial detail. In particular, the performance of Jiang-Conrath and Lin are more reliable and stable than that of the other two in this experiment, as proven by (a) consistently showing that Yeast and Candida are more similar (as compared to Plant) at different scales, and (b) small deviations of the similarity values after excluding a majority of nodes from several lower scales. This study provides a deeper understanding of the application of semantic similarity to biomedical ontologies, and shed light on how to choose appropriate semantic similarity measures for biomedical engineering.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

DOE OSTI2024

Building a FAIR data ecosystem for incorporating single-cell transcriptomics data into agricultural genome to phenome research

Introduction The agriculture genomics community has numerous data submission standards available, but the standards for describing and storing single-cell (SC, e.g., scRNA- seq) data are comparatively underdeveloped. Methods To bridge this gap, we leveraged recent advancements in human genomics infrastructure, such as the integration of the Human Cell Atlas Data Portal with Terra, a secure, scalable, open-source platform for biomedical researchers to access data, run analysis tools, and collaborate. In parallel, the Single Cell Expression Atlas at EMBL-EBI offers a comprehensive data ingestion portal for high-throughput sequencing datasets, including plants, protists, and animals (including humans). Developing data tools connecting these resources would offer significant advantages to the agricultural genomics community. The FAANG data portal at EMBL-EBI emphasizes delivering rich metadata and highly accurate and reliable annotation of farmed animals but is not computationally linked to either of these resources. Results Herein, we describe a pilot-scale project that determines whether the current FAANG metadata standards for livestock can be used to ingest scRNA-seq datasets into Terra in a manner consistent with HCA Data Portal standards. Importantly, rich scRNA-seq metadata can now be brokered through the FAANG data portal using a semi-automated process, thereby avoiding the need for substantial expert curation. We have further extended the functionality of this tool so that validated and ingested SC files within the HCA Data Portal are transferred to Terra for further analysis. In addition, we verified data ingestion into Terra, hosted on Azure, and demonstrated the use of a workflow to analyze the first ingested porcine scRNA-seq dataset. Additionally, we have also developed prototype tools to visualize the output of scRNA-seq analyses on genome browsers to compare gene expression patterns across tissues and cell populations. This JBrowse tool now features distinct tracks, showcasing PBMC scRNA-seq alongside two bulk RNA-seq experiments. Discussion We intend to further build upon these existing tools to construct a scientist-friendly data resource and analytical ecosystem based on Findable, Accessible, Interoperable, and Reusable (FAIR) SC principles to facilitate SC-level genomic analysis through data ingestion, storage, retrieval, re-use, visualization, and comparative annotation across agricultural species.

Genetics & Heredity↗

NASA NTRS2011

An Earthling to an Astronaut: Medical Challenges

Humans can travel safely into space in low Earth orbit (LEO) or to near-Earth objects if several medical, physiological, environmental, and human factors issues risks are mitigated. Research must be performed in order to set standards in these four areas, and current NASA standards are contained in the Space Flight Human System Standards volumes 1 and 2, and crew medical certification standards. These three sets of standards drive all of the clinical, biomedical research and environmental technology development for the NASA human space flight program. These standards also drive the identification of specific risks to crew health and safety, and we currently manage 65 human system risks within the human space flight program. Each risk has a specific program of research, technology development, and development of operational procedures to mitigate the risks. Some of the more important risks tat will be discussed in this talk include exposure to radiation, behavioral health due to confinement in a closed cabin, physiological changes such as loss of bone, muscle and exercise capability, reduction in immune system capability, environmental threats of maintaining an adequate atmosphere and water for drinking, avoidance of toxic or infectious material, protection of hearing, and human factors issues of equipment and task design. A nutritious and varied food supply must also be provided. All of these risks will be discussed and current strategies for mitigating these risks for long-duration human space flight. In mitigating these 65 human system risks, novel approaches to problem solving must be employed to find the most appropriate research and technology based applications. Some risk mitigations are developed internally to NASA while others are found through research grants, technology procurements, and more recently open innovation techniques to seek solutions from the global technical community. Examples and results will be presented from all of these approaches including the more recent use of prizes to stimulate innovation.

Davis, Jeffrey R.↗

DOE OSTI2026

Evaluating the efficiency of touch-spun scaffolds in producing dense cell cultures for tissue engineering applications

Developing efficient scaffolds for long-term cell cultivation remains a challenge in tissue engineering. Biomimetic approaches aim to create a three-dimensional (3D) extracellular matrix (ECM)-like fiber network with a tunable hierarchical structure to promote sufficient cell attachment, differentiation, and overall viability. Among the fiber fabrication methods documented in the literature, mechanical fiber drawing techniques, such as touch-spinning, have garnered significant research interest. This is due to the simplicity of the equipment, the ability to control fiber diameter and interfiber spacing at the nanoscale without the need for external fields, and the absence of specific requirements for material dielectric properties. Despite the advantages of mechanically drawn scaffolds in biomedical research, the methodologies for cell culturing and analysis for these materials have not been adequately addressed. In this study, we assess the potential of touch-spun scaffolds in promoting NIH/3T3-GFP fibroblast cell growth for tissue engineering applications. Polycaprolactone/polyethylene oxide (PCL/PEO)-based fiber arrays with a controlled interfiber spacing of 91.9 ± 25.0 μm (N = 50) were fabricated using a modified touch-spinning apparatus and then assembled into 2D and 3D scaffolds through additive manufacturing technology. A comparative cell analysis conducted for single- and multi-layered structures showed that the 3D touch-spun scaffolds support healthy growth of up to 6.5 million fibroblast cells within 21 days and offer enhanced cell viability compared to conventional 2D fiber scaffolds, as confirmed by the Presto Blue assay. Furthermore, the metabolic activity of fibroblasts on 3D scaffolds assessed by the MTT test is approximately four times higher than that of the positive control, making the 3D touch-spun materials ideal for long-term cell culture applications.

Peranidze, Kristina [University of Georgia, Athens↗

NASA NTRSDate not supplied

Increasing Data Discovery and Re-Use: The Space Life Sciences Ontology

Two of the most important goals of the adoption of the FAIR principles are increasing the ability of agents to find and re-use research data. Achieving these goals for space life sciences research is even more pressing, given the relatively expensive and scarce nature of these data. We have reported in the past on the progress made by exemplar life sciences data systems towards implementing FAIR, showing gaps particularly in the “interoperability area” of the principles; the lack of common conceptual models for space life science research is one reason for this gap. There were few available resources that define, annotate, categorize or otherwise relate various kinds of metadata describing the acquisition, nature, and intent of investigational space life sciences data. To address this gap, NASA is working with the Open Biological and Biomedical Ontology Foundry (https://obofoundry.org/) to develop the Space Life Science Ontology (SLSO) that is intended to support archival and other kinds of systems that operate using these data. The scope of the ontology includes concepts regarding those aspects of investigation design and execution specific or unique to space environments, such as types of specialized equipment, operating organizations, and documentation. The ontology is continually being developed and published to the life science community (https://github.com/nasa/LSDAO/); at the time of this publication, the SLSO newly and uniquely defines 30 types (classes), 90 properties, and 14 relations specific to space life sciences metadata. In addition, the SLSO reuses (imports) some 2,360 types (classes), 49 properties, and 393 relations from other ontologies that are relevant to these kinds of metadata. In addition to its role as a common conceptualization for space biomedical research activities, the SLSO can also be used to provide automated support for traditionally difficult and expensive activities such as data curation and cross-system data integration and analysis.

fair↗

NASA NTRS2005

Cognitive Functioning in Space Exploration Missions: A Human Requirement

Solving cognitive issues in the exploration missions will require implementing results from both Human Behavior and Performance, and Space Human Factors Engineering. Operational and research cognitive requirements need to reflect a coordinated management approach with appropriate oversight and guidance from NASA headquarters. First, this paper will discuss one proposed management method that would combine the resources of Space Medicine and Space Human Factors Engineering at JSC, other NASA agencies, the National Space Biomedical Research Institute, Wyle Labs, and other academic or industrial partners. The proposed management is based on a Human Centered Design that advocates full acceptance of the human as a system equal to other systems. Like other systems, the human is a system with many subsystems, each of which has strengths and limitations. Second, this paper will suggest ways to inform exploration policy about what is needed for optimal cognitive functioning of the astronaut crew, as well as requirements to ensure necessary assessment and intervention strategies for the human system if human limitations are reached. Assessment strategies will include clinical evaluation and fitness-to-perform evaluations. Clinical intervention tools and procedures will be available to the astronaut and space flight physician. Cognitive performance will be supported through systematic function allocation, task design, training, and scheduling. Human factors requirements and guidelines will lead to well-designed information displays and retrieval systems that reduce crew time and errors. Means of capturing process, design, and operational requirements to ensure crew performance will be discussed. Third, this paper will describe the current plan of action, and future challenges to be resolved before a lunar or Mars expedition. The presentation will include a proposed management plan for research, involvement of various organizations, and a timetable of deliverables.

Fiedler, Edan↗

NASA NTRS2003

A National Virtual Specimen Database for Early Cancer Detection

Access to biospecimens is essential for enabling cancer biomarker discovery. The National Cancer Institute's (NCI) Early Detection Research Network (EDRN) comprises and integrates a large number of laboratories into a network in order to establish a collaborative scientific environment to discover and validate disease markers. The diversity of both the institutions and the collaborative focus has created the need for establishing cross-disciplinary teams focused on integrating expertise in biomedical research, computational and biostatistics, and computer science. Given the collaborative design of the network, the EDRN needed an informatics infrastructure. The Fred Hutchinson Cancer Research Center, the National Cancer Institute,and NASA's Jet Propulsion Laboratory (JPL) teamed up to build an informatics infrastructure creating a collaborative, science-driven research environment despite the geographic and morphology differences of the information systems that existed within the diverse network. EDRN investigators identified the need to share biospecimen data captured across the country managed in disparate databases. As a result, the informatics team initiated an effort to create a virtual tissue database whereby scientists could search and locate details about specimens located at collaborating laboratories. Each database, however, was locally implemented and integrated into collection processes and methods unique to each institution. This meant that efforts to integrate databases needed to be done in a manner that did not require redesign or re-implementation of existing system

distributed↗

NASA NTRS2011

Mission Possible: BioMedical Experiments on the Space Shuttle

Biomedical research, both applied and basic, was conducted on every Shuttle mission from 1981 to 2011. The Space Shuttle Program enabled NASA investigators and researchers from around the world to address fundamental issues concerning living and working effectively in space. Operationally focused occupational health investigations and tests were given priority by the Shuttle crew and Shuttle Program management for the resolution of acute health issues caused by the rigors of spaceflight. The challenges of research on the Shuttle included: limited up and return mass, limited power, limited crew time, and requirements for containment of hazards. The sheer capacity of the Shuttle for crew and equipment was unsurpassed by any other launch and entry vehicle and the Shuttle Program provided more opportunity for human research than any program before or since. To take advantage of this opportunity, life sciences research programs learned how to: streamline the complicated process of integrating experiments aboard the Shuttle, design experiments and hardware within operational constraints, and integrate requirements between different experiments and with operational countermeasures. We learned how to take advantage of commercial-off-the-shelf hardware and developed a hardware certification process with the flexibility to allow for design changes between flights. We learned the importance of end-to-end testing for experiment hardware with humans-in-the-loop. Most importantly, we learned that the Shuttle Program provided an excellent platform for conducting human research and for developing the systems that are now used to optimize research on the International Space Station. This presentation will include a review of the types of experiments and medical tests flown on the Shuttle and the processes that were used to manifest and conduct the experiments. Learning Objective: This paper provides a description of the challenges related to launching and implementing biomedical experiments aboard the Space Shuttle.

Bopp, E.↗

NASA NTRS1992

OSSA Space Station Freedom science utilization plans

Long duration exposure to an essentially zero-gravity environment is a phenomenon exclusive to the Space Station Freedom that cannot be duplicated on Earth. The Freedom Station will offer periods of time on orbit extending to weeks and months rather than hours or days, allowing for in-depth space based research and analysis to a degree never before achieved. OSSA remains committed to exploiting the unique capabilities provided by the Space Station as well as other space-based facilities to study the nature of physical, chemical, and biological processes in a low-gravity environment and to apply these studies to advance science and applications in such fields as biomedical research, plant and animal physiology, exobiology, biotechnology, materials science, fluid physics, and combustion science. The OSSA focus is on progressive science investigations, many requiring hands-on scientist involvement using sophisticated experiment hardware. OSSA science utilization planning for the Freedom Station is firmly established. For this presentation, this planning is discussed in three general areas: OSSA goals and overall approach, the current and on-going program, and plans for space station utilization. In the first area, OSSA addresses its overall approach to space science research, its commitment to transition to Space Station Freedom, and its top-level strategy for the utilization of Freedom. The current and on-going program is next discussed, focusing on the various Spacelab series of missions which are providing the stepping-stones to Space Station Freedom. Selected science results from SLS-1 and USML-1 are cited which underline the value of properly outfitted laboratories in space in which crew-intensive experiment interactions are possible. The presentation is concluded with a discussion of top-level goals and strategies for utilizing the Freedom Station by OSSA's Life Sciences Division and its Microgravity Science and Applications Division.

Cressy, Philip J.↗

DOE OSTI2023

The First Virtual Human Global Summit: Prepublication Meeting Report

This is the prepublication report for the First Virtual Human Global Summit held in October 2023. Organized collaboratively by Frederick National Laboratory for Cancer Research, Brookhaven National Laboratory, University College London, and Eviden, the 2023 Virtual Human Global Summit convened global thought leaders to bring together multiple perspectives across domains and organizations. The intent of the Summit was to foster collaboration among key leaders internationally whose combined efforts are required to advance patient-focused precision medicine through medical digital twins. Participants represented cancer and biomedical research, industry, infrastructure, clinical research, community health, non-profit organizations, government, and general public interests. The Summit included over 80 attendees across three continents including native American tribes. The Summit was held to share insights about the state of the art for medical digital twins, provide motivating opportunities and identify key challenges along the path to improved health and wellness through virtual human models and personalized digital twins. The Summit included sessions emphasizing the primary areas of research, infrastructure, clinical application, government support, and adoption/sustainability. Several examples of digital twins were referenced or mentioned through the course of the Summit including digital twin approaches in cancer, radiation oncology, molecular scale digital twins, diabetes, and sepsis. The summit report includes perspectives on the current state, challenges and guidance across research, infrastructure, clinical translation and community adoption, as well as multiple key insights from industry perspectives.

99 GENERAL AND MISCELLANEOUS↗

NASA NTRS1986

Selection of an appropriate animal model for study of bone loss in weightlessness

Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

Wolinsky, I.↗

DOE OSTI2016

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↗

DOE OSTI2016

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↗

DOE OSTI2016

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↗

DOE OSTI2016

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↗

NASA NTRS2024

NASA's Human Research Program: Evolving Collaborations to Enable the Future of Human Spaceflight

Since its formation in 2007, the NASA Human Research Program’s (HRP) mission has been to protect the health and performance of astronauts as they explore beyond low Earth orbit. The HRP helps enable exploration spaceflight through a focused program of research that leads to the development and delivery of solutions to protect human health and performance during and after these missions. This research is conducted primarily in ground analogs of the spaceflight environment and on the International Space Station (ISS). Over the last 3 years, NASA has undergone transformative changes with the flight of Artemis I, the formation of the Commercial Low Earth Orbit Destinations Program, commercial flights to the ISS, and collaboration with new international partners participating in human spaceflight. The HRP has embraced these new opportunities and is collaborating on all these fronts to collect biomedical research data. Artemis I marked the arrival of NASA’s new human spaceflight exploration missions. NASA established the Moon to Mars Program Office to design a roadmap for the exploration of the lunar surface and the journey beyond to Mars. The HRP has a critical role in conducting research and delivering technologies that will lead to solutions that protect human health and performance, and is working closely with the Moon to Mars Office to ensure these deliverables are ready in time to support their strategy. The HRP is also developing the partnership strategies required to support these deliverables. Commercial space flights, both free flyer and suborbital missions and private astronaut missions to the ISS, are providing broader opportunities and more subjects to characterize spaceflight-induced changes to the human system and to test countermeasures. To better use these opportunities to achieve its mission, the HRP has been working to understand the commercial spaceflight companies’ needs and then partnering with them on aspects of mutual interest. In addition, the HRP continues to engage in long-standing relationships with its international partners through the International Space Life Sciences Working Group and other joint international groups. The HRP is interested in sharing its knowledge and collaborating on projects of mutual interest with new countries that are developing capabilities for human spaceflight. The next 10 years will shape how humanity partners on exploration missions to Mars, and the HRP is committed to enabling and developing collaborative strategies with commercial and international partners to keep humans safe and productive as they explore longer and further into space.

Human research↗

NASA NTRS1997

Space Biosensor Systems: Implications for Technology Transfer

To meet the need for continuous, automated monitoring of animal subjects, including; humans, during space flight, NASA is developing advanced physiologic sensor and biotelemetry system technologies. The ability to continuously track basic physiological parameters, such as heart rate, blood pH, and body temperature, in untethered subjects in space is a challenging task. At NASA's Ames Research Center, where a key focus is gravitational biology research, engineers have teamed with life scientists to develop wireless sensor systems for automated physiologic monitoring of animal models as small as the rat. This technology is also being adapted, in collaboration with medical professionals, to meet human clinical monitoring needs both in space and on the ground. Thus, these advanced monitoring technologies have important dual-use functions; they meet space flight data collection requirements and constraints, while concurrently addressing a number of monitoring and data acquisition challenges on the ground in areas of clinical monitoring and biomedical research. Additional applications for these and related technologies are being sought and additional partnerships established that enhance development efforts, reduce costs and facilitate technology infusion between the public and private sectors. This paper describes technology transfer and co-development projects that have evolved out of NASA's miniaturized, implantable chemical sensor development efforts.

Hines, J. W.↗