Photonics Monitoring and Modeling Core Abstract The Photonics Monitoring and Modeling Core (PMMC) consists of three core photonics based novel diagnostic technologies and a highly monitored mid-size animal model (rabbit) testing facility based at the University of California, Irvine, Beckman Laser Institute that support investigations at UC Irvine, UC San Diego, and the University of Colorado. The Core will provide all investigators with photonics technologies across all animal models to enable accurate, precise, quantitative and semi-quantitative, high-resolution imaging and monitoring capabilities in-vivo. The Core will provide technology and support at the U. C. Irvine rabbit testing facility, as well as in laboratories at the U. of Colorado for inhalation injury small animal studies (Drs. White, Veress), and Large Animal Core projects (Dr. Bebarta), supporting projects 1 (methyl isocyanate), 2 (mustard), 3 (methylmercaptan), and 4 (cyanide). The Core photonics based technologies include: 1) swept-source optical coherence tomography for real-time, fiber optic, micron resolution, 3-D imaging of airways for assessment of acute and chronic airway injury for chronic mustard exposure and methyl isocyanate exposures in rats and pigs (projects 1, 2 and the Large Animal Core), 2) diffuse optical spectroscopy and continuous wave near infrared spectroscopy for assessment of effects of the metabolic poisons, cyanide and methylmercaptan, and monitoring of tissue oxygenation and Cytochrome C oxidase redox states in the rabbit and swine models (projects 3 and 4), and 3) real-time micro-sensors for continuous tissue lactate monitoring in animals with metabolic poison exposures (projects 3, 4, and the Large Animal Core). The core will also provide state-of-the-art rabbit testing facility and established core models for metabolic agent antidote development supporting projects 3 and 4. Advanced technology capabilities will be extended to the U. of Colorado as part of the PMMC deliverables, and will function there in addition to their ongoing availability in the photonics testing facility and animal operating rooms at UC Irvine Beckman Laser Institute. As shown in our prior chemical defense research, these core technologies enable more accurate, precise, and noninvasive determination of injury and treatment effectiveness, dramatically accelerating antidote development and reducing animal numbers required for definitive results. Thus, the Core is integrally involved in Projects 1, 2, 3, 4, the Large Animal Core, and in the overarching structure of this ?pipeline from in-vitro, to small animal, to moderate and large animal? accelerated chemical agent antidote drug development proposal.

Public Health Relevance

Humans exposed to poisonous chemicals through accidents or acts of terrorism can suffer great pain, permanent injuries and death. This project will provide advanced technologies and models to discover and develop antidotes for poisonous chemical exposure injuries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54ES027698-02
Application #
9357597
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Rancourt, Raymond C; Rioux, Jacqueline S; Veress, Livia A et al. (2018) Methyl isocyanate inhalation induces tissue factor-dependent activation of coagulation in rats. Drug Chem Toxicol :1-7
McGraw, Matthew D; Dysart, Marilyn M; Hendry-Hofer, Tara B et al. (2018) Bronchiolitis Obliterans and Pulmonary Fibrosis after Sulfur Mustard Inhalation in Rats. Am J Respir Cell Mol Biol 58:696-705
Fukuda, Satoshi; Enkhbaatar, Perenlei; Nelson, Christina et al. (2018) Lack of durable protection against cotton smoke-induced acute lung injury in sheep by nebulized single chain urokinase plasminogen activator or tissue plasminogen activator. Clin Transl Med 7:17
Idell, Steven; Rahman, Najib M (2018) Intrapleural Fibrinolytic Therapy for Empyema and Pleural Loculation: Knowns and Unknowns. Ann Am Thorac Soc 15:515-517
Logue, Brian A; Zhang, Zhiling; Manandhar, Erica et al. (2018) Determination of methyl isopropyl hydantoin from rat erythrocytes by gas-chromatography mass-spectrometry to determine methyl isocyanate dose following inhalation exposure. J Chromatogr B Analyt Technol Biomed Life Sci 1093-1094:119-127
Miao, Yusi; Jing, Joseph C; Desai, Vineet et al. (2018) Automated 3D segmentation of methyl isocyanate-exposed rat trachea using an ultra-thin, fully fiber optic optical coherence endoscopic probe. Sci Rep 8:8713
Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M et al. (2018) Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats. Am J Respir Cell Mol Biol 58:107-116
McGraw, Matthew D; Osborne, Christopher M; Mastej, Emily J et al. (2017) Editor's Highlight: Pulmonary Vascular Thrombosis in Rats Exposed to Inhaled Sulfur Mustard. Toxicol Sci 159:461-469
Anantharam, Poojya; Whitley, Elizabeth M; Mahama, Belinda et al. (2017) Cobinamide is effective for treatment of hydrogen sulfide-induced neurological sequelae in a mouse model. Ann N Y Acad Sci 1408:61-78
Summerhill, Eleanor M; Hoyle, Gary W; Jordt, Sven-Eric et al. (2017) An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness. Ann Am Thorac Soc 14:1060-1072

Showing the most recent 10 out of 13 publications