Characterization of In-Vivo 1H-NMR Biomarkers for Pulmonary Phospholipidosis
EMSL Project ID
17497
Abstract
The primary goal of this project is to test the potential utility of slow MAS 1H-NMR methods for directly monitoring pulmonary phospholipid accumulation in live animals and in real-time. It is anticipated that the direct biochemical analysis of lung tissue will eliminate the many problems associated with ex vivo sample preparation. This may greatly improve current understanding of the potential health risks associated with its induction by either inhaled materials and/or pharmacological agents.To carry out the proposed work, mice will be used as test animals, silica dust will be used as model particulate matter (PM), and standard laboratory evaluations on excised lung tissues will be carried out to validate in vivo slow-MAS results. Additionally, standard magnetic resonance imaging of the lungs of mice prior to and after silica exposure will be performed to detect any accompanying inflammation. Work is also proposed using cell cultures from other projects in this focus area in order to more fully integrate research efforts with ongoing activities. For this, more traditional high-resolution NMR techniques will be employed, including the use of (13C, or 15N) isotope enriched substrates to obtain the metabolite profile of cell cultures from related projects. Slow-MAS NMR will also be employed to study dense cell systems or cell aggregates where standard NMR fails. It is expected that a link between the onset pulmonary phospholipidosis in animals and that in cultured cells from in vitro studies will be established by using such an integrated approach. Finally, the noninvasive NMR methods (both slow-MAS NMR and MRI) will be applied to study pulmonary response of live mice exposed to other PMs such as silica coated with lipopolysaccharide (LPS) and biological/zoonotic agents, initially using Yersinia ruckeri, the enteric redmouth disease bacterium found in fish.
Project Details
Project type
Capability Research
Start Date
2006-04-18
End Date
2007-05-21
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members