Project: Research project

Project Details


The noble gas xenon is a safe and effective general anesthetic. Rapidly
absorbed via the lung into the blood-stream, it concentrates in lipid-
rich tissue with a time-dependence related to blood flow. A major
isotope, Xe, has a spin 1/2 nucleus with a chemical shift remarkably
sensitive to van de Waals environment (range, 300 ppm). Its T and T
values are quite sensitive to O2 concentration and other factors. The
crucial point is that, prior to administration, Xe can readily be
hyperpolarized, 105-106 fold by spin exchange with optically pumped
rubidium: its NMR signal strength (and thus time and space resolution)
at 20 mM, would be comparable to that of tissue water proton at 80-100
M: This unique property of Xe, as well as its distinctly different
behavior compared to H2O in(a) cell and tissue compartmentalization, (b)
and subcellular exchange kinetics, will provide a new adequate quantities
of hyperpolarized Ce (Xet). Procedures for imaging, Combined
Spectroscopy and Imaging (CIS), and image-guided analysis of local T and
T probability distributions (Relaxography), well-established in our
laboratory for H and Na, will be applied to the new modality. Parameters
for determining and optimizing time and space resolution will be obtained
using pattern-drilled Teflon phantoms for Xegas. Parameters for CSI will
be obtained using a water-octanol-gas phantom. Overall behavior in the
mouse will assayed in several large voxels-the lung gas space, the whole
brain, and a large muscle. The dynamics of Xe exchange,
compartmentalization and relaxation at the cellular and subcellular level
will be determined from the behavior of the chemical shift, line shape,
T and T2 in nonimaging studies of model systems of hierachiacal
complexity, for a range of O2 concentrations. The dynamics of transport,
distribution, and lifetime of Xe in the mouse and rat in vivo will be
investigated in other major organs, and peripheral tissues. The
pharmacokinetics behavior of an anesthetic is important in its own right.
Finally, three well-known mouse and rat paradigms will be studied (a)
effects of hypoxia, hyperopia and hypercapnia (excess CO2) on blood flow
and Xe in brain and elsewhere; (b) effects of stimulating individual
mystical vibrissae (facial whiskers) on Xe in the 'barrel field' area of
the somatosensory region of the mouse brain; (c) effect on Xe images
(correlated with H imaging and CONTIN analysis of T) of development of
tumors following injection of 2X10 KHT sarcoma cells into the mouse
gastrocnemius, and similar studies with a metastasizing adenocarcinoma
and a brain glioma.
Effective start/end date4/1/943/31/00


  • National Institutes of Health: $171,266.00
  • National Institutes of Health: $288,452.00


  • Medicine(all)


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