PHYSIOLOGICAL MR STUDIES USING HYPERPOLARIZED 129XE

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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.