The spin- + nuclei of 129 Xe can be """"""""hyperpolarized"""""""" to 10 5 times their thermal equilibrium value, by spin-exchange collisions with Rb atoms that have been """"""""optically pumped"""""""" by circularly polarized light entirely into one electron spin state. The enhanced signal from hyperpolarized 129 Xe makes it an intriguing MR probe. The field has developed considerably in the past three years, since the PI and collaborators invented hyperpolarized Xe-MRI (HypX-MRI) by acquiring MR images of excised mouse lungs that had been inflated with hyperpolarized 129 Xe. Improved lung space imaging has been demonstrated by others, using the stronger signal from hyperpolarized 3He, but 129 Xe is the more interesting nucleus, since its high lipid solubility renders it a promising probe of organs and tissues. We propose to develop the novel technology of HypX-MRI into a research and diagnostic tool for the study of the states of the brain, with the specific intention of elucidating brain function and pathology. Xenon's lipophilicity, its high sensitivity to its environment, and its high detectable after hyperpolarization, allow for the design of experimental approaches radically different from those used in conventional MRI. Inhaled 129Xe rapidly diffuses into the pulmonary blood and is distributed to distal tissues by the circulation. Successful hyperpolarized 129 Xe MRI and spectroscopy of the brain crucially depends on whether the T 1 of 129 Xe in blood is long enough for sufficient magnetization to reach the target tissue. Our measurement of a sufficiently long T 1 (13.5 sec) in oxygenated blood encourages HypX-MRI studies of brain tissue. We propose to develop HYPX- MRI into a sensitive, non-invasive, and quantitative method for mapping functional activity of the brain, through measuring regional cerebral blood flow (rCBF), and through the sensitivity of 129 Xe's MR parameters to the environment. Xenon's differential solubility in the white and gray matter of the brain, and its large range of chemical shift and relaxation times in different environments, also suggests that HypX-MRI may be useful in delineation of various brain pathologies. After constructing a laser-based optical-pumping system to routinely accumulate liter-large quantities of hyperpolarized 129 Xe, it will be interfaced with a storage and delivery system. Special pulse sequences will be developed to best utilize the large, but non-renewable, magnetization which is a special feature of hyperpolarized noble gasMR studies. HypeX MR investigations, in vivo, using animals should permit evaluation of the feasibility of using this novel technique to study rCFB and brain function, and a variety of neurological and psychiatric brain disorders, in humans.
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