This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lithium (Li) is efficacious in the treatment of bipolar illness and recurrent episodes of mania. Since Li is a CMS drug, its concentration in the brain might be expected to relate more closely to clinical response. The distribution of lithium in the brain is of importance in Li therapy and in localizing its action in the brain. Thus, an in vivo measure of brain Li concentration is necessary. Magnetic resonance (MR), a method that does not involve any ionizing radiation or radioactive isotopes, can be used to observe Li non-destructively in an in vivo setup. As a part of the overall goal to quantify and map brain lithium, we will develop Spectroscopic Imaging (SI) with nuclear Overhauser enhancement of Li nucleus under the limits of Specific Absorbed Radiation (SAR). Further developments will be undertaken using shorter brain only coil operating in the quadrature mode. Optimization of the method will include: a) volume localization and b) outer volume saturation prior to SI data collection. Li intensities in the rat brain will be measured using the most optimal method. The SI data are then corrected for Point Spread Function (PSF) induced intensity changes. Concentrations are obtained upon comparing the intensities with those from equivalent voxels from a phantom of known concentration. Finally, the MR method will be validated against the """"""""gold standard"""""""" such as atomic absorption (AA) method and the agreement between the two methods established. The newly validated methodology will be used to map out Li distribution in the rat brain at different stages of Li passage through the brain. Regional pharmacokinetics will be studied from broad anatomical areas of relevance to bipolar illness.
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