Lithium-7 MR Studies of Rat Brain at 7 Tesla

描述（由申请人提供）：锂（Li）对治疗双相情感障碍和反复发作的躁狂症有效。由于Li是一种CMS药物，其在脑中的浓度可能与临床反应更密切相关。锂离子在脑内的分布对锂离子治疗及其在脑内作用的定位具有重要意义。因此，有必要对脑内Li浓度进行体内测量。磁共振（MR）是一种不涉及任何电离辐射或放射性同位素的方法，可用于在体内对Li进行非破坏性观察。作为量化和绘制脑锂总体目标的一部分，我们将开发Li核在特定吸收辐射（SAR）限制下的核Overhauser增强光谱成像（SI）。进一步的发展将采用更短的大脑线圈在正交模式下操作。该方法的优化将包括：a)体积定位和b)在SI数据收集之前的外部体积饱和。用最优的方法测量大鼠脑中的Li强度。然后根据点扩散函数（PSF）引起的强度变化对SI数据进行校正。浓度是通过将强度与来自已知浓度的幻影的等效体素的强度进行比较而获得的。最后，将MR方法与原子吸收法（AA）等“金标准”进行验证，并建立两种方法之间的一致性。新验证的方法将用于绘制Li通过大脑的不同阶段在大鼠大脑中的分布。区域药代动力学将从与双相情感障碍相关的广泛解剖领域进行研究。

DESCRIPTION (provided by applicant): 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.