Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging

Lithium (Li) and its salts have been demonstrated to be the most effective drug in both acute and prophylactic treatment of bipolar disorder. The exact molecular mechanisms and particular target regions accounting for its mood-stabilizing effect remain unknown. Knowledge of Li distribution and its regional pharmacokinetic properties in the living brain is of value in localizing its action in the brain. Pharmacokinetic measurements in different anatomical regions of the human brain are not yet available. Limited pharmacokinetic measurements in rat brain subvolumes have been performed using atomic absorption technique. However, a noninvasive way of estimating the pharmacokinetics in different regions of the brain where the drug exerts its beneficial effects would allow such methods to be used in the study of patients undergoing Li therapy. Earlier (7)Li MR studies on rat brain regions have provided preliminary pharmacokinetic information from the whole brain. Using (7)Li MR spectroscopic imaging (SI) technology, Li distribution in brain regions of the rat at therapeutic dosages has been recently demonstrated by us. Here we report feasibility of local pharmacokinetic measurements on brain regions obtained by magnetic resonance SI technology. Our results suggest that Li is most active in a region stretching from the anterior cingulate cortex and striatum to the caudal midbrain, with greatest activity including the preoptic area and hypothalamic region. Some activity was seen in prefrontal cortex, but only minimal amounts in the region of the cerebellum and metencephalic brainstem.     

NMR Studies of Intra- and Extracellular Red Blood Cell Lithium by Transverse Relaxation Measurements and Shift Reagents

Lithium salts are used in the treatment and prophylaxis of bipolar or mood disorders. The mechanism of action by which the cation exerts its therapeutic influence is unknown. A knowledge of brain Li concentration, its distribution in the brain, and its properties in the cellular microenvironment may have a strong influence on the understanding of Li function. The differentiation of lithium in the intra and extracellular environments has been achieved in a noninvasive manner in red blood cell (RBC) model. The two distinct transverse relaxation (T₂) components have been observed in the blood sample drawn from lithium treated rats. These results indicate two different environments for Li with a fast (T_2f) and a slow (T_2s) component in the RBC model corresponding fractions that contribute to each relaxation component. The results compare well with the intra- and extracellular RBC lithium measured using shift reagents. Our studies indicate that the T₂ method has utility in estimating the intracellular Li in systems that exhibit similar T₂ behavior. The studies performed at different Li doses in the rat model indicate that the method may have utility in following a wide range of intracellular Li.     

Measurement of the ~2H(~7Be,~6Li)~3He reaction rate and its contribution to the primordial lithium abundance

In the standard Big Bang nucleosynthesis(SBBN) model, the lithium puzzle has attracted intense interest over the past few decades, but still has not been solved. Conventionally, the approach is to include more reactions flowing into or out of lithium, and study the potential effects of those reactions which were not previously considered.~7Be(d,~3He)~6Li is a reaction that not only produces~6Li but also destroys~7Be, which decays to~7Li, thereby affecting~7Li indirectly. Therefore, this reaction could alleviate the lithium discrepancy if its reaction rate is sufficiently high.However, there is not much information available about the~7Be(d,~3He)~6Li reaction rate. In this work, the angular distributions of the~7Be(d,~3He)~6Li reaction are measured at the center of mass energies Ecm = 4.0 Me V and 6.~7Me V with secondary~7Be beams for the first time. The excitation function of the~7Be(d,~3He)~6Li reaction is first calculated with the computer code TALYS and then normalized to the experimental data, then its reaction rate is deduced. A SBBN network calculation is performed to investigate its influence on the~6Li and~7Li abundances. The results show that the~7Be(d,~3He)~6Li reaction has a minimal effect on~6Li and~7Li because of its small reaction rate. Therefore,the~7Be(d,~3He)~6Li reaction is ruled out by this experiment as a means of alleviating the lithium discrepancy.     

HT-7装置液态锂限制器实验中锂的腐蚀与沉积特性的研究

在磁约束聚变等离子体装置中, 面对等离子体的第一壁将直接影响高温等离子体性能及第一壁寿命, 具有表面自我修复的、能有效抑制边界粒子再循环的液态金属锂第一壁越来越被重视, 其中液态锂第一壁与等离子体相互作用的研究尤其重要. 本文研究了HT-7装置液态锂限制器实验中锂的表面腐蚀及在装置内沉积特性、及其对等离子体性能影响. 实验表明, 当锂与等离子体相互作用较弱时, 锂以微弱的蒸发及溅射形式从表面腐蚀并进入等离子体, 表现为锂的线辐射有所增强, 等离子体内杂质水平降低, 氢再循环降低, 有利于等离子体约束性能提高; 当锂与等离子体间的相互作用比较强时, 锂主要以锂滴形式直接进入等离子体, 引起锂的辐射爆发, 最终引发等离子体放电破裂. 通过对锂斑及样品的分析发现, 锂主要沉积在限制器周围, 并且在低场侧及沿着等离子体电流方向沉积居多, 表现为极向和环向分布不均匀, 这也导致边界粒子再循环分布的不均匀. 这些实验为研究液态锂第一壁与等离子体相互作用, 分析液态锂第一壁在托卡马克装置上应用具有重要参考意义.     

Applications of (7)Li NMR in biomedicine

The applications of (7)Li NMR spectroscopy and imaging in biology and experimental medicine have been progressing steadily. The interest derives primarily from the clinical use of Li salts to treat mania and manic-depressive illness. One area of investigation is ionic transport across the cellular membrane and compartmentation, so as to elucidate the mechanism(s) of therapeutic action and toxicity in clinical practice. The second is the development of a noninvasive, in vivo analytical tool to measure brain Li concentrations in humans, both as an adjunct to treatment and as a mechanistic probe. Here we review progress to date in this area.     

7Li MR measures of blood lithium--correlation with chemical analysis data

Lithium is used in the treatment and prophylaxis of manic-depressive illness. A narrow therapeutic range of lithium (0.4-1.2 meq/l) requires constant monitoring of these levels to avoid neurotoxicity and overdose. It is general practice to measure plasma lithium levels as a guide to monitor the therapy. Efforts to predict the concentration of Li at its active sites in the brain have led to the use of red blood cells (RBCs) because they are similar to neuronal cells. Thus RBC lithium is a very relevant clinical parameter for monitoring therapy and to observe the changes at intracellular levels under varying treatment conditions. A measure of both plasma and RBC lithium may be of significant value to physicians and researchers as lithium profile for RBCs correlate more closely with the brain lithium than plasma lithium. Although methods to measure lithium in blood such as atomic absorption or flame photometry exist, a complete quantitation of both plasma and RBC lithium requires a tedious physical separation of the two components prior to chemical analysis. On the other hand, lithium MR technique, via the use of shift reagents, can provide both plasma and RBC lithium in a single study. Here we have performed a correlation study of lithium results obtained from MR with the vitros dry-slide method on blood samples from rats treated with lithium. The results show a high degree of correlation between the two methods. Additionally, the MR measurements made on dilute samples of blood indicate that small blood samples with lithium concentration in the neighborhood of 0.08 meq/l can be measured with high accuracy and reproducibility needed for clinical purposes.     

A study on the influence of ethanol over the primary cultured rat cortical neurons by using the scanning electron microscopy

As an inhibitor and toxic factor of central nervous system, ethanol inhibits the action of the neurons and causes various kinds of neuronal damage. However, the precise mechanisms that ethanol-induced neuronal damage in the central nervous system remain unclear. In spite of thousands of published studies, little information is available on the neurons' morphological alteration in the central nervous system. In this study, we investigated the morphological alterations of the primary cultured rat cortical neurons after they were treated by different concentrations of ethanol using the scanning electron microscopy. Our results showed that the moderate or high concentration of ethanol could lead to morphological changes of these cultured rat cortical neurons, and they were closely associated with the duration of time. Our study will provide a new base for further studies on the effects of ethanol in the central nervous system.     

Inorganic solid Li ion conductors: An overview

This short review presents the state-of-the-art knowledge on crystalline, composite and amorphous inorganic solid lithium ion conductors, which are of interest as potential solid electrolytes in lithium batteries and might replace the currently used polymeric lithium ion conductors. The discussion of crystalline Li ion conductors includes perovskite-type Lithium Lanthanum Titanates, NASICON-type, LiSICON- and Thio-LiSICON-type Li ion conductors, as well as garnet-type Li ion conducting oxides. The part on composite Li ion conductors discusses materials containing oxides and mesoporous oxides. In the amorphous Li ion conductor part, mechanical attrition of Li compounds, oxide and sulfide-based glasses as well as LIPON and related systems are presented.     

Reduced side-lobe Airy beams

The primary interest in the finite-energy Airy beam derives from the special properties possessed by the maximum intensity at its central lobe. However, the defining spatial dependence, the Airy function, is an oscillatory function that consists of decaying side lobes. For some applications these side lobes may create deleterious effects. Fortunately, a nonsymmetric apodization of the beam in Fourier space is shown to enhance the central lobe as the side lobes are reduced and clipped. The properties of the central lobe are unaffected over a large proportion of the propagation path.     

Molecular dynamics calculation on three lithium atoms in planar cluster model C150H30 for glassy carbon

As the preliminary step to elucidate the charge-discharge mechanism in the glassy carbon cathode of lithium (Li) secondary battery, the molecular dynamics (MD) calculation was applied at molecular mechanics 2 (MM2) level for three Li atoms stabilized in the form of regular triangle in the central area of the hydrogen terminated planar cluster, C₁₅₀H₃₀. The stabilized Li sites are given on the basis of the structural optimization. Up to 10 K, the triangular Li aggregate kept at almost the same figure as that formed by three stabilization sites, rotating parallel to the cluster plane, goes around the central area of it, whereupon interatomic vibrational stretching is observed. Below 75 K, the aggregate of three Li atoms separates to a pair of two atoms and one Li atom arbitrarily, however, reformation of the pair occurs periodically among three atoms with the lapse of simulation time. Then, three Li atoms move correlatively irrespective of the long interatomic distance of 18 Å at maximum. However, at 100 K one Li atom goes out of the cluster model directly and the rest of two atoms continues the revolutional movement with the rotation as a pair in the central area of the cluster model. Thus, three Li atoms show the appreciably stable movements in the glassy carbon by forming the aggregate or the atomic pair, which will be responsible for the hysteresis in the charge-discharge cycle of lithium secondary battery.     

锂离子电池硅基负极材料嵌锂行为的第一性原理研究

采用基于密度泛函理论的第一性原理平面波赝势方法,计算不同数量的锂离子引起的硅材料晶体结构的变化以及在嵌锂过程中形成Li_xSi(x=1、2、2.4、4.4)合金相的形成能与电子结构.采用LST/QST方法计算过渡态,模拟合金体相中的锂离子迁移过程.计算结果表明,随着嵌锂数量的增加,硅晶胞的体积在不断增大;Li_xSi合金相的形成能为负值,表明在嵌锂过程中锂离子和硅原子可以自发形成这些合金相,其中Li₇Si₃合金最容易形成;随着嵌锂量的增加,锂离子在费米能级处s轨道提供的电子数逐渐增加,锂硅合金在费米能级处的电子数量呈增大趋势,表明锂硅合金的导电性越来越优;常温下Li₂Si体相中很难直接形成锂离子空位,但锂离子空位的迁移过程很容易发生.     

Tomographic study of the three-dimensional distribution of a high-fluence implant in a polymer

6 Li⁺ ions were implanted into PMMA at high flux up to fluences of 1×10¹⁵ cm^-2 under angles of 0° to 70° towards the surface normal. The Li depth distributions were determined by means of neutron depth profiling, and compared with theoretical simulations. The three-dimensional Li distribution was reconstructed from the one-dimensional depth profiles by means of a tomographic technique. It turned out that the measured Li depth distributions can be described by a superposition of Gaussian and exponential functions. This points at considerable Li mobility during or after the ion implantation, with trapping in unsaturable traps in the ion-irradiated region which roughly follow the electronic energy transfer distribution. The Li redistribution is more pronounced along the track direction than transversely to it. The normalized Li distributions in various implantation directions were fed into our tomographic program to reconstruct the three-dimensional distribution of the deposited lithium. As expected, the lithium preferentially distributes along the ion tracks. This work is another hint that mobility of implanted ions in solids does not proceed isotropically, but is strongly influenced by the radiation-damage distributions. Received: 11 May 1998 / Accepted: 9 September 1998 / Published online: 24 February 1999     

Study of the primordial lithium abundance

Lithium isotopes have attracted an intense interest because the abundance of both 6Li and 6Li from big bang nucleosynthesis (BBN) is one of the puzzles in nuclear astrophysics. Many investigations of both astrophysical observation and nucleosynthesis calculation have been carried out to solve the puzzle, but it is not solved yet. Several nuclear reactions involving lithium have been indirectly measured at China Institute of Atomic Energy, Beijing. The Standard BBN (SBBN) network calculations are then perfo...     

10B-editing 1H-detection and 19F MRI strategies to optimize boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumours. It is based on the nuclear reaction (10B + n th --> [11B*] --> alpha + 7Li + 2.79 MeV) that occurs when 10B captures a thermal neutron to yield alpha particles and recoiling 7Li nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the selective accumulation of the 10B carriers in the tumour and on the high thermal neutron capture cross-section of 10B. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through 10B nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-borono-phenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the 19F-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double-resonance 10B-editing 1H-detection sequence, named M-Bend, exploiting the J-coupling interaction between 10B and 1H nuclei. Conversely, the BPA map was obtained by 19F-BPA using 19F-MRI. Both images were obtained at 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure.     

fMRI在经颅直流电刺激研究中的应用进展

经颅直流电刺激（tDCS）是一种新颖的神经系统疾病治疗手段,可非侵入性调控中枢神经活动.它具有安全、成本低、疗效显著等特点,因此在神经科学等领域被大量研究和应用.功能磁共振成像（fMRI）具备高时空分辨率的优势,近年来被广泛用于tDCS治疗效果的评估及其作用机制的研究.本文从临床研究与动物模型实验两方面总结fMRI技术应用于tDCS研究中的最新进展,并讨论其应用前景.     

A spatiotemporal study on the distribution of intraperitoneally injected nitroxide radical in the rat head using an in vivo ESR imaging system

We have developed a rapid-scan in vivo electron spin resonance (ESR) imaging system operating at 700 MHz based on an air-cored two-coil Helmholtz designed resistive magnet. Using this system, we performed ESR-CT for the intraperitoneally injected nitroxide radical, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, in the rat head. The imaging data were collected over the time course range from 5 to 47 min after injection at an interval of 3 min and a series of ESR-CT images were reconstructed at the same slice plane (1 cm anterior to interaural line). The series of ESR-CT images thus obtained by rapid scans provided detailed spatiotemporal information on the distribution of the injected nitroxide radical in the rat head. The brain was imaged as a nitroxide-deficient area while the blood vessels and/or extracranium tissues as a nitroxide-rich area. During periods when high intensities of ESR signals were maintained, spots of nitroxide-accumulation were imaged at the central part of the brain. The spots were assigned to the middle sized blood vessels in the brain.     

Charge-changing cross sections of the neutron-rich isotopes8,9,11Li

Total charge-changing cross sections have been measured for⁸Li on C and Pb targets, for⁹Li on C, Al, Cu, Sn and Pb targets, as well as for¹¹Li on C, Sn and Pb targets at about 80 MeV/nucleon. These data are compared to measured total reaction cross sections and Glauber-type calculations using Hartree-Fock density distributions. These comparisons allow to draw conclusions on the proton density distribution of the neutronrich lithium isotopes. The results show that even for the most exotic nucleus¹¹Li the proton distribution is only very weakly influenced by the long tail in the neutron density distribution already established in several experiments.     

Study of the primordial lithium abundance

Lithium isotopes have attracted an intense interest because the abundance of both ⁶Li and ⁷Li from big bang nucleosynthesis (BBN) is one of the puzzles in nuclear astrophysics. Many investigations of both astrophysical observation and nucleosynthesis calculation have been carried out to solve the puzzle, but it is not solved yet. Several nuclear reactions involving lithium have been indirectly measured at China Institute of Atomic Energy, Beijing. The Standard BBN (SBBN) network calculations are then performed to investigate the primordial Lithium abundance. The result shows that these nuclear reactions have minimal effect on the SBBN abundances of ⁶Li and ⁷Li.     

A detection-theoretic framework for modeling informational masking

There has been growing interest in recent years in masking that appears to have its origin at a central level of the auditory nervous system-so-called informational masking (IM). Masker uncertainty and target-masker similarity have been identified as the two major factors affecting IM; however, no theoretical framework currently exists that would give precise meaning to these terms necessary to evaluate their relative importance or model their effects. The present paper offers a first attempt at such a framework constructed within the doctrines of the theory of signal detection.     

磷酸铁锂正极材料的研究进展

锂离子电池正极材料磷酸铁锂(LiFePO4)的理论比容量为170mAh·g-1,电压平台为3.5V(vs.Li/Li+),安全性好,原材料来源丰富,成本低,对环境友好,因此成为当前研究热点之一.文章从LiFePO4的晶体结构和充放电机制入手,分析了其导电性和倍率性能差的原因,回顾了其充放电机制研究的进展,综述了各种改善LiFePO4导电性、提高其倍率性能的方法,最后对LiFePO4正极材料的研究方向进行了展望.