锰离子增强磁共振成像(MEMRI)技术及其在研究大鼠嗅觉和脑缺血中的应用
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摘要
锰离子增强磁共振成像是近几年发展起来的一种新的磁共振功能成像技术,是显示神经传导路径和研究大脑功能的有力工具。本论文的目的是实现并发展锰离子增强磁共振成像方法,并将该方法应用于研究大鼠嗅觉神经传导和局部脑缺血过程中的钙离子超载过程。
     首先,通过选择合适的脉冲序列、控制锰离子浓度和优化实验设计,用翻转恢复T_1加权序列得到大鼠嗅球高空间分辨率的层状结构图像,并清晰显示了锰离子在嗅球层状结构中的沉积,使得锰离子增强磁共振成像技术可用来研究大鼠嗅觉系统中细微结构的功能。然后,用锰离子增强磁共振成像技术在活体上得到大鼠嗅上皮到嗅球正向神经传导的功能投射关系,表明锰离子增强磁共振成像技术可以用来显示嗅觉神经功能连接。通过观察锰离子在大鼠嗅球层状结构中的传递,发现嗅觉信息是从嗅球外层向内层进行传导,并得到静息状态下锰离子在嗅球层状结构中的传递速率。通过比较静息状态和气味刺激条件下锰离子在大鼠嗅觉系统中的传递速率,揭示了麻醉状态的大鼠对气味刺激也有功能反应,并且气味刺激会加速锰离子在嗅觉通路中的传递,表明锰离子增强磁共振成像技术可以用来研究嗅觉神经功能。最后,我们用锰离子增强磁共振成像技术研究了大鼠局部脑缺血模型中的钙离子超载现象,结果表明缺血过程中存在锰离子沉积的区域小于扩散加权高信号区域,证明该方法可为评判存在不可逆缺血损伤的缺血中心区域提供新的信息。
Recently, there are growing interests in a new functional magnetic resonance imaging technique namely manganese enhanced magnetic resonance imaging (MEMRI), which can be used for tracing neuronal tracts and studying brain functions in vivo. The purposes of the work presented in this dissertation is to implement and develop the MEMRI technique and use it to trace neuronal tracts in the olfactory system of rat and to study the phenomenon of "calcium overloading" in a rat model of focal cerebral ischemia.
    Firstly, after choosing the proper imaging sequences and optimizing the concentration of Mn~(2+) applied and the design of the experiments, we used inversion-recovery prepared T_1-weighted imaging sequence to obtain high spatial resolution images of the olfactory bulbs (OB) in rat, in which the laminar structures of the bulbs can be unambiguously identified. The high spatial resolution images of the OB enable us to study the transportation of Mn~(2+) ion among the laminar structures of the OB. The transportation rate of Mn~(2+) among the laminar structures was shown to be approximately 0.2 mm/hour under resting condition.
    Secondly, we used MEMRI to trace anterogradely neuronal projections from the olfactory epithelium (OE) to the OB in rat. Our results agreed well with what predicted by the well-known "zone-to-zone" and "glomerular convergence" principles. We compared the transportation rates of Mn~(2+) along the olfactory pathway under resting condition and under odor stimulation. It was found that, even in urethane-anesthetized rats, Mn~(2+) moves faster in the olfactory pathway when under odor stimulation.
    Finally, we used MEMRI to monitor the so-called "calcium overload" in a rat model of focal cerebral ischemia. It was found that the total area of brain regions with Mn~(2+) accumulation was less than the area of the ischemic brain regions shown by diffusion-weighted imaging (DWI). We suggest that MEMRI can provide a new dimension of information in the early detection of ischemic core and in identifying ischemic penumbra.
引文
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    1. Lin, Y.J.and Koretsky, A.P., Manganese ion enhances.T_1-weighted MRI during brain activation: an approach to direct imaging of brain function.Magn Reson Med, 1997.38(3): p.378-88.
    2. Silva, A.C., Lee, J.H., Aoki, I., et al., Manganese-enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations.NMR Biomed, 2004.17(8): p.532-43.
    3. Koretsky, A.P.and Silva, A.C., Manganese-enhanced magnetic resonance imaging (MEMRI).NMR Biomed, 2004.17(8): p.527-31.
    4. Pautler, R.G., Silva, A.C., and Koretsky, A.P., In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging.Magn Reson Med, 1998.40(5): p.740-8.
    5. Pautler, R.G and Koretsky, A.P., Tracing odor-induced activation in the olfactory bulbs of mice using manganese-enhanced magnetic resonance imaging.Neuroimage, 2002.16(2): p.441-8.
    6. Cross, D.J., Minoshima, S., Anzai, Y., et al., Statistical mapping of functional olfactory connections of the rat brain in vivo.Neuroimage, 2004.23(4): p.1326-35.
    7. Schoenfeld, T.A.and Knott, T.K., Evidence for the disproportionate mapping of olfactory airspace onto the main olfactory bulb of the hamster.J Comp Neurol, 2004.476(2): p.186-201.
    8. Land, L.J., Localized projection of olfactory nerves to rabbit olfactory bulb.Brain Res, 1973.63: p.153-66.
    9. Nezlin, L.P.and Sehild, D., Individual olfactory sensory neurons project into more than one glomerulus in Xenopus laevis tadpole olfactory bulb.J Comp Neurol, 2005.481(3): p.233-9.
    10. Levai, O., Breer, H., and Strotmann, J., Subzonal organization of olfactory sensory neurons projecting to distinct glomeruli within the mouse olfactory bulb.J Comp Neurol, 2003.458(3): p.209-20.
    11. Royal, S.J.and Key, B., Development of P2 olfactory glomeruli in P2-internal ribosome entry site-tau-LacZ transgenic mice.J Neurosci, 1999.19(22): p.9856-64.
    12. Conzelmann, S., Levai, O., Bode, B., et al., A novel brain receptor is expressed in a distinct population of olfactory sensory neurons.Eur J Neurosci, 2000.12(11): p.3926-34.
    1. Lin, Y. J. and Koretsky, A. P., Manganese ion enhances T_1-weighted MRI during brain activation: an approach to direct imaging of brain function. Magn Reson Med, 1997. 38(3): p. 378-88.
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