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迈向大鼠脑内活体动态同位素异构体分析:使用LCModel对13C NMR谱进行自动定量分析

Toward dynamic isotopomer analysis in the rat brain in vivo: automatic quantitation of 13C NMR spectra using LCModel.

作者信息

Henry Pierre-Gilles, Oz Gülin, Provencher Stephen, Gruetter Rolf

机构信息

Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota Medical School, 2021 6th Street SE, Minneapolis, MN 55455, USA.

出版信息

NMR Biomed. 2003 Oct-Nov;16(6-7):400-12. doi: 10.1002/nbm.840.

DOI:10.1002/nbm.840
PMID:14679502
Abstract

The LCModel method was adapted to analyze localized in vivo (13)C NMR spectra obtained from the rat brain in vivo at 9.4 T. Prior knowledge of chemical-shifts, J-coupling constants and J-evolution was included in the analysis. Up to 50 different isotopomer signals corresponding to 10 metabolites were quantified simultaneously in 400 microl volumes in the rat brain in vivo during infusion of [1,6-(13)C(2)]glucose. The analysis remained accurate even at low signal-to-noise ratio of the order of 3:1. The relative distribution of isotopomers in glutamate, glutamine and aspartate determined in vivo in 22 min was in excellent agreement with that measured in brain extracts. Quantitation of time series of (13)C spectra yielded time courses of total (13)C label incorporation into up to 16 carbon positions, as well as time courses of individual isotopomer signals, with a temporal resolution as low as 5 min (dynamic isotopomer analysis). The possibility of measuring in vivo a wealth of information that was hitherto accessible only in extracts is likely to expand the scope of metabolic studies in the intact brain.

摘要

采用LCModel方法分析在9.4 T磁场下从大鼠活体脑内获得的局部活体(13)C NMR谱。分析过程中纳入了化学位移、J耦合常数和J演化的先验知识。在输注[1,6 - (13)C2]葡萄糖期间,在大鼠活体脑内400微升体积中同时对对应于10种代谢物的多达50种不同的同位素异构体信号进行了定量分析。即使在低至3:1的信噪比情况下,该分析仍保持准确。在22分钟内活体测定的谷氨酸、谷氨酰胺和天冬氨酸中同位素异构体的相对分布与在脑提取物中测得的结果高度吻合。对(13)C谱的时间序列进行定量分析,得出了多达16个碳位置的总(13)C标记掺入的时间进程以及各个同位素异构体信号的时间进程,时间分辨率低至5分钟(动态同位素异构体分析)。能够在活体中测量到迄今为止仅在提取物中才能获得的大量信息,这可能会拓宽对完整脑内代谢研究的范围。

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