Journal of the Korean Magnetic Resonance Society (한국자기공명학회논문지)

Korean Magnetic Resonance Society (한국자기공명학회)
권호 표지
DOI QR코드

DOI QR Code

Analysis of in vitro 2D-COSY on Human Brain Metabolites for Molecular Stereochemistry

  • Kim, Sang-Young (Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea) ;
  • Woo, Dong-Cheol (Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea) ;
  • Bang, Eun-Jung (Metabolome Analysis Team, Korea Basic Science Institute) ;
  • Kim, Sang-Soo (Department of Molecular Genetics, College of Medicine, The Catholic University of Korea) ;
  • Lim, Hyang-Sook (Department of Molecular Genetics, College of Medicine, The Catholic University of Korea) ;
  • Choi, Chi-Bong (Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea) ;
  • Choe, Bo-Young (Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea)
  • Published : 2008.06.20
Download PDF
⟨ Previous Next ⟩

Abstract

To investigate the 3-bond connectivity of human brain metabolites by scalar coupling interaction through 2D-correlation spectroscopy (COSY) techniques using high field NMR spectroscopy. All NMR experiments were performed at 298K on Unity Inova 500 or 600 (Varian Inc.) equipped with a triple resonance probe head with z-shield gradient. Human brain metabolites were prepared with 10% $D_2O$. Two dimensional 2D COSY spectra were acquired with 4096 complex data points in $t_2$ and 128 or 256 increments in $t_1$ dimension. The spectral width was 9615.4 Hz and solvent suppression was achieved using presaturation using low power irradiation of the water resonance during 2s of relaxation delay. NMR data were processed using VNMRJ (Varian Instrument) software and all the chemical shifts were referenced to the methyl resonance of N-acetyl aspartate (NAA) peak at 2.0 ppm. Total 10 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), lactate (Lac), taurine (Tau), ${\gamma}$-aminobutyricacid (GABA), alanine (Ala) were included for major target metabolites. Symmetrical 2D-COSY spectra were successfully acquired. Total 14 COSY cross peaks were observed even though there were parallel/orthogonal noisy peaks induced by water suppression. Except for Cr, all of human brain metabolites produced COSY cross peaks. The spectra of NAA methyl proton at 2.02 ppm and Glu methylene proton ($CH_2(3)$) at 2.11 ppm and Gln methylene proton ($CH_2(3)$) at 2.14 ppm were overlapped in the similar resonance frequency between 2.00 ppm and 2.15 ppm. The present study demonstrated that in vitro 2D-COSY represented the 3-bond connectivity of human brain metabolites by scalar coupling interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2D-COSY study. Also it would be helpful to determine the molecular stereochemistry in vivo by using two-dimensional MR spectroscopy.

Keywords

References

  1. Tofts PS, Brix G, Buckley DL, et al. Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusible tracer: Standardized quantities and symbols. JMRI, 10, 223-232 (1999). https://doi.org/10.1002/(SICI)1522-2586(199909)10:3<223::AID-JMRI2>3.0.CO;2-S
  2. Li KL, Jackson A. New hybrid technique for accurate and reproducible quantitation of dynamic contrast-enhanced MRI data. Magn Reson Med , 50, 1286-1295 (2003). https://doi.org/10.1002/mrm.10652
  3. Calamante F, Pell GS, Thomas DL. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab , 19, 701-735 (1999).
  4. Barbier EL, Lamalle L, Décorps M. Methodology of brain perfusion imaging JMRI , 13, 496-520 (2001). https://doi.org/10.1002/jmri.1073
  5. Xavier G, Jeroen H, Tchoyoson L. Perfusion Imaging Using Arterial Spin Labeling. Topics in Magnetic Resonance Imaging, 15, 10-27 (2004). https://doi.org/10.1097/00002142-200402000-00003
  6. Howard RA, Timothy PL. Clinical Perspectives in Perfusion: Neuroradiologic Applications. Topics in Magnetic Resonance Imaging, 15, 28-40 (2004). https://doi.org/10.1097/00002142-200402000-00004
  7. Jahng GH, Zhu XP, Matson GB, Weiner MW, Schuff N. Improved perfusion-weighted MRI by a novel double inversion with proximal labeling of both tagged and control acquisitions. Magn Reson Med., 49, 307-314 (2003). https://doi.org/10.1002/mrm.10339
  8. Li KL, Zhu XP, Hylton N, Jahng GH, Weiner MW, Schuff N. Four-phase singlecapillary stepwise model for kinetics in arterial spin labeling MRI. Magn Reson Med ., 53, 511-518 (2005). https://doi.org/10.1002/mrm.20390
  9. Richard B. Buxton et al. A General Kinetic Model for Quantitative Perfusion Imaging with Arterial Spin Labeling. Magn Reson Med., 40, 383-396 (1998). https://doi.org/10.1002/mrm.1910400308
  10. Luh WM, Wong EC, Bandettini PA, Hyde JS. QUIPSS II with thin-slice TI1 periodic saturation: A method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med ., 41, 1246-1254 (1999). https://doi.org/10.1002/(SICI)1522-2594(199906)41:6<1246::AID-MRM22>3.0.CO;2-N
  11. Lai S, Wang JJ, Jahng GH. FAIR exempting separate T 1 measurement (FAIREST): a novel technique for online quantitative perfusion imaging and multi-contrast fMRI NMR in Biomedicine, 14, 507-516 (2001). https://doi.org/10.1002/nbm.738
  12. Wang JJ, Alsop DC, Li L., Listerud J, Gonzalez JB, Schnall MD, Detre JA. Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla. Magn Reson Med , 48, 242-254 (2002). https://doi.org/10.1002/mrm.10211
  13. Johnson NA, Jahng GH, Weiner MW, et al. Pattern of Cerebral Hypoperfusion in Alzheimer Disease and Mild Cognitive Impairment Measured with Arterial Spinlabeling MR Imaging: Initial Experience Radiology , 234, 851-859 (2005).
  14. Jahng GH, Song EM, Zhu XP et al. Human Brain: Reliability and Reproducibility of Pulsed Arterial Spin-labeling Perfusion. MR Imaging Radiology , 234, 909-916 (2005).
  15. Kennan RP, Rolf Jäger HR. $T_2$- and $T_2*$-W DCE-MRI: Blood Perfusion and Volume Estimation using Bolus Tracking , Quantitative MRI of the Brain, 2003 John Wiley & Sons, Ltd
  16. Daldrup H, Shames DM, Husseini W, et al. Quantification of the extraction fraction of gadopentetate across breast tumor capillaries. Magn Reson Med., 40, 537-543 (1998). https://doi.org/10.1002/mrm.1910400406
  17. Cha SM, Knopp EA, Johnson G, Andrew Litt A, Glass J, Gruber ML, Lu S, and Zagzag D. Dynamic Contrast-enhanced T2*-weighted MR Imaging of Recurrent Malignant Gliomas Treated with Thalidomide and Carboplatin Am J Neuroradiol, 21, 881-890 (2000).
  18. Cha SM, Knopp EA, Johnson G, Wetzel SG, Andrew W. Litt, and David Zagzag. Intracranial Mass Lesions: Dynamic Contrast-enhanced Susceptibility-weighted Echoplanar Perfusion. MR Imaging Radiology , 223, 11-29 (2002)
  19. Schaefer PW, Ozsunar Y, Julian HE, Leena M. Hamberg, Hunter GJ, Sorensen AJ, Koroshetz WJ, and Gonzalez RG. Assessing Tissue Viability with MR Diffusion and Perfusion Imaging. Am. J. Neuroradiol., Mar., 24, 436-443 (2003).
  20. Bruening R, Kwong KK, Vevea MJ, et al. Echo-planar MR determination of relative cerebral blood volume human brain tumors: T1 versus T2 weighting. Am. J. Neuroradiol., 17, 831-840 (1996).
  21. Hacklander T, Reichenbach JR, Hofer M, et al. Measurement of cerebral blood volume via the relaxing effect of low-dose gadopentetate dimeglumine during bolus transit. Am. J. Neuroradiol., 17, 821-830 (1996).
  22. Li KL, Zhu XP, Waterton J, Jackson A. Improved 3D quantitative mapping of blood volume and endothelial permeability in brain tumors. J Magn Reson Imaging, 12, 347-57 (2000). https://doi.org/10.1002/1522-2586(200008)12:2<347::AID-JMRI19>3.0.CO;2-7