Slow Magic Angle Sample Spinning: A Non- or Minimally Invasive Method for High-Resolution 1H Nuclear Magnetic Resonance (NMR) Metabolic Profiling

Part of the Methods in Molecular Biology book series (MIMB, volume 708)


High-resolution 1H magic angle spinning nuclear magnetic resonance (NMR), using a sample spinning rate of several kilohertz or more (i.e., high-resolution magic angle spinning (hr-MAS)), is a well-established method for metabolic profiling in intact tissues without the need for sample extraction. The only shortcoming with hr-MAS is that it is invasive and is thus unusable for non-destructive detections. Recently, a method called slow MAS, using the concept of two-dimensional NMR spectroscopy, has emerged as an alternative method for non- or minimally invasive metabolomics in intact tissues, including live animals, due to the slow or ultra-slow sample spinning used. Although slow MAS is a powerful method, its applications are hindered by experimental challenges. Correctly designing the experiment and choosing the appropriate slow MAS method both require a fundamental understanding of the operation principles, in particular the details of line narrowing due to the presence of molecular diffusion. However, these fundamental principles have not yet been fully disclosed in previous publications. The goal of this chapter is to provide an in-depth evaluation of the principles associated with slow MAS techniques by emphasizing the challenges associated with a phantom sample consisting of glass beads and H2O, where an unusually large magnetic susceptibility field gradient is obtained.

Key words

High-resolution 1H-NMR metabolomics tissues organs live animals slow magic angle spinning magic angle turning magnetic susceptibility line broadening molecular diffusion 


  1. 1.
    Mitchell, D. G., Cohen, M. S. (2004) MRI principles, 2nd edn, SAUNDERS (An Imprint of Elsevier) Philadelphia, Pennsylvania.Google Scholar
  2. 2.
    Callaghan, P. T. (1993) Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press, New York, NY.Google Scholar
  3. 3.
    Petroff, O. A. C., Prichard, J. W., Ogino, T., Shulman, R. G. (1998) Proton magnetic-resonance spectroscopic studies of agonal carbohydrate-metabolism in rabbit brain. Neurology 38, 1569–1574.Google Scholar
  4. 4.
    Cheng, L. L., Ma, M. J., Becerra, L., Ptak, T., Tracey, I., Lackner, A., Gonzalez, R. G. (1997) Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA 94, 6408–6413.PubMedCrossRefGoogle Scholar
  5. 5.
    Weybright, P., Millis, K., Campbell, N., Cory, D. G., Singer, S. (1998) Gradient, high-resolution, magic angle spinning 1H nuclear magnetic resonance spectroscopy of intact cells. Magn Reson Med 39, 337–345.PubMedCrossRefGoogle Scholar
  6. 6.
    Bollard, M. E., Murray, A. J., Clarke, K., Nicholson, J. K., Griffin, J. L. (2003) A study of metabolic compartmentation in the rat heart and cardiac mitochondria using high-resolution magic angle spinning 1H NMR spectroscopy. FEBS Lett 553, 73–78.PubMedCrossRefGoogle Scholar
  7. 7.
    Tate, A. R., Foxall, P. J., Holmes, E., Moka, D., Spraul, M., Nicholson, J. K., Lindon, J. C. (2000) Distinction between normal and renal cell carcinoma kidney cortical biopsy samples using pattern recognition of 1H magic angle spinning (MAS) NMR spectra. NMR Biomed 13, 64–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Righi, V., Mucci, A., Schenetti, L., Tosi, M. R., Grigioni, W. F., Corti, B., Bertaccini, A., Franceschelli, A., Sanguedolce, F., Schiavina, R., Martorana, G., Tugnoli, V. (2007) Ex vivo HR-MAS magnetic resonance spectroscopy of normal and malignant human renal tissues. Anticancer Res 27, 3195–3204.PubMedGoogle Scholar
  9. 9.
    Chen, J. H., Wu, Y. V., Decarolis, P., O’Connor, R., Somberg, C. J., Singer, S. (2008) Resolution of creatine and phosphocreatine 1H signals in isolated human skeletal muscle using HR-MAS 1H NMR. Magn Reson Med 59, 1221–1224.PubMedCrossRefGoogle Scholar
  10. 10.
    Bollard, M. E., Garrod, S., Holmes, E., Lindon, J. C., Humpfer, E., Spraul, M., Nicholson, J. K. (2000) High-resolution 1H and 1H–13C magic angle spinning NMR spectroscopy of rat liver. Magn Reson Med 44, 201–207.PubMedCrossRefGoogle Scholar
  11. 11.
    Garrod, S., Humpfer, E., Spraul, M., Connor, S. C., Polley, S., Connelly, J., Lindon, J. C., Nicholson, J. K., Holmes, E. (1999) High-resolution magic angle spinning 1H NMR spectroscopic studies on intact rat renal cortex and medulla. Magn Reson Med 41, 1108–1118.PubMedCrossRefGoogle Scholar
  12. 12.
    Garrod, S., Humpher, E., Connor, S. C., Connelly, J. C., Spraul, M., Nicholson, J. K., Holmes, E. (2001) High-resolution 1H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in intact renal and hepatic tissue. Magn Reson Med 45, 781–790.PubMedCrossRefGoogle Scholar
  13. 13.
    Lindon, J. C., Nicholson, J. K., Holmes, E. (eds.) (2007) The Handbook of Metabonomics and Metabolomics, Elsevier, New York, NY.Google Scholar
  14. 14.
    Antzutkin, O. N., Shekar, S. C., Levitt, M. H. (1995) Two-dimensional sideband separation in magic-angle-spinning NMR. J Magn Reson A 115, 7–19.CrossRefGoogle Scholar
  15. 15.
    Hu, J. Z., Wang, W., Liu, F., Solum, M. S., Alderman, D. W., Pugmire, R. J., Grant, D. M. (1995) Magic-angle-turning experiments for measuring chemical–shift-tensor principal values in powdered solids. J Magn Reson A 113, 210–222.CrossRefGoogle Scholar
  16. 16.
    Wind, R. A., Hu, J. Z., Rommereim, D. N. (2001) High resolution 1H NMR spectroscopy in organs and tissues using slow magic angle spinning. Magn Reson Med 46, 213–218.PubMedCrossRefGoogle Scholar
  17. 17.
    Bertram, H. C., Hu, J. Z., Rommereim, D. N., Wind, R. A., Andersen, H. J. (2004) Dynamic high-resolution 1H and 31P NMR spectroscopy and 1H T2 measurements in postmortem rabbit muscles using slow magic angle spinning. J Agric Food Chem 52, 2681–2688.PubMedCrossRefGoogle Scholar
  18. 18.
    Hu, J. Z., Wind, R. A., Rommereim, D. N. (2006) 1H relaxation times of metabolites in biological samples obtained with non-destructive ex vivo slow-MAS NMR. Magn Reson Chem 44, 269–275.PubMedCrossRefGoogle Scholar
  19. 19.
    Hu, J. Z., Rommereim, D. N., Minard, K. R., Woodstock, A., Harrer, B. J., Wind, R. A., Phillips, R. P., Sime, P. J. (2008) Metabolomics in lung inflammation: a high-resolution 1H NMR study of mice exposed to silica dust. Toxicol Mech Meth 18, 385–398.CrossRefGoogle Scholar
  20. 20.
    Hu, J. Z., Wind, R. A., Mclean, J., Gorby, Y. A., Resch, C. T., Fredrickson, J. K. (2004) High-resolution 1H NMR spectroscopy of metabolically active microorganisms using non-destructive magic angle spinning. Spectroscopy 19, 98–102.Google Scholar
  21. 21.
    Minard, K. R., Guo, X., Wind, R. A. (1998) Quantitative 1H MRI and MRS microscopy of individual V79 lung tumor spheroids. J Magn Reson 133, 368–373.PubMedCrossRefGoogle Scholar
  22. 22.
    Hu, J. Z., Rommerein, D. N., Wind, R. A. (2002) High resolution 1H NMR spectroscopy in rat liver using magic angle turning at a 1 Hz spinning rate. Magn Reson Med 47, 829–836.PubMedCrossRefGoogle Scholar
  23. 23.
    Wind, R. A., Hu, J. Z., Rommereim, D. N. (2003) High-resolution 1H NMR spectroscopy in a live mouse subjected to 1.5 Hz magic angle spinning. Magn Reson Med 50, 1113–1119.PubMedCrossRefGoogle Scholar
  24. 24.
    Wind, R. A., Hu, J. Z., Majors, P. D. (2006) Localized in vivo isotropic–anisotropic correlation 1H NMR spectroscopy using ultraslow magic angle spinning. Magn Reson Med 55, 41–49.PubMedCrossRefGoogle Scholar
  25. 25.
    Wind, R. A., Hu, J. Z., Majors, P. D. (2005) Slow-MAS NMR: a new technology for in vivo metabolomic studies. Drug Discov Today Technol 2, 291–294.CrossRefGoogle Scholar
  26. 26.
    Wind, R. A., Hu, J. Z. (2006) In vivo and ex vivo high-resolution 1H NMR in biological systems using low-speed magic angle spinning. Prog Nucl Magn Reson Spectrosc 49, 207–259.CrossRefGoogle Scholar
  27. 27.
    Lüdeke, K. M., Röschmann, P., Tischler, R. (1985) Susceptibility artifacts in NMR imaging. Magn Reson Imaging 3, 329–343.PubMedCrossRefGoogle Scholar
  28. 28.
    Jackson, J. D. (1962) Classical Electrodynamics, 2nd edn, Wiley, New York.Google Scholar
  29. 29.
    Boxerman, J. L., Hamberg, L. M., Rosen, B. R., Weisskoff, R. M. (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34, 555–566.PubMedCrossRefGoogle Scholar
  30. 30.
    Kennan, R. P., Zhong, J., Gore, J. C. (1994) Intravascular susceptibility contrast mechanisms in tissues. Magn Reson Med 31, 9–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Edmond, D. T., Wormald, M. R. (1988) Theory of resonance in magnetically inhomogeneous specimens and some useful calculations. J Magn Reson 77, 223–232.Google Scholar
  32. 32.
    Chu, S. C., Xu, Y., Balschi, J. A., Springer, C. S. Jr. (1990) Bulk magnetic susceptibility shifts in NMR studies of compartmentalized samples: Use of paramagnetic reagents. Magn Reson Med 13, 239–262.PubMedCrossRefGoogle Scholar
  33. 33.
    Yablonskiy, D. A., Haacke, E. M. (1994) Theory of NMR signal behavior in magnetically inhomogeneous tissues: The static dephasing regime. Magn Reson Med 32, 749–763.PubMedCrossRefGoogle Scholar
  34. 34.
    Bihan, D. L., Basser, P. J. (1995) Molecular diffusion and nuclear magnetic resonance, in (Bihan, D. L., ed.), Diffusion and Perfusion Magnetic Resonance Imaging, pp. 5–17. Raven Press, New York, NY.Google Scholar
  35. 35.
    Leu, G., Tang, X., Peled, S., Maas, W. E., Singer, S., Cory, D. G., Sen, P. N. (2000) Amplitude modulation and relaxation due to diffusion in NMR experiments with a rotating sample. Chem Phys Lett 332,344–350.CrossRefGoogle Scholar
  36. 36.
    Cotts, R. M., Hoch, M. J. R., Sun, T., Markert, J. T. (1989) Pulsed field gradient stimulated echo methods for improved NMR diffusion measurements in heterogeneous systems. J Magn Reson 83, 252–266.Google Scholar
  37. 37.
    Torrey, H. C. (1956) Bloch equation with diffusion terms. Phys Rev 104, 563–566.CrossRefGoogle Scholar
  38. 38.
    Callaghan, P. T. (1993) Principles of Nuclear Magnetic Resonance Microscopy, pp. 160–161. Clarendon Press, Oxford.Google Scholar
  39. 39.
    Abragam, A. (1961) The Principles of Nuclear Magnetism, p. 61. Oxford University Press, Oxford.Google Scholar
  40. 40.
    Ernst, R. R., Bodenhausen, G., Wokaun, A. (1997) Principles of Nuclear Magnetic Resonance in One and Two Dimensions, p. 332, Clarendon Press, Oxford Science Publication.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Pacific Northwest National LaboratoryRichlandUSA

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