Magnetic Resonance Spectroscopy of Traumatic Brain Injury and Concussion

  • Stefan Blüml
  • William M. Brooks


Imaging modalities such as CT and magnetic resonance imaging (MRI) are powerful tools to detect and assess focal injury such as hemorrhagic lesions and edema and brain swelling in severe injury. However, acute and chronic injury at a cellular level is sometimes difficult to discern from normal features by anatomical imaging. Magnetic resonance spectroscopy (MRS) offers a unique non-invasive approach to assess injury at microscopic levels by quantifying cellular metabolites. Most clinical MRI systems are equipped with this option and MRS is thus a widely available modality. For the brain in particular, MRS has been a powerful research tool and has also been proven to provide additional clinically relevant information for several disease families such as brain tumors, metabolic disorders, and systemic diseases. The most widely-available MRS method, proton (1H; hydrogen) spectroscopy, is FDA approved for general use and can be ordered by clinicians for patient studies if indicated. The findings obtained with MRS in concussion and more severe head trauma are heterogeneous, reflecting the different time after injury, degree of injury and different physiologic and pathologic response of the brain to injury in individuals. The most important findings are that elevated lactate (and lipids) in apparently normal tissue observed 2–5 days after injury are indicators of severe global hypoxic injury and poor outcome. Also, N-acetylaspartate (NAA), a marker for “healthy” neurons and axons, is generally reduced in traumatic brain injury signaling neuronal and axonal loss/damage. The extent of NAA reduction after injury is an objective and quantitative surrogate marker for the severity of injury and is useful for outcome prediction.

Key Words

MR spectroscopy metabolism trauma concussion N-acetyl-aspartate lactate choline 


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  1. Badar-Goffer, R.S., Ben-Yoseph, O., Bachelard, H.S., Morris, P.G. (1992). Neuronal-glial metabolism under depolarizing conditions. A 13C-n.m.r. study. Biochemedical Journal, 282 (Pt 1), 225–230.Google Scholar
  2. Baslow, M.H. (2000). Functions of N-acetyl-L-aspartate and N-acetyl-L-aspartylglutamate in the vertebrate brain: role in glial cell-specific signaling. Journal of Neurochemistry, 75(2),453–459.PubMedCrossRefGoogle Scholar
  3. Bloch, F. (1946). Nuclear Induction. Physical. Reveview, 70, 460.CrossRefGoogle Scholar
  4. Bluml, S., Seymour, K.J., Ross, B.D. (1999). Developmental changes in choline-and ethanolamine-containing compounds measured with proton-decoupled (31) P MRS in in vivo human brain. Magnetic Resonance Medicine, 42(4), 643–654.CrossRefGoogle Scholar
  5. Bottomley, P.A. (1984). Inventor Selective volume method for performing localized NMR spectroscopy. USA patent US patent 4 480 228.Google Scholar
  6. Bottomley, P.A. (1987). Spatial localization in NMR spectroscopy in vivo. Annals of New Yourk Academy of Science, 508, 333–348.Google Scholar
  7. Brand, A., Richter-Landsberg, C., Leibfritz, D. (1993). Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Developmental Neuroscience, 15(3–5), 289–298.PubMedGoogle Scholar
  8. Brooks, W.M., Friedman, S.D., Gasparovic, C. (2001). Magnetic resonance spectroscopy in traumatic brain injury. Journal of Head Trauma Rehabilitation, 16(2), 149–164.PubMedCrossRefGoogle Scholar
  9. Brooks, W.M., Stidley, C.A., Petropoulos, H., Jung, R.E., Weers, D.C., Friedman, S.D., Barlow, M.A., Sibbitt, W.L., Jr., Yeo, R.A. (2000). Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study. Journal of Neurotrauma, 17(8), 629–640.PubMedCrossRefGoogle Scholar
  10. Cecil, K.M., Hills, E.C., Sandel, M.E., Smith, D.H, Mclntosh, T.K., Mannon, L.J., Sinson, G.P., Bagley, L.J., Grossman, R.I., Lenkinski, R.E. (1998). Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. Journal of Neurosurgery, 88(5), 795–801.PubMedCrossRefGoogle Scholar
  11. Choe, B.Y., Suh, T.S., Choi, K.H., Shinn, K.S., Park, C.K., Kang, J.K. (1995). Neuronal dysfunction in patients with closed head injury evaluated by in vivo 1H magnetic resonance spectroscopy. Invest Radiology, 30(8), 502–506.Google Scholar
  12. Condon, B., Oluoch-Olunya, D., Hadley, D., Teasdale, G., Wagstaff, A. (1998). Early 1H magnetic resonance spectroscopy of acute head injury: four cases. Journal of Neurotrauma, 15(8), 563–571.PubMedCrossRefGoogle Scholar
  13. Daikhin, Y., Yudkoff, M. (2000). Compartmentation of brain glutamate metabolism in neurons and glia. Journal of Nutrition, 130(4S Suppl), 1026S–1031S.PubMedGoogle Scholar
  14. Danielsen, E.R., Henriksen, O. (1994). Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites. NMR Biomedical, 7(7),311–318.Google Scholar
  15. Erecinska, M., Silver, I.A. (1990). Metabolism and role of glutamate in mammalian brain. Progress in Neurobiology, 35(4), 245–296.PubMedCrossRefGoogle Scholar
  16. Flint, A.C., Liu, X., Kriegstein, A.R. (1998). Nonsynaptic glycine receptor activation during early neocortical development. Neuron, 20(1), 43–53.PubMedCrossRefGoogle Scholar
  17. Frahm, J., Merboldt, K., Haenicke, W. (1987). Localized proton spectroscopy using stimulated echos. Journal of Magnetic Resonance, 72, 502–508.Google Scholar
  18. Friedman, S.D., Brooks, W.M., Jung. R.E., Chiulli, S.J., Sloan, J.H., Montoya, B.T., Hart, B.L., Yeo, RA. (1999). Quantitative proton MRS predicts outcome after traumatic brain injury. Neurology, 52(7), 1384–1391.PubMedGoogle Scholar
  19. Garnett, M.R., Blamire, A.M., Corkill, R.G., Cadoux-Hudson, T.A., Rajagopalan, B., Styles, P. (2000). Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. Brain, (Pt 10), 2046–2054.Google Scholar
  20. Gasparovic, C., Arfai, N., Smid, N., Feeney, D.M. (2001). Decrease and recovery of N-acetylaspartate/creatine in rat brain remote from focal injury. Journal of Neurotrauma, 18(3), 241–246.PubMedCrossRefGoogle Scholar
  21. Gill, S.S., Thomas, D.G., Van Bruggen, N., Gadian, D.G., Peden, C.J., Bell, J.D., Cox, I.J., Menon, D.K., Iles, R.A., Bryant, D.J., et al. (1990). Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. Journal of Computational Assistance in Tomography, 14(4), 497–504.CrossRefGoogle Scholar
  22. Govindaraju, V., Gauger, G.E., Manley, G.T., Ebel, A., Meeker, M., Maudsley, A.A. (2004). Volumetric proton spectroscopic imaging of mild traumatic brain injury. AJNR American Journal of Neuroradiology, 25(5), 730–737.PubMedGoogle Scholar
  23. Haseler, L.J., Arcinue, E., Danielsen, E.R., Bluml, S., Ross, B.D. (1997). Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of neuronal damage in shaken baby syndrome. Pediatrics 99(1), 4–14.PubMedCrossRefGoogle Scholar
  24. Holshouser, B., A., Ashwal, S., Luh, G.Y., Shu, S., Kahlon, S., Auld, K.L., Tomasi, L.G., Perkin, R.M., Hinshaw, D.B., Jr. (1997). Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children. Radiology, 202(2), 487–496.PubMedGoogle Scholar
  25. Holshouser, B.A., Ashwal, S., Shu, S., Hinshaw, D.B., Jr. (2000). Proton MR spectroscopy in children with acute brain injury: comparison of short and long echo time acquisitions. Journal of Magnetic Resonance Imaging, 11(1), 9–19.PubMedCrossRefGoogle Scholar
  26. Holshouser, B.A., Tong. K.A., Ashwal, S. (2005). Proton MR spectroscopic imaging depicts diffuse axonal injury in children with traumatic brain injury. AJNR American Journal Neuroradiology, 26(5), 1276–1285.Google Scholar
  27. Howe, F.A., Barton, S.J., Cudlip, S.A., Stubbs, M., Saunders, D.E., Murphy, M., Wilkins, P., Opstad, K.S, Doyle, V.L., McLean, M.A., Bell, B.A., Griffiths, J.R. (2003). Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magnetic Resonance Medicine, 49(2), 223–232.CrossRefGoogle Scholar
  28. Jope, R.S., Jenden, D.J. (1979). Choline and phospholipid metabolism and the synthesis of acetylcholine in rat brain. Journal of Neuroscience Research, 4(1), 69–82.PubMedCrossRefGoogle Scholar
  29. Kovanlikaya, A., Panigrahy, A., Krieger, M.D., Gonzalez-Gomez, I., Ghugre, N., McComb, J.G., Gilles, F.H., Nelson, M.D., Bluml, S. (2005). Untreated Pediatric Primitive Neuroectodermal Tumor in Vivo: Quantitation of Taurine with MR Spectroscopy. Radiology, 236(3), 1020–1025.PubMedGoogle Scholar
  30. Kreis, R. (1992). Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-l MR spectroscopy. Radiology, 182(1), 19–27.PubMedGoogle Scholar
  31. Kreis, R. (1997). Quantitative localized 1H MR spectroscopy for clinical use. Progress in NMR Spectroscopy, 31, 155–195.CrossRefGoogle Scholar
  32. Kreis, R., Ernst, T., Ross, B.D. (1993). Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magnetic Resonance Medicine, 30(4), 424–437.Google Scholar
  33. Kreis, R., Hofmann, L., Kuhlmann, B., Boesch, C., Bossi, E., Hueppi, P.S. (2002). Brain Metabolite Composition During Early Human Brain Development as Measured by Quantitative In Vivo 1H Magnetic Resonance Spectroscopy. Magnetic Resonance Medicine, 48, 949–958.CrossRefGoogle Scholar
  34. Lien, Y.H., Shapiro, J.I, Chan, L. (1990). Effects of hypernatremia on organic brain osmoles. Journal of Clinical Invest, 85(5), 1427–1435.Google Scholar
  35. Macmillan, C.S., Wild, J.M., Wardlaw, J.M., Andrews, P.J., Marshall, I., Easton, V.J. (2002). Traumatic brain injury and subarachnoid hemorrhage: in vivo occult pathology demonstrated by magnetic resonance spectroscopy may not be “ischaemic”. A primary study and review of the literature. Acta Neurochemistry, (Wien), 144(9), 853–862.CrossRefGoogle Scholar
  36. Magistretti, P.J., Pellerin, L., Rothman, D.L., Shulman, R.G. (1999). Energy on demand. Science, 283(5401), 496–497.PubMedCrossRefGoogle Scholar
  37. Miller, B.L. (1991). A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomedicine, 4(2), 47–52.Google Scholar
  38. Moreno-Torres, A., Martinez-Perez, I., Baquero, M., Campistol, J., Capdevila, A., Arus, C., Pujol, J. (2004). Taurine detection by proton magnetic resonance spectroscopy in medulloblastoma: Contribution to noninvasive differential diagnosis with cerebellar astrocytomas. Neurosurgery, 55, 824–829.PubMedCrossRefGoogle Scholar
  39. Ordidge, R.J., Connelly, A., B., Lohman, J.A. (1986). Image-selected in-vivo spectroscopy (ISIS). A new technique for spatially selective NMR spectroscopy. Journal of Magnetic Resonance, 66, 283–294.Google Scholar
  40. Panigrahy, A., Krieger, M., Gonzalez-Gomez I, Liu. X., McComb, J., Finlay, J., Nelson, M., Gilles, F., Blüml. S. (2005). Quantitative short echo time 1H magnetic resonance spectroscopy of untreated pediatric brain tumors: Pre-operative diagnosis and characterization. AJNR American Journal Neuroradiology, in press.Google Scholar
  41. Pfefferbaum, A., Adalsteinsson, E., Spielman, D., Sullivan, E.V., Lim, K.O. (1999). In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging. Magnetic Resonance Medicine, 41(2), 276–284.CrossRefGoogle Scholar
  42. Provencher, S.W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance Medicine, 30(6), 672–679.Google Scholar
  43. Purcell, E.M., Torrey, H.C., Pound, R.V. (1946). Resonance absorption by nuclear magnetic moments in a solid. Physical Review, 69, 37–38.CrossRefGoogle Scholar
  44. Ricci, R., Barbarella, G., Musi, P., Boldrini, P., Trevisan, C., Basaglia, N. (1997). Localised proton MR spectroscopy of brain metabolism changes in vegetative patients. Neuroradiology, 39(5), 313–319.PubMedCrossRefGoogle Scholar
  45. Ross, B.D., Ernst, T., Kreis, R., Haseler, L.J., Bayer, S., Danielsen, E., Bluml, S., Shonk, T., Mandigo, J.C., Caton, W., Clark, C., Jensen, S.W., Lehman, N.L., Arcinue, E., Pudenz, R., Shelden, C.H. (1998). 1H MRS in acute traumatic brain injury. Journal of Magnetic Resonance Imaging 8(4), 829–840.PubMedGoogle Scholar
  46. Schuhmann, M.U., Stiller, D., Skardelly, M., Thomas, S., Samii, M., Brinker, T. (2002). Long-time in-vivo metabolic monitoring following experimental brain contusion using proton magnetic resonance spectroscopy. Acta Neurochir Supplement, 81, 209–212.Google Scholar
  47. Seymour, K.J., Bluml, S., Sutherling, J., Sutherling, W., Ross, B.D. (1999). Identification of cerebral acetone by 1H-MRS in patients with epilepsy controlled by ketogenic diet. Magma, 8(1), 33–42.PubMedCrossRefGoogle Scholar
  48. Shutter, L., Tong, K.A., Holshouser, B.A. (2004). Proton MRS in acute traumatic brain injury: role for glutamate/glutamine and choline for outcome prediction. Journal of Neurotrauma, 21(12), 1693–1705.PubMedCrossRefGoogle Scholar
  49. Signorctti, S., Marmarou, A., Tavazzi, B., Lazzarino, G., Beaumont, A., Vagnozzi, R. (2001). N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. Journal of Neurotrauma, 18(10), 977–991.CrossRefGoogle Scholar
  50. Tallan, H.H. (1957). Studies on the distribution of N-acetyl-L-aspartic acid in brain. Journal of Biological Chemistry, 224(1), 41–45.PubMedGoogle Scholar
  51. Videen, J.S. (1995). Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. Journal of Clinical Investigation, 95(2), 788–793.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Stefan Blüml
    • 1
  • William M. Brooks
    • 2
  1. 1.Department of RadiologyChildrens Hospital Los AngelesLos Angeles
  2. 2.Hoglund Brain Imaging CenterUniversity of Kansas Medical CenterKansas City

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