Traumatic Brain Injury and Concussion

  • Alexander P. Lin
  • Stefan Blüml


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 noninvasive approach to assess injury at microscopic levels by quantifying cellular metabolites. 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. In the cases of mild traumatic brain injury, choline (Cho) has been shown to be reflective of diffuse axonal injury and alterations in neurotransmitters such as glutamate (Glu) and gamma amino butyric acid (GABA) have also been shown.


Traumatic Brain Injury Head Injury Magnetic Resonance Spectroscopy Severe Traumatic Brain Injury Mild Traumatic Brain Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Langlois JA, Rutland-Brown W, Thomas KE. The incidence of traumatic brain injury among children in the United States: differences by race. J Head Trauma Rehabil. 2005;20(3):229–38.PubMedCrossRefGoogle Scholar
  2. 2.
    Brooks WM, Friedman SD, Gasparovic C. Magnetic resonance spectroscopy in traumatic brain injury. J Head Trauma Rehabil. 2001;16(2):149–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Govindaraju V, Gauger GE, Manley GT, Ebel A, Meeker M, Maudsley AA. Volumetric proton spectroscopic imaging of mild traumatic brain injury. AJNR Am J Neuroradiol. 2004;25(5):730–7.PubMedGoogle Scholar
  4. 4.
    Macmillan CS, Wild JM, Wardlaw JM, Andrews PJ, Marshall I, Easton VJ. 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 Neurochir (Wien). 2002;144(9):853–62. discussion 862.CrossRefGoogle Scholar
  5. 5.
    Brooks WM, Stidley CA, Petropoulos H, et al. Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study. J Neurotrauma. 2000;17(8):629–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Gasparovic C, Arfai N, Smid N, Feeney DM. Decrease and recovery of N-acetylaspartate/creatine in rat brain remote from focal injury. J Neurotrauma. 2001;18(3):241–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Schuhmann MU, Stiller D, Skardelly M, Thomas S, Samii M, Brinker T. Long-time in-vivo metabolic monitoring following experimental brain contusion using proton magnetic resonance spectroscopy. Acta Neurochir Suppl. 2002;81:209–12.PubMedGoogle Scholar
  8. 8.
    Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. Energy on demand. Science. 1999;283(5401):496–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Signoretti S, Marmarou A, Tavazzi B, Lazzarino G, Beaumont A, Vagnozzi R. N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. J Neurotrauma. 2001;18(10):977–91.PubMedCrossRefGoogle Scholar
  10. 10.
    Miller BL. A review of chemical issues in 1 H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed. 1991;4(2):47–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Jope RS, Jenden DJ. Choline and phospholipid metabolism and the synthesis of acetylcholine in rat brain. J Neurosci Res. 1979;4(1):69–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Brand A, Richter-Landsberg C, Leibfritz D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci. 1993;15(3–5):289–98.PubMedCrossRefGoogle Scholar
  13. 13.
    Badar-Goffer RS, Ben-Yoseph O, Bachelard HS, Morris PG. Neuronal-glial metabolism under depolarizing conditions. A 13C-n.m.r. study. Biochem J. 1992;282(Pt 1):225–30.PubMedGoogle Scholar
  14. 14.
    Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO. 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. Magn Reson Med. 1999; 41(2):276–84.PubMedCrossRefGoogle Scholar
  15. 15.
    Ross BD, Ernst T, Kreis R, et al. 1 H MRS in acute traumatic brain injury. J Magn Reson Imaging. 1998;8(4):829–40.PubMedCrossRefGoogle Scholar
  16. 16.
    Garnett MR, Blamire AM, Corkill RG, Cadoux-Hudson TA, Rajagopalan B, Styles P. Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. Brain. 2000;123(Pt 10):2046–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Holshouser BA, Ashwal S, Shu S, Hinshaw Jr DB. Proton MR spectroscopy in children with acute brain injury: comparison of short and long echo time acquisitions. J Magn Reson Imaging. 2000;11(1):9–19.PubMedCrossRefGoogle Scholar
  18. 18.
    Friedman SD, Brooks WM, Jung RE, et al. Quantitative proton MRS predicts outcome after traumatic brain injury. Neurology. 1999;52(7):1384–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Ricci R, Barbarella G, Musi P, Boldrini P, Trevisan C, Basaglia N. Localised proton MR spectroscopy of brain metabolism changes in vegetative patients. Neuroradiology. 1997;39(5):313–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Holshouser BA, Ashwal S, Luh GY, et al. Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children. Radiology. 1997;202(2):487–96.PubMedGoogle Scholar
  21. 21.
    Haseler LJ, Arcinue E, Danielsen ER, Bluml S, Ross BD. Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of neuronal damage in shaken baby syndrome. Pediatrics. 1997;99(1):4–14.PubMedCrossRefGoogle Scholar
  22. 22.
    Condon B, Oluoch-Olunya D, Hadley D, Teasdale G, Wagstaff A. Early 1 H magnetic resonance spectroscopy of acute head injury: four cases. J Neurotrauma. 1998;15(8):563–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Holshouser BA, Tong KA, Ashwal S. Proton MR spectroscopic imaging depicts diffuse axonal injury in children with traumatic brain injury. AJNR Am J Neuroradiol. 2005;26(5):1276–85.PubMedGoogle Scholar
  24. 24.
    Cecil KM, Hills EC, Sandel ME, et al. Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. J Neurosurg. 1998;88(5):795–801.PubMedCrossRefGoogle Scholar
  25. 25.
    Choe BY, Suh TS, Choi KH, Shinn KS, Park CK, Kang JK. Neuronal dysfunction in patients with closed head injury evaluated by in vivo 1 H magnetic resonance spectroscopy. Invest Radiol. 1995;30(8):502–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Shutter L, Tong KA, Holshouser BA. Proton MRS in acute traumatic brain injury: role for glutamate/glutamine and choline for outcome prediction. J Neurotrauma. 2004;21(12):1693–705.PubMedCrossRefGoogle Scholar
  27. 27.
    Kay T, Harrington DE, et al. Definition of mild traumatic brain injury. J Head Trauma Rehabilitat. 1993;8(3):86–7.CrossRefGoogle Scholar
  28. 28.
    Lin A, Ross BD, Harris K, Wong W. Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. NeuroRx. 2005;2(2):197–214.PubMedCrossRefGoogle Scholar
  29. 29.
    Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, Little DM. White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain. 2007;130(10):2508–19.PubMedCrossRefGoogle Scholar
  30. 30.
    Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21(5):375–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Iverson GL, Gaetz M, Lovell MR, Collins MW. Cumulative effects of concussion in amateur athletes. Brain Inj. 2004;18(5):433–43.PubMedCrossRefGoogle Scholar
  32. 32.
    Meehan 3rd WP, Bachur RG. Sport-related concussion. Pediatrics. 2009;123(1):114–23.PubMedCrossRefGoogle Scholar
  33. 33.
    CDC. Nonfatal traumatic brain injuries from sports and recreation activities–United States, 2001–2005. MMWR. 2007;56(29):733–7.Google Scholar
  34. 34.
    Field M, Collins MW, Lovell MR, Maroon J. Does age play a role in recovery from sports-related concussion? A comparison of high school and collegiate athletes. J Pediatr. 2003;142(5):546–53.PubMedCrossRefGoogle Scholar
  35. 35.
    Cimatti M. Assessment of metabolic cerebral damage using proton magnetic resonance spectroscopy in mild traumatic brain injury. J Neurosurg Sci. 2006;50(4):83–8.PubMedGoogle Scholar
  36. 36.
    Henry LC, Tremblay SB, Boulanger Y, Ellemberg D, Lassonde M. Neurometabolic changes in the acute phase following sports concussions correlate with symptom severity. J Neurotrauma. 2009;27:65–76.CrossRefGoogle Scholar
  37. 37.
    Vagnozzi R, Signoretti S, Tavazzi B, et al. Temporal window of metabolic brain vulnerability to concussion: A pilot 1 H-magnetic resonance spectroscopic study in concussed athletes-Part III. Neurosurgery. 2008;62(6):1286–96.PubMedCrossRefGoogle Scholar
  38. 38.
    Belanger HG, Spiegel E, Vanderploeg RD. Neuropsychological performance following a history of multiple self-reported concussions: A meta-analysis. J Int Neuropsychol Soc. 2009;11:1–6.CrossRefGoogle Scholar
  39. 39.
    Omalu BI, Bailes J, Hammers JL, Fitzsimmons RP. Chronic traumatic encephalopathy, suicides and parasuicides in professional American athletes: The role of the forensic pathologist. Am J Forensic Med Pathol. 2010;31:130–2.PubMedCrossRefGoogle Scholar
  40. 40.
    McKee A, Cantu R, Nowinski C, et al. Chronic traumatic encephalopathy in athletes. J Neuropath and Exp Neurol. 2009;68:709–35.CrossRefGoogle Scholar
  41. 41.
    Guskiewicz KM, Marshall SW, Bailes J, et al. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 2007;39(6):903–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Martland HS. PUNCH DRUNK. J Am Med Assoc. 1928;91(15):1103–7.CrossRefGoogle Scholar
  43. 43.
    Millspaugh J. Dementia Pugilistica. US Naval Medical Bulletin. 1937;35(3):297–303.Google Scholar
  44. 44.
    Ramadan S, Mountford CE. Two-dimensional magnetic resonance spectroscopy on biopsy and in vivo. In: Webb GA, editor. Annual reports on NMR spectroscopy, vol. 65. Burlington: Academic; 2009. p. 161–99.Google Scholar
  45. 45.
    Thomas MA, Hattori N, Umeda M, Sawada T, Naruse S. Evaluation of two-dimensional L-COSY and JPRESS using a 3 T MRI scanner: from phantoms to human brain in vivo. NMR Biomed. 2003;16(5):245–51.PubMedCrossRefGoogle Scholar
  46. 46.
    Lin A, Ramadan S, Stanwell P, et al. In vivo L-COSY MR distinguishes glutamate from glutamine and shows neuropathic pain to cause a buildup of glutamine in the brain. Proc Int Soc Magn Reson Med. 2010;18:381.Google Scholar
  47. 47.
    Gopinath SP, Valadka AB, Goodman JC, Robertson CS. Extracellular glutamate and aspartate in head injured patients. Acta Neurochir. 2000;76:437–8.Google Scholar
  48. 48.
    Bullock R, Zauner A, Woodward JJ, et al. Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg. 1998;89(4):507–18.PubMedCrossRefGoogle Scholar
  49. 49.
    Shohami E, Shapira Y, Yadid G, Reisfeld N, Yedgar S. Brain phospholipase A2 is activated after experimental closed head injury in the rat. J Neurochem. 1989;53(5):1541–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Nilsson P, Hillered L, Ponten U, Ungerstedt U. Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab. 1990;10(5):631–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Deutschman CS, Konstantinides FN, Raup S, Thienprasit P, Cerra FB. Physiological and metabolic response to isolated closed-head injury. Part 1: Basal metabolic state: correlations of metabolic and physiological parameters with fasting and stressed controls. J Neurosurg. 1986;64(1):89–98.PubMedCrossRefGoogle Scholar
  52. 52.
    Cecil KM, Hills EC, Sandel ME, et al. Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. J Neurosurg. 1998;88(5):795–801.PubMedCrossRefGoogle Scholar
  53. 53.
    Garnett MR, Blamire AM, Rajagopalan B, Styles P, Cadoux-Hudson TAD. Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: a magnetic resonance spectroscopy study. Brain. 2000;123(7):1403–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Govindaraju V, Gauger GE, Manley GT, Ebel A, Meeker M, Maudsley AA. Volumetric proton spectroscopic imaging of mild traumatic brain injury. Am J Neuroradiol. 2004;25(5):730–7.PubMedGoogle Scholar
  55. 55.
    Kirov I, Fleysher L, Babb JS, Silver JM, Grossman RI, Gonen O. Characterizing ‘mild’ in traumatic brain injury with proton MR spectroscopy in the thalamus: Initial findings. Vol 21: Informa Healthcare; 2007:1147–1154.Google Scholar
  56. 56.
    Cohen BA, Inglese M, Rusinek H, Babb JS, Grossman RI, Gonen O. Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury. Am J Neuroradiol. 2007;28(5):907–13.PubMedGoogle Scholar
  57. 57.
    Nakabayashi M, Suzaki S, Tomita H. Neural injury and recovery near cortical contusions: a clinical magnetic resonance spectroscopy study. J Neurosurg. 2007;106(3):370–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Gasparovic C, Yeo R, Mannell M, et al. Neurometabolite concentrations in gray and white matter in mild traumatic brain injury: a 1H Magnetic resonance spectroscopy study. J Neurotrauma. 2009;26:1635–43.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Alexander P. Lin
    • 1
  • Stefan Blüml
    • 2
  1. 1.Department of RadiologyBrigham and Women’s HospitalBostonUSA
  2. 2.Department of Radiology, Children’s Hospital Los Angeles, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations