Advertisement

Functional MRI of the Spinal Cord

  • Patrick StromanEmail author
  • Massimo Filippi
Protocol
Part of the Neuromethods book series (NM, volume 119)

Abstract

Evidence to date shows that fMRI of the spinal cord (spinal fMRI) can reliably demonstrate regions involved with sensation of tactile, thermal, and painful stimuli, and with motor tasks. Spinal fMRI acquisition methods based on BOLD contrast have been recently optimized. Results have demonstrated the ability of spinal fMRI to provide objective assessments of sensory and motor function, and discriminate responses when modulated by cognitive/emotional factors. Studies have been also carried out with patients with cord trauma, and in people with multiple sclerosis (MS). The availability of essentially automated analysis, large extent coverage of the spinal cord, and spatial normalization to permit comparisons with reference results and labeling of active regions are being implemented with the aim to translate the method into a practical clinical assessment tool.

The research completed so far indicates that spinal fMRI will be able to demonstrate where the neuronal activity is altered at any level (cervical, thoracic, lumbar, or sacral), whether or not information is reaching the cord from the periphery, and whether or not there is descending modulation of the response. It may also be able to provide an objective measure of pain, and to demonstrate the extent and mechanism of changes over time after an injury.

Key words

Spinal fMRI Blood oxygen level dependent Multiple sclerosis Cord trauma Pain 

References

  1. 1.
    Figley CR, Stroman PW (2007) Investigation of human cervical and upper thoracic spinal cord motion: implications for imaging spinal cord structure and function. Magn Reson Med 58(1):185–189PubMedCrossRefGoogle Scholar
  2. 2.
    Figley CR, Yau D, Stroman PW (2008) Attenuation of lower-thoracic, lumbar, and sacral spinal cord motion: implications for imaging human spinal cord structure and function. AJNR Am J Neuroradiol 29(8):1450–1454PubMedCrossRefGoogle Scholar
  3. 3.
    Yoshizawa T, Nose T, Moore GJ, Sillerud LO (1996) Functional magnetic resonance imaging of motor activation in the human cervical spinal cord. Neuroimage 4(3 Pt 1):174–182PubMedCrossRefGoogle Scholar
  4. 4.
    Menon RS, Ogawa S, Kim SG, Ellermann JM, Merkle H, Tank DW, Ugurbil K (1992) Functional brain mapping using magnetic resonance imaging. Signal changes accompanying visual stimulation. Invest Radiol 27(Suppl 2):S47–S53PubMedCrossRefGoogle Scholar
  5. 5.
    Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG, Merkle H, Ugurbil K (1992) Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci U S A 89(13):5951–5955PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Stroman PW, Nance PW, Ryner LN (1999) BOLD MRI of the human cervical spinal cord at 3 tesla. Magn Reson Med 42(3):571–576PubMedCrossRefGoogle Scholar
  7. 7.
    Madi S, Flanders AE, Vinitski S, Herbison GJ, Nissanov J (2001) Functional MR imaging of the human cervical spinal cord. AJNR Am J Neuroradiol 22(9):1768–1774PubMedGoogle Scholar
  8. 8.
    Backes WH, Mess WH, Wilmink JT (2001) Functional MR imaging of the cervical spinal cord by use of median nerve stimulation and fist clenching. AJNR Am J Neuroradiol 22(10):1854–1859PubMedGoogle Scholar
  9. 9.
    Stroman PW, Ryner LN (2001) Functional MRI of motor and sensory activation in the human spinal cord. Magn Reson Imaging 19(1):27–32PubMedCrossRefGoogle Scholar
  10. 10.
    Stroman PW, Krause V, Malisza KL, Frankenstein UN, Tomanek B (2001) Characterization of contrast changes in functional MRI of the human spinal cord at 1.5 T. Magn Reson Imaging 19(6):833–838PubMedCrossRefGoogle Scholar
  11. 11.
    Bandettini PA, Wong EC, Jesmanowicz A, Hinks RS, Hyde JS (1994) Spin-echo and gradient-echo EPI of human brain activation using BOLD contrast: a comparative study at 1.5 T. NMR Biomed 7(1–2):12–20PubMedCrossRefGoogle Scholar
  12. 12.
    Figley CR, Leitch JK, Stroman PW (2010) In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change. Magn Reson Imaging 28(8):1234–1243PubMedCrossRefGoogle Scholar
  13. 13.
    Figley CR, Stroman PW (2012) Measurement and characterization of the human spinal cord SEEP response using event-related spinal fMRI. Magn Reson Imaging 30(4):471–484PubMedCrossRefGoogle Scholar
  14. 14.
    Stroman PW, Krause V, Malisza KL, Frankenstein UN, Tomanek B (2002) Extravascular proton-density changes as a non-BOLD component of contrast in fMRI of the human spinal cord. Magn Reson Med 48(1):122–127PubMedCrossRefGoogle Scholar
  15. 15.
    Stroman PW, Lee AS, Pitchers KK, Andrew RD (2008) Magnetic resonance imaging of neuronal and glial swelling as an indicator of function in cerebral tissue slices. Magn Reson Med 59(4):700–706PubMedCrossRefGoogle Scholar
  16. 16.
    Stroman PW, Malisza KL, Onu M (2003) Functional magnetic resonance imaging at 0.2 Tesla. Neuroimage 20(2):1210–1214PubMedCrossRefGoogle Scholar
  17. 17.
    Bosma RL, Stroman PW (2014) Assessment of data acquisition parameters, and analysis techniques for noise reduction in spinal cord fMRI data. Magn Reson Imaging 32(5):473–481PubMedCrossRefGoogle Scholar
  18. 18.
    Komisaruk BR, Mosier KM, Liu WC, Criminale C, Zaborszky L, Whipple B, Kalnin A (2002) Functional localization of brainstem and cervical spinal cord nuclei in humans with fMRI. AJNR Am J Neuroradiol 23(4):609–617PubMedGoogle Scholar
  19. 19.
    Cohen-Adad J, Gauthier CJ, Brooks JC, Slessarev M, Han J, Fisher JA, Rossignol S, Hoge RD (2010) BOLD signal responses to controlled hypercapnia in human spinal cord. Neuroimage 50(3):1074–1084PubMedCrossRefGoogle Scholar
  20. 20.
    Maieron M, Iannetti GD, Bodurka J, Tracey I, Bandettini PA, Porro CA (2007) Functional responses in the human spinal cord during willed motor actions: evidence for side- and rate-dependent activity. J Neurosci 27(15):4182–4190PubMedCrossRefGoogle Scholar
  21. 21.
    Summers PE, Ferraro D, Duzzi D, Lui F, Iannetti GD, Porro CA (2010) A quantitative comparison of BOLD fMRI responses to noxious and innocuous stimuli in the human spinal cord. Neuroimage 50(4):1408–1415PubMedCrossRefGoogle Scholar
  22. 22.
    Nash P, Wiley K, Brown J, Shinaman R, Ludlow D, Sawyer AM, Glover G, Mackey S (2013) Functional magnetic resonance imaging identifies somatotopic organization of nociception in the human spinal cord. Pain 154(6):776–781PubMedCrossRefGoogle Scholar
  23. 23.
    Eippert F, Finsterbusch J, Bingel U, Buchel C (2009) Direct evidence for spinal cord involvement in placebo analgesia. Science 326(5951):404PubMedCrossRefGoogle Scholar
  24. 24.
    Sprenger C, Eippert F, Finsterbusch J, Bingel U, Rose M, Buchel C (2012) Attention modulates spinal cord responses to pain. Curr Biol 22(11):1019–1022PubMedCrossRefGoogle Scholar
  25. 25.
    Geuter S, Buchel C (2013) Facilitation of pain in the human spinal cord by nocebo treatment. J Neurosci 33(34):13784–13790PubMedCrossRefGoogle Scholar
  26. 26.
    van de Sand MF, Sprenger C, Buchel C (2015) BOLD responses to itch in the human spinal cord. Neuroimage 108:138–143PubMedCrossRefGoogle Scholar
  27. 27.
    Figley CR, Stroman PW (2011) The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals. Eur J Neurosci 33(4):577–588PubMedCrossRefGoogle Scholar
  28. 28.
    Stroman PW, Krause V, Frankenstein UN, Malisza KL, Tomanek B (2001) Spin-echo versus gradient-echo fMRI with short echo times. Magn Reson Imaging 19(6):827–831PubMedCrossRefGoogle Scholar
  29. 29.
    Stroman PW, Tomanek B, Krause V, Frankenstein UN, Malisza KL (2003) Functional magnetic resonance imaging of the human brain based on signal enhancement by extravascular protons (SEEP fMRI). Magn Reson Med 49(3):433–439PubMedCrossRefGoogle Scholar
  30. 30.
    Stroman PW, Kornelsen J, Lawrence J, Malisza KL (2005) Functional magnetic resonance imaging based on SEEP contrast: response function and anatomical specificity. Magn Reson Imaging 23(8):843–850PubMedCrossRefGoogle Scholar
  31. 31.
    Cahill CM, Stroman PW (2011) Mapping of neural activity produced by thermal pain in the healthy human spinal cord and brain stem: a functional magnetic resonance imaging study. Magn Reson Imaging 29(3):342–352PubMedCrossRefGoogle Scholar
  32. 32.
    Ghazni NF, Cahill CM, Stroman PW (2010) Tactile sensory and pain networks in the human spinal cord and brain stem mapped by means of functional MR imaging. AJNR Am J Neuroradiol 31(4):661–667PubMedCrossRefGoogle Scholar
  33. 33.
    Kozyrev N, Figley CR, Alexander MS, Richards JS, Bosma RL, Stroman PW (2012) Neural correlates of sexual arousal in the spinal cords of able-bodied men: a spinal fMRI investigation. J Sex Marital Ther 38(5):418–435PubMedCrossRefGoogle Scholar
  34. 34.
    Lawrence JM, Kornelsen J, Stroman PW (2011) Noninvasive observation of cervical spinal cord activity in children by functional MRI during cold thermal stimulation. Magn Reson Imaging 29(6):813–818PubMedCrossRefGoogle Scholar
  35. 35.
    Rempe T, Wolff S, Riedel C, Baron R, Stroman PW, Jansen O, Gierthmuhlen J (2014) Spinal fMRI reveals decreased descending inhibition during secondary mechanical hyperalgesia. PLoS One 9(11):e112325PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Rempe T, Wolff S, Riedel C, Baron R, Stroman PW, Jansen O, Gierthmuhlen J (2014) Spinal and supraspinal processing of thermal stimuli: an fMRI study. J Magn Reson Imaging 41(4):1046–1055PubMedCrossRefGoogle Scholar
  37. 37.
    Stroman PW (2009) Spinal fMRI investigation of human spinal cord function over a range of innocuous thermal sensory stimuli and study-related emotional influences. Magn Reson Imaging 27(10):1333–1346PubMedCrossRefGoogle Scholar
  38. 38.
    Lawrence JM, Stroman PW, Kollias SS (2008) Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes. Neuroradiology 50(3):273–280PubMedCrossRefGoogle Scholar
  39. 39.
    Stroman PW, Bosma RL, Tsyben A (2012) Somatotopic arrangement of thermal sensory regions in the healthy human spinal cord determined by means of spinal cord functional MRI. Magn Reson Med 68(3):923–931PubMedCrossRefGoogle Scholar
  40. 40.
    Bosma RL, Stroman PW (2014) Spinal cord response to stepwise and block presentation of thermal stimuli: a functional MRI study. J Magn Reson Imaging 41(5):1318–1325PubMedCrossRefGoogle Scholar
  41. 41.
    Stroman PW, Coe BC, Munoz DP (2011) Influence of attention focus on neural activity in the human spinal cord during thermal sensory stimulation. Magn Reson Imaging 29(1):9–18PubMedCrossRefGoogle Scholar
  42. 42.
    Dobek CE, Beynon ME, Bosma RL, Stroman PW (2014) Music modulation of pain perception and pain-related activity in the brain, brainstem, and spinal cord: an fMRI study. J Pain 15(10):1057–1068PubMedCrossRefGoogle Scholar
  43. 43.
    Agosta F, Valsasina P, Absinta M, Sala S, Caputo D, Filippi M (2009) Primary progressive multiple sclerosis: tactile-associated functional MR activity in the cervical spinal cord. Radiology 253(1):209–215PubMedCrossRefGoogle Scholar
  44. 44.
    Agosta F, Valsasina P, Caputo D, Rocca MA, Filippi M (2009) Tactile-associated fMRI recruitment of the cervical cord in healthy subjects. Hum Brain Mapp 30(1):340–345PubMedCrossRefGoogle Scholar
  45. 45.
    Agosta F, Valsasina P, Caputo D, Stroman PW, Filippi M (2008) Tactile-associated recruitment of the cervical cord is altered in patients with multiple sclerosis. Neuroimage 39(4):1542–1548PubMedCrossRefGoogle Scholar
  46. 46.
    Agosta F, Valsasina P, Rocca MA, Caputo D, Sala S, Judica E, Stroman PW, Filippi M (2008) Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis. Magn Reson Med 59(5):1035–1042PubMedCrossRefGoogle Scholar
  47. 47.
    Valsasina P, Agosta F, Absinta M, Sala S, Caputo D, Filippi M (2010) Cervical cord functional MRI changes in relapse-onset MS patients. J Neurol Neurosurg Psychiatry 81(4):405–408PubMedCrossRefGoogle Scholar
  48. 48.
    Valsasina P, Agosta F, Caputo D, Stroman PW, Filippi M (2008) Spinal fMRI during proprioceptive and tactile tasks in healthy subjects: activity detected using cross-correlation, general linear model and independent component analysis. Neuroradiology 50(10):895–902PubMedCrossRefGoogle Scholar
  49. 49.
    Valsasina P, Rocca MA, Absinta M, Agosta F, Caputo D, Comi G, Filippi M (2012) Cervical cord FMRI abnormalities differ between the progressive forms of multiple sclerosis. Hum Brain Mapp 33(9):2072–2080PubMedCrossRefGoogle Scholar
  50. 50.
    Cadotte DW, Bosma R, Mikulis D, Nugaeva N, Smith K, Pokrupa R, Islam O, Stroman PW, Fehlings MG (2012) Plasticity of the injured human spinal cord: insights revealed by spinal cord functional MRI. PLoS One 7(9):e45560PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Stroman PW, Kornelsen J, Bergman A, Krause V, Ethans K, Malisza KL, Tomanek B (2004) Noninvasive assessment of the injured human spinal cord by means of functional magnetic resonance imaging. Spinal Cord 42(2):59–66PubMedCrossRefGoogle Scholar
  52. 52.
    Kornelsen J, Stroman PW (2007) Detection of the neuronal activity occurring caudal to the site of spinal cord injury that is elicited during lower limb movement tasks. Spinal Cord 45(7):485–490PubMedCrossRefGoogle Scholar
  53. 53.
    Stroman PW (2011) Essentials of functional MRI. Taylor & Francis Group, LLC, Boca Raton, FLCrossRefGoogle Scholar
  54. 54.
    Murphy K, Bodurka J, Bandettini PA (2007) How long to scan? The relationship between fMRI temporal signal to noise ratio and necessary scan duration. Neuroimage 34(2):565–574PubMedCrossRefGoogle Scholar
  55. 55.
    Finsterbusch J, Eippert F, Buchel C (2012) Single, slice-specific z-shim gradient pulses improve T2*-weighted imaging of the spinal cord. Neuroimage 59(3):2307–2315PubMedCrossRefGoogle Scholar
  56. 56.
    Figley CR, Stroman PW (2009) Development and validation of retrospective spinal cord motion time-course estimates (RESPITE) for spin-echo spinal fMRI: improved sensitivity and specificity by means of a motion-compensating general linear model analysis. Neuroimage 44(2):421–427PubMedGoogle Scholar
  57. 57.
    Brooks JC, Beckmann CF, Miller KL, Wise RG, Porro CA, Tracey I, Jenkinson M (2008) Physiological noise modelling for spinal functional magnetic resonance imaging studies. Neuroimage 39(2):680–692PubMedCrossRefGoogle Scholar
  58. 58.
    Verma T, Cohen-Adad J (2014) Effect of respiration on the B0 field in the human spinal cord at 3T. Magn Reson Med 72(6):1629–1636PubMedCrossRefGoogle Scholar
  59. 59.
    Myronenko A, Song XB (2009) Image registration by minimization of residual complexity. Proc Cvpr IEEE. pp 49–56Google Scholar
  60. 60.
    Myronenko A, Song XB (2010) Intensity-based image registration by minimizing residual complexity. IEEE Trans Med Imag 29(11):1882–1891CrossRefGoogle Scholar
  61. 61.
    Stroman PW, Figley CR, Cahill CM (2008) Spatial normalization, bulk motion correction and coregistration for functional magnetic resonance imaging of the human cervical spinal cord and brainstem. Magn Reson Imaging 26(6):809–814PubMedCrossRefGoogle Scholar
  62. 62.
    Lang J, Bartram CT (1982) Fila radicularia of the ventral and dorsal radices of the human spinal cord. Gegenbaurs Morphol Jahrb 128(4):417–462PubMedGoogle Scholar
  63. 63.
    Gray H (1995) Gray’s anatomy: the anatomical basis of medicine and surgery. In: Williams PL, Bannister LH, Berry MM, Collins P, Dyson M, Dussek JE, Ferguson MWJ (eds) Gray’s anatomy: the anatomical basis of medicine and surgery. Churchill-Livingstone, London, pp 975–1011Google Scholar
  64. 64.
    Talairach J, Tournoux P (1988) Co-planar sterotaxic atlas of the human brain. Thieme Medical Publishers Inc, New YorkGoogle Scholar
  65. 65.
    Naidich TP, Duvernoy HM, Delman BN, Sorensen AG, Kollias SS, Haacke EM (2009) Internal architecture of the brain stem with key axial sections. Duvernoy’s atlas of the human brain stem and cerebellum. Springer, New York, pp 79–82CrossRefGoogle Scholar
  66. 66.
    McArdle JJ, McDonald RP (1984) Some algebraic properties of the Reticular Action Model for moment structures. Br J Math Stat Psychol 37(Pt 2):234–251PubMedCrossRefGoogle Scholar
  67. 67.
    Craggs JG, Staud R, Robinson ME, Perlstein WM, Price DD (2012) Effective connectivity among brain regions associated with slow temporal summation of C-fiber-evoked pain in fibromyalgia patients and healthy controls. J Pain 13(4):390–400PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Buchel C, Friston K (2001) Interactions among neuronal systems assessed with functional neuroimaging. Rev Neurol 157(8–9 Pt 1):807–815PubMedGoogle Scholar
  69. 69.
    Buchel C, Friston KJ (1997) Modulation of connectivity in visual pathways by attention: cortical interactions evaluated with structural equation modelling and fMRI. Cereb Cortex 7(8):768–778PubMedCrossRefGoogle Scholar
  70. 70.
    Bollen KA (1989) Structural equations with latent variables. Wiley, New YorkCrossRefGoogle Scholar
  71. 71.
    Millan MJ (2002) Descending control of pain. Prog Neurobiol 66(6):355–474PubMedCrossRefGoogle Scholar
  72. 72.
    Barry RL, Smith SA, Dula AN, Gore JC (2014) Resting state functional connectivity in the human spinal cord. eLife 3:e02812PubMedPubMedCentralGoogle Scholar
  73. 73.
    Kashkouli Nejad K, Sugiura M, Thyreau B, Nozawa T, Kotozaki Y, Furusawa Y, Nishino K, Nukiwa T, Kawashima R (2014) Spinal fMRI of interoceptive attention/awareness in experts and novices. Neural Plast 2014:679509PubMedPubMedCentralGoogle Scholar
  74. 74.
    Smith SD, Kornelsen J (2011) Emotion-dependent responses in spinal cord neurons: a spinal fMRI study. Neuroimage 58(1):269–274PubMedCrossRefGoogle Scholar
  75. 75.
    Kornelsen J, Smith SD, McIver TA (2014) A neural correlate of visceral emotional responses: evidence from fMRI of the thoracic spinal cord. Soc Cogn Affect Neurosci 10(4):584–588PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Khan HS, Bosma RL, Beynon M, Dobek C, McIver T, Stroman PW (2013) Pain processing networks in the brain and spinal cord mapped using Functional Magnetic Resonance Imaging. Program number II6 66.01. 2013 Meeing Planner San Diego, CA; Society for NeuroscienceGoogle Scholar
  77. 77.
    McIver TA, Kornelsen J, Smith SD (2013) Limb-specific emotional modulation of cervical spinal cord neurons. Cogn Affect Behav Neurosci 13(3):464–472PubMedCrossRefGoogle Scholar
  78. 78.
    Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29(3):162–173PubMedCrossRefGoogle Scholar
  79. 79.
    Friston KJ, Josephs O, Zarahn E, Holmes AP, Rouquette S, Poline J (2000) To smooth or not to smooth? Bias and efficiency in fMRI time-series analysis. Neuroimage 12(2):196–208PubMedCrossRefGoogle Scholar
  80. 80.
    Stroman PW, Wheeler-Kingshott C, Bacon M, Schwab JM, Bosma R, Brooks J, Cadotte D, Carlstedt T, Ciccarelli O, Cohen-Adad J, Curt A, Evangelou N, Fehlings MG, Filippi M, Kelley BJ, Kollias S, Mackay A, Porro CA, Smith S, Strittmatter SM, Summers P, Tracey I (2014) The current state-of-the-art of spinal cord imaging: methods. Neuroimage 84:1070–1081PubMedCrossRefGoogle Scholar
  81. 81.
    Wheeler-Kingshott CA, Stroman PW, Schwab JM, Bacon M, Bosma R, Brooks J, Cadotte DW, Carlstedt T, Ciccarelli O, Cohen-Adad J, Curt A, Evangelou N, Fehlings MG, Filippi M, Kelley BJ, Kollias S, Mackay A, Porro CA, Smith S, Strittmatter SM, Summers P, Thompson AJ, Tracey I (2014) The current state-of-the-art of spinal cord imaging: applications. Neuroimage 84:1082–1093PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Diagnostic Radiology, c/o Center for Neuroscience StudiesQueen’s UniversityKingstonCanada
  2. 2.Department of Physics, c/o Center for Neuroscience StudiesQueen’s UniversityKingstonCanada
  3. 3.Neuroimaging Research Unit, Institute of Experimental Neurology, Division of NeuroscienceSan Raffaele Scientific Institute and Vita-Salute San Raffaele UnviersityMilanItaly
  4. 4.Department of Neurology, Division of NeuroscienceSan Raffaele Scientific Institute and Vita-Salute San Raffaele UniversityMilanItaly

Personalised recommendations