Advertisement

BOLD fMRI pp 71-92 | Cite as

Challenges in fMRI and Its Limitations

  • R. Todd Constable
Chapter

Abstract

This chapter will explore some of the challenges of functional magnetic resonance imaging (fMRI), particularly the constraints encountered in terms of spatial and temporal resolution, as well as the factors that limit the ability of MRI to detect functional activation. These issues of sensitivity and resolution are intimately related and not easily separable; for example, increasing spatial resolution usually can only be achieved at the expense of temporal resolution and sensitivity loss. In addition to examining the factors limiting the sensitivity and resolution of fMRI, this chapter will explore some of the trade-offs involved in optimizing one or more of these variables.

Keywords

Cerebral Blood Flow Cerebral Blood Volume Arterial Spin Label Echo Planar Imaging fMRI Experiment 
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.

References

  1. 1.
    Yang Y, Wen H, Mattay VS, Balaban RS, Frank JA, Duyn JH. Comparison of 3D BOLD functional MRI with spiral acquisition at 1.5T and 4.0T. Neuroimage. 1999;9:446–451.PubMedCrossRefGoogle Scholar
  2. 2.
    Yacoub E, Shmuel A, Pfeuffer J, Van De Moortele PF, Adriany G, Andersen P, Vaughan JT, Merkle H, Ugurbil K, Hu X. Imaging brain function in humans at 7 Tesla. Magn Reson Med. 2001;45(4):588–594.PubMedCrossRefGoogle Scholar
  3. 3.
    Ojemann JG, Akbudak E, Snyder AZ, McKinstry RC, Raichle ME, Conturo TE. Anatomic localization and quantitative analysis of gradient refocused echo-planar fMRI susceptibility artifacts. Neuroimage. 1997;6:156–167.PubMedCrossRefGoogle Scholar
  4. 4.
    Merboldt KD, Finsterbusch J, Frahm J. Reducing inhomogeneity artifacts in functional MRI of human brain activation—thin sections versus gradient compensation. J Magn Reson. 2000;145(2):184–191.PubMedCrossRefGoogle Scholar
  5. 5.
    Wadghiri YZ, Johnson G, Turnbull DH. Sensitivity and performance time in MRI dephasing artifact reduction methods. Magn Reson Med. 2001;45:470–476.PubMedCrossRefGoogle Scholar
  6. 6.
    Constable RT, Spencer DD. Repetition time in echo planar functional MR ­imaging. Magn Reson Med. 2001;46(4):748–755.PubMedCrossRefGoogle Scholar
  7. 7.
    Constable RT. Functional MR imaging using gradient echo EPI in the presence of large static field inhomogeneities. J Magn Reson Imaging. 1995;5(6):746–752.PubMedCrossRefGoogle Scholar
  8. 8.
    Yang QX, Dardzinski BJ, Li S, Smith MB. Multi-gradient echo with susceptibility inhomogeneity compensation (MGESIC): demonstration of fMRI in the olfactory cortex at 3.0T. Magn Reson Med. 1997;37:331–335.PubMedCrossRefGoogle Scholar
  9. 9.
    Glover GH. 3D z-shim method for reduction of susceptibility effects in BOLD fMRI. Magn Reson Med. 1999;42(2):290–299.PubMedCrossRefGoogle Scholar
  10. 10.
    Frahm J, Merboldt JD, Hanicke W. Direct flash MR imaging of magnetic field inhomogeneities by gradient compensation. Magn Reson Med. 1988;6:474–480.PubMedCrossRefGoogle Scholar
  11. 11.
    Cho ZH, Ro YM. Reduction of susceptibility artifact in gradient-echo imaging, Magn Reson Med. 1992;23:193–200.PubMedCrossRefGoogle Scholar
  12. 12.
    Stenger VA, Boada FE, Noll DC. Multishot 3D slice-select tailored RF pulses for MRI. Magn Reson Med. 2002;48(1):157–165.PubMedCrossRefGoogle Scholar
  13. 13.
    Song AW. Single-shot EPI with signal recovery from susceptibility induced losses. Magn Reson Med. 2001;46:407–411.PubMedCrossRefGoogle Scholar
  14. 14.
    Yang Y. Perfusion MR Imaging with pulsed arterial spin-labeling: Basic principles and applications in functional brain imaging. Concepts Magn Reson. 2002;14:347–357.CrossRefGoogle Scholar
  15. 15.
    Constable RT, Kennan RP, Puce A, McCarthy G, Gore JC. Functional MR imaging using fast spin echo at 1.5T. Magn Reson Med. 1994;31:686–690.PubMedCrossRefGoogle Scholar
  16. 16.
    Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM. MR contrast due to intravascular magnetic-susceptibility perturbations. Magn Reson Med. 1995;34:555–566.PubMedCrossRefGoogle Scholar
  17. 17.
    Weisskoff RM, Zuo CS, Boxerman JL, Rosen BR. Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med. 1994;31:601–610.PubMedCrossRefGoogle Scholar
  18. 18.
    Kennan RP, Zhong JH, Gore JC. Intravascular susceptibility contrast mechanisms in tissues. Magn Reson Med. 1994;31:9–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Raj D, Anderson AW, Gore JC. Respiratory effects in human functional magnetic resonance imaging due to bulk susceptibility changes. Phys Med Biol. 2001;46(12):3331–3340.PubMedCrossRefGoogle Scholar
  20. 20.
    Cavaglia M, Dombrowski SM, Drazba J, Vasanji A, Bokesch PM, Janigro D. Regional variation in brain capillary density and vascular response to ischemia. Brain Res. 2001;910(1–2):81–93.PubMedCrossRefGoogle Scholar
  21. 21.
    Heeger DJ, Huk AC, Geisler WS, Albrecht DG. Spike versus BOLD: What does neuroimaging tell us about neuronal activity? Nat Neurosci. 2000;3(7):631–633.PubMedCrossRefGoogle Scholar
  22. 22.
    Rees G, Friston K, Koch C. A direct quantitative relationship between functional properties of human and macaque V5. Nat Neurosci. 2000;3:716–723.PubMedCrossRefGoogle Scholar
  23. 23.
    Logothetis NK, Guggenberger H, Peled S, Pauls J. Neurophysiological investigation of the basis of the fMRI signal change. Nat Neurosci. 1999;2:555–562.PubMedCrossRefGoogle Scholar
  24. 24.
    Hyder F, Rothman DL, Shulman RG. Total neuroenergetics support localized brain activity: implications for the interpretation of fMRI. Proc Natl Acad Sci USA. 2002;99(16):10771–10776.PubMedCrossRefGoogle Scholar
  25. 25.
    Smith AJ, Blumenfeld H, Behar KL, Rothman DL, Shulman RG, Hyder F. Cerebrla energetics and spiking frequency: the neurophysiological basis of fMRI. Proc Natl Acad Sci USA. 2002;99(16):10765–19770.PubMedCrossRefGoogle Scholar
  26. 26.
    Turner R. How much cortex can a vein drain? Downstream dilution of activation-related cerebral blood oxygenation changes. Neuroimage. 2002;16:1062–1067.PubMedCrossRefGoogle Scholar
  27. 27.
    Menon RS, Goodyear BG. Submillimeter functional localization in human striate cortex using BOLD contrast at 4 Tesla: Implications for the vascular point spread function. Magn Reson Med. 1999;41:230–235.PubMedCrossRefGoogle Scholar
  28. 28.
    Gati JS, Menon RS, Ugurbil K, Rutt BK. Experimental determination of the BOLD field strength dependence in vessels and tissue. Magn Reson Med. 1997;38:296–302.PubMedCrossRefGoogle Scholar
  29. 29.
    Cheng K, Waggoner RA, Tanaka K. Mapping human ocular dominance columns with high field (4T) functional magnetic resonance imaging. Proc Intl Soc Magn Reson Med. 2000;8:978.Google Scholar
  30. 30.
    Song AW, Wong EC, Tan SG, Hyde JS. Diffusion weighted fMRI at 1.5T. Magn Reson Med. 1996;35:155–158.PubMedCrossRefGoogle Scholar
  31. 31.
    Andersson L, Bolling M, Wirestam R, Holtas S, Stahlberg F. Combined diffusion weighting and CSF suppression in functional MRI. NMR Biomed. 2002;15:235–240.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhong J, Kennan RP, Gore JC. Effects of susceptibility variations on NMR measurements of diffusion. J Magn Reson. 1991;95:267–280.Google Scholar
  33. 33.
    Lee SP, Silva AC, Ugurbil K, Kim SG. Diffusion-weighted spin-echo fMRI at 9.4T: microvascular/tissue contribution to BOLD signal changes. Magn Reson Med. 1999;42(5):919–928.PubMedCrossRefGoogle Scholar
  34. 34.
    Song AW, Woldorff MG, Gangstead S, Mangun GR, McCarthy G. Enhanced spatial localization of neuronal activation using simultaneous apparent-diffusion-coefficient and blood-oxygenation functional magnetic resonance imaging. Neuroimage. 2002;17:742–750.PubMedCrossRefGoogle Scholar
  35. 35.
    Frostig RD, Lieke EE, Ts’o DY, Grinvald A. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution imaging of intrinsic signals. Proc Natl Acad Sci USA. 1990;87:6082–6086.PubMedCrossRefGoogle Scholar
  36. 36.
    Malonek D, Grinvald A. Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: Implications for functional brain mapping. Science. 1996;272:551–554.PubMedCrossRefGoogle Scholar
  37. 37.
    Ernst T, Hennig J. Observation of a fast response in functional MR. Magn Reson Med. 1994;32:146–149.PubMedCrossRefGoogle Scholar
  38. 38.
    Menon RS, Ogawa S, Strupp JP, Anderson P, Ugurbil K. BOLD based functional MRI at 4 Tesla includes capillary bed contribution: Echo-planar imaging correlates with previous optical imaging using intrinsic signals. Magn Reson Med. 1995;33:453–459.PubMedCrossRefGoogle Scholar
  39. 39.
    Hu X, Le TH, Ugurbil K. Evaluation of the early response in fMRI in individual subjects using short stimulus duration. Magn Reson Med. 1997;37:877–884.PubMedCrossRefGoogle Scholar
  40. 40.
    Duong TQ, Kim DS, Ugurbil K, Kim SG. Spatiotemporal dynamics of the BOLD fMRI signals: towards mapping submillimeter cortical columns using the early negative response. Magn Reson Med. 2000;44(2):231–242.PubMedCrossRefGoogle Scholar
  41. 41.
    Kim DS, Duong DQ, Kim S-G. High resolution mapping of iso-orientation columns by fMRI. Nat Neurosci. 2000;3:164–169.PubMedCrossRefGoogle Scholar
  42. 42.
    Buxton RB. The elusive initial dip. Neuroimage. 2001;13:953–958.PubMedCrossRefGoogle Scholar
  43. 43.
    Lindauer U, Royl G, Leithner C, Kuhl M, Gold L, Gethmann J, Kohl-Bareis M, Villringer A, Diirnagl U. No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. Neuroimage. 2001;13:986–999.CrossRefGoogle Scholar
  44. 44.
    Jones M, Berwick J, Johnston D, Mayhew J. Concurrent optical imaging spectroscopy and laser-doppler flowmetry: The relationship between blood flow, oxygenation, and volume in rodent barrel cortex. Neuroimage. 2001;13:1000–1013.CrossRefGoogle Scholar
  45. 45.
    Studholme C, Constable RT, Duncan JS. Accurate alignment of functional EPI data to anatomical MRI physics based distortion model. IEEE Trans Med Imaging. 2001;19(11):1115–1127.Google Scholar
  46. 46.
    Jezzard P, Balaban RS. Correction for geometric distortion in EPI from Bo variations. Magn Reson Med. 1995;34:65–73.PubMedCrossRefGoogle Scholar
  47. 47.
    Jezzard P, Clare S. Sources of distortion in functional MRI data. Hum Brain Mapp. 1999;8(2–3):80–85.PubMedCrossRefGoogle Scholar
  48. 48.
    Reber PJ, Wong EC, Buxton RB, Frank LR. Correction of off resonance related distortion in echo planar images from Bo field variations. Magn Reson Med. 1995;34:65–73.CrossRefGoogle Scholar
  49. 49.
    Robson MD, Gore JC, Constable RT. Measurement of the point spread function in MRI using constant time imaging. Magn Reson Med. 1997;38(5):733–740.PubMedCrossRefGoogle Scholar
  50. 50.
    Zeng H, Constable RT. Image distortion correction in EPI: Comparison of field mapping with point spread function mapping. Magn Reson Med. 2002;48:137–146.PubMedCrossRefGoogle Scholar
  51. 51.
    Houston GC, Papadakis NG, Carpenter A, Hall LD, Mukherjee B, James MF, Huang CLH. Mapping of the cerebral response to hypoxia measured using graded asymmetric spin echo. Magn Reson Imag. 2000;18:1043–1054.CrossRefGoogle Scholar
  52. 52.
    Zheng J, Ehrhardt JC, Cizadlo T, Yuh WTC. Comparison of inversion-recovery asymmetric spin-echo EPI and gradient-echo EPI for brain motor activation study. J Magn Reson Imaging. 1997;7:843–847.PubMedCrossRefGoogle Scholar
  53. 53.
    Scheffler K, Seifritz E, Bilecen D, Venkatesan R, Hennig J, Deimling M, Haacke EM. Detection of BOLD changes by means of a frequency-sensitive trueFISP technique: preliminary results. NMR Biomed. 2001;14:490–496.PubMedCrossRefGoogle Scholar
  54. 54.
    Calamante F, Thomas DL, Pell GS, Wiersma J, Turner R. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab. 1999;19:701–735.PubMedCrossRefGoogle Scholar
  55. 55.
    Singer JR. Blood flow rates by nuclear magnetic resonance measurements. Science. 1959;130;1652–1653.PubMedCrossRefGoogle Scholar
  56. 56.
    Edelman RR, Siewert B, Darby DG, Thangaraj V, Nobre AC, Mesulam MM, Warrash S. Quantitative mapping of cerebral blood flow and functional localization with echo-planar MR imaging and signal targeting with alternating radio frequency. Radiology. 1994;192:513–520.PubMedGoogle Scholar
  57. 57.
    Edelman RR, Chen Q. EPISTAR MRI: Multislice mapping of cerebral blood flow. Magn Reson Med. 1998;40:800–805.PubMedCrossRefGoogle Scholar
  58. 58.
    Kim SG. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med. 1995;34:293–301.PubMedCrossRefGoogle Scholar
  59. 59.
    Yang Y, Frank JA, Hou L, Ye FQ, McLaughlin AC, Duyn JH. Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin-labeling. Magn Reson Med. 1998;39:825–832.PubMedCrossRefGoogle Scholar
  60. 60.
    Hoge RD, Atkinson J, Gill B, Crelier GR, Marrett S, Pike GB. Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model. Magn Reson Med. 1999;42:849–863.PubMedCrossRefGoogle Scholar
  61. 61.
    Crelier GR, Hoge RD, Munger P, Pike GB. Perfusion based functional magnetic resonance imaging with single shot RARE and GRASE acquisitions. Magn Reson Med. 1999;41:132–136.PubMedCrossRefGoogle Scholar
  62. 62.
    Yang Y, Gu H, Zhan W, Xu S, Silbersweig DA, Stern E. Simultaneous perfusion and BOLD imaging using reverse spiral scanning at 3T: characterization of functional contrast and susceptibility artifacts. Magn Reson Med. 2002;48(2):278–289.PubMedCrossRefGoogle Scholar
  63. 63.
    Detre JA, Leigh JS, Williams DS, Koretsky AP. Perfusion imaging. Magn Reson Med. 1992;23:37–45.PubMedCrossRefGoogle Scholar
  64. 64.
    Gonzalez-At JB, Alsop DC, Detre JA. Cerebral perfusion and arterial transit time changes during task activation determined with continuous arterial spin labeling. Magn Reson Med. 2000;43:739–746.PubMedCrossRefGoogle Scholar
  65. 65.
    Yongbi MN, Yang Y, Frank JA, Duyn JH. Multislice perfusion imaging in human brain using the C-FOCI inversion pulse: comparison with hyperbolic secant. Magn Reson Med. 1999;42:1098–1105.PubMedCrossRefGoogle Scholar
  66. 66.
    Alsop DC, Detre JA. Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow. J Cereb Blood Flow Metab. 1996;16:1236–1249.PubMedCrossRefGoogle Scholar
  67. 67.
    Zhang W, Williams DS, Koretsky AP. Measurement of brain perfusion by volume-localized NMR spectroscopy using inversion of arterial water spins: accounting for transit time and cross-relaxation. Magn Reson Med. 1992;25:362–371.PubMedCrossRefGoogle Scholar
  68. 68.
    Wong EC, Buxton RB, Frank LR. Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling. NMR Biomed. 1997;10(4–5):237–249.PubMedCrossRefGoogle Scholar
  69. 69.
    Ye FQ, Yang Y, Duyn J, Mattay VS, Frank JA, Weinberger DR, McLaughlin AC. Quantitation of regional cerebral blood flow increases during motor activation: A multislice, steady-state, arterial spin tagging study. Magn Reson Med. 1999;42:404–407.PubMedCrossRefGoogle Scholar
  70. 70.
    Darby DG, Nobre AC, Thangaraj V, Edelman R, Mesulam MM, Warach S. Cortical activation in the human brain during lateral saccades using EPISTAR functional magnetic resonance imaging. Neuroimage. 1996;3:53–62.PubMedCrossRefGoogle Scholar
  71. 71.
    Lai S, Wang J, Jahng G-H. FAIR exempting separate T1 measurement (FAIREST): a novel technique for online quantitative perfusion imaging and multi-contrast fMRI. NMR Biomed. 2001;14:507–516.PubMedCrossRefGoogle Scholar
  72. 72.
    Belliveau JW, Kennedy DN, McKinstry RC, Buchbinder BR. Weisskoff RM, Cohen MS, Vevea JM, Brady TJ, Rosen BR. Functional mapping of the human visual cortex by magnetic resonance imaging. Science. 1991;254(4):716.PubMedCrossRefGoogle Scholar
  73. 73.
    Constable RT, Carpentier A, Pugh K, Westerveld M, Oszunar Y, Spencer DD. Investigation of the human hippocampal formation using a randomized-event-related paradigm and z-shimmed functional MRI. Neuroimage. 2000;12:55–62.PubMedCrossRefGoogle Scholar
  74. 74.
    Constable RT, Spencer DD. Composite image formation in z-shimmed functional MR imaging. Magn Reson Med. 1999;42(1):110–117.PubMedCrossRefGoogle Scholar
  75. 75.
    Yacoub E, Shmuel A, Pfeuffer J, Van De Moortele PF, Adriany G, Ugurbil K, Hu X. Investigation of the initial dip in fMRI at 7 Tesla. NMR Biomed. 2001;14(7–8):408–412.PubMedCrossRefGoogle Scholar
  76. 76.
    Yacoub E, Hu X. Detection of the early decrease in fMRI signal in the motorarea. Magn Reson Med. 2001;45:184–190.PubMedCrossRefGoogle Scholar
  77. 77.
    Ogawa S, Lee T-M, Stepnoski R, Chen W, Zhu X-H, Ugurbil K. An approach to probes some neural systems interaction by functional MRI at neural timescale down to milliseconds. Proc Natl Acad Sci USA. 2000;97(20):11026–11031.PubMedCrossRefGoogle Scholar
  78. 78.
    Miezin FM, Maccotta L, Ollinger JM, Petersen SE, Buckner RL. Characterizing the hemodynamic response: effects of presentation rate, sampling procedure, and the possibility of ordering brain activity based on relative timing. Neuroimage. 2000;11:735–759.PubMedCrossRefGoogle Scholar
  79. 79.
    Jovicich J, Norris DG. Functional MRI of the human brain with GRASE-basedBOLD contrast. Magn Reson Med. 1999;41:871–876.PubMedCrossRefGoogle Scholar
  80. 80.
    Niendorf T. On the application of susceptibility-weighted ultra-fast low-angle RARE experiments in functional MR imaging, Magn Reson Med. 1999;41:1189–1198.PubMedCrossRefGoogle Scholar

Copyright information

© Springer New York 2010

Authors and Affiliations

  • R. Todd Constable
    • 1
  1. 1.Department of Diagnostic Radiology, Neurosurgery, and Biomedical Engineering; and the Magnetic Resonance Research CenterYale University School of MedicineNew HavenUSA

Personalised recommendations