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The BOLD Effect

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In vivo NMR Imaging

Part of the book series: Methods in Molecular Biology ((MIMB,volume 771))

Abstract

The purpose of this chapter is to introduce the novice NMR imager to blood oxygen level dependent (BOLD) contrast as well as remind the seasoned veteran of its beauty. Introduction to many of the factors that influence the BOLD signal is given higher priority than pursuing any subset in exquisite detail. Instead, references are given for readers seeking intense investigations into a given aspect. The hope is that this overview inspires the reader with the elegant simplicity of BOLD contrast while not, at first, intimidating too much with the underlying complexity. As one’s knowledge of NMR matures so too will one’s understanding, appreciation, and application of BOLD MRI. BOLD contrast derives from variations in the magnetic susceptibility of blood due to variations in the concentration of deoxyhemoglobin. These magnetic susceptibility effects produce local magnetic fields around blood vessels that can result in phase dispersion of nearby spins and, therefore, changes in signal intensity in NMR images. After providing brief historical context for BOLD, this chapter will follow the trail of magnetic susceptibility through definition, its source and location in vivo, and how the source and location in vivo interact with anatomical (e.g., blood vessel size) and imaging considerations (e.g., pulse sequence) to influence the BOLD signal. We will conclude by briefly highlighting clinical and preclinical applications using BOLD contrast.

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References

  1. Pauling, L., and Coryell, C. D. (1936) The magnetic properties and structure of hemoglobin, oxyhemoglobin and carbonmonoxyhemoglobin. Proc Natl Acad Sci USA 22, 210–216.

    Article  PubMed  CAS  Google Scholar 

  2. Thulborn, K. R., Waterton, J. C., Matthews, P. M., and Radda, G. K. (1982) Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. Biochim Biophys Acta 714, 265–270.

    PubMed  CAS  Google Scholar 

  3. Ogawa, S., Lee, T. M., Kay, A. R., and Tank, D. W. (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci USA 87, 9868–9872.

    Article  PubMed  CAS  Google Scholar 

  4. Ogawa, S., Menon, R. S., Tank, D. W., Kim, S. G., Merkle, H., Ellermann, J. M., and Ugurbil, K. (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J 64, 803–812.

    Article  PubMed  CAS  Google Scholar 

  5. Haacke, E. M., Lai, S., Yablonskiy, D. A., and Lin, W. (1995) In vivo validation of the BOLD mechanism: A review of signal changes in gradient echo functional MRI in the presence of flow. Int J Imaging Syst Technol 6, 153–163.

    Article  Google Scholar 

  6. van Zijl, P. C., Eleff, S. M., Ulatowski, J. A., Oja, J. M., Ulug, A. M., Traystman, R. J., and Kauppinen, R. A. (1998) Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging. Nat Med 4, 159–167.

    Article  PubMed  Google Scholar 

  7. Schenck, J. F. (1996) The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibility of the first and second kinds. Med Phys 23, 815–850.

    Article  PubMed  CAS  Google Scholar 

  8. Haacke, E. M., Brown, R. W., Thompson, M. R., and Venkatesan, R. (1999) Magnetic Resonance Imaging: Physical Principles and Sequence Design. Wiley, New York, NY.

    Google Scholar 

  9. Wajcman, H., Kiger, L., and Marden, M. C. (2009) Structure and function evolution in the superfamily of globins. C R Biol 332, 273–282.

    Article  PubMed  CAS  Google Scholar 

  10. Strandberg, B. (2009) Chapter 1: Building the ground for the first two protein structures: Myoglobin and haemoglobin. J Mol Biol 392, 2–10.

    Article  PubMed  CAS  Google Scholar 

  11. Ganong, W. F. (2005) Review of Medical Physiology. McGraw-Hill Companies, Columbus.

    Google Scholar 

  12. Stuart, J., and Nash, G. B. (1990) Red cell deformability and haematological disorders. Blood Rev 4, 141–147.

    Article  PubMed  CAS  Google Scholar 

  13. Berne, R. M., and Levy, M. N. (2001) Cardiovascular Physiology, Eighth ed. Mosby, St. Louis.

    Google Scholar 

  14. Boxerman, J. L., Hamberg, L. M., Rosen, B. R., and Weisskoff, R. M. (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34, 555–566.

    Article  PubMed  CAS  Google Scholar 

  15. Norris, D. G. (2006) Principles of magnetic resonance assessment of brain function. J Magn Reson Imaging 23, 794–807.

    Article  PubMed  Google Scholar 

  16. Boxerman, J. L., Bandettini, P. A., Kwong, K. K., Baker, J. R., Davis, T. L., Rosen, B. R., and Weisskoff, R. M. (1995) The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magn Reson Med 34, 4–10.

    Article  PubMed  CAS  Google Scholar 

  17. Buxton, R. B. (2001) The elusive initial dip. Neuroimage 13, 953–8.

    Article  PubMed  CAS  Google Scholar 

  18. Stefanovic, B., and Pike, G. B. (2004) Human whole-blood relaxometry at 1.5 T: Assessment of diffusion and exchange models. Magn Reson Med 52, 716–723.

    Article  PubMed  Google Scholar 

  19. Weisskoff, R. M., Zuo, C. S., Boxerman, J. L., and Rosen, B. R. (1994) Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med 31, 601–610.

    Article  PubMed  CAS  Google Scholar 

  20. Yablonskiy, D. A., and Haacke, E. M. (1994) Theory of NMR signal behavior in magnetically inhomogeneous tissues: the static dephasing regime. Magn Reson Med 32, 749–763.

    Article  PubMed  CAS  Google Scholar 

  21. Matthews, P. M., and Jezzard, P. (2004) Functional magnetic resonance imaging. J Neurol Neurosurg Psychiatry 75, 6–12.

    PubMed  CAS  Google Scholar 

  22. Amaro, E., Jr., and Barker, G. J. (2006) Study design in fMRI: Basic principles. Brain Cogn 60, 220–232.

    Article  PubMed  Google Scholar 

  23. Neuroskeptic. (2009) fMRI Gets Slap in the Face with a Dead Fish (September 16, 2009). Retrieved December 5, 2009, from http://neuroskeptic.blogspot.com/2009/09/fmri-gets-slap-in-face-with-dead-fish.html.

  24. Haller, S., and Bartsch, A. J. (2009) Pitfalls in FMRI. Eur Radiol 19, 2689–2706.

    Article  PubMed  Google Scholar 

  25. Adcock, J. E., Wise, R. G., Oxbury, J. M., Oxbury, S. M., and Matthews, P. M. (2003) Quantitative fMRI assessment of the differences in lateralization of language-related brain activation in patients with temporal lobe epilepsy. Neuroimage 18, 423–438.

    Article  PubMed  CAS  Google Scholar 

  26. Biswal, B., Yetkin, F. Z., Haughton, V. M., and Hyde, J. S. (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34, 537–541.

    Article  PubMed  CAS  Google Scholar 

  27. Lowe, M. J., Phillips, M. D., Lurito, J. T., Mattson, D., Dzemidzic, M., and Mathews, V. P. (2002) Multiple sclerosis: low-frequency temporal blood oxygen level-dependent fluctuations indicate reduced functional connectivity initial results. Radiology 224, 184–192.

    Article  PubMed  Google Scholar 

  28. Damoiseaux, J. S., Rombouts, S. A., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., and Beckmann, C. F. (2006) Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 103, 13848–13853.

    Article  PubMed  CAS  Google Scholar 

  29. Greicius, M. D., Supekar, K., Menon, V., and Dougherty, R. F. (2009) Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex 19, 72–78.

    Article  PubMed  Google Scholar 

  30. Gloviczki, M. L., Glockner, J., Gomez, S. I., Romero, J. C., Lerman, L. O., McKusick, M., and Textor, S. C. (2009) Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease. Invest Radiol 44, 566–571.

    Article  PubMed  CAS  Google Scholar 

  31. Lebon, V., Brillault-Salvat, C., Bloch, G., Leroy-Willig, A., and Carlier, P. G. (1998) Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient-echo NMRI and myoglobin NMRS during leg ischemia. Magn Reson Med 40, 551–558.

    Article  PubMed  CAS  Google Scholar 

  32. Lebon, V., Carlier, P. G., Brillault-Salvat, C., and Leroy-Willig, A. (1998) Simultaneous measurement of perfusion and oxygenation changes using a multiple gradient-echo sequence: application to human muscle study. Magn Reson Imaging 16, 721–729.

    Article  PubMed  CAS  Google Scholar 

  33. Donahue, K. M., Van Kylen, J., Guven, S., El-Bershawi, A., Luh, W. M., Bandettini, P. A., Cox, R. W., Hyde, J. S., and Kissebah, A. H. (1998) Simultaneous gradient-echo/spin-echo EPI of graded ischemia in human skeletal muscle. J Magn Reson Imaging 8, 1106–1113.

    Article  PubMed  CAS  Google Scholar 

  34. Toussaint, J. F., Kwong, K. K., Mkparu, F. O., Weisskoff, R. M., LaRaia, P. J., Kantor, H. L., and M’Kparu, F. (1996) Perfusion changes in human skeletal muscle during reactive hyperemia measured by echo-planar imaging. Magn Reson Med 35, 62–69.

    Article  PubMed  CAS  Google Scholar 

  35. Hoehn, M. (2003) Functional magnetic resonance imaging. In: van Bruggen, N. and Roberts, T. (eds.), Biomedical Imaging in Experimental Neuroscience. CRC Press, Boca Raton.

    Google Scholar 

  36. Van der Linden, A., Van Meir, V., Boumans, T., Poirier, C., and Balthazart, J. (2009) MRI in small brains displaying extensive plasticity. Trends Neurosci 32, 257–266.

    Article  PubMed  Google Scholar 

  37. Li, L. P., Ji, L., Lindsay, S., and Prasad, P. V. (2007) Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole-body scanner. J Magn Reson Imaging 25, 635–638.

    Article  PubMed  Google Scholar 

  38. Greve, J. M., Williams, S. P., Bernstein, L. J., Goldman, H., Peale, F. V., Jr., Bunting, S., and van Bruggen, N. (2008) Reactive hyperemia and BOLD MRI demonstrate that VEGF inhibition, age, and atherosclerosis adversely affect functional recovery in a murine model of peripheral artery disease. J Magn Reson Imaging 28, 996–1004.

    Article  PubMed  Google Scholar 

  39. Schneider, J. T., and Faber, C. (2008) BOLD imaging in the mouse brain using a turboCRAZED sequence at high magnetic fields. Magn Reson Med 60, 850–859.

    Article  PubMed  Google Scholar 

  40. Baudelet, C., Cron, G. O., and Gallez, B. (2006) Determination of the maturity and functionality of tumor vasculature by MRI: correlation between BOLD-MRI and DCE-MRI using P792 in experimental fibrosarcoma tumors. Magn Reson Med 56, 1041–1049.

    Article  PubMed  Google Scholar 

  41. Fox, P. T., and Raichle, M. E. (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci USA 83, 1140–1144.

    Article  PubMed  CAS  Google Scholar 

  42. Engel, S. A., Glover, G. H., and Wandell, B. A. (1997) Retinotopic organization in human visual cortex and the spatial precision of functional MRI. Cereb Cortex 7, 181–192.

    Article  PubMed  CAS  Google Scholar 

  43. Dickerson, B. C., and Sperling, R. A. (2008) Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer’s disease: insights from functional MRI studies. Neuropsychologia 46, 1624–1635.

    Article  PubMed  Google Scholar 

  44. Pineiro, R., Pendlebury, S., Johansen-Berg, H., and Matthews, P. M. (2001) Functional MRI detects posterior shifts in primary sensorimotor cortex activation after stroke: evidence of local adaptive reorganization? Stroke 32, 1134–1139.

    Article  PubMed  CAS  Google Scholar 

  45. Staffen, W., Mair, A., Zauner, H., Unterrainer, J., Niederhofer, H., Kutzelnigg, A., Ritter, S., Golaszewski, S., Iglseder, B., and Ladurner, G. (2002) Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task. Brain 125, 1275–1282.

    Article  PubMed  CAS  Google Scholar 

  46. Filippi, M., and Rocca, M. A. (2009) Functional MR imaging in multiple sclerosis. Neuroimaging Clin N Am 19, 59–70.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Biomedical Imaging, Genentech, Inc., South San Francisco, CA, 94080, USA

    Joan M. Greve

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  1. Joan M. Greve
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Correspondence to Joan M. Greve .

Editor information

Editors and Affiliations

  1. ERC Project BiosensorImaging, Leibniz-Institut für Molekulare Pharmako, Robert-Roessle-Str. 10, Berlin, 13125, Germany

    Leif Schröder

  2. Inst. Klinische Radiologie, AG Experimentelle, Universität Münster, Haus Rosenbach Waldeyerstr. 1, Münster, 48149, Germany

    Cornelius Faber

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Greve, J.M. (2011). The BOLD Effect. In: Schröder, L., Faber, C. (eds) In vivo NMR Imaging. Methods in Molecular Biology, vol 771. Humana Press. https://doi.org/10.1007/978-1-61779-219-9_8

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  • DOI: https://doi.org/10.1007/978-1-61779-219-9_8

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-218-2

  • Online ISBN: 978-1-61779-219-9

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