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Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging

Nature Medicinevolume 4pages159167 (1998) | Download Citation

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Abstract

The ability to measure the effects of local alterations in blood flow, blood volume and oxygenation by nuclear magnetic resonance has stimulated a surge of activity in functional MRI of many organs, particularly in its application to cognitive neuroscience. However, the exact description of these effects in terms of the interrelations between the MRI signal changes and the basic physiological parameters has remained an elusive goal. We here present this fundamental theory for spin-echo signal changes in perfused tissue and validate it in vivo in the cat brain by using the physiological alteration of hypoxic hypoxia. These experiments show that high-resolution absolute blood volume images can be obtained by using hemoglobin as a natural intravascular contrast agent. The theory also correctly predicts the magnitude of spin-echo MRI signal intensity changes on brain activation and thereby provides a sound physiological basis for these types of studies.

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References

  1. 1

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

  2. 2

    Moonen, C.T.W. van Zijl, P.C.M. Le Bihan, D., Frank, J. & Becker, E.D. Functional magnetic resonance imaging in medicine and physiology. Science 250, 53–61 (1990).

  3. 3

    Belliveau, J., et al. Functional mapping of the human visual cortex by magnetic resonance imaging. Science 254, 716–719 (1991).

  4. 4

    Shulman, R.G., Rothman, D.L. & Blamire, A.M. Nuclear magnetic resonance imaging and spectroscopy of human brain function. Proc. Natl. Acad. Sci. USA 90, 3127–3133 (1993).

  5. 5

    Ogawa, S., et al. Functional brain mapping by blood oxygenation level dependent contrast magnetic resonance imaging. Biophys. J. 64, 803–812 (1993).

  6. 6

    Ogawa, S., Lee, T.M. & Barrere, B. The sensitivity of magnetic resonance image signals of a rat brain to changes in the cerebral venous blood oxygenation. Magn. Reson. Med. 29, 205–210 (1993).

  7. 7

    Fabry, M.E. & San George, R.C. Effect of magnetic susceptibility on nuclear magnetic resonance signals arising from red cells. Biochemistry 22, 4119–4125 (1983).

  8. 8

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

  9. 9

    Kwong, K.K., et al. Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc. Natl. Acad. Sci. USA 89, 5675–5679 (1992).

  10. 10

    Ogawa, S., et al. Intrinsic signal changes accompanying sensory stimulation: Functional brain mapping with magnetic resonance imaging. Proc. Natl. Acad. Sci. USA 89, 5951 (1992).

  11. 11

    Bandettini, PA, Wong, E.C., Hinks, R.S., Tikofsky, R.S. & Hyde, J.S. Time course EPI of human brain function during task activation. Magn. Reson. Med. 25, 390–397 (1992).

  12. 12

    Atalay, M.K., Forder, J.R., Chacko, V.P., Kawamoto, S. & Zerhouni, E.A. Oxygenation in the rabbit myocardium: Assessment with susceptibility-dependent MR imaging. Radiology 189, 759–764 (1993).

  13. 13

    Karczmar, G.S., et al. Effects of hyperoxia on T2* and resonance frequency weighted magnetic resonance images of rodent tumors. NMR Biomed. 7, 3–11 (1994).

  14. 14

    Robinson, S.P., Howe, F.A. & Griffiths, J.R. Noninvasive monitoring of carbogen-induced changes in tumor blood flow and oxygenation by functional magnetic resonance imaging. Int. J. Radial Oncol. Biol. Phys. 33, 961–962 (1995).

  15. 15

    Turner, R., Le Bihan, D., Moonen, C.T.W. DesPres, D. & Frank, J. . Echo-planar time course MRI of cat brain oxygenation changes. Magn. Reson. Med. 22, 159–166 (1991).

  16. 16

    Jezzard, P., et al. Comparison of EPI gradient-echo contrast changes in cat brain caused by respiratory challenges with direct simultaneous evaluation of cerebral oxygenation via a cranial window. NMR Biomed. 7, 35–44 (1994).

  17. 17

    de Crespigny, A.J., Wendland, M.F., Derugin, N., Kozniewska, E. & Moseley, M.E. Real-time observation of transient focal ischemia and hyperemia in cat brain. Magn. Reson. Med. 27, 391–397 (1992).

  18. 18

    Roussel, S.A., van Bruggen, N., King, M.D. & Gadian, D.G. Identification of collaterally perfused areas following focal cerebral ischemia in the rat by comparison of gradient echo and diffusion-weighted MRI. J. Cereb. Blood Flow Metab. 15, 578–586 (1995).

  19. 19

    Prielmeyer, F., Nagatomo, Y. & Frahm, J. Cerebral blood oxygenation in rat brain during hypoxic hypoxia: Quantitative MRI of effective transverse relaxation rates. Magn. Reson. Med. 31, 678–681 (1994).

  20. 20

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

  21. 21

    Bandettini, P.A. & Wong, E.C. Effects of biophysical and physiologic parameters on brain activation-induced R2* and R2 changes: Simulations using a deterministic diffusion model. Int. J. Imag. Syst. Techn. 6, 133–152 (1995).

  22. 22

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

  23. 23

    Fox, P.T., Raichle, M.E., Mintun, M.A. & Dence, C. Nonoxidative glucose consumption during focal physiologic neural activity. Science 241, 462–464 (1988).

  24. 24

    Hyder, F., et al. Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected by 1H[13C] NMR. Proc. Natl. Acad. Sci. USA 93, 7612–17 (1996).

  25. 25

    Barinaga, M. What makes brain neurons run? Science 276, 196–198 (1997).

  26. 26

    Siesjo, B.K. Brain Energy Metabolism. (Wiley & Sons, Chichester, (1978).

  27. 27

    Koehler, R.C., Traystman, R.J., Zeger, S., Rogers, M.C. & Jones, M.D., jr . Comparison of cerebrovascular response to hypoxic and carbomonoxic hypoxia in newborn and adult sheep. J. Cereb. Blood Flow Metab. 4, 115–122 (1984).

  28. 28

    Ekström-Jodal, B., Elfverson, j. & von Essen, C. Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs. Acta Neurol. Scand. 60, 26–35 (1979).

  29. 29

    Bandettini, P.A., Wong, E.C., jesmanowicz, A., Hinks, R.S. & Hyde, J.S. Spin-echo and gradient-echo EPI of human brain activation using BOLD contrast: A comparative study at 1.5 T. NMR Biomed. 7, 12–20 (1994).

  30. 30

    Sharan, M., Jones, M.D. Jr,, Koehler, R.C., Traystman, R.J. & Popel, A.S. A compart-mental model for oxygen transport in brain microcirculation. Ann. Biomed. Eng. 17, 13–38 (1989).

  31. 31

    Leenders, K.L., et al. Cerebral blood flow, blood volume and oxygen utilization: Normal values and effect of age. Brain 113, 27–47 (1990).

  32. 32

    Pawlik, C., Rackl, A. & Bing, R.J. Quantitative capillary topography and blood flow in the cerebral cortex of cats: An in vivo microscopic study. Brain Res. 208, 35–58 (1981).

  33. 33

    Ulatowski, J.A., et al. Cerebral O2 transport with hematocrit reduced by cross-linked hemoglobin transfusion. Am. J. Physiol. 270, H466–H475 (1996).

  34. 34

    Herbst, M.D. & Goldstein, J.H. A review of water diffusion measurement by NMR in red blood cells. Am. J. Physiol. 256, C1097–C1104 (1989).

  35. 35

    Bryant, R.G., Marill, K., Blackmore, C. & Francis, C. Magnetic relaxation in blood and blood clots. Magn. Reson. Med. 13, 133–144 (1990).

  36. 36

    Gomori, J.M., Grossman, R.I., Yu-lp, C. & Asakura, T. NMR relaxation times of blood: dependence on field strength, oxidation state, and cell integrity. J. Comput Assist Tomogr. 11, 684–690 (1987).

  37. 37

    Gilles, P., Petö, S., Moiny, F., Mispelter, J. & Cuenod, C.-A. Proton transverse nuclear magnetic relaxation in oxidized blood: A numerical approach. Magn. Reson. Med. 33, 93–100 (1995).

  38. 38

    Meyer, M.-E. Yu, O., Eclancher, B., Grucker, D. & Chambron, J. NMR relaxation rates and blood oxygenation level. Magn. Reson. Med. 34, 234–241 (1995).

  39. 39

    Ye, F.Q. & Allen, P.S. Relaxation enhancement of the transverse magnetization of water protons in paramagnetic suspensions of red blood cells. Magn. Reson. Med. 34, 713–720 (1995).

  40. 40

    Allerhand, A. & Gutowsky, H.S. Spin-echo NMR studies of chemical exchang. I. Some general aspectse. J. Chem. Phys. 41, 2115–2126 (1964).

  41. 41

    Eichling, J., Raichle, M., Grubb, R. & Ter-Pogossian, M. Evidence of the limitations of water as a freely diffusable tracer in brain of the Rhesus monkey. Circ. Res. 35, 358–364 (1974).

  42. 42

    Paulson, O., Hertz, M., Bolwig, T. & Lassen, N. Filtration and diffusion of water across the blood brain barrier in man. Microvasc. Res. 13, 113–124 (1977).

  43. 43

    Wu, X., Ewert, D.L., Y.-H.,L. & Ritman, E.L. In vivo relation of intramyocardial blood volume to myocardial perfusion. Evidence supporting microvascular site for auto-regulation. Circulation 85, 730–737 (1992).

  44. 44

    Grubb, R.L., Raichle, M.E., Eichling, J.O. & Ter-Pogossian, M.M. The effects of changes in PaCO2 on cerebral blood volume, blood flow and vascular mean transit time. Stroke 5, 630–639 (1974).

  45. 45

    Shockley, R.P. & LaManna, J.C. Determination of rat cerebral cortical blood volume changes by capillary mean transit time analysis during hypoxia, hypercapnia and hyperventilation. Brain Res. 454, 170–178 (1988).

  46. 46

    Smith, A.L., Neufeld, G.R., Ominsky, A.J. & Wollman, R. Effect of arterial CO2 tension on cerebral blood flow, mean transit time and vascular volume. J. Appl. Physiol. 31, 701–707 (1971).

  47. 47

    Brooks, R.A., Di Chiro, G. & Keller, M.R. Explanation of cerebral white-gray contrast in computed tomography. J. Comput. Assist. Tomogr. 4, 489–491 (1980).

  48. 48

    Ueki, M., Mies, G. & Hossmann, K.A. Effect of α-chloralose, halothane, pentobarbi-tal and nitrous oxide anesthesia on metabolic coupling in the somatosensory cortex of rat. Acta Anaesth. Scand. 36, 318–322 (1992).

  49. 49

    Hoppel, B.E., et al. Measurement of regional blood oxygenation and cerebral hemodynamics. Magn. Reson. Med. 30, 715–723 (1993).

  50. 50

    Boxerman, J.L., et al. The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magn. Reson. Med. 34, 4–10 (1995).

  51. 51

    Song, A.W., Wong, E.C., Tan, S.G. & Hyde, J.S. Diffusion weighted fMRI at 1.5T. Magn. Reson. Med. 35, 155–158 (1996).

  52. 52

    Rostrup, E., Larsson, H.B.W. Toft, P.B., Garde, K. & Hendriksen, O. Signal changes in gradient echo images of human brain induced by hypo- and hyperoxia. NMR Biomed. 8, 41–47 (1995).

  53. 53

    Madsen, P.L., et al. Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: Evidence obtained with the Kety-Schmidt technique. J. Cereb. Blood Flow Metab. 15, 485–491 (1995).

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Affiliations

  1. Department of Radiology, Johns Hopkins University Medical School, 217 Traylor Building, 720 Rutland Avenue, Baltimore, Maryland, 21205, USA

    • Peter C.M. van Zijl
    • , Scott M. Eleff
    • , Joni M.E. Oja
    •  & Aziz M. Uluǧ
  2. Department of Anesthesiology and Critical Care, Johns Hopkins University Medical School, Meyer 8-138, 600 North Wolfe Street, Baltimore, Maryland, 21205, USA

    • Scott M. Eleff
    • , John A. Ulatowski
    •  & Richard J. Traystman
  3. NMR Research Group, A.L Virtanen Institute, University of Kuopio, Neulaniementic 2, P.O. Box 1627, FIN-70211, Kuopio, Finland

    • Joni M.E. Oja
    •  & Risto A. Kauppinen

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https://doi.org/10.1038/nm0298-159

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