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01-06-2007 | Original Paper

A Primer on Functional Magnetic Resonance Imaging

Authors: Gregory G. Brown, Joanna E. Perthen, Thomas T. Liu, Richard B. Buxton

Published in: Neuropsychology Review | Issue 2/2007

Abstract

In this manuscript, basic principles of functional magnetic resonance imaging (fMRI) are reviewed. In the first section, two intrinsic mechanisms of magnetic resonance image contrast related to the longitudinal and transverse components of relaxing spins and their relaxation rates, T₁ and T₂, are described. In the second section, the biophysical mechanisms that alter the apparent transverse relaxation time, \(T_2^*\), in blood oxygenation level dependent (BOLD) studies and the creation of BOLD activation maps are discussed. The physiological complexity of the BOLD signal is emphasized. In the third section, arterial spin labeling (ASL) measures of cerebral blood flow are presented. Arterial spin labeling inverts or saturates the magnetization of flowing spins to measure the rate of delivery of blood to capillaries. In the fourth section, calibrated fMRI, which uses BOLD and ASL to infer alterations of oxygen utilization during behavioral activation, is reviewed. The discussion concludes with challenges confronting studies of individual cases.

Aguirre, G. K., Detre, J. A., & Wang, J. (2005). Perfusion fMRI for functional neuroimaging. International Review of Neurobiology, 66, 213–236.PubMed

Aguirre, G. K., Detre, J. A., Zarahn, E., & Alsop, D. C. (2002). Experimental design and the relative sensitivity of BOLD and perfusion fMRI. NeuroImage, 15, 488–500.CrossRefPubMed

Aguirre, G. K., Zarahn, E., & D’esposito, M. (1998). The variability of human, BOLD hemodynamic responses. NeuroImage, 8, 360–369.CrossRefPubMed

Alsop, D. C. (2006). Perfusion imaging of the brain: Contribution to clinical MRI. In R. R. Edelman, J. R. Hesselink, M. B. Zlatkin, & J. V. Cures III (Eds.), Clinical magnetic resonance imaging (3rd edn., Vol. 1, pp. 333–357). Philadelphia: Saunders Elsevier.

Attwell, D., & Iadecola, C. (2002). The neural basis of functional brain imaging signals. Trends in Neurosciences, 25, 621–625.CrossRefPubMed

Attwell, D., & Laughlin, S. B. (2001). An energy budget for signaling in the grey matter of the brain. Journal of Cerebral Blood Flow and Metabolism, 21, 1133–1145.PubMed

Bandettini, P. A., Wong, E. C., Hinks, R. S., Tikofsky, R. S., & Hyde, J. S. (1992). Time course EPI of human brain function during task activation. Magnetic Resonance in Medicine, 25, 390–397.CrossRefPubMed

Bandettini, P. A., & Cox, R. W. (2000). Event-related fMRI contrast when using constant interstimulus interval: Theory and experiment. Magnetic Resonance in Medicine, 43, 540–548.CrossRefPubMed

Berger, T. W. (1984). Neural representation of associative learning in the hippocampus. In L. R. Squire & N. Butters (Eds.), Neuropsychology of memory (pp. 443–461). New York: The Guilford Press.

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

Boxerman, J. L., Hamberg, L. M., Rosen, B. R., & Weisskoff, R. M. (1995b). MR contrast due to intravascular magnetic susceptibility perturbations. Magnetic Resonance in Medicine, 34, 555–566.CrossRefPubMed

Boynton, G. M., Engel, S. A., Glover, G. H., & Heeger, D. J. (1996). Linear systems analysis of functional magnetic resonance imaging in humans. The Journal of Neuroscience, 16, 4207–4221.PubMed

Brown, G. G., Eyler Zorrilla, L. T., Georgy, B., Kindermann, S. S., Wong, E. C., & Buxton, R. B. (2003). BOLD and perfusion response to finger-thumb apposition after acetazolamide administration: Differential relationship to global perfusion. Journal of Cerebral Blood Flow and Metabolism, 23, 829–837.PubMed

Burock, M. A., Buckner, R. L., Woldorff, M. G., Rosen, B. R., & Dale, A. M. (1998). Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI. NeuroReport, 9, 3735–3739.CrossRefPubMed

Buxton, R. B. (2002). Introduction to functional magnetic resonance imaging. Cambridge: Cambridge University Press.

Buxton, R. B., Uludag, K., Dubowitz, D. J., & Liu, T. T. (2004). Modeling the hemodynamic response to brain activation. Neuroimage, 23(Suppl. 1), 220–233.CrossRef

Buxton, R. B., Wong, E. C., & Frank, L. R. (1998). Dynamics of blood flow and oxygenation changes during brain activation: the balloon model. Magnetic Resonance in Medicine, 39, 855–864.CrossRefPubMed

Chiarelli, P., Bulte, D. P., Piechnik, S., & Jezzard, P. (2007). Sources of systematic bias in hpercapnia-calibrated functional MRI estimation of oxygen metabolism. NeuroImage, 34, 35–43.CrossRefPubMed

Cohen, M. S. (1997). Parametric analysis of fMRI data using linear systems methods. NeuroImage, 6, 93–103.CrossRefPubMed

Dale, A. M. (1999). Optimal experimental design for event-related fMRI. Human Brain Mapping, 8, 109–114.CrossRefPubMed

Dale, A. M., & Buckner, R. L. (1997). Selective averaging of rapidly presented individual trials using fMRI. Human Brain Mapping, 5, 329–340.CrossRef

Daniels, F., & Alberty, R. A. (1966). Physical chemistry (3rd edn.). New York: John Wiley & Sons.

Davis, T. L., Kwong, K. K., Weisskoff, R. M., & Rosen, B. R. (1998). Calibrated functional MRI: Mapping the dynamics of oxidative metabolism. Proceedings of the National Academy of Science USA, 95, 1834–1839.CrossRef

Detre, J. A., Leigh, J. S., WIlliams, D. S., & Koretsky, A. P. (1992). Perfusion imaging. Magnetic Resonance in Medicine, 23, 37–45.CrossRefPubMed

Donaldson, D. I., & Buckner, R. L. (2001). Effective paradigm design. In P. Jezzard, P. M. Matthews, & S. M. Smith (Eds.), Functional MRI: An Introduction to methods (pp. 177–195). New York: Oxford University Press.

Edelman R. R., Siewert B., Darby D. G., Thangaraj V., Nobre A. C., Mesulam M. M., & Warach, S. (1994). Qualitative mapping of cerebral blood flow and functional localization with echo-planar MR imaging and signal targeting with alternating radio frequency. Radiology, 192, 513–520.PubMed

Elster, A. D., & Burdette, J. H. (2001). Questions & answers in magnetic resonance imaging (2nd edn.). St. Louis: Mosby.

Frahm, J., Krüger, G., Merboldt, K.-D., & Kleinschmidt, A. (1996). Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal activation in man. Magnetic Resonance in Medicine, 35, 143–148.CrossRefPubMed

Friston, K. J., Josephs, O., Rees, G., & Turner, R. (1998). Nonlinear event-related responses in fMRI. Magnetic Resonance in Medicine, 39, 41–52.CrossRefPubMed

Friston, K. J., Price, C. J., Fletcher, P., Moore, C., Frackowiak, R. S. J., & Dolan, R. J. (1996). The trouble with cognitive subtraction. NeuroImage, 4, 97–104.CrossRefPubMed

Fujita, N., Matsumoto, K., Tanaka, H., Watanabe, Y., & Murase, K. (2006). Quantitative study of changes in oxidative metabolism during visual stimulation using absolute relaxation rates. NMR in Biomedicine, 19, 60–68.CrossRefPubMed

Garcia, D. M., Bazelaire, C. D., & Alsop, D. (2005). Pseudo-continuous flow drive adiabatic inversion for arterial spin labeling. Paper presented at the 13th ISMRM Sicentific Meeting, Miami Beach.

Gjedde, A. (2001). Brain energy metabolism and the physiological basis of the haemodynamic response. In P. Jezzard, P. M. Matthews, & S. M. Smith (Eds.), Functional MRI: An Introduction to methods (pp. 37–65). New York: Oxford University Press.

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

Guyton, A. C. (1977). Basic human physiology: Normal function and mechanisms of disease (2nd edn.). Philadelphia: W.B. Saunders Company.

Hajnal, J. V., Bydder, G. M., & Young, I. R. (1995). fMRI: Does correlation imply activation. NMR in Biomedicine, 8, 97–100.CrossRefPubMed

Hoge, R. D., Atkinson, J., Gill, B., Crelier, G. R., Marrett, S., & Pike, G. B. (1999). Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. Proceedings of the National Academy of Science USA, 96(16), 9403–9408.CrossRef

Horvath, I., Sandor, N. T., Ruttner, Z., & McLaughlin, A. C. (1994). Role of nitric oxide in regulating cerebrocortical oxygen consumption and blood flow during hypercapnia. Journal of Cerebral Blood Flow and Metabolism, 14, 503–509.PubMed

Huettel, S. A., Song, A. W., & McCarthy, G. (2004). Functional Magnetic Resonance Imaging. Sunderland, MA: Sinauer Associates.

Hyder, F. (2004). Neuroimaging with calibrated FMRI. Stroke, 35(Suppl 1), 2635–2641.CrossRefPubMed

Jezzard, P., Matthews, P. M., & Smith, S. M. (Eds.). (2001). Functional MRI: An Introduction to methods. New York: Oxford University Press.

Jones, M., Berwick, J., Hewson-Stoate, N., Gias, C., & Mayhew, J. (2005). The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation. Neuroimage, 27, 609–623.CrossRefPubMed

Karu, Z. Z. (1995). Signals and systems made ridiculously simple. Cambridge, MA: ZiZi Press.

Kastrup, A., Kruger, G., Neumann-Haefelin, T., Glover, G. H., & Moseley, M. E. (2002). Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation. Neuroimage, 15, 74–82.CrossRefPubMed

Kemeny S., Ye, F. Q., Birn, R., & Braun, A. R. (2005). Comparison of continuous overt speech fMRI using BOLD and arterial spin labeling. Human Brain Mapping, 24, 173–183.CrossRefPubMed

Kety, S. S., & Schmidt, C. F. (1948). The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. The Journal of Clinical Investigation, 27, 484–492.PubMedCrossRef

Kim, S. G., Rostrup, E., Larsson, H. B. W., Ogawa, S., & Paulson, O. B. (1999) Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation. Magnetic Resonance in Medicine, 41, 1152–1161.CrossRefPubMed

Kim, S.-G., & Tsekos, N. V. (1997). Perfusion imaging by a flow-sensitive alternating inversion recovery (FAIR) technique: Application to functional brain imaging. Magnetic Resonance in Medicine, 37, 425–435.CrossRefPubMed

Kwong, K. K., Chesler, D. A., Weisskoff, R. M., Donahue, K. M., Davis, T. L., Ostergaard, L., Campbell, T. A., & Rosen, B. R. (1995). MR perfusion studies with T1-weighted echo planar imaging. Magnetic Resonance in Medicine, 34, 878–887.CrossRefPubMed

Latest IMV PET census shows fast growth in PET/CT installations. 2004 (Nov. 18). News from IMV’s Medical Information Division. http://www.imvlimited.com/mid/news_c.html.

Latest IMV study shows MRI clinical utilization expanding. 2005 (Feb. 19). News from IMV’s Medical Information Division. http://www.imvlimited.com/ mid/news_a.hmtl.

Leontiev, O., & Buxton, R. B. (2007). Reproducibility of BOLD, perfusion, and CMRO(2) measurements with calibrated-BOLD fMRI. NeuroImage, 35, 175–184.CrossRefPubMed

Leontiev, O., Dubowitz, D. J., & Buxton, R. B. (2007). CBF/CMRO2 coupling measured with calibrated-BOLD fMRI: Sources of bias. Manuscript submitted for publication.

Liu T. T. (2004). Efficiency, power, and entropy in event-related fMRI with multiple trial types. Part II: Design of experiments. NeuroImage, 21, 401–413.CrossRefPubMed

Liu T. T., Behzadi, Y., Restom, K., Uludag, K., Lu, K., Buracas, G. T., Dubowitz, D. J., & Buxton, R. B. (2004). Caffeine alters the temporal dynamics of the visual BOLD response. NeuroImage, 23, 1402–1413.CrossRefPubMed

Liu, T. T., & Brown, G. G. (2007). Measurement of cerebral perfusion with arterial spin labeling: Part 1. methods. Journal of the International Neuropsychological Society.

Liu T. T., & Frank, L. R. (2004). Efficiency, power, and entropy in event-related FMRI with multiple trial types. Part I: Theory. NeuroImage, 21, 387–400. Erratum in NeuroImage (2004), 22, 1427.

Liu, T. T., Frank, L. R., Wong, E. C., & Buxton, R. B. (2001). Detection power, estimation efficiency, and predictability in event-related fMRI. NeuroImage, 13, 759–773.CrossRefPubMed

Liu, T. T., & Wong, E. C. (2005). A signal processing model for arterial spin labeling functional MRI. NeuroImage, 24, 207–215.CrossRefPubMed

Liu, T. T., Wong, E. C., Frank, L. R., & Buxton, R. B. (2002). Analysis and design of perfusion-based event-related fMRI experiments. NeuroImage, 16, 269–282.CrossRefPubMed

Ly, C. V., & Verstreken, P. (2006). Mitochondria at the synapse. Neuroscientist, 12, 291–299.CrossRefPubMed

Mandeville, J. B., Marota, J. J. A., Ayata, C., Zaharchuk, G., Moskowitz, M. A., Rosen, B. R., & Weisskoff, R. M. (1999b). Evidence of a cerebrovascular post-arteriole Windkessel with delayed compliance. Journal of Cerebral Blood Flow and Metabolism, 19, 679–689.PubMed

Mandeville, J. B., Marota, J. J. A., Kosofsky, B. E., Keltner, J. R., Weissleder, R., Rosen, B. R., & Weisskoff, R. M. (1998). Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation. Magnetic Resonance in Medicine, 39, 615–624.CrossRefPubMed

Mildner, T., Zysset, S., Trampel, R., Driesel, W., & Möller, H. E. (2005). Towards quantification of blood-flow changes during cognitive task activation using perfusion-based fMRI. NeuroImage, 27, 919–926.CrossRefPubMed

Miller, K. L., Luh, W. M., Liu, T. T., Martinez, A., Obata, T., Wong, E. C., Frank, L. R., & Buxton, R. B. (2001). Nonlinear temporal dynamics of the cerebral blood flow response. Human Brain Mapping, 13, 1–12.CrossRefPubMed

Moncada, S., & Bolanos, J. P. (2006). Nitric oxide, cell bioenergetics and neurodegeneration. Journal of Neurochemistry, 97, 1676–1689.CrossRefPubMed

Mumford, J. A., Hernandez-Garcia, L., Lee, G. R., & Nichols, T. A. (2006) Estimation efficiency and statistical power in arterial spin labeling fMRI. NeuroImage, 33, 103–114.CrossRefPubMed

Novack, P., Shenkin, H. A., Bortin, L., Goluboff, B., & Soffe, A. M. (1953). The effects of carbon dioxide inhalation upon the cerebral blood flow and cerebral oxygen consumption in vascular disease. The Journal of Clinical Investigation, 32, 696–702.PubMed

Obata, T., Liu, T. T., Miller, K. L., Luh, W. M., Wong, E. C., Frank, L. R., & Buxton, R. B. (2004). Discrepancies between BOLD and flow dynamics in primary and supplementary motor areas: application of the balloon model to the interpretation of BOLD transients. NeuroImage, 21, 144–153.CrossRefPubMed

Ogawa, S., Tso-Ming, L., Nayak, A. S., & Glynn, P. (1990). Oxygen-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magnetic Resonance in Medicine, 14, 68–78.CrossRefPubMed

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

Rao, S. M., Salmeron, B. J., Durgerian S., Janowiak, J. A., Fischer, M., Risinger, R. C., Conant, L. L., & Stein, E. A. (2000). Effects of methylphenidate on functional MRI blood-oxygen-level-dependent contrast. American Journal of Psychiatry, 157, 1697–1699.CrossRefPubMed

Restom, K., Behzadi, Y., & Liu, T. T. (2006). Physiological noise reduction for arterial spin labeling functional MRI. NeuroImage, 31, 1104–1115.CrossRefPubMed

Rundus, D. (1971). Analysis of rehearsal processes in free recall. Journal of Experimental Psychology, 89, 63–77.CrossRef

Shmuel, A., Yacoub, E., Pfeuffer, J., Van de Moortele, P. F., Adriany, G., Hu, X., Ugurbil, K. (2002). Sustained negative BOLD, blood flow and oxygen consumption response and its coupling to the positive response in the human brain. Neuron, 36, 1195–1210.CrossRefPubMed

Sicard, K. M., & Duong, T. Q. (2005) Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals. NeuroImage, 25, 850–858.CrossRefPubMed

St Lawrence, K. S., Ye, F. Q., Lewis, B. K., Frank, J. A., & McLaughlin, A. C. (2003). Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation. Magnetic Resonance in Medicine, 50, 99–106.CrossRefPubMed

Stefanovic, B., Warnking, J. M., Kobayashi, E., Bagshaw, A. P., Hawco, C., Dubeau, F., Gotman, J., & Pike, G. B. (2005). Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges. NeuroImage, 28, 205–215.CrossRefPubMed

Stefanovic, B., Warnking, J. M., & Pike, G. B. (2004). Hemodynamic and metabolic responses to neuronal inhibition. NeuroImage, 22, 771–778.CrossRefPubMed

Sternberg, S. (1969). The discovery of processing stages: Extension of Donders method. Acta Psychologica, 30, 276–315.CrossRef

Thulborn, K. R., Waterton, J. C., Matthews, P. M., & Rada, G. K. (1982). Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. Biochimica et Biophysica Acta, 714, 265–270.PubMed

Tjandra, T., Brooks, J. C., Figueiredo, P., Wise, R., Matthews, P. M., & Tracey, I. (2005). Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging: Implications for clinical trial design. NeuroImage, 27, 393–401.CrossRefPubMed

Townsend, J. T., & Ashby, F. G. (1983). Stochastic modeling of elementary psychological processes. New York: Cambridge University Press.

Twieg, D. B. (1983) The k-trajectory formulation of the NMR imaging process with applications in analsysis and synthesis of imaging methods. Medical Physics, 10, 610–621.CrossRefPubMed

Uludag, K., & Buxton, R. B. (2004). Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation. Magnetic Resonance in Medicine, 51, 1088–1089; author reply 1090.

Uludağ, K., Dubowitz, D. J., & Buxton, R. B. (2006). Basic principles of functional MRI. In R. R. Edelman, J. R. Hesselink, M. B. Zlatkin, & J. V. Crues III (Eds.), Clinical magnetic resonance imaging (3rd edn., Vol. 1, pp. 249–287). Philadelphia: Saunders Elsevier.

Uludag, K., Dubowitz, D. J., Yoder, E. J., Restom, K., Liu, T. T., & Buxton, R. B. (2004). Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI. NeuroImage, 23, 148–155.CrossRefPubMed

Wang, J., Aguirre, G. K., Kimberg, D. Y., Roc, A. C., Li, L., & Detre, J. A. (2003). Arterial spin labeling perfusion fMRI with very low task frequency. Magnetic Resonance in Medicine, 49, 796–802.CrossRefPubMed

Wong, E. C., Buxton, R. B., & Frank, L. R. (1997). Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling. NMR in Biomedicine, 10, 237–249.CrossRefPubMed

Wong, E. C., Buxton, R. B., & Frank, L. R. (1998a). Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II). Magnetic Resonance in Medicine, 39, 702–708.CrossRefPubMed

Wong, E. C., Buxton, R. B., & Frank, L. R. (1998b). A theoretical and experimental comparison of continuous and pulsed arterial spin labeling techniques for quantitative perfusion imaging. Magnetic Resonance in Medicine, 40, 348–355.CrossRefPubMed

Wong, E. C., Cronin, M., Wu, W. C., Inglis, B., Frank, L. R., & Liu, T. T. (2006). Velocity-selective arterial spin labeling. Magnetic Resonance in Medicine, 55, 1334–1341.CrossRefPubMed

Wong, E. C., Luh, W.-M., & Liu, T. T. (2000). Turbo ASL: Arterial spin labeling with higher SNR and temporal resolution. Magnetic Resonance in Medicine, 44, 511–515.

Yang, S. P., & Krasny, J. A. (1995). Cerebral blood flow and metabolic responses to sustained hypercapnia in awake sheep. Journal of Cerebral Blood Flow and Metabololism, 15, 115– 123.

Zappe, A. C., Uludag, K., Rainer, G., & Logothetis, N. K. (2005). Influence of moderate hypercapnia on neural activity in monkey by simultaneous intracortical recordings and fMRI at 4.7T. In: 35th meeting, Society for Neuroscience, Washington D.C., p 10.11.

Zarahn, E., Aguirre, G., & D’Esposito, M. (1997). A trial-based experimental design for fMRI. Neuroimage, 6, 122– 138.CrossRefPubMed

Title: A Primer on Functional Magnetic Resonance Imaging
Authors: Gregory G. Brown
Joanna E. Perthen
Thomas T. Liu
Richard B. Buxton
Publication date: 01-06-2007
Publisher: Springer US
Published in: Neuropsychology Review / Issue 2/2007
Print ISSN: 1040-7308
Electronic ISSN: 1573-6660
DOI: https://doi.org/10.1007/s11065-007-9028-8

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