Abstract
In a human magnetic resonance diffusion-weighted imaging (DWI) investigation at 3 T and high diffusion sensitivity weighting (b = 1,800 s/mm2), which emphasizes the contribution of water in the extra-vascular compartment and minimizes that of the vascular compartment, we observed that visual stimulation with a flashing checkerboard at 8 Hz for a period of 600 s in eight subjects resulted in significant increases in DWI signals (mean +2.70%, range +0.51 to 8.54%). The increases in DWI signals in activated areas of the visual cortex indicated that during stimulation, the apparent diffusion coefficient (ADC) of extra-vascular compartment water decreased. In response to continuous stimulation, DWI signals gradually increased from pre-stimulation controls, leveling off after 400–500 s. During recovery from stimulation, DWI signals gradually decreased, approaching control levels in 300–400 s. In this study, we show for the first time that the effects of visual stimulation on DWI signals in the human visual cortex are cumulative over an extended period of time. We propose that these relatively slow stimulation-induced changes in the ADC of water in the extra-vascular compartment are due to transient changes in the ratio of faster diffusing free water to slower diffusing bound water and reflect brain water transport processes between the vascular and extra-vascular compartments at the cellular level. The nature of these processes including possible roles of the putative glucose water import and N-acetylaspartate water export molecular water pumps in brain function are discussed.
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Abbreviations
- ADC:
-
Apparent diffusion coefficient
- AQP4:
-
Aquaporin 4
- ASPA:
-
Aspartoacylase
- BOLD:
-
Blood oxygenation level dependent
- CD:
-
Canavan disease
- D :
-
Diffusion coefficient
- DWI:
-
Diffusion-weighted imaging
- ECF:
-
Extracellular fluid
- fMRI:
-
Functional magnetic resonance imaging
- Glc:
-
Glucose
- Hz:
-
Hertz
- MWP:
-
Molecular water pump
- NAA:
-
N-Acetylaspartate
- ROI:
-
Region of interest
- T:
-
Tesla
References
Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Neilsen S (2002) Aquaporin water channels—from atomic structure to clinical medicine. J Physiol 542:3–16
Andrew RD, Labron MW, Boehnke SE, Carnduff L, Kirov SA (2007) Physiological evidence that pyramidal neurons lack functional water channels. Cereb Cortex 17:787–802
Bammer R, Stollberger R, Augustin M, Simbrunner J, Offenbacher H, Kooijman H, Ropele S, Kapeller P, Wach P, Ebner F, Fazekas F (1999) Diffusion-weighted imaging with navigated interleaved echo-planar imaging and a conventional gradient system. Radiology 211:799–806
Baslow MH (1998) Function of the N-acetyl-L-histidine system in the vertebrate eye. Evidence in support of a role as a molecular water pump. J Mol Neurosci 10:193–208
Baslow MH (1999) The existence of molecular water pumps in the nervous system. A review of the evidence. Neurochem Int 34:77–90
Baslow MH (2010) Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain’s “operating system”: how NAA metabolism supports meaningful intercellular frequency-encoded communications. Amino Acids 39(5):1139–1145
Baslow MH, Guilfoyle DN (2002) Effect of N-acetylaspartic acid on the diffusion coefficient of water: a proton magnetic resonance phantom method for measurement of osmolyte-obligated water. Analyt Biochem 311(2):133–138
Baslow MH, Guilfoyle DN (2007) Using proton magnetic resonance imaging and spectroscopy to understand brain “activation”. Brain Lang 102:153–164
Baslow MH, Hrabe J, Guilfoyle DN (2007) Dynamic relationship between neurostimulation and N-acetylaspartate metabolism in the human visual cortex. Evidence that NAA functions as a molecular water pump during visual stimulation. J Mol Neurosci 32:235–245
Buffoli B (2010) Aquaporin biology and nervous system. Curr Neuropharmacol 8:97–104
Choe S, Rosenberg JM, Abramson J, Wright EM, Grabe M (2010) Water permeation through the sodium-dependent galactose cotransporter vSGLT. Biophys J 99(7):L56–L58
Darquie A, Poline J-B, Poupon C, Saint-Jalmes H, Le Bihan D (2001) Transient decrease in water diffusion observed in human occipital cortex during visual stimulation. PNAS 98:9391–9395
Foglio E, Rodella LF (2010) Aquaporins and neurodegenerative diseases. Curr Neuropharmacol 8:112–121
Frahm J, Kruger G, Merboldt KD, Kleinschmidt A (1996) Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man. Magn Reson Med 35:143–148
Kvittingen EA, Guldal G, Borsting S, Skalpe IO, Stokke O, Jellum E (1986) N-acetylaspartic aciduria in a child with a progressive cerebral atrophy. Clin Chim Acta 158:217–227
Le Bihan D, Urayama S, Toshihiko A, Hanakawa T, Fukuyama H (2006) Direct and fast detection of neuronal activation in the human brain with diffusion MRI. PNAS 103:8263–8268
Liu Z, Zheng D, Wang X, Zhang J, Xie S, Xiao J, Jiang X (2011) Apparent diffusion coefficients of metabolites in patients with MELAS using diffusion-weighted MR spectroscopy. Am J Neuroradiol 32:898–902
Mangia S, Tkac I, Gruetter R, Van de Moortele P-F, Maraviglia B, Ugurbil K (2007) Sustained neuronal activation raises oxidative metabolism to a new steady-state level: evidence from 1H NMR spectroscopy in the human visual cortex. J Cereb Blood Flow Metab 27:1055–1063
Meinild A-K, Klaerke DA, Loo DDF, Wright EM, Zeuthen T (1998) The human Na+-glucose cotransporter is a molecular water pump. J Physiol 508:15–21
Niendorf T, Dijkhuizen RM, Norris DG, van Lookeren Campagne M, Nicolay K (1996) Biexponential diffusion attenuation in various states of brain tissue: implications for diffusion weighted imaging. Magn Reson Med 36:847–857
Pfeuffer J, Tkac I, Gruetter R (2000) Extracellular-intracellular distribution of glucose and lactate in the rat brain assessed noninvasively by diffusion-weighted 1H nuclear magnetic resonance spectroscopy in vivo. J Cereb Blood Flow Metab 20:736–746
Plumridge TH, Waigh RD (2002) Water structure theory and some implications for drug design. J Pharm Pharmacol 54:1155–1179
Pradhan S, Goyal G (2011) Teaching NeuroImages: honeycomb appearance of the brain in a patient with Canavan disease. Neurology 76:e68
Reese TG, Heid O, Weisskoff RM, Wedeen VJ (2003) Reduction of eddy current induced distortion in diffusion MRI using a twice refocused spin echo. Magn Reson Med 49:177–182
Sarchielli P, Tarducci R, Presciutti O, Gobbi G, Pelliccioli GP, Stipa G, Alberti A, Capocchi G (2005) Functional 1H-MRS findings in migraine patients with and without aura assessed interictally. Neuroimage 24:1025–1031
Tait MJ, Saadoun S, Bell BA, Papadopoulos MC (2008) Water movements in the brain: role of aquaporins. Trends Neurosci 31(1):37–43
Wheatley DN (1998) Diffusion theory, the cell and the synapse. Biosystems 45:151–163
Wiame E, Tyteca D, Pierrot N, Collard F, Amyere M, Noel G, Desmedt J, Nassogne M-C, Vikkula M, Octave J-N, Vincent M-F, Courtoy PJ, Boltshauser E, Van Shaftingen E (2010) Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. Biochem J 425:127–136
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Baslow, M.H., Hu, C. & Guilfoyle, D.N. Stimulation-Induced Decreases in the Diffusion of Extra-vascular Water in the Human Visual Cortex: a Window in Time and Space on Mechanisms of Brain Water Transport and Economy. J Mol Neurosci 47, 639–648 (2012). https://doi.org/10.1007/s12031-011-9700-6
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DOI: https://doi.org/10.1007/s12031-011-9700-6