Time-resolved functional 1H MR spectroscopic detection of glutamate concentration changes in the brain during acute heat pain stimulation

Non-invasive in vivo detection of cortical neurotransmitter concentrations and their changes in the presence of pain may help to better understand the biochemical principles of pain processing in the brain. In the present study acute heat pain related changes of the excitatory neurotransmitter glutamate were investigated in the anterior insular cortex of healthy volunteers by means of time-resolved functional proton magnetic resonance spectroscopy ((1)H-MRS). Dynamic metabolite changes were estimated with a temporal resolution of five seconds by triggering data acquisition to the time course of the cyclic stimulus application. An overall increase of glutamate concentration up to 18% relative to the reference non-stimulus condition was observed during the application of short pain stimuli.

[1]  Fahmeed Hyder,et al.  In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. , 2003, Annual review of physiology.

[2]  Jan Sedlacik,et al.  Susceptibility weighted imaging at ultra high magnetic field strengths: Theoretical considerations and experimental results , 2008, Magnetic resonance in medicine.

[3]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[4]  J R Reichenbach,et al.  [Quantitation of glutamate in the brain by using MR proton spectroscopy at 1.5 T and 3 T]. , 2008, RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.

[5]  Leif Hertz,et al.  Glutamate, a neurotransmitter—And so much more A synopsis of Wierzba III , 2006, Neurochemistry International.

[6]  Krish D. Singh,et al.  fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention , 2002, NeuroImage.

[7]  Federico Giove,et al.  In vivo quantitative 1H MRS of cerebellum and evaluation of quantitation reproducibility by simulation of different levels of noise and spectral resolution. , 2004, Magnetic resonance imaging.

[8]  U. Klose.  In vivo proton spectroscopy in presence of eddy currents , 1990, Magnetic resonance in medicine.

[9]  M. Bronskill,et al.  T1, T2 relaxation and magnetization transfer in tissue at 3T , 2005, Magnetic resonance in medicine.

[10]  Robert Bartha,et al.  Effect of signal‐to‐noise ratio and spectral linewidth on metabolite quantification at 4 T , 2007, NMR in biomedicine.

[11]  Oded Gonen,et al.  Human brain‐structure resolved T2 relaxation times of proton metabolites at 3 tesla , 2007, Magnetic resonance in medicine.

[12]  P Jezzard,et al.  Functional changes in CSF volume estimated using measurement of water T2 relaxation , 2009, Magnetic resonance in medicine.

[13]  B D Ross,et al.  Absolute Quantitation of Water and Metabolites in the Human Brain. I. Compartments and Water , 1993 .

[14]  E Moser,et al.  Proton T 1 and T 2 relaxation times of human brain metabolites at 3 Tesla , 2001, NMR in biomedicine.

[15]  Rex E. Jung,et al.  A novel technique to study the brain's response to pain: Proton magnetic resonance spectroscopy , 2005, NeuroImage.

[16]  Joseph F. Clark,et al.  N-acetylaspartate as a reservoir for glutamate. , 2006, Medical hypotheses.

[17]  M Bianciardi,et al.  The physiology and metabolism of neuronal activation: in vivo studies by NMR and other methods. , 2003, Magnetic resonance imaging.

[18]  K L Casey,et al.  Forebrain mechanisms of nociception and pain: analysis through imaging. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[19]  G. E. Smith.  The Human Brain , 1924, Nature.

[20]  Uwe Himmelreich,et al.  Magnetic Resonance Spectroscopy Detects Biochemical Changes in the Brain Associated with Chronic Low Back Pain: A Preliminary Report , 2006, Anesthesia and analgesia.

[21]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[22]  Leif Hertz,et al.  Intercellular metabolic compartmentation in the brain: past, present and future , 2004, Neurochemistry International.

[23]  V. Govindaraju,et al.  Proton NMR chemical shifts and coupling constants for brain metabolites , 2000, NMR in biomedicine.

[24]  D. Chialvo,et al.  Chronic Pain and the Emotional Brain: Specific Brain Activity Associated with Spontaneous Fluctuations of Intensity of Chronic Back Pain , 2006, The Journal of Neuroscience.

[25]  Ian Marshall,et al.  Reproducibility of GABA measurements using 2D J-resolved magnetic resonance spectroscopy. , 2007, Magnetic resonance imaging.

[26]  C Büchel,et al.  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. , 2002, Brain : a journal of neurology.

[27]  R. Kauppinen,et al.  Nondestructive Detection of Glutamate by 1H Nuclear Magnetic Resonance Spectroscopy in Cortical Brain Slices from the Guinea Pig: Evidence for Changes in Detectability During Severe Anoxic Insults , 1991, Journal of neurochemistry.

[28]  K Ugurbil,et al.  In vivo 1H NMR spectroscopy of the human brain at 7 T , 2001, Magnetic resonance in medicine.

[29]  Ronald Melzack,et al.  The McGill pain questionnaire: from description to measurement. , 2005, Anesthesiology.

[30]  W M Bovée,et al.  Improved quantification of in vivo1H NMR spectra by optimization of signal acquisition and processing and by incorporation of prior knowledge into the spectral fitting , 1990, Magnetic resonance in medicine.

[31]  A. V. Apkarian,et al.  Brain chemistry reflects dual states of pain and anxiety in chronic low back pain , 2001, NeuroImage.

[32]  R G Shulman,et al.  Interpreting functional imaging studies in terms of neurotransmitter cycling. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Mark A Brown,et al.  Time‐domain combination of MR spectroscopy data acquired using phased‐array coils , 2004, Magnetic resonance in medicine.

[34]  David Borsook,et al.  Neuroimaging revolutionizes therapeutic approaches to chronic pain , 2007, Molecular pain.

[35]  K. Uğurbil,et al.  Sustained Neuronal Activation Raises Oxidative Metabolism to a New Steady-State Level: Evidence from 1H NMR Spectroscopy in the Human Visual Cortex , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[36]  Daniel J Clauw,et al.  Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. , 2008, Arthritis and rheumatism.

[37]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[38]  K. Uğurbil,et al.  Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo , 2007, Magnetic resonance in medicine.

[39]  Klaas Nicolay,et al.  1H MR spectroscopy of the brain: absolute quantification of metabolites. , 2006, Radiology.

[40]  E. Reiman,et al.  Thermosensory activation of insular cortex , 2000, Nature Neuroscience.

[41]  C. Büchel,et al.  Dissociable Neural Responses Related to Pain Intensity, Stimulus Intensity, and Stimulus Awareness within the Anterior Cingulate Cortex: A Parametric Single-Trial Laser Functional Magnetic Resonance Imaging Study , 2002, The Journal of Neuroscience.

[42]  Jürgen Gallinat,et al.  Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla , 2004, NeuroImage.

[43]  Arvind Caprihan,et al.  Comparative reliability of proton spectroscopy techniques designed to improve detection of J‐coupled metabolites , 2008, Magnetic resonance in medicine.