Selectively Probing the Magnetic Resonance Signals of γ-Aminobutyric Acid in Human Brains In Vivo.

BACKGROUND Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in human brains, playing a role in the pathogenesis of various psychiatric disorders. Current methods have some non-neglectable shortcomings and noninvasive and accurate detection of GABA in human brains is long-term challenge. PURPOSE To develop a pulse sequence capable of selectively detecting and quantifying the 1 H signal of GABA in human brains based on optimal controlled spin singlet order. STUDY TYPE Prospective. SUBJECTS/PHANTOM A phantom of GABA (pH = 7.3 ± 0.1) and 11 healthy subjects (5 females and 6 males, body mass index: 21 ± 3 kg/m2 , age: 25 ± 4 years). FIELD STRENGTH/SEQUENCE 7 Tesla, 3 Tesla, GABA-targeted magnetic resonance spectroscopy (GABA-MRS-7 T, GABA-MRS-3 T), magnetization prepared two rapid acquisition gradient echoes sequence. ASSESSMENT By using the developed pulse sequences applied on the phantom and healthy subjects, the signals of GABA were successfully selectively probed. Quantification of the signals yields the concentration of GABA in the dorsal anterior cingulate cortex (dACC) in human brains. STATISTICAL TESTS Frequency. RESULTS The 1 H signals of GABA in the phantom and in the human brains of healthy subjects were successfully detected. The concentration of GABA in the dACC of human brains was 3.3 ± 1.5 mM. DATA CONCLUSION The developed pulse sequences can be used to selectively probe the 1 H MR signals of GABA in human brains in vivo. EVIDENCE LEVEL 1 TECHNICAL EFFICACY STAGE: 1.

[1]  Guang Yang,et al.  Distinguishing glutamate and glutamine in in vivo 1H MRS based on nuclear spin singlet order filtering , 2022, Magnetic resonance in medicine.

[2]  G. Remington,et al.  Gamma‐aminobutyric acid (GABA) levels in the midcingulate cortex and clozapine response in patients with treatment‐resistant schizophrenia: A proton magnetic resonance spectroscopy (1H‐MRS) study , 2022, Psychiatry and clinical neurosciences.

[3]  Yu-Xiao Li,et al.  Multiple-targeting NMR signal selection by optimal control of nuclear spin singlet. , 2022, Journal of magnetic resonance.

[4]  G. Northoff,et al.  Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder , 2021, Molecular Psychiatry.

[5]  Daxiu Wei,et al.  Preparation of long-lived states in a multi-spin system by using an optimal control method. , 2020, Chemphyschem : a European journal of chemical physics and physical chemistry.

[6]  A. Henning,et al.  Test–Retest Reliability of the Brain Metabolites GABA and Glx With JPRESS, PRESS, and MEGA‐PRESS MRS Sequences in vivo at 3T , 2020, Journal of magnetic resonance imaging : JMRI.

[7]  C. Griesinger,et al.  Singlet-filtered NMR spectroscopy , 2020, Science Advances.

[8]  Caroline A. Lea-Carnall,et al.  Number of subjects required in common study designs for functional GABA magnetic resonance spectroscopy in the human brain at 3 Tesla , 2019, The European journal of neuroscience.

[9]  Robin A. de Graaf,et al.  In Vivo NMR Spectroscopy , 2019 .

[10]  Martin Wilson,et al.  Robust retrospective frequency and phase correction for single‐voxel MR spectroscopy , 2018, Magnetic resonance in medicine.

[11]  D. Weinberger,et al.  Role of gamma-amino-butyric acid in the dorsal anterior cingulate in age-associated changes in cognition , 2018, Neuropsychopharmacology.

[12]  A. V. D. van der Kouwe,et al.  Real-time Correction of Motion and Imager Instability Artifacts during 3D γ-Aminobutyric Acid-edited MR Spectroscopic Imaging. , 2017, Radiology.

[13]  K. Ivanov,et al.  Nuclear Spin Singlet Order Selection by Adiabatically Ramped RF Fields. , 2016, The journal of physical chemistry. B.

[14]  L. Kegeles.  Brain GABA Function and Psychosis. , 2016, The American journal of psychiatry.

[15]  David A Lewis,et al.  In vivo measurement of GABA transmission in healthy subjects and schizophrenia patients. , 2015, The American journal of psychiatry.

[16]  C. John Evans,et al.  Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA , 2014, NeuroImage.

[17]  R. Walsworth,et al.  Preparation of nuclear spin singlet states using spin-lock induced crossing. , 2013, Physical review letters.

[18]  Roland Kreis,et al.  The need for updates of spin system parameters, illustrated for the case of γ‐aminobutyric acid , 2012, NMR in biomedicine.

[19]  Peter R Luijten,et al.  Efficient spectral editing at 7 T: GABA detection with MEGA‐sLASER , 2012, Magnetic resonance in medicine.

[20]  B. Gulanski,et al.  Intravenous Ethanol Infusion Decreases Human Cortical γ-Aminobutyric Acid and N-Acetylaspartate as Measured with Proton Magnetic Resonance Spectroscopy at 4 Tesla , 2012, Biological Psychiatry.

[21]  M. Levitt,et al.  Singlet nuclear magnetic resonance of nearly-equivalent spins. , 2011, Physical chemistry chemical physics : PCCP.

[22]  M. Levitt,et al.  Storage of nuclear magnetization as long-lived singlet order in low magnetic field , 2010, Proceedings of the National Academy of Sciences.

[23]  Navin Khaneja,et al.  Optimal control in NMR spectroscopy: numerical implementation in SIMPSON. , 2009, Journal of magnetic resonance.

[24]  I. Lyoo,et al.  Increased GABA levels in medial prefrontal cortex of young adults with narcolepsy. , 2008, Sleep.

[25]  G B Matson,et al.  A detailed analysis of localized J‐difference GABA editing: theoretical and experimental study at 4 T , 2008, NMR in biomedicine.

[26]  P K Bhattacharyya,et al.  Spectral quality control in motion‐corrupted single‐voxel J‐difference editing scans: An interleaved navigator approach , 2007, Magnetic resonance in medicine.

[27]  Timo O. Reiss,et al.  Optimal control of coupled spin dynamics: design of NMR pulse sequences by gradient ascent algorithms. , 2005, Journal of magnetic resonance.

[28]  Marina Carravetta,et al.  Long-lived nuclear spin states in high-field solution NMR. , 2004, Journal of the American Chemical Society.

[29]  J. Krystal,et al.  Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. , 2002, The American journal of psychiatry.

[30]  P F Renshaw,et al.  In vivo detection of GABA in human brain using a localized double‐quantum filter technique , 1997, Magnetic resonance in medicine.

[31]  E. Terasawa,et al.  gamma-Aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[32]  D. McCormick,et al.  GABA as an inhibitory neurotransmitter in human cerebral cortex. , 1989, Journal of neurophysiology.

[33]  P. Bottomley.  Spatial Localization in NMR Spectroscopy in Vivo , 1987, Annals of the New York Academy of Sciences.

[34]  R. Witkamp,et al.  The influence of a tomato food matrix on the bioavailability and plasma kinetics of oral gamma-aminobutyric acid (GABA) and its precursor glutamate in healthy men. , 2022, Food & function.

[35]  Geoffrey Bodenhausen,et al.  Singlet-state exchange NMR spectroscopy for the study of very slow dynamic processes. , 2007, Journal of the American Chemical Society.