Normalizing data from GABA-edited MEGA-PRESS implementations at 3 Tesla.

Standardization of results is an important milestone in the maturation of any truly quantitative methodology. For instance, a lack of measurement agreement across imaging platforms limits multisite studies, between-study comparisons based on the literature, and inferences based on and the generalizability of results. In GABA-edited MEGA-PRESS, two key sources of differences between implementations are: differences in editing efficiency of GABA and the degree of co-editing of macromolecules (MM). In this work, GABA editing efficiency κ and MM-co-editing μ constants are determined for three widely used MEGA-PRESS implementations (on the most common MRI platforms; GE, Philips, and Siemens) by phantom experiments. Implementation-specific κ,μ-corrections were then applied to two in vivo datasets, one consisted of 8 subject scanned on the three platforms and the other one subject scanned eight times on each platform. Manufacturer-specific κ and μ values were determined as: κGE=0.436, κSiemens=0.366 and κPhilips=0.394 and μGE=0.83, μSiemens=0.625 and μPhilips=0.75. Applying the κ,μ-correction on the Cr-referenced data decreased the coefficient of variation (CV) of the data for both in vivo data sets (multisubjects: uncorrected CV=13%, κ,μ-corrected CV=5%, single subject: uncorrected CV=23%, κ,μ-corrected CV=13%) but had no significant effect on mean GABA levels. For the water-referenced results, CV increased in the multisubject data (uncorrected CV=6.7%, κ,μ-corrected CV=14%) while it decreased in the single subject data (uncorrected CV=24%, κ,μ-corrected CV=21%) and manufacturer was a significant source of variance in the κ,μ-corrected data. Applying a correction for editing efficiency and macromolecule contamination decreases the variance between different manufacturers for creatine-referenced data, but other sources of variance remain.

[1]  R. Edden,et al.  In vivo magnetic resonance spectroscopy of GABA: a methodological review. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[2]  R. Edden,et al.  Spectral‐editing measurements of GABA in the human brain with and without macromolecule suppression , 2015, Magnetic resonance in medicine.

[3]  Jürgen R. Reichenbach,et al.  In vivo detection of acute pain-induced changes of GABA+ and Glx in the human brain by using functional 1H MEGA-PRESS MR spectroscopy , 2015, NeuroImage.

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

[5]  Martin G Pomper,et al.  An imbalance between excitatory and inhibitory neurotransmitters in amyotrophic lateral sclerosis revealed by use of 3-T proton magnetic resonance spectroscopy. , 2013, JAMA neurology.

[6]  David J McGonigle,et al.  Diurnal stability of γ‐aminobutyric acid concentration in visual and sensorimotor cortex , 2009, Journal of magnetic resonance imaging : JMRI.

[7]  Stewart H Mostofsky,et al.  Reduced GABA concentration in attention-deficit/hyperactivity disorder. , 2012, Archives of general psychiatry.

[8]  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.

[9]  Xiangling Mao,et al.  Brain γ‐aminobutyric acid (GABA) detection in vivo with the J‐editing 1H MRS technique: a comprehensive methodological evaluation of sensitivity enhancement, macromolecule contamination and test–retest reliability , 2016, NMR in biomedicine.

[10]  S. Holland,et al.  NMR relaxation times in the human brain at 3.0 tesla , 1999, Journal of magnetic resonance imaging : JMRI.

[11]  E. Martin,et al.  In vivo detection of GABA and glutamate with MEGA‐PRESS: Reproducibility and gender effects , 2011, Journal of magnetic resonance imaging : JMRI.

[12]  Richard A. E. Edden,et al.  Multi-Regional Investigation of the Relationship between Functional MRI Blood Oxygenation Level Dependent (BOLD) Activation and GABA Concentration , 2015, PloS one.

[13]  Peter Jezzard,et al.  Efficient γ‐aminobutyric acid editing at 3T without macromolecule contamination: MEGA‐SPECIAL , 2011, NMR in biomedicine.

[14]  C. Rae A Guide to the Metabolic Pathways and Function of Metabolites Observed in Human Brain 1H Magnetic Resonance Spectra , 2013, Neurochemical Research.

[15]  Muhammad G Saleh,et al.  Edited 1H magnetic resonance spectroscopy in vivo: Methods and metabolites , 2017, Magnetic resonance in medicine.

[16]  R. Gruetter,et al.  In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time , 1999, Magnetic resonance in medicine.

[17]  Peter B Barker,et al.  Measuring T2 in vivo with J‐difference editing: Application to GABA at 3 tesla , 2012, Journal of magnetic resonance imaging : JMRI.

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

[19]  A. Doerfler,et al.  In vivo quantification of intracerebral GABA by single-voxel (1)H-MRS-How reproducible are the results? , 2010, European journal of radiology.

[20]  T. Scheenen,et al.  Multi‐center reproducibility of neurochemical profiles in the human brain at 7 T , 2015, NMR in biomedicine.

[21]  Richard A. E. Edden,et al.  Voxel Placement Precision for GABA-Edited Magnetic Resonance Spectroscopy , 2017, Open journal of radiology.

[22]  Dost Öngür,et al.  Creatine abnormalities in schizophrenia and bipolar disorder , 2009, Psychiatry Research: Neuroimaging.

[23]  Mark Tommerdahl,et al.  Title: Reduced Gabaergic Inhibition and Abnormal Sensory Symptoms in Children with Tourette Syndrome Running Head: Abnormal Gaba Levels and Sensory Processing in Ts Submitted for the Steven Hsiao Special Issue Nicolaas Puts, Phd Author Contributions Introduction , 2022 .

[24]  Peter Jezzard,et al.  Frequency and phase drift correction of magnetic resonance spectroscopy data by spectral registration in the time domain , 2015, Magnetic resonance in medicine.

[25]  D Matthaei,et al.  1H NMR chemical shift selective (CHESS) imaging. , 1985, Physics in medicine and biology.

[26]  Peter B Barker,et al.  Spatial effects in the detection of γ‐aminobutyric acid: Improved sensitivity at high fields using inner volume saturation , 2007, Magnetic resonance in medicine.

[27]  R. Edden,et al.  Macromolecule‐suppressed GABA‐edited magnetic resonance spectroscopy at 3T , 2012, Magnetic resonance in medicine.

[28]  X. Mao,et al.  Motor cortex glutathione deficit in ALS measured in vivo with the J-editing technique , 2014, Neuroscience Letters.

[29]  R. B. Kingsley,et al.  WET, a T1- and B1-insensitive water-suppression method for in vivo localized 1H NMR spectroscopy. , 1994, Journal of magnetic resonance. Series B.

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

[31]  Mohammad Sabati,et al.  Multivendor implementation and comparison of volumetric whole‐brain echo‐planar MR spectroscopic imaging , 2015, Magnetic resonance in medicine.

[32]  S F Keevil,et al.  Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain. , 1998, Magnetic resonance imaging.

[33]  Luke Bloy,et al.  GABA estimation in the brains of children on the autism spectrum: Measurement precision and regional cortical variation , 2014, NeuroImage.

[34]  Martin Tegenthoff,et al.  Impact of frequency drift on gamma‐aminobutyric acid‐edited MR spectroscopy , 2014, Magnetic resonance in medicine.

[35]  G. Bloch,et al.  Brain GABA editing without macromolecule contamination , 2001, Magnetic resonance in medicine.

[36]  Peter B Barker,et al.  J‐difference editing of gamma‐aminobutyric acid (GABA): Simulated and experimental multiplet patterns , 2013, Magnetic resonance in medicine.

[37]  Alfons Schnitzler,et al.  Low visual cortex GABA levels in hepatic encephalopathy: links to blood ammonia, critical flicker frequency, and brain osmolytes , 2015, Metabolic Brain Disease.

[38]  R. Edden,et al.  Gannet: A batch‐processing tool for the quantitative analysis of gamma‐aminobutyric acid–edited MR spectroscopy spectra , 2014, Journal of magnetic resonance imaging : JMRI.

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

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

[41]  M. Garwood,et al.  Simultaneous in vivo spectral editing and water suppression , 1998, NMR in biomedicine.

[42]  G Helms,et al.  Volume correction for edema in single‐volume proton MR spectroscopy of contrast‐enhancing multiple sclerosis lesions , 2001, Magnetic resonance in medicine.

[43]  K. Behar,et al.  Analysis of macromolecule resonances in 1H NMR spectra of human brain , 1994, Magnetic resonance in medicine.

[44]  R. Edden,et al.  Measuring the longitudinal relaxation time of GABA in vivo at 3 tesla , 2013, Journal of magnetic resonance imaging : JMRI.