title: Brain γ-aminobutyric acid (GABA) detection in vivo with the J-editing (1) H MRS technique: a comprehensive methodological evaluation of sensitivity enhancement, macromolecule contamination and test-retest reliability.
abstract: Abnormalities in brain γ-aminobutyric acid (GABA) have been implicated in various neuropsychiatric and neurological disorders. However, in vivo GABA detection by (1) H MRS presents significant challenges arising from the low brain concentration, overlap by much stronger resonances and contamination by mobile macromolecule (MM) signals. This study addresses these impediments to reliable brain GABA detection with the J-editing difference technique on a 3-T MR system in healthy human subjects by: (i) assessing the sensitivity gains attainable with an eight-channel phased-array head coil; (ii) determining the magnitude and anatomic variation of the contamination of GABA by MM; and (iii) estimating the test-retest reliability of the measurement of GABA with this method. Sensitivity gains and test-retest reliability were examined in the dorsolateral prefrontal cortex (DLPFC), whereas MM levels were compared across three cortical regions: DLPFC, the medial prefrontal cortex (MPFC) and the occipital cortex (OCC). A three-fold higher GABA detection sensitivity was attained with the eight-channel head coil compared with the standard single-channel head coil in DLPFC. Despite significant anatomical variation in GABA + MM and MM across the three brain regions (p < 0.05), the contribution of MM to GABA + MM was relatively stable across the three voxels, ranging from 41% to 49%, a non-significant regional variation (p = 0.58). The test-retest reliability of GABA measurement, expressed as either the ratio to voxel tissue water (W) or to total creatine, was found to be very high for both the single-channel coil and the eight-channel phased-array coil. For the eight-channel coil, for example, Pearson's correlation coefficient of test vs. retest for GABA/W was 0.98 (R(2)  = 0.96, p = 0.0007), the percentage coefficient of variation (CV) was 1.25% and the intraclass correlation coefficient (ICC) was 0.98. Similar reliability was also found for the co-edited resonance of combined glutamate and glutamine (Glx) for both coils. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Robyn
authors.initials: R
authors.lastname: Gonzales
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Tacara N
authors.initials: TN
authors.lastname: Soones
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Dyke
authors.affiliation: NIMH Magnetic Resonance Spectroscopy Core Unit, Bethesda, MD, USA.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: van der Veen
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.|Department of Radiology, Columbia University, New York, NY, USA.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
mesh_terms: D000328:Adult; D000465:Algorithms; D005260:Female; D006801:Humans; D046911:Macromolecular Substances / Q000032:analysis / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D017397:Prefrontal Cortex / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
chemical_list: D046911:Macromolecular Substances; D005680:gamma-Aminobutyric Acid
keywords: 1H MRS; GABA; Glutamate; Glx; J-editing; mobile macromolecules; phased-array coil; test-retest reliability