Quantification of γ-aminobutyric acid (GABA) in1H MRS volumes composed heterogeneously of grey and white matter.
The quantification of γ-aminobutyric acid (GABA) concentration using localised MRS suffers from partial volume effects related to differences in the intrinsic concentration of GABA in grey (GM) and white (WM) matter. These differences can be represented as a ratio between intrinsic GABA in GM and WM: rM. Individual differences in GM tissue volume can therefore potentially drive apparent concentration differences. Here, a quantification method that corrects for these effects is formulated and empirically validated. Quantification using tissue water as an internal concentration reference has been described previously. Partial volume effects attributed to rMcan be accounted for by incorporating into this established method an additional multiplicative correction factor based on measured or literature values of rMweighted by the proportion of GM and WM within tissue-segmented MRS volumes. Simulations were performed to test the sensitivity of this correction using different assumptions of rMtaken from previous studies. The tissue correction method was then validated by applying it to an independent dataset of in vivo GABA measurements using an empirically measured value of rM. It was shown that incorrect assumptions of rMcan lead to overcorrection and inflation of GABA concentration measurements quantified in volumes composed predominantly of WM. For the independent dataset, GABA concentration was linearly related to GM tissue volume when only the water signal was corrected for partial volume effects. Performing a full correction that additionally accounts for partial volume effects ascribed to rMsuccessfully removed this dependence. With an appropriate assumption of the ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be corrected for partial volume effects, potentially leading to a reduction in between-participant variance, increased power in statistical tests and better discriminability of true effects.
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK. mmikkel5@jhmi.edu.|Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. mmikkel5@jhmi.edu.|F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. mmikkel5@jhmi.edu.
Mark
0000-0002-0349-3782
M
Mikkelsen
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.
Krish D
KD
Singh
MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
Jennifer A
JA
Brealy
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.|MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
David E J
DE
Linden
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.
C John
CJ
Evans
D000328:Adult; D000465:Algorithms; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D009778:Occipital Lobe / Q000033:anatomy & histology / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D066127:White Matter / Q000033:anatomy & histology / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D005680:gamma-Aminobutyric Acid
GABA; MRS; grey matter; metabolite quantification; partial volume effects; tissue correction; tissue segmentation; white matter