Mescher–Garwood point resolved spectroscopy (MEGA-PRESS) data were analyzed using GANNET 3.0 (http://www.gabamrs.com/ ) in Matlab 2020b (Mathworks) (Edden et al., 2014 (link)). Moreover, macromolecules (MM) and homocarnosine (Rothman et al., 1997 (link)) contribute to the GABA signal at 3 ppm; therefore, it is referred to as GABA+ rather than GABA. Since the glutamine (Gln) signal was not separated from the glutamine (Glu) signal, we reported the Glx (the combined signals of Glu and Gln) level in our study. The ratios of the integrals of neurotransmitters (GABA+ or Glx) and water signals, corrected with T1/T2 relaxation and tissue composition, were used to calculate water-scaled GABA+ or Glx levels in institutional units (IUs) (Mullins et al., 2014 (link); Harris et al., 2015 (link)).
Based on 3D T1-weighted brain images, the fractional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) content within each spectroscopic voxel were calculated using an automatic brain segmentation program, FAST (FMRIB's automated segmentation tool) in the FSL package (Oxford University, Oxford, UK) (Zhang et al., 2001 (link)).
Amide proton transfer-weighted (APTw) images were generated directly from the scanner, and they were co-registered and overlaid with geometrically identically acquired 3D T1WI images on a dedicated workstation called “IntelliSpace Portal” (Philips Healthcare, Best, the Netherlands) (Figure 2 ). The regions of interest (ROIs) were manually drawn on the fused image by two radiologists with 10 years of experience in neurological imaging blinded to clinical and cognitive information of all participants, to delineate the segments of the right hippocampus in the maximum cross-sectional layer; to avoid areas of infarction, necrosis, and hemorrhage; and to calculate the average value. The MTR asymmetry (MTRasym) map at the offset of 3.5 ppm is called the APTw image: APTw = MTRasym (3.5 ppm) = MTR (3.5 ppm) – MTR (−3.5 ppm) = [Ssat (−3.5 ppm) – Ssat (3.5 ppm)]/S0.
Based on 3D T1-weighted brain images, the fractional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) content within each spectroscopic voxel were calculated using an automatic brain segmentation program, FAST (FMRIB's automated segmentation tool) in the FSL package (Oxford University, Oxford, UK) (Zhang et al., 2001 (link)).
Amide proton transfer-weighted (APTw) images were generated directly from the scanner, and they were co-registered and overlaid with geometrically identically acquired 3D T1WI images on a dedicated workstation called “IntelliSpace Portal” (Philips Healthcare, Best, the Netherlands) (
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