Improving magnetic resonance spectroscopy in the brainstem periaqueductal gray using spectral registration

Functional understanding of the periaqueductal gray (PAG), a clinically relevant brainstem region, can be advanced using ¹ H-MRS. However, the PAG's small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve ¹ H-MRS quality in the PAG using spectral registration for frequency and phase error correction; (2) investigate whether spectral registration is particularly useful in cases of greater head motion; and (3) examine metabolite quantification using literature-based or individual-based water relaxation times.

Spectra were acquired in 33 healthy volunteers (50.1 years, SD = 17.19, 18 females) on a 3 T Philipps MR system using a point-resolved spectroscopy (PRESS) sequence optimized with very selective saturation pulses (OVERPRESS) and voxel-based flip angle calibration (effective volume of interest size: 8.8 × 10.2 × 12.2 mm³ ). Spectra were fitted using LCModel and SNR, NAA peak linewidths and Cramér-Rao lower bounds (CRLBs) were measured after spectral registration and after minimal frequency alignment.

Spectral registration improved SNR by 5% (p = 0.026, median value post-correction: 18.0) and spectral linewidth by 23% (p < 0.001, 4.3 Hz), and reduced the metabolites' CRLBs by 1% to 15% (p < 0.026). Correlational analyses revealed smaller SNR improvements with greater head motion (p = 0.010) recorded using a markerless motion tracking system. Higher metabolite concentrations were detected using individual-based compared to literature-based water relaxation times (p < 0.001).

This study demonstrates high-quality ¹ H-MRS acquisition in the PAG using spectral registration. This shows promise for future ¹ H-MRS studies in the PAG and possibly other clinically relevant brain regions with similar methodological challenges.