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

Abstract

Purpose: Functional understanding of the periaqueductal grey (PAG), a physiologically and clinically highly relevant brainstem region, can be advanced using proton magnetic resonance spectroscopy (1H-MRS). However, the PAG's small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve 1H-MRS data 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 two metabolite quantification approaches using literature-based or individual-based water relaxation times. Methods: Spectra were acquired in 33 healthy volunteers (50.1 years, SD=17.19, 18 females) on a 3T Philipps MR system using a point-resolved spectroscopy sequence optimized with very selective saturation pulses (OVERPRESS) and voxel-based flip angle calibration (effective volume of interest size: 8.8x10.2x12.2 mm3). Results: Spectral registration significantly improved signal-to-noise ratios (SNR; p=0.048, median value [interquartile range]: 18.0 [17.00-20.00]) and spectral linewidth (N-acetylaspartate peak: p<0.001, 4.3 Hz [3.96-4.85]), as well as metabolite fit (p's<0.046) compared to post-processing with minimal frequency alignment using interleaved unsuppressed water peaks. Correlational analyses revealed smaller improvements in SNR in cases of greater head motion (p=0.002) recorded with a markerless motion tracking system. Metabolite concentrations were higher when quantified using individual-based compared to literature-based water relaxation times (p's<0.001). Conclusion: This study demonstrates that high-quality 1H-MRS can be acquired in the PAG using spectral registration. This offers new opportunities for future 1H-MRS studies in the PAG and possibly also other clinically relevant brain regions with similar methodological challenges.