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Testing the reliability of novel Voxel Placement approaches for Magnetic Resonance Spectroscopy

Chhabra, H.; Hehl, M.; Cuypers, K.; Dydak, U.; Nitsche, M. A.; Genc, E.; Burke, M.

2026-08-21 neuroscience
10.64898/2026.08.11.744164 bioRxiv
Show abstract

BackgroundSingle-voxel magnetic resonance spectroscopy (MRS) is a non-invasive method for measuring clinically and cognitively relevant metabolites. Reliable measurements require precise voxel placement across sessions and participants. We developed a scanner-console-based approach to improve voxel placement precision. MethodsIn a crossover design (n=7; six sessions each), we compared test-retest reliability of three voxel placement methods in a reference benchmark (left parietal cortex) and a technically challenging region (left ventromedial prefrontal cortex). Methods included (1) conventional anatomy-based placement, (2) mask-guided real-time positioning (MGRP), and (3) semiautomated session-locked voxel repositioning (SSVR). Resting-state MRS data were acquired using PRESS and MEGA-PRESS. Within-subject reliability of voxel placement and metabolite concentrations, namely, total N-acetylaspartate (tNAA), total Creatine (tCr), GABA (gamma-aminobutyric acid), and Glx (glutamate + glutamine) are reported using the coefficient of variation (CV), the intraclass correlation coefficient (ICC), minimal detectable change (MDC), and the spatial overlap. ResultsSSVR markedly improved voxel placement reliability, increasing spatial overlap (up to 88%) and achieving near-perfect geometric reproducibility (ICC = 0.99) compared to conventional anatomy-based placement and MGRP. SSVR improved tissue composition consistency and reduced metabolite variability in the technically challenging region (variability reduction of [~]70% tCr, [~]59% tNAA, and [~]51% Glx) while further refining already stable measurements in the benchmark region (tNAA from [~]15% to [~]10%). ConclusionBoth MGRP and SSVR improved voxel placement and metabolite measurement reproducibility compared with conventional anatomy-based placement. SSVR further enhanced within-subject reproducibility across repeated sessions, particularly in the technically challenging region, providing a robust approach for longitudinal single-voxel MRS studies.

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