High-resolution whole-brain magnetic resonance spectroscopic imaging in youth at risk for psychosis

Celereau, E.; Lucchetti, F.; Aleman-Gomez, Y.; Dwir, D.; Cleusix, M.; Ledoux, J.-B.; Jenni, R.; Bach Cuadra, M.; Schilliger, Z.; Solida, A.; Armando, M.; Plessen, K. J.; Hagmann, P.; Conus, P.; Klauser, A.; Klauser, P.

doi:10.1101/2025.06.22.660965

bioRxiv · 10.1101/2025.06.22.660965

High-resolution whole-brain magnetic resonance spectroscopic imaging in youth at risk for psychosis

Celereau, E.·Lucchetti, F.·Aleman-Gomez, Y.·Dwir, D.·Cleusix, M.·Ledoux, J.-B.·Jenni, R.·Bach Cuadra, M.·Schilliger, Z.·Solida, A.·Armando, M.·Plessen, K. J.·Hagmann, P.·Conus, P.·Klauser, A.·Klauser, P.

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Abstract

Advances in three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI) allow for the high-resolution mapping of multiple neurometabolites throughout the entire brain in vivo and within clinically compatible time frames. Leveraging this capability, we created a voxel-based pipeline that corrects and spatially normalizes whole-brain maps of total N-acetylaspartate (tNAA), myo-inositol (Ins), choline compounds, glutamate + glutamine, and creatine + phosphocreatine. We examined 2 different 3D-MRSI dataset: first, a clinical sample of adolescents and young adults at risk for psychosis (n= 21) meeting DSM-5 criteria for Attenuated Psychosis Syndrome (APS) or Schizotypal Personality Disorder (SCZT), and age-/sex-matched healthy controls (n =13); and second, a non-clinical sample of adolescents (n = 61) scanned on a different site. The objective of the study was threefold: first, to assess the reproducibility of 3D-MRSI measures across datasets and scanning sites; second, to validate the feasibility of whole-brain, voxel-based analyses on 3D-MRSI data; and third, to test the sensitivity of this approach. Metabolite distributions showed reproducible regional variation in standard space between the two independent samples and scanning sites (r ranging from 0.82 to 0.99). Relative to controls, at-risk participants exhibited higher tNAA levels in frontal grey matter; the SCZT subgroup additionally displayed widespread cortical and subcortical elevations of Ins levels compared with both APS and controls. Voxel-based analyses of structural (i.e., gray and white matter volumes or densities) and diffusion (i.e., generalized fractional anisotropy) parameters yielded no significant differences between patients and controls. These preliminary findings suggest that high-resolution 3D-MRSI may be sensitive enough to detect subtle neurometabolic alterations at the group level in the early stages of psychotic disorders when structural or diffusion measures show no difference. High-resolution whole-brain metabolic mapping may have the potential to help with early identification of young people at risk for psychosis or other mental disorders.

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Celereau, E., Lucchetti, F., Aleman-Gomez, Y., Dwir, D., Cleusix, M., Ledoux, J.-B., Jenni, R., Bach Cuadra, M., Schilliger, Z., Solida, A., Armando, M., Plessen, K. J., Hagmann, P., Conus, P., Klauser, A., Klauser, P.. 2025-06-24. High-resolution whole-brain magnetic resonance spectroscopic imaging in youth at risk for psychosis. https://doi.org/10.1101/2025.06.22.660965

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