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

Recent developments in acquisition and reconstruction of 3-dimensional magnetic-resonance spectroscopic imaging (3D-MRSI) enable the high-resolution mapping of multiple neurometabolites in the whole-brain, in vivo. 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 a clinical cohort 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), as well as an independent non-clinical sample of adolescents (n = 61). We first aimed at assessing the reproducibility of MRSI measures across datasets and scanning sites, then validate the feasibility of a whole-brain voxel-based analyses on 3D-MRSI data and eventually 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 in frontal grey matter; the SCZT subgroup additionally displayed widespread cortical and subcortical Ins elevations compared with both APS and controls. Voxel-based analyses of structural (i.e., gray and white matter volumes or densities) and dijusion (i.e., generalized fractional anisotropy) parameters yielded no significant dijerences between risk participants and controls. These findings suggest the sensitivity of high-resolution 3D-MRSI for detecting subtle neurometabolic alterations at the group level in the early stages of psychotic disorders. Detailed brain metabolic mapping has the potential to help with early identification of young people at risk for psychosis or other mental disorders.