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Constructing the human brain metabolic connectome with MR spectroscopic imaging reveals cerebral biochemical organization
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Journal Article
Constructing the human brain metabolic connectome with MR spectroscopic imaging reveals cerebral biochemical organization
2025
Overview
Network science has mapped brain structural and functional organization, yet capturing metabolic contrast remains a major gap in connectomics. Using fast, high-resolution 3D whole-brain proton magnetic resonance spectroscopic imaging (
1
H-MRSI), we derive a within-subject metabolic connectome in 51 healthy subjects, defined as pairwise correlations among five metabolites (tCr, tNAA, Glx, Ins, Cho) across gray-matter parcels. Results show stability, consistency and replicability, including validation in an independent sample (
N
= 13) scanned at a different site. A dimensionality reduction analysis shows that the leading metabolic similarity mode forms a continuous caudal-to-rostral gradient across gray-matter regions. We show that this progression is reflective of a balance between local metabolic homogeneity and global metabolic diversity, and can be summarized by a principal path through the metabolic network. While the most metabolically active regions overlap with structural hubs, overall metabolic similarity aligns weakly with tractography-based structural connectivity but more closely with cytoarchitectonic similarity and gene co-expression matrices. These findings introduce the metabolic similarity gradient as a signature of the brain’s biochemical organization and position MRSI as a biologically grounded dimension for connectomics in health and disease.
Using whole-brain MRSI, this study builds a metabolic connectome derived from five metabolite signals. It reveals a network topology balancing local similarity and global diversity, mirroring structural, cytoarchitectonic and genetic organization.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
