Molecular basis of diffusion MRI in human hippocampus revealed by ultrahigh resolution diffusion at 14.1 Tesla and spatial transcriptome

Motivation: The biological mechanisms underlying diffusion MRI (dMRI) phenotypes remain unclear, limiting their clinical applications. Goal(s): This study aims to explore the molecular basis of dMRI phenotypes from both genetic and cellular perspectives. Approach: High-resolution ex-vivo human hippocampal MRI scans at 14.1T, combined with spatial transcriptome and single-nucleus RNA sequencing data from the same subjects, were analyzed using voxel-wise Spearman correlation and Gene Ontology (GO) enrichment analysis. Results: The study found that isotropic diffusivity metrics were related to synapses and neurons, while anisotropic metrics were associated with myelin sheath, ribosomes and oligodendrocytes, providing support for the clinical applications of dMRI biomarkers. Impact: This study combined dMRI data with transcriptomic data, and revealed the molecular basis of dMRI phenotypes from a microscale perspective. This paradigm could be extended to other imaging modalities and applications in clinical disorders.