Mapping the molecular landscape of the living brain: integrating spatial transcriptomics and qMRI

Disease modifying therapies targeting specific molecular disease processes are becoming increasingly available for neurodegenerative disorders. However, profiling molecular features of neurodegeneration in living patients is challenging due to limited accessibility to brain tissue. In this work, we demonstrate that we can infer cell type presence and expression of molecular pathways at a sub-cortical level from ultra-high resolution 7T quantitative MRI by leveraging in-depth molecular characterisation of spatial transcriptomics (ST) data. We demonstrate the applicability of our approach to characterising disease by predicting molecular features in a Parkinson’s disease cohort. From qMRI data we predict disruption to the distribution of oligodendrocytes in the grey-matter cortex consistent with altered oligodendrocyte maturation. Our method contributes to advancing precision medicine in neurodegeneration, with promising attributes including cost-effectiveness, tolerability and clinical accessibility, with potential for clinical impact.