Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis

Quantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate ( R 1), effective transverse relaxation rate ( R 2 ∗ ), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes ( R 2 ∗ at 3T, R 1 at 7T), endothelial cells ( R 1 and MTsat at 3T), microglia ( R 1 and MTsat at 3T, R 1 at 7T), and oligodendrocytes ( R 1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types. ### Competing Interest Statement The Max Planck Institute for Human Cognitive and Brain Sciences has an institutional research agreement with Siemens Healthcare. NW holds a patent on acquisition of MRI data during spoiler gradients (US 10,401,453 B2). NW was a speaker at an event organized by Siemens Healthcare and was reimbursed for the travel expenses.