Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain

Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through C-13-enriched diets. A C-13 magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient C-13-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.

Automated summary

This study presents a new method called epigenetic MRI (eMRI) that allows nondestructive measurement of global gene expression in the brain by directly imaging DNA methylation. The method uses C-13-enriched diets to label DNA through methionine metabolic pathways, and a C-13 magnetic resonance spectroscopic imaging technique to map the spatial distribution of labeled DNA. The study validated eMRI using pigs and discovered regional differences in global DNA methylation. The eMRI signal has the potential to enable new investigations of human brain function, behavior, and disease.