biostudies-literatureLam FCarle-Illinois College of MedicineBeckman Institute for Advanced Science and Technology, University of Illinois, Urbana-ChampaignIllinois Sociogenomics Initiativee2119891119https://www.ebi.ac.uk/biostudies/studies/S-EPMC8915962biostudies-literatureUnknown119(10)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 ¹³C-enriched diets. A ¹³C 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 ¹³C-labeling of brain DNA. We alProceedings of the National Academy of Sciences of the United States of AmericaEpigenetic MRI: Noninvasive imaging of DNA methylation in the brain.PMC8915962No numberLam FLiang ZPLi KCRobinson GESilverman SKCao CHitchens TKChu JChoi JSDilger RNfalseEpigenetic 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 ¹³C-enriched diets. A ¹³C 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 ¹³C-labeling of brain DNA. We al2022-01-01T00:00:00Z2022 Mar2025-04-26T03:50:27.758Z2025-04-06T10:58:40.43ZS-EPMC89159623523545810.1073/pnas.2119891119