Epigenetic MRI: Noninvasive Imaging of DNA Methylation in the Brain

It has been recognized that an integration of neuronal and genetic mechanisms supports brain function, regulates behaviour, and underpins response to environmental or disease stimuli. Several different technologies are available for imaging and studying neuronal activity in living brains, such as functional magnetic resonance imaging (fMRI), and have been translated to humans. However, the tools available to measure gene expression are destructive. Here we present a method, called epigenetic MRI (eMRI), that overcomes this limitation. eMRI achieves for the first time direct and noninvasive imaging of DNA methylation, a major gene expression regulator, in intact brains. eMRI exploits the methionine metabolic pathways that are responsible for DNA methylation to label the methyl-cytosine in brain genomic DNA through carbon-13 enriched diets. It then uses a novel carbon-13 magnetic resonance spectroscopic imaging (13C-MRSI) method to map the spatial distribution of labeled DNA. We demonstrated successful 13C labeling of brain DNA through diet using mass spectrometry, and robust and specific detection of labeled DNA using 13C-MRSI. We used eMRI and a biomedical piglet model to produce the first DNA methylation map of an intact brain hemisphere. With both noninvasive labeling and imaging, we expect eMRI to be readily translated to humans and thus enable many new investigations into the epigenetic basis of brain function, behavior, and disease.