Genetic tools to manipulate MRI contrast

Advances in molecular biology in the early 1970s have revolutionized research strategies for studying complex biological processes, which in turn created a high demand for new means to visualize these dynamic biological changes non-invasively and in real-time. In that respect, magnetic resonance imaging (MRI) technology was a perfect fit, due the versatile possibility to alter the different contrast mechanisms. Genetic manipulations are now being translated to MRI trough the development of reporters and sensors, as well as imaging transgenic and knockout mice. In the past few years, a new molecular biology toolset, namely optogenetics, has emerged, which allows for the manipulation of cellular behavior using light. This technology provides a few particularly attractive features for combination with newly developed MRI techniques for probing in vivo cellular, and in particular neural, processes – specifically the ability to control focal, genetically-defined cellular populations with high temporal resolution using equipment that is magnetically inert and does not interact with radiofrequency pulses. Recent works demonstrate that the combination of optogenetics and functional MRI (fMRI) can provide an appropriate platform to investigate in vivo, at the cellular and molecular levels, the neuronal basis of fMRI signals. In addition, this novel combination of optogenetics with fMRI has the potential to resolve pre-synaptic vs. post-synaptic changes of neuronal activity and changes in the activity of large neuronal networks in the context of plasticity associated with development, learning and pathophysiology.