Molecular fMRI of neurochemical signaling

Magnetic resonance imaging (MRI) is the most widely applied technique for brain-wide measurement of neural function in humans and animals. In conventional functional MRI (fMRI), brain signaling is detected indirectly, via localized activity-dependent changes in regional blood flow, oxygenation, and volume, to which MRI contrast can be readily sensitized. Although such hemodynamic fMRI methods are powerful tools for analysis of brain activity, they lack specificity for the many molecules and cell types that play functionally distinct roles in neural processing. A suite of techniques collectively known to as "molecular fMRI," addresses this limitation by permitting MRI-based detection of specific molecular processes in deep brain tissue. This review discusses how molecular fMRI is coming to be used in the study of neurochemical dynamics that mediate intercellular communication in the brain. Neurochemical molecular fMRI is a potentially powerful approach for mechanistic analysis of brain-wide function, but the techniques are still in early stages of development. Here we provide an overview of the major advances and results that have been achieved to date, as well as directions for further development.