Abstract:
Functional magnetic resonance imaging (fMRI) with contrast agents sensitive to neural activity could have great impact in neuroscience by combining noninvasive whole-brain coverage with molecular-level specificity for neuronal events. My laboratory is developing molecular fMRI approaches based on molecular sensors we have designed to detect intra- and extracellular signalling events in the nervous system.  Our sensors are built on a variety of chemical platforms, ranging from small molecules to nanoparticles.  Protein-based contrast agents are of particular interest to us because of the possibility of gene-based brain delivery strategies and the availability of powerful protein engineering techniques.  Here we describe molecular engineering of several MRI sensors for neural activity, as well as the first efforts in our laboratory to perform functional neuroimaging with molecular specificity in living brains.