Improving MRI Detection Limits
MRI is generally considered an insensitive technique, and monitoring genetic activity with MRI-based reporter genes requires tens of thousands of labeled cells in each imaging voxel. This project seeks to increase this detection limit by at least an order of magnitude, enabling researchers to monitor genetic activity in (ideally) double-digit numbers of cells per voxel, potentially even approaching single-cell sensitivity. The conceptual basis of this approach is a mechanism for engineering intercellular communication to allow reporter-generated signals from small numbers of cells to spread to additional cells within the same voxel, thereby amplifying the net signal obtained from the voxel. If successful, this approach will allow MRI (specifically, MRI-based reporters) to be used for basic studies involving rare biological events, such as metastatic gene activity in a primary tumor and activity in sparse neuronal ensembles.