We propose a concurrent multiphoton magnetic resonance imaging (COMPMRI) system for mouse imaging, in response to RFA-EY-16-001, BRAIN Initiative: New Concepts and Early-Stage Research for Large-Scale Recording and Modulation in the Nervous System (R21). We synergistically combine multiphoton microscopy (MPM), which offers cellular imaging resolution with penetration depth, and Magnetic resonance imaging (MRI), which is routinely used to capture large-scale neural activities across many regions of the brain. To understand molecular cellular origin of the large-scale neural activity, we need simultaneous imaging both at cellular resolution and over the whole brain, which is concurrent MPM and MRI as in our proposed COMPMRI. Furthermore, we will leverage our latest breakthrough in MPM using 3-photon excitation with long wavelength that enables through-skull cellular resolution imaging, making it possible to perform MPM at multiple cortical regions. Our proposed COMPMRI will take advantage of this 3-photon microscopy and the large bore size of a 3T human MRI system to scan the brain of a live mouse. Our proposed COMPMRI system will allow simultaneous study of neural activities localized in a region and distributed over the whole brain.

The proposed program, if successfully completed, leads to a concurrent multiphoton magnetic resonance imaging (COMPMRI) system for mouse imaging. The successful completion of this program will have a broad impact on a wide variety of biological and biomedical research fields where non-invasive, high-resolution imaging over multiple areas of mouse brain is required.