Single-Cell Photoacoustic Molecular Imaging at Centimeter Depth

This project will develop a new photoacoustic technology that will enable cellular-resolution molecular imaging deep inside live tissue—a breakthrough that will revolutionize brain research and have a broad impact beyond neuroscience. Deep tissue molecular imaging at single-cell resolution presents an enduring challenge: light focusing and penetration are strongly limited by tissue scattering and absorption, while conventional deep-penetrating ultrasound imaging, magnetic resonance imaging, and positron emission tomography can only provide mesoscopic resolution. Photoacoustic imaging uniquely combines light and ultrasound for deep penetration and molecular contrast. However, existing ultrasonic sensors are orders of magnitude less sensitive than required to detect the weak signal from individual cells at depths.

To break the penetration-resolution tradeoff, this project will harness the quantum physics of exceptional points for a first-in-class ultrasonic sensor with an unprecedented increase in sensitivity over conventional sensors. Using the new sensor, this team will develop photoacoustic localization molecular microscopy for deep tissue high resolution imaging at high speeds. They will demonstrate how this new technology enables simultaneous monitoring of large neural populations at spike-resolution at an unprecedented scale across the entire rodent brain during behavior—revolutionizing how researchers study brains.