EAGER: Space-Time-Pulsed Engineered-Excitation For Diffraction-Free Imaging

Brown University, Providence RI

Investigators

Abstract

Fluorescence imaging in live animals is transforming brain science. However, the light that travels through brain tissue undergoes unwanted scrambling or its trajectory as the tissue becomes thick, which ultimately alters the original direction of travel. Thus, it remains a challenge to obtain clear, high-resolution images of the brain for fluorescence imaging at depths beyond the thickness of human hair. This work will develop a new type of optical microscopy—space-time-pulsed engineered-excitation for diffraction-free imaging (SPEEDI)—that makes use of exotic space-time wave packets (STWPs), which have been found to resist scrambling by objects encountered along its travel path. Experiments pursued will incorporate various types of tissue specimens, and results will be compared to those obtained us other conventional types of microscopy techniques. The project will also provide a platform to recruit students from diverse backgrounds to learn about microscopy. Scientific concepts learned from the project will also be integrated into an existing optics course. The proposed technology will allow imaging across all Neocortical layers using one-photon (1P) sources, which are significantly more affordable than multiphoton sources, broadly enhancing accessibility. SPEEDI would be able to provide 1P imaging at depth with cellular precision without surgical removal, and it would enable depth-resolved use of 1P-optimized indicators, including the next generation voltage indicators. As SPEEDI is based on utilizing a new type of optical field, all of the advantages afforded from using twophoton and three-photon sources would also apply, e.g., further enhancement of penetration depth and signal-to-background ratio. In addition, the novel level of control obtained by modifying the underlying spatiotemporal spectral structure of SPEEDI enables exquisite manipulation of the properties of the STWPs in space and time, providing diffraction-free and dispersion-free propagation (of any order in the time domain), tunable group velocity, and temporal focusing over short distances in any medium. This level of exquisite control of the spatiotemporal properties will permit the introduction of ultra-high group-velocity dispersion (GVD) into the space-time wave packets (STWP), which will broaden rapidly on a controllable length scale even in free space or a low-GVD medium. Therefore, by first introducing group-delay dispersion (GDD) into the initial generic pulse used to synthesize the STWP, the GVD enables the temporal focusing of the pulse at a prescribed depth. Indeed, the focusing depth can be tuned by either changing the initial GDD or modifying the GVD introduced into the STWP, both of which can be realized electronically with no moving parts. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.