Two-Photon Lensless Micro-endoscopy with in-situ Wavefront Correction

Multi-core fiber-bundle endoscopes provide a minimally-invasive solution for deep tissue imaging and opto-genetic stimulation, at depths beyond the reach of conventional microscopes. Recently, wavefront-shaping has enabled lensless bundle-based micro-endoscopy by correcting the wavefront distortions induced by core-to-core inhomogeneities. However, current wavefront-shaping solutions require access to the fiber distal end for determining the bend-sensitive wavefront-correction. Here, we show that it is possible to determine the wavefront correction in-situ, without any distal access. Exploiting the nonlinearity of two-photon excited fluorescence, we adaptively determine the wavefront correction in-situ, using only proximal detection of epi-detected fluorescence. We experimentally demonstrate diffraction-limited, three-dimensional, two-photon lensless microendoscopy with commercially-available ordered- and disordered multi-core fiber bundles.