High resolution Fluorescence lifetime IMaging Micro-Endoscopy (FLIMME) using a single multimode fiber

Endoscopic optical imaging using a single multimode fiber (MMF) has emerged as a promising approach for highly compact, minimally invasive, and high-resolution imaging. Unlike conventional fiber bundles, MMF-based endomicroscopes exploit the controlled excitation of multiple spatially overlapping modes in a single MMF. of core diameters of tens of micrometers. to deliver and collect light to form images with sub-micrometer resolution. Here, we introduce a fluorescence lifetime imaging microscopy (FLIM) modality to the MMF endomicroscope. We use amplitude modulation of a 405 nm single-mode light source at radio frequency (RF) and lock-in detection of autofluorescence to obtain intensity and lifetime images at sub-micrometer resolution. We experimentally demonstrate the capability of the ultrathin endomicroscope to perform label-free imaging in thick ex vivo murine submandibular gland tissue. With a temporal resolution of 0.03 ns, the FLIM images show distinguished structures of lifetime differences down to 0.5 ns. The combination of sub-micrometer fluorescence intensity and lifetime images in a minimally invasive endomicroscope opens new avenues for label-free cancer detection.