Endomicroscopy Technologies for High-Resolution Nonlinear Optical Imaging and Optical Coherence Tomography

Recent advances in fiber-optics, micro-optics and miniaturized optical and/or mechanical scanners have promoted rapid development and clinical translation of nonlinear optical (e.g., two-photon fluorescence and second harmonic generation) microscopy and optical coherence tomography (OCT), enabling depth-resolved endomicroscopic imaging of internal organs with unprecedented resolution. This paper presents a review of nonlinear optical imaging and OCT endomicroscopy technologies with emphasis on their major building blocks, including the commonly used 2D/3D beam scanning mechanisms and miniature objective lenses. The advantages and challenges associated with various endomicroscopes are also discussed. Special designs and engineering considerations are presented for a few representative endomicroscopes, including an all-fiber-optic rapid scanning nonlinear optical imaging endomicroscope, a high-resolution OCT balloon imaging catheter, and an ultrathin OCT imaging needle. Some exemplary imaging results achieved with these endomicroscopy technologies are presented, demonstrating the promising role of these emerging endomicroscopy technologies for basic laboratory research and for translational early disease detection and image-guided interventions.