High-resolution multimodal flexible coherent Raman endoscope

TL;DR

This paper introduces a flexible, multimodal coherent Raman endoscope capable of high-resolution, real-time, label-free imaging deep inside tissues, advancing in-vivo optical histology and surgical guidance.

Contribution

It presents a novel fiber design and miniaturized optics enabling distortion-free, multimodal Raman imaging with high resolution and large field of view in a compact endoscope.

Findings

Achieved 0.8 μm spatial resolution in tissue imaging.

Demonstrated multimodal imaging including CARS, 2-photon fluorescence, SHG.

Operates at 0.8 frames per second with a 320 μm field of view.

Abstract

Coherent Raman scattering microscopy is a fast, label-free and chemically specific imaging technique that has a high potential for future in-vivo optical histology. However, its imaging depth into tissues is limited to the sub-millimeter range by absorption and scattering. Performing coherent Raman imaging in a fiber endoscope system is a crucial step to image deep inside living tissues and provide the information inaccessible with current microscopy tools. However the development of coherent Raman endoscopy has been hampered by several issues in the fiber delivery of the excitation pulses and signal collection. Here, we present a flexible, compact, and multimodal nonlinear endoscope (4.2 mm outer diameter, 71 mm rigid length) based on a resonantly scanned hollow-core Kagom\'e-lattice double-clad fiber. The fiber design allows distortion-less, background-free delivery of femtosecond excitation pulses and the back-collection of nonlinear signals through the same fiber. Sub-micron spatial resolution together with large field of view is made possible by the combination of a miniature objective lens together with a silica microsphere lens inserted into the fiber core. We demonstrate coherent anti-Stokes Raman scattering, 2-photon fluorescence and second harmonic generation imaging with 0.8 {\mu}m resolution over a field of view up to 320 {\mu}m and at a rate of 0.8 frames/s. These results pave the way for intra-operative label-free imaging applied to real-time histopathology diagnosis and surgery guidance.