High-resolution multimodal flexible coherent Raman endoscope

Coherent Raman scattering microscopy is a fast, label-free, and chemically specific imaging technique that shows high potential for future in vivo optical histology. However, the imaging depth in tissues is limited to the sub-millimeter range because of absorption and scattering. Realization of coherent Raman imaging using a fiber endoscope system is a crucial step towards imaging deep inside living tissues and providing information that is inaccessible with current microscopy tools. Until now, the development of coherent Raman endoscopy has been hampered by several issues, mainly related to the fiber delivery of the excitation pulses and signal collection. Here, we present a flexible, compact, coherent Raman, and multimodal nonlinear endoscope (4.2 mm outer diameter, 71 mm rigid length) based on a resonantly scanned hollow-core Kagomé-lattice double-clad fiber. The fiber design enables distortion-less, background-free delivery of femtosecond excitation pulses and back-collection of nonlinear signals through the same fiber. Sub-micrometer spatial resolution over a large field of view is obtained by combination of a miniature objective lens with a silica microsphere lens inserted into the fiber core. We demonstrate high-resolution, high-contrast coherent anti-Stokes Raman scattering, and second harmonic generation endoscopic imaging of biological tissues over a field of view of 320 µm at a rate of 0.8 frames per second. These results pave the way for intraoperative label-free imaging applied to real-time histopathology diagnosis and surgery guidance.Endoscopy: Bringing coherent Raman microscopy into the bodyA powerful technique called coherent Raman scattering microscopy could be used to visualize and study tissue inside the body thanks to a new light-transmitting fiber technology. Coherent Raman scattering generates images based on the interaction of light with  molecules. It opens a window into cells and tissues that reveals information unavailable with simple illumination by light. Applying the technique deep within the body has proved difficult due to technical problems in delivering the necessary ultra-short pulses of light, and collecting the signals that are scattered back. Researchers in France and Germany, led by Hervé Rigneault at the Fresnel Institute in France, combined several innovations in fiber technology to bring high-resolution coherent Raman imaging into previously hidden locations. Their flexible endoscope literally shines new light to assist the diagnosis and surgical treatment of cancer and other diseases.

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