Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging

Abstract

We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery.

Keywords: (110.0110) Imaging systems; (220.0220) Optical design and fabrication.

Fig. 1

The schematic optical design of the miniaturized endo-microscope of fiber-based, multimodal, nonlinear probe.

Fig. 2

The optical imaging path schematic of the multimodal, nonlinear endo-microscopy probe.

Fig. 3

(a) MTF performance of the as-built multimodal, nonlinear endo-microscopy probe; (b) Spot diameters (represent resolutions) at different FOVs of the multimodal nonlinear endo-microscopy probe.

Fig. 4

(a). Photo shows PM1300 fiber part of the multimodal, nonlinear endo-microscopy probe; (b) Photo shows the collimator part of the multimodal, nonlinear endo-microscopy probe; (c) Photo shows the endo-microscopy part of the multimodal, nonlinear endo-microscopy probe; (d) resolution experiment setup of the endo-microscope; (e), (f), and (g) present the transmission images in 575 nm (e), 660 nm (f), and 850nm (g) from endo-microscopy imaging of USAF resolution target.

Fig. 5

CARS and SHG images of prostate epithelial cells obtained using an upright microscope. (a) CARS image. Yellow arrow points to a cell nucleus. (b) SHG image of the same region of the prostate cancer tissue, showing a void in the fibers in the region of the epithelial cells.