Abstract
The translation of CARS imaging towards real time, high resolution, chemically selective endoscopic tissue imaging applications is limited by a lack of sensitivity in CARS scanning probes sufficiently small for incorporation into endoscopes. We have developed here a custom double clad fiber (DCF)-based CARS probe which is designed to suppress the contaminant Four-Wave-Mixing (FWM) background generated within the fiber and integrated it into a fiber based scanning probe head of a few millimeters in diameter. The DCF includes a large mode area (LMA) core as a first means of reducing FWM generation by ~3 dB compared to commercially available, step-index single mode fibers. A micro-fabricated miniature optical filter (MOF) was grown on the distal end of the DCF to block the remaining FWM background from reaching the sample. The resulting probe was used to demonstrate high contrast images of polystyrene beads in the forward-CARS configuration with > 10 dB suppression of the FWM background. In epi-CARS geometry, images exhibited lower contrast due to the leakage of MOF-reflected FWM from the fiber core. Improvements concepts for the fiber probe are proposed for high contrast epi-CARS imaging to enable endoscopic implementation in clinical tissue assessment contexts, particularly in the early detection of endoluminal cancers and in tumor margin assessment.
Highlights
Coherent anti-Stokes Raman spectroscopy (CARS) is a label-free imaging modality that, by interrogating vibrational modes of bonds important in biological systems (e.g. CH2 and CH3 bonds present in large numbers in lipids and proteins as well as the O-P-O bonds in nucleic acid backbones), generates chemically selective contrast in tissue imaging
This approach, combining illumination and collection in a single fiber and relying on miniature fiber scanner technology, enables CARS to be performed with small diameter probe heads suitable for endoscopy
Compared to the commercially available PM780-HP fiber, the developed large mode area (LMA) double clad fiber (DCF) design provides a 2-fold reduction in both the FWM generated in the fiber and the bending losses at coiling diameters required in endoscopy
Summary
Coherent anti-Stokes Raman spectroscopy (CARS) is a label-free imaging modality that, by interrogating vibrational modes of bonds important in biological systems (e.g. CH2 and CH3 bonds present in large numbers in lipids and proteins as well as the O-P-O bonds in nucleic acid backbones), generates chemically selective contrast in tissue imaging. A second approach having been proposed by Wang et al [8] relies on orthogonal polarizations of the pump and Stokes fields in a multimode polarizationmaintaining fiber, minimizing the interaction between them and minimizing the FWM signal In this scheme, the polarizations need to be realigned using a dual-wavelength waveplate upon exiting the fiber in order to generate the CARS signal at the sample. In this paper we present an SFE-based scanning probe head containing a unique doubleclad fiber (DCF) serving to both deliver the pump and Stokes pulses to the sample through the fiber core as well as provide a collection path for CARS signal in the inner (collection) cladding This fiber is designed to reduce the level of FWM background which is generated within its single-mode core, as well as to ensure that bending losses are minimized so that it can be applied to challenging endoscopic applications. Based on the inherent physical separation of the pump and Stokes delivery channel from the CARS signal collecting channel, we present a strategy to block the remaining FWM background from reaching the sample by using a microfabricated long-pass optical filter (MOF) scheme grown over the fiber core, leaving the cladding uncoated for CARS signal collection
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