Fiber delivered probe for efficient CARS imaging of tissues

Abstract

We demonstrate a fiber-based probe for maximum collection of the coherent anti-Stokes Raman scattering (CARS) signal in biological tissues. We discuss the design challenges including capturing the back-scattered forward generated CARS signal in the sample and the effects of fiber nonlinearities on the propagating pulses. Three different single mode fibers (fused silica fiber, photonic crystal fiber and double-clad photonic crystal fiber) were tested for the probe design. We investigated self-phase modulation, stimulated Raman scattering (SRS) and four-wave-mixing (FWM) generation in the fiber: nonlinear processes expected to occur in a two-beam excitation based probe. While SPM and SRS induced spectral broadening was negligible, a strong non phase-matched FWM contribution was found to be present in all the tested fibers for excitation conditions relevant to CARS microscopy of tissues. To spectrally suppress this strong contribution, the probe design incorporates separate fibers for excitation light delivery and for signal detection, in combination with dichroic optics. CARS images of the samples were recorded by collecting the back-scattered forward generated CARS signal in the sample through a multi-mode fiber. Different biological tissues were imaged ex vivo in order to assess the performance of our fiber-delivered probe for CARS imaging, a tool which we consider an important advance towards label-free, in vivo probing of superficial tissues.

Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice

“…Importantly, the label-free detection of lipids provided by CARS can be combined with endoscopic probing, opening the door for in vivo optical examination of intravascular lesions. Recently, signifi cant progress has been made with integrating nonlinear optical modalities, such as SHG and CARS, in a fi ber-based probe ( 38 ), underscoring the potential of the nonlinear imaging approach for research of cardiovascular disease.…”

Raman spectroscopy: techniques and applications in the life sciences

“…This allowed images with contrast generated by features from most of the biological Raman spectral window, as shown in Figure 23(b) (also compatible with SHG/TPEF). CARS-based endoscopy was also demonstrated on various ex vivo thick tissue samples by Balu et al [240].…”

Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy

“…Therefore, effective deployment of CARS imaging should be done from the arterial lumen. This deployment requires CARS endoscopy, where the delivery of the excitation laser and collection of emitted signal are accomplished using fl exible fi ber optics, miniaturized objective, and scan heads ( 84,85 ). Ideally, CARS endoscopy should be deployed on a catheter bundle that is also capable of optical coherent tomography and IVUS ( 75 ).…”