Abstract
.Coherent Raman fiber probes have not yet found their way into the clinic despite their immense potential for label-free sensing and imaging. This is mainly due to the traditional bulky laser systems required to create the high peak power laser pulses needed for coherent Raman, as well as the complications that arise from the propagation of this type of energy through silica. Specifically, a coherent anti-Stokes Raman scattering (CARS) probe that could select its integration volume at high resolution, away from the tip of the fiber, is particularly interesting in the case of electrode implantation neurosurgeries, wherein it is possible to place optical fibers on-board the chronic electrode and provide optical guidance during its implantation, through the semi-transparent tip. To this clinical end, we have created an all fiber CARS system, consisting of small, rapidly tunable, turn-key fiber-lasers, capable of creating high wavenumber CARS spectra on the order of tens-of-milliseconds. The use of traditional silica fibers is made possible by the use of the laser’s long pulse-widths (25 ps). The probe itself has an outer diameter of allowing it to fit within commercially available metal tubes that can replace deep brain stimulation (DBS) stylets. Using this system, we identified brain tissue types in intact nonhuman primates’ brains and showed the ability to delineate white and gray matters with high resolution. Its advantages over spontaneous Raman stem from the orders of magnitude improvement in spatial resolution, its inherent translatability to three-dimensional (3-D) imaging, as well as the theoretical ability to remove parasitic Raman signal from probe encasements, such as a DBS electrode. The system is planned to have clinical implications in neurosurgical guidance as well as diseased tissue detection.
Highlights
IntroductionCoherent anti-Stokes Raman scattering (CARS) microscopy is a well-established technique for studying biological systems in a label-free manner, at video-rate speeds.[1,2] spontaneous and coherent Raman microscopies both look at inelastic scattering from a sample, caused by inherent molecular vibrations, CARS has the advantage of a greater signal generation, intrinsic three-dimensional (3-D) sectioning (due to its nonlinear nature), and a blue-shifted signal, which allows easy removal of background fluorescent signals.[3] CARS microscopy is a useful tool for probing single molecular vibrations present in a sample, the hyperspectral information routinely acquired in spontaneous Raman microscopy provides much more diagnostic information
Spontaneous and coherent Raman microscopies both look at inelastic scattering from a sample, caused by inherent molecular vibrations, Coherent anti-Stokes Raman scattering (CARS) has the advantage of a greater signal generation, intrinsic three-dimensional (3-D) sectioning, and a blue-shifted signal, which allows easy removal of background fluorescent signals.[3]
CARS microscopy is a useful tool for probing single molecular vibrations present in a sample, the hyperspectral information routinely acquired in spontaneous Raman microscopy provides much more diagnostic information
Summary
Coherent anti-Stokes Raman scattering (CARS) microscopy is a well-established technique for studying biological systems in a label-free manner, at video-rate speeds.[1,2] spontaneous and coherent Raman microscopies both look at inelastic scattering from a sample, caused by inherent molecular vibrations, CARS has the advantage of a greater signal generation, intrinsic three-dimensional (3-D) sectioning (due to its nonlinear nature), and a blue-shifted signal, which allows easy removal of background fluorescent signals.[3] CARS microscopy is a useful tool for probing single molecular vibrations present in a sample, the hyperspectral information routinely acquired in spontaneous Raman microscopy provides much more diagnostic information.
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