Intact primate brain tissue identification using a completely fibered coherent Raman spectroscopy system

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.

Portable all-fiber dual-output widely tunable light source for coherent Raman imaging

“…However, as the system made use of synchronized ytterbium-doped and erbium-doped fiber lasers, only vibrational resonances in the CH-stretch region (2700 to 3100 cm−1) were accessible due the limited gain bandwidth of the fiber lasers [17,18]. For the same reason, a recently presented fiber-endoscopic CARS spectroscopy system for non-laboratory applications, based on a synchronized ytterbium-doped fiber laser and a diode laser, was limited to the CH-stretch region as well [19]. Although vibrational components in the CH-stretch region in many cases give sufficient contrast for tomographic assessment, many applications focus on vibrational components outside the CH-stretch region.…”

Identification of distinctive features in human intracranial tumors by label‐free nonlinear multimodal microscopy

“…The translation of the technique in the operating theater requires its integration in endoscopic-like systems. Different approaches were already demonstrated either based on the use of GRIN lenses [16,36], optical fibers [15,43], multicore optical fibers [20] or other types of specially engineered fibers [19]. For all these systems, the FoV is comprised between 80 and 300 μm [36,44].…”

Rise of Raman spectroscopy in neurosurgery: a review

“…In 2018, DePaoli et al 16 presented a CR probe to investigate ex vivo primate brain tissue using a previously designed wavelength-sweeping system. 45 The system was composed of a compact fiber-based pulsed laser source [Halifax Biomedical, Fig.…”

“…For example, deep brain stimulation (DBS) for PD could be optically guided using laser Doppler flow (LDF) measurements, 12 diffuse reflectance spectroscopy (DRS), [13][14][15] and coherent Raman (CR) spectroscopy. 16 During epilepsy surgery, hyperspectral imaging is being investigated to help guide resection. 17 Finally, in closed biopsies, OCT has been used to image blood vessels to minimize hemorrhage rates 18 and RS has shown promise in effective tumor targeting.…”