Human brain tissue identification using coherent anti-Stokes Raman scattering spectroscopy and diffuse reflectance spectroscopy for deep brain stimulation surgery.

Significance: We assess the feasibility of using diffuse reflectance spectroscopy (DRS) and coherent anti-Stokes Raman scattering spectroscopy (CARS) as optical tools for human brain tissue identification during deep brain stimulation (DBS) lead insertion, thereby providing a promising avenue for additional real-time neurosurgical guidance. Aim: We developed a system that can acquire CARS and DRS spectra during the DBS surgery procedure to identify the tissue composition along the lead trajectory. Approach: DRS and CARS spectra were acquired using a custom-built optical probe integrated in a commercial DBS lead. The lead was inserted to target three specific regions in each of the brain hemispheres of a human cadaver. Spectra were acquired during the lead insertion at constant position increments. Spectra were analyzed to classify each spectrum as being from white matter (WM) or gray matter (GM). The results were compared with tissue classification performed on histological brain sections. Results: DRS and CARS spectra obtained using the optical probe can identify WM and GM during DBS lead insertion. The tissue composition along the trajectory toward a specific target is unique and can be differentiated by the optical probe. Moreover, the results obtained with principal component analysis suggest that DRS might be able to detect the presence of blood due to the strong optical absorption of hemoglobin. Conclusions: It is possible to use optical measurements from the DBS lead during surgery to identify WM and GM and possibly the presence of blood in human brain tissue. The proposed optical tool could inform the surgeon during the lead placement if the lead has reached the target as planned. Our tool could eventually replace microelectrode recordings, which would streamline the process and reduce surgery time. Further developments are required to fully integrate these tools into standard clinical procedures.

Wavelength-swept spontaneous Raman spectroscopy system improves fiber-based collection efficiency for whole brain tissue classification.

Significance: Raman spectroscopy is a valuable technique for tissue identification, but its conventional implementation is hindered by low efficiency due to scattering. Addressing this limitation, we are further developing the wavelength-swept Raman spectroscopy approach. Aim: We aim to enhance Raman signal detection by employing a laser capable of sweeping over a wide wavelength range to sequentially excite tissue with different wavelengths, paired with a photodetector featuring a fixed narrow-bandpass filter for collecting the Raman signal at a specific wavelength. Approach: We experimentally validate our technique using a fiber-based swept-source Raman spectroscopy setup. In addition, simulations are conducted to assess the efficacy of our approach in comparison with conventional spectrometer-based Raman spectroscopy. Results: Our simulations reveal that the wavelength-swept configuration leads to a significantly stronger signal compared with conventional spectrometer-based Raman spectroscopy. Experimentally, our setup demonstrates an improvement of at least 200× in photon detection compared with the spectrometer-based setup. Furthermore, data acquired from different regions of a fixed monkey brain using our technique achieves 99% accuracy in classification via k -nearest neighbor analysis. Conclusions: Our study showcases the potential of wavelength-swept Raman spectroscopy for tissue identification, particularly in highly scattering media, such as the brain. The developed technique offers enhanced signal detection capabilities, paving the way for future in vivo applications in tissue characterization.

Millimetric scale two-photon Bessel-Gauss beam light sheet microscopy with three-axis isotropic resolution using an axicon lens.

Significance: Typical light sheet microscopes suffer from artifacts related to the geometry of the light sheet. One main inconvenience is the non-uniform thickness of the light sheet obtained with a Gaussian laser beam. Aim: We developed a two-photon light sheet microscope that takes advantage of a thin and long Bessel-Gauss beam illumination to increase the sheet extent without compromising the resolution. Approach: We use an axicon lens placed directly at the output of an amplified femtosecond laser to produce a long Bessel-Gauss beam on the sample. We studied the dopaminergic system and its projections in a whole cleared mouse brain. Results: Our light sheet microscope allows an isotropic resolution of 2.4 µm in all three axes of the scanned volume while keeping a millimetric-sized field of view, and a fast acquisition rate of up to 34 mm2/s. With slight modifications to the optical setup, the sheet extent can be increased to 6 mm. Conclusion: The proposed system's sheet extent and resolution surpass currently available systems, enabling the fast imaging of large specimens.

MCVD-based GRIN-axicon for the generation of scalable Bessel-Gauss beams.

In this Letter, we introduce a graded-index (GRIN)-lens combination named GRIN-axicon, which is a versatile component capable of generating high-quality scalable Bessel-Gauss beams. To the best of our knowledge, the GRIN-axicon is the only optical component that can be introduced in both larger-scale laboratory setups and miniaturized all-fiber optical setups, while having an easy control of the dimensioning of the generated focal line. We show that a GRIN lens with a hyperbolic secant refractive index profile with a sharp central dip and no ripples generates a Bessel-Gauss beam with a high-intensity central lobe when coupled to a simple lens. Such fabrication characteristics are very suitable for the modified chemical vapor deposition (MCVD) process and enable easy manufacturing of an adaptable component that can fit in any optical setup.

Toric lens analysis as a focal ring and Bessel beam generator.

We propose an analytical solution of the focal ring generated at the focus of a toric lens. The analytical field of the focal ring is used with a Fourier transform lens to generate a Bessel beam. A comparative analysis between the use of an illuminated annular aperture, an axicon, and a toric lens to generate a Bessel beam is performed, and the benefits and drawbacks of each are discussed. This highlights the advantages of using a toric lens with a Gaussian beam to produce a focal line of increasing intensity, which is advantageous for applications such as high depth-of-field microscopy.

Diffusion of chiral molecules and propagation of structural chirality in anisotropic liquids.

Diffusion in nature is usually considered as a smooth redistribution process. However, it appears that the diffusion of chiral molecules and the propagation of chirality may proceed in quite different ways. Indeed, in the present work, unexpected quantization of the spatial concentration of chiral molecules is discovered in self-aligned molecular liquids. It is shown that the interpenetration of two liquids is forming discrete diffusion barrier walls resulting in steplike concentration distribution of chiral molecules in space. The concentration gradient is at least an order of magnitude stronger from both sides of the barrier wall compared to the gradient between those walls. It is also shown that this microscopic diffusion process may be controlled by macroscopic boundary conditions imposed on the host molecular system. Both of those phenomena are related to the collective long-range orientational "elastic" interactions of molecules of the host. The observed phenomena may radically change our understanding of diffusion of chiral molecules, among others, in biological tissue, which contains many examples of self-aligned molecular liquids. This, in turn, has the potential to revolutionize drug design and delivery techniques.