From Research to Diagnostic Application of Raman Spectroscopy in Neurosciences: Past and Perspectives

Abstract

In recent years, Raman spectroscopy has been more and more frequently applied to address research questions in neuroscience. As a non-destructive technique based on inelastic scattering of photons, it can be used for a wide spectrum of applications including neurooncological tumor diagnostics or analysis of misfolded protein aggregates involved in neurodegenerative diseases. Progress in the technical development of this method allows for an increasingly detailed analysis of biological samples and may therefore open new fields of applications. The goal of our review is to provide an introduction into Raman scattering, its practical usage and also commonly associated pitfalls. Furthermore, intraoperative assessment of tumor recurrence using Raman based histology images as well as the search for non-invasive ways of diagnosis in neurodegenerative diseases are discussed. Some of the applications mentioned here may serve as a basis and possibly set the course for a future use of the technique in clinical practice. Covering a broad range of content, this overview can serve not only as a quick and accessible reference tool but also provide more in-depth information on a specific subtopic of interest.

Keywords: Machine learning; Neurodegeneration; Neurooncology; Neuropathology; Neurosurgery; Raman spectroscopy.

Figure 1

Occurring optical phenomena when irradiating a biological sample with a photon source (laser). Left: Vibrational states (v₀, v₁, v₂) involved in Rayleigh and Raman scattering. In case of elastic scattering (Raleigh scattering), incoming photons temporarily change the vibrational state of a molecule - after this excitation, the molecule returns back to the initial vibrational state (v₀). In the case of Stokes Raman scattering, a molecule gains energy due to the excitation process and finally ends up in a higher vibrational state (it rises from v₀ to v₁) – the scattered photon has lower energy than the incident light. In Anti-Stokes scattering the molecule ends up on a lower vibrational state after excitation compared to the ground state (it falls from v₁ to v₀) – therefore, the scattered photon gains energy. Right: In contrast, the phenomenon of fluorescence occurs when a molecule absorbs light and thus is temporarily transferred to a higher electronic state (v’₀, v’₁, v’₂).

Figure 2

Schematic and simplified representation of a Raman spectrometer set up.