Investigations of aluminum foil, CaF\({}_{2}\), quartz, low-emissivity, and Ag-coated and Au-coated microscope slides as potential substrates for Raman spectroscopy have been successfully performed [28; 29]. Although the fluorescence signal can easily be six orders of magnitude higher than the Raman signal [18], which would result in an impossible identification of Raman peaks, taking the aforementioned factors into account, application of Raman-based microscopy for tissue analysis has been demonstrated multiple times. The subsequent applications of Raman microscopy to classify tissue do not specify the Raman spectroscopy technique. Currently, more than 25 different types of known Raman techniques, including enhanced Raman spectroscopic techniques such as stimulated Raman scattering (SRS), coherent anti-Stokes Raman scattering (CARS) as well as surface- (SERS) and tip-enhanced (TERS) Raman scattering have emerged [30]. Raman microscopy was successfully applied by various researchers for ex-vivo examination of pathological changes of different tissue types such as breast [31; 32], brain [33; 34; 35; 36], colon [37], skin [38; 39; 40], and spinal cord [41; 42]. Nearly all researchers prepared a histological stain (H&E staining) of the previously measured sample or a serial section to accompany an ex-vivo chemical image as it is an established method to visualize and analyze the morphology of the tissue [43]. The video capability to record the brightfield images of H&E-stained samples are often included in the Raman system. Besides the regular brightfield photographs, companies offer the integration of conventional microscopic modalities such as darkfield, polarized light, and epifluorescence within the Raman microscope [44]. Combinations of different modalities are referred to as multimodal imaging approaches [45]. One commonly used combination is Raman spectroscopy and infrared (IR) spectroscopy, which is an absorption-based vibrational spectroscopic technique. Kochan et al. [46] used Raman and IR imaging to study alteration in murine brain tissue. Reviews of tissue classifications with IR and/or Raman spectroscopy are published by Bunaciu et al. [47] and Lyng et al. [48]. Lasch and Noda [49] complemented Raman and IR spectroscopy by MALDI TOF mass spectrometry to analyze hamster brain tissue. An overview of several tissue studies based on mass spectrometry and vibrational spectroscopy was recently given by Tuck et al. [43]. Combinations of Raman spectroscopy and the above-mentioned morphological imaging techniques have been developed as well. Bovenkamp et al. [50] and Egodage et al. [51] used OC tomography and Raman spectroscopy to analyze tissue. Bocklitz et al. [52] combined CARS, TPEF, and SHG to calculate a computational H&E stain for fast characterization of tissue architecture as well as the biochemical composition. Based on the calculated image, a region of interest (ROI) was determined for subsequent molecular selective diagnostic using Raman spectroscopy. If multiple measurement techniques are combined within one instrument, it is called a multimodal system [53]. To the best of the authors' knowledge, the design of a multimodal imaging system combining brightfield, darkfield, and polarization microscopy, spontaneous Raman spectroscopy and VIS/NIR reflectance spectroscopy in the incident light mode as well as brightfield microscopy in the transmitted light mode have not been reported to distinguish grey matter (GM) and white matter (WM) of normal (under healthy conditions) brain tissue. GM and WM are two main areas within the brain that can be clearly differentiated [54]. GM is characterized by protein-rich neuronal bodies. WM does not contain neuronal bodies. The lipid-rich WM is characterized by a high presence of myelinated axons [54]. For Raman spectroscopy, this difference in lipid and protein content has been used to distinguish GM and WM based on intensity peak ratios and the sum of two intensity peak ratios by a series of researchers [33; 34; 35; 35; 46; 55].