## 2 Literature Review
A systematic study of several means for fluorescence image-guided glioma surgery, based on preclinical and clinical assessments, is reported in [22]. In other works, photo-acoustic imaging was also used for potential intraoperative tumor margin detection [23]. Photo-acoustic tomography (PAT) has been utilized for breast cancer imaging, brain imaging, and other applications. Even though the limited penetration depth of the technique can be overcome by utilizing microwaves or radiowaves, ultrasounds sustain intense artifact effects upon the reflection of signals from gas to liquid structures and gas to solid ones due to differentiations in acoustic impedances. In addition, ultrasounds suffer from considerable signal attenuation and corruption (phase distortion) in dense/compact structures (thick bones properties), such as the human skull. As a further observation, such acoustic signals are characterized by a decreased ability to efficiently penetrate through gas hollows (such as lung tissues and/or brain tumors). Finally, in order to efficiently detect ultrasonic waves, direct communication/connection of the sensor module (transducer) and the biological structure (tissue sample) is required. In [24], the authors investigated the feasibility of the multispectral dye-enhanced polarized light imaging method to delineate non-melanoma tumor margins, a tissue type where regions of increased hemoglobin concentration and dye absorption need to be isolated. This work successfully distinguished and identified the tumor margins using the specific imaging modality. Apart from the imaging modalities mentioned above, nanoscale structures are also used to enhance margin detection. For example, nanotechnology-based contrast agents enhance optical imaging methods and aid in margin detection. Gold nanoparticles (GNPs) are particularly suited for this purpose as they absorb and scatter light strongly and the presence of gold metal intensifies the signal greatly. These gold nanoparticles are coupled with a dye and used in Raman spectroscopy and other optical spectroscopic techniques to produce the surface-enhanced Raman spectroscopic (SERS) effect. Near IR lasers and fluorescence detectors are also combined to record the Raman signals and measure fluorescence in the presence of gold nanoparticles, which concentrate in tumor regions. Due to their nano size, they can easily penetrate blood vessels that are leaky due to the tumor and get trapped in the edge of these tumors as such blood vessels are dominant in tumor edges. This effect enhances margin detection enormously. Similar studies introduced the use of gold nanoparticles in NIR narrow-band imaging (NIR NBI) [25], utilizing two lighting emitting diodes (LEDs) with wavelengths at the green and NIR range to illuminate the GNP infiltrated blood vessels. A charge-coupled device (CCD) captures the reflected illumination signal from the sample. In the corresponding results, the gold nanoparticles clearly demarcated the tumor margins, demonstrating the potential of this technology in intraoperative detection. Targeted gold nanoparticles that deliver a fluorescent payload to tumors have also been used to demarcate the tumor from normal tissues [26]. During the last decade, [PERSON] et al. [27; 28; 29; 30] have extensively worked on a number of approaches for the differentiation of healthy and cancerous cells, introducing label-free NIR-IR polarimetric diffuse reflectance-based cancer detection methodologies in conjunction with a wavelet and fractal analysis. Visualizing the interaction of IR with healthy and malignant (cancerous) lung cells through polarimetry under diffuse reflectance geometry, in connection with polarimetric exploratory data analysis (pEDA) [29] enables the development of robust and competent diagnostic tools.