Improving the accuracy of brain tumor surgery via Raman-based technology

Abstract

<jats:p>Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H &amp; E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors.</jats:p>

Modalities for image- and molecular-guided cancer surgery

“…However, the use of radioactive material requires special biosafety permits, additional training, and safety procedures for both personnel and patients. 41,42 Analogous to ultrasonography, but reflections of near-infrared light are detected instead of sound 43,44 ; the information is obtained by differences in reflected energy and scattering intensity 21 An ambient ionization technique.…”

“…Yes, depending on technique 41 Yes 21,43 , tomographic images of biological tissue are generated (morphology) 11,41,46 No, it is based on tissue-specific molecular signatures 47 2D/3D 2D, 3D is possible by using stacked images or measuring at a different depth 2D and 3D depending on detector used 44 A spectrum is generated, not an image 15,48,49 Need for contrast agent No, it is a label-free method as it uses intrinsic properties of molecules 42 No, depends on optical scattering and reflectance of tissue to generate contrast 41,44,46 No, it is a label-free technique 15,48,49 Cost (machine and facility) € € €€ 47 Acquisition cost € € € Time (acquisition and reconstruction) Short (1-10 min) 41 . Spontaneous Raman scattering: acquisition time 0⋅05 s for a single high-quality spectrum.…”

“…Spontaneous Raman scattering: acquisition time 0⋅05 s for a single high-quality spectrum. Coherent Raman imaging is faster (μs/pixel) 41,42 , with limited spectral quality…”

“…To create additional contrast, plasmonic particles or organic polymers coupled with antibodies could be used. Stimulated Raman scattering can be used to monitor dynamic changes, alterations in tissue cellularity, axonal density and protein/lipid ratio 42 . A possible limitation of translating Raman spectroscopy into clinical practice is the question of how small fields of view could be applied to the validation of a tumour bed, which is relatively large.…”

“…For this, an image-resect-image technique was used in which the arm movement was predefined. This method led to an additional operating time of 10 min for image acquisition, which was not considered obstructive to surgical workflow 41,42 . Use similar to fluorescence-guided surgery but with more anatomical information 11,58 Mostly used for quality control of resection cavity and lump assessment 12,33 Used for SLN detection, surgical orientation and for quality control of resection cavity 37,59 Depth 1 cm 3,4 Several centimetres 4 1 cm, depending on radiotracer used 33,60 No Nanomolar sensitivity with high specificity based on multispectral imaging…”