Label-free detection of brain tumors in a 9L gliosarcoma rat model using stimulated Raman scattering-spectroscopic optical coherence tomography

Abstract

Significance: In neurosurgery, it is essential to differentiate between tumor and healthy brain regions to maximize tumor resection while minimizing damage to vital healthy brain tissue. However, conventional intraoperative imaging tools used to guide neurosurgery are often unable to distinguish tumor margins, particularly in infiltrative tumor regions and low-grade gliomas.Aim: The aim of this work is to assess the feasibility of a label-free molecular imaging tool called stimulated Raman scattering-spectroscopic optical coherence tomography (SRS-SOCT) to differentiate between healthy brain tissue and tumor based on (1) structural biomarkers derived from the decay rate of signals as a function of depth and (2) molecular biomarkers based on relative differences in lipid and protein composition extracted from the SRS signals.Approach: SRS-SOCT combines the molecular sensitivity of SRS (based on vibrational spectroscopy) with the spatial and spectral multiplexing capabilities of SOCT to enable fast, spatially and spectrally resolved molecular imaging. SRS-SOCT is applied to image a 9L gliosarcoma rat tumor model, a well-characterized model that recapitulates human high-grade gliomas, including high proliferative capability, high vascularization, and infiltration at the margin. Structural and biochemical signatures acquired from SRS-SOCT are extracted to identify healthy and tumor tissues.Results: Data show that SRS-SOCT provides light-scattering-based signatures that correlate with the presence of tumors, similar to conventional OCT. Further, nonlinear phase changes from the SRS interaction, as measured with SRS-SOCT, provide an additional measure to clearly separate tumor tissue from healthy brain regions. We also show that the nonlinear phase signals in SRS-SOCT provide a signal-to-noise advantage over the nonlinear amplitude signals for identifying tumors.Conclusions: SRS-SOCT can distinguish both spatial and spectral features that identify tumor regions in the 9L gliosarcoma rat model. This tool provides fast, label-free, nondestructive, and spatially resolved molecular information that, with future development, can potentially assist in identifying tumor margins in neurosurgery.

Raman Spectroscopy: A Tool for Molecular Fingerprinting of Brain Cancer

“…A multimodal SRS-SOCT (spectroscopic optical coherence tomography) setup was exploited by Soltani and group to assess its capability to distinguish between a normal and tumorous brain in a 9 L gliosarcoma rat model. It was found from the work that SOCT can resolve spatial and spectral features of the SRS comparatively easily which leads to faster data acquisition of even larger regions, which makes the multimodal setup a good option to consider for clinical use . Orringer et al were the first ones to come up with a SRS microscopy for intraoperative use in the clinic and also SRH, virtual H&E staining.…”

“…It was found from the work that SOCT can resolve spatial and spectral features of the SRS comparatively easily which leads to faster data acquisition of even larger regions, which makes the multimodal setup a good option to consider for clinical use. 76 Orringer et al were the first ones to come up with a SRS microscopy for intraoperative use in the clinic and also SRH, virtual H&E staining. The virtual stained images were obtained with 2 s per frame FOV in a mosaic pattern, stitched, and recolored, taking only 2.5 min for a whole mosaic.…”

Multimodal Raman spectroscopy and optical coherence tomography for biomedical analysis

“…Due to the need for high‐powered femtosecond lasers to stimulate CARS, multiple higher‐order optical processes could also be used as additional label‐free contrast mechanisms, including stimulated Raman scattering (SRS), and higher‐order harmonic generation. Clinical applications for CARS‐ and SRS‐OCT have been explored for optic nerve imaging [151], characterization of human bone [152], brain tumor detection [153], and adipose tissue [154]. Although, the high cost and tissue‐damaging effects of fast‐pulsed lasers limit the accessibility of such devices for in vivo use.…”

Raman spectroscopy: A prospective intraoperative visualization technique for gliomas

“…Such a feature allows Raman spectroscopy to identify the chemical composition patterns of the corresponding samples. Several studies have used Raman spectroscopy in animals ( 7 – 9 ) and human samples ( 10 – 12 ) for chemical composition patterns to distinguish tumor from normal brain tissue, with excellent performance results similar to the accuracy of pathology. Moreover, the Rapidity and non-invasive properties of Raman spectroscopy also enable its potential as an intraoperative inspection method to improve the EOR of glioma surgery, so as to improve surgical outcomes and promote patient prognosis ( 13 – 15 ).…”