Guiding Brain Tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-Held Raman Scanner

Abstract

The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold–silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room.

Cancer characterization and diagnosis with SERS-encoded particles

“…While demonstrating the tremendous analytical potential of the technique, this setup restricts the applicability to rather small tissue areas (unless exceedingly long integration times are applied or to the detriment of the necessary spatial resolution). Thus, major efforts have been devoted to the development of advanced instrumentations capable of addressing these issues (Bohndiek et al 2013;Garai et al 2015;Kang et al 2016;Karabeber et al 2014;Mallia et al 2015;McVeigh et al 2013;Mohs et al 2010;Wang et al 2016;Zavaleta et al 2013).…”

“…Handheld Raman devices were also combined with SEPs for in vivo intraoperative tumor imaging (Karabeber et al 2014;Mohs et al 2010) to provide a flexible instrumental tool, enabling the precise localization of small foci of the tumor which would otherwise remain undetected if scanning is only performed with the traditionally fixed angle setup.…”

Surgical Guidance via Multiplexed Molecular Imaging of Fresh Tissues Labeled With SERS-Coded Nanoparticles

“…Since SERS NPs are not currently approved for human use, systemic administration has only been employed for in vivo imaging studies in animals [33,34,44,51–53]. For the imaging of tumor xenografts, image contrast has been achieved 5 – 24 hours after injecting SERS NPs into the tail vein of mice (Figs.…”

Stimulated Raman scattering microscopy for rapid brain tumor histology

“…Surface enhanced Raman scattering (SERS)-based methods have the advantages of signi¯cantly enhanced Raman signals during in vivo imaging, but they require exogenous labeling with nanoparticles. 30 …”