Dual-Modality Surface-Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation

摘要

Difficulty in visualizing glioma margins intraoperatively remains a major issue in the achievement of gross total tumor resection and, thus, better clinical outcome of glioblastoma (GBM) patients. Here we investigated the potential of a new combined optical + optoacoustic imaging method for intraoperative brain tumor delineation. We devised a strategy using our newly developed gold nanostar synthesis method, Raman reporter chemistry, and silication method to produce dual-modality contrast agents for combined surface-enhanced resonance Raman scattering (SERRS)- and multispectral optoacoustic tomography (MSOT) imaging. Following intravenously injection of the SERRS-MSOT-nanostars in brain tumor bearing Nestin-tv-a;Ink4a/Arf^−/−;Pten^fl/fl mice, sequential cross-sectional MSOT imaging was performed in vivo and followed by ex vivo Raman imaging for analysis of signal congruency.MSOT was able to accurately depict GBMs up to a depth of several millimeters three-dimensionally with high specificity. The MSOT signal was found to correlate well with the SERRS images. Because SERRS enables uniquely sensitive high resolution surface detection, it could represent an ideal complementary imaging modality to MSOT, which enables real-time, deep tissue imaging in 3D. This dual-modality SERRS-MSOT-nanostar contrast agent reported here was shown to enable high precision depiction of the extent of infiltrating GBMs by Raman- and MSOT imaging in a clinically relevant murine GBM model and could pave new ways for improved image-guided resection of brain tumors.